Fitting the HIV Epidemic in Zambia: A Two-Sex Micro-Simulation Model

BACKGROUND: In describing and understanding how the HIV epidemic spreads in African countries, previous studies have not taken into account the detailed periods at risk. This study is based on a micro-simulation model (individual-based) of the spread of the HIV epidemic in the population of Zambia, where women tend to marry early and where divorces are not frequent. The main target of the model was to fit the HIV seroprevalence profiles by age and sex observed at the Demographic and Health Survey conducted in 2001. METHODS AND FINDINGS: A two-sex micro-simulation model of HIV transmission was developed. Particular attention was paid to precise age-specific estimates of exposure to risk through the modelling of the formation and dissolution of relationships: marriage (stable union), casual partnership, and commercial sex. HIV transmission was exclusively heterosexual for adults or vertical (mother-to-child) for children. Three stages of HIV infection were taken into account. All parameters were derived from empirical population-based data. Results show that basic parameters could not explain the dynamics of the HIV epidemic in Zambia. In order to fit the age and sex patterns, several assumptions were made: differential susceptibility of young women to HIV infection, differential susceptibility or larger number of encounters for male clients of commercial sex workers, and higher transmission rate. The model allowed to quantify the role of each type of relationship in HIV transmission, the proportion of infections occurring at each stage of disease progression, and the net reproduction rate of the epidemic (R(0) = 1.95). CONCLUSIONS: The simulation model reproduced the dynamics of the HIV epidemic in Zambia, and fitted the age and sex pattern of HIV seroprevalence in 2001. The same model could be used to measure the effect of changing behaviour in the future

Hormonal contraception, sexual behaviour and HIV prevalence among women in Cameroon

<p>Abstract</p> <p>Background</p> <p>Data on the effect of contraceptive methods, other than the condom, on HIV acquisition is not clear. The aim of this study was to describe hormonal contraceptive use, sexual behaviour and HIV prevalence among women in Cameroon in order to provide baseline information for future analytical studies.</p> <p>Methods</p> <p>This is a cross-sectional descriptive study based a nationally representative sample of 4486 sexually active women aged 15–49 years who participated in the 2004 Cameroon Demographic and Health Survey.</p> <p>Results</p> <p>The overall HIV prevalence was 7.4% (332/4486). The HIV prevalence was higher in the 25–35 year age group (10.03%), urban residents (9.39%), and formerly married (18.48%), compared to their compatriots. The prevalence was lower in women with five or more living child (3.67%), women in the low wealth index category (3.79%) and women who had no formal education (3.37%). The HIV prevalence was higher among women who had two or more partners in the last 12 months (10.26%) and women who reported to have had four or more partners in their lifetime (12.40%). The prevalence of HIV was higher among current hormonal contraceptive users (6.63%) compared to the current non-users (3.06%), among ever users of hormonal contraception (13.27%) compared to the never users (7.11%).</p> <p>Conclusion</p> <p>We conclude that the prevalence of HIV among sexually active women in Cameroon varies according to sociodemographic characteristics, sexual behaviour and hormonal contraceptive use. Our findings underscore the need to counsel women using hormonal contraception to be aware that hormonal methods do not protect against HIV infection. Given the biologic plausibility of the link between hormonal contraception and HIV infection, future research should focus on carefully designed prospective studies to establish the temporal relationship and estimate the incidence of HIV infection among women using and not using hormonal contraceptive methods.</p

Effective Theory Approach to the Spontaneous Breakdown of Lorentz Invariance

We generalize the coset construction of Callan, Coleman, Wess and Zumino to theories in which the Lorentz group is spontaneously broken down to one of its subgroups. This allows us to write down the most general low-energy effective Lagrangian in which Lorentz invariance is non-linearly realized, and to explore the consequences of broken Lorentz symmetry without having to make any assumptions about the mechanism that triggers the breaking. We carry out the construction both in flat space, in which the Lorentz group is a global spacetime symmetry, and in a generally covariant theory, in which the Lorentz group can be treated as a local internal symmetry. As an illustration of this formalism, we construct the most general effective field theory in which the rotation group remains unbroken, and show that the latter is just the Einstein-aether theory.Comment: 45 pages, no figures

