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This manuscript provides information for replicating the Coasting agent-based model presented in “Simulating emerging coastal tourism vulnerabilities: an agent-based modelling approach”. The model description follows the Overview, Design Concepts, and Details + Human Decision-making (ODD+D) protocol. Moreover, this paper includes implementation details on global sensitivity analysis and scenario discovery. Finally, we provide supplementary tables and figures for scenario discovery results not included in the main paper. Highlights: • Model description for simulating emerging environmental vulnerabilities in a coastal tourism context • Coasting’s design facilitates model adaptations to other coastal tourism destinations • Implementation details for applying global sensitivity analysis and scenario discovery to vulnerability assessments, Graphical abstract Image, graphical abstract

Purpose The state of Israel represents a unique transplant environment; deprived from neighboring countries organ sharing, and operating under a distinctive religious limitation. Furthermore, as the single Israeli Lung transplant center our center is required to provide transplant solutions to a verity of recipients which may be considered in many transplant centers as sub-optimal candidates. Hence, the usage of the extremely limited donor pool is in constant debate. In recent years we have been using in increasing frequency lungs from older donors (> 60), and thus we have been deliberating whether these organs should be transplanted in older Vs younger recipients. Hence, our goal was to review Israel's Lung transplant data base to evaluate the longevity of old Vs. young donor lungs transplanted in young Vs. old recipients. Methods Israel's Lung transplant data base was reviewed from January 2012to December 2017. Both clinical and demographic characteristics were extracted. Short and long-term survival were evaluated. Results 247 donor lungs were used to preform 262 lung transplants; 167 donors were younger than 60 years (67.1%) and 80 donors were older than 60 years (22.39%). We choose to focus on the 1-year survival of the Bi-lateral orthotopic lung transplantation patients. We found a statistically significant survival difference one-year post transplant between the 4 groups (0.02): While the survival rate was ∼81% when both the donors and the recipients were younger than 60 years, it dropped to ∼ 57%-63% once the donors were older than 60 years (Figure 1). Conclusion In this unique environment of both recipients and donors’; young donors transplanted into young recipients had the best survival at 1-year post-transplant. Once, using older donors the survival at 1-year post-transplant was reduced regardless if transplanted into young or old recipients. Future analysis, should address the concept claiming that using old lungs is better than no lungs in a large scale multi center studies.

Purpose The world SARS-CoV-2 pandemic has affected global health, including the health of lung transplant recipients. There is very little data reported on the outcomes of SARS-CoV-2 on this gruop of patients Methods Retrospective cohort study approved of all LTx recipients with symptoms consistent with COVID-19 investigated with naso-pharyngeal swabs and reverse PCR for SARS-COV-2. Postive test for SARS-COV-2 Inserted to our cohort and investigated their files. We also conducted pooled analysis of published cases of covid 19 cases of lung transplant recipients Results We identified eleven cases of COVID-19 among a cohort of 348 LTx recipients. All but two patients were hospitalized. Seven patients required intensive care and six died (55% mortality). Non-survivors had lower baseline FEV1 than survivors and worse and/or deteriorating chest radiographic scores during admission. No effect of medical therapy including steroids and remdesivir could be determined. This mortality rate compared poorly general hospitalized COVID-19 patients at our institution (13%) and national mortality rate of 0.3% in the general population. Incidence of COVID-19 was similar to the general population (0.3%). In a pooled analysis of published cases, we determined mortality of 28% across different reports of lung transplant patients with COVID-19. Conclusion COVID-19 disease is very severe in lung transplant recipients. In the absence of effective therapy and vaccination, transplant physicians should concentrate their efforts on prevention of disease and encourage meticulous preventative behavior by recipients under their care.

