Uptake of Home-Based HIV Testing,Linkage to Care,and Community Attitudes about ART in Rural KwaZulu-Natal,South Africa: Descriptive Results from the First Phase of the ANRS 12249 TasP Cluster-Randomised Trial

BackgroundThe 2015 WHO recommendation of antiretroviral therapy (ART) for all immediately following HIV diagnosis is partially based on the anticipated impact on HIV incidence in the surrounding population. We investigated this approach in a cluster-randomised trial in a high HIV prevalence setting in rural KwaZulu-Natal. We present findings from the first phase of the trial and report on uptake of home-based HIV testing, linkage to care, uptake of ART, and community attitudes about ART.ConclusionsHome-based HIV testing was well received in this rural population, although men were less easily contactable at home; immediate ART was acceptable, with good viral suppression and retention. However, only about half of HIV-positive people accessed care within 6 mo of being identified, with nearly two-thirds accessing care by 12 mo. The observed delay in linkage to care would limit the individual and public health ART benefits of universal testing and treatment in this population.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01509508","term_id":"NCT01509508"}}NCT01509508     

On the selection of thresholds for predicting species occurrence with presence‐only data

Presence‐only data present challenges for selecting thresholds to transform species distribution modeling results into binary outputs. In this article, we compare two recently published threshold selection methods (maxSSS and maxF_pb) and examine the effectiveness of the threshold‐based prevalence estimation approach. Six virtual species with varying prevalence were simulated within a real landscape in southeastern Australia. Presence‐only models were built with DOMAIN, generalized linear model, Maxent, and Random Forest. Thresholds were selected with two methods maxSSS and maxF_pb with four presence‐only datasets with different ratios of the number of known presences to the number of random points (KP–RP_ratio). Sensitivity, specificity, true skill statistic, and F measure were used to evaluate the performance of the results. Species prevalence was estimated as the ratio of the number of predicted presences to the total number of points in the evaluation dataset. Thresholds selected with maxF_pb varied as the KP–RP_ratio of the threshold selection datasets changed. Datasets with the KP–RP_ratio around 1 generally produced better results than scores distant from 1. Results produced by We conclude that maxF_pb had specificity too low for very common species using Random Forest and Maxent models. In contrast, maxSSS produced consistent results whichever dataset was used. The estimation of prevalence was almost always biased, and the bias was very large for DOMAIN and Random Forest predictions. We conclude that maxF_pb is affected by the KP–RP_ratio of the threshold selection datasets, but maxSSS is almost unaffected by this ratio. Unbiased estimations of prevalence are difficult to be determined using the threshold‐based approach.     

Phthalates Are Metabolised by Primary Thyroid Cell Cultures but Have Limited Influence on Selected Thyroid Cell Functions In Vitro

Phthalates are plasticisers added to a wide variety of products, resulting in measurable exposure of humans. They are suspected to disrupt the thyroid axis as epidemiological studies suggest an influence on the peripheral thyroid hormone concentration. The mechanism is still unknown as only few in vitro studies within this area exist. The aim of the present study was to investigate the influence of three phthalate diesters (di-ethyl phthalate, di-n-butyl phthalate (DnBP), di-(2-ethylhexyl) phthalate (DEHP)) and two monoesters (mono-n-butyl phthalate and mono-(2-ethylhexyl) phthalate (MEHP)) on the differentiated function of primary human thyroid cell cultures. Also, the kinetics of phthalate metabolism were investigated. DEHP and its monoester, MEHP, both had an inhibitory influence on 3''-5''-cyclic adenosine monophosphate secretion from the cells, and MEHP also on thyroglobulin (Tg) secretion from the cells. Results of the lactate dehydrogenase-measurements indicated that the MEHP-mediated influence was caused by cell death. No influence on gene expression of thyroid specific genes (Tg, thyroid peroxidase, sodium iodine symporter and thyroid stimulating hormone receptor) by any of the investigated diesters could be demonstrated. All phthalate diesters were metabolised to the respective monoester, however with a fall in efficiency for high concentrations of the larger diesters DnBP and DEHP. In conclusion, human thyroid cells were able to metabolise phthalates but this phthalate-exposure did not appear to substantially influence selected functions of these cells.     

