Effect of anti-retroviral therapy on oxidative stress in hospitalized HIV-infected adults with and without TB.

BackgroundHIV infection and opportunistic infections cause oxidative stress (OS), which is associated with tissue damage. Anti-retroviral therapy (ART) is used to treat HIV and decrease the risk of opportunistic infections, but it is unclear whether ART reduces OS. Association of ART with OS was investigated.MethodsWe stratified a convenience sample of frozen serum or plasma from HIV-infected, ART-naïve (n=21); HIV-infected, ART-treated (n=14); HIV and PTB co-infected, ART-naïve (n=21); HIV and PTB co-infected, ART-treated (n=25) patients. Controls (n=21) were HIV-negative adults without TB symptoms. Concentration of OS markers namely: transaminases (ALT and AST), gamma glutamyl transpeptidase (GGT), albumin, total protein, malondialdehyde (MDA), vitamin C, and total anti-oxidant status (TAS) were determined.ResultsAST (p<0.001), GGT (p<0.001), total protein (p=0.001) and MDA (p<0.001) were higher in HIV patients compared to controls. Vitamin C (P<0.0001) and albumin (p<0.01) were lower in HIV-patients relative to controls. ART was only associated with higher albumin (p=0.001), higher GGT (p=0.02) and lower vitamin C (p=0.009). HIV and PTB co-infection was only significantly associated with higher GGT (p=0.01) and AST (p=0.03).ConclusionWe identified severe OS among HIV-patients. ART was associated with both increased and reduced markers of OS hence suggesting that ART may not attenuate OS

Point-of-care C-reactive protein-based tuberculosis screening for people living with HIV: a diagnostic accuracy study.

BackgroundSymptom-based screening for tuberculosis is recommended for all people living with HIV. This recommendation results in unnecessary Xpert MTB/RIF testing in many individuals living in tuberculosis-endemic areas and thus poor implementation of intensified case finding and tuberculosis preventive therapy. Novel approaches to tuberculosis screening are needed to help achieve global targets for tuberculosis elimination. We assessed the performance of C-reactive protein (CRP) measured with a point-of-care assay as a screening tool for active pulmonary tuberculosis.MethodsFor this prospective study, we enrolled adults (aged ≥18 years) living with HIV with CD4 cell count less than or equal to 350 cells per μL who were initiating antiretroviral therapy (ART) from two HIV/AIDS clinics in Uganda. CRP concentrations were measured at study entry with a point-of-care assay using whole blood obtained by fingerprick (concentration ≥10 mg/L defined as screen positive for tuberculosis). Sputum samples were collected for Xpert MTB/RIF testing and culture. We calculated the sensitivity and specificity of point-of-care CRP and WHO symptom-based screening in reference to culture results. We repeated the sensitivity analysis with Xpert MTB/RIF as the reference standard.FindingsBetween July 8, 2013, and Dec 15, 2015, 1237 HIV-infected adults were enrolled and underwent point-of-care CRP testing. 60 (5%) patients with incomplete or contaminated cultures were excluded from the analysis. Of the remaining 1177 patients (median CD4 count 165 cells per μL [IQR 75-271]), 163 (14%) had culture-confirmed tuberculosis. Point-of-care CRP testing had 89% sensitivity (145 of 163, 95% CI 83-93) and 72% specificity (731 of 1014, 95% CI 69-75) for culture-confirmed tuberculosis. Compared with WHO symptom-based screening, point-of-care CRP testing had lower sensitivity (difference -7%, 95% CI -12 to -2; p=0·002) but substantially higher specificity (difference 58%, 95% CI 55 to 61; p<0·0001). When Xpert MTB/RIF results were used as the reference standard, sensitivity of point-of-care CRP and WHO symptom-based screening were similar (94% [79 of 84] vs 99% [83 of 84], respectively; difference -5%, 95% CI -12 to 2; p=0·10).InterpretationThe performance characteristics of CRP support its use as a tuberculosis screening test for people living with HIV with CD4 count less than or equal to 350 cells per μL who are initiating ART. HIV/AIDS programmes should consider point-of-care CRP-based tuberculosis screening to improve the efficiency of intensified case finding and increase uptake of tuberculosis preventive therapy.FundingNational Institutes of Health; President's Emergency Plan for AIDS Relief; University of California, San Francisco, Nina Ireland Program for Lung Health

Ultrasensitive detection of lipoarabinomannan with plasmonic grating biosensors in clinical samples of HIV negative patients with tuberculosis.

