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

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure &lt;= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

A História da Alimentação: balizas historiográficas

Os M. pretenderam traçar um quadro da História da Alimentação, não como um novo ramo epistemológico da disciplina, mas como um campo em desenvolvimento de práticas e atividades especializadas, incluindo pesquisa, formação, publicações, associações, encontros acadêmicos, etc. Um breve relato das condições em que tal campo se assentou faz-se preceder de um panorama dos estudos de alimentação e temas correia tos, em geral, segundo cinco abardagens Ia biológica, a econômica, a social, a cultural e a filosófica!, assim como da identificação das contribuições mais relevantes da Antropologia, Arqueologia, Sociologia e Geografia. A fim de comentar a multiforme e volumosa bibliografia histórica, foi ela organizada segundo critérios morfológicos. A seguir, alguns tópicos importantes mereceram tratamento à parte: a fome, o alimento e o domínio religioso, as descobertas européias e a difusão mundial de alimentos, gosto e gastronomia. O artigo se encerra com um rápido balanço crítico da historiografia brasileira sobre o tema

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Growth and development of Serrana kids from Montesinho Natural Park (NE of Portugal)

This study was to evaluate meat potential of Serrana goats, raised under harsh conditions of the mountains of NE Portugal. Sixteen males of the local Serrana goat breed were taken from different herds in Montesinho Natural Park in NE Portugal. Allometric coefficients of different body tissues and carcass were calculated. Shoulder and leg were earlier developing than loin and breast. Muscle was isometric (b = 1.07; P 2 0.05) and bone was the most precocious tissue (b = 0.763; PI 0.01). Different fat deposits were later developing, with allometric coefficients (PI 0.01) higher than 1 .O, and the order of fat deposition was: subcutaneous fat, intermuscular fat, mesenteric fat, kidney knob and channel fat (KKCF - the perinephric and retroperitoneal fat) and omental fat. Subcutaneous and intermuscular fat deposits, which were later developing in relation to BW, were isometric in relation to total fat of carcass. All fat deposits in the different carcass joints (with the exception of fat deposits in leg and shoulder and the subcutaneous fat in loin and neck) had allometric coefficients (PsO.01) higher than 1.0. Sites of the later subcutaneous fat deposition were breast and chump, whereas later intermuscular fat depositions were in loin and breast. The results suggest that intermuscular fat is later developing than subcutaneous fat in relation to half carcass weight. The higher proportion of muscle and lower proportion of subcutaneous and intermuscular fat deposits indicate the potentialities of the Serrana breed as a source of lean meat, according to the consumption preferences of the Mediterranean area of the European Union. El principal objetivo del estudio ha sido evaluar la composición de las canales de cabritos de raza Serrana y determinar los coeficientes alométricos de los diferentes tejidos del cuerpo y de la canal. Para este trabajo se utilizaron 16 cabritos de la raza localmente designada como Serrana, elegidos de diferentes rebaños del Parque Natural de Montesinho ubicado en el NE de Portugal. La espalda y pierna tuvieron un desarrollo más precoz que el lomo y el costillar. El coeficiente alométrico del peso de la cabeza (b = 0,69; P ≤ 0,01) confirmó su precoz desarrollo respecto al peso vivo vacío. El muscúlo fué isométrico (b = 1,07, no significativamente diferente de 1,0, para P ≥ 0,05) y el hueso fué claramente el tejido más precoz respecto al peso vivo vacío ( b = 0,76; significativamente diferente de 1,0, para P ≤ 0,01). En lo que concierne a los diferentes depósitos adiposos tuvieron un desarrollo tardío, con coeficientes alométricos significativamente (P ≤ 0,01) mayores de 1,0 y el orden de deposición de grasa respecto al peso vivo vació fué: subcutánea, intermuscular, mesentérica, pélvico-renal y omental. Sin embargo los depósitos de grasa subcutánea e intermuscular, que tuvieron un desarrollo tardío respecto al peso vivo vacío, fueron isométricos respecto a la grasa total de la canal. Todos los depósitos de grasa de las diferentes piezas de la canal tuvieron coeficientes alométricos significativamente mayores de 1,0 (P ≤ 0,01). Las piezas donde la deposición de grasa subcutánea fué más tardia fueron el badal y la cadera, mientras que las deposiciones de grasa intermuscular más tardías tuvieron lugar en el lomo y pecho. Los resultados indicaron que la grasa intermuscular tuvo un desarrollo más tardio que la grasa subcutánea. Le principal objectif de cette étude était d'évaluer la composition des carcasses des chevreaux de race Serrana et de déterminer les coefficients d'allométrie au niveau des différents tissus du corps et de la carcasse. Pour réaliser ce travail, 16 chevreaux de race locale appelée Serrana on été utilisés, ayant été choisis parmi différents troupeaux du Parc Naturel de Montesinho, situé au NE du Portugal. L'épaule et le gigot ont eu un développement plus précoce que le dos et que le carré couvert. Le coefficient d'allométrie du poids de la tête (b = 0,69; P ≤ 0,01) a confirmé son développement précoce par rapport au poids vif vide. Le muscle a été isométrique (b = 1,07; significativement pas différent de 1,0, pour P ≤ 0,05) et l'os s'est avéré le tissu le plus précoce par rapport au poids vif vide (b = 0,76; significativement différent de 1,0, pour P ≤ 0,01). En ce qui concerne les différents dépôts de gras, il faut dire qu'ils ont eu un développement tardif, en ayant des coefficients allométriques significativement plus élevés que 1,0 (P ≤ 0,01), et l'ordre du dépôt de gras par rapport au poids vif vide a été le suivant: sous-cutane, intermusculaire, mésentérique, pelvico-rénal et omental. Néanmoins, les dépôts de gras sous-cutane et intermusculaire, qui avaient eu un développement tardif par rapport au poids vif vide, ont été isométriques par rapport au total du gras de la carcasse. Tous les dépôts de gras des différents pièces de la carcasse ont eu des coefficients allométriques significativement plus élévés que 1,0, (P ≤ 0,01). Les pièces où le dépôt du gras sous-cutane a été plus tardif ont été le carré découvert et la selle, tandis que les dépôts du gras intermusculaire plus tardif ont eu lieu au niveau du dos et de la poitrine. Les résultats ont indiqué que le gras intermusculaire a eu un développement plus tardif que le gras sous-cutané

Variation between geographical populations of Lutzomyia (Nyssomyia) whitmani (Antunes & Coutinho, 1939) sensu lato (diptera:psychodidae:phlebotominae) in Brazil

Phylogenetic analysis of morphometric and biological characters indicated that there are two distinct forms of Lutzomyia whitmani in Brazil: one is present both north and south of the River Amazonas in the State of Para while the other occurs in northeast Brazil, in the State of Ceara, and further south, including the type locality in State of Bahia. The Amazonian form is reportedly neither strongly anthropophilic nor synanthropic, and it is the vector of Leishmania shawi; whereas the southern form is often collected peridomestically, while biting man, and has been found infected with Le.(V.) braziliensis. The ratio of the length of the genital filaments to that the genital pump was found to be consistently smaller in males of the Amazonian populations. A middle repetitive DNA element was isolated by differentially screening a genomic library made using Amazonian material, and the sequence was diagnostic for this form of Lu. whitmani (being absent or occurring in low copy number in the southern form). The total evidence suggests there are at least two, geographically-isolated forms of Lu. whitmani, which may represent different cryptic species