scispace - formally typeset
Search or ask a question

Showing papers by "University of the Witwatersrand published in 2012"


Journal ArticleDOI
Rafael Lozano1, Mohsen Naghavi1, Kyle J Foreman2, Stephen S Lim1  +192 moreInstitutions (95)
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2010 aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex, using the Cause of Death Ensemble model.

11,809 citations


Journal ArticleDOI
Georges Aad1, T. Abajyan2, Brad Abbott3, Jalal Abdallah4  +2964 moreInstitutions (200)
TL;DR: In this article, a search for the Standard Model Higgs boson in proton-proton collisions with the ATLAS detector at the LHC is presented, which has a significance of 5.9 standard deviations, corresponding to a background fluctuation probability of 1.7×10−9.

9,282 citations


Journal ArticleDOI
Theo Vos, Abraham D. Flaxman1, Mohsen Naghavi1, Rafael Lozano1  +360 moreInstitutions (143)
TL;DR: Prevalence and severity of health loss were weakly correlated and age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010, but population growth and ageing have increased YLD numbers and crude rates over the past two decades.

7,021 citations


Journal ArticleDOI
Christopher J L Murray1, Theo Vos2, Rafael Lozano1, Mohsen Naghavi1  +366 moreInstitutions (141)
TL;DR: The results for 1990 and 2010 supersede all previously published Global Burden of Disease results and highlight the importance of understanding local burden of disease and setting goals and targets for the post-2015 agenda taking such patterns into account.

6,861 citations



Journal ArticleDOI
TL;DR: Oral TDF and TDF-FTC both protect against HIV-1 infection in heterosexual men and women, and both study medications significantly reduced the HIV- 1 incidence among both men andWomen.
Abstract: Background Antiretroviral preexposure prophylaxis is a promising approach for preventing human immunodeficiency virus type 1 (HIV-1) infection in heterosexual populations. Methods We conducted a randomized trial of oral antiretroviral therapy for use as preexposure prophylaxis among HIV-1–serodiscordant heterosexual couples from Kenya and Uganda. The HIV-1–seronegative partner in each couple was randomly assigned to one of three study regimens — once-daily tenofovir (TDF), combination tenofovir–emtricitabine (TDF–FTC), or matching placebo — and followed monthly for up to 36 months. At enrollment, the HIV-1–seropositive partners were not eligible for antiretroviral therapy, according to national guidelines. All couples received standard HIV-1 treatment and prevention services. Results We enrolled 4758 couples, of whom 4747 were followed: 1584 randomly assigned to TDF, 1579 to TDF–FTC, and 1584 to placebo. For 62% of the couples followed, the HIV-1–seronegative partner was male. Among HIV-1–seropositive par...

2,752 citations


Journal ArticleDOI
TL;DR: New understandings of the diverse and dynamic effects on adolescent health include insights into the effects of puberty and brain development, together with social media, which provide important opportunities to improve health, both in adolescence and later in life.

1,780 citations


Journal ArticleDOI
TL;DR: Adverse effects reported with aflibercept combined with FOLFIRI included the characteristic anti-vascular endothelial growth factor effects and also reflected an increased incidence of some chemotherapy-related toxicities.
Abstract: Purpose Treatment for metastatic colorectal cancer (mCRC) commonly involves a fluoropyrimidine-based chemotherapy regimen such as infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) or fluorouracil, leucovorin, and oxaliplatin, often combined with bevacizumab or an epidermal growth factor receptor monoclonal antibody. We studied the effect of adding the novel antiangiogenic agent aflibercept (also known as ziv-aflibercept in the United States) to FOLFIRI in patients with mCRC previously treated with oxaliplatin, including patients who received prior bevacizumab. Patients and Methods Patients were randomly assigned to receive aflibercept (4 mg/kg intravenously; 612 patients) or placebo (614 patients) every 2 weeks in combination with FOLFIRI. Treatment was administered until disease progression or unacceptable toxicity. The primary end point was overall survival. Results Adding aflibercept to FOLFIRI significantly improved overall survival relative to placebo plus FOLFIRI (hazard ratio [HR], 0.817; 95.34% CI, 0.713 to 0.937; P .0032) with median survival times of 13.50 versus 12.06 months, respectively. Aflibercept also significantly improved progression-free survival (PFS; HR, 0.758; 95% CI, 0.661 to 0.869; P .0001), with median PFS times of 6.90 versus 4.67 months, respectively. The effects on overall survival and PFS exhibited a consistent trend across prespecified subgroup analyses, including bevacizumab pretreated patients. Response rate was 19.8% (95% CI, 16.4% to 23.2%) with aflibercept plus FOLFIRI compared with 11.1% (95% CI, 8.5% to 13.8%) with placebo plus FOLFIRI (P .0001). Adverse effects reported with aflibercept combined with FOLFIRI included the characteristic anti–vascular endothelial growth factor effects and also reflected an increased incidence of some chemotherapy-related toxicities.

