Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Biological heterogeneity in idiopathic pulmonary arterial hypertension identified through unsupervised transcriptomic profiling of whole blood

Idiopathic pulmonary arterial hypertension (IPAH) is a rare but fatal disease diagnosed by right heart catheterisation and the exclusion of other forms of pulmonary arterial hypertension, producing a heterogeneous population with varied treatment response. Here we show unsupervised machine learning identification of three major patient subgroups that account for 92% of the cohort, each with unique whole blood transcriptomic and clinical feature signatures. These subgroups are associated with poor, moderate, and good prognosis. The poor prognosis subgroup is associated with upregulation of the ALAS2 and downregulation of several immunoglobulin genes, while the good prognosis subgroup is defined by upregulation of the bone morphogenetic protein signalling regulator NOG, and the C/C variant of HLA-DPA1/DPB1 (independently associated with survival). These findings independently validated provide evidence for the existence of 3 major subgroups (endophenotypes) within the IPAH classification, could improve risk stratification and provide molecular insights into the pathogenesis of IPAH

A quantitative assessment of the status of reef fish communities from a large-scale probability survey in southern Florida

Numerous reef fish monitoring programs worldwide produce the data necessary to describe the status and trends of coral reefs; however, quantitative description of status at ecosystem scales has been challenging. Our goal was to use southern Florida’s coral reefs as the template to complete a holistic, ecosystem-scale evaluation of reef fish community status using large-scale diver surveys that sampled across a spatial gradient of human urbanization, exploitation, and fishery protection. Key aspects of the analysis were: (i) identification of a low human impact reference area as the basis for quantifying resource condition; (ii) selection of indicator variables that helped discriminate two classes of impacts: habitat quality and fishing; (iii) application of estimation methods that facilitated distinguishing anthropogenic impacts from inherent productivity of different habitats; and (iv) use of a sustainability benchmark to gauge the resource condition of the reference area. The reference-centering analysis approach reduced reliance on qualitative judgements by an expert panel and outputted results on a scale that was informative and could be easily interpreted by a variety of audiences. Our findings identified habitat quality issues in the most urbanized region, southeast Florida, and pervasive fishing issues throughout the ecosystem, including the remote Dry Tortugas region

Integrating the US Caribbean reef fish visual census into fishery stock assessments

The United States Caribbean reef fish visual census (RVC) is a fishery-independent survey of the coral reef fish community, comprised of hundreds of species, designed to provide quantitative information for data-poor fisheries to support regional stock assessments. The Caribbean RVC, implemented in 2014 as part of the National Coral Reef Monitoring Program (NCRMP), uses a probabilistic stratified random sampling design capitalizing on the strong mean-variance relationship of population abundance dependent on hardbottom habitats and depths. Here we highlight RVC data for queen triggerfish in Puerto Rico, where survey precision improved from CVs of 20.6% in 2014 to 12.6% in 2021, which produced accurate and cost-effective estimates of key assessment metrics like size-structured relative population abundance and biomass. We estimated a relatively stable exploited-phase average population abundance for 2014–2021 at 2.3 million queen triggerfish with a biomass of 1246 metric tons. To support stock assessments using “statistical catch at age” models, we generated a 2001–2021 time series of several population metrics by a statistical conversion of spatially-restricted pre-NCRMP data to the RVC frame. To cross-check assessment modeling, we combined 2014–2021 RVC results with life history demographics in an alternative length-based risk analysis (LBRA) model to evaluate stock sustainability consequences using two lifetime growth scenarios. LBRA models indicated low overfishing risks. We concluded that only a few quality fishery independent surveys are needed to obtain understanding of stock sustainability status, and that RVC not only provides reliable data for single-species stock assessments, but also for design evaluation of marine protected areas and ecosystem-based fishery management

Length-based risk analysis of management options for the southern Florida USA multispecies coral reef fish fishery

Exploitation impacts and management options for 15 coral reef fish species central to the commercial and recreational fisheries of the southern Florida USA coral reef ecosystem were evaluated using a length-based risk analysis (LBRA) framework. Population abundance-at-length composition data were obtained from several regional federal-state sampling programs. These and updated life history demographic data were integrated into a length-based numerical cohort model to generate LBRA fishery sustainability metrics from a probabilistic perspective. Three of five groupers, eight of eight snappers, and two of two grunts were below the 40% spawning potential ratio (SPR) stock sustainability minimum; ten of these stocks are at \u3c 20% of their historical spawning biomass, some as low as 5%. Therefore, to ameliorate overfishing for the 13 stocks with sustainability risks ≥ role= presentation style= box-sizing: border-box; margin: 0px; padding: 0px; display: inline-block; line-height: normal; font-size: 16.2px; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; position: relative; \u3e≥ 98%, fisheries management requires increased minimum sizes of first capture Lc role= presentation style= box-sizing: border-box; margin: 0px; padding: 0px; display: inline-block; line-height: normal; font-size: 16.2px; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; position: relative; \u3eLc and significant reductions in fishing mortality F role= presentation style= box-sizing: border-box; margin: 0px; padding: 0px; display: inline-block; line-height: normal; font-size: 16.2px; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; position: relative; \u3eF. To achieve sustainability and reduce sustainability risks area-time protections are also needed. While lack of data often limits the evaluation of management options, this paper establishes benchmarks from which data-limited approaches can move forward. In addition, the approach can be used to cross-check other data-rich analyses. A goal of this work is to effectively balance sustainability risks with fishery production to mitigate overfishing likelihoods and to increase the probability of sustainable fisheries

