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International wild Atlantic salmon management priorities have moved from exploitation to conservation since the 1990s, recognizing the need to protect diversity and abundance at individual river levels amid widespread declines. Here we review international salmon-stock assessments and describe a simple, transferable catch-advice framework, established for management of fisheries that conforms to international obligations. The risk assessment approach, applied at the river scale, jointly incorporates uncertainty in estimated and forecasted returning salmon numbers with the level of uncertainty around spawning requirements (Conservation Limits). Outputs include quantification of risk of stocks not attaining conservation limits (CL) and surpluses above CL on stocks able to support sustainable exploitation via total allowable catches (TAC), with monitoring by rod catch or fish counter. Since management implementation and cessation of at-sea mixed-stock fisheries, there has been a deterioration in the performance of many individual stocks, without any sustained increase in fisheries open to harvest. Given declines in mid-latitude Atlantic salmon populations over 30 years, the novel framework presented provides an approach to protect stocks failing to meet spawning thresholds while supporting sustainable exploitation of those achieving them. On-going management policy of adopting scientific advice and allowing exploitation only on stocks exceeding CLs is central to the objective of protecting salmon stocks.

Overweight and obesity are rapidly becoming the “new normal” in developed countries, which promotes a widespread negative impact on human health. Amongst recently developed obesity medications are the serotonin 2C receptor (5-HT2CR) agonist lorcaserin and glucagon-like peptide-1 receptor (GLP-1R) agonists, but the brain circuits employed by these medications to produce their therapeutic effects remain to be fully defined. 5-HT2CRs and GLP-1Rs are widely distributed in the brain, including in the key homeostatic region the nucleus of the solitary tract (NTS) where GLP-1 is produced by preproglucagon (PPGNTS) neurons. PPGNTS cells were profiled using histochemistry and single nucleus RNA sequencing (Nuc-Seq) of mouse brainstem. Transcriptomic analyses revealed 5-HT2CR expression was widespread in PPGNTS clusters. Demonstrating the functional significance of this co-expression, lorcaserin required PPGNTS to reduce food intake. Analysis of second order neurons revealed that local GLP1-R neurons within the NTS are necessary for 5-HT2CRNTS food intake suppression. In contrast, GLP-1RNTS were not required for GLP-1R agonist liraglutide and exendin-4’s short term feeding reduction, suggesting scope for lorcaserin and GLP1-R agonist combination therapy. In support of this, lorcaserin+liraglutide and lorcaserin+exendin-4 produced greater reductions in food intake when administered in combination as compared to monotherapies. These data provide insight into the therapeutic mechanisms of lorcaserin and identify a combination strategy to improve the therapeutic profile of lorcaserin and GLP1-R agonists.

United States Air Force Test Pilot School students ( N = 6) participated in a study involving an agent-directed human pilot (“Blue agent”) in dogfighting scenarios against an adversary (“Red agent”). The adversary used three levels of difficulty as follows: low, medium, and high. An agent appropriateness scale was developed to gauge how appropriate the Blue agent’s behaviors were during each dogfight. Results demonstrated that agent appropriateness varied by Red agent difficulty. These results suggest that agent appropriateness is an essential element in human-autonomy teaming research. Practitioners should seek to develop agent appropriateness measures suitable for the particular context and technology in question.

Chemicals in consumer products are a major contributor to human chemical coexposures. Consumers purchase and use a wide variety of products containing potentially thousands of chemicals. There is a need to identify potential real-world chemical coexposures to prioritizeWe aimed to develop and implement a data-driven procedure for identifying prevalent chemical combinations to which humans are exposed through purchase and use of consumer products.We applied frequent itemset mining to an integrated data set linking consumer product chemical ingredient data with product purchasing data from 60,000 households to identify chemical combinations resulting from co-use of consumer products.We identified co-occurrence patterns of chemicals over all households as well as those specific to demographic groups based on race/ethnicity, income, education, and family composition. We also identified chemicals with the highest potential for aggregate exposure by identifying chemicals occurring in multiple products used by the same household. Last, a case study of chemicals active in estrogen and androgen receptorIntegration and comprehensive analysis of household purchasing data and product-chemical information provided a means to assess human near-field exposure and inform selection of chemical combinations for high-throughput screening in

This case study presents preliminary findings of an extensive offshore reef survey, funded by the European Maritime and Fisheries Fund Marine Biodiversity Scheme, along Ireland’s Northwest continental margin. The 2017 study focuses on one specific canyon system, and its biological habitats in relation to geomorphic features. The survey is primarily concerned with identifying geogenic and biogenic reefs and associated biological communities. High-definition video footage was acquired using a remotely operated underwater vehicle. We present five separate transects from within a previously undescribed canyon system with little anthropogenic interference. The video data identifies biologically sensitive, reef-forming, cold-water coral species at numerous locations. Typical fauna include anemones, sponges, crustaceans, corals, echinoderms, elasmobranchs, flatfish, and deep-sea fish such as the orange roughy. The findings will contribute to the provision of conservation objectives as established by the Government of Ireland’s National Parks and Wildlife Service.

