Bayesian inference reveals positive but subtle effects of experimental fishery closures on marine predator demographics

Global forage-fish landings are increasing, with potentially grave consequences for marine ecosystems. Predators of forage fish may be influenced by this harvest, but the nature of these effects is contentious. Experimental fishery manipulations offer the best solution to quantify population-level impacts, but are rare. We used Bayesian inference to examine changes in chick survival, body condition and population growth rate of endangered African penguins Spheniscus demersus in response to 8 years of alternating time-area closures around two pairs of colonies. Our results demonstrate that fishing closures improved chick survival and condition, after controlling for changing prey availability. However, this effect was inconsistent across sites and years, highlighting the difficultly of assessing management interventions in marine ecosystems. Nevertheless, modelled increases in population growth rates exceeded 1% at one colony; i.e. the threshold considered biologically meaningful by fisheries management in South Africa. Fishing closures evidently can improve the population trend of a forage-fish-dependent predator-we therefore recommend they continue in South Africa and support their application elsewhere. However, detecting demographic gains for mobile marine predators from small no-take zones requires experimental time frames and scales that will often exceed those desired by decision makers

Inflammatory Gene Regulatory Networks in Amnion Cells Following Cytokine Stimulation: Translational Systems Approach to Modeling Human Parturition

A majority of the studies examining the molecular regulation of human labor have been conducted using single gene approaches. While the technology to produce multi-dimensional datasets is readily available, the means for facile analysis of such data are limited. The objective of this study was to develop a systems approach to infer regulatory mechanisms governing global gene expression in cytokine-challenged cells in vitro, and to apply these methods to predict gene regulatory networks (GRNs) in intrauterine tissues during term parturition. To this end, microarray analysis was applied to human amnion mesenchymal cells (AMCs) stimulated with interleukin-1β, and differentially expressed transcripts were subjected to hierarchical clustering, temporal expression profiling, and motif enrichment analysis, from which a GRN was constructed. These methods were then applied to fetal membrane specimens collected in the absence or presence of spontaneous term labor. Analysis of cytokine-responsive genes in AMCs revealed a sterile immune response signature, with promoters enriched in response elements for several inflammation-associated transcription factors. In comparison to the fetal membrane dataset, there were 34 genes commonly upregulated, many of which were part of an acute inflammation gene expression signature. Binding motifs for nuclear factor-κB were prominent in the gene interaction and regulatory networks for both datasets; however, we found little evidence to support the utilization of pathogen-associated molecular pattern (PAMP) signaling. The tissue specimens were also enriched for transcripts governed by hypoxia-inducible factor. The approach presented here provides an uncomplicated means to infer global relationships among gene clusters involved in cellular responses to labor-associated signals

Pathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins.

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung developmental disorder caused by heterozygous point mutations or genomic deletion copy-number variants (CNVs) of FOXF1 or its upstream enhancer involving fetal lung-expressed long noncoding RNA genes LINC01081 and LINC01082. Using custom-designed array comparative genomic hybridization, Sanger sequencing, whole exome sequencing (WES), and bioinformatic analyses, we studied 22 new unrelated families (20 postnatal and two prenatal) with clinically diagnosed ACDMPV. We describe novel deletion CNVs at the FOXF1 locus in 13 unrelated ACDMPV patients. Together with the previously reported cases, all 31 genomic deletions in 16q24.1, pathogenic for ACDMPV, for which parental origin was determined, arose de novo with 30 of them occurring on the maternally inherited chromosome 16, strongly implicating genomic imprinting of the FOXF1 locus in human lungs. Surprisingly, we have also identified four ACDMPV families with the pathogenic variants in the FOXF1 locus that arose on paternal chromosome 16. Interestingly, a combination of the severe cardiac defects, including hypoplastic left heart, and single umbilical artery were observed only in children with deletion CNVs involving FOXF1 and its upstream enhancer. Our data demonstrate that genomic imprinting at 16q24.1 plays an important role in variable ACDMPV manifestation likely through long-range regulation of FOXF1 expression, and may be also responsible for key phenotypic features of maternal uniparental disomy 16. Moreover, in one family, WES revealed a de novo missense variant in ESRP1, potentially implicating FGF signaling in the etiology of ACDMPV

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Ecophysiological traits associated with the competitive ability of invasive Australian acacias

