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Background Cardiac rehabilitation improves prognosis and symptoms in cardiac patients. In 2020, due to the COVID-19 pandemic, cardiac rehabilitation services were temporarily suspended between April and August. We aimed to investigate the effect of cardiac rehabilitation suspension during the COVID-19 pandemic on patients’ exercise capacity and metabolic parameters. Methods Included were patients undergoing cardiac rehabilitation following hospital admission for ACS. Exercise capacity, weight and body fat percentage were compared between baseline, pre- and post-lockdown visits. Results A total of 281 patients participated in the cardiac rehabilitation program prior to its suspension. Of them, only 198 (70%) patients returned to the program on its renewal and were included in the analysis. Exercise capacity improved significantly in the pre-lockdown stress test compared to baseline. However, there was a significant decrease in exercise capacity in the post compared to pre-lockdown test (8.1±6.3 and 7.1±2.1 METs in pre- and post-lockdown measurements, respectively, p Conclusions Cardiac rehabilitation suspension for 4 months during COVID-19 pandemic caused a significant reduction in exercise capacity and increased weight and body fat percent. These findings highlight the importance of remote cardiac rehabilitation services that can continue uninterrupted in times of pandemic.

Cardiac surgery and cardiopulmonary bypass (CPB) are associated with a systemic inflammatory reaction that occasionally induces a life-threatening organ dysfunction caused by the dysregulated host response to the damage-associated molecular patterns (DAMPs). In severe inflammation, cell-free DNA (cfDNA) and histones are released by inflammatory cells and damaged tissue and act as DAMPs. We sought to characterize the changes in circulating cell-free DNA (cfDNA) levels during CPB. Primary outcomes were renal failure, ventilation time (>18 hr), length of stay (LOS) in the intensive care unit (ICU) (>48hr), hospital LOS (>15 days), and death. We looked for associations with blood tests and comparison to standard scores. In a prospective cohort study, we enrolled 71 patients undergoing non-emergent coronary artery bypass grafting. Blood was drawn at baseline, 20 and 40 minutes on CPB, after cross-clamp removal, and 30 minutes after chest closure. cfDNA was measured by our fast fluorescent method. Baseline cfDNA levels [796 (656–1063) ng/ml] increased during surgery, peaked after cross-clamp removal [2403 (1981–3357) ng/ml] and returned to baseline at recovery. The difference in cfDNA from 20 to 40 minutes on CPB (ΔcfDNA 40–20) inversely correlated with peripheral vascular disease (PVD), longer ventilation time, and longer ICU and hospital length of stay (LOS). Receiver operating characteristic (ROC) curve of ΔcfDNA 40–20 for long ICU-LOS (>48hr) was with an area under the curve (AUC) of 0.738 (p = 0.022). ROC AUC of ΔcfDNA 40–20 to long Hospital LOS (>15 days) was 0.787 (p = 0.006). Correction for time on CPB in a multivariate logistic regression model improved ROC-AUC to 0.854 (p = 0.003) and suggests that ΔcfDNA 40–20 is an independent risk factor. To conclude, of measured parameters, including STS and Euroscore, the predictive power of ΔcfDNA 40–20 was the highest. Thus, measurement of ΔcfDNA 40–20 may enable early monitoring of patients at higher risk. Further studies on the mechanism behind the negative association of ΔcfDNA 40–20 with PVD and outcomes are warranted.

