Impact and Cost-Effectiveness of Point-Of-Care CD4 Testing on the HIV Epidemic in South Africa.

Rapid diagnostic tools have been shown to improve linkage of patients to care. In the context of infectious diseases, assessing the impact and cost-effectiveness of such tools at the population level, accounting for both direct and indirect effects, is key to informing adoption of these tools. Point-of-care (POC) CD4 testing has been shown to be highly effective in increasing the proportion of HIV positive patients who initiate ART. We assess the impact and cost-effectiveness of introducing POC CD4 testing at the population level in South Africa in a range of care contexts, using a dynamic compartmental model of HIV transmission, calibrated to the South African HIV epidemic. We performed a meta-analysis to quantify the differences between POC and laboratory CD4 testing on the proportion linking to care following CD4 testing. Cumulative infections averted and incremental cost-effectiveness ratios (ICERs) were estimated over one and three years. We estimated that POC CD4 testing introduced in the current South African care context can prevent 1.7% (95% CI: 0.4% - 4.3%) of new HIV infections over 1 year. In that context, POC CD4 testing was cost-effective 99.8% of the time after 1 year with a median estimated ICER of US$4,468/DALY averted. In healthcare contexts with expanded HIV testing and improved retention in care, POC CD4 testing only became cost-effective after 3 years. The results were similar when, in addition, ART was offered irrespective of CD4 count, and CD4 testing was used for clinical assessment. Our findings suggest that even if ART is expanded to all HIV positive individuals and HIV testing efforts are increased in the near future, POC CD4 testing is a cost-effective tool, even within a short time horizon. Our study also illustrates the importance of evaluating the potential impact of such diagnostic technologies at the population level, so that indirect benefits and costs can be incorporated into estimations of cost-effectiveness

Critical phenomena in a highly constrained classical spin system: Neel ordering from the Coulomb phase

Many classical, geometrically frustrated antiferromagnets have macroscopically degenerate ground states. In a class of three-dimensional systems, the set of degenerate ground states has power-law correlations and is an example of a Coulomb phase. We investigate Neel ordering from such a Coulomb phase, induced by weak additional interactions that lift the degeneracy. We show that the critical point belongs to a universality class that is different from the one for the equivalent transition out of the paramagnetic phase, and that it is characterised by effective long-range interactions; alternatively, ordering may be discontinuous. We suggest that a transition of this type may be realised by applying uniaxial stress to a pyrochlore antiferromagnet.Comment: 4 pages, 3 figure

Calibration update of the COMBO-17 CDFS catalogue

We present an update to the photometric calibration of the COMBO-17 catalogue on the Extended Chandra Deep Field South, which is now consistent with the GaBoDS and MUSYC catalogues. As a result, photometric redshifts become slightly more accurate, with <0.01 rms and little bias in the delta_z/(1+z) of galaxies with R<21 and of QSOs with R<24. With increasing photon noise the rms of galaxies reaches 0.02 for R<23 and 0.035 at R~23.5. Consequences for the rest-frame colours of galaxies at z<1 are discussed.Comment: A&A research note, resubmitted 02 Oct 2008, 4 pages in print forma

Predictions of children’s emotionality from evolutionary and epigenetic hypotheses

Sex-dependent effects of mismatched prenatal-postnatal maternal conditions are predicted by combining two evolutionary hypotheses: that foetal conditions provide a forecast of likely postnatal environments (Predictive Adaptive Response), and that the female foetus is better adapted than the male to maternal adversity (Trivers-Willard hypothesis). Animal studies have implicated glucocorticoid mechanisms modifiable by effects of postnatal tactile stimulation on glucocorticoid receptor gene expression. In this study we examined behavioural predictions in humans based on these evolutionary and epigenetic models. Mothers in a general population cohort provided self-reported anxiety scores at 20 weeks pregnancy, and at 9 weeks, 14 months and 3.5 years postpartum, and frequency of infant stroking at 9 weeks. Mothers and teachers reported child symptoms at 7 years. SEM models with maximum-likelihood estimates made use of data from 887 participants. There was a three-way interaction between prenatal and postnatal anxiety and maternal stroking in the prediction of irritability, seen only in girls. This arose because lower maternal stroking was associated with higher irritability, only in the mismatched, low-high and high-low maternal anxiety groups. We provide evidence that mechanisms likely to have evolved well before the emergence of humans, contribute to the development of children’s emotionality and risk for depression

On the secondary star of the cataclysmic variable 1RXS J094432.1+035738

We present V and Rc band photometry and optical near-infrared spectroscopy of the cataclysmic variable 1RXS J094432.1+035738. We detected features of a cool secondary star, which can be modeled with a red dwarf of spectral type M2 (+0.5 -1.0) V at a distance of 433 +- 100 pc.Comment: Accepted for publication in Astronomy and Astrophysic

SARS-CoV replication and pathogenesis in an in vitro model of the human conducting airway epithelium

