Co-trimoxazole prophylaxis in HIV : the evidence

BibliographyHuman immunodeficiency virus (HIV) damages the body’s immune system, making secondary (or opportunistic) infections more common. Treatment and prevention of such infections is integral to the management of patients with HIV infection. Co-trimoxazole is a prophylactic treatment that has a wide range of action against common bacteria, parasites, fungi and yeasts. As part of a minimum care package, UNAIDS/ WHO recommends co-trimoxazole prophylaxis for HIVinfected adults with symptomatic disease (WHO stage II, III or IV), or asymptomatic individuals with CD4 counts ≤500 cells/μl, and for all HIV-positive pregnant women after the first trimester.1 Co-trimoxazole is also recommended for use in children with proven HIV infection and infants exposed to HIV (from 4 - 6 weeks of age until infection with HIV is ruled out).2 The object of this report is to summarise the effects of co-trimoxazole prophylaxis on morbidity and mortality among HIV-infected individuals

Eccentrically Loaded Bolted Connections for Type 304 and 3CR12 Stainless Steel Lipped Channels

In this paper the results of a study on eccentrically loaded bolted connections in lipped channels are presented. The steels chosen for this study are AISI Type 304 and Type 3CR12 stainless steel. It is concluded in this investigation that an acceptable prediction of the strength of eccentrically loaded bolted connections of stainless steel lipped channels may be obtained through the combination between the eccentric loaded equation and the normal bolted connection equations for stainless steel

Pro-inflammatory role of monocyte-derived CX3CR1int macrophages in Helicobacter hepaticus-induced colitis

Cells of the monocyte-macrophage lineage play important roles in the pathogenesis of inflammatory bowel diseases, but they are also present in the normal healthy intestine, where they are critical for maintaining homeostasis. It has been unclear whether the pro-inflammatory roles of intestinal macrophages reflect altered behaviour of the existing resident cells, or if they involve recruitment of a distinct cell type. Here we have explored these ideas using the model of colitis induced by Helicobacter hepaticus (Hh) in the context of neutralisation or deletion of interleukin 10 (IL-10). Granulocytes and monocytes made up most of the inflammatory myeloid infiltrates found in the colon of Hh-infected colitic mice, rising to a peak within 2 weeks of Hh inoculation, but taking several months to resolve completely. The inflammatory response was dependent on the combined presence of Hh and absence of IL-10, and was accompanied by increased production of inflammatory mediators such as IL-1β, TNFα, IL-6 and IL-23p19 by infiltrating myeloid cells, mostly relatively immature cells of the macrophage lineage that express intermediate levels of CX3CR1. In contrast, the population of mature CX3CR1hi macrophages did not expand as markedly during colitis, and these cells made little contribution to inflammatory mediator production. Taking into account their numerical dominance in the myeloid compartment, we conclude that newly recruited monocytes are the main source of pro-inflammatory mediators in colitis induced in the absence of IL-10 signalling, and that altered behaviour of mature macrophages is not a major component of this pathology

The potential for climate-driven bathymetric range shifts: sustained temperature and pressure exposures on a marine ectotherm, Palaemonetes varians

Range shifts are of great importance as a response for species facing climate change. In the light of current ocean-surface warming, many studies have focused on the capacity of marine ectotherms to shift their ranges latitudinally. Bathymetric range shifts offer an important alternative, and may be the sole option for species already at high latitudes or those within enclosed seas; yet relevant data are scant. Hydrostatic pressure (HP) and temperature have wide ranging effects on physiology, importantly acting in synergy thermodynamically, and therefore represent key environmental constraints to bathymetric migration. We present data on transcriptional regulation in a shallow-water marine crustacean (Palaemonetes varians) at atmospheric and high HP following 168-h exposures at three temperatures across the organisms' thermal scope, to establish the potential physiological limit to bathymetric migration by neritic fauna. We observe changes in gene expression indicative of cellular macromolecular damage, disturbances in metabolic pathways and a lack of acclimation after prolonged exposure to high HP. Importantly, these effects are ameliorated (less deleterious) at higher temperatures, and exacerbated at lower temperatures. These data, alongside previously published behavioural and heat-shock analyses, have important implications for our understanding of the potential for climate-driven bathymetric range shift

Electron-hadron shower discrimination in a liquid argon time projection chamber

By exploiting structural differences between electromagnetic and hadronic showers in a multivariate analysis we present an efficient Electron-Hadron discrimination algorithm for liquid argon time projection chambers, validated using Geant4 simulated data

Calibration of optimal execution of financial transactions in the presence of transient market impact

Trading large volumes of a financial asset in order driven markets requires the use of algorithmic execution dividing the volume in many transactions in order to minimize costs due to market impact. A proper design of an optimal execution strategy strongly depends on a careful modeling of market impact, i.e. how the price reacts to trades. In this paper we consider a recently introduced market impact model (Bouchaud et al., 2004), which has the property of describing both the volume and the temporal dependence of price change due to trading. We show how this model can be used to describe price impact also in aggregated trade time or in real time. We then solve analytically and calibrate with real data the optimal execution problem both for risk neutral and for risk averse investors and we derive an efficient frontier of optimal execution. When we include spread costs the problem must be solved numerically and we show that the introduction of such costs regularizes the solution.Comment: 31 pages, 8 figure

Agricultural cropland extent and areas of South Asia derived using Landsat satellite 30-m time-series big-data using random forest machine learning algorithms on the Google Earth Engine cloud

