Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Cerium dioxide nanoparticles affect in vitro fertilization in mice

International audienceDue to their catalytic and oxidative properties, cerium dioxide nanoparticles (CeO(2)NPs) are widely used as diesel additive or as promising therapy in cancerology; yet, scarce data are available on their toxicity, and none on their reproductive toxicity. We showed a significant decrease of fertilization rate, assessed on 1272 oocytes, during in vitro fertilization (IVF) carried out in culture medium containing CeO2NP at very low concentration (0.01mg.l(-1)). We also showed significant DNA damage induced in vitro by CeO2NP on mouse spermatozoa and oocytes at 0.01mg.l(-1) using Comet assay. Transmission Electron Microscopy did not detect any nanoparticles in the IVF samples at 0.01mg.l(-1), but showed, at high concentration (100mg.l(-1)), their endocytosis by the cumulus cells surrounding oocytes and their accumulation along spermatozoa plasma membranes and oocytes zona pellucida. We did not observe any nanoparticles in the cytoplasm of spermatozoa, oocytes or embryos. This study demonstrates for the first time the impact of CeO2NP on in vitro fertilization, as well as their genotoxicity on mouse spermatozoa and oocytes, at low nanoparticle concentration exposure. Decreased fertilization rates may result from: (1) CeO2NP's genotoxicity on gametes; (2) a mechanical effect, disrupting gamete interaction and (3) oxidative stress induced by CeO2NP. These results add new and important insights with regard to the reproductive toxicity of nanomaterials requesting urgent evaluation, and support several publications on metal nanoparticles reprotoxicity. Our data highlight the need for in vivo studies after low-dose exposure

Novel grading system for CADASIL severity: A multicenter cross-sectional study

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited progressive cerebral microangiopathy with considerable phenotypic variability. The purpose of this study was to describe the generalizability of a recently proposed grading system of CADASIL across multiple centers in the United States. Methods: Electronic medical records (EMR) of an initial neurological assessment of adult patients with confirmed CADASIL were reviewed across 5 tertiary referral medical centers with expertise in CADASIL. Demographic, vascular risk factors, and neuroimaging data were abstracted from EMR. Patients were categorized into groups according to the proposed CADASIL grading system: Grade 0 (asymptomatic), Grade 1 (migraine only), Grade 2 (stroke, TIA, or MCI), Grade 3 (gait assistance or dementia), and Grade 4 (bedbound or end-stage). Inter-rater reliability (IRR) of grading was tested in a subset of cases. Results: We identified 138 patients with a mean age of 50.9 ± 13.1 years, and 57.2% were female. The IRR was acceptable over 33 cases (κ=0.855, SD 0.078, p<0.001) with 81.8% being concordant. There were 15 patients (10.9%) with Grade 0, 50 (36.2%) with Grade 1, 61 (44.2%) with Grade 2, 12 (8.7%) with Grade 3, and none with Grade 4. Patients with a lower severity grade (grade 0 vs 3) tended to be younger (49.5 vs. 61.9 years) and had a lower prevalence of hypertension (50% vs. 20%, p = 0.027) and diabetes mellitus (0% vs. 25%, p = 0.018). A higher severity grade was associated with an increased number of vascular risk factors (p = 0.02) and independently associated with hypertension and diabetes (p<0.05). Comparing Grade 0 vs. 3, cortical thickness tended to be greater (2.06 vs. 1.87 mm; p = 0.06) and white matter hyperintensity volume tended to be lower (54.7 vs. 72.5 ml; p = 0.73), but the differences did not reach significance. Conclusion: The CADASIL severity grading system is a pragmatic, reliable system for characterizing CADASIL phenotype that does not require testing beyond that done in standard clinical practice. Higher severity grades tended to have a higher vascular risk factor burden. This system offers a simple method of categorizing CADASIL patients which may help to describe populations in observational and interventional studies

The Foraminiferal Response to Climate Stressors Project: Tracking the Community Response of Planktonic Foraminifera to Historical Climate Change