BACKGROUND:Timely diagnosis of tuberculosis disease is critical for positive patient outcomes, yet potentially millions go undiagnosed or unreported each year. Sputum is widely used as the testing input, but limited by its complexity, heterogeneity, and sourcing problems. Finding methods to interrogate noninvasive, non-sputum clinical specimens is indispensable to improving access to tuberculosis diagnosis and care. In this work, economical plasmonic gratings were used to analyze tuberculosis biomarker lipoarabinomannan (LAM) from clinical urine samples by single molecule fluorescence assay (FLISA) and compared with gold standard sputum GeneXpert MTB/ RIF, culture, and reference ELISA testing results. METHODS AND FINDINGS:In this study, twenty sputum and urine sample sets were selected retrospectively from a repository of HIV-negative patient samples collected before initiation of anti-tuberculosis therapy. GeneXpert MTB/RIF and culture testing of patient sputum confirmed the presence or absence of pulmonary tuberculosis while all patient urines were reference ELISA LAM-negative. Plasmonic gratings produced by low-cost soft lithography were bound with anti-LAM capture antibody, incubated with patient urine samples, and biotinylated detection antibody. Fluorescently labeled streptavidin revealed single molecule emission by epifluorescence microscope. Using a 1 fg/mL baseline for limit of detection, single molecule FLISA demonstrated good qualitative agreement with gold standard tests on 19 of 20 patients, including accurately predicting the gold-standard-negative patients, while one gold-standard-positive patient produced no observable LAM in urine. CONCLUSIONS:Single molecule FLISA by plasmonic grating demonstrated the ability to quantify tuberculosis LAM from complex urine samples of patients from a high endemic setting with negligible interference from the complex media itself. Moreover, agreement with patient diagnoses by gold standard testing suggests that single molecule FLISA could be used as a highly sensitive test to diagnose tuberculosis noninvasively

A Study of Refusal Strategy in English by the Students of Department of English Language Education

ABSTRACT The refusal strategies produced by both native English speakers and non-native English speakers have been a prominent area of interest for many researchers. Refusal is a face threatening act (FTA) for it can risk the face of persons in the interaction (the speaker and the hearer). However, it is found that very few studies concerning refusal strategy in English had been conducted in Indonesian setting especially in Aceh. Aimed to explore foreign language learners’ pattern of refusal, the current study is carried out with two research questions as the focus, which are (1) to seek the refusal strategies applied by the students at the Department of English Language Education of UIN Ar-Raniry and (2)to find out whether the students are aware of the power status of the interlocutor. This study is based on mixed-method approach. The writer used triangulation in obtaining the data needed which is to cross validate data from different sources for the similar phenomenon . They are the Discourse Completion Test and interview. The participants taking part in this study are 10 senior students in Department of English Language Education of UIN Ar-Raniry. They were selected based on the accomplishment of speaking and Discourse Analysis subjects. The result of this study showed that the participants frequently applied indirect strategy when refusing regardless the person’s power status. They use it not only to interact with higher status person but also to the lower status. Furthermore, they are also aware of the different power status of the interlocutor they are speaking to

