Timing of antiretroviral therapy initiation in adults with HIV-associated tuberculosis: Outcomes of therapy in an urban hospital in KwaZulu-Natal

Background. HIV-associated tuberculosis (TB) is common in South Africa. The optimal time for initiating antiretroviral therapy (ART) in co-infected patients is a clinical challenge.Aim. We aimed to compare clinical outcomes of patients with HIV-associated TB who commenced ART at different stages of TB therapy.Methods. A retrospective chart review was conducted of 458 patients who initiated ART at .28 days (immediate), 29 - 56 days (early) and .57 days (delayed) after commencing TB therapy, and clinical outcomes after 6 months of ART were compared.Results. There was a higher mortality in the immediate group, although this was not significant. Renal impairment (hazard ratio (HR) 2.5; 95% confidence interval (CI) 1.3 - 4.9; p=0.004) and inpatient ART initiation (HR 3.7; 95% CI 1.6 - 8.2; p=0.001) were risk factors for HIVassociatedTB mortality. A baseline haemoglobin concentration .10 g/dl (HR 0.2; 95% CI 0.1 - 0.6; p=0.003), extrapulmonary as opposed to pulmonary TB (PTB) (HR 0.3; 95% CI 0.1 - 0.7; p=0.005) and extrapulmonary plus PTB as opposed to PTB (HR 0.3, 95% CI 0.1 - 0.6; p=0.002) were significantly associated with decreased mortality.Conclusion. The timing of initiation of ART after commencing TB therapy was not significantly associated with increased mortality or survival. Patients with more advanced disease were more likely to die. Early HIV testing and ART initiation is recommended to decrease mortality

Vertical Convergence of Turbulent and Double-Diffusive Heat Flux Drives Warming and Erosion of Antarctic Winter Water in Summer

The seasonal warming of Antarctic Winter Water (WW) is a key process that occurs along the path of deep water transformation to intermediate waters. These intermediate waters then enter the upper branch of the circumpolar overturning circulation. Despite its importance, the driving mechanisms that mediate the warming of Antarctic WW remain unknown, and their quantitative evaluation is lacking. Using 38 days of glider measurements of microstructure shear, we characterize the rate of turbulent dissipation and its drivers over a summer season in the northern Weddell Sea. Observed dissipation rates in the surface layer are mainly forced by winds and explained by the stress scaling (r2 = 0.84). However, mixing to the base of the mixed layer during strong wind events is suppressed by vertical stratification from sea ice melt. Between the WW layer and the warm and saline circumpolar deep water, a subsurface layer of enhanced dissipation is maintained by double-diffusive convection (DDC). We develop a WW layer temperature budget and show that a warming trend (0.2°C over 28 days) is driven by a convergence of heat flux through mechanically driven mixing at the base of the mixed layer and DDC at the base of the WW layer. Notably, excluding the contribution from DDC results in an underestimation of WW warming by 23%, highlighting the importance of adequately representing DDC in ocean models. These results further suggest that an increase in storm intensity and frequency during summer could increase the rate of warming of WW with implications for rates of upper-ocean water mass transformation.publishedVersio

Stirring of sea ice meltwater enhances submesoscale fronts in the Southern Ocean

In the sea ice-impacted Southern Ocean, the spring melt of sea ice modifies the upper ocean. These modified waters subduct and enter the global overturning circulation. Submesoscale processes act to modulate the stratification of the mixed layer and therefore mixed layer properties. Sparse observations mean that the role of submesoscales in exchange across the base of the mixed layer in this region is not well constrained. The goal of this study is to determine the interplay between sea ice melt, surface boundary layer forcing, and submesoscale flows in regulating the mixed layer structure in the Antarctic Marginal Ice Zone. High-resolution observations suggest that fine-scale lateral fronts, representative of submesoscale mixed layer eddies (MLEs), arise from mesoscale gradients produced by northwards advecting sea ice meltwater. The strong salinity-driven stratification at the base of the mixed layer confined the MLEs to the upper ocean, limiting submesoscale vertical fluxes across the mixed layer base. This strong stratification prevents the local subduction by submesoscale flow of these modified waters, suggesting that the subduction site that links to the global overturning circulation does not correspond with the location of sea ice melt. However, the presence of MLEs enhanced the magnitude of lateral gradients through stirring and increased the potential for Ekman-driven cross-frontal flow to modulate the stability of the mixed layer and mixed layer properties. The inclusion, particularly of submesoscale Ekman Buoyancy Flux parameterizations, in coupled-climate models, may improve the representation of mixed layer heat and freshwater transport in the ice-impacted Southern Ocean during summer

