A modified mathematical model for HIV transmission, AIDS and intervention strategies in Ireland

The aim of this project was to modify transmission models previously developed to describe HIV transmission in Ireland through more precise estimates of parameters delineating sexual and needle sharing behaviour and AIDS related mortality, with a view to examining the extent of spread from IVDUs to the general heterosexual population. To provide predictions on HIV transmission and AIDS cases up to the year 2010 and to examine the sensitivity of the predictions to changes in the key parameters under different assumptions on intervention strategies. Essential data of relevance to HIV transmission were acquired (through the cooperation of the Department of Health, the AIDS Resource Centre, the Drug Treatment Centre, the Ana Liffey Drug Project, and St James’s Hospital, Dublin) and analysed. The parameters obtained from the descriptive and survival analyses were used in a refined deterministic model of HIV transmission which was solved numerically. An attempt at a solution using perturbation methods was undertaken. Results provided a plausible range of projected new HIV infections and AIDS cases up to the year 2010. The model projects that if present behaviour continues, approximately 1009 new infections may be expected in Dublin by the year 2000, and 1496 new infections by 2010. Small changes in the values of key parameters induce significant changes in projected trends, particularly in the longer term. However all projections point to the fact that •Non-IVDU women are particularly susceptible to HIV infection •Early introduction of behaviour change makes a significant difference to the growth of the epidemic •Expanding the Drug Treatment System could help to significantly reduce the spread of HIV •Central collation of data is essential if rational implementation of intervention plans is to be achieve

Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke

Genetic factors have been implicated in stroke risk but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) in ischemic stroke and its subtypes in 3,548 cases and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 cases and 6,281 controls. We replicated reported associations between variants close to PITX2 and ZFHX3 with cardioembolic stroke, and a 9p21 locus with large vessel stroke. We identified a novel association for a SNP within the histone deacetylase 9(HDAC9) gene on chromosome 7p21.1 which was associated with large vessel stroke including additional replication in a further 735 cases and 28583 controls (rs11984041, combined P = 1.87×10−11, OR=1.42 (95% CI) 1.28-1.57). All four loci exhibit evidence for heterogeneity of effect across the stroke subtypes, with some, and possibly all, affecting risk for only one subtype. This suggests differing genetic architectures for different stroke subtypes

Factors deterring schools from mixed attainment teaching practice

Mixed-attainment teaching has strong support from research and yet English schools are far more likely to teach students in ‘ability’ groups. Although research has considered some of the specific benefits of mixed-attainment grouping, there has been little attention to the reasons schools avoid it. This article explores data from the pilot and recruitment phases of a large-scale study into grouping practices and seeks to identify reasons for the low rate of mixed attainment grouping in English secondary schools. We report on our struggle to recruit schools, and explore the different explanations provided by teachers as to why mixed attainment practice is seen as problematic. The difficulties are characterised as a vicious circle where schools are deterred by a paucity of exemplars and resources and the educational climate is characterised as fearful, risk-averse and time-poor. Suggestions are made as to strategies to support schools in taking up mixed attainment practices

Assessing the uncertainties of model estimates of primary productivity in the tropical Pacific Ocean

Author Posting. © Elsevier B.V., 2009. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Journal of Marine Systems 76 (2009): 113-133, doi:10.1016/j.jmarsys.2008.05.010.Depth-integrated primary productivity (PP) estimates obtained from satellite ocean color based models (SatPPMs) and those generated from biogeochemical ocean general circulation models (BOGCMs) represent a key resource for biogeochemical and ecological studies at global as well as regional scales. Calibration and validation of these PP models are not straightforward, however, and comparative studies show large differences between model estimates. The goal of this paper is to compare PP estimates obtained from 30 different models (21 SatPPMs and 9 BOGCMs) to a tropical Pacific PP database consisting of ~1000 14C measurements spanning more than a decade (1983- 1996). Primary findings include: skill varied significantly between models, but performance was not a function of model complexity or type (i.e. SatPPM vs. BOGCM); nearly all models underestimated the observed variance of PP, specifically yielding too few low PP (< 0.2 gC m-2d-2) values; more than half of the total root-mean-squared model-data differences associated with the satellite-based PP models might be accounted for by uncertainties in the input variables and/or the PP data; and the tropical Pacific database captures a broad scale shift from low biomass-normalized productivity in the 1980s to higher biomass-normalized productivity in the 1990s, which was not successfully captured by any of the models. This latter result suggests that interdecadal and global changes will be a significant challenge for both SatPPMs and BOGCMs. Finally, average root-mean-squared differences between in situ PP data on the equator at 140°W and PP estimates from the satellite-based productivity models were 58% lower than analogous values computed in a previous PP model comparison six years ago. The success of these types of comparison exercises is illustrated by the continual modification and improvement of the participating models and the resulting increase in model skill.This research was supported by a grant from the National Aeronautics and Space Agency Ocean Biology and Biogeochemistry program (NNG06GA03G), as well as by numerous other grants to the various participating investigator