1,185 citations


Journal ArticleDOI
27 Apr 2012-PLOS ONE
TL;DR: Among women with interpersonal violence history or currently in abusive relationships, full survey content disclosure was done with fear; the partner responses were negative, and few women reported receiving threatening remarks but none reported being assaulted.
Abstract: Objective To explore how survey respondents perceived their experiences and the impact of participating in a survey, and to assess adverse consequences resulting from participation. Design Qualitative study involving purposefully selected participants who had participated in a household-based survey. Methods This qualitative study was nested within a survey that investigated the prevalence of gender-based violence perpetration and victimization with adult men and women in South Africa. 13 male- and 10 female-in-depth interviews were conducted with survey respondents. Results A majority of informants, without gender-differences, perceived the survey interview as a rare opportunity to share their adverse and or personal experiences in a 'safe' space. Gender-differences were noted in reporting perceptions of risks involved with survey participation. Some women remained fearful after completing the survey, that should breach of confidentiality or full survey content disclosure occur, they may be victimized by partners as a punishment for survey participation without men's approval. A number of informants generally discussed their survey participation with others. However, among women with interpersonal violence history or currently in abusive relationships, full survey content disclosure was done with fear; the partner responses were negative, and few women reported receiving threatening remarks but none reported being assaulted. In contrast no man reported adverse reaction by others. Informants with major life adversities reported that the survey had made them to relive the experiences causing them sadness and pain at the time. No informant perceived the survey as emotionally harmful or needed professional support because of survey questions. Rather the vast majority perceived benefit from survey participation. Conclusion Whilst no informant felt answering the survey questions had caused them emotional or physical harm, some were distressed and anxious, albeit temporarily. Research protocols need to put in place safeguards where appropriate so that this group receives support and protection.

1,070 citations


Journal ArticleDOI
TL;DR: In this article, the authors identify seven generic policy-relevant principles for enhancing the resilience of desired ES in the face of disturbance and ongoing change in social-ecological systems (SES).
Abstract: Enhancing the resilience of ecosystem services (ES) that underpin human well-being is critical for meeting current and future societal needs, and requires specific governance and management policies. Using the literature, we identify seven generic policy-relevant principles for enhancing the resilience of desired ES in the face of disturbance and ongoing change in social-ecological systems (SES). These principles are (P1) maintain diversity and redundancy, (P2) manage connectivity, (P3) manage slow variables and feedbacks, (P4) foster an understanding of SES as complex adaptive systems (CAS), (P5) encourage learning and experimentation, (P6) broaden participation, and (P7) promote polycentric governance systems. We briefly define each principle, review how and when it enhances the resilience of ES, and conclude with major research gaps. In practice, the principles often co-occur and are highly interdependent. Key future needs are to better understand these interdependencies and to operationalize and apply...