Non-cystic fibrosis bronchiectasis (NCFBr) is a major cause of morbidity due to frequent infectious exacerbations. We analyzed the influence of patient age and bronchiectasis location on the bacterial profile of patients with NCFBr. This retrospective cohort study included 339 subjects diagnosed with an infectious exacerbation of NCFBr during the 9-year period between January 2006 and December 2014. Bronchoalveolar lavage (BAL) cultures and high-resolution computed tomography scans (HRCT) were utilized to characterize the location of the bronchiectasis and bacteriologic pathogenic profile. In univariate logistic regression, the frequency of Haemophilus influenzae was higher in patients aged ≤64 years (OR = 0.969, p 0.0001, 95 % CI 0.954-0.983), whereas the frequency of Pseudomonas aeruginosa (OR = 1.027, p = 0.008, 95 % CI 1.007-1.048) and Enterobacteriaceae (OR = 1.039, p = 0.01, 95 % CI 1.009-1.069) were significantly higher in patients aged64 years. The lobar distribution of bronchiectasis in the subjects was 25.9 % in the right middle lobe (RML), 20.7 % in the right lower lobe (RLL), 20.4 % in the left lower lobe (LLL), 13.8 % in the lingula, 13 % in the right upper lobe (RUL), and 6.2 % in the left upper lobe (LUL). In the lower lobes, H. influenzae was the dominant species isolated, whereas in the RUL it was P. aeruginosa and in the LUL it was non- tuberculous mycobacterium (NTM). H. influenzae was more prevalent in younger patients, whereas P. aeruginosa, Enterobacteriaceae and NTM predominated in older patients. Different pathogens were associated with different lobar distributions. The RML, RLL and LLL showed a greater tendency to develop bronchiectasis than other lobes.

Coastal tourism destinations face a range of climate-related changes. Prevailing challenges include understanding emerging changes and future uncertainties. A dynamic vulnerability approach is a promising way to analyse emerging socio-ecological vulnerabilities. This research presents an innovative coupling of the human-environment system in the agent-based model Coasting, and is applied to Curacao's coastal tourism. We observe how operator numbers and environmental attractiveness, proxies for socio-ecological vulnerabilities, change over time. Global sensitivity analysis highlights the main interacting factors behind socio-ecological vulnerabilities. Scenario discovery explores the main drivers contributing to undesirable vulnerabilities. The model's findings provide key insights on which factors tourism destinations need to focus on to prevent socio-ecological vulnerabilities.

Purpose AAT has been reported to have anti-apoptotic and anti-inflammatory effects in addition to the canonical anti protease activity. This study aimed to evaluate the safety and efficacy of human, α-1 antitrypsin (AAT) [GLASSIA®] add-on pharmacotherapy in the treatment of patients undergoing first lung transplantation. Methods Thirty patients aged 18 and above (Table 1) were randomized 2:1 to receive SOC or SOC with intravenous AAT at the time of the lung transplant as a loading dose (90 mg/kg), and then 5 doses (30 mg/kg) every 2 days, followed by 3 biweekly (120 mg/kg), and 10 monthly (240 mg/kg) doses to 48 weeks. The following parameters were monitored: PGD, acute rejection, pulmonary function, and adverse events. Results We report here the short term (6 month) outcomes as part of an interim analysis. Patient demographics are shown in Table 1. AAT was associated with a trend to an increase in PaO2/FiO2 and a decrease in PGD grade at day 3, and a decrease in the duration of mechanical ventilation after surgery. Acute rejection was observed in 4 AAT patients (21%) vs 3 SOC only patients (30%) and pulmonary infections were observed in 10 AAT (53%) vs 5 events in 4 (40%) SOC only patients. There were no adverse events that were considered to be related to study drug. Mortality was similar between arms and all the events (6) were related to sepsis. Conclusion AAT treatment is safe and might improve PGD characteristics and mechanical ventilation duration after lung transplantation.