The South Asia (India, Pakistan, Bangladesh, Nepal, Sri Lanka and Bhutan) has a staggering 900 million people (~43% of the population) who face food insecurity or severe food insecurity as per United Nations, Food and Agriculture Organization’s (FAO) the Food Insecurity Experience Scale (FIES). The existing coarse-resolution (≥250-m) cropland maps lack precision in geo-location of individual farms and have low map accuracies. This also results in uncertainties in cropland areas calculated fromsuch products. Thereby, the overarching goal of this study was to develop a high spatial resolution (30-m or better) baseline cropland extent product of South Asia for the year 2015 using Landsat satellite time-series big-data and machine learning algorithms (MLAs) on the Google Earth Engine (GEE) cloud computing platform. To eliminate the impact of clouds, 10 time-composited Landsat bands (blue, green, red, NIR, SWIR1, SWIR2, Thermal, EVI, NDVI, NDWI) were derived for each of the three timeperiods over 12 months (monsoon: Days of the Year (DOY) 151–300; winter: DOY 301–365 plus 1–60; and summer: DOY 61–150), taking the every 8-day data from Landsat-8 and 7 for the years 2013–2015, for a total of 30-bands plus global digital elevation model (GDEM) derived slope band. This 31-band mega-file big data-cube was composed for each of the five agro-ecological zones (AEZ’s) of South Asia and formed a baseline data for image classification and analysis. Knowledgebase for the Random Forest (RF) MLAs were developed using spatially well spread-out reference training data (N = 2179) in five AEZs. The classification was performed on GEE for each of the five AEZs using well-established knowledge-base and RF MLAs on the cloud. Map accuracies were measured using independent validation data (N = 1185). The survey showed that the South Asia cropland product had a producer’s accuracy of 89.9% (errors of omissions of 10.1%), user’s accuracy of 95.3% (errors of commission of 4.7%) and an overall accuracy of 88.7%. The National and sub-national (districts) areas computed from this cropland extent product explained 80-96% variability when compared with the National statistics of the South Asian Countries. The full-resolution imagery can be viewed at full-resolution, by zooming-in to any location in South Asia or the world, atwww.croplands. org and the cropland products of South Asia downloaded from The Land Processes Distributed Active Archive Center (LP DAAC) of National Aeronautics and Space Administration (NASA) and the United States Geological Survey (USGS): https://lpdaac.usgs.gov/products/gfsad30saafgircev001/

A Crystal Structure of the Bifunctional Antibiotic Simocyclinone D8, Bound to DNA Gyrase

Simocyclinones are bifunctional antibiotics that inhibit bacterial DNA gyrase by preventing DNA binding to the enzyme. We report the crystal structure of the complex formed between the N-terminal domain of the Escherichia coli gyrase A subunit and simocyclinone D8, revealing two binding pockets that separately accommodate the aminocoumarin and polyketide moieties of the antibiotic. These are close to, but distinct from, the quinolone-binding site, consistent with our observations that several mutations in this region confer resistance to both agents. Biochemical studies show that the individual moieties of simocyclinone D8 are comparatively weak inhibitors of gyrase relative to the parent compound, but their combination generates a more potent inhibitor. Our results should facilitate the design of drug molecules that target these unexploited binding pockets

Recombination rate and selection strength in HIV intra-patient evolution

The evolutionary dynamics of HIV during the chronic phase of infection is driven by the host immune response and by selective pressures exerted through drug treatment. To understand and model the evolution of HIV quantitatively, the parameters governing genetic diversification and the strength of selection need to be known. While mutation rates can be measured in single replication cycles, the relevant effective recombination rate depends on the probability of coinfection of a cell with more than one virus and can only be inferred from population data. However, most population genetic estimators for recombination rates assume absence of selection and are hence of limited applicability to HIV, since positive and purifying selection are important in HIV evolution. Here, we estimate the rate of recombination and the distribution of selection coefficients from time-resolved sequence data tracking the evolution of HIV within single patients. By examining temporal changes in the genetic composition of the population, we estimate the effective recombination to be r=1.4e-5 recombinations per site and generation. Furthermore, we provide evidence that selection coefficients of at least 15% of the observed non-synonymous polymorphisms exceed 0.8% per generation. These results provide a basis for a more detailed understanding of the evolution of HIV. A particularly interesting case is evolution in response to drug treatment, where recombination can facilitate the rapid acquisition of multiple resistance mutations. With the methods developed here, more precise and more detailed studies will be possible, as soon as data with higher time resolution and greater sample sizes is available.Comment: to appear in PLoS Computational Biolog

Experiences of support garments following bowel stoma formation: analysis of free-text responses in a cross-sectional survey

Aim: To explore the experiences of support garments when adjusting to bodily change following bowel stoma formation. Design: Thematic analyses of free-text responses in a cross-sectional survey of the stoma population in 2018. Methods: Free-text responses were invited so that respondents could describe their experiences in more detail. A process of induction was chosen to allow for themes to emerge directly from the data. The concept ‘embodiment’ was used as a theoretical framework during interpretation. Results: 1425 people with a bowel stoma responded to the survey, of whom 598 provided free-text responses. Four themes about experiences of support garments in the context of changed bodily experiences following stoma formation were identified: body complications, which is about experiences of using support garments to prevent or self-manage parastomal hernia; body appearance, which is about hiding the stoma and stoma appliance; body function, which is about managing stoma appliance complications; and body sensation, which is mainly about negative experiences of ill-fitting garments. Conclusion: Support garments can be understood as items that are used by people during an ongoing process of adjusting to bodily changes following stoma formation and as part of an ongoing process of reconstructing new embodied selves. Impact: This is the first study to explore people’s experiences of support garments following bowel stoma formation. Support garments are used in the self-management of body complications, appearance, function and sensations. Stoma nurses may draw on the findings of this study to advise patients about the benefits of garments for adjusting to bodily change, and garment suppliers should address people’s negative experiences by improving garments