Stirring of Sea‐Ice Meltwater Enhances Submesoscale Fronts in the Southern Ocean

In the sea‐ice‐impacted Southern Ocean, the spring sea‐ice melt and its impact on physical processes set the rate of surface water mass modification. These modified waters will eventually subduct near the polar front and enter the global overturning circulation. Submesoscale processes modulate the stratification of the mixed layer (ML) and ML properties. Sparse observations in polar regions mean that the role of submesoscale motions in the exchange of properties across the base of the ML is not well understood. The goal of this study is to determine the interplay between sea‐ice melt, surface boundary layer forcing, and submesoscale flows in setting properties of the surface ML in the Antarctic marginal ice zone. High‐resolution observations suggest that fine‐scale lateral fronts arise from either/both mesoscale and submesoscale stirring of sea‐ice meltwater anomalies. The strong salinity‐driven stratification at the base of the ML confines these fronts to the upper ocean, limiting submesoscale vertical fluxes across the ML base. This strong stratification prevents the local subduction of modified waters by submesoscale flows, suggesting that the subduction site that links to the global overturning circulation does not correspond with the location of sea‐ice melt. However, surface‐enhanced fronts increase the potential for Ekman‐driven cross‐frontal flow to modulate the stability of the ML and ML properties. The parameterization of submesoscale processes in coupled‐climate models, particularly those contributing to the Ekman buoyancy flux, may improve the representation of ML heat and freshwater transport in the ice‐impacted Southern Ocean during summer

The "ART" of Linkage: Pre-Treatment Loss to Care after HIV Diagnosis at Two PEPFAR Sites in Durban, South Africa

BACKGROUND. Although loss to follow-up after antiretroviral therapy (ART) initiation is increasingly recognized, little is known about pre-treatment losses to care (PTLC) after an initial positive HIV test. Our objective was to determine PTLC in newly identified HIV-infected individuals in South Africa. METHODOLOGY/PRINCIPAL FINDINGS. We assembled the South African Test, Identify and Link (STIAL) Cohort of persons presenting for HIV testing at two sites offering HIV and CD4 count testing and HIV care in Durban, South Africa. We defined PTLC as failure to have a CD4 count within 8 weeks of HIV diagnosis. We performed multivariate analysis to identify factors associated with PTLC. From November 2006 to May 2007, of 712 persons who underwent HIV testing and received their test result, 454 (64%) were HIV-positive. Of those, 206 (45%) had PTLC. Infected patients were significantly more likely to have PTLC if they lived =10 kilometers from the testing center (RR=1.37; 95% CI: 1.11-1.71), had a history of tuberculosis treatment (RR=1.26; 95% CI: 1.00-1.58), or were referred for testing by a health care provider rather than self-referred (RR=1.61; 95% CI: 1.22-2.13). Patients with one, two or three of these risks for PTLC were 1.88, 2.50 and 3.84 times more likely to have PTLC compared to those with no risk factors. CONCLUSIONS/SIGNIFICANCE. Nearly half of HIV-infected persons at two high prevalence sites in Durban, South Africa, failed to have CD4 counts following HIV diagnosis. These high rates of pre-treatment loss to care highlight the urgent need to improve rates of linkage to HIV care after an initial positive HIV test.US National Institute of Allergy and Infectious Diseases (R01 AI058736, K24 AI062476, K23 AI068458); the Harvard University Center for AIDS Research (P30 AI42851); National Institutes of Health (K24 AR 02123); the Doris Duke Charitable Foundation (Clinical Scientist Development Award); the Harvard University Program on AID

