This report details the lipid composition of nascent HDL (nHDL) particles formed by the action of the ATP binding cassette transporter A1 (ABCA1) on apolipoprotein A-I (apoA-I). nHDL particles of ...different size (average diameters of ∼12, 10, 7.5, and <6 nm) and composition were purified by size-exclusion chromatography. Electron microscopy suggested that the nHDL were mostly spheroidal. The proportions of the principal nHDL lipids, free cholesterol, glycerophosphocholine, and sphingomyelin were similar to that of lipid rafts, suggesting that the lipid originated from a raft-like region of the cell. Smaller amounts of glucosylceramides, cholesteryl esters, and other glycerophospholipid classes were also present. The largest particles, ∼12 nm and 10 nm diameter, contained ∼43% free cholesterol, 2–3% cholesteryl ester, and three apoA-I molecules. Using chemical cross-linking chemistry combined with mass spectrometry, we found that three molecules of apoA-I in the ∼9–14 nm nHDL adopted a belt-like conformation. The smaller (7.5 nm diameter) spheroidal nHDL particles carried 30% free cholesterol and two molecules of apoA-I in a twisted, antiparallel, double-belt conformation. Overall, these new data offer fresh insights into the biogenesis and structural constraints involved in forming nascent HDL from ABCA1.
This study shows the effects of nuclear waste glass production on Monofrax K‐3 refractory corrosion. A continuously fed research‐scale melter containing an Fe‐ and Ni‐rich simulated nuclear waste ...feed with borosilicate glass‐forming chemicals was cyclically melted at 1150°C and idled at 1050°C for a total of 11 weeks. Chemical maps using scanning electron microscopy show the interactions between the quenched melt and the refractory. Nanoscale X‐ray‐computed tomography was used for a three‐dimensional visualization of certain parts of the interface. Unreacted K‐3 consists of primarily corundum (Al,Cr)2O3 and spinel (Fe2+,Mg)(Al,Cr)2O4 interlocking crystalline phases. Some of the Cr from the refractory interacts with the Ni and Fe from the melt to form a reaction layer comprising (Ni,Fe2+)(Cr,Fe3+)2O4 spinel crystals. Simultaneously, melt components (Na,Si) infiltrate into the refractory. This interaction proceeds at the expense of the integrity of the refractory structure. Intact refractory grains (e.g., (Al,Cr)2O3) as well as the reaction layer itself can lose mechanical integrity and spall off into the melt, especially near the top of the melter. As the reaction layer can be a protective boundary for the refractory against further melt infiltration, a reduction in the reaction layer thickness allows an increase in refractory corrosion.
Species abundance distributions (SADs) follow one of ecology's oldest and most universal laws - every community shows a hollow curve or hyperbolic shape on a histogram with many rare species and just ...a few common species. Here, we review theoretical, empirical and statistical developments in the study of SADs. Several key points emerge. (i) Literally dozens of models have been proposed to explain the hollow curve. Unfortunately, very few models are ever rejected, primarily because few theories make any predictions beyond the hollow-curve SAD itself. (ii) Interesting work has been performed both empirically and theoretically, which goes beyond the hollow-curve prediction to provide a rich variety of information about how SADs behave. These include the study of SADs along environmental gradients and theories that integrate SADs with other biodiversity patterns. Central to this body of work is an effort to move beyond treating the SAD in isolation and to integrate the SAD into its ecological context to enable making many predictions. (iii) Moving forward will entail understanding how sampling and scale affect SADs and developing statistical tools for describing and comparing SADs. We are optimistic that SADs can provide significant insights into basic and applied ecological science.
Accurate influenza activity forecasting helps public health officials prepare and allocate resources for unusual influenza activity. Traditional flu surveillance systems, such as the Centers for ...Disease Control and Prevention's (CDC) influenza-like illnesses reports, lag behind real-time by one to 2 weeks, whereas information contained in cloud-based electronic health records (EHR) and in Internet users' search activity is typically available in near real-time. We present a method that combines the information from these two data sources with historical flu activity to produce national flu forecasts for the United States up to 4 weeks ahead of the publication of CDC's flu reports.
We extend a method originally designed to track flu using Google searches, named ARGO, to combine information from EHR and Internet searches with historical flu activities. Our regularized multivariate regression model dynamically selects the most appropriate variables for flu prediction every week. The model is assessed for the flu seasons within the time period 2013-2016 using multiple metrics including root mean squared error (RMSE).
