Journals on Biomedical Engineering |BJSTR

Evaluation of a Biodegradable Synthetic Matrix for Lateral Ankle Ligament Surgical Repair Augmentation: An Open Label Controlled Multicenter Retrospective Review

Introduction

Ankle sprains account for up to 40% of all athletic injuries, and 85% of ankle injuries involve the lateral ligamentous complex [1]. Initial patient treatment is conservative, but continued ligament laxity may require surgical intervention. Chronic recurrent lateral ankle instability occurs after 10% to 20% of acute ankle sprains [2]. Although multiple surgical procedures for anterior talofibular ligament (ATFL) repair or ligament reconstruction are well described, the modified Broström repair technique is most widely utilized [3,4]. Yet, reoperation rates have been reported as high as 14% following surgical repair [5]. Lateral ligament repair can be performed alone or with augmentation. For patients with poor tissue quality, medical comorbidities and complex repairs, the use of autograft, allograft, or synthetic augmentation devices may improve healing. Early tissue necrosis and resorption of avascular tissue grafts can lead to loss of biomechanical properties and ultimate load to failure [6-8]. Several synthetic grafts have been developed as alternatives to auto- or allograft replacements. Soft tissue augmentation devices have historically been designed with a rigid structure unmatched to the elastic modulus of the targeted musculoskeletal tissues [3,9]. A degradable biomaterial matrix woven from wet-spun fibers of polycaprolactone based-polyurethane urea (PUUR) provides an augmentation device closer to the elastic modulus of ligament. PUUR textile strips (Artelon Flexband®, Marietta, GA), have been reported for numerous orthopedic soft tissue reconstructive applications [9-13]. PUUR elastomers have an extensive safety record and are widely used biomaterials in catheters, vascular prosthesis, and artificial hearts due to their adaptable mechanical properties and documented biocompatibility [14- 17]. The biomechanical properties of PUUR and the woven textile nature create manufacturing adaptability to optimize tensile properties to mimic native tissue. This improves functional kinematics by providing resistance to stress relaxation and creep while decreasing stress shielding.

Although PUUR has been used in >60,000 cases to date in the reconstruction of soft tissues throughout the body, a direct comparison of lateral ankle ligament repair, with and without PUUR augmentation, has not been previously conducted. The purpose of this study was to perform a retrospective medical chart review to assess the safety and efficacy determined by clinical evaluation, VAS, and physical therapy milestones in patients undergoing a modified Broström procedure with and without PUUR augmentation. In addition, patients enrolled in the retrospective study were contacted to complete a longer-term patient outcome and satisfaction survey following at least 1-year post-operative.

Methods

Patient Identification

Following appropriate ethics approval, a retrospective review of patients diagnosed with chronic lateral ankle instability who underwent a modified Broström procedure either alone (MB) or with PUUR augmentation (PUUR) between January 2018 and June 2022 was conducted. Patients that had surgery performed by any of the nine participating foot and ankle surgeons and had postoperative hospital or ASC safety and efficacy data were evaluated for eligibility. All study surgeons performed both augmented and non-augmented repairs. At all participating study institutions, consecutive chart review was performed to identify patients who met all of the inclusion and none of the exclusion criteria (Table 1). 226 patients met study qualifications (MB = 83, PUUR = 143). Data was extracted from both written and electronic medical records. Physician and patient reported outcomes and revision rates were established via chart review from patient scheduled and unscheduled follow up clinic visits. Clinical post-surgical follow up for this procedure typically concludes at 12 weeks, therefore, to collect longer-term outcome measures outside of the clinical follow up window, we attempted to contact all patients via phone at a minimum of one year post operative and asked to complete a satisfaction and functional survey.

Table 1: Study Selection Criteria.

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Surgical Technique

PUUR used in the study consisted of strips of varying size (0.3- 0.5cm X 8-32cm). For patients that underwent augmentation with the PUUR matrix, the modified Broström procedure was performed first followed by tensioning of the PUUR device anchored on either end via bone tunnels (Figure 1). Using the provided kit, guide wires were placed into the anterior fibula and into extra-articular talus body/ neck junction. Bone tunnels were created and the PUUR graft was inserted into the talus first. The modified Brostrom procedure was completed and the PUUR graft was placed overtop or superficial to the repair and inserted into the fibula bone tunnel. Additional procedures such as synovectomy and arthroscopy were commonly performed as needed. A summary of additional procedures in each group is presented (Table 2).

Figure 1

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Table 2: Concomitant Procedures

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Characteristics and Outcome Assessments

Patient demographics, diagnosis, and injury history including previous treatments for the index ankle were collected. Clinical evaluations included physician’s assessment of healing progression measured by typical patient post-op examination (i.e. wound healing, stability measurements, ROM, swelling, etc). Visual analog scale (VAS) for pain (collected at 2 of 4 participating institutions) was recorded prior to surgery and at 2-, 6-, and 12-week post-surgical visits. Only patients with baseline VAS and VAS at least two follow-up visits were included in VAS analysis. Safety data was assessed by collecting adverse events and complications. While all adverse events were collected, events relating to procedure specific outcomes, including delayed wound healing, wound infection, neuritis, and peri-implant osteolysis were analyzed in greater detail. Complications defined by patients necessitating a return to the operating room were also reported and classified as relating to product, procedure, or neither. Postoperative rehabilitation milestones including non-weight bearing duration, time to physical therapy initiation, total physical therapy duration, and time to transition from boot to brace with ultimate unrestricted full weight bearing (FWB) were analyzed. Given the multi-center study design, the post-operative rehabilitation programs were not standardized across study sites, however, the approach was similar for all sites and the following summary represents an aggregate protocol. From immediate post-operative: non-weight bearing (NWB; 0-4wks), transition to CAM boot with weight bearing as tolerated (WBAT) and transition to PT initiation (2-6wks), transition out of CAM boot to lace-up brace and progression to FWB (6-10 weeks), sport-specific activity initiation (10-12wks) and return to play (RTP; 12+wks). Progression throughout each stage was determined by the physician and collected from the clinical medical records. Identified patients who were at least 1-year post-operative were solicited by phone, and if willing, consented for participation in phone surveys. Ultimately, 46/143 (32.2%) of PUUR patients and 40/83 (48.2%) of MB patients completed the survey which measured residual pain, instability, any additional procedures including revision surgery, quality of life ratings, and overall satisfaction.

Statistical Analysis

All data were recorded in Microsoft Excel (2011, Microsoft Corp., Redmond, WA). The data are presented as frequencies, means, standard errors, ranges, and percentages. All outcomes for the study were defined as the average change in the outcome from baseline. At each timepoint (2-, 6- and 12-weeks post-operative), the mean change from baseline in both groups was evaluated. Where comparisons were possible, scores were analyzed using a student’s t test; a P-value of less than .05 was considered significant. For the comparison of proportions, Chi-square test was used, and a P-value of less than .05 was considered significant.

Results

Patient Characteristics

A total of 226 patients who underwent an MB procedure alone (n=83) or with PUUR augmentation (n=143) were enrolled in the study. There were no differences in patient pre-operative demographics between the two groups (Table 3). Significantly more PUUR patients underwent concomitant procedures at the time of their ATFL repair compared to the MB group (99.3%; 142/143 vs. 80.1%; 67/83; P < .0001). The type and distribution of the most common concomitant procedures between both groups are provided in Table 2. Physician assessment of healing progression was similar between the two groups at the 2-, 6- and 12-week clinical follow-up visits.

Table 3: Patient Demographics.

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VAS

VAS was collected before surgery and at each follow-up visit from patients at 2 of the 4 study sites. Preoperatively, there was no significant difference in pain between groups (MB 6.39, PUUR 5.54, P = 0.08). PUUR augmented patients (n=44) demonstrated significantly lower VAS scores compared to MB alone (n=33) at the 2 (4.68 ± 0.35 vs. 6.26 ±0.37, P< .001), 6 (2.95 ± 0.32 vs. 5.42 ± 0.50, P<.0001) and 12 (2.75 ± 0.26 vs. 4.77 ± 0.41, P<.0001) week post-operative visits (Figure 2). At 6- and 12-week postoperative visits, the mean VAS was significantly reduced compared to baseline in both groups.

Figure 2

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Adverse Events and Complications

Complications: There were 9 reported complications, 3 in the MB group (3.6%) and 6 (4.2%) in the PUUR group (p = 0.83). No complications were reported as product related. There were 2 revisions (2.40%) in the MB group and 1 revision (0.70%) in the PUUR group. The PUUR revision patient sustained a significant ankle repeat injury following a serious fall approximately 1-year post-surgery. This required a revision of the lateral ligament repair with PUUR matrix along with peroneal tenosynovectomy, 1st metatarsal dorsiflexion osteotomy, and ankle arthroscopy with synovectomy. One revision in the MB group occurred 10 days postoperative from reportedly chronic neuropathic pain requiring repeat surgical evaluation with ankle arthroscopic debridement, lateral ankle ligament assessment, and peroneal synovectomy. The second isolated MB group revision was disclosed by the patient in a follow-up call and had occurred outside of the study site of care, requiring anchor removal with soft tissue repair. There were 5 remaining complications in the PUUR group. One patient experienced a deep wound infection requiring irrigation and debridement and antibiotics. Another patient fell down a flight of stairs sustaining a bimalleolar ankle fracture. A separate patient presented with peroneal tendon split tear and underwent peroneal tenolysis. A diabetic patient underwent partial first metatarsal excision, FHL tenolysis and sesamoid excision due to a great toe ulceration. The final patient underwent a tibial osteotomy and open talar osteochondral treatment for a progressive lesion. No cases of implant failure, periimplant fracture, or foreign body reaction were observed. The final complication in the MB group was a patient that required gastrocnemius recession with associated ankle arthrotomy and posterior capsular release.

Adverse Events: Adverse events were collected from all enrolled patients. A total of 53 adverse events (22.1% of patients) occurred. The most common adverse events were delayed wound healing (n = 19 patients)neuritis (n = 7 patients), and superficial wound infection (n = 6 patients). Delayed wound healing occurred in a similar number of patients in both groups (PUUR = 10 vs. MB = 9) and was correlated with a significant increase in BMI (P=.020). Neuritis occurred in 4 MB and 3 PUUR patient. Superficial wound infection did not occur in any MB patients and occurred in 6 PUUR patients, though no deep infection developed. Amongst the remaining [21] additional adverse events, all were classified as either mild or moderate and no adverse events were related to the PUUR device. There were no serious adverse events reported in either group.

Postoperative Rehabilitation: A summary of the major post-operative rehabilitation milestones collected with the number of subjects with evaluable data for each milestone is presented in Table 4. Early PT milestones were similar between groups. Non-weightbearing duration after surgery was similar (PUUR: 4.0 ± 0.1 wks. vs. MB: 3.7 ± 0.2 wks). Similarly, there was no difference in the mean time to physical therapy initiation (PUUR 5.03 ± 0.19 weeks vs. MB 4.96 ± 0.26 weeks); or total physical therapy duration (PUUR 10.1 ± 0.93 weeks vs. MB 11.2 ± 3.2 weeks). However, the time to unrestricted FWB in commercial footwear with or without bracing for patients in the PUUR augmented group was significantly faster compared to MB alone. PUUR augmented patients transitioned to normal footwear an average of 2.4 weeks faster than MB patients (9.04 ± 0.34 wks vs. 11.4 ± 1.79 wks. P = .047).

Table 4: Post-operative Rehabilitation Milestone Summary.

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Patient Survey: In an effort to gain longer term follow up data, best attempts were made to contact all patients that were at least 12 months postoperative to assess residual ankle pain, instability, additional procedures, revisions, quality of life, and overall procedure satisfaction. Patients that provided consent completed the short satisfaction survey. Mean follow-up was 20.8 ± 0.87 months for PUUR patients (n = 46) and 32.5 ± 2.76 months for MB patients (n = 40) (Table 5). Although this is a limited patient response, and clearly does not represent a lost-to-follow up population, this is not surprising given our requests to complete the patient survey were unsolicited and unexpected by these patients. There was a significant difference in both the number of responders (p = 0.02) and length of follow up (p<0.0001) between study groups. Overall, there were no significant differences in answers to survey questions between groups. Patient satisfaction on a ten-point scale with 0 representing not satisfied and 10 representing very satisfied was rated high in both groups (PUUR = 8.5 vs. MB = 8.9; P = .305). Similarly, most patients indicated they would repeat the procedure and would recommend the surgery to a family member. Approximately 50% of patients in both groups reported some degree of occasional pain, though there was no difference in severity between groups. Residual ankle instability was similar across groups (PUUR 26.1% and MB = 20%). A single isolated MB patient reported having a revision surgery outside of the care of a study surgeon.

Table 5: Patient Satisfaction Survey.

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Discussion

This is the first controlled study to assess the safety and clinical efficacy of a PUUR matrix woven textile for ATFL augmentation during modified Broström repair. Pain scores for both groups were significantly decreased from preoperative levels through 12-weeks follow-up (PUUR: 5.5 to 2.35 and MB: 6.4 to 3.29). However, pain in the PUUR group was significantly lower at all follow-up clinical visits (2, 6, 12 weeks) compared to isolated MB group which may be more notable given the greater complexities of the surgical procedures in the augmentation group. The range of patient reported pre-to post-op changes in VAS scores (approximately 6 – 2) over similar time points is consistent with previous publications. In a similar ATFL repair study, Kulwin et al., did not report a comparative decrease in early postoperative pain between patients that underwent MB alone vs. MB patients augmented with suture tape [18]. This discrepancy could be due to differences in study design, surgical procedure, or device used in augmentation. In their report of isolated ATFL repair with augmentation, Xu et al. also reported decreases in pain from pre-surgery in patients undergoing MB with or without suture tape augmentation, but no difference in pain between the 2 groups [19]. A potential benefit of ATFL augmentation is accelerating the postoperative recovery period due to the additional biomechanical support. While there was no difference in NWB duration between MB and PUUR groups, PUUR augmentation led to a statistically significant reduction in time to unrestricted FWB in commercial footwear. As experience with the augmentation device became more evident, the study surgeons began to further expedite the post-operative rehabilitation program with their augmented patients.

There were 2 revisions in the isolated MB group, and 1 in the PUUR augmentation group (2.40% vs 0.70%, respectively). This is similar compared to published results that report revision rates following modified Brostrom procedures at 1.2% [19]. Overall, there were no differences in adverse events between PUUR and MB alone groups. The majority of adverse events noted in both groups were secondary to delayed wound healing (MB = 10% and PUUR = 6.3%). A subgroup analysis demonstrated patients from both groups experiencing delayed wound healing had a significantly higher BMI, which is known to correlate with delayed wound healing [20,21]. All AEs were classified as mild to moderate, and no AEs were considered related to the study device. The safety profile of the PUUR device is similar to that reported by Kelly et al., who reported an overall AE rate of 12.4% (13/105 patients) with PUUR incorporation in various foot and ankle reconstructive procedures. ATFL augmentation during the MB procedure is thought to relieve the injured ligament from excessive stressstrain forces during early to mid-phase healing process. Giza et al. reported PUUR augmented repairs increased ultimate load to failure by 150%, and prevented creep compared to control samples [22]. The resorbable PUUR matrix maintains 90% of its initial strength through the first year of implantation, and then degrades slowly by hydrolysis over a period of up to seven years [23]. In addition to strength, PUUR tensile properties have been demonstrated to alter mechanically driven biological signals and to orchestrate local cell populations during the remodeling process [24] allowing the matrix to promote tissue maturation by promoting cell recruitment, extracellular matrix deposition and angiogenesis [11,25-28].

There are clear limitations within this study given the retrospective nature of the study design. The availability of data was limited to what was present within the medical records both in amount and type (outcome measures) available for collection. In particular, the postoperative rehabilitation evaluation may be confounded by the patients completing therapy at different sites. Despite the constraints of retrospective study designs, the true value is to gather real world evidence of the use of products in everyday clinical practice outside the scope of a rigorously designed protocol that may considerably narrow both practical clinical product application and the participating patient population. A prospective, randomized, controlled trial with validated functional outcome measurements, standardized post-op rehabilitation protocols and lengthier follow-up is ongoing. The results of this study will further enhance the ability to detect any notable differences with augmentation.

Conclusion

This is the first study to directly compare MB with and without PUUR augmentation. PUUR augmentation of the lateral ligamentous complex during ankle instability surgery decreased recovery pain and allowed quicker return to FWB, compared to MB alone. The PUUR matrix was safe with no difference in adverse events compared to a control group. This study shows early results suggesting PUUR augmentation may create the potential to expedite and improve patient outcomes post-operatively compared to modified Broström alone.

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Journal on medical genetics |BJSTR

Medical Support in the Selectively Integrated Returns Intelligent Optimization System – SEIRIOS

Introduction

During the Second Phase of the therapy portfolio selection are required advanced higher moments [2] (ultrakurtosis, hyperultrakurtosis, etc), [3-7], depicting advanced forms of risk. Initially a feasible set of therapeutically combination policies is produced by the evaluated therapy portfolio, resulting to the efficient frontier where the utility function [8-11], is maximized on return under minimal risk, [12-15] expressed as an almost adequate approach of a maximum Sharpe ratio. The paper examines the first step that resolves the second step. I examine 60 Modular networks – MDN- of neural or hybrid neural-genetic combinations: 20 Modular Neural Networks and 40 Hybrid MDNs, of altered topologies to define the optimum classifier for portfolio selection. The paper:

i. Analyses the therapy selection that patients have under further higher moments, in certain returns and risk levels,
ii. Supports further the Isoelastic Utility as a sufficient norm,
iii. Evolves the Therapeutical Portfolio Theory, [16], extracting covered patterns on health fundamentals indices, excluding bias, detecting robust stocks, under Chaotic Entropy of FHR
iv. Investigates the performance of the Modular Networks in hybrid or neural or models, revealing the optimum classification model that fits intense therapy.
v. Utilises the SEIRIOS model on therapeutical portfolio optimisation.

The Entropy of Chaos, [17] in the form of Relative Entropy-TRE produces the Kullback-Leibler Relative Entropy – KLRE – for systems unextensive, on nonlinear, complex systems of long memory. [18-24] evaluated in practice the markets on a KLRE, Tsallis approach.

Systemic Approach

The complicated behavior of patients requires further moments [6,7,12,13,25]:

Robust computing abilities are necessary to the heuristics for the solution process of the non-convex problem. I provide an advanced classifier that detects hidden corporate info, especially hoaxes to support the decision-making process of investors.

Intelligent Computing

The Recurrent and Modular neural and hybrid neuro-genetic networks are comparatively analysed in a variety of classifiers forms.

The Self Organized Features Maps and their Hybrids

The Self Organized Features Maps-SOFM neural net, [26], is optimized for clustering, and data examination. The unsupervised learning trains SOFM producing a 2 Dimensional map. The discretized input surface of training set reduces dimensionality. The SOFM implements competitive learning, whilst the inputs givens as 16 financial indices have an unknown significance in the SOFM nets. In the hybrid forms, Genetic Algorithms-GA [27], were incorporated on the:

i. Inputs layer only,
ii. Inputs and outputs layers only,
iii. All layers,
iv. All layers with cross validation.

The training of each model is extensive to converge to a model of the lowest error. GAs is implemented in different hybrids and the Batch learning method was applied to the SOFM to adjust the weights (Figures 1 & 2).

Figure 1

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Figure 2

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Recurrent Networks and Neural-Genetic Hybrids

The Recurrent Neural Nets -RNN- create a directed cyclical grid in connections of feedback. The RNN have different elaboration than the feedforward systems. RNNs can have chaotic performances. Their ordinal problems are resolved by the Long Short- Term Memory -LSTMapproach [8], in cases of:

i) Temporally extended noisy patterns recognition,
ii) Temporal order in noisy widely separated events recognition,
iii) Temporal distance between events, data extraction,
iv) Smooth & anomalous periodic trajectories, stable generation of precisely timed rhythms,
v) Extended time intervals, robust storage of high-precision real numbers. Genetic Algorithms optimized the RNNs [1,7], on 4 alternative topologies.

The Genetic Algorithms were selected to optimize RNN models, in terms of selecting the inputs, and the performance of neurons. The learning method of On-Line is selected to adjust the Recurrent Hybrids weights, and thus optimize the:

a) Amount of Neurons,
b) Size of Step, and
c) Rate of Momentum, as the output optimised the Momentum and
size of Step in the Gas (Figures 3 & 4).

Figure 3

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Figure 4

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Modular Networks and Neural-Genetic Hybrids

The feedforward Modular – MDN – nets, consist a variation of the Multilayer Perceptrons. The MDNs process inputs in parallel numerous MLPs and recombines the outcomes. The network topology thus forms a structure specialised in the function of each sub-module. From the four MDN topologies, the linear feedforward topology with no bypasses is put in all the models. The MDNs contradicting the MLPs, are lesser interconnected. Thus fewer neurons weights are required for the same size model. Training is boosted with fewer examplars. The optimal operation to provide the MDN topology is fuzzy, feeded by the data, and no reassurance that a module emphasizes the training on a specific part of the data. This paper elaborates 16 Inputs neurons, 1 Output, 706 Exemplars, 4 Upper Neurons without GA into Hidden layers, on the Upper Transfer TanhAxon, Lower Transfer function on the TanhAxon, 4 Lower Neurons, Learning Rule of Momentum, 0.1 Step size, 0.70 Momentums. The learning technique is the Backpropagation, the previous value and a correction term adjusts the weights. Every correction is adjusted by the learning rule. Batch learning technique, 1000 Maximum epochs was the value of the Supervised Learning Control regarding the number of iterations, over the training set to be done by default, the Termination choice is under Minimum MSE below the specified Threshold, in 0.01 threshold, technique of Load best on test. The default Incremental error is significantly less than the Minimum error. The termination on MSE sets the stop criteria on the Cross Validation than the training set. If the MSE of the Cross Validation increases, the model commences overtraining, memorizes the set of training, unable of generalizing the problem (Table 1). Cross validation is used twice in the models on 20 different sets, as an efficient termination of training (Figures 5 & 6).

Table 1: Optimal outcomes of modular, SOFM and recurrent networks overall [14].biomedres-openaccess-journal-bjstr

Figure 5

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Figure 6

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The SEIRIOS Model

Inspired by my models the ORION [12,13,28] the new integrated Selectively Integrated Returns Intelligent Optimisation System – SEIRIOS, initially reads the fundamentals, prices and time, selecting the first classifier of therapy assets, patientss risk profiles, and λ

  • Next SEIRIOS tests the termination criterion of assets and the optimal portfolio is fulfilled.
  • Next uses ChatGPT, GBT4 and BARD to comparatively evaluate the patients sentiments of the past year per asset Next SEIRIOS reads Isi, investors sentiments per stock
  • Else SEIRIOS proceeds in 2 sets: 1 for healthy assets, and 2 for distressed. For ετ =1asset is deleted, else if ετ = 0 then asset healthy
  • Next Ut (Rt (i)) is given
  • Next SEIRIOS evaluates ISi, Ut (Rt (i)) keeping better assets Next, assets are hierarchized on score.
  • Next, assets of highest Sharpe and utility are selected. All other assets are revaluated in new data on step 9
  • Next, the excellent portfolio is produced of maximum UPj ( f ) .
  • The globally optimal health portfolio is U ∗ Pj ( f )

Formulation

Advanced higher moments demonstrated their impact on the model [1,6,7,29], to support a logical reflection of investment patterns and their dynamic behavior. [1,12,13] contributed:

through [1], to manipulation in superior risk. A risky asset works in the Dynamics of Chaos and Stochastic Differential Equation [26]:

where μ the expected asset return, σ the volatility without jumps, J the jump amplitude on asset > −1, random variable.

u = E (J ),{N (t ),t ≥ 0}Poisson process of strength λ , λ udt an average growth by Poisson jump, {W (t ), t ≥ 0} the Brownian motion of probability ({Ft} t ≥ 0, P), {N (t ) , t ≥ 0}and {W (t ), t ≥ 0}independent, [26]. The non-convex problem needs higher computational resources to undergo the heuristics. Inflammatory reaction, false diagnosis, inefficient therapy, hoaxes, require reliable valuation of the firm. The SDE’s (14), solution is [27,30]:

where Pq(Ω,t ) is the maximum Distribution Entropy by Tsallis in Non-extensive statistics. (17) describes the clustering of volatility and long-term memory effect in assets [26]. (11) describes the optimal utility [29,30]. The Kappa distributions can extend its support in the bubbles management (of diagnosis, therapy, inflammation) (Figure 7).

Figure 7

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Data

The data came can be results of medical tests and their desired outcome. In the past the model was tested inv16 financial indexes data of 1411 cases, [30], as the17th index has the classification of executives. The test set was 50% overall, and training 50%. Numerous combinations required to find the optimal MDN and RNN Nets:

i. MDN neural networks
ii. MDN neural nets with Cross Validation
iii. MDN neuro-genetic hybrids with GA on the Inputs only
iv. MDN neuro-genetic hybrids with GA on the Inputs and Ouputs only
v. MDN neuro-genetic hybrids with GA in All Layers
vi. MDN neuro-genetic hybrids with GA in All Layers with Cross Validation
vii. RNN neural networks
viii. RNN neural nets with Cross Validation
ix. RNN neuro-genetic hybrids with GA on the Inputs only
x. RNN neuro-genetic hybrids with GA on the Inputs and Ouputs only
xi. RNN neuro-genetic hybrids with GA in All Layers
xii. RNN neuro-genetic hybrids with GA in All Layers with Cross Validation
xiii. SOFM neural networks
xiv. SOFM neural nets with Cross Validation
xv. SOFM neuro-genetic hybrids with GA on the Inputs only
xvi. SOFM neuro-genetic hybrids with GA on the Inputs and Ouputs only
xvii. SOFM neuro-genetic hybrids with GA in All Layers
xviii. SOFM neuro-genetic hybrids with GA in All Layers with Cross Validation

Results

The Modulars group, [13] MDN Neural Net in 3 layers classified optimally the assets in healthy and distressed: 99.16% and 83.48% respectively, of high fitness of the model to the data in 0.884, the lowest MSE at 0.092, NMSE 0.218 and 4.611%, the AIC was very low at -1230.98 revealing impartiality in a very fast time of 26s as in Table 1. In the Recurrent Networks on the other hand, the optimal performance of the RN Hybrids was in the model of 1 layer with GAs in the inputs only, in high classification rate of the healthy companies at 98.99%, and 96.6% for the distressed, the lowest MSE at 0.038, and 0.0935 in NMSE, the highest fitness of the model into the data 0.986, the AIC had the lowest value at -2062.4 indicating an ideal fitness of the model, similarly for the MDL at -2062.4, at a fast time of 54 minutes and 40seconds, in an over- optimisation hazard. Regarding the SOFMs, the Neural Network of 7 layers had the best results, in mediocre classification, high errors, low fitness, and significant partiality, (Table 1) [31,32].

Concluding Remarks

The Hybrid Recurrent networks of 1hidden layers and Genetics on the input layer only, had superior classification and performance in a fast processing time, the Recurrent Neural Net, ranked second overall in a good performance and a very fast time. The Modular and SOFM networks underperformed significantly and shouldn’t be considered as a classifier potential to an health portfolio optimiser system such as the SEIRIOS.

