75 research outputs found

    MiSearch adaptive pubMed search tool

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    Summary: MiSearch is an adaptive biomedical literature search tool that ranks citations based on a statistical model for the likelihood that a user will choose to view them. Citation selections are automatically acquired during browsing and used to dynamically update a likelihood model that includes authorship, journal and PubMed indexing information. The user can optionally elect to include or exclude specific features and vary the importance of timeliness in the ranking

    Modeling complex genetic and environmental influences on comorbid bipolar disorder with tobacco use disorder

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    Abstract Background Comorbidity of psychiatric and substance use disorders represents a significant complication in the clinical course of both disorders. Bipolar Disorder (BD) is a psychiatric disorder characterized by severe mood swings, ranging from mania to depression, and up to a 70% rate of comorbid Tobacco Use Disorder (TUD). We found epidemiological evidence consistent with a common underlying etiology for BD and TUD, as well as evidence of both genetic and environmental influences on BD and TUD. Therefore, we hypothesized a common underlying genetic etiology, interacting with nicotine exposure, influencing susceptibility to both BD and TUD. Methods Using meta-analysis, we compared TUD rates for BD patients and the general population. We identified candidate genes showing statistically significant, replicated, evidence of association with both BD and TUD. We assessed commonality among these candidate genes and hypothesized broader, multi-gene network influences on the comorbidity. Using Fisher Exact tests we tested our hypothesized genetic networks for association with the comorbidity, then compared the inferences drawn with those derived from the commonality assessment. Finally, we prioritized candidate SNPs for validation. Results We estimate risk for TUD among BD patients at 2.4 times that of the general population. We found three candidate genes associated with both BD and TUD (COMT, SLC6A3, and SLC6A4) and commonality analysis suggests that these genes interact in predisposing psychiatric and substance use disorders. We identified a 69 gene network that influences neurotransmitter signaling and shows significant over-representation of genes associated with BD and TUD, as well as genes differentially expressed with exposure to tobacco smoke. Twenty four of these genes are known drug targets. Conclusions This work highlights novel bioinformatics resources and demonstrates the effectiveness of using an integrated bioinformatics approach to improve our understanding of complex disease etiology. We illustrate the development and testing of hypotheses for a comorbidity predisposed by both genetic and environmental influences. Consistent with our hypothesis, the selected network models multiple interacting genetic influences on comorbid BD with TUD, as well as the environmental influence of nicotine. This network nominates candidate genes for validation and drug testing, and we offer a panel of SNPs prioritized for follow-up.http://deepblue.lib.umich.edu/bitstream/2027.42/112449/1/12881_2009_Article_575.pd

    The free healthcare initiative in Sierra Leone: Evaluating a health system reform, 2010-2015

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    Sophie Witter - orcid: 0000-0002-7656-6188 https://orcid.org/0000-0002-7656-6188This article presents the findings of a theory-based evaluation of the Sierra Leone Free Health Care Initiative (FHCI), using mixed methods. Analytical approaches included time-series analysis of national survey data to examine mortality and morbidity trends, as well as modelling of impact using the Lives Saved Tool and expenditure trend analysis. We find that the FHCI responded to a clear need in Sierra Leone, was well designed to bring about needed changes in the health system to deliver services to the target beneficiaries, and did indeed bring funds and momentum to produce important systemic reforms. However, its ambition was also a risk, and weaknesses in implementation have been evident in a number of core areas, such as drugs supply. We conclude that the FHCI was one important factor contributing to improvements in coverage and equity of coverage of essential services for mothers and children. Modelled cost-effectiveness is high-in the region of US420toUS 420 to US 444 per life year saved. The findings suggest that even-or perhaps especially-in a weak health system, a reform-like fee removal, if tackled in a systematic way, can bring about important health system gains that benefit vulnerable groups in particular.sch_iih33pub5153pub

    Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

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    BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

    Outbreak of Type 2 Vaccine-Derived Poliovirus in Nigeria: Emergence and Widespread Circulation in an Underimmunized Population