The original publication is available at http://onlinelibrary.wiley.com/Aim: We explored morphological and ecophysiological traits that enable invasive Australian acacias to compete with native species for resources (light, water and nutrients) necessary to support the substantial growth associated with successful invasions. Location: Global. Results: Invasive Australian acacias grow large and seed prolifically in invaded regions. The greater capacity for vegetative growth is underpinned by their ability to acquire and efficiently use resources in non-native habitats. Key biological traits that enhance acquisition include (1) rapid and substantial allocation to root mass (up to 6-fold more than co-occurring native species) directed towards deep roots (at least 50% longer than those of natives) and to extensive shallow root networks; (2) heteroblasty, in most species, conferring high relative growth rates as bipinnate seedlings but long-lived, nutrient-conserving phyllodes as adults and (3) strong N2-fixation abilities. Main conclusions: The ecophysiological traits that govern the competitive interaction of invasive Australian acacias with native species are an important component of the recognized suite of factors including introduction history, human use and enemy release that combine to produce successful invasions. Traits interact to give Australian acacias competitive advantage over many native species. One such interaction is that of N2 fixation, which when coupled with slow decomposition of sclerophyllous phyllodes results in alteration of soil nutrient cycling. The lasting legacy of soil N-enrichment hinders the competitive ability of native species and further enhances invasions. The importance of edaphic factors and competitive interactions in determining invasive success should be considered in predictive modelling of species distributions. © 2011 Blackwell Publishing Ltd.Post-prin

Correction to ‘Bayesian inference reveals positive but subtle effects of experimental fishery closures on marine predator demographics'

It has recently come to our attention that we made a coding error while implementing the hierarchical mixed-models describing chick condition and chick survival (equations (2.1) and (2.2), respectively) in ‘Bayesian inference reveals positive but subtle effects of experimental fishery closures on marine predator demographics' [1]. This error meant that the nested random effect described in equation (2.1) and the hierarchical shared frailty term described in equation (2.2) were not implemented correctly in the original analysis. This resulted in our reporting the model parameter estimates with higher precision than should have been the case (table 1 and figure 1). Here we present corrected results (table 1 and figure 1) based on correctly specified models in JAGS [2] applied to the datasets used in our original analysis. Our error, which pertained to the specification of the structure of the priors for the nested random effects (see electronic supplementary material), influenced the derived parameter estimates of the mean chick condition or chick survival during closed and open years (figure 1) more (standard deviations are between 29% and 285% larger in the corrected results) than the estimates for the regression coefficients representing the island effect (–0.8 to 9%), closure effect (4–8%) or their interaction (6–8%). These changes do not alter the predicted influence of the fisheries closures on the population dynamics of endangered African penguins Spheniscus demersus

Detailed methods, additional results and model code. from Bayesian inference reveals positive but subtle effects of experimental fishery closures on marine predator demographics

ESM 1: Additional methods and results for estimating the closures effect sizes and uncertainty; Detailed results from the simulation of new condition data; Population projections – additional methods and results. ESM 2: code used to fit the model to estimate the effect of island closure on chick condition and chick survival

Best practices for assessing forage fish fisheries-seabird resource competition

Worldwide, in recent years capture fisheries targeting lower-trophic level forage fish and euphausiid crustaceans have been substantial (∼20 million metric tons [MT] annually). Landings of forage species are projected to increase in the future, and this harvest may affect marine ecosystems and predator-prey interactions by removal or redistribution of biomass central to pelagic food webs. In particular, fisheries targeting forage fish and euphausiids may be in competition with seabirds, likely the most sensitive of marine vertebrates given limitations in their foraging abilities (ambit and gape size) and high metabolic rate, for food resources. Lately, apparent competition between fisheries and seabirds has led to numerous high-profile conflicts over interpretations, as well as the approaches that could and should be used to assess the magnitude and consequences of fisheries-seabird resource competition. In this paper, we review the methods used to date to study fisheries competition with seabirds, and present “best practices” for future resource competition assessments. Documenting current fisheries competition with seabirds generally involves addressing two major issues: 1) are fisheries causing localized prey depletion that is sufficient to affect the birds? (i.e., are fisheries limiting food resources?), and 2) how are fisheries-induced changes to forage stocks affecting seabird populations given the associated functional or numerical response relationships? Previous studies have been hampered by mismatches in the scale of fisheries, fish, and seabird data, and a lack of causal understanding due to confounding by climatic and other ecosystem factors (e.g., removal of predatory fish). Best practices for fisheries-seabird competition research should include i) clear articulation of hypotheses, ii) data collection (or summation) of fisheries, fish, and seabirds on matched spatio-temporal scales, and iii) integration of observational and experimental (including numerical simulation) approaches to establish connections and causality between fisheries and seabirds. As no single technique can provide all the answers to this vexing issue, an integrated approach is most promising to obtain robust scientific results and in turn the sustainability of forage fish fisheries from an ecosystem perspective