Background Retrospective data demonstrates that robotic-assisted thoracoscopic surgery provides many benefits, such as decreased postoperative pain, lower mortality, shorter length of stay, shorter chest tube duration, and reductions in the incidence of common postoperative pulmonary complications, when compared to video-assisted thoracoscopic surgery. Despite the potential benefits of robotic surgery, there are two major barriers against its widespread adoption in thoracic surgery: lack of high-quality prospective data, and the perceived higher cost of it. Therefore, in the face of these barriers, a prospective randomized controlled trial comparing robotic- to video-assisted thoracoscopic surgery is needed. The RAVAL trial is a two-phase, international, multi-centered, blinded, parallel, randomized controlled trial that is comparing robotic- to video-assisted lobectomy for early-stage non-small cell lung cancer that has been enrolling patients since 2016. Methods The RAVAL trial will be conducted in two phases: Phase A will enroll 186 early-stage non-small cell lung cancer patients who are candidates for minimally invasive pulmonary lobectomy; while Phase B will continue to recruit until 592 patients are enrolled. After consent, participants will be randomized in a 1:1 ratio to either robotic- or video-assisted lobectomy, and blinded to the type of surgery they are allocated to. Health-related quality of life questionnaires will be administered at baseline, postoperative day 1, weeks 3, 7, 12, months 6, 12, 18, 24, and years 3, 4, 5. The primary objective of the RAVAL trial is to determine the difference in patient-reported health-related quality of life outcomes between the robotic- and video-assisted lobectomy groups at 12 weeks. Secondary objectives include determining the differences in cost-effectiveness, and in the 5-year survival data between the two arms. The results of the primary objective will be reported once Phase A has completed accrual and the 12-month follow-ups are completed. The results of the secondary objectives will be reported once Phase B has completed accrual and the 5-year follow-ups are completed. Discussion If successfully completed, the RAVAL Trial will have studied patient-reported outcomes, cost-effectiveness, and survival of robotic- versus video-assisted lobectomy in a prospective, randomized, blinded fashion in an international setting. Trial registration ClinicalTrials.gov, NCT02617186. Registered 22-September-2015. https://clinicaltrials.gov/ct2/show/NCT02617186

Background It is estimated that up to 50% of all disease causing variants disrupt splicing. Due to its complexity, our ability to predict which variants disrupt splicing is limited, meaning missed diagnoses for patients. The emergence of machine learning for targeted medicine holds great potential to improve prediction of splice disrupting variants. The recently published SpliceAI algorithm utilises deep neural networks and has been reported to have a greater accuracy than other commonly used methods. Methods and findings The original SpliceAI was trained on splice sites included in primary isoforms combined with novel junctions observed in GTEx data, which might introduce noise and de-correlate the machine learning input with its output. Limiting the data to only validated and manual annotated primary and alternatively spliced GENCODE sites in training may improve predictive abilities. All of these gene isoforms were collapsed (aggregated into one pseudo-isoform) and the SpliceAI architecture was retrained (CI-SpliceAI). Predictive performance on a newly curated dataset of 1,316 functionally validated variants from the literature was compared with the original SpliceAI, alongside MMSplice, MaxEntScan, and SQUIRLS. Both SpliceAI algorithms outperformed the other methods, with the original SpliceAI achieving an accuracy of ∼91%, and CI-SpliceAI showing an improvement at ∼92% overall. Predictive accuracy increased in the majority of curated variants. Conclusions We show that including only manually annotated alternatively spliced sites in training data improves prediction of clinically relevant variants, and highlight avenues for further performance improvements.

This research examines the entrepreneurship gender gap by offering an additional novel explanation for the higher share of men in entrepreneurial activity focusing on intergenerational parental role. Participants (N = 1288) aged 18–81, including 259 actual entrepreneurs, completed questionnaires about entrepreneurship tendency, personality traits and socioeconomic background. The gender gap in actual entrepreneurship continues a significant difference in entrepreneurial tendency, which is developed in the first and the second stages of the entrepreneurial trajectory. When women reach the third stage of entrepreneurial development, the execution stage, they have already acquired a self-perception of an incapable and incommensurate entrepreneurial personality. The results indicate that role modeling behavioral channel significantly accounts for the gender gap in entrepreneurial personality. The results suggest that both parents contribute to women’s’ inferior perception of entrepreneurial personality and that their contribution affects all four aspects of the entrepreneurial tendency. It appears that the impact of fathers’ role modeling is larger than that of mothers, and furthermore fathers transfer other entrepreneurial role models from their side in the family.