Satellite sensor requirements for monitoring essential biodiversity variables of coastal ecosystems

© The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Ecological Applications 28 (2018): 749-760, doi: 10.1002/eap.1682.The biodiversity and high productivity of coastal terrestrial and aquatic habitats are the foundation for important benefits to human societies around the world. These globally distributed habitats need frequent and broad systematic assessments, but field surveys only cover a small fraction of these areas. Satellite‐based sensors can repeatedly record the visible and near‐infrared reflectance spectra that contain the absorption, scattering, and fluorescence signatures of functional phytoplankton groups, colored dissolved matter, and particulate matter near the surface ocean, and of biologically structured habitats (floating and emergent vegetation, benthic habitats like coral, seagrass, and algae). These measures can be incorporated into Essential Biodiversity Variables (EBVs), including the distribution, abundance, and traits of groups of species populations, and used to evaluate habitat fragmentation. However, current and planned satellites are not designed to observe the EBVs that change rapidly with extreme tides, salinity, temperatures, storms, pollution, or physical habitat destruction over scales relevant to human activity. Making these observations requires a new generation of satellite sensors able to sample with these combined characteristics: (1) spatial resolution on the order of 30 to 100‐m pixels or smaller; (2) spectral resolution on the order of 5 nm in the visible and 10 nm in the short‐wave infrared spectrum (or at least two or more bands at 1,030, 1,240, 1,630, 2,125, and/or 2,260 nm) for atmospheric correction and aquatic and vegetation assessments; (3) radiometric quality with signal to noise ratios (SNR) above 800 (relative to signal levels typical of the open ocean), 14‐bit digitization, absolute radiometric calibration <2%, relative calibration of 0.2%, polarization sensitivity <1%, high radiometric stability and linearity, and operations designed to minimize sunglint; and (4) temporal resolution of hours to days. We refer to these combined specifications as H4 imaging. Enabling H4 imaging is vital for the conservation and management of global biodiversity and ecosystem services, including food provisioning and water security. An agile satellite in a 3‐d repeat low‐Earth orbit could sample 30‐km swath images of several hundred coastal habitats daily. Nine H4 satellites would provide weekly coverage of global coastal zones. Such satellite constellations are now feasible and are used in various applications.National Center for Ecological Analysis and Synthesis (NCEAS); National Aeronautics and Space Administration (NASA) Grant Numbers: NNX16AQ34G, NNX14AR62A; National Ocean Partnership Program; NOAA US Integrated Ocean Observing System/IOOS Program Office; Bureau of Ocean and Energy Management Ecosystem Studies program (BOEM) Grant Number: MC15AC0000

A framework for human microbiome research

A variety of microbial communities and their genes (the microbiome) exist throughout the human body, with fundamental roles in human health and disease. The National Institutes of Health (NIH)-funded Human Microbiome Project Consortium has established a population-scale framework to develop metagenomic protocols, resulting in a broad range of quality-controlled resources and data including standardized methods for creating, processing and interpreting distinct types of high-throughput metagenomic data available to the scientific community. Here we present resources from a population of 242 healthy adults sampled at 15 or 18 body sites up to three times, which have generated 5,177 microbial taxonomic profiles from 16S ribosomal RNA genes and over 3.5 terabases of metagenomic sequence so far. In parallel, approximately 800 reference strains isolated from the human body have been sequenced. Collectively, these data represent the largest resource describing the abundance and variety of the human microbiome, while providing a framework for current and future studies

