355 research outputs found

    Growth and Characterization of MnBi2Te4 Magnetic Topological Insulator

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    We report successful growth of magnetic topological insulator (MTI) MnBi(2)Te(4)singlecrystalby solid state reaction route via self flux method. The phase formation of MnBi(2)Te(4)singlecrystalis strongly dependent on the heat treatment. MnBi(2)Te(4)is grown in various phases i. e., MnBi4Te7, MnBi6Te10 and MnTe as seen in powder X-ray diffraction (PXRD) of crushed resultant crystal. The Rietveld analysis shows some impurity lines along with the main phase MnBi2Te4. Low temperature (10K) magneto-resistance (MR) in applied magnetic field of up to 6 Tesla exhibited - ve MR below 0.5 Tesla and +ve for higher fields. The studied MnBi2Te4, MTI crystal could be a possible candidate for Quantum Anomalous Hall (QAH) effect. Here we are reporting a newly discovered magnetic topological insulator MnBi(2)Te(4)having non-trivial symmetry as well as strong Spin-Orbit Coupling forQAH effect

    Predicting the long-term impact of antiretroviral therapy scale-up on population incidence of tuberculosis.

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    OBJECTIVE: To investigate the impact of antiretroviral therapy (ART) on long-term population-level tuberculosis disease (TB) incidence in sub-Saharan Africa. METHODS: We used a mathematical model to consider the effect of different assumptions about life expectancy and TB risk during long-term ART under alternative scenarios for trends in population HIV incidence and ART coverage. RESULTS: All the scenarios we explored predicted that the widespread introduction of ART would initially reduce population-level TB incidence. However, many modelled scenarios projected a rebound in population-level TB incidence after around 20 years. This rebound was predicted to exceed the TB incidence present before ART scale-up if decreases in HIV incidence during the same period were not sufficiently rapid or if the protective effect of ART on TB was not sustained. Nevertheless, most scenarios predicted a reduction in the cumulative TB incidence when accompanied by a relative decline in HIV incidence of more than 10% each year. CONCLUSIONS: Despite short-term benefits of ART scale-up on population TB incidence in sub-Saharan Africa, longer-term projections raise the possibility of a rebound in TB incidence. This highlights the importance of sustaining good adherence and immunologic response to ART and, crucially, the need for effective HIV preventive interventions, including early widespread implementation of ART

    Acquired HIV drug resistance among adults living with HIV receiving first-line antiretroviral therapy in Rwanda: a cross-sectional nationally representative survey

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    BACKGROUND: We assessed the prevalence of acquired HIV drug resistance (HIVDR) and associated factors among patients receiving first-line antiretroviral therapy (ART) in Rwanda. METHODS: This cross-sectional study included 702 patients receiving first-line ART for at least 6 months with last viral load (VL) results >/=1000 copies/mL. Blood plasma samples were subjected to VL testing; specimens with unsuppressed VL were genotyped to identify HIVDR-associated mutations. Data were analysed using STATA/SE. RESULTS: Median time on ART was 86.4 months (interquartile range [IQR], 44.8-130.2 months), and median CD4 count at ART initiation was 311 cells/mm(3) (IQR, 197-484 cells/mm(3)). Of 414 (68.2%) samples with unsuppressed VL, 378 (88.3%) were genotyped. HIVDR included 347 (90.4%) non-nucleoside reverse transcriptase inhibitor- (NNRTI), 291 (75.5%) nucleoside reverse transcriptase inhibitor- (NRTI) and 13 (3.5%) protease inhibitor (PI) resistance-associated mutations. The most common HIVDR mutations were K65R (22.7%), M184V (15.4%) and D67N (9.8%) for NRTIs and K103N (34.4%) and Y181C/I/V/YC (7%) for NNRTIs. Independent predictors of acquired HIVDR included current ART regimen of zidovudine + lamivudine + nevirapine (adjusted odds ratio [aOR], 3.333 [95% confidence interval (CI): 1.022-10.870]; p = 0.046) for NRTI resistance and current ART regimen of tenofovir + emtricitabine + nevirapine (aOR, 0.148 [95% CI: 0.028-0.779]; p = 0.025), zidovudine + lamivudine + efavirenz (aOR, 0.105 [95% CI: 0.016-0.693]; p = 0.020) and zidovudine + lamivudine + nevirapine (aOR, 0.259 [95% CI: 0.084-0.793]; p = 0.019) for NNRTI resistance. History of ever switching ART regimen was associated with NRTI resistance (aOR, 2.53 [95% CI: 1.198-5.356]; p = 0.016) and NNRTI resistance (aOR, 3.23 [95% CI: 1.435-7.278], p = 0.005). CONCLUSION: The prevalence of acquired HIV drug resistance (HIVDR) was high among patient failing to re-suppress VL and was associated with current ART regimen and ever switching ART regimen. The findings of this study support the current WHO guidelines recommending that patients on an NNRTI-based regimen should be switched based on a single viral load test and suggests that national HIV VL monitoring of patients receiving ART has prevented long-term treatment failure that would result in the accumulation of TAMs and potential loss of efficacy of all NRTI used in second-line ART as the backbone in combination with either dolutegravir or boosted PIs