ObjectiveTo determine 1-year attributable healthcare costs of bronchiolitis.MethodsUsing a population-based matched cohort and incidence-based cost analysis approach, we identified infants ResultsWe identified 58,375 infants with bronchiolitis (mean age 154±95 days, 61.3% males, 4.2% with comorbidities). Total 1-year mean bronchiolitis-attributable costs were $4,313 per patient (95%CI: $4,148–4,477), with $2,847 (95%CI: $2,712–2,982) spent on hospitalizations, $610 (95%CI: $594–627) on physician services, $562 (95%CI: $556–567)] on ED visits, $259 (95%CI: $222–297) on other healthcare costs and $35 ($27–42) on drugs. Attributable bronchiolitis costs were $2,765 (95%CI: $2735–2,794) vs $111 (95%CI: $102–121) in the initial 10 days post index date, $4,695 (95%CI: $4,589–4,800) vs $910 (95%CI: $847–973) in the initial 180 days and $1,158 (95%CI: $1,104–1213) vs $639 (95%CI: $599–679) during days 181–360.Mean 1-year bronchiolitis costs were higher in infants ConclusionsCompared to no bronchiolitis, bronchiolitis incurs five-time and two-time higher healthcare costs within the initial and subsequent six-months, respectively. Most expenses occur in the initial 10 days and relate to hospitalization.

Human coronaviruses (HCoVs) cause mild to severe respiratory infection. Most of the common cold illnesses are caused by one of four HCoVs, namely HCoV-229E, HCoV-NL63, HCoV-HKU1 and HCoV-OC43. Several studies have applied global transcriptomic methods to understand host responses to HCoV infection, with most studies focusing on the pandemic severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome CoV (MERS-CoV) and the newly emerging SARS-CoV-2. In this study, Next Generation Sequencing was used to gain new insights into cellular transcriptomic changes elicited by alphacoronavirus HCoV-229E. HCoV-229E-infected MRC-5 cells showed marked downregulation of superpathway of cholesterol biosynthesis and eIF2 signaling pathways. Moreover, upregulation of cyclins, cell cycle control of chromosomal replication, and the role of BRCA1 in DNA damage response, alongside downregulation of the cell cycle G1/S checkpoint, suggest that HCoV-229E may favors S phase for viral infection. Intriguingly, a significant portion of key factors of cell innate immunity, interferon-stimulated genes (ISGs) and other transcripts of early antiviral response genes were downregulated early in HCoV-229E infection. On the other hand, early upregulation of the antiviral response factor Apolipoprotein B mRNA editing enzyme catalytic subunit 3B (APOBEC3B)was observed. APOBEC3B cytidine deaminase signature (C-to-T) was previously observed in genomic analysis of SARS-CoV-2 but not HCoV-229E. Higher levels of C-to-T mutations were found in countries with high mortality rates caused by SARS-CoV-2. APOBEC activity could be a marker for new emerging CoVs. This study will enhance our understanding of commonly circulating HCoVs and hopefully provide critical information about still-emerging coronaviruses.

Background Early in the COVID-19 pandemic, it was noted that males seemed to have higher case-fatality rates than females. We examined the magnitude and consistency of the sex differences in age-specific case-fatality rates (CFRs) in seven countries. Methods Data on the cases and deaths from COVID-19, by sex and age group, were extracted from the national official agencies from Denmark, England, Israel, Italy, Spain, Canada and Mexico. Age-specific CFRs were computed for males and females separately. The ratio of the male to female CFRs were computed and meta-analytic methods were used to obtained pooled estimates of the male to female ratio of the CFRs over the seven countries, for all age-groups. Meta-regression and sensitivity analysis were conducted to evaluate the age and country contribution to differences. Results The CFRs were consistently higher in males at all ages. The pooled M:F CFR ratios were 1.71, 1.88, 2.11, 2.11, 1.84, 1.78 and 1.49, for ages 20–29, 30–39, 40–49, 50–59, 60–69, 70–79, 80+ respectively. In meta-regression, age group and country were associated with the heterogeneity in the CFR ratios. Conclusions The sex differences in the age-specific CFRs are intriguing. Sex differences in the incidence and mortality have been found in many infectious diseases. For COVID-19, factors such as sex differences in the prevalence of underlying diseases may play a part in the CFR differences. However, the consistently greater case-fatality rates in males at all ages suggests that sex-related factors impact on the natural history of the disease. This could provide important clues as to the mechanisms underlying the severity of COVID-19 in some patients.

