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排序方式: 共有201条查询结果,搜索用时 62 毫秒
101.
Chia-Jung Chang Ho-Chang Kuo Jeng-Sheng Chang Jong-Keuk Lee Fuu-Jen Tsai Chiea Chuen Khor Li-Ching Chang Shih-Ping Chen Tai-Ming Ko Yi-Min Liu Ying-Ju Chen Young Mi Hong Gi Young Jang Martin L. Hibberd Taco Kuijpers David Burgner Michael Levin Jane C. Burns Sonia Davila International Kawasaki Disease Genetics Consortium? Korean Kawasaki Disease Genetics Consortium? Taiwan Kawasaki Disease Genetics Consortium? Yuan-Tsong Chen Chien-Hsiun Chen Jer-Yuarn Wu Yi-Ching Lee 《PloS one》2013,8(8)
The BLK and CD40 loci have been associated with Kawasaki disease (KD) in two genome-wide association studies (GWAS) conducted in a Taiwanese population of Han Chinese ancestry (Taiwanese) and in Japanese cohorts. Here we build on these findings with replication studies of the BLK and CD40 loci in populations of Korean and European descent. The BLK region was significantly associated with KD susceptibility in both populations. Within the BLK gene the rs2736340-located linkage disequilibrium (LD ) comprising the promoter and first intron was strongly associated with KD, with the combined results of Asian studies including Taiwanese, Japanese, and Korean populations (2,539 KD patients and 7,021 controls) providing very compelling evidence of association (rs2736340, OR = 1.498, 1.354–1.657; P = 4.74×10−31). We determined the percentage of B cells present in the peripheral blood mononuclear cell (PBMC) population and the expression of BLK in the peripheral blood leukocytes (leukocytes) of KD patients during the acute and convalescent stages. The percentage of B cells in the PBMC population and the expression of BLK in leukocytes were induced in patients in the acute stage of KD. In B cell lines derived from KD patients, and in purified B cells from KD patients obtained during the acute stage, those with the risk allele of rs2736340 expressed significantly lower levels of BLK. These results suggest that peripheral B cells play a pathogenic role during the acute stage of KD. Decreased BLK expression in peripheral blood B cells may alter B cell function and predispose individuals to KD. These associative data suggest a role for B cells during acute KD. Understanding the functional implications may facilitate the development of B cell-mediated therapy for KD. 相似文献
102.
Michael Schomaker Matthias Egger James Ndirangu Sam Phiri Harry Moultrie Karl Technau Vivian Cox Janet Giddy Cleophas Chimbetete Robin Wood Thomas Gsponer Carolyn Bolton Moore Helena Rabie Brian Eley Lulu Muhe Martina Penazzato Shaffiq Essajee Olivia Keiser Mary-Ann Davies for the International Epidemiologic Databases to Evaluate AIDS–Southern Africa Collaboration 《PLoS medicine》2013,10(11)
Background
There is limited evidence on the optimal timing of antiretroviral therapy (ART) initiation in children 2–5 y of age. We conducted a causal modelling analysis using the International Epidemiologic Databases to Evaluate AIDS–Southern Africa (IeDEA-SA) collaborative dataset to determine the difference in mortality when starting ART in children aged 2–5 y immediately (irrespective of CD4 criteria), as recommended in the World Health Organization (WHO) 2013 guidelines, compared to deferring to lower CD4 thresholds, for example, the WHO 2010 recommended threshold of CD4 count <750 cells/mm3 or CD4 percentage (CD4%) <25%.Methods and Findings
ART-naïve children enrolling in HIV care at IeDEA-SA sites who were between 24 and 59 mo of age at first visit and with ≥1 visit prior to ART initiation and ≥1 follow-up visit were included. We estimated mortality for ART initiation at different CD4 thresholds for up to 3 y using g-computation, adjusting for measured time-dependent confounding of CD4 percent, CD4 count, and weight-for-age z-score. Confidence intervals were constructed using bootstrapping.The median (first; third quartile) age at first visit of 2,934 children (51% male) included in the analysis was 3.3 y (2.6; 4.1), with a median (first; third quartile) CD4 count of 592 cells/mm3 (356; 895) and median (first; third quartile) CD4% of 16% (10%; 23%). The estimated cumulative mortality after 3 y for ART initiation at different CD4 thresholds ranged from 3.4% (95% CI: 2.1–6.5) (no ART) to 2.1% (95% CI: 1.3%–3.5%) (ART irrespective of CD4 value). Estimated mortality was overall higher when initiating ART at lower CD4 values or not at all. There was no mortality difference between starting ART immediately, irrespective of CD4 value, and ART initiation at the WHO 2010 recommended threshold of CD4 count <750 cells/mm3 or CD4% <25%, with mortality estimates of 2.1% (95% CI: 1.3%–3.5%) and 2.2% (95% CI: 1.4%–3.5%) after 3 y, respectively. The analysis was limited by loss to follow-up and the unavailability of WHO staging data.Conclusions
The results indicate no mortality difference for up to 3 y between ART initiation irrespective of CD4 value and ART initiation at a threshold of CD4 count <750 cells/mm3 or CD4% <25%, but there are overall higher point estimates for mortality when ART is initiated at lower CD4 values. Please see later in the article for the Editors'' Summary 相似文献103.
