1,267 research outputs found

    Descriptors of Sepsis Using the Sepsis-3 Criteria: A Cohort Study in Critical Care Units Within the U.K. National Institute for Health Research Critical Care Health Informatics Collaborative

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    OBJECTIVES: To describe the epidemiology of sepsis in critical care by applying the Sepsis-3 criteria to electronic health records. DESIGN: Retrospective cohort study using electronic health records. SETTING: Ten ICUs from four U.K. National Health Service hospital trusts contributing to the National Institute for Health Research Critical Care Health Informatics Collaborative. PATIENTS: A total of 28,456 critical care admissions (14,332 emergency medical, 4,585 emergency surgical, and 9,539 elective surgical). MEASUREMENTS AND MAIN RESULTS: Twenty-nine thousand three hundred forty-three episodes of clinical deterioration were identified with a rise in Sequential Organ Failure Assessment score of at least 2 points, of which 14,869 (50.7%) were associated with antibiotic escalation and thereby met the Sepsis-3 criteria for sepsis. A total of 4,100 episodes of sepsis (27.6%) were associated with vasopressor use and lactate greater than 2.0 mmol/L, and therefore met the Sepsis-3 criteria for septic shock. ICU mortality by source of sepsis was highest for ICU-acquired sepsis (23.7%; 95% CI, 21.9-25.6%), followed by hospital-acquired sepsis (18.6%; 95% CI, 17.5-19.9%), and community-acquired sepsis (12.9%; 95% CI, 12.1-13.6%) (p for comparison less than 0.0001). CONCLUSIONS: We successfully operationalized the Sepsis-3 criteria to an electronic health record dataset to describe the characteristics of critical care patients with sepsis. This may facilitate sepsis research using electronic health record data at scale without relying on human coding

    A new multicompartmental reaction-diffusion modeling method links transient membrane attachment of E. coli MinE to E-ring formation

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    Many important cellular processes are regulated by reaction-diffusion (RD) of molecules that takes place both in the cytoplasm and on the membrane. To model and analyze such multicompartmental processes, we developed a lattice-based Monte Carlo method, Spatiocyte that supports RD in volume and surface compartments at single molecule resolution. Stochasticity in RD and the excluded volume effect brought by intracellular molecular crowding, both of which can significantly affect RD and thus, cellular processes, are also supported. We verified the method by comparing simulation results of diffusion, irreversible and reversible reactions with the predicted analytical and best available numerical solutions. Moreover, to directly compare the localization patterns of molecules in fluorescence microscopy images with simulation, we devised a visualization method that mimics the microphotography process by showing the trajectory of simulated molecules averaged according to the camera exposure time. In the rod-shaped bacterium _Escherichia coli_, the division site is suppressed at the cell poles by periodic pole-to-pole oscillations of the Min proteins (MinC, MinD and MinE) arising from carefully orchestrated RD in both cytoplasm and membrane compartments. Using Spatiocyte we could model and reproduce the _in vivo_ MinDE localization dynamics by accounting for the established properties of MinE. Our results suggest that the MinE ring, which is essential in preventing polar septation, is largely composed of MinE that is transiently attached to the membrane independently after recruited by MinD. Overall, Spatiocyte allows simulation and visualization of complex spatial and reaction-diffusion mediated cellular processes in volumes and surfaces. As we showed, it can potentially provide mechanistic insights otherwise difficult to obtain experimentally

    Colon cancer controls versus population controls in case-control studies of occupational risk factors

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    BACKGROUND: Since updated population registers do not exist in many countries it is often difficult to sample valid population controls from the study base to a case-control study. Use of patient controls is an alternative option if the exposure experience under study for these patients are interchangeable with the experience for population controls. Patient controls may even be preferable from population controls under certain conditions. In this study we examine if colon cancer patients can serve as surrogates for proper population controls in case-control studies of occupational risk factors. METHODS: The study was conducted from 1995 to 1997. Incident colon cancer controls (N = 428) aged 35–69 years with a histological verified diagnosis and population controls (N = 583) were selected. Altogether 254 (59%) of the colon cancer controls and 320 (55%) of the population controls were interviewed about occupational, medical and life style conditions. RESULTS: No statistical significant difference for educational level, medical history or smoking status was seen between the two control groups. There was evidence of a higher alcohol intake, less frequent work as a farmer and less exposure to pesticides among colon cancer controls. CONCLUSIONS: Use of colon cancer controls may provide valid exposure estimates in studies of many occupational risk factors for cancer, but not for studies on exposure related to farming

    Association between insulin resistance and c-reactive protein among Peruvian adults

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    <p>Abstract</p> <p>Objective</p> <p>Insulin resistance (IR), a reduced physiological response of peripheral tissues to the action of insulin, is one of the major causes of type 2 diabetes. We sought to evaluate the relationship between serum C-reactive protein (CRP), a marker of systemic inflammation, and prevalence of IR among Peruvian adults.</p> <p>Methods</p> <p>This population based study of 1,525 individuals (569 men and 956 women; mean age 39 years old) was conducted among residents in Lima and Callao, Peru. Fasting plasma glucose, insulin, and CRP concentrations were measured using standard approaches. Insulin resistance was assessed using the homeostasis model (HOMA-IR). Categories of CRP were defined by the following tertiles: <0.81 mg/l, 0.81-2.53 mg/l, and >2.53 mg/l. Logistic regression procedures were employed to estimate odds ratios (OR) and 95% confidence intervals (CI).</p> <p>Results</p> <p>Elevated CRP were significantly associated with increased mean fasting insulin and mean HOMA-IR concentrations (p < 0.001). Women with CRP concentration >2.53 mg/l (upper tertile) had a 2.18-fold increased risk of IR (OR = 2.18 95% CI 1.51-3.16) as compared with those in the lowest tertile (<0.81 mg/l). Among men, those in the upper tertile had a 2.54-fold increased risk of IR (OR = 2.54 95% CI 1.54-4.20) as compared with those in the lowest tertile.</p> <p>Conclusion</p> <p>Our observations among Peruvians suggest that chronic systemic inflammation, as evidenced by elevated CRP, may be of etiologic importance in insulin resistance and diabetes.</p

    Phylogenomics illuminates the backbone of the Myriapoda Tree of Life and reconciles morphological and molecular phylogenies

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    © The Author(s) 2017 This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. The attached file is the published version of the article

    Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

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    The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO

    Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

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    SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation
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