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List of open access medical journal |BJSTR

Understanding Nursing Retention: A Study on Nurses’ Perceptions Towards Work Efficiency, Workload, and Burnout

Introduction

According to the International Council of Nurses (ICN), the global shortage of nurses is a crisis that continues to adversely impact healthcare (International Council of Nurses Policy Brief, [1]). Reasons include the long working hours, wages that are below expectation, ageing populations, and most recently, the global pandemic which has diverted nurses away from their usual tasks. Having a sufficient nurse to patient ratio not only has many clinical and economic advantages in patient care (Simpson, et al. [2]), it is also essential in the running of a world class medical institution. The demand on healthcare systems has increased drastically in the past year (International Council of Nurses Policy Brief, [1]), but countries have not been able to meet the increasing needs with a corresponding increase in the nursing workforce (International Council of Nurses Policy Brief, [1]). In the first half of 2021 alone, 500 foreign doctors and nurses have resigned in Singapore, compared with 500 in the whole of 2020 and 600 in 2019 (Tan [3]). An extrapolation of the numbers results in a rough attrition rate of 8% for this group of healthcare workers (MOH [4]). A multitude of factors have contributed to this high attrition rate. Firstly, the increased working hours.

It has been over 20 months of continuous daily battles against the pandemic, and not only have a large majority of healthcare workers been unable to take leave since it started, over 90 percent of them will also not be able to clear their accumulated leave (Tan [3]). Additionally, monthly working hours are high, ranging from 160-175 hours per month (Tan [3]). This, coupled with inefficient work processes have increased the workload and stress that hospital nurses face (Hendrich [5]). These same factors are also associated with burnout, (Lin, et al. [6]) which in turn hampers the efforts made to recruit and retain nurses. Ultimately, this negatively affects nurse staffing and patient outcomes (Garcia, et al. [5,7]). Understanding the root cause of high turnover rate related workload would help to retain nurses in hospitals, which can in turn lower the turnover rate. The purpose of this study is to explore nurses’ perceptions towards work efficiency, workload, and burnout in a hospital setting to gain more understanding of their views in enhancing nurses’ retention in hospitals.

Methods

Design and Setting

A quantifying descriptive qualitative method with open-ended questions was used for this study. The demographic data and open-ended survey were developed according to the Grant, et al. [8] study. The survey was used to explore their working environment, perceptions towards their workload, and suggestions regarding work issues. The study was conducted at Ng Teng Fong General Hospital (NTFGH), an acute care hospital in Singapore.

Sample and Survey

Convenient sampling was adopted in this study. The eligible criteria were enrolled or staff nurses who had a minimum of two years of working experience in NTFGH. There were 80 nurses who completed the survey, but only 57 nurses who met the criteria, and were selected for the study. The survey included four sections;

1) Demographic data,
2) Job scope aspects that were inefficient,
3) Factors that cause nurses to burnout, and
4) What can be done to improve nurses’ working experience.

Data Collection and Ethical Considerations

Ethics approval from NUS-IRB was granted before data collection. Permission for the administration of the survey was obtained from the nurse administrators. The invitation flyer and email with the online weblink were then sent out to eligible participants. The participants filled out the survey online and it took 3 weeks for data collection.

Data Analysis

The data was exported into an excel file, before the demographic and quantitative data were imported into SPSS (version 26). Descriptive analysis was used to describe the participants’ characteristics. The content analysis method was used to identify the significant statements and key words. Lastly, qualification of the similar qualitative method was used to quantify the qualitative data and range the most common concepts/codes.

Results

Characteristics of Participants

The participants’ profiles are presented in Table 1. Majority of the participants were female (86.0%). Three quarters of the participants (75.5%) were Staff Nurses, and the remaining one quarter (24.5%) were Enrolled Nurses. The mean age is 32.23 years old. On average the nurses worked for 9.28 years as a nurse, and 6.32 years in this hospital. They worked on average 41.83 hours a week and all the nurses work overtime at least 1 day of the week. Majority of the nurses worked at the inpatient department (96.5%). The nurses self-reported an average score of 3.09, 2.70 and 3.26 out of 5 for feeling overworked, satisfied, and burnt out respectively. When ranking the different aspects, majority of nurses (n=40, 70.2%) felt that patient care could be made more efficient. Coordinating the care of patients, communication, and answering/making phone calls were the subsequent aspects that nurses felt could be made more efficient. Preparing/clearing requisites was least able (n=11, 19.3%) to be made more efficient by nurses. Similarly, majority of nurses (n=37, 64.9%) felt that patient care burned them out the most. Answering/ making phone calls, coordinating the care of patients, and communication were the next few variables that nurses felt burned them out the most. Likewise, preparing/clearing requisites was the task that least (n=7, 12.3%) burns them out. Table 2 presents the ranking of job scope aspects that can be made more efficient, and factors that impact nurses’ burnout.

Table 1: Demographics of Nursing Population (N = 57).

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Table 2: Aspect of job scope that can be made more efficient, and factors impacting nurses’ burnout.

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Nurses’ Perception and Experiences Regarding Work Related Issues

Work Efficiency: The results showed that the participants perceived manpower shortage (n=10, 22.7%) as the main factor that impacted their work efficiency. Tasks which take time away from patient care, (n=9, 20.5%) as well as miscommunication (n=7, 15.9%) were the next two perceived causes of work inefficiency. The nurses suggested increasing manpower (n=18, 34.0%) and having dedicated staff (n=17, 32.1%) in the areas of administration, discharge planning and care appointment, transportation, serving meals, and making calls. Better communication between healthcare teams (n=7, 13.2%) was also suggested.

Burnout: High workload (n=20, 14.9%), manpower shortage (n=14, 20.9%), and unreasonable demands from patients and family (n=10, 14.9%) were listed as the three main causes of burnout. The nurses suggested increasing manpower (n=26, 53.1%) , increasing and enforcing rest (n=7, 14.3%), as well as re-examining workflows (n=4, 8.2%) to be helpful for reducing burnout. Workload: Suggestions on better workload management besides hiring more manpower included better teamwork (n=11, 23.9%), reduced job scope (n=10, 21.7%), as well as a better work life balance (n=5, 10.9%).

Time Spent: Nurses wished to spend less time on documentation (n=12, 32.7%), answering phone calls (n=7, 18.9%), and communication with patient’s family (13.5%), while a large majority of them wished to spend more time on patient care (n=37, 74.0%) and selfcare (n=9, 18.0%).

Accomplishment: Completing daily tasks (n=15, 22.7%), ending work on time (n=14, 21.2%), and patient recovery (n=9, 13.6%) were the three main reasons for nurses to feel accomplished at the end of the day. A comfortable working environment (n=10, 20.0%), good colleagues (n=9, 18.0%), and salary (n=8, 16.0%) were influencing factors for nurses to stay at their job. Table 3 presents nurses’ perceptions and suggestions on work related issues.

Table 3: Nurses’ perception and suggestion on work related issues.

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Discussion and Nursing Implications

In this study, we explored nurses’ perceptions towards work efficiency, workload, and burnout issues.

Work Efficiency

The results showed that the top three main inefficiencies were attributed to a manpower shortage, tasks which take time away from patient care, and miscommunication between healthcare professionals. The problem of a nursing shortage in Singapore is not new (Chua [9]) and the COVID-19 pandemic has only accentuated it (Chia [10]). Manpower shortage made many nurses experience burnout amidst other issues such as a lack of recognition and protection against abuse (Yip, et al. [11]). With insufficient supply to meet the demands in hospitals, it is unsurprising that there are work inefficiencies. The logical solution that was suggested by those surveyed was to hire more nurses. Despite the demand for nurses, these vacancies are still not filled due to the hardships of the job and the reduced influx of foreign nurses (Begum [12]). Thus, the root of the problem that needs to be tackled is how to improve nurses’ working conditions to make the job more desirable. The nurses surveyed also reported that they were often preoccupied by non-patient care centred tasks such as documentation, transportation of patients, and answering calls. The nature of these tasks dictates that nurses spend a significant amount of time away from essential patient care (Yen, et al. [13]) and thus they feel it is inefficient.

To address this, those surveyed suggested hiring dedicated staff to handle these tasks. This would free up nurses for tasks that make better use of their skill sets (Goh [14]). Lastly, the nurses surveyed attributed a significant amount of inefficiencies to miscommunication between healthcare professionals, particularly with doctors. Miscommunication leads to, in the best case, time wasted, and in the worst case, medical errors that severely affect patients (Tjia, et al. [15]). Those surveyed suggested improving the communication framework between healthcare professionals (Matziou, et al. [16]) as this would improve relations between nurses and doctors, and ultimately increase the level of patient care.

Burnout

The study found that the most pressing factors impacting burnout were the high workload, a manpower shortage, and unreasonable demands from patients and their family. The top two factors of a high workload and a manpower shortage are closely related. Nurses surveyed commented that the volume of work that had to be done greatly exceeded the current nurse staffing levels. They remarked that there were “too many things to do at the same time” and that “they cannot possibly be everywhere at once”. These result in insufficient rest, and a long-term high-stress environment which drastically increases burnout rates among nurses (Tan, et al. [17]). Nurses also often faced unreasonable demands and abuse from patients and their families, and this was worsened during the COVID-19 pandemic when nurses had a higher workload. Abuse can come in both the physical and verbal forms and can result in nurses being psychologically traumatised and emotionally drained (Chua [18]). To tackle these issues, the nurses surveyed suggested once again increasing manpower, increasing and enforcing rest times, as well as re-examining workflows. As mentioned previously, increasing manpower is a complex process, and the root of the problem should be targeted instead (Begum [12]). The nurses highlighted that rest should be increased and enforced, and this was related to their other suggestion of workflows having to be re-examined. They identified poor scheduling of staff which caused many nurses to have to be called back to work on their designated rest days, thus decreasing much needed rest and relaxation, and increasing the incidence of burnout. Having sufficient time to rest and relax is essential in preventing burnout (Demerouti [19]), and thus this offers an alternative to help nurses while manpower shortages cannot be adequately dealt with.

Workload

Our study found that nurses perceived their workload to be high, which was closely related to the manpower shortage and burnout they face. The majority of nurses in the study felt that better teamwork would help better manage their workload while hiring more manpower remains challenging. The finding was in congruence with studies (Yanchus, et al. [20,21]) that have addressed how good teamwork is an antidote to high workload and inadequate staffing. Benefits of effective teamwork include improved coordination of care, efficient use of healthcare services and enhanced communication (Babiker, et al. [22]). Nurse leaders can benefit from these findings by recognizing the importance of creating a work environment that promotes collaboration and teamwork among nurses, and the multidisciplinary team they work with (Nutter [21]). In particular, good communication, trust and mutual respect, and accountability are aspects that would aid in the development of a more effective team (Yanchus, et al. [20]). Creating such an environment would enhance the quality of healthcare, improve patient safety, and better engage nurses who want to remain part of a thriving unit (Nutter, [21)).

However, a significant number of nurses felt that better work-life balance, a reduced job scope, and increasing manpower were still the best way forward in managing their workload. This suggests that while increasing teamwork among nurses may be a promising strategy, it is equally imperative to investigate and adjust nurses’ workloads accordingly to safeguard them from possible fatigue (Cho, et al. [23]).

Time Spent

Documentation was the most frequently mentioned task that the nurses wished to spend less time on. Various literature has attributed this to firstly, documentation compromising on patient care (Momenipour, et al. 2019). This is in line with our findings where 65% of the nurses wished to spend more time on patient care instead. Secondly, the perception that the amount of time spent on documentation is disproportionately high (Momenipour, et al. 2019). Lastly, concerns regarding the amount of time invested into documentation in proportion to its utility (Momenipour, et al. 2019). An observational study (Lim, et al. [24]) has shown significantly less time was spent on patient care activities, but more time on documentation by nurses. It has been suggested that efforts should be made to look into how time spent on documentation can be reduced, such as eliminating duplicate documentation so that nurses can devote more time to patient care (Lim, et al. [24]).

Based on our findings, more than three-quarters of the nurses wanted to spend more time on patient care, but they were overwhelmed by other aspects of their job. Being overwhelmed by aspects of their work that are unrelated to patient care can lead to emotional exhaustion and burnout, hence contributing to lower effectiveness (Dyrbye [25]).

Emotional exhaustion can also damage the hospital’s and nursing staff’s reputation from the patient’s point of view (Aiken [26]). While being able to help others was the top reason for students choosing to undertake a nursing degree (Wilkes, et al. [27]), the inability to perform up to their personal expectation could lead to burnout and decreased job satisfaction (Dyrbye [25]). It is important for nursing managers and hospital administrators to adjust the workload of non-patient care items and allow nurses to devote more time to patient care. Self-care was the second most mentioned item that nurses wanted to spend more time on. With Singapore already facing a nursing shortage (Chua [9]) before the COVID-19 pandemic, the nursing manpower shortage was felt even more acutely during the pandemic, further straining the already stretched nursing resources (Chia [10]). Several new initiatives to support the mental well-being of nurses were then launched, which included mental wellness training, selfcare and research programmes, online chat bots, peer-support networks, and counselling services (MOH [4]). However, for nurses that mentioned self-care, they wanted enforcement of sufficient break times and mandatory rest days. Hence, it is instrumental to support the mental well-being of nurses, and this includes sufficient break times and mandatory rest days as well.

Accomplishment

Based on our results, completing daily tasks was the greatest self-reported factor for feeling a sense of accomplishment, followed by ending work on time, and subsequently patient recovery. Completing daily tasks has been linked to personal accomplishment, and it has an effect on the well-being of an individual (Donaldson [28]). A sense of accomplishment has an effect on the reward system pathway in the body, and tasks with intermediate difficulty induces the greatest sense of achievement (Nakai [29]). This result may be of interest to nurse managers and hospital administrators in understanding the perspective and mindset of their nurses. Understanding and creating a manageable set of daily tasks would be critical in defining the nurses’ perception of their ability, as well as promoting a sense of accomplishment. Ending work on time was the second most self-reported factor for accomplishment. We postulate that this could be due to the intense workload the nurses face on a daily basis. Moreover, all the surveyed nurses reported working overtime weekly. Several possible reasons for working overtime include pressure to conform, a high workload, enhancing self-development (Watanabe [30]), and extra overtime income (Stimpfe [31]). Working overtime involuntarily demonstrated a detrimental effect on mental health and work engagement at both the ward and personal level (Watanabe [30,31]). Nursing managers and hospital administrators could take extra steps to investigate this issue.

Influencing Factor to Stay

The greatest factors for nurses staying on in the hospital were a comfortable working environment, followed by good colleagues, and the salary. Having a comfortable working environment is essential for the psychological health of nurses, and the work environment is a significant factor for the retention of nurses (Wei [32]). Research has shown that a comfortable working environment provides nurses with perceptions of autonomy, control over their practice, good nurse-physician relationships, as well as organisational support (Cortelyou-Ward [33]). Nursing managers and hospital administrators could take into consideration how nurses are coping with their working environment and colleagues on a regular basis. Retention rates for newly graduated nurses were significantly higher in working environments that were rated healthy or very healthy compared to working environments that needed improvement (Kramer [34]). Quarterly review of the nurses’ working environment could be implemented to promote a comfortable working environment as well as improve the retention of nurses [35-39].

Limitations

Our study consisted of nurses from one hospital and might not be representative of the situation at other hospitals in Singapore. Only enrolled and staff nurses were involved in this study while other healthcare professionals were not accounted for.

Conclusion

Patient care is at the heart of nursing but the high workload, manpower shortage and workplace inefficiency have contributed to burnout and less time spent on patient care. Nursing managers and hospital administrators must examine what influences nurses to stay, and what gives them a sense of accomplishment in order to retain nurses. Developing retention strategies and interventions, along with examining their effectiveness, are highly recommended for future research.

Author Contributions

• Study design: CWY, SJY, YJH, LME, YK
• Data collection: CWY, SJY, YJH, LME
• Data analysis: CWY, SJY, YJH
• Manuscript writing: CWY, SJY, YJH, YK
• Critical revisions for important intellectual content: YK
• CWY, SJY, YJH contributed equally in the process of this research study.

Conflict of Interest

The authors have declared no conflict of interest.

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Years with Mr. Liewe S. Anema: Personal and Profession

Introduction

The development of an institution or one’s career is usually inseparable from the contribution of other parties both individually and in collaboration through their significant roles, both in formal and informal positions, with strong or weak significance depending on the aspects evaluated and the point of view, as well as the preferences of the evaluating party. One example, in my opinion, the development of Pattimura University in the era of the 1980s, was significantly colored by the contribution of Prof. Dr. Ir. Jan L. Nanere, MSc., of course by utilizing the current development of the Indonesian nation through national and international cooperation programs at that time. The firmness of character, vision and management in his position as Rector provides development opportunities, including physical infrastructure, human resources and the quality of learning as well as the intensity of international cooperation [1] Important scientific figures who worked in Maluku such as the German ‘Blind scientist from Ambon’, Rumphius who left not only legacies but fundamental works such as the Herbarium Amboinense neatly stored in the library of rumphius, Catholic Church in Ambon; A. R. Walles, the ‘father of biogeography’ who laid the imaginary line of Wallacea and co-discoverer (Charles Darwin), the Theorist of Evolution, and author of scientific papers including the book “Malay Archipelago” [2] is an example of a great world figure who built a scientific foundation and inspired world scientists, Indonesia Maluku generation to this day [3,4].

It is recorded that A. R. Wallece in the course of his research was supported by a teenage assistant, Ali from Borneo, who collected about 5000 from Wallace’s bird specimen collection of about eight thousand [5,6]. Shaking Mr. Anem’s hand as an official sign of the collaboration of guidance and learning, witnessed by the Dean of the Faculty of Agriculture in the Dean’s Office around 1985 turned out not only to be a work contract for the completion of undergraduate one, it seemed to be a lifetime. Armed with the latest agricultural science in its field, especially Genetics and Plant Breeding as a graduate of Wageningen University and Research in the conditions of the Faculty at that time was something that was rarely obtaially and institutionally. On a certain scale, Mr. Anema is involved in the learning level both as a mentor, then as a colleague, a friend who helps in many things and a collaborator in solving various problems. This paper intends to briefly record various events that occurred in the development of education and the author’s work in relation to the various roles carried out by Mr. Anema in the course of time. It is intended that it may be a note left as a brief report on the task of carrying out cooperation mandated by the institution. It may also be a point of view of understanding the dynamics and development of institutions and human resources in the period 1980-1990s. It may also be a distraction reading for the current and future generations of Moluccan learners from which certain lessons can be taken.

Methodology

This manuscript was developed from the author’s personal experience, bringing back various events that occurred over the years involving Mr. Anema both directly and indirectly. It is entirely the experience and opinion of the author without confirming or asking for Mr. Anem’s approval even though in some cases asking for help or listening to his words. The rest of the study or literature review is also part of the method of preparing manuscripts in addition to various documentation of images that recall the events that followed. A large number of related publications completed by the author, submitted in the bibliography as evidence of the execution and completion of the assigned work. Most libraries are published in open access journals and thus can be searched on the websites of related journals including the institutions mentioned in the manuscript.

Results and Discussion

Uraul Village (Lord Anema)

Among the houses with sago leaf roofs, right at the corner of the turn of the road of Uraul village, kilo Mater 4 Seram Island stands a concrete house not too big with the side of the triangle of the house facing the road, on the triangle of the whitewashed house it is written in large letters “WALANG TUAN ANEMA”. The residence of Mr. Liewe Sibrano Anema with his wife Mrs. Willy Anema with his adopted daughter Oriza Sativa Anema, then raised the son of a baby boy, Sibrano Anema, for many years served as Sending from the Netherlands including building the Uraul State Church. Thus Uraul became the Village of Origin of Mr. Anema in Indonesia, here he is known and respected. In family events he was invited and involved in it. People knew him and he understood the customs, customs and even habits that became funny. One of his favorite dishes while still active was a little clear sopi (a special term “plain water”) eaten with celeng (wild boar). One of his great works, the construction of the Church, was completed and inaugurated when I was still a student under Mr. Anema’s guidance, I was ordered to bring a trumpet musical instrument from the Batu gantung flute group, stay at his place and participate in ordaining the new Church by blowing trumpets with the Uraul flute group which all used bamboo musical instruments.

This church was later damaged during the Ambon riots, 1999… and then he woke up again. The story of Mr. Anem’s discipline was also revealed in this village where he once left Sunday worship because he waited too long for the pastor who was late to come to lead the service. One time Mr. Anema and I enjoyed Late coffee at a small shop around the Sanur area of Bali. Due to being a customer, Mr. Anema often talks to his shop keeper. The shopkeeper used English and occasionally turned to me looking for the English equivalent for a particular word to say, I said just say it because he mastered Indonesian very fluently. One time the kaffe guard asked “where are you from?, Mr. Anema immediately wanted to answer but I preceded, “I am from Ambon”: I said, “if this ontua (the Old men) is from Seram, he is a Seram Man but long in Holland” (I mean to explain why he is White, big tall). Mr. Anema saw that I was about to get angry but then laughed. Then he made me a bit wrong when I was together at Starbucks coffee complex beach walk Kuta Beach. When queuing to order a coffee latte, the waiter asks for a name to be called after the coffee is finished, I usually give the name pak sam, but before speaking, Mr. Anema first replied “just say Jokowi” (maybe because I often wear a white shirt with long sleeves that are slightly rolled up when the body is slim). When it was my turn to receive the order, the waiter shouted rather loudly “Jokowi”, I was surprised and then grumbled at Mr. Anema for giving Jokowi his name (hm hm hopefully does not diminish respect for President Jokowi).

Cursory Introduction

Around the mid-70s our younger brother, my adopted/foster brother, the fourth Andre (deceased), entered the Rehoboth kindergarten located around the hanging stone Rehoboth Church, Ambon. Our mother (my adoptive/foster mother) Yul’s mother who always shuttled Andre often told me about Andre’s white Dutch school friend who with his parents lived in a complex of education and theological housing, the small field area. That was when I first learned of a group of sending among the Moluccan community. One of the Sending was later discovered by me to be Mr. Liewe Anema and his family. Mr. Anema’s duty as Sending was only later discovered by me through a photo caption written by the late Rev. Jack Ospara, Chairman of the GPM Foundation for People with Disabilities, a former Member of the House of Representatives of the Republic of Indonesia representative of Maluku, a colleague of Mr. Anema. Furthermore, around the mid-early 80s when I was just studying at the Faculty of Agriculture, Pattimura University, I was invited by Ir. Toby Huwae, a lecturer in the Department of Forestry, to become a member of the Batu Gantung Flute / Trumpet blowing group which every week serves “hymns and introductory songs to the congregation”, at Rehoboth Church. We were given a schedule of serving twice a week (morning and evening services) sometimes three times during ecclesiastical holidays. By the Jama’at assembly, a list of our service schedules for a certain period of time is given and hymns that will be sung by the congregation (accompanied by the blowing of the Flute / Trumpet) are delivered by the church kostor to our trainer Mr. Acil Huwae (ganemo village) for training. Every Saturday night, the congregation’s costumer will deliver a list of hymns or if not delivered sometimes the flute loper (Om Uta, inner hanging stone) is asked to pick up the song list. From the sitting position of the flute group on the back balcony, I could observe a group of white people sitting in the front row of congregational seats, among them Mr. Liewe Anema.

Formal Introduction

In the mid-80s I completed all the credits of courses required at the faculty of agriculture. The Semester Credit System (SKS) which was recently implemented at that time allows students who diligently complete all lecture requirements and may be completed within 4 years because students in even or odd semesters who complete lectures with an Achievement Index above 3.0 can offer up to 24 credits (one course is given a credit score of 2 or 3 credits depending on the workload given, namely theory and practicum), and allowed to offer points in even or odd semesters above. As a result, a student can obtain a bachelor’s degree in a short time and continue his studies at a higher level of S2 and S3 at a young age. At the same time, a drop out (DO) provision is also applied for students who do not meet the lowest cumulative achievement index applied, which will negate the term Abadi student held by some senior students because they have more “Demo” than Study. Around that time period, the thought of Normalization of Campus Life (NKK) saw campus people as the Tri Civitas Academica with the core of lecturers, employees and students as a unit of campus development initiated and implemented by the Minister of Education and Culture of the Republic of Indonesia, Dr. Daud Yusuf. Students are not separate parties who pay and gain knowledge on the campus developed by lecturers and administrative employees but are an inseparable part and need to return and develop the campus. In later developments in the conception of Alma Mater Insight, the unity of the Academic Community was expanded to four units with the addition of Alumni to the suit of Prof. Dr. Nugrorho Notosusanto as Minister of Education and Culture.

Completing the theory in a short time, I along with 3 other colleagues were recruited to work with (Prof.) Dr. P. M. Sitaniapessy, MSi (familiarly called Pak Pe – Peter) who just completed a Doctoral program at Bogor Agricultural University (IPB). Pak Pe who is an expert in Agroclimatology / Agrometeorology initiated the idea of determining the planting season in the Maluku region through analysis of regional climate data and divided into four students according to the district at that time; Ambon City, Central Maluku, North Maluku and Southeast Maluku, I went to Central Maluku [7]. In principle, determining the growing season is done by analyzing mainly rainfall data (and temperature) over the last 20 years, studying the amount and pattern of rainfall distribution, whether unimodal or bimodal, the distribution of wet months, dry months per year on the one hand; then study the physiological conditions of plants, especially the distribution of plant water needs in their development stadia for plants or plants that are the object of research or dominant in the study area, on the other hand; Furthermore, study the incidence or coincidence between the date / month / period of rainfall conditions and plant water requirements in plant development stadia. We immediately completed our research proposal and submitted it to Mr. Pe as a supervisor. In this research will only be needed data analysis without having to do field research and thus it will not take long and guided by an expert who is respected in his field and thus the completion of the study will be shorter and the ambition of obtaining cumlaude predicate will be achieved. The problems faced at that time included first, the recording of climate element data was only carried out on climatological stations, secondly there were only a few climatological stations in Maluku and generally only in areas near the provincial capital, third, the recording of climate element data was uncertain whether the span of the last 20 years or only a few years according to the length of time the station was established, fourth, whether the procedure for obtaining data on the climate element in question will be simple or convoluted through complex institutional procedures; Unlike today where climate element data can be obtained directly on a person’s cellphone personally and permanently, accurately and on a daily basis.

During the waiting period to get the data that had been requested by the supervisor through the Faculty, I was called to the Dean of the Faculty of Agriculture at that time, Ir. J. J. Tuhumury MS. When I arrived at the office of the Dean of the Faculty of Agriculture, on the third floor of the old building left by the Russian-made Ambon Institute of Technology (ITA), there was already a European, tall and burly, I raised my head up to meet him. The Dean introduced Mr. Anema and said that he is a guest scientist from the Netherlands who will work in the field of plant breeding and I will be guided by him in the field of plant breeding. Mr. Anema reached out to me, his big hand tightly squeezed my hand that was immersed in it, and officially my personal and professional journey with Mr. Anema began. When we last met, we promised to enjoy a bottle of beer at Legian beach then continue to have dinner at a Greek restaurant. While waiting for the vehicle that would take Mr. Anema to his inn, I realized that I was almost the same height as him. Had asked the size of the height of Mr. Anema first, it turned out to reach more than 1.9 meters. I still need to say goodbye to the old supervisor Prof. Dr. Ir. P. M. Sitaniapessy, MSi, Mr. Pe’s message; “If you feel there is a big opportunity with Mr. Anema, just continue”.