A non-smoking 64-year-old man presented with progressive hoarseness which had developed over the previous 6 months. More recently, he noted weight loss, low grade fever and mild dysphagia. Past medical history was negative for tuberculosis, smoking, malignancy, neck trauma and for thyroid or pulmonary disease. He had difficulty in swallowing solid food but not fluids and had lost 13 kg in body weight over the last 4 months. His body temperature fluctuated between 37 ~ and 38~ He denied night sweats, pruritus or abdominal pain. Physical examination was unremarkable except for temperature of 37"8~ Ausculation of the chest was normal. There was no lymphadenopathy, hepatosplenomegaly or skin changes. Neurological examination was normal. Indirect laryngoscopy revealed paralysis of the left vocal cord. Slit lamp examination revealed no ocular pathology. Blood count, serum electrolytes, calcium and liver function tests were normal. A PPD skin test (10 units of Tuberculin) produced a response of 10mm. Angiotensin converting enzyme levels were normal on two occasions. Erythrocyte sedimentation rate was 15 mm during the first hour. Pulmonary function tests revealed normal expiratory flow rates, normal lung volumes and carbon monoxide diffusion

During the summer of 2000, a countrywide epidemic of West Nile fever (WNF) occurred in Israel, with 417 confirmed cases and 35 deaths. Immunosuppressed patients had a 31% case-fatality rate, which was significantly higher compared to non-immunosuppressed patients (13%). We describe a 42-year-old male lung-transplant recipient with serologically confirmed West Nile virus (WNV) encephalitis and deteriorating level of consciousness. He was treated with 0.4 g/kg intravenous immunoglobulin preparation from Israeli donors that contained a high titer of anti-WNV antibodies (1 : 1600). The patient showed rapid improvement within 24 h and complete disappearance of signs and symptoms within 48 h. This is the second case of an immunosuppressed patient responding to the same preparation of intravenous immunoglobulins. Larger studies are required in order to establish the therapeutic role of immunoglobulins in patients with WNF.

Lymphocytic interstitial pneumonitis (LIP) was classically described by Carrington and Leibow in 1966 in non-AIDS patients (1). This pathological description of diffuse lymphocytic infiltration of the interstitium was later associated with various autoimmune disorders such as Sjogren's syndrome, thyroiditis and others (2). Since the beginning of the AIDS epidemic several reports described the common finding of LIP in children infected with human immume deficiency virus (HIV) (3). Less commonly, LIP was reported in adults, mostly Haitians, with AIDS or AIDS-related complex (4--6). While the pathological and radiological manifestations are well described, little is known about the pathogenesis of this disorder. There is some evidence in children with AIDS that Epstein-Barr virus (EBV) is associated with LIP. Feckler and associates (7) reported the detection of EBV-DNA genome in saliva and lung tissue of a child with LIP and Adinman and colleagues (8) reported similar findings in eight additional AIDS-children with LIP. In order to explore the possible etiologic role of EBV in HIV-seropositive adults with LIP we measured the EBV serology in the peripheral blood of five patients with LIP and compared them to 19 HIV-positive patients without LIP.

The objective of this chapter is to provide two complete teaching modules for MSc students of animal science (in Wageningen University, The Netherlands) with minimal background in modelling, but knowledge in animal nutrition at the BSc level. In working through the first module, students will develop a model simulating rumen digestion and passage dynamics and, during development, will become familiar with the concept of fractional passage and degradation rates. In the second module, students will develop a model simulating protein and fat accretion rates in growing pigs, dealing with the principles of nutrient partitioning in growing animals.