Which stars can form planets: Planetesimal formation at low metallicities

The exoplanet diversity has been linked to the disc environment in which they form, where the host star metallicity and the formation pathways play a crucial role. In the context of the core accretion paradigm, the initial stages of planet formation require the growth of dust material from micrometre size to planetesimal size bodies before core accretion can kick in. Although numerous studies have been conducted on planetesimal formation, it is still poorly understood how this process takes place in low metallicity stellar environments. We explore planetesimals formation in stellar environments primarily with low metallicity. We performed global 1D viscous disc evolution simulations including grain growth, evaporation and condensation of chemical species at ice lines. We followed the formation of planetesimals during disc evolution and tested different metallicities, disc sizes and turbulent viscosity strengths. We find that at solar and sub-solar metallicities, there is a significant enhancement in the midplane dust-to-gas mass ratios at the ice lines but this leads to planetesimal formation only at the water ice line. In our simulations, [Fe/H] = -0.6 is the lowest limit of metallicity for planetesimal formation where a few Earth masses of planetesimals could form. For such extreme disc environments, large discs are more conducive than small discs for forming large amounts of planetesimals at a fixed metallicity, because the pebble flux can be maintained for a longer time resulting in a longer and more efficient planetesimal formation phase. At lower metallicities, planetesimal formation is less supported in quiescent discs compared to turbulent discs, because the pebble flux can be maintained for a longer time. The amount of planetesimals formed at sub-solar metallicities in our simulations places a limit on core sizes that could possibly only result in the formation of super-Earths.Comment: Accepted for publication in A&

Relationships between Anthropogenic Activities and Distribution of Medium to Large Mammal Species Assemblage in Madi Wildlife Corridor: Implication for Biodiversity Conservation in Uganda

Wildlife corridors between protected areas increase connectivity by integrating populations into single demographic units, thereby increasing gene flows within populations and thus probability of survival. This study assessed the relationship between anthropogenic activities and mammal species assemblage within and around Madi wildlife corridor. The study adopted recce walks along a zig-zag line transect and straight line transect methods of game tracking. Global Position System (GPS) was used to map locations of direct mammal sightings, vocalizations, tracks, dung/droppings, diggings, carcasses, and skeletal remains of mammal species. Similarly, anthropogenic activities such as hunting using bow and arrows, rifles, trapping, tree cutting, charcoal burning, bush burning, cultivation, and settlements that seemed to influence assemblage of the mammals in the area of study were mapped. The result showed that the Madi wildlife corridor still contained diverse mammal species including but not limited to; the African Elephants (Loxodonta Africana sp.), Buffaloes (Syncerus caffer) Leopards (Panthera pardus), Spotted Hyena (Crocuta Crocuta), Northern Giraffe (Giraffa Camelopardalis), Uganda kob (Kobus kob thomasi), Hartebeest (Alcelaphus buselaphus) and Reedbuck (Redunca arundinum), which were comparable to that of the adjacent Murchison Falls National Park (MFNP). The relationship between anthropogenic activities and species assemblage showed a negatively skewed distribution of some of the large mammal species specifically Elephants, Giraffes, and Hippopotamus. The study recommends gazettement of a wildlife corridor between MFNP and East Madi Wildlife Reserve to promote wildlife connectivity between two adjacent ecosystem-protected areas in northern Uganda. As a long-term strategy for wildlife conservation, it is crucial to undertake a systematic assessment and prioritization and demarcation of wildlife corridors and development of a comprehensive action plan for securing them. We further recommend development of a national Wildlife Corridor Regulations to provide a framework for the sustainable conservation of biodiversit

Cost- Benefit Analysis of Collaborative Forest Management: A Case Study of Tororo Central Forest Reserve, Eastern Uganda

Forests provide multitude of benefits to humanity in terms of local socio-economic, development, and environmental protection which are often not valued at national level because of lack of a valuation system for the ecosystem services. This study undertook a cost-benefit analysis of Collaborative Forest Management (CFM) implementation at Tororo Central Forest Reserve (TCFR) between Nyangole community and National Forestry Authority (NFA) using Contingent Valuation Method (CVM). The result showed that Nyangole community incurred total discounted costs of USD 74,440.0 on tree planting, forest resource management and protection, tree nursery activities and agriculture. Meanwhile they received total discounted economic benefits of USD 396,720.0 from sale of poles, tree seedlings, training opportunities, fire wood, mango fruits, and food stuffs. Other benefits that accrued to the community were opportunity of receiving visitors at the project, training allowances and other ecosystem services provided by the forest. The benefit-cost ratio of CFM to Nyangole community was 5:1 with positive Net Present Value (NPV). We concluded that the CFM partnership between government and Nyangole yielded benefits to the both parties and recommend that this approach be rolled to other sites within the countr