872 citations


Journal ArticleDOI
TL;DR: A global map of the dominant vector species (DVS) of malaria that makes use of predicted distribution maps for individual species or species complexes is described and highlights the spatial variability in the complexity of the vector situation.
Abstract: Background: Global maps, in particular those based on vector distributions, have long been used to help visualise the global extent of malaria. Few, however, have been created with the support of a comprehensive and extensive evidence-based approach. Methods: Here we describe the generation of a global map of the dominant vector species (DVS) of malaria that makes use of predicted distribution maps for individual species or species complexes. Results: Our global map highlights the spatial variability in the complexity of the vector situation. In Africa, An. gambiae, An. arabiensis and An. funestus are co-dominant across much of the continent, whereas in the AsianPacific region there is a highly complex situation with multi-species coexistence and variable species dominance. Conclusions: The competence of the mapping methodology to accurately portray DVS distributions is discussed. The comprehensive and contemporary database of species-specific spatial occurrence (currently available on request) will be made directly available via the Malaria Atlas Project (MAP) website from early 2012.

Journal ArticleDOI
Georges Aad1, Brad Abbott2, Jalal Abdallah3, S. Abdel Khalek  +3081 moreInstitutions (197)
TL;DR: A combined search for the Standard Model Higgs boson with the ATLAS experiment at the LHC using datasets corresponding to integrated luminosities from 1.04 fb(-1) to 4.9 fb(1) of pp collisions is described in this paper.

Journal ArticleDOI
TL;DR: Transformation of the health system into a national institution that is based on equity and merit and is built on an effective human-resources system could still place South Africa on track to achieve Millennium Development Goals 4, 5, and 6 and would enhance the lives of its citizens.

Journal ArticleDOI
Georges Aad, B. Abbott1, Jalal Abdallah2, A. A. Abdelalim3  +3013 moreInstitutions (174)
TL;DR: In this article, detailed measurements of the electron performance of the ATLAS detector at the LHC were reported, using decays of the Z, W and J/psi particles.
Abstract: Detailed measurements of the electron performance of the ATLAS detector at the LHC are reported, using decays of the Z, W and J/psi particles. Data collected in 2010 at root s = 7 TeV are used, corresponding to an integrated luminosity of almost 40 pb(-1). The inter-alignment of the inner detector and the electromagnetic calorimeter, the determination of the electron energy scale and resolution, and the performance in terms of response uniformity and linearity are discussed. The electron identification, reconstruction and trigger efficiencies, as well as the charge misidentification probability, are also presented.

Journal ArticleDOI
TL;DR: AMG 145 administered every 4 weeks yielded rapid and substantial reductions in LDL-C in heterozygous familial hypercholesterolemia patients despite intensive statin use, with or without ezetimibe, with minimal adverse events and good tolerability.
Abstract: Background—Despite statin treatment, many patients with heterozygous familial hypercholesterolemia do not reach desired low-density lipoprotein cholesterol (LDL-C) targets. AMG 145, a fully human monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9) serine protease, demonstrated significant reductions in LDL-C in phase 1 studies. This phase 2, multicenter, double-blind, randomized, placebo-controlled, dose-ranging study evaluated the efficacy and safety of AMG 145 in heterozygous familial hypercholesterolemia patients. Methods and Results—Patients with heterozygous familial hypercholesterolemia diagnosed by Simon Broome criteria with LDL-C ≥2.6 mmol/L (100 mg/dL) despite statin therapy with or without ezetimibe were randomized 1:1:1 to AMG 145 350 mg, AMG 145 420 mg, or placebo-administered subcutaneously every 4 weeks. The primary end point was percentage change from baseline in LDL-C at week 12. Of 168 patients randomized, 167 received investigational product and were include...

