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The Southern Resident killer whale population (Orcinus orca) was listed as endangered in 2005 and shows little sign of recovery. These fish eating whales feed primarily on endangered Chinook salmon. Population growth is constrained by low offspring production for the number of reproductive females in the population. Lack of prey, increased toxins and vessel disturbance have been listed as potential causes of the whale's decline, but partitioning these pressures has been difficult. We validated and applied temporal measures of progesterone and testosterone metabolites to assess occurrence, stage and health of pregnancy from genotyped killer whale feces collected using detection dogs. Thyroid and glucocorticoid hormone metabolites were measured from these same samples to assess physiological stress. These methods enabled us to assess pregnancy occurrence and failure as well as how pregnancy success was temporally impacted by nutritional and other stressors, between 2008 and 2014. Up to 69% of all detectable pregnancies were unsuccessful; of these, up to 33% failed relatively late in gestation or immediately post-partum, when the cost is especially high. Low availability of Chinook salmon appears to be an important stressor among these fish-eating whales as well as a significant cause of late pregnancy failure, including unobserved perinatal loss. However, release of lipophilic toxicants during fat metabolism in the nutritionally deprived animals may also provide a contributor to these cumulative effects. Results point to the importance of promoting Chinook salmon recovery to enhance population growth of Southern Resident killer whales. The physiological measures used in this study can also be used to monitor the success of actions aimed at promoting adaptive management of this important apex predator to the Pacific Northwest.

Models that simulate the evolution of polar firn are important for several applications in glaciology, including converting ice-sheet elevation change measurements to mass change and interpreting climate records in ice cores. We have developed the Community Firn Model (CFM), an open-source, modular model framework designed to simulate numerous physical processes in firn. The modules include firn densification, heat transport, meltwater percolation and refreezing, water isotope diffusion, and firn-air diffusion. The CFM is designed so that new modules can be added with ease. In this paper, we first describe the CFM and its modules. We then demonstrate the CFM's usefulness in two model applications that utilize two of its novel aspects. The CFM currently has the ability to run any of 13 previously published firn densification models, and in the first application we compare those models' results when they are forced with regional climate model outputs for Summit, Greenland. The results show that the models do not agree well (spread greater than 10 %) when predicting depth-integrated porosity, firn age, or the trend in surface elevation change. In the second application, we show that the CFM's coupled firn-air and firn densification models can simulate noble gas records from an ice core better than a firn-air model alone.

Estimating diet composition is important for understanding interactions between predators and prey and thus illuminating ecosystem function. The diet of many species, however, is difficult to observe directly. Genetic analysis of fecal material collected in the field is therefore a useful tool for gaining insight into wild animal diets. In this study, we used high-throughput DNA sequencing to quantitatively estimate the diet composition of an endangered population of wild killer whales (Orcinus orca) in their summer range in the Salish Sea. We combined 175 fecal samples collected between May and September from five years between 2006 and 2011 into 13 sample groups. Two known DNA composition control groups were also created. Each group was sequenced at a ~330bp segment of the 16s gene in the mitochondrial genome using an Illumina MiSeq sequencing system. After several quality controls steps, 4,987,107 individual sequences were aligned to a custom sequence database containing 19 potential fish prey species and the most likely species of each fecal-derived sequence was determined. Based on these alignments, salmonids made up >98.6% of the total sequences and thus of the inferred diet. Of the six salmonid species, Chinook salmon made up 79.5% of the sequences, followed by coho salmon (15%). Over all years, a clear pattern emerged with Chinook salmon dominating the estimated diet early in the summer, and coho salmon contributing an average of >40% of the diet in late summer. Sockeye salmon appeared to be occasionally important, at >18% in some sample groups. Non-salmonids were rarely observed. Our results are consistent with earlier results based on surface prey remains, and confirm the importance of Chinook salmon in this population's summer diet.