Dynamics of Higher Education Development of Pattimura University

The development of universities in Indonesia in the decade of the 80s – 90s occurred a lot through international cooperation. Development projects with grants and loans for foreign and domestic studies are offered by various countries; USA, Germany, UK, Belgium, Australia and others. as well as other development projects including workshops, domestic courses utilizing major universities including IPB, UGM and others. Eastern Indonesian Universities as they lagged behind in various aspects of the development in comparison to that of Central and Western Indonesia. University groups considered less developed including Pattimura, Ratulangi, Cendrawasi, Hauleu Universities were given special attention to development programs. During this period of time, Indonesia Canada cooperation through the Canadian International Development Agency (CIDA) provides scholarships for staff who meet the requirements for S2 and S3 scholarships in Canada, workshops/courses/training/seminars for short-term staff development in basic sciences in the fields of physics, biology, mathematics, biodiversity etc. The largest part of CIDA’s training output, especially in English, continues their S2 and S3 education in Canada, Australia, Belgium, the United Kingdom and others. An intensive and extensive collaboration project presents project leaders from Canada to have residency in Ambon, Maluku, including the last Dr. Jan Kwack and Wife, to directly manage the cooperation project with a counterparty institution from Pattimura University, Indonesia.

Cooperation with the United States (USA) presents the Tuber development project “Underexploited Tuberous crops Yams and Aroids” in collaboration with Pattimura University and the United States Agency for International Development” (USAID). This project successfully surveyed, mapped, documented the distribution of potential Moluccan tubers, collected in collection gardens and tissue cultures of more than a hundred different cultivars from various regions of the Moluccan islands, conducted field research; agronomist, taxonomy, breeding, chemical content analysis to plant tissue culture and producing new scholars/graduates at the Faculty of Agriculture Unpatti. The collaboration with the Netherlands presents the LTA72 project which successfully maps, describes the climate distribution of small islands in Maluku, about nine climate regions, allowing wider use in agriculture and other fields. The presence of guest scientists directly handles the learning and development of the Faculty as Mr. Anema is certainly part of cooperation with the Netherlands. In this context, recognition also needs to be given to leadership at both the University and Faculty levels and the synergy built between them other than the Indonesian government at the center of power.

Start a Task

After getting the Dean’s endorsement, Mr. Anema was immediately involved as a lecturer at the Faculty of Agriculture. Fluent in Indonesian, he handled the Genetics lecture offered in semester 4 and attended by a number of enthusiastic students (generally mahasiswi). Of course, it is not an easy material to help with the diktats written by Mr. Anema plus a number of textbooks that are freely available to students, even for me who has completed all the credits offered at the Faculty of Agriculture. The material presented by Mr. Anema was mostly related to molecular genetics (basic material and structure of DNA, protein synthesis and related material), a branch of genetics that at that time was only intensively developing in the world and was still unfamiliar to the Faculty of Agriculture whose material was not clearly structured. Despite a number of initial challenges, Mr. Anem’s work can be seen from the academic display of his students at the end of their studies and career development in the future. He continues to build contacts and follow the development of his students, even knowing where they are in various regions in Indonesia. One of a number of early graduates and researchers under Mr. Anema’s guidance, Dr. Ir. Helen Hetharia (deceased) was recruited as staff and continued her S2 and S3 at IPB Bogor after conducting plant breeding training at the University of Pajajaran Bandung on the contact of Mr. Anema. At the request of Mr. Anema we had the opportunity to visit Mrs. Dr. Helen to express our condolences despite several years of death. Genetics can be said to be a vast scientific area.

In its division or teaching can be in the form of Mendelian genetics (Mendelian Genetics) which discusses the regularity of segregation and the free separation of genetic material in the derivation of genetic traits of organisms which is Mendel’s Law, from its discoverer Gregor Mendel, the father of Modern Genetics, including the history of the discovery and further development of Mendel’s law and its implications. Mendel’s laws underlie changes in plant breeding limits and practices, particularly in self-pollinating plants. Second, Genetics of cells or (cytogenetics) discusses among others organelle cells and the various functions they carry including cell division, mitosis and miosis, which in principle proves Mendel’s laws of segregation and free separation, mutations in chromosomes and so on, Population Genetics is related to the Law of Permanence / balance of allele frequencies and genotypes in populations, better known as the Hardy-Weinberg Law with all the necessary requirements. Fourth, quantitative genetics reviews the variation of visible traits (phenotypes) as a result of polygene expression and environmental factors. Quantitative characters of continuum nature are different from qualititative characters that are discrete, plus genetics in prokaryotic organisms (unicellular, without nuclear membrane). Teaching a number of areas of genetics, each of which is quite broad in its discussion, requires separation in courses or teaching staff. Mr. Anema chose to teach the latest part of genetics while still practicing other parts.

Accompanying Mr. Anema I got the responsibility of student practicum, in addition to concentrating on thesis research. There was quite a fierce discussion at the first meeting of field planting practicum material related to the preparation of planting beds. The beds instructed to students felt right, taking the length and width according to the planting distance from the plants to be planted by taking into account the number of rows of plants and taking half the size of the planting distance from each side of the length and width. The height of the beds is made according to the plants to be planted, tubers are usually higher than vegetables, for example. Mr. Anema questioned the edges of clean and neat beds, according to him, the sides should be left with grass or hardened so that the beds do not collapse easily when hit by heavy rainfall, while in our experience, the beds will decrease in height or in extreme conditions the plants can be somewhat submerged but not to the extent of damaging the plants.

On the next field visit we followed Mr. Anem’s direction by giving a little restraint on the side of the bed, he again protested asking for adjustment to the practice that had been done. In further developments, the practice of plant genetics is related to the observation of plant flowering, emasculation and crossing in peanut flowers, preparation of chromosomal dye sats (Aceto Orcein), introduction of microscopes and enlargement of ocular and objective lenses, observation of mitosis in onion and root plants using the squash / Okada method, counting the segregation of one gene (dominant, recessive) and two genes (epistasis) according to Mendel’s Law, Mendel’s reverse proof of Law (segregation) using simulation data (FMIPA IPB Bogor) and several others.

Some Journeys Introduction to the Working Area

At the beginning of our work, we often traveled to Jakarta and various places in Java visiting agricultural centers and institutions and universities for various purposes, including, observing the collection of fruit plants, buying and repairing laboratory fittings and electronic equipment in Jakarta, buying/collecting literature, visiting the Indonesian- Dutch cooperation project of vegetable/legume breeding in Subang and Sukamandi, location and center of rice breeding Bogor and IPB Bogor, discussing with Prof. G. A. Wattimena MSc. Occasionally I was asked to make a record of activities and trips as a report. In Jakarta we usually stay at the PGI (Indonesian Church Association) Guest House located on Jalan Teuku Umar where Mr. Anema will meet or have an event with his and his foreign colleagues. On the way to Jakarta, usually Mr. Anema will first with his family leave to fulfill their activity schedule and I follow by passenger ship (cruise about 5 days Ambon-Jakarta) with an appointment to meet at the port. As a student just starting to travel out of the area, boat trips are often thrilling due to the uncertainty of encounters or the possibility of getting lost in a crowded port. Fortunately, Mr. Anema who is white and tall, surpassing almost any visitor will be easy to see and find in the crowded crowd of passengers and pick-ups.

Preparation of Plant Breeding Study Program Development

The presence of Mr. Anema coincided with the newly formed interest in plant breeding at the Faculty of Agriculture. Although the level of interest is not known/recogized in the level (structure) of Faculty administrative management (according to government regulations), interests are usually formed according to the vision of Faculty development and adjusted to available resources and dynamics of knowledge development. Interest as the forerunner of the formation of the study program prepares factually to then be further proposed for the ratification / official establishment of the study program by the Ministry of Education and Higher Education. The head of interest or precisely the coordinator of the Interest in Genetics/Plant Breeding at that time Dr. Martin J. Tutupay, MS (Pak Butje), completed his S2 in conventional plant breeding at Gajah Mada University then continued his S3 at IPB Bogor with the affiliation of Wageningen University and Research of the Netherlands, with direction from Prof. Em. Ir. G. A. Wattimena, MSc. PhD, from IPB Bogor and a little help from Mr. L. S. Anema. Mr. Butje is working hard to attract students to choose the interest of Genetics and Plant Breeding, it is hoped that later adequate staff recruitment can be carried out.

I was part of delivering a presentation of breeding interest, competing with Agronomy Interest which at that time was the parent of the Study Program (Agronomy), Plant Disease Pests (HAPPEN) and Soil Science (Ilmu Tanah) including at the inauguration camp of the Agronomy Student Association of the Faculty of Agriculture. With little discussion and perhaps personal pressure because Mr. Butje was part of the senior faculty, the guarantee of getting lectures from competent staff especially Mr. Anema from the Netherlands, the plant breeding interest a few years later, attracted students with the best IPK in the Faculty of Agriculture. Later there was a little friction between Mr. Anema and Mr. Butje where Mr. Anema felt that Mr. Butje’s involvement in the Faculty was not entirely because it was divided into functions as a teacher of Sekolah Menengah Atas (Ambon Christian High School).

Systematically, factual development of interest towards the study program is carried out through the preparation of human resources, preparation of curriculum including courses and syllabus / GBPP, preparation of technical implementation units including laboratories and facilities, as well as adequate literature (library) and experimental gardens. The preparation of plant breeding human resources, although not intensively formally discussed, is applied with due regard to specialization in the field of plant breeding, including conventional breeding involving selection from both generational development populations, testing for the production of new varieties and production of hybrid varieties; collection, conservation and testing of genetic resources for germplasm exchange and natural development as well as crosses, and new high-yielding varieties; and the use of biotechnology to expedite / accelerate plant breeding programs. In its application to the recruitment of Plant Breeding staff, this is certainly not easy or difficult to carry out precisely as ideal, but it can be seen in the future or in recent conditions that there is a clear separation in the field of expertise as well as the intersection of the field of expertise of the teaching staff. Mr. Butje played a lot of role in the recruitment of Dr. Ir. Jollanda Effendy MSc. M. Phil. Completed S2 (MSc. Simon Fraser University, Canada and M. Phil. Massey University, New Zealand), S3 (Dr.) IPB, Bogor, areas of expertise include Plant Biology and Molecular Biology, while Mr. Anema played a role in the recruitment of Dr. Ir. Helen Hetharia, MSi., who completed S2 and S3 at IPB Bogor, areas of expertise include Long Bean Plant Restoration and Biotechnology, Dr. Ir. Edison Jambormias, MSi who was later recruited to complete S2 and S3 at IPB Bogor with the field of conventional breeding expertise and Dr. Jane Laisina SP. MSi., completed S2 and S3 at IPB, Bogor in the field of conventional breeding and Biotechnology.

Another senior staff who has been recruited from IPB Bogor is Prof. Ir. Simon H. T. Raharjo, PhD. completed S3 at Simon Fraser University, Canada with expertise in Biotechnology, Gene Transfer, plant tissue culture while I, Dr. Agr. Ir. Semuel Leunufna, MSc. PhD., completed S2 (MSc., University of Guelph) Canada in conventional breeding (soy) and S3 (Dr. Agr., Martin Luther Universitaet, Helle-Wittenberg; PhD. IPK-Gatersleben), Germany in biotechnology, conservation of plant genetic resources (cryopreservation, plant tissue culture). All teaching staff have expertise in Agronomy. The development of teaching staff mentioned a little or a lot, in the context of preparing Unpatti teaching staff, involves the participation of two important figures Prof. Em. Ir. G. A. Wattimena, MSc., PhD., IPB Bogor and Mr. Liewe S. Anema.

Some courses are added to the lectures of interest, especially in the advance semester as part of the preparation for curriculum development; Breeding resistance to environmental stress, Germplasm Conservation, Advanced Plant Breeding, Quantitative Genetics and others where some of them are introduced/copied from courses at other universities in Indonesia. Plant Breeding Against Environmental Stress is organized to be taught togather with staff of other study programs including Plant Pests and Diseases and Agronomy weighted with SKS 3, in principle discussing the effects of water stress (drought and excess water), salinity, temperature, pests and diseases in plants and breeding procedures and techniques in overcoming them. Plant germplasm conservation was initially given a weight of SKS 2 then 3 with the addition of practicum, generally discussing variability in various plants and general conservation methods and techniques applied in conservation efforts. The two courses above and the like are included in the Field of Expertise Course and Local Content Course because of their specifications and generally discuss the local dominant commodities of Maluku. I was asked by the Head of Interest to coordinate the lectures. As a senior staff, Mr. Anema has an office with the head of the project, the Principal Investigator (PI) of the Indonesian Umbian Cooperation Project (Unpatti) – USAID, Ir. Jeff. R. Lalopua MACD, a soil science researcher who graduated from Washington State University, USA, in a separate building from the Main Faculty building, named Gedung Serba Guna. A long office space is given two office desks on both sides, in the middle is a computer desk with desktops, printers and other accessories. As a senior student, I work on the desktop and thus, share an office and easily interact with Mr. Anema as a mentor.

In this period the use of computers is rare, its use still revolves around typing manuscripts using software including word processors, we use word perfect programs and simple statistical calculations on spreadsheets including Anova, regression and others. With a low-capacity flat wide floppy disk, it is not possible to do work involving large files including pictures, photos and so on. Together with Mr. Anema, we were pioneers in the use of information technology (IT) at the University at that time. The multipurpose building was originally intended for the Unpatti-USAID Cooperation on Tuber Crops project equipped with the PI Office and staff space, meeting rooms, collection and cultivation rooms for plant tissue culture laboratories, materials and tissue culture media preparation, laundry rooms, storage warehouses, acclimatization rooms. In addition to the office space for Mr. Anema, we were given a laboratory room for Genetics and Plant Breeding, which was built specifically for laboratory functions complete with two long stone tables next to each other in the middle and stone tables on the sides surrounding the lab room. At the bottom there is a laboratory equipment storage cabinet and the top at hand level is a cabinet where chemicals are stored, while on the other side there is a cooling cabinet and a wooden cabinet storing certain chemicals and plant seeds. Laboratory equipment for practicum and research, at the beginning of development included research microscopes with magnification reaching 1000 times, 10x ocular lenses and 100x ojectives, binoculars, a number of student microscopes, a number of practicum props, absolute alcohol chemicals, glacial acetic acid, orcein, xylol and others especially for research on microscopes and various other equipment, a number of seeds of various varieties in paper bags to be planted periodically as practicum materials and research descriptions of plant morphology including tubers of various cultivars of Dioscorea.

Some of the existing equipment and materials were purchased with funds from Mr. Anema, others were collected from the storage warehouse of Russian heritage materials and equipment at the former Ambon Institute of Technology (ITA) which changed its name to the Faculty of Engineering (FT) Shipping Unpatti, when Rector Prof. Nanere took a policy of dismantling the warehouse and converting spaces at FT. In an effort to transfer a number of equipment and materials to the laboratory, there was little opposition or disinterest from Mr. Anema to the Rector, because the Rector ordered the immediate destruction of all remaining materials when the transfer was not completed, and Mr. Anema was temporarily outside the area.

One large cabinet, slightly rotted in some places because it was stored for a long time in the Russian heritage warehouse, we made the main storage cabinet in the library of breeding interest. A collection of genetics, breeding books of the latest and most important at that time as well as international and national journals in the collection in the library of interest in Plant Breeding. Genetics books by Strickerberger, Lewontin and Suzuki, including a number of recent books by the Inter- University Center of IPB Bogor, gene expression (Dr. Muhammad Yusuf, FMIPA, IPB), agricultural biotechnology (Prof. Dr. G.A. Wattimena, MSi, Agronomy IPB), cytogenetics, and others; Journal of euphitics and a number of other journals related to chromosome and tuber observation, taxonomy, flora malesiana, flora of java, and others can be found in the library. A number of these libraries were obtained from the Netherlands, others were bought or copied, or given free of charge by the authors. Some of the collections were brought by Mr. Anema, others through the assignment of the PI of the Umbian project to me to travel to complete the Tubers library at IPB Bogor. The collection of a large amount of literature by the tuber project is also a source of complement to the library of plant breeding interests.

Experimental gardens are important for learning agricultural science in universities, including the scientific field of plant breeding. In its implementation, we utilize the collection garden or experimental garden of the Unpatt-USAID tuber project located near the campus, in collaboration with the project. In addition to utilizing the field collection of root crops from the Tuber project, we grow our own research crops including thesis research and other crops including legume plants periodically for the practice of vegetative and reproductive morphology observation, description and taxonomy, production evaluation as well as for circulation and propagation of seeds. Once we received a collection of different varieties of soybeans in paper bags, because of carelessness some soybean seeds from several bags spilled out. Mr. Anema was furious when I tried to collect the fallen seeds. I understood then that in breeding, it is very important especially in self-pollinating plants such as soybeans, each bag is kept separate from the others, because each variety is a pure line/strain of continuous self-pollination. Mixing varieties means polluting the purity of the strains and purifying them requires time, cost and labor-consuming cultivation and separation of intersection types.

In conditions where the number of students is small, we plant practicum plants on a project basis with only a small amount of funds from Mr. Anema. I brought in my adoptive brother Waldy with his men to complete the job of preparing the beds with very satisfactory results. Although a bachelor of economics, Waldy is skilled at growing a variety of vegetables in our home, Wailela region. Waldy is very sociable but is also feared even by criminals around and many young people make friends asking for his advice. Some of the young men are involved in the GPM Youth Force organization of which I am chairman, making two groups; who were in spiritual and other activities several times got into fights. Later, the young people around our area became reliable cadres in the community. Research consultations or work-related talks other than being conducted in the office, also took place on our trip together in Mr. Anem’s diesel car which was probably only one in the province sent by ship to Maluku. I would sit in front and ask questions or give opinions on the way back to Karang Panjang, his residence with his family and I would go down around the city of Ambon, to my host mother in Kudamati. At the end of his service, Mr. Anema had difficulty selling his car until finally sent to the island of Sumatra to the new owner who offered it.

Determining the Title of Research and Implementation

Although carrying its own mission, namely the development of genetic teaching and plant breeding at Pattimura University, the presence of Mr. Anema, in many ways, integrated, helped and succeeded in the implementation of the Unpatti-USAID Umbian project, which can be seen through the same work environment, input of thoughts through informal discussions and submission of papers at scientific seminars on project research results by Mr. Anema, determination of my research title and assignment in complementing Project library, tuber survey team, to the implementation of survey and research results material in the final project report including appointment as project research staff for the last year of implementation. In terms of survey and collection of tuber germplasm by the project, in addition to the team surveying the Central Maluku region, Seram Islands, Saparua and Ambon, I was assigned to survey the island of Yamdena and its surroundings. In my conduct with an officer of the Taniminbar islands agriculture service, Pak Made, I traced about half of the island of Yamdena, visited a large number of villages including Tumbur, Lorulun, Bomaki, collected about 40 different cultivars, including Arumat dare, arumat fufulu, arumat atutmune, arumat ngalerap, arumat yarbulan, syabu tarbalyame, syabu kreme, syab nure, syab sruene, described various field characters including local names etc., following the traditional ceremonies of harvesting and planting, burning land and so on in the practice of shifting cultivation practiced by the Yamdena community at that time.

The title of our research is the biggest part of it is Mr. Anema’s contribution; “Taxonomy of some dioscorea specimens, Carbohydrate-Diosgenin ratio and its Impact on Dioscorea breeding procedures” [8]. The background of determining the title of the research can be clearly seen from the important aspects stated. First is the taxonomic section. A total of more than one hundred cultivars of mainly Dioscorea spp. with small numbers of Xanthosoma spp. and Colocasia spp., were collected from a survey in the province of Maluku by the project survey team. An earlier survey 10 years earlier by the IPB Bogor research team had reported 8 species of Dioscorea spread in Maluku out of about 33 species spread in Indonesia and about 400 species in the world. of course, you want to know how many species are still left or how much genetic erosion has occurred in Dioscorea germplasm over the last 10 years (1978 and 1987) in terms of the number of species in Maluku? To answer the above question, of course, it will be necessary to include the dioscorea descriptor, which is a list of morphological characteristics with the addition of a number of other characters including chromosome observations (if possible) and other literature studies, applied to a number of examples of Dioscorea cultivars collected, including in his 17 cultivars of my thesis research material.

The results of morphological descriptions on the Dioscorea germplasm collection in the experimental garden of the tuber project identified 4 different species from the survey area including the islands of Seram, Ambon, Saparua, Yamdena and surrounding areas. The four species in question are D. alata, D. esculenta, D. hispida and D. pentaphylla where D. hispida is represented by only one cultivar and D. petaphilla 2 cultivars. A few years after the end of the tuber project, another species was discovered on the Kei islands that were not surveyed: D. bulbifera. The second aspect is Diosgenin and carbohydrates (chemical content of tubers). Diosgenin is a chemical, secondary metabolism produced by Dioscorea and used in the production of steroid drugs, one of the uses of diosgenin is as an active ingredient in the contraceptive pill a product whose promotion can be found in a number of IT media at that time. Since the 1960s the USDA has introduced and cultivated a number of diocorea species from Latin America, including D. floribunda, D. mexicana for diosgenin production. Analysis of diosgenin content in Dioscorea in Maluku, thus important to understand its commercial value in the future. The carbohydrate content in dioscorea has been widely studied and is one of the main carbohydrate foods that support the food security of the islands in Maluku. How big the amount of carbohydrate content of Maluku tubers is certainly interesting to know and compare with the results of previous studies in other regions in Indonesia and in the selection of cultivars for their designation.

At that time Pattimura University had developed a soil chemistry laboratory at the Faculty of Agriculture that was able to analyze the carbohydrate content of foodstuffs, and with the carbohirat content of tubers was handed over to the soil chemistry laboratory to be carried out on 17 samples of tubers / cultivars of research materials. Analysis of diosgenin content could not be carried out in Indonesia and thus brought to the Netherlands by Mr. Anema for analysis and at that time carried out at the Laboratory of Pharmacognition, Uthrecht University, Uthrecht Netherlands. The whole analysis procedure certainly took time and although it was a bit late to get it to discuss it at length in the thesis discussion, Mr. Anema once handed me a number of documents containing the results of the analysis of diosgenin content in tuber samples that he brought to the Netherlands. It turned out that the results of the analysis showed that the sample used had a low diosgenin content, which was 1 percent. The carbohydrate content of tubers from laboratory analysis shows a fairly high percentage and looks varied according to the color of the tuber flesh where the purple color provides a lower carbohydrate content than the white color. Another observed carbohydrate content in the species D. esculenta of the subgenus Comblium, contains branched chain starch, amylopectin which makes it somewhat difficult to digest compared to D. alata of the subgenus Enantiophyllum which predominantly contains amylose, a straight-chain starch that is relatively easy to digest.

One other aspect of the study was determining the relationship between the specific gravity of tubers and their carbohydrate content or diosgenin. Regression relationships with the resulting equations can be of practical benefit, especially in the case of surveys of distant forest or mountainous areas finding wild species of Dioscorea. In this condition it can be practically predicted / estimated how much carbohydrate or diosgenin content of tubers, by simply carrying a scale, without waiting for the results of chemical analysis or bringing dioscorea tubers that are quite heavy to the laboratory from a distant place. Technically, the implementation of determining the specific gravity of tubers is something that is not easy to do. From the literature offered by Mr. Anema I saw that the equipment used in previous studies determined the specific gravity of an object (biological material), but the same equipment was difficult to construct in the laboratory of Genetics and Plant Breeding of Pattimura University. Simply determine the specific gravity of the object obtained from the weight of the object in the air minus the weight of the object in water, then the value obtained divided by the weight of the object in the air. We construct this condition in the laboratory, then send the image to the supervisor for examination. In an effort to reduce errors, a regression relationship can be obtained for carbohydrate content with R2 of about 78 percent, which means a fairly strong relationship. Specific gravity regression and tuber diosgenin were not performed due to the very low diosgenin content.

From the results of the analysis obtained, conclusions related to the procedure and direction of breeding dioscorea can be put forward; that selection over generations of dioscorea by the Moluccans from the wild form of dioscorea resulted in current cultivars high in carbohydrate content; that the selection carried out was a negative selection of the diosgenin content or produced cultivars with low diosgenin content; that the selection by the community in question occurred unconsciously because diosgenin has a bitter taste and by selecting or consuming and planting continuously from generation to generation cultivars that did not taste bitter, the Moluccans have unconsciously selected cultivars with high carbohydrate content. Regarding the field of taxonomy, it can be concluded that within ten tanun there has been an erosion of the genetic diversity of Dioscorea in Maluku both at the species and cultivar level with the loss of 3 species and of course a large number of cultivars in it and in the species found.

Questioning the Predicate of Cumlaude

During the thesis preparation period, Mr. Anema was in the Netherlands for several activities, he asked to send the thesis that had been prepared to be evaluated with the shipping costs paid back. I was then asked to prepare for the exam when he returned in the near future. A few days before the undergraduate exam was held, Mr. Anema and I discussed with Mr. Jef Lalopua, Principal Inverstigator of the Umbian Project. Mr. Jeff asked and wanted to know the corrections that had been made to the Thesis, Mr. Anma jokingly but also seriously said that the fault lies with me that there is no error in the thesis, if I want to get input and correction from him. I have to make mistakes. I was quiet but understood that I got full marks for my thesis. Assessment of the overall success of a student’s studies in line with the application of the Semester Credit System (SKS) is carried out at several assessment points, first the cumulative achievement index (Grade Point Average-GPA) for courses offered during the study period including real work lectures (KKN), then research and thesis writing, thesis seminars and undergraduate examinations. It should also imply other achievements including co-curricular and extra-curricular activities of students including involvement in professional organizations, student senate and others. The predicate obtained by students according to the weighting on the creteria above includes “Cumlaude”, the highest predicate that can be obtained for universities in Indonesia, slightly below the predicate “Very satisfactory”. To obtain the highest Cumlaude certificate, in the credit system and according to the rules developed in the Faculty of Agriculture, a student must be able to complete his education within a maximum period of 4 years with a cumulative achievement index (GPA) equal to or exceeding 3.5.

I did not get the highest cumulative achievement index (4) for learning and practical work conducted throughout the learning period; some courses do not get A grades for several reasons, one of which is a collision of lecture schedules and / or exams because the courses offered are in different semesters, and there is a change in the schedule in the implementation of the course, thus in the end, the cumulative achievement index is close to 3.7. The thesis seminar was conducted a few days before the undergraduate exam, assessed by the supervisor and head of the department in this case Mr. Anema and Ir. L. L. Orzaer (Mrs. Len Oszaer). After finishing presenting the seminar followed by a round of questions, Mrs. Len filled out the assessment form and submitted one exemplar to Mr. Anema. Back at the office, I then asked Mr. Anema for his assessment regarding the seminar that had just finished, he handed me a blank assessment sheet along with the assessment sheet from Mrs. Len and asked me to rate myself. I briefly looked at the form sheet and the grade given by Mrs. Len, listed the final score of the seminar 98. I filled in 97 on the blank sheet that Mr. Anema gave me and handed it back to him with a little small talk. The undergraduate examination takes place as scheduled, followed by supervisor I, Supervisor II, examiners, examination committee, department and Faculty leaders (Dean). The questions asked and discussions that took place I was able to complete well and felt very happy with the learning results that had been resolved. However, there was a fierce discussion in giving final grades among the examiners, the explanation given later was that I could not be given laude predicate because I completed my studies in more than 4 years or precisely 5-6 years. Because laude predicate is only given at a IPK of 3.5 or above, my final learning results are adjusted to 3.49.