A National Status Report on United States Coral Reefs Based on 2012-2018 Data From National Oceanic and Atmospheric Administration's National Coral Reef Monitoring Program

National Oceanic and Atmospheric Administration's Coral Reef Conservation Program supports the National Coral Reef Monitoring Program (NCRMP) in the United States Pacific, Atlantic, Caribbean, and Gulf of Mexico. NCRMP conducts standardized observations of biological, climatic, and socioeconomic indicators across American Samoa, Guam, the Main Hawaiian Islands, the Northwestern Hawaiian Islands, the Northern Mariana Islands, the Pacific Remote Islands, Florida, the Flower Garden Banks, Puerto Rico, and the United States Virgin Islands. NCRMP provides periodic, national-level assessments of the status of United States coral reef ecosystems and communities connected to them. In 2014, NCRMP partnered with the University of Maryland Center for Environmental Science on an unprecedented collaboration between federal and jurisdictional/state agencies, academia, and non-governmental organizations to synthesize NCRMP data into a reporting format designed to be accessible and relevant to the public and policy makers. The process involved multi-year data analyses of key benthic, fish, and climate indicators. In populated jurisdictions, socioeconomic data were integrated to assess public support for management actions, participation in pro-environmental behaviors, and awareness of threats to coral reefs. Jurisdictions were scored using a report-card scale (0-100%) by establishing references for each indicator using best-available historical data or expert opinion where historical data did not exist or were not statistically comparable. Despite overall ecosystem scores of Fair for all combined Atlantic (70%) and Pacific (74%) jurisdictions, the current trend is downward with a majority of United States coral reefs declining and vulnerable to further degradation. Remote, uninhabited reefs had an advantage with respect to reef fish population scores, i.e., Flower Garden Banks (85%) and Pacific Remote Islands (93%), when compared to populated location scores, i.e., Puerto Rico (63%) and Main Hawaiian Islands (66%). All coral reefs are highly impacted by climate change, and climate impacts were more pronounced than expected on remote reefs, i.e., the Northwestern Hawaiian Islands (58%). Presenting results in a report-card style facilitates communication to the public and policy makers, and provides a useful mechanism to garner support for management actions such as expanding protected areas; enforcing existing regulations; increasing climate change education; reducing land-based sources of pollution; and other actions to improve the trajectory of coral reef ecosystem conditions

Performance of CMS muon reconstruction from proton-proton to heavy ion collisions

International audienceThe performance of muon tracking, identification, triggering, momentum resolution, and momentum scale has been studied with the CMS detector at the LHC using data collected at $\sqrt{s_\mathrm{NN}}$ = 5.02 TeV in proton-proton (pp) and lead-lead (PbPb) collisions in 2017 and 2018, respectively, and at $\sqrt{s_\mathrm{NN}}$ = 8.16 TeV in proton-lead (pPb) collisions in 2016. Muon efficiencies, momentum resolutions, and momentum scales are compared by focusing on how the muon reconstruction performance varies from relatively small occupancy pp collisions to the larger occupancies of pPb collisions and, finally, to the highest track multiplicity PbPb collisions. We find the efficiencies of muon tracking, identification, and triggering to be above 90% throughout most of the track multiplicity range. The momentum resolution and scale are unaffected by the detector occupancy. The excellent muon reconstruction of the CMS detector enables precision studies across all available collision systems

Performance of CMS muon reconstruction from proton-proton to heavy ion collisions

International audienceThe performance of muon tracking, identification, triggering, momentum resolution, and momentum scale has been studied with the CMS detector at the LHC using data collected at $\sqrt{s_\mathrm{NN}}$ = 5.02 TeV in proton-proton (pp) and lead-lead (PbPb) collisions in 2017 and 2018, respectively, and at $\sqrt{s_\mathrm{NN}}$ = 8.16 TeV in proton-lead (pPb) collisions in 2016. Muon efficiencies, momentum resolutions, and momentum scales are compared by focusing on how the muon reconstruction performance varies from relatively small occupancy pp collisions to the larger occupancies of pPb collisions and, finally, to the highest track multiplicity PbPb collisions. We find the efficiencies of muon tracking, identification, and triggering to be above 90% throughout most of the track multiplicity range. The momentum resolution and scale are unaffected by the detector occupancy. The excellent muon reconstruction of the CMS detector enables precision studies across all available collision systems

Performance of CMS muon reconstruction from proton-proton to heavy ion collisions

International audienceThe performance of muon tracking, identification, triggering, momentum resolution, and momentum scale has been studied with the CMS detector at the LHC using data collected at $\sqrt{s_\mathrm{NN}}$ = 5.02 TeV in proton-proton (pp) and lead-lead (PbPb) collisions in 2017 and 2018, respectively, and at $\sqrt{s_\mathrm{NN}}$ = 8.16 TeV in proton-lead (pPb) collisions in 2016. Muon efficiencies, momentum resolutions, and momentum scales are compared by focusing on how the muon reconstruction performance varies from relatively small occupancy pp collisions to the larger occupancies of pPb collisions and, finally, to the highest track multiplicity PbPb collisions. We find the efficiencies of muon tracking, identification, and triggering to be above 90% throughout most of the track multiplicity range. The momentum resolution and scale are unaffected by the detector occupancy. The excellent muon reconstruction of the CMS detector enables precision studies across all available collision systems