SARS coronavirus (SARS-CoV) emerged in 2002 as an important cause of severe lower respiratory tract infection in humans and in vitro models of the lung are needed to elucidate cellular targets and the consequences of viral infection. The severe and sudden onset of symptoms, resulting in an atypical pneumonia with dry cough and persistent high fever in cases of severe acute respiratory virus brought to light the importance of coronaviruses as potentially lethal human pathogens and the identification of several zoonotic reservoirs has made the reemergence of new strains and future epidemics all the more possible. In this chapter, we describe the pathology of SARS-CoV infection in humans and explore the use of two models of the human conducting airway to develop a better understanding of the replication and pathogenesis of SARS-CoV in relevant in vitro systems. The first culture model is a human bronchial epithelial cell line Calu3 that can be inoculated by viruses either as a non-polarized monolayer of cells or polarized cells with tight junctions and microvilli. The second model system, derived from primary cells isolated from human airway epithelium and grown on Transwells, form a pseudostratified mucociliary epithelium that recapitulates the morphological and physiological features of the human conducting airway in vivo. Experimental results using these lung epithelial cell models demonstrate that in contrast to the pathology reported in late stage cases SARS-CoV replicates to high titers in epithelial cells of the conducting airway. The SARS-CoV receptor, human angiotensin 1 converting enzyme 2 (hACE2), was detected exclusively on the apical surface of cells in polarized Calu3 cells and human airway epithelial cultures (HAE), indicating that hACE2 was accessible by SARS-CoV after airway lumenal delivery. Furthermore, in HAE, hACE2 was exclusively localized to ciliated airway epithelial cells. In support of the hACE2 localization data, the most productive route of inoculation and progeny virion egress in both polarized Calu3 and ciliated cells of HAE was the apical surface suggesting mechanisms to release large quantities of virus into the lumen of the human lung. Preincubation of the apical surface of cultures with antisera directed against hACE2 reduced viral titers by 2 logs while antisera against DC-SIGN/DC-SIGNR did not reduce viral replication levels suggesting that hACE2 is the primary receptor for entry of SARS-CoV into the ciliated cells of HAE cultures. To assess infectivity in ciliated airway cultures derived from susceptible animal species we generated a recombinant SARS-CoV by deletion of open reading frame 7a/7b (ORF 7a/b) and insertion of the green fluorescent protein (GFP) resulting in SARS-CoV GFP. SARS-CoV GFP replicated to similar titers as wild type viruses in Vero E6, MA104, and CaCo2 cells. In addition, SARS-CoV replication in airway epithelial cultures generated from Golden Syrian hamster tracheas reached similar titers to the human cultures by 72 hours post infection. Efficient SARS-CoV infection of ciliated cell-types in HAE provides a useful in vitro model of human lung origin to study characteristics of SARS-CoV replication and pathogenesis

The strong coupling constant from lattice QCD with N_f=2 dynamical quarks

We compute $\Lambda_{\bar{MS}}$ for two flavors of light dynamical quarks using non-perturbatively $O(a)$ improved Wilson fermions. We improve on a recent calculation by employing Pad\'e-improved two-loop and three-loop perturbation theory to convert the lattice numbers to the $\bar{MS}$ scheme.Comment: Contribution to Lattice 2001 (matrix elements), typo correcte

On the master equation approach to diffusive grain-surface chemistry: the H, O, CO system

We have used the master equation approach to study a moderately complex network of diffusive reactions occurring on the surfaces of interstellar dust particles. This network is meant to apply to dense clouds in which a large portion of the gas-phase carbon has already been converted to carbon monoxide. Hydrogen atoms, oxygen atoms, and CO molecules are allowed to accrete onto dust particles and their chemistry is followed. The stable molecules produced are oxygen, hydrogen, water, carbon dioxide (CO2), formaldehyde (H2CO), and methanol (CH3OH). The surface abundances calculated via the master equation approach are in good agreement with those obtained via a Monte Carlo method but can differ considerably from those obtained with standard rate equations.Comment: 13 pages, 5 figure

Associations between maternal prenatal cortisol and fetal growth are specific to infant sex: findings from the Wirral Child Health and Development Study

Recent findings highlight that there are prenatal risks for affective disorders that are mediated by glucocorticoid mechanisms, and may be specific to females. There is also evidence of sex differences in prenatal programming mechanisms and developmental psychopathology, whereby effects are in opposite directions in males and females. As birth weight is a risk for affective disorders, we sought to investigate whether maternal prenatal cortisol may have sex-specific effects on fetal growth. Participants were 241 mothers selected from the Wirral Child Health and Development Study (WCHADS) cohort (n=1233) using a psychosocial risk stratifier, so that responses could be weighted back to the general population. Mothers provided saliva samples, which were assayed for cortisol, at home over 2 days at 32 weeks gestation (on waking, 30-min post-waking and during the evening). Measures of infant birth weight (corrected for gestational age) were taken from hospital records. General population estimates of associations between variables were obtained using inverse probability weights. Maternal log of the area under the curve cortisol predicted infant birth weight in a sex-dependent manner (interaction term P=0.029). There was a positive and statistically significant association between prenatal cortisol in males, and a negative association in females that was not statistically significant. A sex interaction in the same direction was evident when using the waking (P=0.015), and 30-min post-waking (P=0.013) cortisol, but not the evening measure. There was no interaction between prenatal cortisol and sex to predict gestational age. Our findings add to an emerging literature that suggests that there may be sex-specific mechanisms that underpin fetal programming