Microtubule cytoskeleton and morphogenesis in the amoebae of the myxomycete Physarum polycephalum

Summary— The amoebae of the myxomycete Physarum polycephalum are of interest in order to analyze the morphogenesis of the microtubule and microfilament cytoskeleton during cell cycle and flagellation. The amoebal interphase microtubule cytoskeleton consists of 2 distinct levels of organization, which correspond to different physiological roles. The first level is composed of the 2 kinetosomes or centrioles and their associated structures. The anterior and posterior kinetosomes forming the anterior and posterior flagella are morphologically distinguishable. Each centriole plays a role in the morphogenesis of its associated satellites and specific microtubule arrays. The 2 distinct centrioles correspond to the 2 successive maturation stages of the pro-centrioles which are built during prophase. The second level of organization consists of a prominent microtubule organizing center (mtoc 1) to which the anterior centriole is attached at least during interphase. This mtoc plays a role in the formation of the mitotic pole. These observations based on ultrastructural and physiological analyses of the amoebal cystoskeleton are now being extended to the biochemical level. The complex formed by the 2 centrioles and the mtoc 1 has been purified without modifying the microtubule-nucleating activity of the mtoc 1. Several microtubule-associated proteins have been characterized by their ability to bind taxol-stabilized microtubules. Their functions (e.g., microtubule assembly, protection of microtubules against dilution or cold treatment, phosphorylating and ATPase activities) are under investigation. These biochemical approaches could allow in vitro analysis of the morphogenesis of the amoebal microtubule cytoskeleton.     

Seasonal utilization of different seston carbon sources by the ribbed mussel, Geukensia demissa (Dillwyn) in a mid-Atlantic salt marsh

Seston in salt marshes contains a temporally and spatially complex mixture of natural microparticulate organic material, including phytoplankton, vascular plant detritus, bacteria, heterotrophic nanoflagellates and benthic diatoms. Quantitative information is available concerning how suspension-feeding consumers, such as the ribbed mussel, Geukensia demissa (Dillwyn), utilize some of these components to satisfy their carbon demands. Despite this information there is still a limited understanding of how the relative nutritive contribution of these different dietary items may shift during the year associated with variations in both seston composition and the mussel's physiological condition. To investigate if the mussel's ability to use specific constituents of natural seston varies seasonally, we ran a series of pulse-chase 14C feeding experiments under ambient conditions in March, May, August and November 1996. Phytoplankton, cellulosic detritus, bacteria, heterotrophic nanoflagellates and benthic diatoms were radiolabeled and supplemented in small amounts to natural marsh water for feeding to mussels. The fate of 14C in mussel tissues, feces, respiration and excretion was quantified and contrasted among the different diet types and seasons. Microcapsules containing radiolabeled carbohydrate and protein were used as standards to differentiate possible between-experiment variations in seston composition from seasonal changes in the mussel's feeding and digestive physiology. Mussel clearance rates for all diets were highest in summer and autumn and lowest in winter and spring. In contrast, seasonal shifts in digestive physiology were only found for certain diets. The seasonal range of assimilation efficiencies for microcapsule standards (18-29%) and field-collected microheterotrophs (bacteria 76-93% and heterotrophic nanoflagellates 87-94%) did not differ significantly during the year, whereas summer and autumn assimilation efficiencies for cellulosic detritus (22-24%), phytoplankton (71-79%) and benthic diatoms (89-93%) were up to twofold greater than those in winter and spring (13%, 40-59% and 45-81%, respectively). We conclude that the digestive physiology (e.g., digestive enzyme production) of mussels responds to shifts in dietary components during the year.     

Is object search mediated by object-based or image-based representations?