Evolution of cold dry snow and firn plays important roles in glaciology; however, the physical formulation of a densification law is still an active research topic. We forced eight firn-densification models and one seasonal-snow model in six different experiments by imposing step changes in temperature and accumulation-rate boundary conditions; all of the boundary conditions were chosen to simulate firn densification in cold, dry environments. While the intended application of the participating models varies, they are describing the same physical system and should in principle yield the same solutions. The firn models all produce plausible depth-density profiles, but the model outputs in both steady state and transient modes differ for quantities that are of interest in ice core and altimetry research. These differences demonstrate that firn-densification models are incorrectly or incompletely representing physical processes. We quantitatively characterize the differences among the results from the various models. For example, we find depth-integrated porosity is unlikely to be inferred with confidence from a firn model to better than 2 m in steady state at a specific site with known accumulation rate and temperature. Firn Model Intercomparison Experiment can provide a benchmark of results for future models, provide a basis to quantify model uncertainties and guide future directions of firn-densification modeling.

Objective: Exposure to endotoxin, a component of gram-negative bacterial cell walls, is widespread in many industrial settings and in the ambient environment. Heavy-exposure environments include livestock farms, cotton textile facilities, and saw mills. Concentrations are highly variable in nonoccupational indoor and outdoor environments. Endotoxin is a potent inflammagen with recognized health effects, including fever, shaking chills, septic shock, toxic pneumonias, and respiratory symptoms. Somewhat paradoxically, given the putative role of inflammation in carcinogenesis, various lines of evidence suggest that endotoxin may prevent cancer initiation or limit tumor growth. The hypothesis that components of bacteria may retard cancer progression dates back to William B. Coley's therapeutic experiments (\"bacterial vaccine\") in the 1890s. Data Sources: In this article, we review epidemiologic, clinical trial, and experimental studies pertinent to the hypothesis that endotoxin prevents cancer. Since the 1970s, epidemiologic studies of cotton textile and other endotoxin-exposed occupational groups have consistently demonstrated reduced lung cancer risks. Experimental animal toxicology research and some limited therapeutic trials in cancer patients offer additional support for an anticarcinogenic potential. The underlying biological mechanisms of anticarcinogenesis are not entirely understood but are thought to involve the recruitment and activation of immune cells and proinflammatory mediators (e.g., tumor necrosis factor a and interleukin-1 and -6). Conclusions: In view of the current state of knowledge, it would be premature to recommend endotoxin as a cancer-chemopreventive agent. Nonetheless, further epidemiologic and experimental investigations that can clarify further dose-effect and exposure-timing relations could have substantial public health and basic biomedical benefits.

In the western United States, the long-term recovery of many Pacific salmon populations is inextricably linked to freshwater habitat quality. Industrial activities from the past century have left a legacy of pollutants that persist, particularly near working waterfronts. The adverse impacts of these contaminants on salmon health have been studied for decades, but the population-scale consequences of chemical exposure for salmonids are still poorly understood. We estimated acute and delayed mortality rates for seaward migrating juvenile Chinook salmon that feed and grow in a Superfund-designated area in the Lower Willamette River in Portland, Oregon. We combined previous, field-collected exposure data for juvenile Chinook salmon together with reduced growth and disease resistance data from earlier field and laboratory studies. Estimates of mortality were then incorporated into a life cycle model to explore chemical habitat-related fish loss. We found that 54% improved juvenile survival-potentially as a result of future remediation activities-could increase adult Chinook salmon population abundance by more than 20%. This study provides a framework for evaluating pollution remediation as a positive driver for species recovery.

Polygenic risk scores (PRS) have shown successes in clinics, but most PRS methods focus only on participants with distinct primary continental ancestry without accommodating recently-admixed individuals with mosaic continental ancestry backgrounds for different segments of their genomes. Here, we develop GAUDI, a novel penalized-regression-based method specifically designed for admixed individuals. GAUDI explicitly models ancestry-differential effects while borrowing information across segments with shared ancestry in admixed genomes. We demonstrate marked advantages of GAUDI over other methods through comprehensive simulation and real data analyses for traits with associated variants exhibiting ancestral-differential effects. Leveraging data from the Women’s Health Initiative study, we show that GAUDI improves PRS prediction of white blood cell count and C-reactive protein in African Americans by > 64% compared to alternative methods, and even outperforms PRS-CSx with large European GWAS for some scenarios. We believe GAUDI will be a valuable tool to mitigate disparities in PRS performance in admixed individuals. Most polygenic risk score (PRS) methods focus only on individuals with distinct primary continental ancestry, without accommodating recently-admixed individuals. Here, the authors develop a novel penalized regression-based PRS method specifically designed for admixed individuals.