C YCLOSPORINE (CyA) is a cyclic undecapeptide with immunosuppressive properties commonly used in transplanted patients and in autoimmune diseases. Cyclosporine reversibly inhibits T-cell-mediated responses by reduction of interleukin-2 synthesis and lymphokine production as well as inhibition of alpha interferon synthesis. The therapeutic range of the drug is narrow, as toxicity limits the use. Frequent monitoring of blood levels can minimize drug toxicity. The most important undesirable effect is renal impairment, with body weight gain, hypertension, and increased serum creatinine levels. Neurologic and dermal complications, gastrointestinal intolerance, hepatotoxicity, and endocrine side effects were also reported.‘-’ Cyclosporine is primarily eliminated in the liver by the cytochrome P-450 hepatic enzymes mainly by oxidative processes.“-’ More than 90% of the IV dose is excreted by the bile while urinary elimination remains below 6% of the administered dose. Known metabolites conserve the cyclic oligopeptide structure of CYA,‘,~ and data suggest that they have a longer half-life than cyclosporine.‘,h To achieve lung targeting of CyA, we developed a coated form of the drug with the rationale of producing lung small-size arteriole embolization, as was done previously with Actinomycin D.” We analyzed CyA tissue level in lungs, kidneys, brain, heart, liver, and blood by radioimmunoassay (RIA), after injecting various doses of the drug.

OSTTRANSPLANT diabetes mellitus (PTDM) has gained widespread attention due to the micro- and macrovascular complications that increase the morbidity and mortality rates of patients receiving solid organs. A higher incidence of PTDM has been associated with immunosuppressive therapy. This study compares glucose metabolism in heart transplant recipients receiving either FK506 or cyclosporine. METHODS Two groups of heart transplant recipients, differing in their immunosuppressive regimen—FK506 or cyclosporin—were followed for periods up to 6 years. Blood levels of glucose and of the respective immunosuppressive agent were measured regularly, and, if needed, anti-hyperglycemic treatment prescribed. The concomitant therapy with low-dose steroids and azathioprine was the same for both cohorts. T-test were performed to compare with the mean values of the two groups. RESULTS

The authors have developed a module extractor called VAMP, that cooperates with a standard formatter. They describe the VAMP approach to literate programming. Literate programming identifies a method of documentation which explains to people what a computer is supposed to do. Generally, this means that refinement steps are documented in such a way that modules can be extracted from the documentation files. The tool has been in use since 1982. The experiences are predominantly positive, in spite of the overhead implicit in the methodology. The fact that VAMP is independent of both programming language and formatter distinguishes it from WEB and its derivatives. >

Purpose Survival of lung transplant recipients is improving constantly. During surveillance, patients are exposed to ionizing radiation from various imaging procedures, however, the cumulative radiation exposure and subsequent cancer risk after lung transplantation is not known. The purpose of this study was to estimate cumulative radiation exposure during follow-up after lung transplantation and its likely effect on the lifetime risk of cancer. Methods and Materials We included all patients who underwent lung transplantation at our center and survive at least 4 years since January 2000. Follow-up continued until March 21, 2012 or until death. We identified all procedures with radiation exposure and malignancies developed during study period. Estimation of the effective dose exposure and subsequent cancer risk were derived from previous reports. Results The study included 107 patients. Mean follow-up was 6.49±1.74 years for each patient (range 4-11). Radiation exposure during mean follow-up was 137.8 mSv. This represents an additional cancer risk of 0.55%. Chest X-ray was the most frequent procedure performed, nevertheless, CT scan contributed the largest radiation dose. A group of 24 cases of cancer in 21 patients (19.6%) were identified. Types of cancer are as follows: skin cancer-8 cases, lung cancer-6 cases, Transitional cell carcinoma-4 cases, post transplantation lymphoproliferative disease-2 cases, Kaposi sarcoma, Cholagiocarcinoma, Stomach carcinoma and Breast carcinoma-1 case each. The average radiation exposure in the group who developed cancer was 141.68±23 mSv and the average radiation exposure in the non-cancer group was 135.72±27 mSv. The difference between the two groups was not statistically significant (p=0.22). Conclusions Lung transplant recipients are exposed to 7.77 times greater radiation dose compared to radiation dose from medical imaging in the general population. Nevertheless, the lifetime increase in cancer risk due to radiation is small. Radiation exposure is not a major factor causing the increase in cancer incidence in lung transplant recipients.