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    Wild poliovirus has remained endemic in northern Nigeria because of low coverage achieved in the routine immunization program and in supplementary immunization activities (SIAs). An outbreak of infection involving 315 cases of type 2 circulating vaccine-derived poliovirus (cVDPV2; >1% divergent from Sabin 2) occurred during July 2005–June 2010, a period when 23 of 34 SIAs used monovalent or bivalent oral poliovirus vaccine (OPV) lacking Sabin 2. In addition, 21 “pre-VDPV2” (0.5%–1.0% divergent) cases occurred during this period. Both cVDPV and pre-VDPV cases were clinically indistinguishable from cases due to wild poliovirus. The monthly incidence of cases increased sharply in early 2009, as more children aged without trivalent OPV SIAs. Cumulative state incidence of pre-VDPV2/cVDPV2 was correlated with low childhood immunization against poliovirus type 2 assessed by various means. Strengthened routine immunization programs in countries with suboptimal coverage and balanced use of OPV formulations in SIAs are necessary to minimize risks of VDPV emergence and circulation

    The Atacama Cosmology Telescope: A Measurement of the DR6 CMB Lensing Power Spectrum and its Implications for Structure Growth

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    We present new measurements of cosmic microwave background (CMB) lensing over 94009400 sq. deg. of the sky. These lensing measurements are derived from the Atacama Cosmology Telescope (ACT) Data Release 6 (DR6) CMB dataset, which consists of five seasons of ACT CMB temperature and polarization observations. We determine the amplitude of the CMB lensing power spectrum at 2.3%2.3\% precision (43σ43\sigma significance) using a novel pipeline that minimizes sensitivity to foregrounds and to noise properties. To ensure our results are robust, we analyze an extensive set of null tests, consistency tests, and systematic error estimates and employ a blinded analysis framework. The baseline spectrum is well fit by a lensing amplitude of Alens=1.013±0.023A_{\mathrm{lens}}=1.013\pm0.023 relative to the Planck 2018 CMB power spectra best-fit Λ\LambdaCDM model and Alens=1.005±0.023A_{\mathrm{lens}}=1.005\pm0.023 relative to the ACT DR4+WMAP\text{ACT DR4} + \text{WMAP} best-fit model. From our lensing power spectrum measurement, we derive constraints on the parameter combination S8CMBLσ8(Ωm/0.3)0.25S^{\mathrm{CMBL}}_8 \equiv \sigma_8 \left({\Omega_m}/{0.3}\right)^{0.25} of S8CMBL=0.818±0.022S^{\mathrm{CMBL}}_8= 0.818\pm0.022 from ACT DR6 CMB lensing alone and S8CMBL=0.813±0.018S^{\mathrm{CMBL}}_8= 0.813\pm0.018 when combining ACT DR6 and Planck NPIPE CMB lensing power spectra. These results are in excellent agreement with Λ\LambdaCDM model constraints from Planck or ACT DR4+WMAP\text{ACT DR4} + \text{WMAP} CMB power spectrum measurements. Our lensing measurements from redshifts z0.5z\sim0.5--55 are thus fully consistent with Λ\LambdaCDM structure growth predictions based on CMB anisotropies probing primarily z1100z\sim1100. We find no evidence for a suppression of the amplitude of cosmic structure at low redshiftsComment: 45+21 pages, 50 figures. Prepared for submission to ApJ. Also see companion papers Madhavacheril et al and MacCrann et a

    The Atacama Cosmology Telescope: DR6 Gravitational Lensing Map and Cosmological Parameters