Journal ArticleDOI
TL;DR: In this article, the authors used Cox proportional hazards regression and marginal structural modeling to assess the effect of contraceptive use on HIV-1 risk and found that women who used hormonal contraception had higher risk of acquiring HIV than those who did not.
Abstract: Summary Background Hormonal contraceptives are used widely but their effects on HIV-1 risk are unclear. We aimed to assess the association between hormonal contraceptive use and risk of HIV-1 acquisition by women and HIV-1 transmission from HIV-1-infected women to their male partners. Methods In this prospective study, we followed up 3790 heterosexual HIV-1-serodiscordant couples participating in two longitudinal studies of HIV-1 incidence in seven African countries. Among injectable and oral hormonal contraceptive users and non-users, we compared rates of HIV-1 acquisition by women and HIV-1 transmission from women to men. The primary outcome measure was HIV-1 seroconversion. We used Cox proportional hazards regression and marginal structural modelling to assess the effect of contraceptive use on HIV-1 risk. Findings Among 1314 couples in which the HIV-1-seronegative partner was female (median follow-up 18·0 [IQR 12·6–24·2] months), rates of HIV-1 acquisition were 6·61 per 100 person-years in women who used hormonal contraception and 3·78 per 100 person-years in those who did not (adjusted hazard ratio 1·98, 95% CI 1·06–3·68, p=0·03). Among 2476 couples in which the HIV-1-seronegative partner was male (median follow-up 18·7 [IQR 12·8–24·2] months), rates of HIV-1 transmission from women to men were 2·61 per 100 person-years in couples in which women used hormonal contraception and 1·51 per 100 person-years in couples in which women did not use hormonal contraception (adjusted hazard ratio 1·97, 95% CI 1·12–3·45, p=0·02). Marginal structural model analyses generated much the same results to the Cox proportional hazards regression. Interpretation Women should be counselled about potentially increased risk of HIV-1 acquisition and transmission with hormonal contraception, especially injectable methods, and about the importance of dual protection with condoms to decrease HIV-1 risk. Non-hormonal or low-dose hormonal contraceptive methods should be considered for women with or at-risk for HIV-1. Funding US National Institutes of Health and the Bill & Melinda Gates Foundation.

Journal ArticleDOI
Georges Aad1, Brad Abbott2, J. Abdallah3, S. Abdel Khalek4  +3073 moreInstitutions (193)
TL;DR: In this paper, a Fourier analysis of the charged particle pair distribution in relative azimuthal angle (Delta phi = phi(a)-phi(b)) is performed to extract the coefficients v(n,n) =.
Abstract: Differential measurements of charged particle azimuthal anisotropy are presented for lead-lead collisions at root sNN = 2.76 TeV with the ATLAS detector at the LHC, based on an integrated luminosity of approximately 8 mu b(-1). This anisotropy is characterized via a Fourier expansion of the distribution of charged particles in azimuthal angle relative to the reaction plane, with the coefficients v(n) denoting the magnitude of the anisotropy. Significant v(2)-v(6) values are obtained as a function of transverse momentum (0.5 = 3 are found to vary weakly with both eta and centrality, and their p(T) dependencies are found to follow an approximate scaling relation, v(n)(1/n)(p(T)) proportional to v(2)(1/2)(p(T)), except in the top 5% most central collisions. A Fourier analysis of the charged particle pair distribution in relative azimuthal angle (Delta phi = phi(a)-phi(b)) is performed to extract the coefficients v(n,n) = . For pairs of charged particles with a large pseudorapidity gap (|Delta eta = eta(a) - eta(b)| > 2) and one particle with p(T) < 3 GeV, the v(2,2)-v(6,6) values are found to factorize as v(n,n)(p(T)(a), p(T)(b)) approximate to v(n) (p(T)(a))v(n)(p(T)(b)) in central and midcentral events. Such factorization suggests that these values of v(2,2)-v(6,6) are primarily attributable to the response of the created matter to the fluctuations in the geometry of the initial state. A detailed study shows that the v(1,1)(p(T)(a), p(T)(b)) data are consistent with the combined contributions from a rapidity-even v(1) and global momentum conservation. A two-component fit is used to extract the v(1) contribution. The extracted v(1) isobserved to cross zero at pT approximate to 1.0 GeV, reaches a maximum at 4-5 GeV with a value comparable to that for v(3), and decreases at higher p(T).

Journal ArticleDOI
Georges Aad1, Georges Aad2, Brad Abbott2, Brad Abbott3  +5592 moreInstitutions (189)
TL;DR: The ATLAS trigger system as discussed by the authors selects events by rapidly identifying signatures of muon, electron, photon, tau lepton, jet, and B meson candidates, as well as using global event signatures, such as missing transverse energy.
Abstract: Proton-proton collisions at root s = 7 TeV and heavy ion collisions at root(NN)-N-s = 2.76 TeV were produced by the LHC and recorded using the ATLAS experiment's trigger system in 2010. The LHC is designed with a maximum bunch crossing rate of 40 MHz and the ATLAS trigger system is designed to record approximately 200 of these per second. The trigger system selects events by rapidly identifying signatures of muon, electron, photon, tau lepton, jet, and B meson candidates, as well as using global event signatures, such as missing transverse energy. An overview of the ATLAS trigger system, the evolution of the system during 2010 and the performance of the trigger system components and selections based on the 2010 collision data are shown. A brief outline of plans for the trigger system in 2011 is presented.