Structure, function and diversity of the healthy human microbiome

Author Posting. © The Authors, 2012. This article is posted here by permission of Nature Publishing Group. The definitive version was published in Nature 486 (2012): 207-214, doi:10.1038/nature11234.Studies of the human microbiome have revealed that even healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics and early microbial exposure have all been implicated. Accordingly, to characterize the ecology of human-associated microbial communities, the Human Microbiome Project has analysed the largest cohort and set of distinct, clinically relevant body habitats so far. We found the diversity and abundance of each habitat’s signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals. The project encountered an estimated 81–99% of the genera, enzyme families and community configurations occupied by the healthy Western microbiome. Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure, and ethnic/racial background proved to be one of the strongest associations of both pathways and microbes with clinical metadata. These results thus delineate the range of structural and functional configurations normal in the microbial communities of a healthy population, enabling future characterization of the epidemiology, ecology and translational applications of the human microbiome.This research was supported in part by National Institutes of Health grants U54HG004969 to B.W.B.; U54HG003273 to R.A.G.; U54HG004973 to R.A.G., S.K.H. and J.F.P.; U54HG003067 to E.S.Lander; U54AI084844 to K.E.N.; N01AI30071 to R.L.Strausberg; U54HG004968 to G.M.W.; U01HG004866 to O.R.W.; U54HG003079 to R.K.W.; R01HG005969 to C.H.; R01HG004872 to R.K.; R01HG004885 to M.P.; R01HG005975 to P.D.S.; R01HG004908 to Y.Y.; R01HG004900 to M.K.Cho and P. Sankar; R01HG005171 to D.E.H.; R01HG004853 to A.L.M.; R01HG004856 to R.R.; R01HG004877 to R.R.S. and R.F.; R01HG005172 to P. Spicer.; R01HG004857 to M.P.; R01HG004906 to T.M.S.; R21HG005811 to E.A.V.; M.J.B. was supported by UH2AR057506; G.A.B. was supported by UH2AI083263 and UH3AI083263 (G.A.B., C. N. Cornelissen, L. K. Eaves and J. F. Strauss); S.M.H. was supported by UH3DK083993 (V. B. Young, E. B. Chang, F. Meyer, T. M. S., M. L. Sogin, J. M. Tiedje); K.P.R. was supported by UH2DK083990 (J. V.); J.A.S. and H.H.K. were supported by UH2AR057504 and UH3AR057504 (J.A.S.); DP2OD001500 to K.M.A.; N01HG62088 to the Coriell Institute for Medical Research; U01DE016937 to F.E.D.; S.K.H. was supported by RC1DE0202098 and R01DE021574 (S.K.H. and H. Li); J.I. was supported by R21CA139193 (J.I. and D. S. Michaud); K.P.L. was supported by P30DE020751 (D. J. Smith); Army Research Office grant W911NF-11-1-0473 to C.H.; National Science Foundation grants NSF DBI-1053486 to C.H. and NSF IIS-0812111 to M.P.; The Office of Science of the US Department of Energy under Contract No. DE-AC02-05CH11231 for P.S. C.; LANL Laboratory-Directed Research and Development grant 20100034DR and the US Defense Threat Reduction Agency grants B104153I and B084531I to P.S.C.; Research Foundation - Flanders (FWO) grant to K.F. and J.Raes; R.K. is an HHMI Early Career Scientist; Gordon&BettyMoore Foundation funding and institutional funding fromthe J. David Gladstone Institutes to K.S.P.; A.M.S. was supported by fellowships provided by the Rackham Graduate School and the NIH Molecular Mechanisms in Microbial Pathogenesis Training Grant T32AI007528; a Crohn’s and Colitis Foundation of Canada Grant in Aid of Research to E.A.V.; 2010 IBM Faculty Award to K.C.W.; analysis of the HMPdata was performed using National Energy Research Scientific Computing resources, the BluBioU Computational Resource at Rice University

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research