ImportanceVEXAS (vacuoles, E1-ubiquitin-activating enzyme, X-linked, autoinflammatory, somatic) syndrome is a disease with rheumatologic and hematologic features caused by somatic variants in UBA1. Pathogenic variants are associated with a broad spectrum of clinical manifestations. Knowledge of prevalence, penetrance, and clinical characteristics of this disease have been limited by ascertainment biases based on known phenotypes.ObjectiveTo determine the prevalence of pathogenic variants in UBA1 and associated clinical manifestations in an unselected population using a genomic ascertainment approach.Design, Setting, and ParticipantsThis retrospective observational study evaluated UBA1 variants in exome data from 163 096 participants within the Geisinger MyCode Community Health Initiative. Clinical phenotypes were determined from Geisinger electronic health record data from January 1, 1996, to January 1, 2022.ExposuresExome sequencing was performed.Main Outcomes and MeasuresOutcome measures included prevalence of somatic UBA1 variation; presence of rheumatologic, hematologic, pulmonary, dermatologic, and other findings in individuals with somatic UBA1 variation on review of the electronic health record; review of laboratory data; bone marrow biopsy pathology analysis; and in vitro enzymatic assays.ResultsIn 163 096 participants (mean age, 52.8 years; 94% White; 61% women), 11 individuals harbored likely somatic variants at known pathogenic UBA1 positions, with 11 of 11 (100%) having clinical manifestations consistent with VEXAS syndrome (9 male, 2 female). A total of 5 of 11 individuals (45%) did not meet criteria for rheumatologic and/or hematologic diagnoses previously associated with VEXAS syndrome; however, all individuals had anemia (hemoglobin: mean, 7.8 g/dL; median, 7.5 g/dL), which was mostly macrocytic (10/11 [91%]) with concomitant thrombocytopenia (10/11 [91%]). Among the 11 patients identified, there was a pathogenic variant in 1 male participant prior to onset of VEXAS-related signs or symptoms and 2 female participants had disease with heterozygous variants. A previously unreported UBA1 variant (c.1861A>T; p.Ser621Cys) was found in a symptomatic patient, with in vitro data supporting a catalytic defect and pathogenicity. Together, disease-causing UBA1 variants were found in 1 in 13 591 unrelated individuals (95% CI, 1:7775-1:23 758), 1 in 4269 men older than 50 years (95% CI, 1:2319-1:7859), and 1 in 26 238 women older than 50 years (95% CI, 1:7196-1:147 669).Conclusions and RelevanceThis study provides an estimate of the prevalence and a description of the clinical manifestations of UBA1 variants associated with VEXAS syndrome within a single regional health system in the US. Additional studies are needed in unselected and genetically diverse populations to better define general population prevalence and phenotypic spectrum.

Interbreeding between artificially-selected and wild organisms can have negative fitness consequences for the latter. In the Northwest Atlantic, farmed Atlantic salmon recurrently escape into the wild and enter rivers where small, declining populations of wild salmon breed. Most farmed salmon in the region derive from an ancestral source population that occupies a nonacidified river (pH 6.0–6.5). Yet many wild populations with which escaped farmed salmon might interbreed inhabit acidified rivers (pH 4.6–5.2). Using common garden experimentation, and examining two early-life history stages across two generations of interbreeding, we showed that wild salmon populations inhabiting acidified rivers had higher survival at acidified pH than farmed salmon or F1 farmed-wild hybrids. In contrast, however, there was limited evidence for reduced performance in backcrosses, and F2 farmed-wild hybrids performed better or equally well to wild salmon. Wild salmon also survived or grew better at nonacidified than acidified pH, and wild and farmed salmon survived equally well at nonacidified pH. Thus, for acid tolerance and the stages examined, we found some evidence both for and against the theory that repeated farmed-wild interbreeding may reduce adaptive genetic variation in the wild and thereby negatively affect the persistence of depleted wild populations.

This document is a U.S. government work and is not subject to copyright in the United States. IndiSeas ("Indicators for the Seas") is a collaborative international working group that was established in 2005 to evaluate the status of exploited marine ecosystems using a suite of indicators in a comparative framework. An initial shortlist of seven ecological indicators was selected to quantify the effects of fishing on the broader ecosystem using several criteria (i.e., ecological meaning, sensitivity to fishing, data availability, management objectives and public awareness). The suite comprised: (i) the inverse coefficient of variation of total biomass of surveyed species, (ii) mean fish length in the surveyed community, (iii) mean maximum life span of surveyed fish species, (iv) proportion of predatory fish in the surveyed community, (v) proportion of under and moderately exploited stocks, (vi) total biomass of surveyed species, and (vii) mean trophic level of the landed catch. In line with the Nagoya Strategic Plan of the Convention on Biological Diversity (2011-2020), we extended this suite to emphasize the broader biodiversity and conservation risks in exploited marine ecosystems. We selected a subset of indicators from a list of empirically based candidate biodiversity indicators initially established based on ecological significance to complement the original IndiSeas indicators. The additional selected indicators were: (viii) mean intrinsic vulnerability index of the fish landed catch, (ix) proportion of non-declining exploited species in the surveyed community, (x) catch-based marine trophic index, and (xi) mean trophic level of the surveyed community. Despite the lack of data in some ecosystems, we also selected (xii) mean trophic level of the modelled community, and (xiii) proportion of discards in the fishery as extra indicators. These additional indicators were examined, along with the initial set of IndiSeas ecological indicators, to evaluate whether adding new biodiversity indicators provided useful additional information to refine our understanding of the status evaluation of 29 exploited marine ecosystems. We used state and trend analyses, and we performed correlation, redundancy and multivariate tests. Existing developments in ecosystembased fisheries management have largely focused on exploited species. Our study, using mostly fisheries independent survey-based indicators, highlights that biodiversity and conservation-based indicators are complementary to ecological indicators of fishing pressure. Thus, they should be used to provide additional information to evaluate the overall impact of fishing on exploited marine ecosystems.

Climate change impacts on fisheries will undoubtedly have socioeconomic impacts on coastal communities and the seafood market. However, it is a challenge to integrate climate change information in a form that can be used efficiently by adaptation planners, policy makers, and fishery managers. In this study, we frame a climate change impact assessment using a geographical perspective based on the management units of the dominant fishery, in this case, American lobster in Nova Scotia, Canada. The information considered here includes economic dependence on the fishery, population size, diversity of the fishery revenue, status of harbor infrastructure, total replacement cost of each harbor, increased relative sea level and flooding, and the vulnerability of offshore lobster to ocean warming and changes in zooplankton composition and anticipatory changes in fishery productivity across management borders. Using two ocean models to provide multi-decadal scale projections of bottom temperature, changes in offshore lobster distribution are projected to have a neutral, or positive impact on the region as a whole. However, when lobster vulnerability is combined with climate change related vulnerabilities of coastal fishing communities, it is evident that adaptation planning is needed for long-term sustainability. This impact assessment provides both a framework and information for further in-depth analyses by climate change adaptation planners and fishery managers.