I didn’t think about it at the time, but then realized that such judgments were very unfair and wrong and very detrimental and erased all the hard work that had been done during the learning period. It is not wrong not to give the title laude for reasons that have already become an agreement. But lowering the entire cumulative achievement index to 3.49 to adjust to the predicate given is very wrong because IPK is the result of student work and is his right. To get a IPK of 3.7 students have to study hard, manage time, endure sleepiness, hunger and so on as well as in preparing research, writing a thesis, preparing seminars and so on to get full marks, 98 and 97 and so on. Eliminating or eliminating all grades and giving a grade of 3.49 not only harms students on exams but also their future and reduces the pride of parents who have sacrificed so much for their children’s success.

Genetic Transplant FMIPA IPB Bogor

Dr. Muhammad Yusuf, Head of the Genetics laboratory of the Faculty of Mathematics and Natural Sciences (FMIPA) IBP Bogor, a PhD. graduate from France, was invited as a lecturer at a biotechnology workshop at Pattimura University in his position as Head of the Indonesian Inter-University Center (PAU) for Biotechnology. The workshops are part of the basic sciences development program of the CIDA-Unpatti project. The interesting material encouraged me to participate in conveying questions in Mr. Yusuf’s delivery. At the end of the workshop, Mr. Yusuf invited me, with Mr. Anem’s approval and talks with the leadership of CIDA-Unpatti as a financial supporter, to intern in his laboratory. Apprenticeship or transplant in principle is a staff assigned to an institution or university that first developed to work and learn from the progress achieved in order to then practice it at the institution / university of origin. Together with two assistants of Mr. Yusuf at that time, Ence Dharmo Jaya Sopeno PhD (Pak Ence), then graduated from Wageningen University and Research and Dr. Utut Widiastuti (bu Utut-IPB Bogor) we managed Practicum and Genetics lectures. The Molecular Genetics lecture was given by Mr. Yusuf in a large lecture hall that accommodated hundreds of students at once, I was asked to sit in (attend lectures but no other obligations), but then asked to take the final exam. For practicum purposes, students are divided into 4 groups according to the number of practicum teachers/assistants. The first group was taught by Mr. Yusuf, the second group was taught by Mr. Ence, the third group was taught by me and the fourth group was taught by Mrs. Utut. Learning materials and practicum materials are the same for each group. A number of practicum materials are taught and practiced including Mendel’s Law and its proof using computer simulation products for the segregation of 5 different genes, the inheritance of traits in fruit flies including sex and segregation traits and other materials. Fruit flies whose life cycle is about 4 weeks are excellent learning material because the nature of segragation can be seen in individuals and explained using a chessboard. Fruit flies should be carefully farmed and fed around the clock with boiled sweet potatoes.

For the study, I was given the task of researching and counting the number of chromosomes of large chilies (Capsicum annum L.) using plant material that was also being researched in our lab. Chromosome counting studies utilize Colchicine material on specific consentrations. The use of cochinine will disrupt the formation of spindle threads in cell division (mitosis and miosis) and in the absence of spindle threads, chromosomes will not arrange in the equatorial plane at the metaphase cell division stage but are scattered in cells with large sizes in other words cell division does not occur and chromosomes are in tetraploid (polyploid) form. In my research I used root organs and organs of newly developing young flowers. The use of flower organs at the beginning of formation / growth succeeded in displaying good chromosomal preparations, Mr. Yusuf and I counted together the number of chromosomes scattered on the preparations after being photographed at the SEAMEO-BIOTROP laboratory, Bogor. The publication of our writing was hampered because the report was written on a typewriter and its correction required retyping the entire manuscript while the internship time was nearing completion. Another task is to attend advanced genetics lectures with Prof. Alex Hartana, PhD (Mr. Alex). Mr. Alex uses the thick book Thick Genetic Analysis from Lewontin, Griffiht and Suzuki. Intensive lectures with students with good achievements made me stressed, but the final results did not disappoint. Although the senior lecturer, Mr. Alex got married a bit late and his marriage with colleagues at IPB became an interesting story by several lab colleagues.

In addition to the various functions carried out, Mr. Yusuf also seems to be a counselor of PT Benih Prima, evaluating the planting of breeding plants in order to strengthen the standards of planting and producing seeds and selling them later. Technically, periodic inspections were assigned to Mr. Ence and I was included. We were given motorbikes and periodically visited the planting site of PT Benih prima. Mr. Ence’s wedding was also a unique talk, the wedding plan was set and I planned to get the invitation but Mr. Ence’s father-inlaw passed away and was immediately called home to get married in front of his father-in-law’s body. The wedding seemed to be attended by only a few friends including Mr. Yusuf. Meeting Mr. Ence again in Berlin, 2003 at the Indonesian-European Indonesian student scientific conference, we presented the material to the same group, biotechnology, previously I offered to be the moderator of Mr. Ence’s paper but there was a change from what was scheduled by the committee. Mr. Ence talked about his children.

Master of Science, Crop Science Department, University of Guelph, Guelph, Ontario, Canada

Indonesia-Canada cooperation through CIDA offers scholarships to study in Canada but with heavy requirements including TOEFL must reach 570. To support the policy, CIDA organizes intensive English courses gradually starting with Basic English Language Training (BELT) and even Pre-BELT, held at Pattimura University to English for Academic Purposes (EAP 1 and 2), UGM Jokjakarta and Jakarta, supported by the Rector’s policy to free Young Lecturers from excessive academic tasks and concentrate on learning English. Although not many attend Canada, the improved English language skills have led a large number of Unpatti staff to attend further education to a number of foreign countries including the United Kingdom, Belgium, Australia, the Philippines etc. In the placement selection, I was asked to determine between BELT and Pre BELT-2, I chose pre BELT-2 and then got the opportunity to EAP 1 and 2 without going through BELT then passed the selection to Canada and was accepted at the University of Guelph, in the small town of Guelph, Ontario Province, Canada, historically used to be part of the University of Toronto, then stood alone. Following lectures at U of G, both undergraduate courses and graduate courses, I realized the importance of understanding the language of instruction well and appreciating the high language requirements imposed by CIDA.

Meeting before leaving for Canada, Mr. Anema told of a Van-couver brother and a classmate at Wageningen University who worked at the University of Guelph, while handing over a letter to be handed over to Prof. Theisj Tolenaar, Mr. Anema’s friend. Prof. Tolenaar is a respected plant physiologist in the Crop Science Department of U of G both by his graduate students and by colleagues and international scientists. Each teaching staff at Crop Science UoG is rigorously selected and ends their duties as Prof. Emeritus because of their brilliant scientific work. Unlike Prof. Tolenaar, I was accepted into the Plant Breeding specialization under the guidance of Prof. Jack W. Tanner. I was asked by graduate students coordiator Prof. Lyn Kannenberg, to choose between Prof. Tanner, Prof. Steve Bowley and Prof. Duane Falk. The advisory committee consisted of Prof. Wally Beversdorf who later moved to the company Ceiba gaigi, Prof. Dave Hume, chair of the Department of Crop Science, Prof. Rick Upholt and Prof. Tom Micheals. Under the guidance of Prof. Jack Tanner and the solid soybean breeding team, I worked and studied intensively, completing 11 courses while researching and writing a thesis [9]. The five examining professors expressed satisfaction on the final exam assessment sheet. The learning atmosphere is familiar and friendly but strict and demands high achievement, making every graduate student, especially international stdents and especially from Asia have to work extra hard.

For international students, after completing a study assignment, there is usually an opportunity to become a Canadian citizen, work and build a life, even if certain requirements are required or the government is selective in accepting applications to become immigrants. Political events or conflicts within a country are usually quite convincing grounds for proposing to become landed immigrants in Canada by paying administrative costs of about 400 Canadian dollars, at that time, for example the Chinese Tiannanmen incident. A close friend from Menado, Indonesia, and his family decided to stay, and currently live a prosperous life and vacation a lot to various countries. For Indonesian students who receive scholarships (including grants) for international cooperation, given or registered in the Cabinet Secretary letter (SETKAB) and get a State Service Passport, usually a service period of 2n + 1 year is applied to the original institution after studying abroad where n is the length of study abroad.

The Scholars; Unforgetable Memories from Canada

To commemorate my university days and life in Canada, I wrote a number of articles and published them in newspapers, local dailies, usually the daily Pagi Siwlima [10-37]. Articles that are quite long are usually divided into two daily pages and in two or three issues until completion. The dozens of articles were compiled into a small book of more than 300 pages and titled the Scholar; unforgettable memories from Canada. Every time an article was published, I would rush to buy a daily, but it often happened that the daily published that day was sold out in a subscribed place. It seems that the Moluccans, especially on the island of Ambon, like to read the articles I wrote or maybe it was a coincidence. My adoptive mother also loved to read it and I usually bought and brought it for the adoptive mother to read, several times she jokingly called me “writer”.

For science work, I translated a book written by one of my professors at the UoG Crop Science Department, Prof. Niel Stoskopf with two colleagues from different institutions, entitled Plant Breeding; Theory and Practice. The more than 500-page tome, translated into Indonesian of more than 600 pages, reviews in detail the history of plant breeding, the use of statistics in plant breeding, the selection of elders for crosses, conventional breeding methods and techniques, and the release of new varieties while emphasizing the importance of biotechnology in speeding up conventional breeding procedures. First published in early 1992 and to date it has not been replaced by quality and relevance in the practice and teaching of plant breeding, agree with the opinions of scientists I have heard. I also heard a little comment from Prof. Lyn Kannennberg, Graduate Student Coordinator, Crop Science Department, on our trip from Guelph to Bettendorf Iowa to attend the Corn Breeding Conference, explaining how Prof. Stoskopf transferred the complicated and uneasy knowledge and practice of plant breeding into beautiful, readable language. This book I use in plant breeding lectures, although not in its entirety chapters. At least two important international scientific conferences we attended; American Society of Agronomy (ASA), Crop Science Society of America (CSSA) and Soil Science Society of America (SCCA) Conference, Cincinnati Ohio, 1993 and Corn Breeding Conference, Bettendorf, Iowa USA, 1994, became important lessons in my future scientific development, in which I was accepted and listed as a member of CSAA, ASA, SSSA (Crop Science Vol. 36 March – April, 1996: 515 – 538). Additionally, I was invited to become a member of the American Association for the Advancement of Science (AAAS), 1994 by Special Invitation.

Invitation Netherlands; Renkum, Amsterdam

I received an e-mail from Mr. Anema a few days after defending my thesis at the Department of Crop Science at the University of Guelph, was invited to the Netherlands and had several talks. Graduation (convocation) was still a few months away, October 1995, and in the waiting period, the opportunity to have informal talks with other colleagues or work approaches with professors, while some gave positive responses or looked for opportunities to continue their PhD either in Canada or the USA could still be explored, but I decided to respond to Mr. Anema’s invitation. Immediately I went to the university administration asking for a list of study results containing courses with results obtained during the study, discussing the trip to Indonesia with the sponsor in Van Couver and requesting a trip back through the Netherlands. Mrs. Robin Kask, the coordinating secretary of the CIDA scholarship recipients, agreed and prepared a return ticket, namely through the Van Couver to meet Mrs. Thea Hinds, the coordinator of the Canadian scholarship recipients, and complete administrative matters including sending a number of books and goods directly to Indonesia.

In the visa process at the Dutch Embassy in Toronto, there is a slight obstacle, namely the need for an official invitation letter from the former supervisor as an inviter, while the flight departure schedule is the next day. It turned out that the invitation letter could be completed and the next day I was given a visa and went straight to the departure airport to Amsterdam Airport Schiphol.

I lived for some time in Renkum with the Anema family; Willy’s mother and their two adopted children, Oriza who has just entered school and is very excited and Sippi (Sibrano) who is still often held by her mother. Some of the scheduled activities with family or with Mr. Anema include visiting the heritage house of Mr. Anema’s parents in Amsterdam, sightseeing trips around Amterdam and its surroundings, enjoying beer on garten beers scattered in the city of Amsterdam in the summer. I also took several private trips, including visiting Uthrecht, the Hague and other cities, such as Dutch cities can be visited in a short time by train. Professional talks included meeting the invitation of a group of student activists and staff of Wageningen University who wanted to interview about the issue of Yamdena Island which was quite hot at that time. The policy of clearing forests on Yamdena island for sugarcane cultivation for the sugar industry in Indonesia, received international attention. Problems that caused criticism from a number of experts at that time included land suitability, especially soil that was easily eroded and so on which would have an impact on land productivity and environmental crisis. Until now, the planting and development project of the sugarcane industry on the island of Yamdena is no longer heard from. It turned out later that the shipment of goods to Indonesia from Canada experienced a problem where on the Jakarta-Ambon transport trip, the container with the side of my goods was submerged in water and damaged most of the goods inside; Seeking redress required conditions that were even more difficult to complete at the time.

Nutsbarmachung Der Pflanzengeneticher Resourchen Als Beitrag Zur Ernehrungsicherung (Utilization of Genetic Resources as A Contribution to Food Security)

Returning to the original institution in 1995, although there was a lot of academic work that had to be completed without the company of Mr. Anema again, it felt that there was no right momentum to fully contribute to the development of the institution. I found an advanced training advertisement on the theme of food security in the Federal Republic of Germany and despite being in a completely foreign language, I tried to send the requested files to the embassy of the Federal Republic of Germany to Indonesia, Jakarta. It turned out that it was successful and along with 2 other Indonesians were given a short course in German and departed for Munich to attend training preceded by 4 months of language courses at the SprachInstitut Muenchen (SM) led by Dr. W. Rall (Frau Dr. Rall). About 135 participants from about 35 Asian, African and Latin American countries lived in the House Internatioal (HI) near Munich’s 1972 Olempiade Stadium where there was an association of Israeli athletes by the Black September group, a beautiful area especially in autumn and historic and thrilling.

The beauty of the Bavarian region that we immersed during language training and cultural visits to various tourist and cultural objects including museums Bayerische Motoren Werke– BMW, Schloss Neuschwanstein, Oktoberfest events, colorful scattering of leaves by the treatment of the seasons etc. is reminiscent of Frau Lange Neorsewan, a German Embassy official who evaluated my application for training and encouraged me to participate including with promoting the beauty of his native Bavaria. After returning from training, I usually call Frau Lange, every time, to convey my arrival in Jakarta; often invited to share his experiences in the office he even had coffee in Frau Lange’s office room after getting about 4-5 stages of inspection / check point and was picked up directly before entering the Embassy yard, also apologized for repeated checks for security reasons, Hosting is very important. My adoptive mother loved to laugh out loud when all these experiences were told to her. The training, sponsored by the German International Development Institute and the German Centre for Food and Agriculture (Deutsche Stiftung fuer Internationale Entwicklung/Zentralle Ernaehrung und Landwirtschaft – DSE/ ZEL), was divided into several areas including forestry, animal husbandry, and conservation of plant genetic resources. Our group then consisted of participants from Ethiopia, Egypt, Syria, Bangladesh, Nepal, China and Indonesia with Dr. Hehne in charge of training assisted by his assistant Dr. Alchinawi an Iraqi of German nationality and most of the time the training was done through work involvement by doing at the institute for Plant genetics and Crop plant Research (IPK) Gatersleben, located in a small village, Gatersleben, Saxony Anhalt State, part of the former East German Socialist Republic.

Centered on the Gene Bank Department (Chairman of Dr. Adreas Borner/Prof. Andreas Granner) and Taxonomy (Chairman of Prof. Karl Hammer), I moved between laboratory or working groups of Molecular Markers (Head of Dr. Klaus Dehmer), In vitro-Culture and cryopreservation (Head of Dr. Joachim Keller) and plant characterization and identification. Periodically we make short and multi-day visits to a number of other institutions including the Dresden apple gene bank, the plant breeding institute, the Gatersleben IPK germplasm collection branches, the Austrian community society gene bank and are fully briefed, attending a number of lectures at the Department of Agriculture (ZEL) Zchortau, Leipzig (Prof. Fuchs), presenting papers at the International Seminar on Germplasm Conservation, and other activities. A very intensive training with solid programmed activities and high discipline but very fun because of the literacy built between participants and IPK employees who are mostly middle-aged mothers. We learn from them, know each other’s names and birthdays and celebrate, tell stories and laugh after work. I tried to describe the conditions we experienced in the valedictorian that I gave on behalf of my fellow participants. Prof. Dr. Habil. Ulrich Wobus, the head of IPK at that time was present and he took the time to say hello briefly before leaving the farewell ceremony. Fierce disagreements and debates among participants as well as the application of discipline by the assistant training coordinator also occurred and were a fun part and learning resource of the training.

On the occasion of attending the training, I also tried to get a professor’s recommendation to make it easier to continue learning at the doctorate level and through the services of the head of the laboratory where I worked (Dr. Joachim Keller), the recommendation was signed by Prof. Konrad Bachman, Department of Taxonomy. I then submitted the application file to obtain a German scientific exchange scholarship (Deutsche Akademicher Austauch Diesnt – DAAD) and accepted. A few years after completing the Ph.D. program at Martin Luther Universitaet Halle-Wittenberg and IPK Gatersleben, Prof. Dr. Andreas Granner who is the Head of the Gene Bank Department and Head of the Institute for Plant Genetics and Crop Plant Research (IPK) Gatersleben, together with Dr. Joachim Keller, head of the lab. where I work, wrote on the job application recommendations that I was one of the best in German training classes and it became the basis for continuing doctoral studies at IPK Gatersleben and Martin Luther Universitaet Halle- Wittenberg under the guidance of Prof. Dr. W. E. Weber. A number of articles related to the above training are presented in the bibliography [38-47].

Deutsche Sprachprüfung Für Den Hochschulzugang – DSH (German Test for University Studies)

The recipients of DAAD scholarships departing in 2000 amounted to around 60 people divided into 2 intensive German language training classes for 6 months at the Goethhe Institute Jakarta, some of whom came from Pattimura University, which like other universities is active in developing human resources. The experience of living and speaking German for a year while attending the training gave a great advantage at the Goether Institut training, Jakarta, I was among the two or three participants with excellent predicate (sehr gut, summa cumlaude) and was given the opportunity to deliver a waiver speech on behalf of the scholarship recipients. Language training is continued in Germany in several regions/cities/institutions according to regional divisions as well as universities and fields of study of student work. Together with some colleagues, I was assigned to the Goethe Institut Dresden in the city of Dresden with a training period two months shorter than other Indonesian participants. Intensive training with various learning methods and classmates from various nationalities; Russia, Colombia, Australia, Syria, Belgium, Bulgaria, Italy, India, USA, Brazil etc., plus the great beauty of Dresden, provide opportunities for a more developed understanding of the language although German is not as easy to understand as many fellow learners suggest. Class learning is more aimed at understanding German culture, it feels like studying German literature (my guess is even though I have never attended a German Literature lecture); poets, art workers, great inventors, the beauty of the city and the architecture of its buildings, history in addition to studying language structure (grammar) and vocabulary specifically, essay writing, story comprehension etc.

In practical material, our class once toured around Germany by train visit various important monuments including the residences of Goethe, Schiller, Martin Luther, the historic city of Weimar and others. To practice social language, a week-long “Kneipen Tag” (Bar Day) is scheduled where students from different countries will visit and meet in a bar or beer garden, order a few drinks, interact in German language while building friendships with each other. Deutsche Sprachprüfung für den Hochschulzugang auslaendischer Studienbewerber – DSH is one of the main barriers to entering universities in Germany especially for international students, and to pass this standard it seems that one needs be made german (culturally) first and then carefully study the academic part through the test guidelines and previous test materials before taking the DSH test. With the slight advantage of having previously lived in Germany for a year, I tried to read the newspapers even though not every word was understood, practiced with previous test materials to get used to the DSH test and then dared to write a letter to Frau Sachse the head of the Goethe Institut Dresden and ask for the support of the Professor to take the DSH Test organized by Technische Universitaet Dresden und GOETHE Institut Dresden. The test is divided into two, writing and interview, unofficially I was informed that I had passed the written exam which means free from the interview exam, but was officially asked to take the interview exam. After the test interview, Frau Sache approached and said: “Her Leunufna, Sie sind deutlich bestanden”.

Doctor Agriculturaraum (Dr. Agr.) Martin Luther Universitaet Halle-Wittenberg – Gatersleben IPK

The laboratory / working group / arbeitsgruppe in vitro Kultur und Kryolagerung is familiar to me when starting PhD research because I have undergone several months of training and have been introduced to the techniques and research materials to be carried out. With a well-developed working atmosphere with skilled technicians responsible for specific tasks, senior researchers and coordination of work by Dr. Joachim Keller and Secretary Frau Doris Buechner, I have a very supportive place in carrying out tasks, receiving a wide range of support, direction and input that greatly assists the research work. Prof. Dr. W. E. Weber is a senior Professor at the Department of Plant Breeding, Martin Luther University (MLU) Halle-Wittenberg Faculty of Agriculture. As Doctor Vater (Promoter) he manages and is responsible for the entire promotion program of my PhD including evaluating research progress through regular seminars in the Department, consultation and completion of the dissertation, regular reports to DAAD sponsors, Phd examinations, administrative needs and so on. A person who is very happy to be approached by students although often strict with subordinates.

One time after finishing the seminar where he was always the moderator for all participants, I as usual met him in the office while mentioning the questions raised by the seminar participants, asking for a more detailed explanation and a little cornering. I say: “die wollen auch die Zellen statistich berechnen” (they want a statistically counting of living cells), a little exaggerating, the question is how many cells are alive when removed from liquid nitrogen (cryopreservation) in order to re-grow into new plants, in the observation of the Electron microscope?, something that is still difficult to know. I expected a soothing explanation from him but Prof. Weber responded by saying “I laughed dead” (Ich lach Mich Tot). Although it was a pleasure to be defended, I was shocked and choked up. The promotion of a PhD. in Germany is generally done only by Universities and not at Research Institutes including IPK Gatersleben where I work and research. In later developments IPK Gatersleben developed his own Doctoral program and was followed by a large number of PhD students who researched at this institution, including me. The program includes participation in lectures in gaterleben (Gatersleben Lectures) by various invited speakers, learning or using additional laboratory techniques in addition to the techniques used in the laboratory where work, presenting seminars related to own research and other topics that are free to choose and attending other seminars. Program coordinator Dr. Andreas Houben asked to collect evidence of participation in Gatersleben lectures to get a diploma, I did not have time to do so, although I did deliver a seminar defending a dissertation at the Vavilov Seminar, a seminar at the Bank Department which was considered very prestigious. However, I often use two PhD degrees, feeling that I have completed all the requirements, somewhat different from the currently promoted system where PhD students from domestic universities complete part of their programs at foreign universities and are then tested and get double degrees recognized by both institutions. From the studies conducted during the promotion period of the PhD., a number of scientific articles were published both in international journals and in conference proceedings and as presentation material at various scientific meetings in the period to date, [48-79].

During the holiday period entering Christmas while in Germany, I was invited by Mr. Anema to the Netherlands to celebrate together. Germany’s railways are among the best in Europe and perhaps in the world, boasting timekeep, speed and comfort with beautiful surrounding scenery. While sometimes you have to hurry up when you switch trains once or twice between Regioanal Bahn (RB), Intercity (IC) etc., a trip to Holland is exactly what to be proud of. We spent the Christmas holidays on the island of Texel at Mr. Anem’s holiday home as a family, enjoying good cuisine from Mrs. Willi while Oriza had become a young woman and Sipi was still spoiled for her adoptive parents. On the eve of Christmas, we planned to attend the worship together at the peak of the celebration, but before the time of the service, Sipi insisted to buy pizza which was a place a little far from the residence. While waiting to make pizza, there was a trumpet sound from a very close place, it turned out that Christmas service was taking place and I followed it. On the way back I told Mr. Anema that I was not obliged to attend the worship together for a while because I had finished it while waiting for pizza making, as the saying goes “once grabbing oars, two three islands exceeded”, we laughed out loud. Of course, the peak of Christmas celebrations together is not missed.

Two days before the Dissertation defense exam, Mr. Anema visited me in Gatersleben. The Guest House room I stayed in was new when I entered with modern furniture that is rarely used due to the hectic work schedule and extracurricular activities, has become somewhat less shiny after 4 years. We took the time to enjoy beer on garten beer while catching up with their latest developments, in Quetlinburg, a small town near Gatersleben that has been neatly arranged for hundreds of years and has become one of the world heritage cultural sites. Another world heritage cultural city is Wernigerode, we visited later after touring the surrounding area. In addition to the wellknown IPK institute, the surrounding area is still rural, well organized with a number of farmland and forest trees.

Two small towns, Aschersleben and Halberstad flank the village of Gatersleben along the railway, along with other smaller villages Weggeleben, Hedesrleben, Harsleben there are small stations where trains drop off passengers. Gatersleben and the surrounding region are not only famous for IPK, but also for racism (Auslanderfeindlichkeit), something that for me is not true at all. I once entered the news of a local newspaper with a picture of a face plastered and a comment with a rather large headline written. ‘How do you respond to racism in Gatersleben”; asked reporters. “Are you going to run or fight or just shut up or how?”: He continued. “I feel safe”, I replied; in my country recently, there was a major conflict that killed thousands of people (Maluku conflict 1998-2002). The Dissertation defense examination was attended by Prof. Weber (Supervisor / Doctor Vater), Prof. Schuller (Study Program), the leadership element of the Faculty of Agriculture (Landwirtschaftliche Fakultaet) MLU, Prof. Andreas Granner (Supervisory committee and Head of IPK Gatersleben concurrently Head of Department of IPK Gene Bank Gatersleben), Dr. Joachim Keller (Head of Lab./Working group In vitro kultur und Kryolagerung, Department of Gene Bank IPK Gatersleben, Direct supervisor) and Dr. Zoglauer, Technische Universitaet, TU- Berlin (Guest examiner). When invited to enter the exam arena, Mr. Anema approached me and said, “Semi, for every question, there is an answer”, probably asking me not to hesitate to answer every question submitted. I completed the exam with Cumlaude Predicate, officially read and written on the Diploma.

After three years working as a DAAD scholarship recipient, I signed an employment contract or was hired as a research staff at the Gatersleben IPK for a year, certainly a record of achievement that will underlie further job applications, as well as additional income compared to being a scholarship recipient. Another thing is our closeness among laboratory colleagues (Mitarbeitern/inen). Most of my colleagues took the time to attend the dissertation exam (Verteidigung) and I tried to express my gratitude by sitting close to each other without having to speak. When invited to deliver a word in front of my colleagues, I introduced Mr. Anema by saying that he was my undergraduate supervisor, lived in Maluku for a long time and understood the language and culture of Maluku including jokes / humor. A colleague asked to explain an example of our joke, but I didn’t explain it, a moment I regretted later. One day Mr. Anema and I want to meet Prof. Em. G.A. Wattimena (deceased), something we usually do when we are in Bogor. We have been touring the Baranang Siang Campus between offices, laboratories, administrative departments and other laboratories and feel tired walking around the campus. Because it coincides with Friday and prayer time for Muslims, we only found many Friday worship participants in a number of prayer rooms scattered on the IPB campus. Still haven’t found sir. Wattimena, we stopped and I turned to Mr. Anema asking where else to look. Mr. Anema replied quickly; “Maybe we go to Mushola”, we then laughed knowing that Prof. Wattimena is a Christian. In Maluku, Muslims and Christians often joke with each other and even certain television broadcasts are scheduled for similar events such as “Onggo (Dominggus) and Dullah (Abdullah)”, although sometimes these religious differences are targeted by incitement to spark disputes.