Our method reduces the RMSE of the publicly available alternative (Healthmap flutrends) method by 33, 20, 17 and 21%, for the four time horizons: real-time, one, two, and 3 weeks ahead, respectively. Such accuracy improvements are statistically significant at the 5% level. Our real-time estimates correctly identified the peak timing and magnitude of the studied flu seasons.
Our method significantly reduces the prediction error when compared to historical publicly available Internet-based prediction systems, demonstrating that: (1) the method to combine data sources is as important as data quality; (2) effectively extracting information from a cloud-based EHR and Internet search activity leads to accurate forecast of flu.
Recent work in both 304L and 316L stainless steel produced by additive manufacturing (AM) has shown that in addition to the unique, characteristic microstructures formed during the process, a fine ...dispersion of sub-micron particles, with a chemistry different from either the powder feedstock or the expected final material, are evident in the final microstructure. Such fine-scale features can only be resolved using transmission electron microscopy (TEM) or similar techniques. The present work uses electron microscopy to study both the initial powder feedstock and microstructures in final AM parts. Special attention is paid to the chemistry and origin of these nanoscale particles in several different metal alloys, and their impact on the final build. Comparisons to traditional, wrought material will be made.
Death by suicide is a highly preventable yet growing worldwide health crisis. To date, there has been a lack of adequately powered genomic studies of suicide, with no sizable suicide death cohorts ...available for analysis. To address this limitation, the authors conducted the first comprehensive genomic analysis of suicide death using previously unpublished genotype data from a large population-ascertained cohort.
The analysis sample comprised 3,413 population-ascertained case subjects of European ancestry and 14,810 ancestrally matched control subjects. Analytical methods included principal component analysis for ancestral matching and adjusting for population stratification, linear mixed model genome-wide association testing (conditional on genetic-relatedness matrix), gene and gene set-enrichment testing, and polygenic score analyses, as well as single-nucleotide polymorphism (SNP) heritability and genetic correlation estimation using linkage disequilibrium score regression.
Genome-wide association analysis identified two genome-wide significant loci (involving six SNPs: rs34399104, rs35518298, rs34053895, rs66828456, rs35502061, and rs35256367). Gene-based analyses implicated 22 genes on chromosomes 13, 15, 16, 17, and 19 (q<0.05). Suicide death heritability was estimated at an h
value of 0.25 (SE=0.04) and a value of 0.16 (SE=0.02) when converted to a liability scale. Notably, suicide polygenic scores were significantly predictive across training and test sets. Polygenic scores for several other psychiatric disorders and psychological traits were also predictive, particularly scores for behavioral disinhibition and major depressive disorder.
Multiple genome-wide significant loci and genes were identified and polygenic score prediction of suicide death case-control status was demonstrated, adjusting for ancestry, in independent training and test sets. Additionally, the suicide death sample was found to have increased genetic risk for behavioral disinhibition, major depressive disorder, depressive symptoms, autism spectrum disorder, psychosis, and alcohol use disorder compared with the control sample.
HIV prevalence varies markedly throughout Africa, and it is often presumed areas of higher HIV prevalence (i.e., hotspots) serve as sources of infection to neighboring areas of lower prevalence. ...However, the small-scale geography of migration networks and movement of HIV-positive individuals between communities is poorly understood. Here, we use population-based data from ~22,000 persons of known HIV status to characterize migratory patterns and their relationship to HIV among 38 communities in Rakai, Uganda with HIV prevalence ranging from 9 to 43%. We find that migrants moving into hotspots had significantly higher HIV prevalence than migrants moving elsewhere, but out-migration from hotspots was geographically dispersed, contributing minimally to HIV burden in destination locations. Our results challenge the assumption that high prevalence hotspots are drivers of transmission in regional epidemics, instead suggesting that migrants with high HIV prevalence, particularly women, selectively migrate to these areas.