    Capacity of health facilities for diagnosis and treatment of HIV/AIDS in Ethiopia

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    Background: There are dearth of literature on the capacity of the health system to diagnose and treat HIV/AIDS in Ethiopia. In this study we evaluated the capacity of health facilities for HIV/AIDS care, its spatial distribution and variations by regions and zones in Ethiopia. Methods: We analyzed the Service Provision Assessment plus (SPA+) survey data that were collected in 2014 in all regions of Ethiopia. We assessed structural, process and overall capacity of the health system based on the Donabedian quality of care model. We included 5 structural and 8 process indicators and overall capacity score was constructed by taking the average of all indicators. Multiple linear regression was done using STATA 14 to assess the association of the location and types of health facilities with overall capacity score. Maps displaying the average capacity score at Zonal level were produced using ArcGIS Desktop v10.3 (Environmental Systems Research Institute Inc., Redlands CA, USA). Results: A total of 873 health facilities were included in the analysis. Less than 5% of the private facilities provided antiretroviral therapy (ART); had national ART guideline, baseline CD4 count or viral load and tuberculosis screening mechanisms. Nearly one-third of the health centers (34.9%) provided ART. Public hospitals have better capacity score (77.1%) than health centers (45.9%) and private health facilities (24.8%). The overall capacity score for urban facilities (57.1%) was higher than that of the rural (38.2%) health facilities (Ξ² = 15.4, 95% CI: 11.7, 19.2). Health centers (Ξ² = βˆ’ 21.4, 95% CI: -25.4, βˆ’ 17.4) and private health facilities (Ξ² = βˆ’ 50.9, 95% CI: -54.8, βˆ’ 47.1) had lower overall capacity score than hospitals. Facilities in Somali (Ξ² = βˆ’ 13.8, 95% CI: -20.6, βˆ’ 7.0) and SNNPR (Ξ² = βˆ’ 5.0, 95% CI: -9.8, βˆ’ 0.1) regions had lower overall capacity score than facilities in the Oromia region. Zones located in emerging regions such as Gambella and Benishangul Gumz and in remote areas of Oromia and SNNPR had lower capacity score in terms of process indicators. Conclusions: There is a significant geographical heterogeneity on the capacity of health facilities for HIV/AIDS care and treatment in Ethiopia. Targeted capacity improvement initiatives are recommended with focus on health centers and private health facilities, and emerging Regions and the rural and remote areas

    The Vissannapeta eucrite

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    A wholly encrusted single stone that fell in Vissannapeta, Andhra Pradesh, India has been identified as a cumulate eucrite based on its primary texture and mineral composition: anorthite (An92.4-94.6), orthopyroxene (En49.1-51.8Fs44.2-49.7Wo1.2-4.0), and clinopyroxene (En38.8-46.8Fs14.8-33.6Wo19.6-46.4). The stone is pyramidal in shape, and the crust shows rib-like flow features indicating that it had an oriented passage through the atmosphere towards the terminal stage of its flight. Conditions of its fall, mineralogical characteristics, and results of measurements of cosmogenic radioactivity (26Al, 22Na, and 54Mn) and track density are described. Aluminum-26 and 22Na in Vissannapeta are ∼ 75% of the expected values and also lower by a similar factor compared to the activities measured in Piplia Kalan, another eucrite, which fell ∼ 18 months before Vissannapeta. Because higher activity of 22Na and 54Mn would be expected from solar cycle modulation of galactic cosmic rays, these results, as well as the track density gradient, indicate that Vissannapeta was a small body (≤ 120 kg) in the interplanetary space wherein the nuclear cascade due to galactic cosmic rays did not develop fully. Tracks, surface morphology, and crustal features indicate at least two fragmentation events in the atmosphere

    Genetic Diversity in the Collaborative Cross Model Recapitulates Human West Nile Virus Disease Outcomes

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    ABSTRACTWest Nile virus (WNV) is an emerging neuroinvasive flavivirus that now causes significant morbidity and mortality worldwide. The innate and adaptive immune responses to WNV infection have been well studied in C57BL/6J inbred mice, but this model lacks the variations in susceptibility, immunity, and outcome to WNV infection that are observed in humans, thus limiting its usefulness to understand the mechanisms of WNV infection and immunity dynamics. To build a model of WNV infection that captures human infection outcomes, we have used the Collaborative Cross (CC) mouse model. We show that this model, which recapitulates the genetic diversity of the human population, demonstrates diversity in susceptibility and outcomes of WNV infection observed in humans. Using multiple F1 crosses of CC mice, we identified a wide range of susceptibilities to infection, as demonstrated through differences in survival, clinical disease score, viral titer, and innate and adaptive immune responses in both peripheral tissues and the central nervous system. Additionally, we examined the Oas1b alleles in the CC mice and confirmed the previous finding that Oas1b plays a role in susceptibility to WNV; however, even within a given Oas1b allele status, we identified a wide range of strain-specific WNV-associated phenotypes. These results confirmed that the CC model is effective for identifying a repertoire of host genes involved in WNV resistance and susceptibility. The CC effectively models a wide range of WNV clinical, virologic, and immune phenotypes, thus overcoming the limitations of the traditional C57BL/6J model, allowing genetic and mechanistic studies of WNV infection and immunity in differently susceptible populations.IMPORTANCEMouse models of West Nile virus infection have revealed important details regarding the innate and adaptive immune responses to this emerging viral infection. However, traditional mouse models lack the genetic diversity present in human populations and therefore limit our ability to study various disease outcomes and immunologic mechanisms subsequent to West Nile virus infection. In this study, we used the Collaborative Cross mouse model to more effectively model the wide range of clinical, virologic, and immune phenotypes present upon West Nile virus infection in humans