Journal ArticleDOI
01 Aug 2012-Sleep
TL;DR: This study corroborates the multifaceted nature of sleep problems, which is strongly linked to poorer general well-being and quality of life, and psychiatric comorbidities.
Abstract: OBJECTIVE:To estimate the prevalence of sleep problems and the effect of potential correlates in low-income settings from Africa and Asia, where the evidence is lacking. DESIGN: Cross-sectional. SETTING: Community-wide samples from 8 countries across Africa and Asia participating in the INDEPTH WHO-SAGE multicenter collaboration during 2006-2007. The participating sites included rural populations in Ghana, Tanzania, South Africa, India, Bangladesh, Vietnam, and Indonesia, and an urban area in Kenya. PARTICIPANTS: There were 24,434 women and 19,501 men age 50 yr and older. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Two measures of sleep quality, over the past 30 days, were assessed alongside a number of sociodemographic variables, measures of quality of life, and comorbidities. Overall, 16.6% of participants reported severe/extreme nocturnal sleep problems, with a striking variation across the 8 populations, ranging from 3.9% (Purworejo, Indonesia and Nairobi, Kenya) to more than 40.0% (Matlab, Bangladesh). There was a consistent pattern of higher prevalence of sleep problems in women and older age groups. In bivariate analyses, lower education, not living in partnership, and poorer self-rated quality of life were consistently associated with higher prevalence of sleep problems (P < 0.001). In multivariate logistic regression analyses, limited physical functionality or greater disability and feelings of depression and anxiety were consistently strong, independent correlates of sleep problems, in both women and men, across the 8 sites (P < 0.001). CONCLUSIONS: A large number of older adults in low-income settings are currently experiencing sleep problems, which emphasizes the global dimension of this emerging public health issue. This study corroborates the multifaceted nature of sleep problems, which are strongly linked to poorer general well-being and quality of life, and psychiatric comorbidities

Journal ArticleDOI
TL;DR: Efforts to enhance the research platform include using automated measurement techniques to estimate cause of death by verbal autopsy, full ‘reconciliation’ of in- and out-migrations, follow-up of migrants departing the study area, and optimizing public access to HDSS data are priorities.
Abstract: The Agincourt health and socio-demographic surveillance system (HDSS), located in rural northeast South Africa close to the Mozambique border, was established in 1992 to support district health systems development led by the post-apartheid ministry of health. The HDSS (90 000 people), based on an annual update of resident status and vital events, now supports multiple investigations into the causes and consequences of complex health, population and social transitions. Observational work includes cohorts focusing on different stages along the life course, evaluation of national policy at population, household and individual levels and examination of household responses to shocks and stresses and the resulting pathways influencing health and well-being. Trials target children and adolescents, including promoting psycho-social well-being, preventing HIV transmission and reducing metabolic disease risk. Efforts to enhance the research platform include using automated measurement techniques to estimate cause of death by verbal autopsy, full 'reconciliation' of in- and out-migrations, follow-up of migrants departing the study area, recording of extra-household social connections and linkage of individual HDSS records with those from sub-district clinics. Fostering effective collaborations (including INDEPTH multi-centre work in adult health and ageing and migration and urbanization), ensuring cross-site compatibility of common variables and optimizing public access to HDSS data are priorities.