BackgroundThe extent of myocardial fibrosis in patients with severe aortic stenosis might have an important prognostic value. Non-invasive imaging to quantify myocardial fibrosis by measuring extracellular volume fraction might have an important clinical utility prior to aortic valve intervention.MethodsSeventy-five consecutive patients with severe aortic stenosis, and 19 normal subjects were prospectively recruited and underwent pre- and post-contrast computed tomography for estimating myocardial extracellular volume fraction. Serum level of galectin-3 was measured and 2-dimensional echocardiography was performed to characterize the extent of cardiac damage using a recently published aortic stenosis staging classification.ResultsExtracellular volume fraction was higher in patients with aortic stenosis compared to normal subjects (40.0±11% vs. 21.6±5.6%; respectively, pConclusionIn patients with severe aortic stenosis undergoing computed tomography before aortic valve intervention, quantification of extracellular volume fraction correlated with functional status and markers of left ventricular decompensation, and predicted the 12-months composite adverse clinical outcomes. Implementation of this novel technique might aid in the risk stratification process before aortic valve interventions.

Severe acute respiratory disease coronavirus 2 (SARS-CoV-2) which causes corona virus disease (COVID-19) was first identified in Wuhan, China in December 2019 and has since led to a global pandemic. Importations of SARS-CoV-2 to Israel in late February from multiple countries initiated a rapid outbreak across the country. In this study, SARS-CoV-2 whole genomes were sequenced from 59 imported samples with a recorded country of importation and 101 early circulating samples in February to mid-March 2020 and analyzed to infer clades and mutational patterns with additional sequences identified Israel available in public databases. Recorded importations in February to mid-March, mostly from Europe, led to multiple transmissions in all districts in Israel. Although all SARS-CoV-2 defined clades were imported, clade 20C became the dominating clade in the circulating samples. Identification of novel, frequently altered mutated positions correlating with clade-defining positions provide data for surveillance of this evolving pandemic and spread of specific clades of this virus. SARS-CoV-2 continues to spread and mutate in Israel and across the globe. With economy and travel resuming, surveillance of clades and accumulating mutations is crucial for understanding its evolution and spread patterns and may aid in decision making concerning public health issues.

The pathogenesis of spinal cord injury (SCI) remains poorly understood and treatment remains limited. Emerging evidence indicates the severity of post-SCI inflammation and an ongoing controversy in the roles of astrocytes with studies identifying astrocytes as associated both with ongoing inflammation and damage as well as potentially having a protective role. We have completed an extensive systematic study with MRI, histopathology, proteomics and ELISA analyses designed to further define the severe protracted and damaging inflammation after SCI in a rat model. We have identified 3 distinct phases of SCI: acute (first 2 days), inflammatory (starting day 3) and resolution (>3 months) in 16 weeks follow up. Actively phagocytizing, CD68+/CD163- macrophages infiltrate myelin-rich necrotic areas converting them into cavities of injury (COI) when deep in the spinal cord. Alternatively, superficial SCI areas are infiltrated by granulomatous tissue, or arachnoiditis where glial cells are obliterated. In the COI, CD68+/CD163- macrophage numbers reach a maximum in the first 4 weeks and then decline. Myelin phagocytosis is present at 16 weeks indicating ongoing inflammatory damage. The COI and arachnoiditis are defined by a wall of progressively hypertrophied astrocytes. MR imaging indicates persistent spinal cord edema that is linked to the severity of inflammation. Microhemorrhages in the spinal cord around the lesion are eliminated, presumably by reactive astrocytes within the first week post-injury. Acutely increased levels of TNF-α, IL-1β, IFN-γ and other pro-inflammatory cytokines, chemokines and proteases decrease and anti-inflammatory cytokines increase in later phases. In this study we elucidated a number of fundamental mechanisms in pathogenesis of SCI and have demonstrated a close association between progressive astrogliosis and reduction in the severity of inflammation.

Stimulus-specific adaptation (SSA) is the reduction in responses to a common stimulus that does not generalize, or only partially generalizes, to other stimuli. SSA has been studied mainly with sounds that bear no behavioral meaning. We hypothesized that the acquisition of behavioral meaning by a sound should modify the amount of SSA evoked by that sound. To test this hypothesis, we used fear conditioning in rats, using two word-like stimuli, derived from the English words “danger” and “safety”, as well as pure tones. One stimulus (CS+) was associated with a foot shock whereas the other stimulus (CS-) was presented without a concomitant foot shock. We recorded neural responses to the auditory stimuli using chronically implanted multi-electrode arrays, recording responses telemetrically in freely moving animals before and after conditioning. Consistent with our hypothesis, SSA changed in a way that depended on the behavioral role of the sound: the contrast between standard and deviant responses remained the same or decreased for CS+ stimuli but increased for CS- stimuli, showing that SSA is shaped by experience. In most cases the sensory responses underlying these changes in SSA increased following conditioning. Unexpectedly, the responses to CS+ word-like stimuli showed a specific, substantial decrease, which we interpret as evidence for substantial inhibitory plasticity.

