51 research outputs found
Investigation at High Subsonic Speeds of a Body-contouring Method for Alleviating the Adverse Interference at the Root of a Sweptback Wing
The prognostic value of somatosensory evoked potentials in children after cardiac arrest:the SEPIA Study
Feasibility of non-invasive neuro-monitoring during extracorporeal membrane oxygenation in children
Introduction Detection of neurological complications during extracorporeal membrane oxygenation (ECMO) may be enhanced with non-invasive neuro-monitoring. We investigated the feasibility of non-invasive neuro-monitoring in a paediatric intensive care (PIC) setting. Methods In a single centre, prospective cohort study we assessed feasibility of recruitment, and neuro-monitoring via somatosensory evoked potentials (SSEP), electroencephalography (EEG) and near infrared spectroscopy (NIRS) during venoarterial (VA) ECMO in paediatric patients (0–15 years). Measures were obtained within 24h of cannulation, during an intermediate period, and finally at decannulation or echo stress testing. SSEP/EEG/NIRS measures were correlated with neuro-radiology findings, and clinical outcome assessed via the Pediatric cerebral performance category (PCPC) scale 30 days post ECMO cannulation. Results We recruited 14/20 (70%) eligible patients (median age: 9 months; IQR:4–54, 57% male) over an 18-month period, resulting in a total of 42 possible SSEP/EEG/NIRS measurements. Of these, 32/42 (76%) were completed. Missed recordings were due to lack of access/consent within 24 h of cannulation (5/42, 12%) or PIC death/discharge (5/42, 12%). In each patient, the majority of SSEP (8/14, 57%), EEG (8/14, 57%) and NIRS (11/14, 79%) test results were within normal limits. All patients with abnormal neuroradiology (4/10, 40%), and 6/7 (86%) with poor outcome (PCPC ≥4) developed indirect SSEP, EEG or NIRS measures of neurological complications prior to decannulation. No study-related adverse events or neuro-monitoring data interpreting issues were experienced. Conclusion Non-invasive neuro-monitoring (SSEP/EEG/NIRS) during ECMO is feasible and may provide early indication of neurological complications in this high-risk population
A communal catalogue reveals Earth's multiscale microbial diversity
Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth's microbial diversity.Peer reviewe
A communal catalogue reveals Earth’s multiscale microbial diversity
Our growing awareness of the microbial world’s importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth’s microbial diversity
Human malarial disease: a consequence of inflammatory cytokine release
Malaria causes an acute systemic human disease that bears many similarities, both clinically and mechanistically, to those caused by bacteria, rickettsia, and viruses. Over the past few decades, a literature has emerged that argues for most of the pathology seen in all of these infectious diseases being explained by activation of the inflammatory system, with the balance between the pro and anti-inflammatory cytokines being tipped towards the onset of systemic inflammation. Although not often expressed in energy terms, there is, when reduced to biochemical essentials, wide agreement that infection with falciparum malaria is often fatal because mitochondria are unable to generate enough ATP to maintain normal cellular function. Most, however, would contend that this largely occurs because sequestered parasitized red cells prevent sufficient oxygen getting to where it is needed. This review considers the evidence that an equally or more important way ATP deficency arises in malaria, as well as these other infectious diseases, is an inability of mitochondria, through the effects of inflammatory cytokines on their function, to utilise available oxygen. This activity of these cytokines, plus their capacity to control the pathways through which oxygen supply to mitochondria are restricted (particularly through directing sequestration and driving anaemia), combine to make falciparum malaria primarily an inflammatory cytokine-driven disease
Shared genetic risk between eating disorder- and substance-use-related phenotypes:Evidence from genome-wide association studies
First published: 16 February 202
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
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
Exploration of Shared Genetic Architecture Between Subcortical Brain Volumes and Anorexia Nervosa
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