Gute Nacht Freunde, DAAD Chapter Indonesia

When I returned to Indonesia, I wrote a small book, half a page of paper, a little over a hundred pages thick, entitled “Kleine Geshichten Aus Deutschland” (Little Stories From Germany) as part of my memories in Germany. The preferred title of the DAAD Chairman seems to be “Geshichten Aus Deutschland” (Stories From Germany), I infer from his preface. Through a senior DAAD official I asked DAAD Leader Frau llona Krüger-Rechmann to write an introduction to the book. After several appointments and coming to the DAAD Office, I was asked to wait a while. The head of the DAAD then came out to meet me with the booklet I had written, sat down and immediately sang Gute Nacht Freunde by German Songwriter and Singer Reinhart Mey, which became one of the sub-titles in the little story I presented. This song as well as the singer became my favorite when I was at the Goethe Institut Dresden. I immediately, without being asked, sang along loudly and we both loudly finished a verse of the song.

Gute Nacht Freunde, Es wird Zeit für mich zu geh’n
(Good night guys, it’s time for me to go),
Was ich noch zu sagen hätte, dauert einer Zigarette
(What I want to say, the length is limited to a cigarette),
Und ein letztes Glas im steh’n
(And the last remaining glass)…
Für den Tag für die Nacht unter eurem Dach habt Dank
For day and night under your roof, thank you
Für den Platz an eurem Tisch, für jedes Glas, das ich trank
For every place on your table, for every glass of drink I sip
für den Teller, den ihr mit zu den euren stellt,
for a plate for me that is put together with your plate
als sei selbstverständlicher nichts auf der Welt
As if it were commonplace, there was nothing

I still wanted to continue the other verse but Frau Kugel Rechman stopped and grabbed the ballpoint pen beside her and signed the preface she had prepared. It feels like this song aptly describes every experience experienced in Germany during the year of Training and 4 years of completion of the PhD program.

Current Conditions of Unpatti Plant Breeding Development

It must be admitted that all facilities built with Mr. Anema could not be maintained and continued in development instead disappeared or destroyed due to several reasons including impartial policies for further development, social conflicts that took place in Maluku and involved the Unpatti Poka Campus, as well as lack of good management personnel. One thing that can be noted is the success of teaching staff in the field of plant breeding and genetics completing the Doctoral education level and is expected to coordinate in the development of interests and plant breeding study programs in a good and directed manner. Some other related activities that are still being carried out by Mr. Anema include efforts to recover important lost literature, the addition of new literature from abroad to complete the library and several other projects. The plant breeding study program of Faculty of Agriculture Unpatti was only formed less than five years ago. Starting from writing a term of reference (TOR) of about 2-3 pages where Mr. Anema as one of the supporters. I handed over the TOR to the Head of the Department of Agricultural Cultivation, Handri Amanupunyo SP. MP. and a copy was delivered to the then Vice Rector for Academic Affairs Dr. R. Uluputti to be championed to become the Plant Genetic Resources Breeding and Conservation Study Program. When its establishment was approved at the central level, Mr. Ridho visited the Faculty and discussed it with several other staff colleagues to review the data and curriculum of the study program that was formed and named Plant breeding because in Indonesia there is only a name for the Plant Breeding Study Program.

There was a long debate regarding the naming of study programs between Breeding and Biotechnology versus Breeding and Conservation. For me it is clear, firstly that biotechnology is a tool in conventional breeding that accelerates the achievement of breeding results that generally take years, some biotechnology techniques are even a separate breeding method shortening the selection time from generation to generation. Conservation, on the other hand, is a conception or an understanding of science and techniques that involves the preservation of plant genetic resources as a reservoir of genetic material in which important genes are collected so that they can be exploited and integrated into breeding populations to achieve superior breeding results according to the goals to be achieved. Second, the issue of conservation is an important matter in general in Indonesia, especially in Maluku with the physiography of small islands, hilly, mountainous topography, steep slopes, small cultivation land, high biodiversity and endemic but with a narrow population or with a small buffer zone so that it is prone to erosion and extinction. Biotechnology as a newly developing field of science may be quite appealing, sexy, attractive to the younger generation or said to have high selling power but the same technology is also used in the field of conservation as empowered as plant genetics and by intagrating it into the breeding and conservation study program, all interests and arguments expressed can be accommodated. The naming between Plant Breeding and PGR Breeding and Conservation is an innovation that is in line with the conception of the Merdeka-Belajar-Kampus Merdeka – MBKM (Freedom of Learning-Freedom of Campus) directed by the Ministry of Education and Culture of the Republic of Indonesia where the campus is free to manage the elaboration and development of its knowledge, as long as it is with the right arguments, according to the vision that refers to the development of its territory. It often happens that small universities refer to and model the rules and practices developed at the center or large University and forget about the uniqueness of one’s own territory.

The naming then needs to be described in the curriculum with courses that will characterize the name for the achievement of the desired goals (Graduate Learning Outcomes-CPL) and of course the implementation of quality practical lectures with fully filled learning materials and time. With the number of credits that must be fulfilled around 140-150 credits or a total of 50-60 courses divided into Compulsory Courses, General Basics, Vocational Basics, vocational specialties and local content are expected to answer the challenges of regional development as well as readiness to compete for the job market in various coverage areas. A further challenge that for me needs attention is the competence of teaching staff. Although a number of teachers have obtained high degrees in the world of S2, S3 education, not all are recognized as competent as teachers (lecturers) in the national education system and the government has provided competency measuring tools, namely through competency examinations to obtain adequate certificates and benefits. This often does not get attention by the institution or maybe because there is still a lack of teaching staff needed and causes problems including in terms of preparing teaching documents such as Semester Learning Plans (RPS), Lecturer Workload (BKD) and others as well as in its implementation, such as insufficient lectures, material and required time periods and others.

Getting around the above problems, one of them can be approached through a blend-based learning system (Blended Learning), one of the forms outlined in the Guide for the Preparation of Higher Education Curriculum in the Industrial Era 4.0 to Support Independent Learning – Independent Campus [80]. The learning system that has been tested successfully on the campus of the Faculty of Agriculture, Pattimura University is able to combine competent lecturers from major universities both in Indonesia and from abroad and lecturers at the original university campus to provide intensive and maximum learning in accordance with the desired CPL.In order to implement the above inputs, one of them is needed leadership that is competent in formulating and implementing the vision-mission and managing available resources to achieve the desired goals where to obtain such leadership requires a structured, inclusive, honest and fair networking and election system at every level of leadership, especially at the highest leadership of the institution and then preserved into a tradition for sustainable development.

Efforts to Recover and Enlarge Bibliography

A number of important and historical libraries including literature that were lost with the loss of the genetics and plant breeding library, although the multipurpose building still stands intact after the Moluccan social conflict, Mr. Anema arranged efforts to restore it through the procurement of additional libraries from Europe by writing to university libraries or professors who ended their tenure and intended to donate literature collected during his tenure and Collect information on whether there is a library rescue in the conflict. The second attempt has not yielded good results considering his presence in Ambon is usually not for a long time. The first attempt was quite successful with the delivery of a container containing a large number of textbooks intended for the Faculty of Theology of the Christian University of Maluku (UKIM) and about 250 titles of which were agricultural libraries intended for the Faculty of Agriculture, Pattimura University, Ambon. The container that has arrived in Ambon is very difficult to remove from the port because of various procedural problems imposed by the port. To overcome this, Mr. Anema asked for help from his colleague, Rev. Jack Ospara, who was then a member of the House of Representatives of the Republic of Indonesia in the Maluku constituency. Rev. Jack risked his position as a member of the House of Representatives to influence the port and paid a fee to remove the container containing the literature.

Literature collected in the collection at the UKIM library which was then moved to Kusu-kusu Village for rescue from social conflicts. During my visit to Ambon, I was asked by Mr. Anema to jointly review the Kusu-kusu Library and observe the library that had been neatly arranged on the library shelves and discussed with the head of UKIM library, Rev. Lex Relmasira, MACE. In an effort to return literature in agriculture to the Faculty of Agriculture Unpatti, the two of us again met the Dean of the Faculty of Theology, Dr. Sonny Hetharia, MTh. then the Rector of UKIM, Rev. Dr. C. A. Alyona, M.Th., together with Rev. Jack Ospara, S. TH, M. TH. and Rev. Lex Relmasira to talk about it. In the discussion session, there was no agreement to return literature to the Faculty of Agriculture Unpatti. I was under the impression that UKIM wanted to keep the literature.

Diversity of Banana Varieties Maluku Unpatti – Wageningen University and Research – Agrofair Company

Having positive international contacts is definitely an advantage in the development of the institution. In 2016 I received leaked information from Mr. Anema in the Netherlands that a professor from the Department of Bio-based Research Wageningan University and Research planned a survey and research project on the diversity of Moluccan bananas,and was asked to write a letter of request for cooperation with Prof. Ersnt Woltering PhD, currently Prof. Emeritus (Em.), If I wanted to get involved. Prof. Woltering agreed and together with other fellow professors, in collaboration with the multinational company Agrofair Company of the Netherlands represented by the managing director, Mr. Hans-Willem Van der Waal, we conducted an intensive survey and data collection on the island of Ambon for a period of about 2 weeks including public lectures by Prof. Ernst and Mr. Van der Waal at the Faculty of Agriculture, Pattimura University and a number of focus group discussions (FGD). The results of our research were published in the African Journal of Agricultural Research 14(33):1693-1712 DOI:10.5897/AJAR2018.13541, October 2018 [81], then published as a book chapter by BP International in a book entitled Research Advances and Challenges in Agricultural Sciences Prof. Marcello Iriti, Eds, Vol. 1, 2 January 2024 , Pages 47-79 https:// doi.org/10.9734/bpi/racas/v1/7014B Published: 2024-01-02 [82] (Prof. Marcello Iriti, Eds, 2024) in addition to being presented as a virtual presentation at the 6th Edition of Euro Global Conference on Food Science and Technology, 2023, Valencia, Spain [83].

Blended Learning – Value Chain Project: Indonesia-Netherlands

Mr. Luud Clerks of the Agrofair Company of which Mr. Van der Wall is Managing Director proposed a project to the Netherlands Organization for the Internationalization of Education (NUFFIC) entitled “Setting Up a Blended Learning Program for Sustainable Inclusive Agricultural Value Chain In Indonesia”. Mr. Luud invited me to discuss it with Pattimura University to participate in being a beneficiary of the project or where the project took place where two counterpart institutions were also involved, Bogor Agricultural University (IPB) Indonesia and Maastricht School of Management (MSM) Netherlands. I sent an SMS to the Rector of Pattimura University asking for a willingness to meet, the Rector directed to the Vice Rector for Academic Affairs (VR 1) and I met WR 1 who proposed to discuss with the Head of the Research Institute. Given the short time to complete the data and files before submitting the proposal to the funding institution, I decided to discuss it with the Dean of the Faculty of Agriculture and was accepted. Mr. Luud’s proposal was then accepted by NUFFIC and we made preparations for the implementation of the project preceded by an exploratory visit by project leader Mr. Luud Clerks, Agrofair Company; Counterpart, Dr. Diederik de Boer, Maastrich School of Management (MSM) and Dr. Idqan Fahmi, IPB Bogor, were received by me who acted as local managers and a number of staff of the Faculty of Agriculture.

The opportunity to visit a number of important institutions and meet experts and business activists in the Netherlands and then focus on learning the cultivation and international trade of cavendis bananas in the world’s largest exporter country, Ecuador, was part of an important learning experience as a BLVC project manager and Pattimura University delegation. The institutions mentioned include Wageningen University and Research, Naturalis Biodiversity Center, Leiden, Verstagen Spices and Sauces Company, Rotterdam, Agrofair Company Headquarters, Barrendrecht etc., as well as farmers’ associations with every link of the chain of value chains of the world Cavendis banana trade. The project which was planned to last 3 years, was extended to 4 years without additional costs due to the Covid-19 pandemic disaster and earthquakes thousands of times in the Maluku islands, one of which had a magnitude of 5.9 on the Richter scale, cracked the campus building of the Faculty of Agriculture where the project activity center was located, stopping all lecture activities. In addition to periodic reports and final reports submitted to NUFFIC, all project activities are published in the Open Access Journal of Agricultural Research (OAJAR), 2021, under the title Preparing and Implementing the Project “Setting Up a Blended Learning Program for Sustainable Inclusive Agricultural Value Chain Development in Indonesia (BLVC); Indonesia-Netherlands Joint Project, in Maluku Islands [84] was later published as a book chapter by BP International under the title Implementation of Indonesia – Netherlands Joint Project-in Maluku Islands: Activities and Outcomes, edited by Prof. Chen Chin Chang under the title Emerging Issues in Agricultural Sciences [85].

Other publications as a further development of the results of the project research were delivered in annual seminars/webiars and proceedings [86] which summarized the presentations of lecturers and students including key speakers, as well as journal publications related to five important Moluccan communities, cloves, nutmeg, bananas, coconuts and sago. Some of them are published in journals and presented at webinars both locally, nationally and internationally [87- 96] including; Development of Maluku Nutmeg (Myristica Fragrans Houtt.): Collaborations, Opportunities and Challenges , European Journal of Applied Sciences: Vol. 10 No. 3 (2022): European Journal of Applied Sciences [97], Development of Maluku Nutmeg Towards Sustainable Living, National Webnar, [98] The Spice Path, Cultural Road to “Sustainable Living” organized by the Archipelago Solidarity Foundation (ARSO), Kemendikbud-Dikti and kompas, https://www. youtube.com/watch?app=desktop&v=Is4yDx-S_TA. The rest of the publications in BJSTR related to the bioprospecting of the Sky Stick Banana [99] and analysis of the banana value chain in Maluku were published in the International Journal of Innovations in Agriculture, 2020, [100].

A total of 11 best students were produced from the project through two lecture editions of Maluku-specific community-based agricultural Value Chain Analysis with programs; 15 face-to-face and online lectures related to concepts and theories of value chain analysis and development as well as value chain research methods and tools; assignment and practicum as well as concrete analysis in one of the selected communities from the five proposed communities, based on literature studies and/or field research; participation in two-day seminars/webinars in each academic year at the Faculty of Agriculture, Pattimura University; preparation of material and presentation of research results on the second day of the two-day seminar held. Each student is awarded an international certificate signed by four institutions; Agrofair Company Netherlands, Maastricht Schhol of Management (MSM), Netherlands, Bagor Agricultural University (IPB), Bogor Indonesia, and Pattimura University, Indonesia.

As an effort to institutionalize the project output of a platform or forum for discussion and implementation of development in the form of nutmeg community “nutmeg innovation platform” involving research institutions (BPTP Maluku), Regional Planning and Development Agency (BAPPEDA) Maluku, Pattimura University (Faculty of Agriculture, MIPA), vocational education institutions on Ambon Island and Seram Island, Micro, Small, Medium Enterprises (MSMEs) Maluku, small to multinational companies, local and international businessmen, government bureaucracy, farmers and farmer groups and communities. This cooperation charter was signed as a Memorandum of Understanding (MoU) by the Governor of Maluku Irjen Pol. Murad Ismail, Rector of Pattimura University Prof. Johannes Sapteno and Managing Director of Agrofair Company, Mr. Hans Willem Van der Waal.

Triple-Helix Strategy, Maluku Living Laboratory

The introduction to Mr. Frits Blessing (Pak Frits) began with a visit with a banana diversity research team to the nutmeg exporting family company Hila Kaitetu, PT Olop, Ambon Island. Mr. Frits is a senior advisor for nutmeg development in Maluku in collaboration with PT Olop as well as with other nutmeg development family companies including Kamboti Pusaka Maluku, fostering farmers and businesspeople and preparing quality nutmeg for export to the Netherlands. In addition to nutmeg, Mr. Frits also paid attention to the development of other fields in Maluku including the conception of close cooperation between various stakeholders that is popular (in Europe) with the term triple Helix; Research Institutes, private parties / businesses and the Government, then added communities / including farmers became the Helix Quadruple and later the term quintuple Helix appeared with the addition of mass media / journalists components. The term clearly arises from the structure of the DNA rope ladder found by James Watson and Fransis Krick in the form of rope ladders that are tightly twisted to each other connected through bonds between nitrogenous bases as steps related to phosphate sugar which is the main framework of the ladder. This picture provides a close cooperation and mutual support to produce important products for the development of organizations, regions, institutions etc.

On one occasion seminar, open science meeting (2017) managed at Gajah Mada University with the theme “Towards Resillient Society” as part of the implementation of bilateral cooperation between Indonesia and belands, Mr. Frits sought a presentation session specifically discussing Maluku, https://opensciencemeeting.org/science-and-applied- research-in-a-3-helix-settingthe-maluku-case/. Mr. Frits and I co-chaired the session featuring a number of speakers from Pattimura University, the Maluku Regional Government / Ambon Municipality, as well as a number of educational/research/biodiversity conservation institutions from the Netherlands. The results of the seminar were summarized in proceedings distributed to the participants, through both co-chairs [101,102]. Through good connections internationally, Mr. Frits was invited to deliver lectures related to the development of Maluku nutmeg through the nutmeg innovation platform, to graduate students of the Institute Mines Telecom Business School Paris, for the care course of Prof. Anuragini Shirish (https://www. linkedin.com/in/anuragini-shirish-054012b/?originalSubdomain=- fr). As part of the founder of the Maluku nutmeg Innovation Platform, I was asked by Mr. Frits as a refutator and assessor in a student group presentation, virtually [103]. A number of seminar meetings and intensive discussions and cooperation planning with Mr. Frits were carried out with the city of Madya Ambon, LIPI Ambon and Pattimura University related to waste management in Ambon City, development of biodiversity collection gardens etc., including initiating the thought of Maluku as a Living Laboratory where various research and development activities in various aspects are pursued mainly by involving the younger generation.

Maluku Biodiversity Conservation Center

As always Mr. Anema often commutes between Indonesia, Maluku in particular and the Netherlands, always I will be given a message of his arrival and an appointment to enjoy a bottle of beer. In our meeting in Jakarta, when returning from Germany, I submitted a TOR of about 3 pages related to germplasm conservation, while discussing it, this paper, along with other writings was later developed and published and presented at a national seminar in Maluku [104,105]. Sometime later after returning from the Netherlands for the umpteenth time he gathered a number of colleagues from the Faculty of Agriculture to conduct an audience with the Governor of Maluku, BridJen (Ret.) K. A. Ralahalu, discussing the conservation of Moluccan genetic resources and the possibility of establishing a conservation institution. The hearing gave birth to several recommendations, first it is necessary to hold a comparative study with Papua Province to then seek to make regulations related to sago conservation or make a sago PERDA by BPRD Maluku, second, a delegation needs to be sent to attend a seminar which is also related to germplasm conservation which will take place in Bogor, third needs to be explored conservation funding procedures through the Dept for Nature Swapt (DNS), a system of foreign debt relief offered by several countries to Indonesia in exchange for biodiversity conservation programs/activities, the fourth is in accordance with the initial spirit of the meeting, namely the establishment of a Moluccan genetic conservation institution.

The comparative study to Papua province at that time as far as I know has not been carried out, but I and several colleagues were asked to prepare a scientific basis for the establishment of the sago regional regulation whose preparation was then more on biodiversity conservation in general. Until now, the sago regional regulation or biodiversity has not been socialized even though information circulated that the sago regional regulation has been produced. Participation in the national seminar in Bogor was represented by me, and Dr. A. Leatemia, we met Former Unpatti Rector Prof. J. L. Nanere at the seminar location while Mr. Liewe Anema was unable to attend. The assessment of funding through DNS is currently still a literature study and there are no concrete results, then the formation of a conservation organization was carried out after an audience at the level of the Department of Agricultural cultivation and a Decree of Establishment was made by the head of the Department with Dr. Max Pattinama as the head of the organization. In subsequent developments, there was an intensive debate regarding activities, vision and mission in the development of the institution and I declared my resignation as part of the conservation organization majoring in Agricultural Cultivation, Faculty of Agriculture Unpatti, through a letter of resignation submitted to the chairman.

A few months after resigning I prepared a proposal to be submitted to the Governor of Maluku, Year 2006 [106]. The proposed institution is centered and implemented at the Maluku Province level with the Governor of Maluku as Protector, but with a broad scale of cooperation including local, national and international. The proposal in which Mr. Anema and Prof. Em. G. A. Wattimena as part of the advisory body, was accepted and then submitted for opinions to several service heads. I met with the Head of the Forest Service and talked about it sometime before the end of Governor Bridgen K. A. Ralahalu’s term. At the international conference “the 9th International Conference on Small Islands Culture (ISIC 9th)” held in Tual-Langgur, Maluku, Indonesia, 10 – 13 July 2013, opened by the Governor of Maluku Bridjen (ret.) Ralahalu, I met Prof. Mike Evans from Southern Cross University Australia, currently Dean of Irving K. Barber Faculty of Arts and Social Sciences Okanagan, University of British Columbia (UBC) Canada. Prof. Mike Evans, michael.evans@ubc.ca interested in the conservation of genetic resources for food security, a theme that I presented on poster [107] that I presented at the conference. We discussed and developed it more deeply, agreed to publish it as an article in an international journal with Prof. Evans as corresponding author. A few months later our article was published in the Journal of Marine and Island Cultures [108] and later became one of the main reference materials in presentations at an international conference organized by the Faculty of Agriculture, Pattimura University [109]. Furthermore, I asked for Prof. Evans’ willingness to become one of the members of the advisory board of the Maluku biodiversity conservation center (PPKM), he expressed his willingness and was sent proposals and reports on the development of the institution.

After two terms of BridJend Ralahulu’s administration ending his term as Governor of Maluku, I met him on one occasion in his office as a Party branch leader, discussed conservation institutions including a number of policies he had during his tenure as Governor as well as asked for his willingness as chairman of the PPKM Advisory board and was approved. I was asked to contact Dr. Sihaloho, the acting head of the Maluku Regional Development Agency (BAPEDDA) during his administration to obtain a co-authored book outlining some of Ralahalu’s strategic policies. Another input was to request an audience with Governor Ir.S. Assagaf who was then in office to discuss further the PPKM institution. Various discussions, inputs and literature materials obtained were then part of a publication compiled with Mr. Liewe Anema in Bali and submitted to the European Journal of Applied Science (EJAS) [110].

The audience with Governor Ir. S. Assegaf did not last long, but was also producive. He set aside time at 10.00 a.m. the next day when asked for an audience on an occasion to open a semester public lecture at the Faculty of Agriculture, Pattimura University. Important things discussed include, one that the establishment of the Maluku Biodiversity Conservation Center (PPKM) legally/officially will be based on a Decree (SK) of the Governor of Maluku and for this I need to contact the Legal Bureau of the Maluku Governor’s Office, secondly the establishment of PPKM needs to be discussed with the Maluku Agriculture Office. The second thing has been carried out through a focused discussion (FGD) involving several important staff of the Maluku Agricultural Office through the direction of the Head of Service, Ir. Diana Padang, MSi. The second thing has not had time to be fulfilled.

Foundation for People with Disabilities of the Protestant Church of Maluku (GPM)

Rev. Jack Ospara, a well-known figure in Maluku for his involvement not only in the service of the Maluku Protestant Church congregation both as a pastor / servant of God and as part of the gerja management organization through the Daily Workers Body of the GPM Synod, but also as a community leader and Member of the Indonesian People’s Representative Council for the Maluku Electoral Area. A colleague and friend of Mr. Anema who helped each other in a number of tasks performed. Rev. Jack Ospara is the founder and chairman of the Board of Trustees of the GPM Foundation for Persons with Disabilities in which Mr. Anema sits as a member of the trustees. In the last few years before being called home to the creator, Rev. Jack invited me to a meeting attended by a number of managers and trustees of the foundation. I was asked and appointed at the meeting, to be the chairman of the foundation development institution with the main task of formulating proposals for foundation development, especially efforts to provide education and training for people with disabilitieswho become students of the foundation to be able to stand alone to support their lives in the future.

He is optimistic about a number of parties who are willing to provide financial support for the development if the planning has been completed. In addition to a number of assets owned, a plot of family land and an additional number of hectares granted to other areas for the development of the foundation are ready to be measured and mapped in the White Elpa area and will be the location for the development of training facilities including agriculture and animal husbandry. I prepared several fellow land mappers from the Department of Soil, Faculty of Agriculture, Unpatti under the direction of Ir. Elly Gaspers, SU, to immediately go to the location after several preparatory meetings. Its implementation was then abandoned with the death of the Chairman of the Foundation Rev. Jack Ospara.

Mr. Anema took the initiative to gather the chairman/executive secretary and a number of administrators and trustees held a meeting to discuss the sustainability of the Foundation. Mr. Anema and I further visited a number of foundation schools and met principals and teachers in the Latuhalat and Mardika areas to listen to problems and possible solutions in the future. The efforts made with Mr. Anema are enough to give new enthusiasm for the future development of the foundation, but the most important thing is the legal status/legality of the foundation organization after the death of the founder and chairman of the board of trustees of the foundation. Mr. Anem’s efforts to approach the family do not seem to have given optimal results.

Village Development Center Team Prof. Em. G. A. Wattimena

Professor Gustaf Adolf Wattimena, a Moluccan scientist who is respected in Indonesia and abroad. The permanent lecturer of Bogor Agricultural Institute (IPB) Bogor with MSc. and PhD. The graduate of the University of Wisconsin is one of the few Indonesian scientists who is a reference for the development of biotechnology in the country. At the end of his term of service he was awarded prof. Emeritus as part of the appreciation of outstanding achievements obtained during his work as a scientist.Prof. Em. Wattimena fostered many Moluccan students, especially from the Faculty of Agriculture and Fisheries Unpatti who continued their learning at IPB Bogor, both directly as a thesis/dissertation supervisor and indirectly, both academically and outside academia. His house is often a stopover and reference for consultations for seniors regarding the current conditions and development policies of Faultas and Pattimura University in the context of national development in his time.

It is undeniable that sometimes there are differences in attitude with postgraduate students from Maluku because of the discipline applied to themselves and those around them and wanting a high academic performance at the IPB Alma mater. He often reminded not to avoid lectures (courses) that are difficult and require hard work. In my opinion and some fellow IPB graduate students, even other colleagues outside IPB, he deserves to be given a work mark as a tribute to the Moluccans and a booster of enthusiasm and pride in a scientist as great as Prof. Em. G. A. Wattimena. We prepared a project proposal, consulted with a number of Moluccan colleagues both at IPB Bogor, Jakarta and others as well as Prof. Em. Wattimena. We put Ir. J. J. Tuhumury former Dean of the Faculty of Agriculture as chairman, me as secretary and Mr. Anema as deputy head of the project implementation team called the Village Development Center Prof. Em. G. A. wattimena. Mr. Anema as the current head of the implementation team, has visited Prof. Em’s birth village. Wattimena is exploring interest and the possibility of further project development. The project proposal was published in the Dewa general daily, Ambon [111].