Planktonic Foraminifera are ubiquitous marine protozoa inhabiting the upper ocean. During life, they secrete calcareous shells, which accumulate in marine sediments, providing a geological record of past spatial and temporal changes in their community structure. As a result, they provide the opportunity to analyze both current and historical patterns of species distribution and community turnover in this plankton group on a global scale. The FORCIS project aims to unlock this potential by synthesizing a comprehensive global database of abundance and diversity observations of living planktonic Foraminifera in the upper ocean over more than 100 years starting from 1910. The database will allow for unravelling the impact of multiple global-change stressors acting on planktonic Foraminifera in historical times, using an approach that combines statistical analysis of temporal diversity changes in response to environmental changes with numerical modeling of species response based on their ecological traits

The FORCIS database : A global census of planktonic Foraminifera from ocean waters

Unidad de excelencia María de Maeztu CEX2019-000940-MPlanktonic Foraminifera are unique paleo-environmental indicators through their excellent fossil record in ocean sediments. Their distribution and diversity are affected by different environmental factors including anthropogenically forced ocean and climate change. Until now, historical changes in their distribution have not been fully assessed at the global scale. Here we present the FORCIS (Foraminifera Response to Climatic Stress) database on foraminiferal species diversity and distribution in the global ocean from 1910 until 2018 including published and unpublished data. The FORCIS database includes data collected using plankton tows, continuous plankton recorder, sediment traps and plankton pump, and contains ~22,000, ~157,000, ~9,000, ~400 subsamples, respectively (one single plankton aliquot collected within a depth range, time interval, size fraction range, at a single location) from each category. Our database provides a perspective of the distribution patterns of planktonic Foraminifera in the global ocean on large spatial (regional to basin scale, and at the vertical scale), and temporal (seasonal to interdecadal) scales over the past century

The FORCIS database: A global census of planktonic Foraminifera from ocean waters

Planktonic Foraminifera are unique paleo-environmental indicators through their excellent fossil record in ocean sediments. Their distribution and diversity are affected by different environmental factors including anthropogenically forced ocean and climate change. Until now, historical changes in their distribution have not been fully assessed at the global scale. Here we present the FORCIS (Foraminifera Response to Climatic Stress) database on foraminiferal species diversity and distribution in the global ocean from 1910 until 2018 including published and unpublished data. The FORCIS database includes data collected using plankton tows, continuous plankton recorder, sediment traps and plankton pump, and contains similar to 22,000, similar to 157,000, similar to 9,000, similar to 400 subsamples, respectively (one single plankton aliquot collected within a depth range, time interval, size fraction range, at a single location) from each category. Our database provides a perspective of the distribution patterns of planktonic Foraminifera in the global ocean on large spatial (regional to basin scale, and at the vertical scale), and temporal (seasonal to interdecadal) scales over the past century.ISSN:2052-446

Size-scaling of planktonic Foraminifera number concentrations in the water column

Data and R code for " size-scaling of planktonic Foraminifera number concentrations in the water column " by Sonia Chaabane, Thibault de Garidel-Thoron, Xavier Giraud, Julie Meilland, Geert-Jan A. Brummer, Lukas Jonkers, P. Graham Mortyn, Mattia Greco, Nicolas Casajus, Michal Kucera, Azumi Kuroyanagi, Hélène Howa, Fanny M. Monteiro, Gregory Beaugrand, Ralf Schiebel The codes serve to generate the new normalization approach in order to not estimate number concentration of planktonic Foraminifera (ind/m3) in the finer and larger size fractions than the collection size fraction range. We use data from the FORCIS database that have been collected from the global ocean at different depths over the past century. We find a general cumulative distribution over the size fractions that can be described using a Michaelis Menten function. This yields multiplication factors by which one fraction can be normalized to any other size fraction equal to or larger than 100 µm. The resulting size normalization model was tested with data from various depths and compared to an earlier size normalization solution. Scripts written by Sonia Chaabane DATA SOURCES * FORCIS database https://doi.org/10.5281/zenodo.7390792 DATA 1. data_raw_from_excel.RDS CODES 1. Prepare_data.R: Read the data and prepare it for the analyses 2. Calculate_f&amp;Shalf.R: Analyse the data and build the model 3. Model_validation.R: compare the actual vs. estimated number concentration 4. Berger_number_concentration_estimations.R: compare the actual vs. estimated number concentration using Berger 1969 correction scheme 5. Cross validation.R: Application of the FORCIS number concentration-size correction scheme on independent dataset 6. Modelfunctions.