Background: Perfluorooctanoate (PFOA) is a synthetic chemical widely detectable in blood of nonoccupationally exposed persons. Its human health effects are not well-characterized. Methods: We conducted a mortality study in a cohort of 3993 employees of an ammonium perfluorooctanoate (APFO) manufacturing facility. APFO rapidly dissociates to PFOA in blood. We estimated standardized mortality ratios (SMRs) compared with the general population, and fit time-dependent Cox regression models to estimate the risks using an internal-cohort referent population. A priori diseases of interest were liver, pancreatic, prostate, and testicular cancer; cirrhosis of the liver; and cerebrovascular disease. Results: APFO exposure was not associated with liver, pancreatic or testicular cancer or with cirrhosis of the liver. SMRs (95% CI) for prostate cancer with no, probable and definite exposure strata were 0.4 (0.1–0.9), 0.9 (0.4–1.8), and 2.1 (0.4–6.1), respectively, and for cerebrovascular disease 0.5 (0.3–0.8), 0.7 (0.4–1.1), and 1.6 (0.5–3.7), respectively. The diabetes SMR for probable exposure was 2.0 (1.0–3.2). Compared with an internal referent population of nonexposed workers, moderate or high exposures to ammonium perfluorooctanoate were positively associated with prostate cancer (HR = 3.0 [0.9–9.7] and 6.6 [1.1–37.7], respectively) and with cerebrovascular disease (1.8 [0.9–3.1] and 4.6 [1.3–17.0], respectively). Diabetes was associated with moderate exposure 3.7 (1.4–10.1); no deaths from diabetes occurred in workers with high exposure. Conclusion: We did not observe ammonium perfluorooctanoate exposure to be associated with liver, pancreatic, and testicular cancer or cirrhosis of the liver. Exposure was associated (albeit inconsistently) with prostate cancer, cerebrovascular disease, and diabetes.

Expression quantitative trait methylation (eQTM) analysis identifies DNA CpG sites at which methylation is associated with gene expression. The present study describes an eQTM resource of CpG-transcript pairs derived from whole blood DNA methylation and RNA sequencing gene expression data in 2115 Framingham Heart Study participants. We identified 70,047 significant cis CpG-transcript pairs at p  < 1E−7 where the top most significant eGenes (i.e., gene transcripts associated with a CpG) were enriched in biological pathways related to cell signaling, and for 1208 clinical traits (enrichment false discovery rate [FDR] ≤ 0.05). We also identified 246,667 significant trans CpG-transcript pairs at p  < 1E−14 where the top most significant eGenes were enriched in biological pathways related to activation of the immune response, and for 1191 clinical traits (enrichment FDR ≤ 0.05). Independent and external replication of the top 1000 significant cis and trans CpG-transcript pairs was completed in the Women’s Health Initiative and Jackson Heart Study cohorts. Using significant cis CpG-transcript pairs, we identified significant mediation of the association between CpG sites and cardiometabolic traits through gene expression and identified shared genetic regulation between CpGs and transcripts associated with cardiometabolic traits. In conclusion, we developed a robust and powerful resource of whole blood eQTM CpG-transcript pairs that can help inform future functional studies that seek to understand the molecular basis of disease.

Mainstream concepts of circularity often overlook local socio-material practices in favour of market-driven, techno-based solutions. This paper argues for a community-based approach to foster a grounded socio-economic transition. It explores the potential of circularity initiatives becoming urban living labs (ULLs) by integrating institutional understandings of circularity with local vocabularies and practices. It aims to disentangle the tensions that such integration might have to overcome and define the (latent) potentials embedded in local practices. The study focuses on Fixoteket Hammarkullen, a collaborative initiative in a late modernist suburb of Gothenburg in Sweden. Using a qualitative methodology combining a historical narrative approach with actor–network theory sensitivity, it traces Fixoteket’s evolution from an experimental reuse centre to a municipally managed space. Drawing on interviews, document analysis, site observations and a workshop, the contextual conditions that shaped Fixoteket’s development are examined. These shifting relationships, roles and power dynamics have (dis)connected Fixoteket from the local community. Re-anchoring circularity in local vocabularies and networks could (re)activate its potential as a ULL. These understandings about the processes, collaborations and relationships can inform community-rooted social infrastructures and foster more inclusive, context-sensitive urban sustainability transitions.