ULMONARY INFECTIOUS complications are common in patients after solid organ transplantation (SOT) or bone marrow transplantation (BMT) and are responsible for significant morbidity and mortality. Early diagnosis of infectious complications is extremely important for the outcome of transplant recipients 1‐3 The purpose of this study was to examine the role of fiberoptic bronchoscopy (FOB) in transplant recipients with suspected pulmonary infections. METHODS The study was conducted at the Institute of Pulmonary Medicine. Rabin Medical Center, Beilinson Campus (a tertiary-care university hospital). We retrospectively examined data of patients posttransplantation who required FOB from May 5, 1999 until May 2002. Indications for FOB were suspected pulmonary infection by either abnormal chest X-ray or respiratory symptoms. Lung transplant recipients with surveillance bronchoscopies were excluded from the study. Patients underwent bronchoalveolar lavage (BAL); specimens were analyzed as bacteriology, virology, fungal, and mycobacterial cultures. In 65% of cases, transbronchial biopsies (TBBs) were done; specimens were sent to pathological examination as well as silver and cytomegalovirus (CMV)-specific stains.

significantly worse in PGD 3 group compared to PGD 0-1, and 2 (0.001)(Figure 1A). Within the PGD 3 population, early outcomes were significantly better in group A compared to groups B and C. Median time extubation were 4,14,and 17 days(p 0.01), ICU LOS were 8,21,and 20 days(p 0.004), Hospital LOS were 31,41, and 32 days(p-0.15) and 90 day mortality were 6, 26, and 37%(p 0.003) in groups A, B and C respectively. Group A demonstrated better overall survival (Figure 1B). Conclusions: PGD 3 is a heterogeneous group. Patients requiring ECMO and those with persisting poor function for 72hs have significantly worse short and long term outcomes. These findings suggest that further refinement of current ISHLT PGD grading system is required to more accurately classify patients.

ATRIAL fibrillation (AF) is the most common dysrhythmia seen early after major thoracic surgery. Atrial dysrhythmia has been observed in children undergoing lung transplantation, but AF after adult lung transplantation in the early postoperative period has not previously been reported. A Heart and Lung Transplantation Unit in the Department of Cardiothoracic Surgery in a university hospital is the setting for this retrospective analysis.

During the years 1974 to 1986, 44 young soldiers (mean age 21 ± 3 years) died suddenly and unexpectedly in the Israel Defense Forces. Cardiac causes accounted for 54 percent of deaths; neurologic causes, 14 percent of deaths; other diseases, 9 percent; and in 23 percent, cause of death was unknown. Although most sudden deaths are considered unpredictable, preceding symptoms were reported in more than one half of the patients. We found that syncope had occurred in 23 percent of cases, chest pain in 11 percent, and febrile disease in 16 percent. Exercise-associated syncope occurred in 16 percent and exercise-associated death occurred in most (86 percent) of those cases. Diagnosis at the time of the preceding symptoms failed to predict the fatal diseases in most cases. Our report points out the high incidence of syncope prior death in young soldiers with sudden death. Although further prospective controlled studies are needed in order to confirm that impression, we suggest that the possibility of syncope followed by sudden death should be kept in mind while evaluating young patients presenting with exercise-associated syncope.

It is well-known that all Boolean functions of n variables can be computed by a logic circuit with O(2n/n) gates (Lupanov's theorem) and that there exist Boolean functions of n variables which require logic circuits of this size (Shannon's theorem). We present corresponding results for Boolean functions computed by VLSI circuits, using Thompson's model of a VLSI chip. We prove that all Boolean functions of n variables can be computed by a VLSI circuit of O(2n) area and period 1, and we prove that there exist Boolean functions of n variables for which every (convex) VLSI chip must have Ω(2n) area.

An unusual case of temporal arteritis presenting with sensorineural hearing loss is presented. Deafness was improved dramatically by corticosteroid treatment. The diagnosis of temporal arteritis should be considered in elderly patients presenting with sensorineural hearing loss.