Mechanisms linking intimate partner violence and prevention of mother-to-child transmission of HIV: A qualitative study in South Africa.

: Prevention of mother-to-child transmission (PMTCT) can virtually eliminate HIV infection among infants, yet up to one-third of women miss PMTCT steps. Little is known about how partner dynamics such as intimate partner violence (IPV) influence pregnant and postpartum women's adherence to PMTCT. We conducted 32 qualitative interviews with HIV-positive pregnant and postpartum women in Johannesburg who experienced IPV. Trained researchers conducted in-depth interviews over the period of May 2014-Nov 2015 using narrative and social constructionist approaches. Interviews were transcribed verbatim and analyzed thematically and inductively using Dedoose qualitative software. Twenty-six women experienced recent IPV and one-third had poor adherence to PMTCT. Women's experience of partner violence influenced PMTCT behaviors through four pathways. First, fear of partner disclosure led some women to hide their HIV status to avoid a violent reaction. Despite strategic non-disclosure, several maintained good adherence by hiding medication or moving out from their partner's home. Second, IPV caused feelings of depression and anxiety that led to intentionally or accidentally missing medication. Five women stopped treatment altogether, in a type of passive suicidality, hoping to end the distress of IPV. Third, men's controlling behaviors reduced access to friends and family, limiting social support needed for good adherence. Fourth, in a protective pathway, women reported good adherence partly due to their mothering role. The identity around motherhood was used as a coping technique, reminding women that their infant's wellbeing depended on their own health. PMTCT is essential to prevent vertical HIV transmission, but women living with IPV face multiple pathways to non-adherence. Addressing IPV in antenatal care can support the health of women and infants and may enhance PMTCT coverage.<br/

Brain penetrant LRRK2 inhibitor

This is the author accepted manuscript. The final version is available from ACS via the DOI in this record. Activating mutations in leucine-rich repeat kinase 2 (LRRK2) are present in a subset of Parkinson's disease (PD) patients and may represent an attractive therapeutic target. Here, we report that a 2-anilino-4-methylamino-5- chloropyrimidine, HG-10-102-01 (4), is a potent and selective inhibitor of wild-type LRRK2 and the G2019S mutant. Compound 4 substantially inhibits Ser910 and Ser935 phosphorylation of both wild-type LRRK2 and G2019S mutant at a concentration of 0.1-0.3 μM in cells and is the first compound reported to be capable of inhibiting Ser910 and Ser935 phosphorylation in mouse brain following intraperitoneal delivery of doses as low as 50 mg/kg. © 2012 American Chemical Society.NIHMedical Research CouncilMichael J Fox foundation for Parkinson’s disease researchPharmaceutical companies supporting the DSTT (AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck KgaA and Pfizer

Sex differences in mathematics and reading achievement are inversely related: within- and across-nation assessment of 10 years of PISA data

We analyzed one decade of data collected by the Programme for International Student Assessment (PISA), including the mathematics and reading performance of nearly 1.5 million 15 year olds in 75 countries. Across nations, boys scored higher than girls in mathematics, but lower than girls in reading. The sex difference in reading was three times as large as in mathematics. There was considerable variation in the extent of the sex differences between nations. There are countries without a sex difference in mathematics performance, and in some countries girls scored higher than boys. Boys scored lower in reading in all nations in all four PISA assessments (2000, 2003, 2006, 2009). Contrary to several previous studies, we found no evidence that the sex differences were related to nations’ gender equality indicators. Further, paradoxically, sex differences in mathematics were consistently and strongly inversely correlated with sex differences in reading: Countries with a smaller sex difference in mathematics had a larger sex difference in reading and vice versa. We demonstrate that this was not merely a between-nation, but also a within-nation effect. This effect is related to relative changes in these sex differences across the performance continuum: We did not find a sex difference in mathematics among the lowest performing students, but this is where the sex difference in reading was largest. In contrast, the sex difference in mathematics was largest among the higher performing students, and this is where the sex difference in reading was smallest. The implication is that if policy makers decide that changes in these sex differences are desired, different approaches will be needed to achieve this for reading and mathematics. Interventions that focus on high-achieving girls in mathematics and on low achieving boys in reading are likely to yield the strongest educational benefits

M-Branes and Metastable States

We study a supersymmetry breaking deformation of the M-theory background found in arXiv:hep-th/0012011. The supersymmetric solution is a warped product of R^{2,1} and the 8-dimensional Stenzel space, which is a higher dimensional generalization of the deformed conifold. At the bottom of the warped throat there is a 4-sphere threaded by \tilde{M} units of 4-form flux. The dual (2+1)-dimensional theory has a discrete spectrum of bound states. We add p anti-M2 branes at a point on the 4-sphere, and show that they blow up into an M5-brane wrapping a 3-sphere at a fixed azimuthal angle on the 4-sphere. This supersymmetry breaking state turns out to be metastable for p / \tilde{M} < 0.054. We find a smooth O(3)-symmetric Euclidean bounce solution in the M5-brane world volume theory that describes the decay of the false vacuum. Calculation of the Euclidean action shows that the metastable state is extremely long-lived. We also describe the corresponding metastable states and their decay in the type IIA background obtained by reduction along one of the spatial directions of R^{2,1}.Comment: 33 pages, 5 figures; v2 note adde

On the curvature of vortex moduli spaces

We use algebraic topology to investigate local curvature properties of the moduli spaces of gauged vortices on a closed Riemann surface. After computing the homotopy type of the universal cover of the moduli spaces (which are symmetric powers of the surface), we prove that, for genus g>1, the holomorphic bisectional curvature of the vortex metrics cannot always be nonnegative in the multivortex case, and this property extends to all Kaehler metrics on certain symmetric powers. Our result rules out an established and natural conjecture on the geometry of the moduli spaces.Comment: 25 pages; final version, to appear in Math.