Size-scaling of planktonic Foraminifera number concentrations in the water column

Data and R code for " size-scaling of planktonic Foraminifera number concentrations in the water column " by Sonia Chaabane, Thibault de Garidel-Thoron, Xavier Giraud, Julie Meilland, Geert-Jan A. Brummer, Lukas Jonkers, P. Graham Mortyn, Mattia Greco, Nicolas Casajus, Michal Kucera, Azumi Kuroyanagi, Hélène Howa, Fanny M. Monteiro, Gregory Beaugrand, Ralf Schiebel The codes serve to generate the new normalization approach in order to not estimate number concentration of planktonic Foraminifera (ind/m3) in the finer and larger size fractions than the collection size fraction range. We use data from the FORCIS database that have been collected from the global ocean at different depths over the past century. We find a general cumulative distribution over the size fractions that can be described using a Michaelis Menten function. This yields multiplication factors by which one fraction can be normalized to any other size fraction equal to or larger than 100 µm. The resulting size normalization model was tested with data from various depths and compared to an earlier size normalization solution. Scripts written by Sonia Chaabane DATA SOURCES * FORCIS database https://doi.org/10.5281/zenodo.7390792 DATA 1. data_raw_from_excel.RDS CODES 1. Prepare_data.R: Read the data and prepare it for the analyses 2. Calculate_f&amp;Shalf.R: Analyse the data and build the model 3. Model_validation.R: compare the actual vs. estimated number concentration 4. Berger_number_concentration_estimations.R: compare the actual vs. estimated number concentration using Berger 1969 correction scheme 5. Cross validation.R: Application of the FORCIS number concentration-size correction scheme on independent dataset 6. Modelfunctions.

The FORCIS database: A global census of planktonic Foraminifera from ocean waters

Abstract Planktonic Foraminifera are unique paleo-environmental indicators through their excellent fossil record in ocean sediments. Their distribution and diversity are affected by different environmental factors including anthropogenically forced ocean and climate change. Until now, historical changes in their distribution have not been fully assessed at the global scale. Here we present the FORCIS (Foraminifera Response to Climatic Stress) database on foraminiferal species diversity and distribution in the global ocean from 1910 until 2018 including published and unpublished data. The FORCIS database includes data collected using plankton tows, continuous plankton recorder, sediment traps and plankton pump, and contains ~22,000, ~157,000, ~9,000, ~400 subsamples, respectively (one single plankton aliquot collected within a depth range, time interval, size fraction range, at a single location) from each category. Our database provides a perspective of the distribution patterns of planktonic Foraminifera in the global ocean on large spatial (regional to basin scale, and at the vertical scale), and temporal (seasonal to interdecadal) scales over the past century

Women and health professionals’ perspectives on a conditional cash transfer programme to improve pregnancy follow-up: a qualitative analysis of the NAITRE randomised controlled study

Objectives Women of low socioeconomic status have been described as having suboptimal prenatal care, which in turn has been associated with poor pregnancy outcomes. Many types of conditional cash transfer (CCT) programmes have been developed, including programmes to improve prenatal care or smoking cessation during pregnancy, and their effects demonstrated. However, ethical critiques have included paternalism and lack of informed choice. Our objective was to determine if women and healthcare professionals (HPs) shared these concerns.Design Prospective qualitative research.Setting We included economically disadvantaged women, as defined by health insurance data, who participated in the French NAITRE randomised trial assessing a CCT programme during prenatal follow-up to improve pregnancy outcomes. The HP worked in some maternities participating in this trial.Participants 26 women, 14 who received CCT and 12 who did not, mostly unemployed (20/26), and - 7 HPs.Interventions We conducted a multicentre cross-sectional qualitative study among women and HPs who participated in the NAITRE Study to assess their views on CCT. The women were interviewed after childbirth.Results Women did not perceive CCT negatively. They did not mention feeling stigmatised. They described CCT as a significant source of aid for women with limited financial resources. HP described the CCT in less positive terms, for example, expressing concern about discussing cash transfer at their first medical consultation with women. Though they emphasised ethical concerns about the basis of the trial, they recognised the importance of evaluating CCT.Conclusions In France, a high-income country where prenatal follow-up is free, HPs were concerned that the CCT programme would change their relationship with patients and wondered if it was the best use of funding. However, women who received a cash incentive said they did not feel stigmatised and indicated that these payments helped them prepare for their baby’s birth.Trial registration number NCT0240285