Journal ArticleDOI
TL;DR: The concept of hegemonic masculinity has had a profound impact on gender activism and has been taken up particularly in health interventions as discussed by the authors, with a focus on relations between men, to the neglect of relations with women, paradoxically acknowledging the power that men had over women.
Abstract: The concept of hegemonic masculinity has had a profound impact on gender activism and has been taken up particularly in health interventions. The concept was part of a conceptual gendered vocabulary about men which opened up analytical space for research on masculinity and prompted a generation of gender interventions with men. Academic work focused primarily on relations between men, to the neglect of relations with women, while paradoxically acknowledging the power that men had over women. Interventions that drew on theories of masculinities focused on the content of hegemonic masculinity, identifying hegemony with oppressive attitudes and practices. Hegemonic masculinity was considered singular and universal, with little acknowledgment given to research-based work that argued for a model of multiple hegemonic masculinities. An unintended consequence of efforts to promote gender equity through a focus on men and hegemony has been a recent popular discursive backlash. In this, Jacob Zuma and Julius Malem...

Journal ArticleDOI
TL;DR: In this article, the authors explore, define, reconcile and depict corporate identity (CI), corporate brand (CB) and corporate reputation (CR) in a framework that reflects the dimensions of these constructs, discriminates between them and represents their inter-relatedness.
Abstract: Purpose – The main purpose of this paper is to explore, define, reconcile and depict corporate identity (CI), corporate brand (CB) and corporate reputation (CR) in a framework that reflects the dimensions of these constructs, discriminates between them and represents their inter‐relatedness. Design/methodology/approach – The paper draws on key literature relating to CI, CB and CR. Findings – The paper develops a framework that explains and aligns the drivers of CB and CR. Practical implications – Managers will be able to use the framework to help them align and optimise brand and reputation building efforts of their organisation. Academics will be able to use the framework as a basis for empirical research. Originality/value – The article reconciles disparate views from a number of theoretical streams that have investigated CI, CB and CR and develops a comprehensive framework that shows that although the management and measurement of the constructs may overlap, the constructs themselves are not interchangeable.

Journal ArticleDOI
TL;DR: This article analyzed sedimentary charcoal records to show that the changes in fire regime over the past 21,000 yrs are predictable from changes in regional climates and showed that fire increases monotonically with changes in temperature and peaks at intermediate moisture levels.
Abstract: Climate is an important control on biomass burning, but the sensitivity of fire to changes in temperature and moisture balance has not been quantified. We analyze sedimentary charcoal records to show that the changes in fire regime over the past 21,000 yrs are predictable from changes in regional climates. Analyses of paleo- fire data show that fire increases monotonically with changes in temperature and peaks at intermediate moisture levels, and that temperature is quantitatively the most important driver of changes in biomass burning over the past 21,000 yrs. Given that a similar relationship between climate drivers and fire emerges from analyses of the interannual variability in biomass burning shown by remote-sensing observations of month-by-month burnt area between 1996 and 2008, our results signal a serious cause for concern in the face of continuing global warming.

Journal ArticleDOI
TL;DR: Bedaquiline may contribute to the management of multidrug-resistant tuberculosis by effecting more rapid sputum culture negativity and by preventing acquired resistance to companion drugs.
Abstract: The 2-year follow-up results for a randomized placebo-controlled study of 47 patients with multidrug-resistant pulmonary tuberculosis treated with either the new diarylquinoline TMC207, recently renamed bedaquiline, or placebo, added to the first 8 weeks of a background regimen, are presented. Bedaquiline significantly reduced the time to culture conversion over 24 weeks (hazard ratio, 2.253; 95% confidence interval, 1.08 to 4.71; P = 0.031). With the exception of nausea reported in 26% of patients receiving bedaquiline and none receiving placebo, adverse events occurred at similar frequencies in both groups of patients: bilateral hearing impairment, extremity pain, acne, and noncardiac chest pain occurred in 13 and 21%, 17 and 13%, 9 and 17%, and 4 and 17% of patients, respectively, receiving bedaquiline or placebo. Excluding resistance to ethambutol and ethionamide, only one patient receiving bedaquiline acquired resistance to companion drugs, but five patients receiving placebo (4.8% versus 21.7%; P = 0.18) acquired resistance to companion drugs, and resistance to ofloxacin was acquired in four patients receiving placebo and none receiving bedaquiline (0% versus 22%; 0 = 0.066). In all, 23 patients (49%), including 13 receiving placebo (54%) and 10 receiving bedaquiline (44%), discontinued the study prior to its completion, 12 during the first 24 weeks of treatment. Eight subjects were withdrawn for noncompliance or default, and seven withdrew consent, citing the rigorous program of investigations for safety and pharmacokinetic monitoring. Bedaquiline may contribute to the management of multidrug-resistant tuberculosis by effecting more rapid sputum culture negativity and by preventing acquired resistance to companion drugs.