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    We present cosmological constraints from a gravitational lensing mass map covering 9400 sq. deg. reconstructed from CMB measurements made by the Atacama Cosmology Telescope (ACT) from 2017 to 2021. In combination with BAO measurements (from SDSS and 6dF), we obtain the amplitude of matter fluctuations σ8=0.819±0.015\sigma_8 = 0.819 \pm 0.015 at 1.8% precision, S8σ8(Ωm/0.3)0.5=0.840±0.028S_8\equiv\sigma_8({\Omega_{\rm m}}/0.3)^{0.5}=0.840\pm0.028 and the Hubble constant H0=(68.3±1.1)kms1Mpc1H_0= (68.3 \pm 1.1)\, \text{km}\,\text{s}^{-1}\,\text{Mpc}^{-1} at 1.6% precision. A joint constraint with CMB lensing measured by the Planck satellite yields even more precise values: σ8=0.812±0.013\sigma_8 = 0.812 \pm 0.013, S8σ8(Ωm/0.3)0.5=0.831±0.023S_8\equiv\sigma_8({\Omega_{\rm m}}/0.3)^{0.5}=0.831\pm0.023 and H0=(68.1±1.0)kms1Mpc1H_0= (68.1 \pm 1.0)\, \text{km}\,\text{s}^{-1}\,\text{Mpc}^{-1}. These measurements agree well with Λ\LambdaCDM-model extrapolations from the CMB anisotropies measured by Planck. To compare these constraints to those from the KiDS, DES, and HSC galaxy surveys, we revisit those data sets with a uniform set of assumptions, and find S8S_8 from all three surveys are lower than that from ACT+Planck lensing by varying levels ranging from 1.7-2.1σ\sigma. These results motivate further measurements and comparison, not just between the CMB anisotropies and galaxy lensing, but also between CMB lensing probing z0.55z\sim 0.5-5 on mostly-linear scales and galaxy lensing at z0.5z\sim 0.5 on smaller scales. We combine our CMB lensing measurements with CMB anisotropies to constrain extensions of Λ\LambdaCDM, limiting the sum of the neutrino masses to mν<0.12\sum m_{\nu} < 0.12 eV (95% c.l.), for example. Our results provide independent confirmation that the universe is spatially flat, conforms with general relativity, and is described remarkably well by the Λ\LambdaCDM model, while paving a promising path for neutrino physics with gravitational lensing from upcoming ground-based CMB surveys.Comment: 30 pages, 16 figures, prepared for submission to ApJ. Cosmological likelihood data is here: https://lambda.gsfc.nasa.gov/product/act/actadv_prod_table.html ; likelihood software is here: https://github.com/ACTCollaboration/act_dr6_lenslike . Also see companion papers Qu et al and MacCrann et al. Mass maps will be released when papers are publishe

    Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

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    Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

    The Atacama Cosmology Telescope: A measurement of the DR6 CMB lensing power spectrum and its implications for structure growth

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    We present new measurements of cosmic microwave background (CMB) lensing over 9400 deg2 of the sky. These lensing measurements are derived from the Atacama Cosmology Telescope (ACT) Data Release 6 (DR6) CMB data set, which consists of five seasons of ACT CMB temperature and polarization observations. We determine the amplitude of the CMB lensing power spectrum at 2.3% precision (43σ significance) using a novel pipeline that minimizes sensitivity to foregrounds and to noise properties. To ensure that our results are robust, we analyze an extensive set of null tests, consistency tests, and systematic error estimates and employ a blinded analysis framework. Our CMB lensing power spectrum measurement provides constraints on the amplitude of cosmic structure that do not depend on Planck or galaxy survey data, thus giving independent information about large-scale structure growth and potential tensions in structure measurements. The baseline spectrum is well fit by a lensing amplitude of A lens = 1.013 ± 0.023 relative to the Planck 2018 CMB power spectra best-fit ΛCDM model and A lens = 1.005 ± 0.023 relative to the ACT DR4 + WMAP best-fit model. From our lensing power spectrum measurement, we derive constraints on the parameter combination S8CMBL≡σ8Ωm/0.30.25 of S8CMBL=0.818±0.022 from ACT DR6 CMB lensing alone and S8CMBL=0.813±0.018 when combining ACT DR6 and Planck NPIPE CMB lensing power spectra. These results are in excellent agreement with ΛCDM model constraints from Planck or ACT DR4 + WMAP CMB power spectrum measurements. Our lensing measurements from redshifts z ∼ 0.5–5 are thus fully consistent with ΛCDM structure growth predictions based on CMB anisotropies probing primarily z ∼ 1100. We find no evidence for a suppression of the amplitude of cosmic structure at low redshifts
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