72 research outputs found
Projecting long-term past and future climate change within the context of post-closure performance assessments for disposal of radioactive waste
The ‘long tail’ of anthropogenic CO<sub>2</sub> decline in the atmosphere and its consequences for post-closure performance assessments for disposal of radioactive wastes
AbstractThe extended timescales involved in the decay of radioactive wastes to safe levels mean that geological disposal facilities must continue to function effectively long into the future. It is therefore essential to consider long-term climate evolution in post-closure performance assessments in order to evaluate a geological disposal system's response and robustness to a variety of potential environmental changes, driven by both natural and anthropogenic forcings. In this paper, we illustrate the multiple decay components that characterize the primary driver of climate change – atmospheric CO2 – in response to fossil fuel carbon emissions. We perform a multi-exponential analysis on a series of atmospheric CO2 decay curves predicted by an Earth system model and create an empirical response function that encapsulates the long-term (>1 kyr) removal of excess CO2 from the atmosphere. We present this response function as a simple tool for rapidly projecting the future atmospheric CO2 concentration resulting from any plausible cumulative release of CO2. We discuss the implications of the long 'tail' to this atmospheric CO2 decay curve, both in terms of future climate evolution as well as potential impacts on radioactive waste repositories.</jats:p
Speleothem record of mild and wet mid-Pleistocene climate in northeast Greenland
The five interglacials before the Mid-Brunhes Event (MBE) [c.430 thousand years (ka) ago] are generally considered to be globally cooler than those post-MBE. Inhomogeneities exist regionally, however, which suggest that the Arctic was warmer than present during Marine Isotope Stage (MIS) 15a. Using the first speleothem record for the High Arctic, we investigate the climatic response of northeast Greenland between c.588 and c.549 ka ago. Our results indicate an enhanced warmth of at least +3.5 degrees C relative to the present, leading to permafrost thaw and increased precipitation. We find that delta O-18 of precipitation was at least 3 parts per thousand higher than today and recognize two local cooling events (c.571 and c.594 ka ago) thought to be caused by freshwater forcing. Our results are important for improving understanding of the regional climatic response leading up to the MBE and specifically provide insights into the climatic response of a warmer Arctic
Increased population exposure to Amphan‐scale cyclones under future climates
International audienceAbstract Southern Asia experiences some of the most damaging climate events in the world, with loss of life from some cyclones in the hundreds of thousands. Despite this, research on climate extremes in the region is substantially lacking compared to other parts of the world. To understand the narrative of how an extreme event in the region may change in the future, we consider Super Cyclone Amphan, which made landfall in May 2020, bringing storm surges of 2–4 m to coastlines of India and Bangladesh. Using the latest CMIP6 climate model projections, coupled with storm surge, hydrological, and socio‐economic models, we consider how the population exposure to a storm surge of Amphan's scale changes in the future. We vary future sea level rise and population changes consistent with projections out to 2100, but keep other factors constant. Both India and Bangladesh will be negatively impacted, with India showing >200% increased exposure to extreme storm surge flooding (>3 m) under a high emissions scenario and Bangladesh showing an increase in exposure of >80% for low‐level flooding (>0.1 m). It is only when we follow a low‐emission scenario, consistent with the 2°C Paris Agreement Goal, that we see no real change in Bangladesh's storm surge exposure, mainly due to the population and climate signals cancelling each other out. For India, even with this low‐emission scenario, increases in flood exposure are still substantial (>50%). While here we attribute only the storm surge flooding component of the event to climate change, we highlight that tropical cyclones are multifaceted, and damages are often an integration of physical and social components. We recommend that future climate risk assessments explicitly account for potential compounding factors
Motor Subtype as a Predictor of Future Working Memory Performance in Idiopathic Parkinson's Disease
Parkinson’s disease is a progressive neurodegenerative disorder associated with reduced spatial and verbal working memory ability. There are two established motor subtypes of PD, tremor dominant (TD) and postural instability and gait difficulty (PIGD). This study used structural equation modelling to explore the longitudinal relationship between the two subtypes and working memory assessed at a 2-year follow-up. The study comprised 84 males and 30 females (N = 114), aged between 39 and 85 (M = 64.82, SD = 9.23) with confirmed PD. There was no significant relationship between motor subtype at Time 1 and working memory at Time 2. Postural symptom severity at Time 1 predicted Time 2 spatial working memory for the PIGD subtype (p = .011) but not the TD subtype. Tremor symptoms were not associated with Time 2 working memory in either subtype. Predictive significance of Time 1 postural symptoms only in the PIGD subtype suggests an interaction between symptom dominance (subtype) and symptom severity that future subtyping should consider. This study demonstrates a predictive relationship between postural difficulties and working memory performance assessed at a 2-year follow-up. Establishing physical symptoms as predictors of cognitive change could have significant clinical importance
International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.
Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist
International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways
Finishing the euchromatic sequence of the human genome
The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead
Data Descriptor: An open resource for transdiagnostic research in pediatric mental health and learning disorders
Technological and methodological innovations are equipping researchers with unprecedented capabilities for detecting and characterizing pathologic processes in the developing human brain. As a result, ambitions to achieve clinically useful tools to assist in the diagnosis and management of mental health and learning disorders are gaining momentum. To this end, it is critical to accrue large-scale multimodal datasets that capture a broad range of commonly encountered clinical psychopathology. The Child Mind Institute has launched the Healthy Brain Network (HBN), an ongoing initiative focused on creating and sharing a biobank of data from 10,000 New York area participants (ages 5–21). The HBN Biobank houses data about psychiatric, behavioral, cognitive, and lifestyle phenotypes, as well as multimodal brain imaging (resting and naturalistic viewing fMRI, diffusion MRI, morphometric MRI), electroencephalography, eyetracking, voice and video recordings, genetics and actigraphy. Here, we present the rationale, design and implementation of HBN protocols. We describe the first data release (n =664) and the potential of the biobank to advance related areas (e.g., biophysical modeling, voice analysis
Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study
Introduction:
The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures.
Methods:
In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025.
Findings:
Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation.
Interpretation:
After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification
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