Drinking Companion and Smile Developer’s Little Story

Every meeting with Mr. Anema will begin with social media communication and an appointment to enjoy a beer together. Beer is a social drink, common for Dutch, Germans and Europeans in general. We enjoyed beer together in Amsterdam, Quetlinburg, Jakarta, Ambon, Bali and others while telling each other about our days. Later, as we aged, we reduced the number of bottles we drank from two to one or replaced them with coffee lattes, or the occasional iced cream without the addition of other additions to the occasional addition of meat. The culture of the Uraul people also involves homemade sopi from coconut or enau and is often combined with wild boar meat. The concentration of alcohol in sopi is much higher so that the drinking dose is not as large as beer which only contains about 5% alcohol. The people of Teon Nila Serua, my village, have the same custom, using sopifor various traditional events and other purposes, they include those who do not agree if sopi is eradicated in Maluku. Government policy, presented at socialization events or in limited collegial discussions, develops sopi in a more controlled and profitable way, for example, one of them, producing at a trademark for trade that is legal, in accordance with regulations, for personal use on a small scale is acceptable, not necessarily regulated. A person’s closeness to a particular culture is often judged by humorous attitudes born from daily life experiences in society. Pak Anema understood well the funny attitudes and stories of the Moluccans and made us laugh together. I once explained to him that a man from the Moluccans saying “little” has nothing to do with numbers; “Eat a little”, “add a little”, or “sleep a little”, will equal or even more the amount he eats, adds or sleeps, the word little just to reinforce his initial statement. As usual, we then laughed together. In our discussion with a Dean, the Dean wanted to explain about “sopi”, but Mr. Anema changed it to “water”.

Divorce and Marriage for the Second Time

In the preparation period to return to Indonesia from Germany, I occasionally called Renkum and talked to Willy’s mother, Mr. Anema was not at home and occasionally Willy’s mother grumbled. In Jakarta Mr. Anema and I met as usual for drinks together and on one occasion he said seriously that he was divorced from his wife in the Netherlands, we continued drinking without any further conversation. On another occasion I was invited by Mr. Anema to meet Ruth’s friend and some of Ruth’s co-workers, then conveyed their plans to get married and I was asked to be a witness to Mr. Anema’s marriage, as well as assist in the administration of civil registration at the local sub-district office. I agree as a former subordinate and also as a good friend of his. In the meeting between the two families, as well as arranging the wedding procedures, Mr. Anema and I were present and I was given the position of treasurer in the structure of the wedding implementation committee.

The management of civil registration registration is somewhat challenging in terms of operating costs. On the official fee list posted on the notice board of the office, the registration fee is 300. 000 rupiah, but because it already uses intermediaries and it may be known that those who marry are of foreign descent, the cost becomes five times. I initially argued with the clerk but later agreed with the stipulation that some be paid at the Office and others paid later at the wedding after receiving the certificate. The wedding went smoothly, I signed the wedding minutes with slightly trembling hands then as treasurer, paid in full all the performers with funds from the groom.

Seeking Matchmaking

Being in your 60s and not having a life partner has its own advantages and disadvantages. The judgment of the other party can be negative and positive generally depending on their interests and not the interests of the party concerned. In the past, several times I asked Mr. Anema for his willingness to find a suitable partner or without being asked, Mr. Anema seemed to want to meet someone. Currently, the opportunities are getting narrower considering the increasing age. The development of information technology and the openness of the world and people’s attitudes towards arranged marriages seem to have a positive influence on the opportunity to get a soul mate. The emergence of a large number of matchmaking sites and other social media such as Facebook, Instagram, Telegram, TikTok and others provides an opportunity to introduce themselves to their respective choices according to the desired creteria even between different countries.

In a discussion with Mr. Anema once I thought that finding a mate through social media is easier in approach, but there can be incompatibility when meeting. Conversely, direct meetings will immediately be known interest in each but it is rather difficult to start, a supportive liaison is needed, on the other hand it is also rather difficult or rigid to decide if one party does not feel interested. Of course this is a personal opinion.

Adding that I could have given a different age on social media, Mr. Anema argued seriously that it would definitely be known later. The other time I blackened my gray hair and explained that with black hair I could cheat on age, we smiled.

Cover

Working with Mr. Anema means completing work and respecting time, every plan is carried out, problems that arise are resolved and not allowed to become obstacles or reasons for not completing a job. He happened to be in the position of guest of the institution and was known and appreciated by many officials of his time. It is not uncommon for technical work to be completed on its own without going through complicated and convoluted procedures; When completing the laboratory filling work with a number of equipment from the former laboratory of the Ambon Institute of Technology (ITA), he personally lifted the necessary equipment and materials without asking for technical assistance. The same thing happens when meeting officials; several times he immediately entered the office if he wanted to meet the Rector or Governor. When meeting Governor Ralahalu at the Mess Maluku Jakarta, Mr. Anema immediately went to the Governor as soon as he met, but there were other regional governors who had already made an appointment so Mr. Ralahalu signaled to wait a while, then approached us and held the meeting informally.

Mr. Anema asks for hard work and responsibility, building discussion habits, freedom to give opinions and input, providing encouragement and reinforcement and providing necessary facilities for both learning and research, and assessing fairly when being a mentor. After completing my S2 and S3 education levels, I became a colleague, occasionally arguing fiercely at official meetings, being a good friend who was comfortable meeting and discussing, talking about little cuteness and laughing, enjoying life, anywhere and anytime.

Mr. Anema may also reap displeasure from a number of parties, one of which is because he is considered to have violated the applicable procedures, speeded up the completion of work, but many also appreciate because of the results obtained and especially in the past, because of his attention to various things that have escaped the concern of many parties. On the other hand, in the position as a visiting / foreign scientist in institutions, as well as regions, it is precisely in his place to work between or at the level of high officials of institutions and regions, and it is his duty and obligation to complete the work according to the assignment. We have tried to develop genetic learning and plant breeding at Pattimura University at least following the example of Bogor Agricultural University (IPB) with provisions from Wageningen University and Research, and experience from the Netherlands, through the provision of various physical and non-physical infrastructure and further development planning, but the desired sustainability seems to be very dragging in achievement due to various factors that are beyond reach, including social conflicts that take place in Maluku, inconsistent vision and mission that need to be the legacy of the next generation, and other factors.

Acknowledgments

The author thanks his foster parents, Mr. and Mrs. Alex and Jul Pelupessy for supporting his personal and professional development. Different personalities at different institutions and times have offered supports and encouragements.

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Journals on Medical Microbiology |BJSTR

OssDsign Catalyst® Bone Graft Performance in a Three-Level Extreme Lateral Interbody Fusion (XLIF®)

Introduction

Spinal fusion is commonly performed in patients with a variety of pathologies when conservative treatment fails resulting in continued pain and functional limitations. These symptoms decrease the quality of life for an individual to the extent that surgery may be indicated [1]. Minimally invasive interbody fusion techniques using anterolateral approaches such as Extreme lateral interbody fusion (XLIF®, NuVasive, Inc., San Diego, CA) have been developed to avoid disruption of the posterior spinal column, while permitting wide exposure of the disc space, use of larger interbody cages, shorter operating times, less blood loss, and indirect nerve root decompression [2,3]. The use of synthetic bone grafts has become mainstream in recent years with advances in nanoscale architecture, microporosity, and ionic substitution designed to amplify signaling pathways to instruct bone formation [4,5]. A new silicate-enriched (5.8 wt% silicon) calcium phosphate bone graft substitute (Catalyst®, OssDsign A.B.) with nanoscale architecture is gaining popularity among spine surgeons in the US. The following is a report on the use of Catalyst in a challenging three-level XLIF case.

Case Description

This case reports the results of a 60-year-old male (BMI 32.3) with a prior history of high blood pressure and endocrine disease who presented with severe back and leg pain causing severe disability (Visual Analogue Score (VAS) for pain: VAS Back – 8.5/10, VAS Right Leg-5.5/10, VAS Left Leg 8.5/10, and Oswestry Disability Index (ODI) score 76%). He had several lumbar decompression (laminectomy) procedures in the past along with an uninstrumented L5-S1 posterolateral (PLF) fusion and a C3-C7 cervical fusion (ACDF). Pre-operative X-rays (Anterior-Posterior (AP) and Lateral) of the lumbar spine are shown in Figure 1. Magnetic Resonance Imaging (MRI), clinical, and radiographic examination revealed degenerative disc disease (DDD) at 3 levels (L2-L3, L3-L4, and L4-L5). After 6 months of conservative treatment and administration of both narcotic and anti-inflammatory medications, the patient chose to have surgery after having been informed of the potential risks and benefits. The surgery was performed in a staged fashion in May 2022 and consisted of a three-level, minimally invasive, XLIF® at L2-L5 using three PEEK interbody cages, one at each level, approved for use with Catalyst® Bone Graft. Each cage was filled with 8cc of Catalyst, totaling 24cc. The second stage was done two days later adding posterior instrumentation with pedicle screws and rods with local autograft placed in the lateral gutters. There were no intraoperative complications seen in either procedure. The patient returned for follow-up examinations at 3, 6, and 12 months.

Figure 1

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Results

At 3-month follow-up, plain X-rays (AP and lateral images) revealed the instrumentation to be intact and well-positioned. VAS Pain Scores and ODI improved significantly from the pre-operative scores (VAS Back-2/10, VAS Right Leg-1/10, VAS Left Leg 1/10, ODI 46%). At 6-month follow-up, pain, and function further improved and radiographic findings, both X-Ray (Figure 2) and CT scan (Figure 3), showed complete interbody fusion at all three levels. At the 12-month follow-up, the patient was generally pain-free (using only occasional over-the-counter pain relief, Figures 4 & 5) with significantly improved function (VAS Back-1/10, VAS Right Leg-0/10, VAS Left Leg 0/10, ODI 30%). Radiographic findings, both X-ray (Figure 6) and CT scan (Figure 7) at 12 months confirm complete interbody fusion at all three levels. There were no post-operative complications seen during the follow-up period.

Figure 2

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Figure 3

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Figure 4

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Figure 5

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Figure 6

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Figure 7

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Discussion

Recent studies have shown minimally invasive multi-level interbody procedures such as XLIF and others (e.g, OLIF, ALIF and TLIF) to be comparable with respect to fusion rates and global sagittal alignment [6-8]. Catalyst bone graft was shown previously to provide consistent and rapid bone healing in one-level TLIF patients with significantly improved VAS and ODI scores8. The case described here finds earlier than expected interbody fusion at 6 months with corresponding clinical and functional improvement, which was confirmed at the 12-month follow-up visit. This patient’s outcome in a multi-level XLIF with challenging comorbidities (i.e., obesity, multiple previous spine surgeries, endocrine disorder) provides support for the use of this bone graft substitute in more challenging patient scenarios.

Acknowledgement

We particularly thank the Clinical Study Coordinator, Rebekah Vinson, who enabled the recruitment and all the data collection for this Case Study and the OssDsign Spine Registry through which the data has been collected.

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Journals on Emergency medicine |BJSTR

Radiofrequency Ablation Sacroiliac Joint Pain

Introduction

Low back pain is a common concern for many individuals worldwide. In the United States, it affects two-thirds of Americans during their lifetime [1]. The sacroiliac (SI) joint is a frequent cause of low back pain, with its incidence increasing if a patient develops low back pain after lumbar fusion surgery [2]. The spine, pelvis, and legs are functionally interconnected. The SI joint serves as a shock absorber and engages in force transmission between the upper body and legs during activities such as walking, running, jumping, and bending. It acts as a stress reliever and adds resilience to the pelvic girdle, preventing fractures under the tremendous forces it endures during various bipedal activities [3]. Risk factors for SI joint dysfunction include obesity, leg length discrepancy, scoliosis, pregnancy, and repetitive or chronic microtrauma [4]. A leg length discrepancy can increase the stress across the SI joint fivefold. Age-related changes begin early in life and continue throughout. The primary function of the SI joint is to provide stability, allowing little movement. Movement in the SI joint has been measured in all planes but is limited to 2 mm horizontally and less than 6 degrees in rotation. While hypermobility is not typically associated with pain, pain is commonly seen with instability, multiparity, and muscle-related weakness.

Anatomy

The SI joint is a large diarthrodial joint located between the iliac bones and the sacrum (Figure 1). It is synovial only in the anterior superior part with fused posterior inferior part. There is significant variability between individuals regarding the shape and size, the surface area of the SI joint is about 17.5 cm2, and the volume is 0.6–2.5 ml [5]. The innervation of the SI joint is not well established. The ventral and dorsal parts have separate sources of innervation. The dorsal part is innervated by the lateral branches of the L4-S3 dorsal rami, while the ventral part is innervated by the ventral rami [6]. Myelinated and unmyelinated fibers have been found in the capsule, and small fibers positive for substance P and calcitonin gene-related polypeptide have been found in the cartilage [7]. The nociceptors in the SI joints have a higher threshold than those in the facet joints but a lower threshold compared to those in the discs. The network created by the lateral branches of the dorsal rami is the target of diagnostic blocks and ablative therapy [8]. These nerves consistently course over the lateral sacral crest. The SI joint provides stability during movement, better withstanding medially directed forces than torsion or axial compression loads [9]. Torsion and axial forces preferentially injure the weaker anterior joint capsule [10]. Strong ligaments and muscles support the joint, but as we age, our bones can become arthritic, and these ligaments may stiffen, causing the bones to rub together and produce pain.

Figure 1

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In addition to low back pain from irritation to the free nerve endings in the joint, SI joint pain can cause symptoms such as numbness, tingling, or weakness that radiates to the lower extremities [11]. Symptoms are typically worsened by sitting on the affected side, and patients may present with difficulty riding in a car, prolonged sitting or standing, or climbing stairs. SI joint pain can mimic other conditions such as herniated discs or hip pathology, making proper diagnosis crucial. In addition to a detailed medical history, experienced providers use joint manipulation and various functional tests, such as Patrick’s test, Gaenslen’s test, SI joint shear test, Yeoman’s test, compression test, and thrust test, to assist in diagnosis. If pain is reproduced with most of these stress maneuvers, the SI joint is considered the primary pain generator. However, the validity of these maneuvers has been questioned recently [12]. Imaging studies, such as X-ray, CT, or MRI, have poor sensitivity, specificity, and diagnostic utility for SI joint pain. Their main utility is to exclude other dysfunctions in the neighboring spine and hips. Typically, a diagnostic SI joint injection is performed to confirm the cause of the pain. SI joint involvement is confirmed if the patient’s pain level decreases by more than 75% with the diagnostic injection. Image-guided injections, either intra-articular or targeting the lateral sacral network, are the only reliable methods for selecting patients for ablative therapy.

Dual diagnostic blocks with at least 70% pain relief have Level II evidence for accurately diagnosing the SI joint as the source of pain, while single diagnostic blocks with at least 75% pain relief have Level III evidence. Single injections cannot detect false positives, which have a prevalence of 12-26% with dual blocks. Intra-articular injections underdetect SI joint area pain, which is more effectively identified by lateral sacral branch blocks, predicting better ablation outcomes [13]. SI joint pain is initially treated with non-interventional modalities, including physical therapy, NSAIDs, and muscle relaxants. The evidence for NSAIDs in treating SI joint pain is not conclusive and is based on expert opinion. Interventional treatment options include intra-articular steroid injections, prolotherapy, percutaneous sacroiliac joint fusion, and radiofrequency ablation [14]. There are various causes of SI joint pain, both traumatic and non-traumatic. Non-traumatic causes include rheumatoid arthritis, pregnancy, inflammatory bowel disease, and metastatic cancer [15]. Spinal metastases are a frequent complication of cancer that often goes overlooked. Autopsy studies indicate that about 30% of all cancer patients will develop some kind of spinal metastasis [16].

Although the liver and lungs are more common sites for overall metastasis, autopsy reports show that 60-70% of patients with metastatic cancer acquire spinal metastasis. The thoracic spine is the most common location for spinal metastasis (60-80%), followed by the lumbar spine (15-30%) and the cervical spine (<10%) [17]. Such involvement of the spine can cause instability and deformity and may lead to complications such as pathologic vertebral compression fractures (pVCF) and metastatic epidural spinal cord compression (MESCC). Approximately one in ten patients with spinal metastases will develop MESCC, and another 12.6% will develop a pVCF [18]. The SI joint can be subjected to indirect stress from primary, secondary, or metastatic cancer in the spine, resulting in pelvic imbalances and unequal weight distribution. By the time bone metastasis occurs, treatment aims to control pain and maintain quality of life. Understanding the epidemiology should increase awareness of the first symptoms and promote early diagnosis, emphasizing the prevention of future skeletal complications, and thus improving overall outcomes [17] (Figure 2).

Figure 2

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Ablative Therapies for SI Joint

Pain is always best managed when the underlying pathophysiology is treated. However, the pathophysiology of chronic SI joint pain, even when cancer-related, often cannot be effectively treated. The innervation of the SI joint is accessible for ablation, making it a suitable target for intervention. Radiofrequency Ablation (RFA) uses electrical energy to create thermal energy that destroys the nerves causing pain. In 1931, Martin Kirschner used a direct current (DC) via an uninsulated needle to ablate the Gasserian ganglion to treat trigeminal neuralgia [19]. High frequency alternating current (AC) produced controlled lesions, with frequencies (300-500 kHz) similar to those used by radio transmitters, hence the name “radiofrequency ablation” [20]. The rapidly alternating electrical field in RFA causes ion vibrations (including water molecules) at the same frequency, generating heat that denatures proteins and leads to cell death. Although RFA has been a treatment option for SI joint pain since 2001 [21], it may sometimes be overlooked for cancer-related pain. Because RFA is a localized procedure at the site of pain, it tends to have fewer unwarranted systemic side effects compared to oral medications, which is advantageous for palliative care patients. Additionally, there are few contraindications for RFA beyond the standard risks of infection and bleeding common to any surgical procedure. Multiple RFA techniques for the SI joint are used in practice today. These techniques vary in target visualization methods, lesioning techniques, and target sites. The outcome of RFA depends on proper patient selection and accurate needle placement during the ablative treatment.

Target Sites

The SI joint is extensively innervated by the L5 dorsal ramus and the lateral branches of the S1, S2, and S3 dorsal rami of the sacral nerves. The unique innervation of the SI joint and its anatomical variations present various challenges for clinicians. The purpose of this article is to review these different techniques and demonstrate how Radiofrequency Ablation (RFA) can be a valuable intervention for chronic SI joint pain including in terminal cancer patients seeking palliative care options (Figure 3). There are numerous approaches, each with varying levels of evidence. A systemic review favors cooled RF approach over conventional RF. Irrespective of the technique the target is the same, lateral branches form L5- S3. Traditional target sites around the sacral foramina for lesioning have been questioned. Stout et al in a cadaver study demonstrated that RFA lesioning using traditional targets would result in incomplete lesioning in 40% of cases [22]. New specific targets were found through cadaver dissection with overlaying radius epsilon then captured by fluoroscopy. They proposed 4:30 and 6:00 for S1; 2:30, 4:00, and 5:30 for S2 (unchanged); and 1:00 and 2:30 for S3 on the right side. The targets for the left are the mirror image on the right: 6:00 and 7:30 for S1; 6:30, 8:00, and 9:30 for S2; 9:30 and 11:00 for S3. They claimed 95% success rate assuming ablation size is as expected. Robinson et al quantified the relationship between the posterior sacral network and bony anatomical landmarks [23].

Specifically, the first, second, and third transverse sacral tubercles (TSTs) of the lateral sacral crest are consistent bony landmarks identifiable by ultrasound. The study used digitization and 3D modeling to then determine mean distances for posterior sacral foramina and interforaminal distance in tested sacra for males and females. The aim of these anatomical studies is to better quantify the anatomical relationship of nerves to bony landmarks which allows for better accuracy for lesioning with RFA. In general, the lateral branches of L5 and S1-S3 dorsal rami are targeted lateral to the posterior sacral foramina and a larger lesion area will minimize missing a nerve due to anatomical variations. Exact needle locations vary depending on the device and technique being used.

Figure 3

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Lesioning Techniques

Conventional Radiofrequency

Conventional RF is performed using monopolar or bipolar technique. In monopolar technique needle gauge and orientation determine the burn size while in bipolar the spacing between the needle tips must be optimal for ablation as burn area is between the needle tips. Roberts at al studied seventeen different ablation approaches and found bipolar approach is more successful in ablating lateral nerves than conventional monopolar radiofrequency ablation [24]. In conventional monopolar approach, the sacral foramina are imagined as face of the clock and needles are placed at regular intervals around the lateral edge of the foramen. The usual positions are 1:00, 3:00, 5:30 on the right and 11:00, 9:00 and 630 on the left at S1 and S2. At the S3 and S4 levels, the needle clock face positions are 1:30 and 4:30 on the right, and 7:30 and 10:30 on the left (Figure 4). A number of bipolar approaches are used to ensure effective ablation of lateral branches. Multiple needles of various gauges are placed along the line from S1 to S4 5- 10 mm from the lateral margins.

Figure 4

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Needle gauge varies from 22 to 17 and they are placed 4 mm to 15 mm apart. Four commonly used techniques are leapfrog technique (22g needles placed 4mm apart), palisade technique (20 g needles placed 10 mm apart), Nimbus continuum technique (17 g needles placed 15 mm apart), and lateral crest technique (same as palisade). The bipolar approach is considered less cumbersome with reduced cost as produce can be done in a shorter time [15,25] (Figures 5 & 6). Multi-lesion probes such as Simplicity III are available which can produce continuous strip lesions for more complete denervation. The probe has three active sites which create overlapping three monopolar lesions and two bipolar lesions resulting in a total burn area of 9mm x 52.5mm [26] (Figure 7).

Figure 5

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Figure 6

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Figure 7

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Cooled RFA

Cooled RF is a variation of conventional RF approach that has been used to treat SI joint pain since 2013. Thermal energy in standard RFA is limited by desiccation and overheating of the targeted tissue, which limits consistent lesioning during the procedure. In cooled RFA, water is used to keep the needle tip temperature at 60C which results in consistent and uniform heating of the surrounding tissue resulting in on average lesion that is twice the size of lesion compared to conventional RFA which results in more complete ablation of the target nerve fibers [27]. The probe is 17 g in size with a 4 mm active tip. The target points around the sacral foramen are the same as in conventional RF (Figures 8 & 9). The safety and effectiveness of cooled RFA was reviewed in a met analysis by Sun et al. [28] and found that the procedure is effective and safe. The mean drop in pain score was 3.81 or 3.74 depending upon the scale used. Furthermore, one study suggests that repeat cooled RFA procedures resulted in longer pain relief than single procedures. For standard cooled RFA procedures, the average duration of relief was 5.5 months after the first procedure and 9 months after the second procedure. Through a further review of patient records, the study found that RFA reduces utilization of medical care (41%) and repeat RFA resulted in a 59% reduction in utilization of medical care, and a reduction in medical costs accordingly [29].

Figure 8

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Figure 9

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Level of Evidence for Various RF Approaches

Three systemic and one narrative reviews have been published evaluating the effectiveness of various RFA techniques. In the most recent systematic analysis Lee at al analyzed 37 studies encompassing 8 RCT, 14 retrospective and 11 prospective studies including 4 case reports. Despite the variability in types of radiofrequency technology, technique, nerve targets, and study methodology, most studies found that substantial proportions of patients achieved at least 50% or more relief at 1, 3, 6, and 12 months following lateral nerve ablation. Using the GRADE system, evidence was rated at moderate level to effectively reduce pain and disability in majority of patients with posterior joint complex SI joint pain at 1, 3, 6, and 12 months. The level of evidence was upgraded to high quality when only anatomically validated techniques were assessed.

Endoscopic RFA

Recently, endoscopic visualization has been used to localize the posterior sacroiliac ligament in the effort to treat SIJ pain. Ablation of the lateral branch nerves innervating the posterior capsule of the SIJ and overlying soft tissues using a bipolar radiofrequency probe through the endoscope’s working channel has had favorable clinical outcomes [30]. The endoscope allows visualization of sensory nerve fibers with a diameter between 0.21 and 1.51mm, allowing precise targeting of the L5 dorsal rami and lateral sacral branches from S1, S2 and S3 dorsal sacral rami Therefore, this approach may be particularly useful when a patient’s anatomy and/or previous fusion/surgical hardware may obscure the view using traditional fluoroscopic visualization. Chen CM, et al. even compared the efficacy of performing endoscopic rhizotomy vs Cooled RFA approaches for treatment of SIJ pain [31] (Figure 10). The study compared outcomes of 72 patients over the course of 1 year and found better functional outcomes and longer duration of symptoms in the full endoscopic rhizotomy group vs the cooled RFA group. In addition, only 8% (3 out of 36) of patients in the endoscopic group experienced recurrence of pain as opposed to a 61% recurrence rate after 1 year from RFA. Of note, however, the average operation time for the navigation-assisted endoscopic procedure was 61.8 minutes, which was almost double the time for cooled RFA procedure [32].

Figure 10

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Cryoneurolysis

Cryoneurolysis is a technique that targets nerves with extremely cold temperatures to temporarily destroy the nerves (the application of cryoneurolysis). Cryoneurolysis is used in a wide array of pain management plans. Cryoneurolysis probes are larger and would result in larger lesions thus avoiding the pitfall of missing lateral sacral nerve branches seen with various RF approaches. Sahoo et al. [33], outline five case studies that used cryoneurolysis for SI joint pain specifically. All five patients were selected after at least 50% pain improvement to 2 ml intraarticular injection of 2 ml 2% lidocaine. Cryoneurolysis was performed a week later. Ultrasound was utilized to confirm the probes were localized lateral sacral crest and 14g cryoprobe was placed with ultrasound guidance along the lateral crest. Fluoroscopy was used to confirm that the probe is lateral to sacral foramina in AP view and is lying on the sacral bone in lateral view. The optimal position was verified by checking sensory and motor stimulation with electrical stimulation at 50 hertz and 2 hertz respectively (Figures 11 & 12). The technique included two cycles of four minutes split into a three-minute freezing cycle and a one-minute defrosting cycle. Freezing and defrosting was visualized under ultrasound. After this procedure, patients were followed up at one month, three-month, and six-month intervals. At one month, three patients had no complaints of pain and two patients had 1/10 pain. At the three and six months, all the patients reported greater than 50% pain relief. These initial results show promise for cryoneurolysis to be more widely used for SI joint pain. There are many advantages to this procedure as well. One advantage is that cryoneurolysis only requires a single skin entry point as opposed to cooled RFA which requires at least eight points of entry. The complication rate as high as 20% has been reported after RF of SI joint [34]. Cryoneurolysis is potentially a less expensive approach with potential to have lower incidence of numbness and tingling. Cryoneurolysis shows promise as an option for SI joint pain but requires further study.

Figure 11

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Figure 12

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MR-HIFU

Another option for patients with SIJ pain is MRI guided high intensity focused ultrasound (MR-HIFU) [35]. With this technique, patients undergo MRI imaging and use ultrasound probes to generate enough heat that can effectively treat SI joint pain. Thus, the main advantage with this technique is that it is non-invasive and avoids the use of radiation. In addition, with the use of MRI, pain centers can be more precisely targeted over standard X-ray imaging such as with RFA. But the procedures require immobility necessitating some form of anesthesia. Planning is done using a 3D T2w paramedian MRI image directly lateral to sacral foramen. The dorsal L5 ramus and the lateral branches of the S1–S3 dorsal rami are targeted. Target picked are treated with US 1.2 MHz probe using 60-120 W power with the aim to generate temperature over 60C within the tissue. Therefore, MR-HIFU provides alternatives for patients with SI joint pain and who may not be able to undergo ablation with usual radiofrequency approaches. In one case report reported in literature, patients had no pain issue at 6 months follow. This is an attractive technique for patients on anticoagulants as no needle is inserted [36] (Figure 13).