Quality of care assessment in geriatric evaluation and management units: construction of a chart review tool for a tracer condition

<p>Abstract</p> <p>Background</p> <p>The number of elderly people requiring hospital care is growing, so, quality and assessment of care for elders are emerging and complex areas of research. Very few validated and reliable instruments exist for the assessment of quality of acute care in this field. This study's objective was to create such a tool for Geriatric Evaluation and Management Units (GEMUs).</p> <p>Methods</p> <p>The methodology involved a reliability and feasibility study of a retrospective chart review on 934 older inpatients admitted in 49 GEMUs during the year 2002–2003 for fall-related trauma as a tracer condition. Pertinent indicators for a chart abstraction tool, the Geriatric Care Tool (GCT), were developed and validated according to five dimensions: access to care, comprehensiveness, continuity of care, patient-centred care and appropriateness. Consensus methods were used to develop the content. Participants were experts representing eight main health care professions involved in GEMUs from 19 different sites. Items associated with high quality of care at each step of the multidisciplinary management of patients admitted due to falls were identified. The GCT was tested for intra- and inter-rater reliability using 30 medical charts reviewed by each of three independent and blinded trained nurses. Kappa and agreement measures between pairs of chart reviewers were computed on an item-by-item basis.</p> <p>Results</p> <p>Three quarters of 169 items identifying the process of care, from the case history to discharge planning, demonstrated good agreement (kappa greater than 0.40 and agreement over 70%). Indicators for the appropriateness of care showed less reliability.</p> <p>Conclusion</p> <p>Content validity and reliability results, as well as the feasibility of the process, suggest that the chart abstraction tool can gather standardized and pertinent clinical information for further evaluating quality of care in GEMU using admission due to falls as a tracer condition. However, the GCT should be evaluated in other models of acute geriatric units and new strategies should be developed to improve reliability of peer assessments in characterizing the quality of care for elderly patients with complex conditions.</p

Measurement of the branching fraction and CP content for the decay B(0) -> D(*+)D(*-)

This is the pre-print version of the Article. The official published version can be accessed from the links below. Copyright @ 2002 APS.We report a measurement of the branching fraction of the decay B0→D*+D*- and of the CP-odd component of its final state using the BABAR detector. With data corresponding to an integrated luminosity of 20.4  fb-1 collected at the Υ(4S) resonance during 1999–2000, we have reconstructed 38 candidate signal events in the mode B0→D*+D*- with an estimated background of 6.2±0.5 events. From these events, we determine the branching fraction to be B(B0→D*+D*-)=[8.3±1.6(stat)±1.2(syst)]×10-4. The measured CP-odd fraction of the final state is 0.22±0.18(stat)±0.03(syst).This work is supported by DOE and NSF (USA), NSERC (Canada), IHEP (China), CEA and CNRS-IN2P3 (France), BMBF (Germany), INFN (Italy), NFR (Norway), MIST (Russia), and PPARC (United Kingdom). Individuals have received support from the A.P. Sloan Foundation, Research Corporation, and Alexander von Humboldt Foundation