The Getting It Right First Time (GIRFT) programme is a quality improvement initiative covering the National Health Service in England. The programme aims to standardise clinical practices and improve ...patient and system level outcomes by utilising data‐driven insights and clinically‐led recommendations. There are GIRFT workstreams for every medical and surgical specialty, including urology. Defining features of the GIRFT methodology are that it is clinically led by experienced clinicians, data‐driven, and specialty specific. Each specialty workstream conducts deep‐dive visits to every hospital, analysing performance data and engaging with clinicians and management to identify and share improvement priorities. For urology, GIRFT has completed deep‐dive visits and published reports outlining priority areas for development. Reports include recommendations pertaining to streamlining care pathways, reducing the acuity of care environments, enhancing emergency services, optimising utilisation of outpatient services, and workforce training and utilisation. The GIRFT academy provides guides for implementing best practices specific to priority areas of care. These include important disease pathways, and GIRFT‐advocated innovations such as urology investigation units and urology area networks. GIRFT offers clinical transformation, cost reduction, equity in access to care, and leaner models of care that are often more environmentally sustainable. Evaluation efforts of the programme have focussed on assessing the adoption of GIRFT recommendations, understanding barriers to change, and modelling the climate impact of advocated practices.
Objectives To evaluate the carbon footprint of the perioperative transurethral resection of bladder tumour (TURBT) pathway from decision to treat to postoperative discharge, and model potential ...greenhouse gas (GHG) emissions reduction strategies. Materials and Methods This process‐based attributional cradle‐to‐grave life‐cycle assessment (LCA) of GHG emissions modelled the perioperative TURBT pathway at a hospital in Southwest England. We included travel, energy and water use, all reusable and consumable items, and laundry and equipment sterilisation. Resource use for 30 patients undergoing surgery was recorded to understand average GHG emissions and the inter‐case variability. Sensitivity analysis was performed for manufacturing location, pharmaceutical manufacturing carbon‐intensity, and theatre list utilisation. Results The median (interquartile range) perioperative TURBT carbon footprint was 131.8 (119.8–153.6) kg of carbon dioxide equivalent. Major pathway categories contributing to GHG emissions were surgical equipment (22.2%), travel (18.6%), gas and electricity (13.3%), and anaesthesia/drugs and associated adjuncts (27.0%), primarily due to consumable items and processes. Readily modifiable GHG emissions hotspots included patient travel for preoperative assessment, glove use, catheter use, irrigation delivery and extraction, and mitomycin C disposal. GHG emissions were higher for those admitted as inpatients after surgery. Conclusions This cradle‐to‐grave LCA found multiple modifiable GHG emissions hotspots. Key mitigation themes include minimising avoidable patient travel, rationalising equipment use, optimally filling operating theatre lists, and safely avoiding postoperative catheterisation and hospital admission where possible. A crucial next step is to design and deliver an implementation strategy for the environmentally sustainable changes demonstrated herein.
Objectives
To describe the contemporary evolution of day‐case bladder outflow obstruction (BOO) surgery in England and to profile day‐case BOO surgery practices across England in terms of the types ...of operation performed and their safety profiles.
Materials and Methods
This was a retrospective observational analysis of Hospital Episode Statistics and UK Office for National Statistics data. All 111 043 recorded operations across 117 hospital trusts over 66 months, from 1 January 2017 to 30 June 2022, were obtained. Operations were identified as one of: transurethral resection of prostate (TURP); laser ablation or enucleation; vapour therapy; prostatic urethral lift (PUL); or bladder neck incision. Monthly day‐case rate trends were plotted across the study period. Descriptive data, day‐case rates and 30‐day hospital readmissions were analysed for each operation type. Multilevel regression modelling with mixed effects was performed to determine whether day‐case surgery was associated with higher 30‐day hospital readmissions.
Results
Day‐case patients were younger, with fewer comorbidities. Time series analysis showed a linear day‐case rate increase from 8.3% (January 2017) to 21.0% (June 2022). Day‐case rates improved for 92/117 trusts in 2021/2022 compared with 2017. Three of the six trusts with the highest day‐case rates performed predominantly day‐case TURP, and the other three laser surgery. Nationally, PUL and vapour surgery had the highest day‐case rates (80.9% and 38.1%). Most inpatient operations were TURP. Multilevel regression modelling found reduced odds of 30‐day readmission after day‐case BOO surgery (all operations pooled), no difference for day‐case vs inpatient TURP, and reduced odds following day‐case LASER operations.
Conclusions
The day‐case rates for BOO surgery have linearly increased. Minimally invasive surgical technologies are commonly performed as day cases, whereas high day‐case rates for TURP and for laser ablation operations are seen in a minority of hospitals. Day‐case pathways to treat BOO can be safely developed irrespective of operative modality.
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