Figure 13

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Conclusion

Radiofrequency ablation is an effective treatment modality for SI joint-related pain from any reason including cancer. New techniques continue to emerge, allowing for more precise and better outcomes. Outcome is very much dependent on proper patient selection. Endoscopic RFA allows for greater visualization and accuracy in patients with varying anatomy and/or obscuring surgical hardware. Cryoneurolysis reduces the number of entry points into the skin and potentially increases duration of pain relief. MR-HIFU provides a non-invasive and more accurate approach to treating SIJ pain which can be especially useful for sick patients who are coagulopathic or taking anticoagulants. Furthermore, refinement of procedural intricacies such as the use of hypertonic saline to increase lesion areas emerge as RFA is becoming more widely used. Moreover, its implementation has shown it is a great overall option to address some of the nuances which are specific to the palliative population Improvement in pain will result in lower opioid need that can lead to better quality of life and lower opioid-related side effects. RFA is an established analgesic intervention for SI joint pain, the option of RFA use should be considered in patients with low back pain.

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Journals on Medical Casereports |BJSTR

The Biology of the Facultative Halophyte Atriplex patula L.

Introduction

The genus Atriplex L. is represented by about 250 species globally. Molecular and morphological data have provided some evidence supporting the inclusion of the Chenopodiaceae in the family Amaranthaceae with the former family Chenopodiaceae now listed as a subfamily Chenopodioideae [1]. However, Welsh et al. [2] and others still use the nomen Chenopodiaceae in systematic treatments. Atriplex patula L. (spear orach, spearscale) is a facultative halophyte that tolerates low to moderate levels of soil salinity [3]. It is a widespread weedy species that occurs in agricultural fields, on roadsides, on the margins of coastal salt marshes, and in other areas where disturbance has occurred. Atriplex patula produces dimorphic seeds which allows the species to be established in unstable habitats [4, 3]. Welsh [1] indicated that A. patula was possibly introduced in North America from Europe, Asia, or North Africa in the 18th century, and its occurrence has been documented in at least 10 provinces in Canada and 29 states in the U.S.A. Chetina et al. [5] have reported that A. patula occurs in saline sites at 59º N near Perm Krai, Russia, and De Cauwer et al. [6] noted that this species is a weed control problem in sugar beet fields in Belgium. Atriplex patula has been suggested for use in habitat remediation because stems and leaves accumulate and store heavy metal pollutants [7]. Herein, we summarize important aspects of this widespread facultative halophyte.

Synonyms, Taxonomy, Variation

Synonymy of the Atriplex patula complex is in a state of confusion. Synonyms of Atriplex patula L. (spear orach, spreading orache, spearscale) in North America have primarily been listed as Atriplex hastata L. subsp. patula (L.) S. Pons, A. hastata var. patula (L.) Farwell, and Teutiopsis patula (L.) Selak [1], whereas Correll and Correll [8] listed A. patula L. as A. patula L. var. hastata (L.) Gray. The nomens A. prostrata Boucher and A. hastata L. sensu Aellen non L. have also been listed as synonyms by Stalter and Lamont [9]. The following taxonomic description of A. patula is summarized from treatments of the species by Correll and Correll, [8], Stalter, [10], Taylor and Wilken, [11], and Welsh, [1]. Atriplex patula is a monoecious annual with a root system that typically extends between 10 to 18 cm below the substrate surface. Stems are erect and branched, glabrous to scaly, and range from 30 cm to 1.5 m in height. Leaves are opposite below and alternate above.

Petioles of lower leaves are up to half as long as the blades. Blades are bright green, 2.5 to 7.0 cm long and nearly as broad, truncate at the base, and acute or obtuse at the apex. The staminate flowers bearing 5 tepals and 5 stamens are borne in a terminal spike or panicle. The pistillate flowers are usually borne in few-flowered axillary or spike-like cymes. Pistillate flowers have 2 stigmas, and the base of the ovary is enclosed in a pair of bracts often reddish at maturity and up to 7 mm long. Seeds are dimorphic. Brown seeds are 2.5 to 4.0 mm wide, and black seeds are 1.0 to 2.0 mm wide. Chromosome numbers for the A. patula complex are 2n = 18 and 2n = 36. In the Netherlands, Van Der Meyden [12] tentatively recognized A. patula L. and A. hastata L. as separate species. However, he noted that there are no sharp distinctions between the two taxa, and numerous overlapping morphological variations exist in leaf blade morphology between the two entities. Van Der Meyden [12] stated that different ploidy levels occur in the complex. Atriplex hastata is a diploid and A. patula is a tetraploid.

Geographic Distribution

Atriplex patula is an annual, weedy, facultative halophyte that has a wide distributional range in North America, Europe, North Africa, and Asia. Correll and Correll [8] reported its range in North America from Newfoundland westward to British Columbia in Canada, and from Newfoundland to South Carolina in the U.S.A. Stalter et al. [13] reported the occurrence of the species in coastal sites in northern Florida. On the Pacific coast of North America, it occurs from British Columbia to California. Ungar [3] indicated that it occurs in low to moderately saline sites in Kansas and Nebraska, and Correll and Correll [8] and Proffitt et al. [14] stated that A. patula is often present in saline sites in Texas and Louisiana. Atriplex patula in widespread in Europe. De Cauwer et al. [6] reported that A. patula is a weed control problem in sugar beet fields in Belgium, and Chetina et al. [5] reported the occurrence of this species in salinized alluvial soils at 59º N latitude at Perm Krai, Russia.

Range of Habitats

Atriplex patula is a weedy, facultative halophyte that occurs in a wide variety of soil types including sandy loams and clays [6], salt impacted alluvial soils [5, 15], and water-logged soils [16]. In sugar beet fields in Belgium, De Cauwer et al. [6] reported that the species is less common in acid sandy soils and is less tolerant to drought than to water-logging. Ungar [3] indicated that A. patula is a summer annual in the Central U.S.A. and can tolerate moderately saline soils under field conditions ranging from 2 ppt to 13 ppt total salts. In North Carolina, Stalter and Lamont [9] stated that habitats for A. patula are beaches and upper margins of brackish and salt marshes. In New England salt marshes, Rand [17-19] reported that this species is usually found in bare areas in the mid to high marsh in topographic zones usually dominated by Juncus gerardii or Iva frutescens. She noted that the annual halophyte Salicornia europaea may compete with A. patula in this harsh physical environment. Proffitt et al. [14] found a similar case in salt marshes in Louisiana where A. patula occurs in bare patches within sites dominated by Sporobolus alterniflorus (Spartina alterniflora).

Physiological Ecology

Atriplex patula has Kranz anatomy in leaves which is indicative of the associated C4 carbon fixation pathway of photosynthesis [1]. The C4 pathway increases efficiency of CO2 usage and subsequent carbon fixation. Salinity is an important factor that affects imbibition of water in seeds, germination, root elongation, and overall plant vitality [20]. NaCl in the substrate affects osmotic balance and specific ions. Salinization influences the production of the low molecular weight amino acid proline in A. patula leaves. Proline acts as an antioxidant and protects cellular protein structure and ultimately increases A. patula resistance to salt in acidic soil conditions [5].

Dimorphic Seeds and Germination

Two types of seeds occur in A. patula. One is black and ranges in size from 1.0 to 2.0 mm in diameter, and the other seed type is brown and ranges in diameter from 1.3 to 3.0 mm [4, 3, 1]. Large brown seeds have three times the mass of smaller black seeds, a thin seed coat, a larger embryo, and absorbs water 100 times faster than unscarified black seeds [20-21]. Nurse et al. [21] stated stated that seed dimorphism enhances survival of the species in variable habitats. Larger brown seeds have a limited dormancy period and germinate rapidly in spring. However, brown seeds are more susceptible to fungal attack than black seeds [21]. Ungar [22] reported that black seeds have a hard seed coat, a long dormancy period, and scarification is required to break dormancy. In the laboratory, unscarified black seeds did not germinate. However, 73% of scarified black seeds germinated [4, 22]. Black seeds have greater resistance to high salinity stress than brown seeds and retain their viability longer than brown seeds [21]. In the laboratory, Ungar [22] found that seeds germinated and seedlings survived salinity concentrations up to 20 ppt. Germination was reduced at salinity values greater than 10 ppt, and germination declined to 17% of controls at 20 ppt. Ungar [22] also noted that seeds are less inhibited to high salinity levels that growing seedlings. In Oregon, Keammerer and Hacker [23] stated that A. patula seed viability was 91% in the high intertidal zone, but they did not mention seed dimorphism.

Competition and Herbivores

Atriplex patula does not fare well in competition with taller or more aggressive species in salt marshes. Minchinton et al. [24] reported that the common reed (Phragmites australis), in the upper margins of New England salt marshes, modifies soil and light conditions and produces a heavy cover of litter. These factors exclude the perennial Solidago sempervirens and the annual A. patula from this topographic zone. Atriplex patula seedling establishment and survival of mature plants only occurs at sites that have not been invaded by P. australis. A chrysomelid beetle (Erynephala maritima) is a herbivore that damages A. patula and the succulent annual halophyte Salicornia europaea in salt marshes in Rhode Island [25]. Damage to A. patula is extensive at mid-tidal elevations which are frequently inundated [17]. She also found that A. patula plants are more extensively damaged when they are not present in dense stands of S. europaea [17]. In field plots cleared of S. europaea beetle herbivory reduced A. patula survival by about 50% and reduced reproduction by 37% [18, 19].

Phytoremediation

Atriplex patula is a species that removes significant amounts of Na ions from salt-impacted soils and stores salt in cellular vacuoles in stems and leaves [15]. They noted that the deep root system improves soil quality and soil permeability in oil field brine spill sites in Saskatchewan, Canada. Mature plants are removed of spill sites and are disposed off-site. High seed production insures a standing crop in the next growing season.

Vickerman et al. [7] examined A. patula for potential habitat improvement and phytoremediation of the heavy metal Se. They found that phytoremediation was greatest in saline sites having low to moderate levels of sulfate. They also indicated that mature plants could be mechanically harvested and disposed off-site.

Management and Role as an Allergen

Atriplex patula is an aggressive annual weed in sugar beet fields in Belgium. Various herbicides have been used to control the species. However, this species exhibits high intraspecific variation in herbicide sensitivity and weed control by herbicides has been shown to be difficult [6]. Atriplex species produce extensive amounts of windblown pollen and may play a role in allergic sensitization [26]. Ferrer et al. [27] noted that pollen of A. patula extracts should be used in a battery of potential allergens for use in diagnosis and treatment of respiratory allergies in patients.

Acknowledgment

We thank Matt Toska and Menahil Shahid undergraduate research students for obtaining reference articles and St. John’s University for providing publication expenses.

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Medical humanities |BJSTR

Non-Small Cell Lung Cancer – A Case of the Bazex

Introduction

Bazex syndrome is a paraneoplastic psoriasiform dermatitis, predominately seen in squamous cell carcinomas (SCC) of aero-digestive tract and non-small cell lung cancers (Räßler, et al. [1]). Lesions are seen mainly in adult males (>60 years old (YO)) >3:1 woman, with an alcohol and smoking history noted in 28% of cases noted to be alcohol and smoking (Räßler, et al. [1]). Clinically, lesions may be erythematous, scaling and appear psoriatic like, which may lead to a delayed diagnosis of cancer while benign skin causes are treated (Räßler, Goetze & Elsner, 2017). Acral lesions may be considered pathognomonic of BAK upon confirmation of carcinoma with common distribution of lesions on: ears (79% & 28%), nails (75% & 57%), nose (63% & 33%), fingers (61% & 29%), hands (57% & 38%), feet (50% & 30%) and less commonly the trunk (13% & n/a), scalp (7% & n/a), elbows (19% & n/a) and cheeks (19% & n/a) (Räßler, et al. [1]). Treatment of the underlying cancer has been found to successfully treat the skin lesions when therapy is established with cases noting response to NSCLC BAK syndrome lesions after chemotherapy, immunotherapy and surgical intervention (Table 1) (Mititelu, et al. [2-4]). The current case reports BAK syndrome in a 76-year-old male following a delayed diagnosis and details his diagnosis and treatment journey to date while he remains on current active first line management. Within the report is a brief review of the lung cancer cases and BAK syndrome, showing literature available via Medline and Pub med from 2011-2021 in the English language using the search term ((Bazex) OR (acrokeratosis)) AND (Title Combined: (lung cancer OR carcinoma)).

Consent

Consent was obtained to use images in relation to this report, identifiers are anonymised and no patient personal information is used within this article.

Time line

December 2020 – January 2023.

Patient Presentation

76-year-old retired white British male presented with 6-month history of psoriatic like plaques on fingers and toes bi-laterally, progressing to the scalp and torso, with >10% weight loss and progressing breathlessness two weeks prior to diagnosis. He has a >40 pack year smoking history and a past medical history of chronic obstructive pulmonary disease (COPD) and hypertension, taking medicines; amlodipine 5mg, acitetin 20mg, atrovastatin 10mg nocte, furosemide 40mg mane, aspirin 75mg, tiotropium 10mcg mane and salbutamol inhaled 100mcg/dose, with no known drug allergies. No family history of Bazex acrokeratosis neoplastica syndrome or lung cancer was present.

Delayed Diagnosis

Initial treatment for scaling dermatosis was initiated by the community doctor with dermol 500 and dermovate cream, which gained no symptomatic benefit over a 6-month period March – September, later given acitetin 20mg with no continued benefit. New shortness of breath triggered a chest x-ray via the community GP which highlighted a supraclavicular mass and a right hilar mass, leading to a two week wait for suspected cancer.

Diagnostics

A computer topography (CT) and a positron emission topography CT scan (PET-CT) confirmed stage 3b lung cancer, with a 7cm mass in the right lower lobe with atelectasis and right upper lobe nodal lesion with a 4cm supraclavicular lesion and a paratracheal node at 3.5cm, confirmed as avid on a positron CT scan. The supraclavicular node was biopsied showing a squamous cell carcinoma with a programmed death ligand -1 as 10% and no actionable mutations, next generation sequencing was not performed.

Stage

T4N3M0 – 3b (Matilla et al. [5]).

Examination

The examination took place prior to cycle one of chemo/immunotherapy, or any anti-cancer treatment on the same day. Comparison over treatment will be detailed in the discussion. Over all the patient was comfortable at rest, with no mobility aids, no oxygen, no indwelling catheters or lines in-situ. The end of bed assessment clearly identified plaques upon finger nails bi-laterally.

Lung Exam

No additional berthing sounds identified, with good air expansion. Saturation was 96% on room air with a respiration rate of 16 breaths per minute at rest.

Heart Exam

No additional sounds or murmurs were identified, with a pulse rate of 58 beats per minute regular and a blood pressure of 103/53.

Abdominal Exam

A single plaque identified in the epigastric area, no scars where noted, with no masses, a soft abdomen on palpation and bowel sounds throughout.

Hands

Plaques (pre-treatment) noted on finger nails bi-laterally, crusting and yellow with thickened perioncychium and mild palm erythema bi-laterally.

Toe nails

Equally to fingers, yellow scaling plaques bi-laterally were noted with erythematous cracks on the heels bi-laterally.

Other

Three lesions were noted on the scalp and one on post oracular on the left side.

Treatment

Triple therapy was initialised based on squamous metastatic NSCLC with a PDL-1 of 10%, given Carboplatin, Paclitaxel and Pembrolizumab was administered in four cycles, following which, Pembrolizumab immunotherapy continued as a single agent treatment (Paz-Ares et al. [6]). Radiotherapy 20 grey in 5 fractions was given to reduced paratracheal mass, with continued Pembrolizumab to 10 cycles before progressive disease n mediastinum and superior vena cava obstruction, before patient died of progressive disease. Scans performed every 3 months measured with iRECIST criteria (Persigehl, et al. [7]), with best outcome partial response (PR) to treatment and an overall time to progression of 10 months from start of treatment.

Discussion

Delayed diagnosis of BAK syndrome may prolong ant-cancer treatment leading to diagnosis at a later stage, limiting treatment options for patients, which parallels the current case who waited 6 months from the onset of plaque lesions to diagnosis of lung cancer (Zarzour, et al. [8]) noted death of a small cell lung cancer patient 6 months following diagnosis despite a 2-year history of hyper pigmented rash over forearms and legs, diagnosed as BAK syndrome (Räßler, et al. [1,8]). Similarly, an epidermal growth factor receptor mutation (EGFR) was diagnosed with metastatic bone lesions after a 5 year history of pruritic, acral lesions, suggesting earlier recognition may of allowed lower diagnostic stage (Zhao et al. [8]). The current case noted a 6 month delay pre-treatment, leading to a diagnosis of 3b NSCLC with supraclavicular lymph node spread, meaning an advanced stage of lung cancer untreatable to radical surgery or radiation, giving a poor prognosis with systemic treatment, although the current treatment regime of chemotherapy combined immunotherapy may lead to prolonged survival (Matilla, et al. [5,6]). Psoriatic lesions occurred in the current case on the hands, feet, nose, nails, auricular helices and scalp in the current case, with a lesion on the trunk suggesting advanced carcinoma correlation (Bazex, et al. [9]). Typically the lesions will respond (Table 1) to anti-cancer therapy as was the case here, the individual who failed to respond died within 6 months of diagnosis, and unusually had SCLC (Zarzour, et al. [8]).

Table 1: Table showing similar cases in lung cancer after a search of Pub med and Medline with the search term ‘’ ((Bazex) OR (acrokeratosis)) AND (Title Combined:(lung cancer OR carcinoma))’’ year 2011- 2021, English language. N=No, Y= Yes, M= Male, F-Female, NSCLC= Non-small cell lung cancer, SCLC+ Small cell lung cancer, N/a = Not applicable.

biomedres-openaccess-journal-bjstr

Previous cases have shown symptomatic benefit from adjuvant treatment with acitretin, used to treat severe psoriasis, at 0.25-1mg/ kg body weight (Bazex, et al. [4,10]). The current case has shown how Pembrolizumab combined with chemotherapy therapy in advanced/ metastatic NSCLC (Paz-Ares, et al. [6]), may reduce plaques in BAK syndrome (Figures 1A-a & 1B-b) which is paralleled by (Aoshima, et al. [2]), who showed a improvement in the distal extremities after 7 cycles of Pembrolizumab. Pathophysiology of BAK syndrome may be related to cross reactivity of tumour antigens irritating the skin, growth factors associated with epidermal growth factor and vitamin deficiency such as Zinc and vitamin A (Amanon, et al. [4,11]) Showed serum immunoglobulin e and eosinophil count elevated in an 82 YO SCC of the lung, with reduced levels after tumour removal, suggesting a role of the Th2-type cytokine response leading to an elevated inflammation, which may cross react causing keratin based skin plaques seen in BAK syndrome, although reactive response to the subcutaneous cancer itself could not be ruled out as well as raised inflammation as a result of patients positive smoking status. The current case survived approximately 12 months post treatment with chemotherapy and pembrolizumab, compared to 15.9 months in the literature for NSCLC SCC patients (Paz-Ares, et al [6,12]). Diagnosis in the current case was on observation capacity, failure to resond to anti- psoriatic medication and response to anti-cancer therapy, although none biopsy may be a limitation here.

Further limitations are a lack of tracked biomarkers throughout treatment, with immunoglobulin E, also not detailed, as suggested to be raised in BAK syndrome by (Amanon, et al. [4,13,14]). Take home messages from the current case highlight that BAK syndrome in SCC NSCLC can be successfully treated with combine chemotherapy and immunotherapy, with lesion/plaque regression corresponding to successful anti-cancer treatment, although the patient did die of advanced NSCLC. Plaques in BAK syndrome are not commonly responsive to psoriatic therapy, and a smoker with a resistant history of psoriatic lesion treatment should be considered for an upper digestive or lung cancer diagnosis to rule out an underlying malignancy (Moore, et al. [15]).

Figure 1

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Competing Interests

No competing interests.

Ethics Approval

Ethical guidelines were followed, with written consent obtained for images.

De-Identification

All information remains anonymized.

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Journals on Medical Microbiology |BJSTR

Morbidity and Mortality of Open and Laparoscopic Cholecystectomy in Males. Multicenter Study

Introduction

Male gender has been mentioned as a risk factor in open or minimally invasive gallbladder surgery. In open surgery, some “anatomical difficulties” in men could be the sharpest right costal angle and greater muscle mass compared to women; It is also mentioned that men seek medical attention late due to work issues [1]; However, in other articles, it is mentioned that men undergo emergency surgery more frequently; in addition to age, which is higher in this group [2]. It is also mentioned that the inflammatory reaction is greater in men, a situation that represents a greater risk in minimally invasive surgery, conditioning a conversion rate of 15% [1-5]; therefore, some authors recommend the need for earlier intervention to reduce the risk of complications [5]. Another risk factor is obesity, which in Mexican population, the male gender represents 73.5% and female gender 76.8%, according to ENSANUT reports from 2022 [6]. According to Tokyo International Consensus classification and other publications, the management to be followed was determined, emphasizing on intervention in the acute phase of cholecystitis to avoid complications, of course, depending on the cholecystitis severity, so they recommend early cholecystectomy (in the first 72 hours after the onset of the disease). Laparoscopic surgery was the modality of choice in 20% of cases that come to be intervened [7].

There is still a debate about whether early intervention should be taken to avoid complications due to the inflammatory process [4,8], arguing that acute gallbladder symptoms usually subside after 2 or 3 days, resolving in 85% of cases within a week [9]; however, as mentioned above, only one-fifth of patients in the acute period are candidates for LC. Other authors have proposed LC at one and a half or three months after the acute phase, due to the risks involved in inflammation, being the most important, the anatomy loss among them, which in addition, we know that the bile ducts are the structures with the most anatomical variants, predominating on the cystic in more than 70% of cases [10], increasing the risk of injury to these structures, including the liver vasculature or even large vessels injury by the laparoscopic procedure itself, such as arteries, vena cava or portal vein; However, it has been seen that performing it in a deferred or interval manner (conservative treatment) is accompanied by 26% of failures, having to be urgently operated, and 28.5% of these patients could present complications such as cholangitis, pancreatitis or a biliary peritonitis [11].

According to literature, in women initially there is a greater inflammatory reaction and greater production of antibodies; However, women offer a greater response to antigens, both innate and adaptive. The immune response basically resides on the X chromosome; In addition, hormonal factors, such as estrogen, stimulate the immune response; on the contrary, androgens inhibit it [12]. Bile duct injury in LC have an incidence between 0.2 and 0.8%; in open surgery, it is less than 0.2% [13]. In relation to sex, Shreenath et al do not consider it as a predictor, but report that conversion secondary to difficult cholecystectomy is frequent in patients with history of hospitalization, previous abdominal surgeries, palpable gallbladder, BMI greater than 27.5 kg/m2 and thickened gallbladder wall. Sex, age, and impact calculation were not identified as predictors [14,15]. In summary, the prevalence of cholelithiasis in Mexico is 14.3%, of which 8.5% are men and 20.5% are women; obesity has been reported to be associated with a cholelithiasis elevated risk [16] and as an important factor in the conversion of LC [17,18]. The most used marker to measure the quality of a surgical procedure is the incidence of complications [19]. Andrade Carbo et al., from Ecuador, reported a higher rate of surgical complications in women compared to men (52% vs. 48% respectively) [20].

Corona DJ y cols., in Mexico on 2006, reported 72% of 111 male patients operated urgently of OC, 55 patients presented complications inherent due to cholecystitis severity [21]. Hospital stay was shorter in LC than OC group with an average of two days vs 4 days in 57% and 34.3% of cases respectively [22]. On the other hand, there is an increase bile duct injury incidence, with the increasing use of LC, although other authors report that they have decreased with the learning curve [23] Most articles mention a conversion rate of 4 to 8%, even up to 20%; the current mortality rate for OC is 0.39% and 0.07% for LC, with an average of 0.016% [24]. Some mention that male sex, obesity, age, wall thickness or stage of the disease are the factors that hinder surgery and therefore, conditioning factors for conversion, so in the absence of consensus to categorize a difficult CL, the scoring scale proposed by Ayón et al. has been used that take into account 7 aspects: adhesions presence, gallbladder wall and size, inadvertent calculus or macrocalculus, Calot’s triangle critical view, surgical time, and how vesicular bed hemostasis was achieved [25].

Methods and Materials

From January 2021 to December 2023, an ambispective, descriptive and analytical multicenter study was carried out of the clinical archive from Dr. Darío Fernández Fierro General Hospital (HGDDFF), Hospital General La Villa (HGV), and Hospital Universitario de Puebla (HUP), of the surgeries performed by General Surgery department to determine the morbidity and mortality of OC and LC in men during emergency or scheduled interventions. Data were collected separately by dividing the hospitals into three groups according to the order mentioned above. The following variables were analyzed: sex, age, BMI, time of evolution of the condition before surgery, transoperative bleeding, surgery time, drains presence, postoperative pain, and hospital stay. The statistical analysis was performed with SPSS-27 to perform the univariate analysis of the variables of interest, describing cumulative incidence and prevalence of injuries, relative and absolute frequencies of the categorical variables and measures of central tendency for the quantitative variables according to the data distribution. The study was carried out strictly in accordance with the Ethical principles of patient confidentiality.

Results

HGDDFF (Group 1)

During the 3 years included in the study period, a total of N=1409 cholecystectomies were carried out, 80% (n = 1127) met the selection criteria, of which 72.49% were female (817/1127) with an average age of 54 years (± 16.6), ranging from 18 to 94 years; 27.5% (310/1127) were male (Graph 1), being more frequent between 30 and 50 years, with an average age of 40 years in 65% of the cases; 15% from 51 to 60 and 20% from 71 to 80 years. In 80.9% of all patients (n=912) were between the ages of 36 and 57 years and in 31%, the most common comorbidities were systemic arterial hypertension (SAH) in 55%, diabetes mellitus (DM2) 45%, hypothyroidism 16%; elective surgeries accounted for 50.57% (570/1127) and 49.43% (557/1127) of emergency surgeries; OC in 4.34% (49) and LC in 96.65% (1078/1127). Average time of 2 h in 53.23% (600/1127). In OC, the surgical time was 90 minutes; in LC 70 minutes on average, with an interval of 30 to 180 minutes. Less than one hour 7%; Minimal bleeding (bleeding defined and calculated by the anesthesiology service ≤ 90 ml) in 92.25% of males, with no statistically significant difference with respect to females (p= 0.509482).

