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301.
302.
Simon Cauchemez Scott Epperson Matthew Biggerstaff David Swerdlow Lyn Finelli Neil M. Ferguson 《PLoS medicine》2013,10(3)
Background
Prior to emergence in human populations, zoonoses such as SARS cause occasional infections in human populations exposed to reservoir species. The risk of widespread epidemics in humans can be assessed by monitoring the reproduction number R (average number of persons infected by a human case). However, until now, estimating R required detailed outbreak investigations of human clusters, for which resources and expertise are not always available. Additionally, existing methods do not correct for important selection and under-ascertainment biases. Here, we present simple estimation methods that overcome many of these limitations.Methods and Findings
Our approach is based on a parsimonious mathematical model of disease transmission and only requires data collected through routine surveillance and standard case investigations. We apply it to assess the transmissibility of swine-origin influenza A H3N2v-M virus in the US, Nipah virus in Malaysia and Bangladesh, and also present a non-zoonotic example (cholera in the Dominican Republic). Estimation is based on two simple summary statistics, the proportion infected by the natural reservoir among detected cases (G) and among the subset of the first detected cases in each cluster (F). If detection of a case does not affect detection of other cases from the same cluster, we find that R can be estimated by 1−G; otherwise R can be estimated by 1−F when the case detection rate is low. In more general cases, bounds on R can still be derived.Conclusions
We have developed a simple approach with limited data requirements that enables robust assessment of the risks posed by emerging zoonoses. We illustrate this by deriving transmissibility estimates for the H3N2v-M virus, an important step in evaluating the possible pandemic threat posed by this virus. Please see later in the article for the Editors'' Summary 相似文献303.
Leigh F. Johnson Joel Mossong Rob E. Dorrington Michael Schomaker Christopher J. Hoffmann Olivia Keiser Matthew P. Fox Robin Wood Hans Prozesky Janet Giddy Daniela Belen Garone Morna Cornell Matthias Egger Andrew Boulle for the International Epidemiologic Databases to Evaluate AIDS Southern Africa Collaboration 《PLoS medicine》2013,10(4)
Background
Few estimates exist of the life expectancy of HIV-positive adults receiving antiretroviral treatment (ART) in low- and middle-income countries. We aimed to estimate the life expectancy of patients starting ART in South Africa and compare it with that of HIV-negative adults.Methods and Findings
Data were collected from six South African ART cohorts. Analysis was restricted to 37,740 HIV-positive adults starting ART for the first time. Estimates of mortality were obtained by linking patient records to the national population register. Relative survival models were used to estimate the excess mortality attributable to HIV by age, for different baseline CD4 categories and different durations. Non-HIV mortality was estimated using a South African demographic model. The average life expectancy of men starting ART varied between 27.6 y (95% CI: 25.2–30.2) at age 20 y and 10.1 y (95% CI: 9.3–10.8) at age 60 y, while estimates for women at the same ages were substantially higher, at 36.8 y (95% CI: 34.0–39.7) and 14.4 y (95% CI: 13.3–15.3), respectively. The life expectancy of a 20-y-old woman was 43.1 y (95% CI: 40.1–46.0) if her baseline CD4 count was ≥200 cells/µl, compared to 29.5 y (95% CI: 26.2–33.0) if her baseline CD4 count was <50 cells/µl. Life expectancies of patients with baseline CD4 counts ≥200 cells/µl were between 70% and 86% of those in HIV-negative adults of the same age and sex, and life expectancies were increased by 15%–20% in patients who had survived 2 y after starting ART. However, the analysis was limited by a lack of mortality data at longer durations.Conclusions
South African HIV-positive adults can have a near-normal life expectancy, provided that they start ART before their CD4 count drops below 200 cells/µl. These findings demonstrate that the near-normal life expectancies of HIV-positive individuals receiving ART in high-income countries can apply to low- and middle-income countries as well. Please see later in the article for the Editors'' Summary 相似文献304.
305.
Marion Sourisseau Maria L. Michta Chati Zony Benjamin Israelow Sharon E. Hopcraft Christopher M. Narbus Ana Parra Martín Matthew J. Evans 《PLoS pathogens》2013,9(3)
Hepatitis C virus (HCV) is a major cause of liver disease worldwide. A better understanding of its life cycle, including the process of host cell entry, is important for the development of HCV therapies and model systems. Based on the requirement for numerous host factors, including the two tight junction proteins claudin-1 (CLDN1) and occludin (OCLN), HCV cell entry has been proposed to be a multi-step process. The lack of OCLN-specific inhibitors has prevented a comprehensive analysis of this process. To study the role of OCLN in HCV cell entry, we created OCLN mutants whose HCV cell entry activities could be inhibited by antibodies. These mutants were expressed in polarized HepG2 cells engineered to support the complete HCV life cycle by CD81 and miR-122 expression and synchronized infection assays were performed to define the kinetics of HCV cell entry. During these studies, OCLN utilization differences between HCV isolates were observed, supporting a model that HCV directly interacts with OCLN. In HepG2 cells, both HCV cell entry and tight junction formation were impaired by OCLN silencing and restored by expression of antibody regulatable OCLN mutant. Synchronized infection assays showed that glycosaminoglycans and SR-BI mediated host cell binding, while CD81, CLDN1 and OCLN all acted sequentially at a post-binding stage prior to endosomal acidification. These results fit a model where the tight junction region is the last to be encountered by the virion prior to internalization. 相似文献
306.