Recent research suggests that visually specific memory representations for previously fixated objects are maintained during scene perception. Here we investigate the degree of visual specificity by asking whether the memory representations are image-based or object-based. To that end we measured the effects of object orientation on the time to search for a familiar object from amongst a set of 7 familiar distractors arranged in a circular array. Search times were found to depend on the relative orientations of the target object and the probe object for both familiar and novel objects. This effect was found to be partly an image matching effect but there was also an advantage shown for the object's canonical view for familiar objects. Orientation effects were maintained even when the target object was specified as having unique or similar shape properties relative to the distractors. Participants' eye movements were monitored during two of the experiments. Eye movement patterns revealed selection for object shape and object orientation during the search process. Our findings provide evidence for object representations during search that are detailed and share image-based characteristics with more high-level characteristics from object memory.     

Repair of a minimal DNA double-strand break by NHEJ requires DNA-PKcs and is controlled by the ATM/ATR checkpoint

Mammalian cells primarily rejoin DNA double-strand breaks (DSBs) by the non-homologous end-joining (NHEJ) pathway. The joining of the broken DNA ends appears directly without template and accuracy is ensured by the NHEJ factors that are under ATM/ATR regulated checkpoint control. In the current study we report the engineering of a mono-specific DNA damaging agent. This was used to study the molecular requirements for the repair of the least complex DSB in vivo. Single-chain PvuII restriction enzymes fused to protein delivery sequences transduce cells efficiently and induce blunt end DSBs in vivo. We demonstrate that beside XRCC4/LigaseIV and KU, the DNA-PK catalytic subunit (DNA-PKcs) is also essential for the joining of this low complex DSB in vivo. The appearance of blunt end 3′-hydroxyl and 5′-phosphate DNA DSBs induces a significantly higher frequency of anaphase bridges in cells that do not contain functional DNA-PKcs, suggesting an absolute requirement for DNA-PKcs in the control of chromosomal stability during end joining. Moreover, these minimal blunt end DSBs are sufficient to induce a p53 and ATM/ATR checkpoint function.     

The muscle ankyrin repeat proteins: CARP, ankrd2/Arpp and DARP as a family of titin filament-based stress response molecules

CARP, ankrd-2/Arpp, and DARP, are three members of a conserved gene family, referred to here as MARPs (muscle ankyrin repeat proteins). The expression of MARPs is induced upon injury and hypertrophy (CARP), stretch or denervation (ankrd2/Arpp), and during recovery following starvation (DARP), suggesting that they are involved in muscle stress response pathways. Here, we show that MARP family members contain within their ankyrin repeat region a binding site for the myofibrillar elastic protein titin. Within the myofibril, MARPs, myopalladin, and the calpain protease p94 appear to be components of a titin N2A-based signaling complex. Ultrastructural studies demonstrated that all three endogenous MARP proteins co-localize with I-band titin N2A epitopes in adult heart muscle tissues. In cultured fetal rat cardiac myocytes, passive stretch induced differential distribution patterns of CARP and DARP: staining for both proteins was increased in the nucleus and at the I-band region of myofibrils, while DARP staining also increased at intercalated discs. We speculate that the myofibrillar MARPs are regulated by stretch, and that this links titin-N2A-based myofibrillar stress/strain signals to a MARP-based regulation of muscle gene expression.     

Extrathymic TCR gene rearrangement in human small intestine: identification of new splice forms of recombination activating gene-1 mRNA with selective tissue expression

Two new 5'-untranslated region (5'UTR) exons were identified in the human gene for the lymphocyte-specific endonuclease recombination activating gene-1 (RAG1) required for the somatic recombination yielding functional Ag receptors. These 5'UTR exons were used in three different splice forms by jejunal lymphocytes of the T cell lineage. RAG1 mRNA containing the previously described 5'UTR exon was not expressed in these cells. Conversely, one of the new 5'UTR exons was not expressed in thymus. The new RAG1 mRNA splice forms were all expressed in immature T cells (CD2(+)CD7(+)CD3(-)). This cell population also expressed high levels of mRNA for the pre-T alpha-chain. In situ hybridization demonstrated jejunal cells expressing the new splice forms of RAG1 mRNA, both intraepithelially and in lamina propria. Pre-T alpha-chain mRNA-expressing cells were detected at the same sites. These results strongly suggest ongoing TCR gene rearrangement in human small intestinal mucosa, yielding T cells specially adapted for this environment. This seems to be achieved by two parallel processes, extrathymic T cell development and peripheral Ag-driven TCR editing.