Graph 1

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Complications in LC

Cystic artery bleeding occurred in 5%, controlled by laparoscopy; bleeding from the surgical site in 1 case; liver thermal injury due to defects in the thermal insulation of the electrocautery. Mortality in 11 patients (0.97%), with a Porta vein injury, which initially due to the urgency, was managed by a general surgeon and caused a late intervention of the vascular surgeon with disastrous results. (Graph 2). In 0.92% (10/1078) of the LC, STC was performed, especially in acute cases. In OC, 6.12% (3/49). Cystic duct leaks occurred in 3 cases, identified and resolved by ERCP. There were 5 bile duct injuries, 4 referred to a fourth level of medical care; 1 was repaired by a surgical oncologist at the time of injury with open Y Roux’s surgery (Strasberg E2 type) (Table 1). In-hospital stay ranged from one to six days; 77% less than 2 days; 3 days in 18%, with the main reason being drainage monitoring. 4 days in 11%, for pain or drainage surveillance in 63%, and in 1 patient, 6 days for choledocholithiasis.

Graph 2

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Table 1: Transoperative Findings. group 1.

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The conversion rate for males was 6.45% (20/310) and 1.83% (15/817) for females. Elective surgeries were dominated by women. Regarding the age group, on 31 patients’ conversion predominated between 41 and 55 years old, and a probability of conversion of 3.1 (OR). According to BMI, CL conversion, especially in emergency cases, was more frequent in 28 patients (43.75%) classified as overweight (25.1 to 30 kg/m2), followed by 16 patients (25%) classified as grade I obesity (30 to 34.9 kg/m2). (Table 2) There was a predominance in symptomatic Cholecystitis (76.56%); which is the most associated condition to conversion in urgent surgery in 28 cases (43.75%) with an OR= 2.45 conversion probability.

Table 2: Group 1, Conversion and Conversion Factors.

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HGV (Group 2)

This hospital serves the population without medical services, in which 674 cholecystectomies were performed, 71.06% (479) women and 28.93% (195) men; of the total, 55.93% were OC (377/674) and 44.06% LC (297/674); 92.43% (623/674) were intervened due to emergency and 7.56% (51/674) were an elective procedure, from which 44 were women and 7 men. Minimum and maximum age in women 16 to 86 years, with a maximum peak between 36 and 40 years; In men, minimum and maximum age 18 to 82 years, with two peaks between 46 and 50 and 56 to 60 years (Graph 3). Among the findings we have a 1.92% conversion rate (6 men and 7 women). In 14 patients (2.07%) STC was performed (9 men, 5 women); There were 3 injuries (2 bile duct and 1 duodenum injury); A biliodigestive fistula was evidenced and resolved in the same surgery; in 72 patients (10.68%) a purulent cholecystitis was found (21 men and 51 women); Biliary peritonitis in 9 patients (6 men, 3 women); hydrocholecyst in 35 (11 males, 24 females); cholangitis 5 (2 men, 3 women-one with septic shock) and Mirizzi syndrome in 4 patients (3 women). The average surgery time in 90% of LC was less than 2 hours.

Graph 3

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HUP (Group 3)

For reasons beyond our control, we do not have current data, only reports from 2009 to 2014 period, in which 78 CL were performed per year, of which the female gender represented more than 70% of the cases with a mean age of 44.4 ±17.2 years, with two conversions (Pérez Ayala, Thesis 2014) and that currently in the ISSSTE Regional Hospital, of the same Federal Entity to transpolate the data, approximately 200 surgeries are performed per year, reported by Dr. Dávila Esparza, a total of 1190 cases, of which 78.9% were female and 21.1% male, with an age range of 18 to 94 years and an average age of 51 years (F:M relation 3.73:1). Average hospital stay was 3.4 days and surgery duration averaged 93 minutes. A conversion rate of 4.8% and bile duct injury at 0.08%. (Dávila Esparza, Thesis 2021)

Discussion

Acute cholecystitis is the second leading cause of consultation in abdominal surgical emergencies; In Mexico, it is estimated that between 200 and 300 thousand LC are performed annually, according to the lecture given at the “12th Mexican Association of Endoscopic Surgery Regional Meeting” at the New Civil Hospital of Guadalajara “Dr. Juan I. Menchaca”, by Dr. Adolfo Cuendis, Gea González General Hospital MD of Endoscopic Surgery Division in Mexico City [26]. Gallbladder problems mainly affect young women between the ages of 20 and 40, who are multi-pregnant or overweight. In men is more associated with eating problems and low fluid intake. From all gallbladder surgeries, 80% are due to gallstone problems. In Mexico, 10 to 20% of the population has gallstones and 30% will develop acute cholecystitis [27,28]. LC is currently the first-line technique for the surgical treatment of gallbladder pathology, with less time spent in hospitalization and convalescence; reduced postoperative pain and operative site infection, and better aesthetic results; However, LC is not without disadvantages, such as a higher percentage of iatrogenic bile duct injury and more challenging controlling profuse bleeding difficulty degree [24,29].

In our study, we found an F:M ratio higher than that reported in the international literature with respect to sex, being 3.34:1, in relation to the reports of 2:1 respectively, perhaps due to the place we occupy in obesity, overweight, DM2, and the fact that our female population is larger, which translates on the necessity to investigate an ethnic factor. Either way, the Puebla ISSSTE Hospital with different economic status employees, F:M was 3.73:1 and HGV, which attends low resources population, was similar from the relation reported in international literature (F:M 2.4:1); We insist, this could be associated due to the predominant obesity on bureaucrats. In terms of surgical time, we are in the average time with the report of Jarkín et al. (9), of 71 minutes in boarding with three laparoscopic ports, and above the results of Manoj Kumar et al. 47 minutes [18].

Recent meta-analyses have shown that early urgent LC provides a benefit in terms of hospital stay, but not in terms of conversion rates and perioperative complications [28]. Currently the LC is the election procedure. There is no standardized management of early-stage LC in our institution, and some articles even contraindicate it in the acute phase [28].

According to some publications, there is no statistically significant difference in the complications of an early and delayed LC; It is recommended to perform it in the first 3 days of the onset of the clinical presentation being urgent surgery more common in men [21]. There is the unknown or assertion if surgery in men is more difficult or presents more complications, perhaps because the inflammatory process is greater or because they present themselves to seek medical attention earlier than women, associated to less pain tolerance or due to work reasons, a situation that favors an intervention during the acute process. This increases the risk of injuries and technical difficulties in surgery, and not necessarily because surgery is more difficult in men, which remains to be clarified with larger studies. Zhu et al. proposed the term 72 golden hours from the onset of the disease to perform LC [4]. In addition to the factors mentioned above that can lead to conversion, we have symptomatic gallstones (biliary colic) and DM2 as predominant factors. Elective surgery is more often in female sex [29,30].

In our study, we found that there was no statistically significant difference between men and women in the minimum bleeding present in 95.92% on the male group (p= 0.509482).

1.76% (n=19) were converted to open surgery, in contrast to what has been reported in the international literature, which reaches figures of up to 20%. Surgical time was obviously longer in acute inflammatory processes. Complications with an OR greater than 1.0 were abscesses with 5 cases in men and 1 in women (OR of 4.23, 95 CI: 0.49-36.29) and liver injury in 1 case in men with an OR of 2.53 (95 CI: 0.10 – 62.41). According to the above, it could be said that more than the male sex being a risk factor, obesity, the stage in which patients are intervened, inflammatory grade and age are predominant factors for a difficult cholecystitis, and it would be necessary to clarify if the inflammatory reaction is greater in men as mentioned by some authors and not the stage of the disease in which they are intervened (acute phase). In relation to the inflammatory reaction and antibodies production, it is mentioned that in women, it is initially bigger, with a greater immune innate and adaptative response to antigens, which is described to be reside in the X chromosome and the hormonal factors (estrogens) that stimulate the immune response, as opposed to androgens that inhibit it [12].

Hayama et al. mention that the risk factors for conversion depend on the stage at which surgery is performed in acute cholecystitis (early surgery less than 240 hours vs late surgery after 240 hours). Necrotizing cholecystitis was a difficulty risk factor in early surgery, while higher white blood cell count, and older age are risk factors in late surgery [31]. It is relevant on these situations to know if we have the possibility of predicting the conversion rate as mentioned by Rothman et al., who give importance to the gallbladder wall thickness (>5 mm), contracted gallbladder, > 65 years of age, male sex, and acute cholecystitis [32]. Other publications list DM, chronic kidney disease, choledocholithiasis and Mirizzi syndrome as risk factors for conversion; patients with jaundice, cholangitis, or pancreatitis [33]. However, we must not forget that the conversion to open surgery is considered an alternative resource for resolution and it is necessary to know how to make the decision on time. Percentages range from 0.08% to 18% [34]. Regarding sex, Shreenath et al. mention that conversion in difficult cholecystectomy is frequent in patients with hospitalization history, previous abdominal surgeries, palpable gallbladder, BMI >27.5 kg/m2 and thickened gallbladder wall.

Variables such as age, sex, and impacted stones were not found to be significant predictors. However, they mention that in the case of men they may outperform women, due to sociocultural factors that predispose a late attendance to medical centers [35]. In addition, Chávez Segura stated the results of studies in relation to sex should be considered inconclusive, because most of the population that goes to hospitals are mostly female [36], which we take as a reservation because it is more frequent in women. It is stated that male sex is a difficult risk factor for LC, although there are no statistically significant results, as there is a criteria diversity [37]. Age is identified as a risk factor for mortality, postoperative complications, and intraoperative conversions to OC, since the older the age, the greater the number of associated diseases and complications [37]. Obesity is a disease associated with acute cholecystitis and surgical modality conversion and is considered as a significant factor. Campos Guzmán et al. consider that overweight and obesity are a risk factor, not only for conversion, but also for the appearance of postoperative complications, prolonged hospital stay and, therefore, higher economic expenditure [37,38].

García Álvarez et al. also mention that the presence of associated diseases, such as biliary colic, obesity, and SAH, increase the risk of conversion [39]. In our investigation, on group 1, 8 conditions that complicate cholecystectomy were detected, in which the male factor has statistical significance (p = 0.003685) when all parameters are compared; when analyzing them individually it can be inferred that the male factor is protective when comparing the same complications in the female gender with a p < 0.0001 statistically significant, in cases of hydrocholecyst OR 0.31 (95 CI: 0.18-0.55); biliary peritonitis OR 0.84 (95 CI: 0.24-2.93). It is noteworthy in the Emergency Hospital that serves the general population without medical services, as expected, OC was performed in most cases (55.93%) and F:M ratio 2.4:1. The aim of this study was to determine whether the male sex factor is associated with a higher risk of surgery and complications in OC and LC in emergency or elective procedures and, as such, in LC, associated with conversion. However, perhaps due to the number of cases, we could not give an adequate answer to the research question, although according to our results, when comparing complications in women and men, the male factor was found to be protective. The important thing is to know when convert to open surgery and resort to related specialties.

Conclusion

Obesity, stage of the disease and age aggravate morbidity and mortality in cholecystectomy. According to our study, sex is not a condition of conversion. Bile duct lesions in our study were within the range reported in the universal literature of 0.2 to 0.8%.

Special Thanks

For Your Technical Assistance to Doctors
Karen Monserrat Guznay Matute
Pedro Sánchez Román.

Conflicts of Interest

The authors declare that there are no conflicts of interest related to this article. They agree to open access publication in accordance with the journal’s policy.

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Journals on Biomedical Imaging |BJSTR

Solar Alpha Particle Radiation Increases Human Mortality – An Example from the Malignant Melanoma Mortality in the Europe and Mediterranean

Introduction

In a series of publications [1-20], a dangerous phenomenon of cosmic origin for humanity was described – the presence of a high correlation between the flows of positively charged particles with high kinetic energy recorded from satellites in the Earth orbit and mortality on the Earth’s surface from many diseases. The main focus of the mentioned publications was on the effect of solar alpha radiation on mortality from diseases, killer number one of mankind – those of the circulatory system. The harmful effects of solar alpha radiation are also observed on many other organs and systems in the human organism, turning this invisible effect into one of the main causes of death for humanity. The mentioned dangerous phenomenon of cosmic origin is unevenly spread on the planet’s surface. Europe and the Mediterranean are among the most affected. However, in [1-20] are described many examples, where this phenomenon is also observable in several countries from the Northern Hemisphere – Asia, America, and even Africa. The European Union has a tradition of maintaining reliable mortality statistics, in which the discussed multifaceted influence of solar alpha radiation on mortality stands out clearly.

Below, based on data from mortality statistics in the European Union, the unexpected association between solar alpha radiation and mortality from malignant melanoma of the skin is shown. According to [21,22], 90% of recorded cases of the deadliest skin cancer, melanoma, are caused by excessive exposure of the skin to ultraviolet radiation, mainly of solar origin. Statistical data show a drastic disparity in the incidence of the three types of skin cancer – basal cell carcinoma, squamous carcinoma, and melanoma, which is strange if it is assumed that all three types of cancer are caused by the same cause – ultraviolet radiation. Melanoma cases in the US are only 2% of all reported skin cancer cases [23]. This fact is probably related to different mechanisms of occurrence of melanoma compared to other types of skin cancer. In support of this statement are the results of 13 studies involving 7,700 cases of melanoma in people of color [24]. Research findings question the occurrence of melanoma as a result of exposure to ultraviolet radiation in individuals of color. Below are the results of a study that reveals a new unsuspected cause of melanoma – highenergy solar corpuscular alpha radiation. The nature of the alpha radiation is different from that of ultraviolet radiation. The processes that alpha radiation can induce in the human body are more intensive than those induced by UV radiation. In addition, the high-energy alpha radiation can also ionize the atoms in the living organism, which drastically worsens the normal metabolism in living cells. This type of radiation may be the leading external cause of melanoma disease.

Methods and Materials

Mortality Data

The analysis below is based on an authoritative source of health data – EUROSTAT [25]. In the study, the parameter annual mortality rate – number of deaths per 100,000 inhabitants was used as a characteristic of mortality. EUROSTAT offers free access to data on mortality rate from causes in the countries of the European Union, the European Economic Area, and the candidate countries for membership in the union. Geographically, these countries occupy Europe and the Mediterranean. Data are grouped by NUTS (Nomenclature Des Unités Territoriales Statistiques in French, the nomenclature of territorial units for statistics). In the study, were used mortality data from the EUROSTAT shortlist in which mortality rates are grouped by causes of death into 92 groups, mostly diseases. The groups are related to the classes in the International Disease Classifier ICD-10, (10th revision). The shortlist contains mortality data for EU countries (NUTS-1) and EU regions (NUTS-2, smaller areas of the larger NUTS-1 countries). Currently (2023) the shortlist includes mortality rate data for the interval 2011 – 2020. Annual mortality rate data were extracted for 353 European regions (NUTS-2) separately from each of the shortlist groups for the interval 2011 – 2019 (the last pre-pandemic year).

Satellite Data

Satellite data on corpuscular radiation – protons and alpha particles recorded by the satellites of the series GOES (Geostationary Operational Environmental Satellites) were obtained from an NOAA site [26]. The satellites of the GOES series fly in geostationary orbit (above the Earth’s equator), at an altitude of 36,000 kilometers above the Earth’s surface, make one lap in 24 hours, that is, they “hang” over a certain point on the Earth’s surface and are not shade by the Earth at their circumference around it. Data on alpha-particle and proton fluxes (unit: (number of particles) cm-2.s-1.sr-1.MeV-1) with energies of the range 3.8 – 21.3 MeV were used. The fluxes were recorded by the satellite high-energy particle detectors: 1. Energetic Particles Sensor (EPS), and 2. Energetic Proton, Electron, and Alpha Detector (EPEAD). The data are available averaged over a 5-minute interval, during which there are up to 25 reports of the instrument.

Data Processing

The correlation coefficients [27] between the annual averaged alpha radiation flux and the annual mortality rate were calculated. A map was created showing (with black isolines) the distribution of the annual mortality for 353 NUTS-2 European regions from the EUROSTAT shortlist death cause: “Malignant melanoma of skin” (EUROSTAT mortality shortlist number 18), for 2012, the year with the highest solar activity in the studied time interval 2011 – 2019. With red isolines, the map shows the distribution across the territory of Europe and the Mediterranean of the correlation coefficient between the annual mortality rate from “Malignant melanoma of skin” with the annually averaged alpha particle flux for the time interval 2011 – 2019. Data on the coordinates, latitude, and longitude [Google Earth] of the centroids of the NUTS-2 regions included in the study were used in the map. Mapping was performed with Golden Software Surfer10. The kriging interpolation procedure was selected. In mathematical statistics, the level of statistical significance [27] is a parameter, indicating the degree of reliability of the calculated correlation coefficient. The smaller the number of this parameter, the more reliably the correlation coefficient is established, i.e. the more reliably a causeand- effect relationship has been established, in the case between the annual flux of solar alpha radiation and mortality from a cause of “Malignant melanoma of skin”. The correlation coefficient and the level of statistical significance are related.

For the 9 years included in the study, a minimum correlation coefficient of 0.668 corresponds to a statistical significance level of 0.05 [27]. In scientific studies, a level of statistical significance no greater than 0.05 is accepted as a criterion for the reliability of the correlation coefficient. The red isolines on the correlation coefficient distribution in the map enclose the regions with statistically significant values of the correlation coefficients around and up to a significance level of 0.05. Correlation coefficients with a significance level above 0.05 are of high reliability (the higher the number, the lower the significance level) i.e. the existence of a causal relationship between cosmic alpha radiation and mortality from the cause “Malignant melanoma of skin” can be considered reliably established in the mentioned areas enclosed by red isolines on the correlation coefficient. If there is a coincidence for some of the maxima for mortality rate and correlation coefficients, then in the region of these maxima, the impact of alpha radiation contributes noticeably to the mortality from “Malignant melanoma of skin”. To the extent that the hypothetical mechanism proposed below explaining the observed phenomenon assumes that charged particles of high energy pass through the atmosphere and reach the Earth’s surface, the energy required for this was calculated from databases and calculators PSTAR and ASTAR [28,29]. Geomagnetic field data were obtained from the INTERMAGNET site [30].

Results

The described dangerous phenomenon is observed in the form of dependence between the annual average flux of radiation from positively charged particles (protons and alpha particles) with high kinetic energy, recorded by satellites in orbit around the Earth, and the annual mortality rate in the statistics of several countries from all continents in the Northern Hemisphere. The countries in whose mortality statistics the phenomenon is observed are located in a band parallel to the equator with approximate boundaries along the parallels of 30° and 60° north latitudes. It is observed in the annual mortality statistics of small countries. It is not noticeable in the statistics of large countries in the same band. It can be inferred that the impact on the Earth’s surface is short-lived and over a limited area the size of a small country, but is masked in large country statistics because it does not affect the entire area of the large country at the same time. This conclusion is confirmed for the USA, for which there is data on mortality in individual states [10]. The mortality statistic of the European Union is suitable for the study because it is based on statistical regions, smaller than a country, but still big enough, to include a statistically sufficient number of inhabitants.

This phenomenon would be expected to influence mortality in countries south of the Equator, but mortality statistics for them are scarce, unreliable, or absent, preventing reliable inferences about such an influence in the Southern Hemisphere. For particle energies of the order of 3.8 – 21.3 MeV, the year-averaged fluxes of protons and alpha particles are highly correlated, i.e. the studied phenomenon of lethality is noticeable in both the mean proton flux and the mean alpha particle flux data. For the reason explained below, only the average flux of high-energy alpha particles is included as the incident radiation in the examples below. Figure 1 shows for the Europe and Mediterranean the distribution of the mortality rate for EUROSTAT shortlist deaths cause: „Malignant melanoma of skin” for 2012, the year of maximum solar activity for the studied interval, and alpha particle flux maximum (black isolines), and the distribution of the statistically significant correlation coefficient between solar alpha particle fluxes and the mortality rate for “Malignant melanoma of skin” (red isolines). The statistically significant influence of alpha radiation on mortality from malignant melanoma of skin is limited to a band parallel to the Equator with approximate dimensions between 40° and 60° north latitude. Not all high mortality areas in the study region fall into it. Over Denmark and Sweden, there is an area of high mortality from malignant melanoma of the skin in which the contribution of alpha radiation to mortality is not noticeable.

Figure 1

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The impact of alpha radiation on mortality in the mentioned band does not continuously cover the entire band but is of the nature of limited spots in it, covering mainly mountainous areas. A pronounced effect – a statistically significant coincidence between areas with increased annual malignant melanoma of skin mortality and its correlation with annual alpha radiation flux is observed for the Alpine region (Italy, Austria, Switzerland), the Carpathians, the Pyrenees, and the Baltic countries. Central Spain and the Central United Kingdom are affected too. Figures 2-9 show the correlated changes in malignant melanoma of skin mortality with alpha radiation flux for these areas.

Figures 2-9 show the time dependence in the interval 2011 – 2019 of two numerical sequences:

• Of the recorded annual fluxes of alpha particles from satellites of the GOES series – 10, 11, 12, 13, and 14, and,
• Of the “Malignant melanoma of skin” annual mortality rate for some of the NUTS-2 regions of the European Union.
The high correlation between the two numerical sequences can be seen, indicating the existence of a causal relationship between them.

Figure 2

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Figure 3

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Figure 4

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Figure 5

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Figure 6

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Figure 7

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Figure 8

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Figure 9

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Discussion

The given examples convincingly prove the existence of an influence of cosmic radiation flux on malignant melanoma mortality. The problem of the mechanism of the described influence remains unclear. A hypothesized mechanism of this influence is outlined below, answering many of the questions that arise.

1) An observed phenomenon – mortality from many diseases in the statistics of many countries located mainly in the 30°N – 60°N band, is strongly correlated with fluxes of positively charged particles with energy of the order of 4 – 21 MeV, recorded by the GOES series satellites in Earth orbit.

2) The recorded alpha particle flows are mostly pulses with a duration of less than 5 minutes (the averaging interval of the recording device).

3) Proposed hypothesis – positively charged particles with high energy penetrate through the Earth’s atmosphere to the Earth’s surface and damage human health, causing death mainly in elderly people.

4) As the average altitude of the affected countries increases, the particle flux- correlated mortality shows an increasing trend [4,10]. It is probably due to the more intense radiation flux penetrating the thinner atmosphere over the mountainous region of Earth’s surface – an argument favoring the hypothesis.

5) The source of the flows of positively charged particles is the Sun – mortality increases with observable processes on the Sun – from Solar Mass Ejections directed to Earth (a phenomenon on the solar surface that could be observed with other astronomical means) [4,8]. The Alpha Magnetic Spectrometer (AMS-02) on the International Space Station measures cosmic rays, excluding those of solar origin (when shielded from the Sun by the station’s solar panels). In particular, it measures the flow of 3He and 4He (alpha particles) in cosmic rays. The measurements show [31] increasing annual flux of alpha particles in cosmic rays for the interval of years from 2011 to 2017 (last available data), while the flux of GOES registered (solar?) alpha particles for the same interval of years is decreasing (Figures 2-9). Indirect evidence for the Sun as a source of high-energy alpha particles is that this assumption convincingly explains the downstream processes that ultimately lead to death.

6) Positively charged solar particles capable of penetrating through the Earth’s atmosphere to the Earth’s surface are high-energy alpha particles. Calculators PSTAR [28] and ASTAR [29] calculate the penetration parameters of protons, respectively alpha particles in different substances, in particular in air. Calculations with data for a homogeneous atmosphere – an atmospheric model with constant density, temperature, and pressure decreasing with height [4] show that only particles whose energy is above 2.4 GeV for protons and over 6.2 GeV for alpha particles can penetrate the Earth’s atmosphere to the surface. There are no registered by GOES satellites protons above 0.7 GeV, but there are registered alpha particles with energy above 3.4 GeV, hypothetically also those with energy above 6.2 GeV [4,10,12], i.e. the particles that penetrate to the Earth’s surface are probably high-energy alpha particles. Only fluxes of alpha particles with a magnitude of at least (1000 particles).cm 2. s-1. MeV-1 is correlated with the mortality of the Earth’s surface.

7) It is assumed that the alpha particles recorded by the satellites were emitted simultaneously with the hypothetical fast alpha particles in a common explosive process (flares?) on the solar surface. It can be calculated that particles with an energy of 7 GeV need 8.87 min to reach the Earth’s surface from the Sun’s surface and registered by satellites particles with energies of 5 – 10 MeV travel about 2 hours. The registered alpha particles do not have enough energy to penetrate the atmosphere, unlike the hypothetical Fast alpha particles that reach the surface of the Earth in minutes from the center of the solar disk. However, the registered alpha particles are an indicator that two hours earlier there was an irradiation of the Earth’s surface with fast (unregistered) alpha particles.

8) Although alpha particle streams irradiate the entire illuminated part of the atmosphere, penetration of fast alpha particles to the surface occurs only in a limited area of the surface (death spot), for which two conditions favoring penetration are combined:

a) The Sun is culminating for the center of the death spot,

b) For the center of the death spot, a coincidence is in effect – the direction of the geomagnetic vector coincides with the direction of the alpha particle intrusion – the alpha particle movement is not affected by the deflecting magnetic force. Such a coincidence occurs twice a year for latitudes in the band from 28°N to 48°N [4]. For latitudes outside this band, such a coincidence is impossible, the fast alpha particles do not reach the Earth’s surface, or their flux on the surface decreases fast with their moving away from the band.

9) During the year, the apparent position of the Sun relative to the point of observation shifts, so that the maximum angle of elevation of the Sun’s disk above the horizon (solar culmination) changes depending on the date.

The latitude and longitude of a point on the Earth’s surface where the solar disk is at its culmination at that moment of registration of the incoming alpha particle flow – the point of registration, can be determined from the date (latitude), and the hours and minutes of registration (longitude). The center of the dead spot can be calculated – it is approximately 30° east of the registration point [10]. The Earth’s angular velocity is 15° per hour. The moment of occurrence of a flow of fast alpha particles cannot be predicted, but the dates of increased risk for a given point on the Earth’s surface between 30°N – 50°N can be calculated by the latitude of the location [10]. For example, for the EUROSTAT NUTS-2 region Vorarlberg, Austria See (Figure 2), with latitude 47°N, the dates with maximum risk are around May 24 and July 20. On these dates, the inclination (63.6°) of the geomagnetic vector for Austria is close in magnitude to or coincides with the culmination of the Sun (the Earth’s atmosphere is thinnest at the moment of the Sun’s culmination, and there is no deflecting magnetic force for alpha particles if they intrude at this time from the Sun). The increased risk of health incidents outdoors around local noon is a further argument for the healthfulness of the indoor midday break (‘siesta’) practiced in Mediterranean countries. The arguments given above reveal a new, previously unsuspected cosmic cause of melanoma mortality – solar corpuscular alpha radiation. This type of radiation may be the leading external cause of melanoma disease. The risk, in particular for melanoma, is highest for inhabitants in the mountainous regions, in ours around local noon.

The risk is also increased during certain days of the year (depending on the latitude of the observation point) during which the solar culmination coincides with the angle of the geomagnetic vector (inclination). If a stream of high-energy solar alpha particles were to hit the Earth at this time, there would be no deflecting magnetic force on them, making it easier for them to reach the Earth’s surface. The predominant part of the recorded pulses of alpha particles forms unnatural series with fixed periods and relatively constant magnitudes, which allows the hypothesis of their artificial origin [12]. The creams and oils that are used to protect the skin from ultraviolet radiation are useless in protecting the human body from the penetration of alpha particles with high enough energy, capable of overcoming the resistance of the atmosphere and reaching the Earth’s surface. The predominant part of the recorded pulses of alpha particles forms unnatural series with fixed periods and relatively constant magnitudes, which allows the hypothesis of their artificial origin [12].

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