Dongzhu Ma Anna Jasinska Jan Kristoff J. Paul Grobler Trudy Turner Yoon Jung Christopher Schmitt Kevin Raehtz Felix Feyertag Natalie Martinez Sosa Viskam Wijewardana Donald S. Burke David L. Robertson Russell Tracy Ivona Pandrea Nelson Freimer Cristian Apetrei The International Vervet Research Consortium 《PLoS pathogens》2013,9(1)
Pathogenesis studies of SIV infection have not been performed to date in wild monkeys due to difficulty in collecting and storing samples on site and the lack of analytical reagents covering the extensive SIV diversity. We performed a large scale study of molecular epidemiology and natural history of SIVagm infection in 225 free-ranging AGMs from multiple locations in South Africa. SIV prevalence (established by sequencing pol, env, and gag) varied dramatically between infant/juvenile (7%) and adult animals (68%) (p<0.0001), and between adult females (78%) and males (57%). Phylogenetic analyses revealed an extensive genetic diversity, including frequent recombination events. Some AGMs harbored epidemiologically linked viruses. Viruses infecting AGMs in the Free State, which are separated from those on the coastal side by the Drakensberg Mountains, formed a separate cluster in the phylogenetic trees; this observation supports a long standing presence of SIV in AGMs, at least from the time of their speciation to their Plio-Pleistocene migration. Specific primers/probes were synthesized based on the pol sequence data and viral loads (VLs) were quantified. VLs were of 104–106 RNA copies/ml, in the range of those observed in experimentally-infected monkeys, validating the experimental approaches in natural hosts. VLs were significantly higher (107–108 RNA copies/ml) in 10 AGMs diagnosed as acutely infected based on SIV seronegativity (Fiebig II), which suggests a very active transmission of SIVagm in the wild. Neither cytokine levels (as biomarkers of immune activation) nor sCD14 levels (a biomarker of microbial translocation) were different between SIV-infected and SIV-uninfected monkeys. This complex algorithm combining sequencing and phylogeny, VL quantification, serology, and testing of surrogate markers of microbial translocation and immune activation permits a systematic investigation of the epidemiology, viral diversity and natural history of SIV infection in wild African natural hosts. 相似文献
104.
105.
106.
Antonio L. Ribeiro Ester C. Sabino Milena S. Marcolino Vera M. C. Salemi Barbara M. Ianni Fábio Fernandes Luciano Nastari André Antunes Márcia Menezes Cláudia Di Lorenzo Oliveira Vandana Sachdev Danielle M. Carrick Michael P. Busch Eduard L. Murphy for the NHLBI Retrovirus Epidemiology Donor Study-II International Component 《PLoS neglected tropical diseases》2013,7(2)
Background
Blood donor screening leads to large numbers of new diagnoses of Trypanosoma cruzi infection, with most donors in the asymptomatic chronic indeterminate form. Information on electrocardiogram (ECG) findings in infected blood donors is lacking and may help in counseling and recognizing those with more severe disease.Objectives
To assess the frequency of ECG abnormalities in T.cruzi seropositive relative to seronegative blood donors, and to recognize ECG abnormalities associated with left ventricular dysfunction.Methods
The study retrospectively enrolled 499 seropositive blood donors in São Paulo and Montes Claros, Brazil, and 483 seronegative control donors matched by site, gender, age, and year of blood donation. All subjects underwent a health clinical evaluation, ECG, and echocardiogram (Echo). ECG and Echo were reviewed blindly by centralized reading centers. Left ventricular (LV) dysfunction was defined as LV ejection fraction (EF)<0.50%.Results
Right bundle branch block and left anterior fascicular block, isolated or in association, were more frequently found in seropositive cases (p<0.0001). Both QRS and QTc duration were associated with LVEF values (correlation coefficients −0.159,p<0.0003, and −0.142,p = 0.002) and showed a moderate accuracy in the detection of reduced LVEF (area under the ROC curve: 0.778 and 0.790, both p<0.0001). Several ECG abnormalities were more commonly found in seropositive donors with depressed LVEF, including rhythm disorders (frequent supraventricular ectopic beats, atrial fibrillation or flutter and pacemaker), intraventricular blocks (right bundle branch block and left anterior fascicular block) and ischemic abnormalities (possible old myocardial infarction and major and minor ST abnormalities). ECG was sensitive (92%) for recognition of seropositive donors with depressed LVEF and had a high negative predictive value (99%) for ruling out LV dysfunction.Conclusions
ECG abnormalities are more frequent in seropositive than in seronegative blood donors. Several ECG abnormalities may help the recognition of seropositive cases with reduced LVEF who warrant careful follow-up and treatment. 相似文献107.