This study examines whether age associates with entrepreneurship tendencies across the lifespan, after taking into account aspects of personality that affect entrepreneurship. Participants (N = 963) aged 18–81, including 200 actual entrepreneurs, completed questionnaires about entrepreneurship tendency, personality traits, and attachment orientations. Results show that age is associated with a reduced tendency to engage in entrepreneurial activity. However, this decline is quite limited, it weakens with age, and is absent after age 50. In addition, the negative association of age with entrepreneurial tendency is smaller in participants with above-median entrepreneurship tendency scores relative to those with below-median scores, and it disappears in actual entrepreneurs. Furthermore, most of the traits that have been previously associated with entrepreneurial tendencies, especially Openness to Experience and Extraversion, remain unchanged with age, accounting for the stability of entrepreneurial tendency over time. The results have implications for policy makers who wish to encourage older adults to engage in entrepreneurial activity.

We use a unique, large survey on health conditions conducted in Israel (10,331 respondents, 52.8% females, mean age 49.8) to explore whether clinical determined depression and/or anxiety has different associations in compare to non-clinical determined terms such as mental health. We find that absolute income is significantly associated with a decrease in negative mental health but have no significant association with depression and/or anxiety prevalence, whereas relative income is significantly associated with a decrease in depression and/or anxiety prevalence but have no significant association with negative mental health. The two specifications differed also with respect to several important risk factors, including personal attributes such as being of African origin, of a non-Jewish Arab minority or divorced. However, they were similar with general characteristics, such as participation in sport and smoking activities, whether a person has children, age and gender. Our results put forth sever questions about the wide use of non-clinical mental health, happiness and wellbeing as a sole proxy for a person's true wellbeing or utility.

Background: Facial anthropometric data are scarce in African children. However, such data may be useful for the design of medical devices for high disease burden settings. The aim of this study was to obtain 3D facial anthropometric data of Congolese children aged 0-5 years. Methods & Findings: The faces of 287 Congolese children were successfully scanned using a portable structured-light based 3D video camera, suitable for field work in low-income settings. The images were analyzed using facial analysis algorithms. Normal growth curves were generated for the following facial dimensions: distance between nares and distance from subnasion to upper lip. At birth, 1 year, and 5 years of age the median dimensions were: 13·92, 14·66, and 17.60 mm, respectively for distance between nares, and 10·16, 10.88, and 13·79 mm, respectively for distance from subnasion to upper lip. Modeled facial contours conveniently clustered into three average sizes which could be used as templates for the design of medical instruments. Interpretation: Capturing of 3D images of infants and young children in LMICs is feasible using portable cameras and computerized analysis. This method and these specific data on Congolese pediatric facial dimensions may assist in the design of appropriately sized medical devices (thermometers, face masks, pulse oximeters, etc.) for this population. Clinical Trial Number: The study was registered at ClinicalTrials.gov (NCT03265756). Funding Statement: Association for Health Innovation in Africa (AFHIA, KMC). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: After obtaining the appropriate Institutional Review Board approval (The Comite d’Ethique du Nord Kivu, and the Research Ethics Board of the University of Alberta) and parental informed consent, we obtained 3D scans from infants and young children.