Hyper-Raman scattering analysis of the vibrations in vitreous boron oxide

Hyper-Raman scattering has been measured on vitreous boron oxide, $v-$B$_2$O$_3$. This spectroscopy, complemented with Raman scattering and infrared absorption, reveals the full set of vibrations that can be observed with light. A mode analysis is performed based on the local D$_{3h}$ symmetry of BO$_3$ triangles and B$_3$O$_3$ boroxol rings. The results show that in $v-$B$_2$O$_3$ the main spectral components can be succesfully assigned using this relatively simple model. In particular, it can be shown that the hyper-Raman boson peak arises from external modes that correspond mainly to librational motions of rigid boroxol rings.Comment: 13 pages, 11 figures, 2 table

Reproductive Decision-Making and Periconception Practices Among HIV-Positive Men and Women Attending HIV Services in Durban, South Africa

Understanding reproductive decisions and periconception behavior among HIV-discordant couples is important for designing risk reduction interventions for couples who choose to conceive. In-depth interviews were conducted to explore reproductive decision-making and periconception practices among HIV-positive women with recent pregnancy (n = 30), and HIV-positive men (n = 20), all reporting partners of negative or unknown HIV-status, and attending HIV services in Durban, South Africa. Transcripts were coded for categories and emergent themes. Participants expressed strong reasons for having children, but rarely knew how to reduce periconception HIV transmission. Pregnancy planning occurred on a spectrum ranging from explicitly intended to explicitly unintended, with many falling in between the two extremes. Male fertility desire and misunderstanding serodiscordance contributed to HIV risk behavior. Participants expressed openness to healthcare worker advice for safer conception and modified risk behavior post-conception, suggesting the feasibility of safer conception interventions which may target both men and women and include serodiscordance counseling and promotion of contraception

Predictors of mortality in patients initiating antiretroviral therapy in Durban, South Africa

Objective. To identify predictors of mortality in patients initiating antiretroviral therapy (ART) in Durban, South Africa. Design. We conducted a retrospective cohort study analysing data on patients who presented to McCord Hospital, Durban, and started ART between 1 January 1999 and 29 February 2004. We performed univariate and multivariate analysis and constructed Kaplan-Meier curves to assess predictors. Results. Three hundred and nine patients were included. Forty-nine (16%) had died by the conclusion of the study. In univariate analysis, the strongest predictors of mortality were a CD4 cell coun

Outcomes of the South African National Antiretroviral Treatment Programme for children: The IeDEA Southern Africa collaboration

Objectives. To assess paediatric antiretroviral treatment (ART)outcomes and their associations from a collaborative cohortrepresenting 20% of the South African national treatment programme.Design and setting. Multi-cohort study of 7 public sectorpaediatric ART programmes in Gauteng, Western Cape andKwaZulu-Natal provinces. Subjects. ART-naive children (.16 years) who commenced treatment with .3 antiretroviral drugs before March 2008.Outcome measures. Time to death or loss to follow-up were assessed using the Kaplan-Meier method. Associations between baseline characteristics and mortality were assessed with Cox proportional hazards models stratified by site. Immune status, virological suppression and growth were described in relation to duration of ART.Results. The median (interquartile range) age of 6 078 childrenwith 9 368 child-years of follow-up was 43 (15 - 83) months, with 29% bein

Finite strain Landau theory of high pressure phase transformations

The properties of materials near structural phase transitions are often successfully described in the framework of Landau theory. While the focus is usually on phase transitions, which are induced by temperature changes approaching a critical temperature T-c, here we will discuss structural phase transformations driven by high hydrostatic pressure, as they are of major importance for understanding processes in the interior of the earth. Since at very high pressures the deformations of a material are generally very large, one needs to apply a fully nonlinear description taking physical as well as geometrical nonlinearities (finite strains) into account. In particular it is necessary to retune conventional Landau theory to describe such phase transitions. In Troster et al (2002 Phys. Rev. Lett. 88 55503) we constructed a Landau-type free energy based on an order parameter part, an order parameter-(finite) strain coupling and a nonlinear elastic term. This model provides an excellent and efficient framework for the systematic study of phase transformations for a wide range of materials up to ultrahigh pressures