The role of P2X7 in pain and inflammation

The P2X7 purinoceptor is unique amongst the P2X receptor family in that its activation is able to stimulate the release of mature, biologically active interleukin-1β (IL-1β), as well as a variety of other proinflammatory cytokines. Coupled with the predominate localisation of this receptor to immunocytes of haemopoetic origin, this receptor is an obvious candidate to play a major and pivotal role in processes of pain and inflammation. Using genetically modified animals that lack the P2X7 receptor, several investigators have shown that these mice do indeed demonstrate a blunted inflammatory response, and fail to develop pain following both inflammatory and neuropathic insult. These animals also show altered cytokine production in response to inflammatory stimulus, which is far broader than merely modulation of IL-1β release. In this short article, we review the role of the P2X7 receptor in modulating the release of cytokines and other mediators, and discuss the findings made from P2X7 receptor-deficient animals. As well as highlighting outstanding questions regarding this intriguing receptor, we also speculate as to the potential therapeutic benefit of P2X7 receptor modulation

Environmental Determinants of the Distribution and Abundance of the Ants, Lasiophanes picinus and L. valdiviensis, in Argentina

The distribution and abundance variation of the terrestrial ants, Lasiophanes picinus and Lasiophanes valdiviensis Emery (Formicinae: Lasiini), which are endemic in Patagonia (Argentina and Chile), are described and a set of environmental factors are examined to explain the observed patterns. Ants were collected using 450 pitfall traps arranged in 50, 100 m2 grid plots each with nine traps within a roughly 150 × 150 km area representative of the subantartic-patagonian transition of Argentina. Five sampling periods each 8-days long were carried out between November 2004 and March 2006. To understand the distributional patterns and their link to environmental variables discriminant analysis was used. Path analysis was performed to test for direct and indirect effects of a set of environmental variables on species abundance variation. L. picinus was more frequently captured and attained higher abundance in the forests, while L. valdiviensis was more frequently captured and more abundant in the scrubs. The maximum daily temperature and mean annual precipitation explained L. picinus distribution (i.e. presence or absence) with an accuracy of 90%. L. valdiviensis distribution was predicted with almost 70% accuracy, taking into account herbal richness. The maximum daily temperature was the only climatic variable that affected ant abundance directly; an increase in temperature led to an increase of L. picinus abundance and a decrease of L. valdiviensis abundance. The amount of resources, as indicated by the percent plant cover, explained the variation of the abundance of both species better than the variety of resources as indicated by plant richness (i.e. models including plant richness had low fit or no fit at all). A direct effect of habitat use by cattle was found, as indicated by the amount of feces in the plots, only when variables related to the amount of resources were replaced by variables with less explanatory power related to the variety of resources. This study provides new data on the ecology of Lasiophanes species in relation to existing hypotheses proposed to explain patterns of abundance variation. Evidence is provided that changes in temperature (i.e. global climate change) may have important consequences on populations of these species

Time-resolved single-crystal X-ray crystallography

In this chapter the development of time-resolved crystallography is traced from its beginnings more than 30 years ago. The importance of being able to “watch” chemical processes as they occur rather than just being limited to three-dimensional pictures of the reactant and final product is emphasised, and time-resolved crystallography provides the opportunity to bring the dimension of time into the crystallographic experiment. The technique has evolved in time with developments in technology: synchrotron radiation, cryoscopic techniques, tuneable lasers, increased computing power and vastly improved X-ray detectors. The shorter the lifetime of the species being studied, the more complex is the experiment. The chapter focusses on the results of solid-state reactions that are activated by light, since this process does not require the addition of a reagent to the crystalline material and the single-crystalline nature of the solid may be preserved. Because of this photoactivation, time-resolved crystallography is often described as “photocrystallography”. The initial photocrystallographic studies were carried out on molecular complexes that either underwent irreversible photoactivated processes where the conversion took hours or days. Structural snapshots were taken during the process. Materials that achieved a metastable state under photoactivation and the excited (metastable) state had a long enough lifetime for the data from the crystal to be collected and the structure solved. For systems with shorter lifetimes, the first time-resolved results were obtained for macromolecular structures, where pulsed lasers were used to pump up the short lifetime excited state species and their structures were probed by using synchronised X-ray pulses from a high-intensity source. Developments in molecular crystallography soon followed, initially with monochromatic X-ray radiation, and pump-probe techniques were used to establish the structures of photoactivated molecules with lifetimes in the micro- to millisecond range. For molecules with even shorter lifetimes in the sub-microsecond range, Laue diffraction methods (rather than using monochromatic radiation) were employed to speed up the data collections and reduce crystal damage. Future developments in time-resolved crystallography are likely to involve the use of XFELs to complete “single-shot” time-resolved diffraction studies that are already proving successful in the macromolecular crystallographic field.</p