Characterization of FUS Mutations in Amyotrophic Lateral Sclerosis Using RNA-Seq

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease resulting in severe muscle weakness and eventual death by respiratory failure. Although little is known about its pathogenesis, mutations in fused in sarcoma/translated in liposarcoma (FUS) are causative for familial ALS. FUS is a multifunctional protein that is involved in many aspects of RNA processing. To elucidate the role of FUS in ALS, we overexpressed wild-type and two mutant forms of FUS in HEK-293T cells, as well as knocked-down FUS expression. This was followed by RNA-Seq to identify genes which displayed differential expression or altered splicing patterns. Pathway analysis revealed that overexpression of wild-type FUS regulates ribosomal genes, whereas knock-down of FUS additionally affects expression of spliceosome related genes. Furthermore, cells expressing mutant FUS displayed global transcription patterns more similar to cells overexpressing wild-type FUS than to the knock-down condition. This observation suggests that FUS mutants do not contribute to the pathogenesis of ALS through a loss-of-function. Finally, our results demonstrate that the R521G and R522G mutations display differences in their influence on transcription and splicing. Taken together, these results provide additional insights into the function of FUS and how mutations contribute to the development of ALS.ALS Foundation NetherlandsAdessium FoundationSeventh Framework Programme (European Commission) (grant number 259867)Thierry Latran FoundationNational Institutes of Health (U.S.) (NIH/NINDS grant R01NS073873)National Institute of Neurological Disorders and Stroke (U.S.) (NIH/NINDS grant numbers 1R01NS065847

Knee Arthroplasty: Disabilities in Comparison to the General Population and to Hip Arthroplasty Using a French National Longitudinal Survey

International audienceBACKGROUND: Knee arthroplasty is increasing exponentially due to the aging of the population and to the broadening of indications. We aimed to compare physical disability and its evolution over two years in people with knee arthroplasty to that in the general population. A secondary objective was to compare the level of disabilities of people with knee to people with hip arthroplasty. METHODOLOGY/PRINCIPAL FINDINGS: 16,945 people representative of the French population were selected in 1999 from the French census and interviewed about their level of disability. This sample included 815 people with lower limb arthroplasty. In 2001, 608 of them were re-interviewed, among whom 134 had knee arthroplasty. Among the other participants re-interviewed, we identified 68 who had undergone knee arthroplasty and 145 hip arthroplasty within the last two years (recent arthroplasty). People with knee arthroplasty reported significantly greater difficulties than the general population with bending forward (odds ratio [OR] = 4.7; 95% confidence interval [CI]: 1.7, 12.6), walking more than 500 meters (OR = 6.0; 95% CI: 1.5, 24.7) and carrying 5 kg kilograms for 10 meters (OR = 4.6; 95% CI: 1.3, 16.4). However, the two years evolution in disability was similar to that in the general population for most activities. The level of mobility was similar between people with recent knee arthroplasty and those with recent hip arthroplasty. Nevertheless, people with recent knee arthroplasty reported a lower level of disability than the other group for washing and bending forward (OR = 0.3; 95% CI: 0.1, 0.6 and OR = 0.4; 95% CI: 0.1, 0.9, respectively). CONCLUSIONS/SIGNIFICANCE: People with knee arthroplasty reported a higher risk of disability than the general population for common activities of daily living but a similar evolution. There was no relevant difference between recent knee and hip arthroplasties for mobility

A destabilized bacterial luciferase for dynamic gene expression studies

Fusions of genetic regulatory elements with reporter genes have long been used as tools for monitoring gene expression and have become a major component in synthetic gene circuit implementation. A major limitation of many of these systems is the relatively long half-life of the reporter protein(s), which prevents monitoring both the initiation and the termination of transcription in real-time. Furthermore, when used as components in synthetic gene circuits, the long time constants associated with reporter protein decay may significantly degrade circuit performance. In this study, short half-life variants of LuxA and LuxB from Photorhabdus luminescens were constructed in Escherichia coli by inclusion of an 11-amino acid carboxy-terminal tag that is recognized by endogenous tail-specific proteases. Results indicated that the addition of the C-terminal tag affected the functional half-life of the holoenzyme when the tag was added to luxA or to both luxA and luxB, but modification of luxB alone did not have a significant effect. In addition, it was also found that alteration of the terminal three amino acid residues of the carboxy-terminal tag fused to LuxA generated variants with half-lives of intermediate length in a manner similar to that reported for GFP. This report is the first instance of the C-terminal tagging approach for the regulation of protein half-life to be applied to an enzyme or monomer of a multi-subunit enzyme complex and will extend the utility of the bacterial luciferase reporter genes for the monitoring of dynamic changes in gene expression