Glioblastoma multiforme (GBM) is the most common and most aggressive subtype of malignant gliomas. The current standard of care for newly diagnosed GBM patients involves maximal surgical debulking, followed by radiation therapy and temozolomide chemotherapy. Despite the advances in GBM therapy, its outcome remains poor with a median survival of less than two years. This poor outcome is partly due to the ability of GBM tumors to acquire adaptive resistance to therapy and in particular to radiation. One of the mechanisms contributing to GBM tumor progression and resistance is an aberrant activation of NF-ĸB, a family of inducible transcription factors that play a pivotal role in regulation of many immune, inflammatory and carcinogenic responses. Acetyl-11-keto-β-boswellic acid (AKBA) is a pentacyclic terpenoid extracted from the gum Ayurvedic therapeutic plant Boswellia serrata. AKBA is anti-inflammatory agent that exhibits potent cytotoxic activities against various types of tumors including GBM. One of the mechanisms underlying AKBA anti-tumor activity is its ability to modulate the NF-ĸB signaling pathway. The present study investigated in vitro and in vivo the effect of combining AKBA with ionizing radiation in the treatment of GBM and assessed AKBA anti-tumor activity and radio-enhancing potential. The effect of AKBA and/or radiation on the survival of cultured glioblastoma cancer cells was evaluated by XTT assay. The mode of interaction of treatments tested was calculated using CalcuSyn software. Inducing of apoptosis following AKBA treatment was evaluated using flow cytometry. The effect of combined treatment on the expression of PARP protein was analysed by Western blot assay. Ectopic (subcutaneous) GBM model in nude mice was used for the evaluation of the effect of combined treatment on tumor growth. Immunohistochemical analysis of formalin-fixed paraffin-embedded tumor sections was used to assess treatment-related changes in Ki-67, CD31, p53, Bcl-2 and NF-ĸB-inhibitor IĸB-α. AKBA treatment was found to inhibit the survival of all four tested cell lines in a dose dependent manner. The combined treatment resulted in a more significant inhibitory effect compared to the effect of treatment with radiation alone. A synergistic effect was detected in some of the tested cell lines. Flow cytometric analysis with Annexin V-FITC/PI double staining of AKBA treated cells indicated induction of apoptosis. AKBA apoptotic activity was also confirmed by PARP cleavage detected by Western blot analysis. The combined treatment suppressed tumor growth in vivo compared to no treatment and each treatment alone. Immunohistochemical analysis showed anti-angiogenic and anti-proliferative activity of AKBA in vivo. It also demonstrated a decrease in p53 nuclear staining and in Bcl-2 staining and an increase in IĸB-α staining following AKBA treatment both alone and in combination with radiotherapy. In this study, we demonstrated that AKBA exerts potent anti-proliferative and apoptotic activity, and significantly inhibits both the survival of glioblastoma cells in vitro and the growth of tumors generated by these cells. Combination of AKBA with radiotherapy was found to inhibit factors which involved in cell death regulation, tumor progression and radioresistence, therefore it may serve as a novel approach for GBM patients.

Most papers on the physical condition of birds during spring migration focused on food availability preceding migratory take-off. Only a few studies examined the effect of climate conditions at the wintering grounds upon autumn arrival on bird physical condition later on. Here, we hypothesized that environmental conditions upon arrival at the wintering grounds, and not necessarily upon departure, have a crucial carry-over effect on bird spring migration. Using 29,000 observations of the lesser whitethroat, Sylvia curruca, and the eastern Bonelli's warbler, Phylloscopus orientalis, we found temperatures upon arrival at the African wintering grounds to be the only climatic variable correlated with birds' body state upon spring stopover in Israel, six months later. Two different mechanisms could explain these results. One possibility is that high temperatures create favorable conditions for insect activity, which allows rapid recovery from autumn migration and hence successful winter survival and maintenance. Another possible scenario is that harsh conditions, due to the heat and dry environment, cause high mortality, permitting survival of larger individuals which, then, enjoy reduced inter- and intra-specific competition. Whatever the mechanism is, our findings suggest that conditions upon autumn arrival, and not necessarily at the end of winter as traditionally thought, may have a major impact on migrating birds.