Journal ArticleDOI
TL;DR: In a prospective study, Craig Cohen and colleagues investigate the association between bacterial vaginosis and the risk of female-to-male HIV-1 transmission.
Abstract: Background Bacterial vaginosis (BV), a disruption of the normal vaginal flora, has been associated with a 60% increased risk of HIV-1 acquisition in women and higher concentration of HIV-1 RNA in the genital tract of HIV-1–infected women. However, whether BV, which is present in up to half of African HIV-1–infected women, is associated with an increase in HIV-1 transmission to male partners has not been assessed in previous studies. Methods and Findings We assessed the association between BV on female-to-male HIV-1 transmission risk in a prospective study of 2,236 HIV-1–seropositive women and their HIV-1 uninfected male partners from seven African countries from a randomized placebo-controlled trial that enrolled heterosexual African adults who were seropositive for both HIV-1 and herpes simplex virus (HSV)-2, and their HIV-1–seronegative partners. Participants were followed for up to 24 months; every three months, vaginal swabs were obtained from female partners for Gram stain and male partners were tested for HIV-1. BV and normal vaginal flora were defined as a Nugent score of 7–10 and 0–3, respectively. To reduce misclassification, HIV-1 sequence analysis of viruses from seroconverters and their partners was performed to determine linkage of HIV-1 transmissions. Overall, 50 incident HIV-1 infections occurred in men in which the HIV-1–infected female partner had an evaluable vaginal Gram stain. HIV-1 incidence in men whose HIV-1–infected female partners had BV was 2.91 versus 0.76 per 100 person-years in men whose female partners had normal vaginal flora (hazard ratio 3.62, 95% CI 1.74–7.52). After controlling for sociodemographic factors, sexual behavior, male circumcision, sexually transmitted infections, pregnancy, and plasma HIV-1 RNA levels in female partners, BV was associated with a greater than 3-fold increased risk of female-to-male HIV-1 transmission (adjusted hazard ratio 3.17, 95% CI 1.37–7.33). Conclusions This study identified an association between BV and increased risk of HIV-1 transmission to male partners. Several limitations may affect the generalizability of our results including: all participants underwent couples HIV counseling and testing and enrolled in an HIV-1 prevention trial, and index participants had a baseline CD4 count ≥250 cells/mm3 and were HSV-2 seropositive. Given the high prevalence of BV and the association of BV with increased risk of both female HIV-1 acquisition and transmission found in our study, if this association proves to be causal, BV could be responsible for a substantial proportion of new HIV-1 infections in Africa. Normalization of vaginal flora in HIV-1–infected women could mitigate female-to-male HIV-1 transmission. Trial Registration: ClinicalTrials.com NCT00194519 Please see later in the article for the Editors' Summary

Journal ArticleDOI
TL;DR: Qualitative interviews and ethnographic observation are used among 16 young women from the rural Eastern Cape to explore ways young women construct their femininities and exercise agency, providing potential for interventions with women that acknowledge existing gender inequalities, validate women's agency, reduce violence and prevent HIV.