307.
308.
Alexandra M. Lopes Kenneth I. Aston Emma Thompson Filipa Carvalho Jo?o Gon?alves Ni Huang Rune Matthiesen Michiel J. Noordam Inés Quintela Avinash Ramu Catarina Seabra Amy B. Wilfert Juncheng Dai Jonathan M. Downie Susana Fernandes Xuejiang Guo Jiahao Sha António Amorim Alberto Barros Angel Carracedo Zhibin Hu Matthew E. Hurles Sergey Moskovtsev Carole Ober Darius A. Paduch Joshua D. Schiffman Peter N. Schlegel Mário Sousa Douglas T. Carrell Donald F. Conrad 《PLoS genetics》2013,9(3)
Gonadal failure, along with early pregnancy loss and perinatal death, may be an important filter that limits the propagation of harmful mutations in the human population. We hypothesized that men with spermatogenic impairment, a disease with unknown genetic architecture and a common cause of male infertility, are enriched for rare deleterious mutations compared to men with normal spermatogenesis. After assaying genomewide SNPs and CNVs in 323 Caucasian men with idiopathic spermatogenic impairment and more than 1,100 controls, we estimate that each rare autosomal deletion detected in our study multiplicatively changes a man''s risk of disease by 10% (OR 1.10 [1.04–1.16], p<2×10−3), rare X-linked CNVs by 29%, (OR 1.29 [1.11–1.50], p<1×10−3), and rare Y-linked duplications by 88% (OR 1.88 [1.13–3.13], p<0.03). By contrasting the properties of our case-specific CNVs with those of CNV callsets from cases of autism, schizophrenia, bipolar disorder, and intellectual disability, we propose that the CNV burden in spermatogenic impairment is distinct from the burden of large, dominant mutations described for neurodevelopmental disorders. We identified two patients with deletions of DMRT1, a gene on chromosome 9p24.3 orthologous to the putative sex determination locus of the avian ZW chromosome system. In an independent sample of Han Chinese men, we identified 3 more DMRT1 deletions in 979 cases of idiopathic azoospermia and none in 1,734 controls, and found none in an additional 4,519 controls from public databases. The combined results indicate that DMRT1 loss-of-function mutations are a risk factor and potential genetic cause of human spermatogenic failure (frequency of 0.38% in 1306 cases and 0% in 7,754 controls, p = 6.2×10−5). Our study identifies other recurrent CNVs as potential causes of idiopathic azoospermia and generates hypotheses for directing future studies on the genetic basis of male infertility and IVF outcomes. 相似文献
309.
Aditya Malkar Neil A. Devenport Helen J. Martin Pareen Patel Matthew A. Turner Phillip Watson Ronald J. Maughan Helen J. Reid Barry L. Sharp C. L. Paul Thomas James C. Reynolds Colin S. Creaser 《Metabolomics : Official journal of the Metabolomic Society》2013,9(6):1192-1201
A method has been developed for metabolite profiling of the salivary metabolome based on protein precipitation and ultra-high performance liquid chromatography coupled with ion mobility-mass spectrometry (UHPLC–IM–MS). The developed method requires 0.5 mL of human saliva, which is easily obtainable by passive drool. Standard protocols have been established for the collection, storage and pre-treatment of saliva. The use of UHPLC allows rapid global metabolic profiling for biomarker discovery with a cycle time of 15 min. Mass spectrometry imparts the ability to analyse a diverse number of species reproducibly over a wide dynamic range, which is essential for profiling of biofluids. The combination of UHPLC with IM–MS provides an added dimension enabling complex metabolic samples to be separated on the basis of retention time, ion mobility and mass-to-charge ratio in a single chromatographic run. The developed method has been applied to targeted metabolite identification and untargeted metabolite profiling of saliva samples collected before and after exercise-induced physiological stress. δ-Valerolactam has been identified as a potential biomarker on the basis of retention time, MS/MS spectrum and ion mobility drift time. 相似文献
310.
Piotr Wysoczanski Robert J. Mart E. Joel Loveridge Christopher Williams Sara B.-M. Whittaker Matthew P. Crump Rudolf K. Allemann 《Biomolecular NMR assignments》2013,7(2):187-191
Here we report the 1H, 13C and 15N resonance assignments of free Bcl-xL and of Bcl-xL in complex with an azobenzene-modified peptide derived from the BH3 domain of the pro-apoptotic Bak. The spectra suggest predominantly folded proteins; chemical shift difference analysis provides a detailed view of the reorganization occurring on peptide binding. 相似文献