BackgroundEsophagectomy for esophageal cancer carries high morbidity and mortality, particularly in older patients. Transthoracic esophagectomy allows formal lymphadenectomy, but leads to greater perioperative morbidity and pain than transhiatal esophagectomy. Epidural analgesia may attenuate the stress response and be less immunosuppressive than opioids, potentially affecting long-term outcomes. These potential benefits may be more pronounced for transthoracic esophagectomy due to its greater physiologic impact. We evaluated the impact of epidural analgesia on survival and recurrence after transthoracic versus transhiatal esophagectomy.MethodsA retrospective cohort study was performed using the linked Surveillance, Epidemiology and End Results (SEER)-Medicare database. Patients aged ≥66 years with locoregional esophageal cancer diagnosed 1994-2009 who underwent esophagectomy were identified, with follow-up through December 31, 2013. Epidural receipt and surgical approach were identified from Medicare claims. Survival analyses adjusting for hospital esophagectomy volume, surgical approach, and epidural use were performed. A subgroup analysis restricted to esophageal adenocarcinoma patients was performed.ResultsAmong 1,921 patients, 38% underwent transhiatal esophagectomy (n = 730) and 62% underwent transthoracic esophagectomy (n = 1,191). 61% (n = 1,169) received epidurals and 39% (n = 752) did not. Epidural analgesia was associated with transthoracic approach and higher volume hospitals. Patients with epidural analgesia had better 90-day survival. Five-year survival was higher with transhiatal esophagectomy (37.2%) than transthoracic esophagectomy (31.0%, p = 0.006). Among transthoracic esophagectomy patients, epidural analgesia was associated with improved 5-year survival (33.5% epidural versus 26.5% non-epidural, p = 0.012; hazard ratio 0.81, 95% confidence interval [0.70, 0.93]). Among the subgroup of esophageal adenocarcinoma patients undergoing transthoracic esophagectomy, epidural analgesia remained associated with improved 5-year survival (hazard ratio 0.81, 95% confidence interval [0.67, 0.96]); this survival benefit persisted in sensitivity analyses adjusting for propensity to receive an epidural.ConclusionAmong patients undergoing transthoracic esophagectomy, including a subgroup restricted to esophageal adenocarcinoma, epidural analgesia was associated with improved survival even after adjusting for other factors.

Understanding the main processes that affect community similarity have been the focus of much ecological research. However, the relative effects of environmental and spatial aspects in structuring ecological communities is still unresolved and is probably scale-dependent. Here, we examine the effect of habitat identity and spatial distance on fine-grained community similarity within a biogeographic transition zone. We compared four hypotheses: i) habitat identity alone, ii) spatial proximity alone, iii) non-interactive effects of both habitat identity and spatial proximity, and iv) interactive effect of habitat identity and spatial proximity. We explored these hypotheses for spiders in three fragmented landscapes located along the sharp climatic gradient of Southern Judea Lowlands (SJL), Israel. We sampled 14,854 spiders (from 199 species or morphospecies) in 644 samples, taken in 35 patches and stratified to nine different habitats. We calculated the Bray-Curtis similarity between all samples-pairs. We divided the pairwise values to four functional distance categories (same patch, different patches from the same landscape, adjacent landscapes and distant landscapes) and two habitat categories (same or different habitats) and compared them using non-parametric MANOVA. A significant interaction between habitat identity and spatial distance was found, such that the difference in mean similarity between same-habitat pairs and different-habitat pairs decreases with spatial distance. Additionally, community similarity decayed with spatial distance. Furthermore, at all distances, same-habitat pairs had higher similarity than different-habitats pairs. Our results support the fourth hypothesis of interactive effect of habitat identity and spatial proximity. We suggest that the environmental complexity of habitats or increased habitat specificity of species near the edge of their distribution range may explain this pattern. Thus, in transitions zones care should be taken when using habitats as surrogate of community composition in conservation planning since similar habitats in different locations are more likely to support different communities.

Measures of population differentiation, such as FST, are traditionally derived from the partition of diversity within and between populations. However, the emergence of population clusters from multilocus analysis is a function of genetic structure (departures from panmixia) rather than of diversity. If the populations are close to panmixia, slight differences between the mean pairwise distance within and between populations (low FST) can manifest as strong separation between the populations, thus population clusters are often evident even when the vast majority of diversity is partitioned within populations rather than between them. For any given FST value, clusters can be tighter (more panmictic) or looser (more stratified), and in this respect higher FST does not always imply stronger differentiation. In this study we propose a measure for the partition of structure, denoted EST, which is more consistent with results from clustering schemes. Crucially, our measure is based on a statistic of the data that is a good measure of internal structure, mimicking the information extracted by unsupervised clustering or dimensionality reduction schemes. To assess the utility of our metric, we ranked various human (HGDP) population pairs based on FST and EST and found substantial differences in ranking order. In some cases examined, most notably among isolated Amazonian tribes, EST ranking seems more consistent with demographic, phylogeographic and linguistic measures of classification compared to FST. Thus, EST may at times outperform FST in identifying evolutionary significant differentiation.