Journal ArticleDOI
TL;DR: Reappraisal of radiocarbon age estimates through Bayesian modeling, and the identification of key elements of San material culture at Border Cave, places the emergence of modern hunter–gatherer adaptation, as the authors know it, to ∼44,000 y ago.
Abstract: Recent archaeological discoveries have revealed that pigment use, beads, engravings, and sophisticated stone and bone tools were already present in southern Africa 75,000 y ago. Many of these artifacts disappeared by 60,000 y ago, suggesting that modern behavior appeared in the past and was subsequently lost before becoming firmly established. Most archaeologists think that San hunter–gatherer cultural adaptation emerged 20,000 y ago. However, reanalysis of organic artifacts from Border Cave, South Africa, shows that the Early Later Stone Age inhabitants of this cave used notched bones for notational purposes, wooden digging sticks, bone awls, and bone points similar to those used by San as arrowheads. A point is decorated with a spiral groove filled with red ochre, which closely parallels similar marks that San make to identify their arrowheads when hunting. A mixture of beeswax, Euphorbia resin, and possibly egg, wrapped in vegetal fibers, dated to ∼40,000 BP, may have been used for hafting. Ornaments include marine shell beads and ostrich eggshell beads, directly dated to ∼42,000 BP. A digging stick, dated to ∼39,000 BP, is made of Flueggea virosa. A wooden poison applicator, dated to ∼24,000 BP, retains residues with ricinoleic acid, derived from poisonous castor beans. Reappraisal of radiocarbon age estimates through Bayesian modeling, and the identification of key elements of San material culture at Border Cave, places the emergence of modern hunter–gatherer adaptation, as we know it, to ∼44,000 y ago.

Journal ArticleDOI
TL;DR: It is shown, in two HIV-1–infected individuals who developed BCN antibodies targeting the glycan at Asn332 on the gp120 envelope, that this glycan was absent on the initial infecting virus, which highlights the dynamic interplay between early antibodies and viral escape in driving the evolution of conserved BCN antibody epitopes.
Abstract: Neutralizing antibodies are likely to play a crucial part in a preventative HIV-1 vaccine. Although efforts to elicit broadly cross-neutralizing (BCN) antibodies by vaccination have been unsuccessful, a minority of individuals naturally develop these antibodies after many years of infection. How such antibodies arise, and the role of viral evolution in shaping these responses, is unknown. Here we show, in two HIV-1-infected individuals who developed BCN antibodies targeting the glycan at Asn332 on the gp120 envelope, that this glycan was absent on the initial infecting virus. However, this BCN epitope evolved within 6 months, through immune escape from earlier strain-specific antibodies that resulted in a shift of a glycan to position 332. Both viruses that lacked the glycan at amino acid 332 were resistant to the Asn332-dependent BCN monoclonal antibody PGT128 (ref. 8), whereas escaped variants that acquired this glycan were sensitive. Analysis of large sequence and neutralization data sets showed the 332 glycan to be significantly under-represented in transmitted subtype C viruses compared to chronic viruses, with the absence of this glycan corresponding with resistance to PGT128. These findings highlight the dynamic interplay between early antibodies and viral escape in driving the evolution of conserved BCN antibody epitopes.

Journal ArticleDOI
TL;DR: A detailed phylogeny based on whole-genome sequencing of representative strains of C. trachomatis from both trachoma and lymphogranuloma venereum biovars from temporally and geographically diverse sources shows that predicting phylogenetic structure using ompA, which is traditionally used to classify Chlamydia, is misleading because extensive recombination in this region masks any true relationships present.
Abstract: Chlamydia trachomatis is responsible for both trachoma and sexually transmitted infections, causing substantial morbidity and economic cost globally. Despite this, our knowledge of its population and evolutionary genetics is limited. Here we present a detailed phylogeny based on whole-genome sequencing of representative strains of C. trachomatis from both trachoma and lymphogranuloma venereum (LGV) biovars from temporally and geographically diverse sources. Our analysis shows that predicting phylogenetic structure using ompA, which is traditionally used to classify Chlamydia, is misleading because extensive recombination in this region masks any true relationships present. We show that in many instances, ompA is a chimera that can be exchanged in part or as a whole both within and between biovars. We also provide evidence for exchange of, and recombination within, the cryptic plasmid, which is another key diagnostic target. We used our phylogenetic framework to show how genetic exchange has manifested itself in ocular, urogenital and LGV C. trachomatis strains, including the epidemic LGV serotype L2b.

Proceedings Article
01 Jul 2012
TL;DR: An overview of fabrication processes, area of application, some recent research studies and the need to focus more research effort on improving the most promising FGM fabrication method (solid freeform SFF) is presented.
Abstract: Proceedings of the World Congress on Engineering 2012 Vol III (WCE 2012), London, UK, 4-6 July 2012