International Advisory Group for the Revision of ICD- Mental andBehavioural Disorders 《World psychiatry》2011,10(2):86-92
The World Health Organization (WHO) is revising the ICD-10 classification
of mental and behavioural disorders, under the leadership of the Department
of Mental Health and Substance Abuse and within the framework of the overall
revision framework as directed by the World Health Assembly. This article
describes WHO’s perspective and priorities for mental and behavioural
disorders classification in ICD-11, based on the recommendations of the International
Advisory Group for the Revision of ICD-10 Mental and Behavioural Disorders.
The WHO considers that the classification should be developed in consultation
with stakeholders, which include WHO member countries, multidisciplinary health
professionals, and users of mental health services and their families. Attention
to the cultural framework must be a key element in defining future classification
concepts. Uses of the ICD that must be considered include clinical applications,
research, teaching and training, health statistics, and public health. The
Advisory Group has determined that the current revision represents a particular
opportunity to improve the classification’s clinical utility, particularly
in global primary care settings where there is the greatest opportunity to
identify people who need mental health treatment. Based on WHO’s mission
and constitution, the usefulness of the classification in helping WHO member
countries, particularly low- and middle-income countries, to reduce the disease
burden associated with mental disorders is among the highest priorities for
the revision. This article describes the foundation provided by the recommendations
of the Advisory Group for the current phase of work. 相似文献
108.
Bridges M Heron EA O'Dushlaine C Segurado R;International Schizophrenia Consortium 《PloS one》2011,6(5):e14802
There are many instances in genetics in which we wish to determine whether two candidate populations are distinguishable on the basis of their genetic structure. Examples include populations which are geographically separated, case-control studies and quality control (when participants in a study have been genotyped at different laboratories). This latter application is of particular importance in the era of large scale genome wide association studies, when collections of individuals genotyped at different locations are being merged to provide increased power. The traditional method for detecting structure within a population is some form of exploratory technique such as principal components analysis. Such methods, which do not utilise our prior knowledge of the membership of the candidate populations. are termed unsupervised. Supervised methods, on the other hand are able to utilise this prior knowledge when it is available.In this paper we demonstrate that in such cases modern supervised approaches are a more appropriate tool for detecting genetic differences between populations. We apply two such methods, (neural networks and support vector machines) to the classification of three populations (two from Scotland and one from Bulgaria). The sensitivity exhibited by both these methods is considerably higher than that attained by principal components analysis and in fact comfortably exceeds a recently conjectured theoretical limit on the sensitivity of unsupervised methods. In particular, our methods can distinguish between the two Scottish populations, where principal components analysis cannot. We suggest, on the basis of our results that a supervised learning approach should be the method of choice when classifying individuals into pre-defined populations, particularly in quality control for large scale genome wide association studies. 相似文献
109.
P Jia L Wang AH Fanous CN Pato TL Edwards;International Schizophrenia Consortium Z Zhao 《PLoS computational biology》2012,8(7):e1002587
With the recent success of genome-wide association studies (GWAS), a wealth of association data has been accomplished for more than 200 complex diseases/traits, proposing a strong demand for data integration and interpretation. A combinatory analysis of multiple GWAS datasets, or an integrative analysis of GWAS data and other high-throughput data, has been particularly promising. In this study, we proposed an integrative analysis framework of multiple GWAS datasets by overlaying association signals onto the protein-protein interaction network, and demonstrated it using schizophrenia datasets. Building on a dense module search algorithm, we first searched for significantly enriched subnetworks for schizophrenia in each single GWAS dataset and then implemented a discovery-evaluation strategy to identify module genes with consistent association signals. We validated the module genes in an independent dataset, and also examined them through meta-analysis of the related SNPs using multiple GWAS datasets. As a result, we identified 205 module genes with a joint effect significantly associated with schizophrenia; these module genes included a number of well-studied candidate genes such as DISC1, GNA12, GNA13, GNAI1, GPR17, and GRIN2B. Further functional analysis suggested these genes are involved in neuronal related processes. Additionally, meta-analysis found that 18 SNPs in 9 module genes had P
meta<1×10−4, including the gene HLA-DQA1 located in the MHC region on chromosome 6, which was reported in previous studies using the largest cohort of schizophrenia patients to date. These results demonstrated our bi-directional network-based strategy is efficient for identifying disease-associated genes with modest signals in GWAS datasets. This approach can be applied to any other complex diseases/traits where multiple GWAS datasets are available. 相似文献
110.
Michel Prud''''homme 《中国科学:生命科学英文版》2005,48(Z2)
This paper presents a brief overview of the world nitrogen fertilizer demand, highlights trends in the global and regional developments of production capacity and provides a medium-term perspective of the global nitrogen supply/demand balance. 相似文献