Objective High grade serous carcinoma (HGSC) is the most common and most aggressive, subtype of epithelial ovarian cancer. It presents as advanced stage disease with poor prognosis. Recent pathological evidence strongly suggests HGSC arises from the fallopian tube via the precursor lesion; serous tubal intraepithelial carcinoma (STIC). However, further definition of the molecular evolution of HGSC has major implications for both clinical management and research. This study aims to more clearly define the molecular pathogenesis of HGSC. Methods Six cases of HGSC were identified at the Northern Ireland Gynaecological Cancer Centre (NIGCC) that each contained ovarian HGSC (HGSC), omental HGSC (OMT), STIC, normal fallopian tube epithelium (FTE) and normal ovarian surface epithelium (OSE). The relevant formalin-fixed paraffin embedded (FFPE) tissue samples were retrieved from the pathology archive via the Northern Ireland Biobank following attaining ethical approval (NIB11:005). Full microarray-based gene expression profiling was performed on the cohort. The resulting data was analysed bioinformatically and the results were validated in a HGSC-specific in-vitro model. Results The carcinogenesis of HGSC was investigated and showed the molecular profile of HGSC to be more closely related to normal FTE than OSE. STIC lesions also clustered closely with HGSC, indicating a common molecular origin. Conclusion This study provides strong evidence suggesting that extrauterine HGSC arises from the fimbria of the distal fallopian tube. Furthermore, several potential pathways were identified which could be targeted by novel therapies for HGSC. These findings have significant translational relevance for both primary prevention and clinical management of the disease.

This paper discusses non-ideal theory as guidance for making bad situations better by morally permissible means. It distinguishes constructive theorizing, which suggests ways of improving specific kinds of bad situation, from cautionary theory, which concerns moral risks of actions under bad conditions. Reflective moral judgment yields cautionary precepts, identifying presumptively unjustifiable modes of action. The paper illustrates the application of precepts cautioning about coercion and the exposure of others to significant risks, by considering the 1955–1956 bus boycott in Montgomery, Alabama, and the ‘Children’s Crusade’ of the 1963 Birmingham desegregation campaign. All such campaigns involve coercive elements, but the paper argues that coercion was not a morally significant factor in either case. Endangerment is another matter: given the violent, sometimes lethal, reactions to civil rights actions under Jim Crow, those two campaigns’ endangerment of innocent persons must be taken very seri...

Conservation of a molecular target across species can be used as a line-of-evidence to predict the likelihood of chemical susceptibility. The web-based Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS; https://seqapass.epa.gov/seqapass/) application was developed to simplify, streamline, and quantitatively assess protein sequence/structural similarity across taxonomic groups as a means to predict relative intrinsic susceptibility. The intent of the tool is to allow for evaluation of any potential protein target while remaining amenable to variable degrees of protein characterization, in the context of available information about the chemical/protein interaction and the molecular target itself. To accommodate this flexibility in the analysis, 3 levels of evaluation were developed. The first level of the SeqAPASS analysis compares primary amino acid sequences to a query sequence, calculating a metric for sequence similarity (including detection of orthologs); the second level evaluates sequence similarity within selected functional domains (eg, ligand-binding domain); and the third level of analysis compares individual amino acid residue positions of importance for protein conformation and/or interaction with the chemical upon binding. Each level of the SeqAPASS analysis provides additional evidence to apply toward rapid, screening-level assessments of probable cross species susceptibility. Such analyses can support prioritization of chemicals for further evaluation, selection of appropriate species for testing, extrapolation of empirical toxicity data, and/or assessment of the cross-species relevance of adverse outcome pathways. Three case studies are described herein to demonstrate application of the SeqAPASS tool: the first 2 focused on predictions of pollinator susceptibility to molt-accelerating compounds and neonicotinoid insecticides, and the third on evaluation of cross-species susceptibility to strobilurin fungicides. These analyses illustrate challenges in species extrapolation and demonstrate the broad utility of SeqAPASS for risk-based decision making and research.