    Relational approaches to poverty in rural India: social, ecological and technical dynamics

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    Poverty is now widely recognised as multidimensional, with indicators including healthcare, housing and sanitation. Yet, relational approaches that foreground political-cultural processes remain marginalised in policy discourses. Focusing on India, we review a wide range of relational approaches to rural poverty. Beginning with early approaches that focus on structural reproduction of class, caste and to a lesser extent gender inequality, we examine new relational approaches developed in the last two decades. The new approaches examine diverse ways in which poverty is experienced and shapes mobilisations against deprivation. They draw attention to poor people’s own articulations of deprivation and alternate conceptions of well-being. They also show how intersecting inequalities of class, caste and gender shape governance practices and political movements. Despite these important contributions, the new relational approaches pay limited attention to technologies and ecologies in shaping the experience of poverty. Reviewing studies on the Green Revolution and wider agrarian transformations in India, we then sketch the outlines of a hybrid relational approach to poverty that combines socio-technical and -ecological dynamics. We argue that such an approach is crucial to challenge narrow economising discourses on poverty and to bridge the policy silos of poverty alleviation and (environmentally) sustainable development

    COVID-19 vaccine-readiness for anti-CD20-depleting therapy in autoimmune diseases

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    Although most autoimmune diseases are considered to be CD4 T cell- or antibody-mediated, many respond to CD20-depleting antibodies that have limited influence on CD4 and plasma cells. This includes rituximab, oblinutuzumab and ofatumumab that are used in cancer, rheumatoid arthritis and off-label in a large number of other autoimmunities and ocrelizumab in multiple sclerosis. Recently, the COVID-19 pandemic created concerns about immunosuppression in autoimmunity, leading to cessation or a delay in immunotherapy treatments. However, based on the known and emerging biology of autoimmunity and COVID-19, it was hypothesised that while B cell depletion should not necessarily expose people to severe SARS-CoV-2-related issues, it may inhibit protective immunity following infection and vaccination. As such, drug-induced B cell subset inhibition, that controls at least some autoimmunities, would not influence innate and CD8 T cell responses, which are central to SARS-CoV-2 elimination, nor the hypercoagulation and innate inflammation causing severe morbidity. This is supported clinically, as the majority of SARS-CoV-2-infected, CD20-depleted people with autoimmunity have recovered. However, protective neutralizing antibody and vaccination responses are predicted to be blunted until naive B cells repopulate, based on B cell repopulation kinetics and vaccination responses, from published rituximab and unpublished ocrelizumab (NCT00676715, NCT02545868) trial data, shown here. This suggests that it may be possible to undertake dose interruption to maintain inflammatory disease control, while allowing effective vaccination against SARS-CoV-29, if and when an effective vaccine is available

    Interferon Regulatory Factor-1 (IRF-1) Shapes Both Innate and CD8+ T Cell Immune Responses against West Nile Virus Infection

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    Interferon regulatory factor (IRF)-1 is an immunomodulatory transcription factor that functions downstream of pathogen recognition receptor signaling and has been implicated as a regulator of type I interferon (IFN)-Ξ±Ξ² expression and the immune response to virus infections. However, this role for IRF-1 remains controversial because altered type I IFN responses have not been systemically observed in IRF-1-/- mice. To evaluate the relationship of IRF-1 and immune regulation, we assessed West Nile virus (WNV) infectivity and the host response in IRF-1-/- cells and mice. IRF-1-/- mice were highly vulnerable to WNV infection with enhanced viral replication in peripheral tissues and rapid dissemination into the central nervous system. Ex vivo analysis revealed a cell-type specific antiviral role as IRF-1-/- macrophages supported enhanced WNV replication but infection was unaltered in IRF-1-/- fibroblasts. IRF-1 also had an independent and paradoxical effect on CD8+ T cell expansion. Although markedly fewer CD8+ T cells were observed in naΓ―ve animals as described previously, remarkably, IRF-1-/- mice rapidly expanded their pool of WNV-specific cytolytic CD8+ T cells. Adoptive transfer and in vitro proliferation experiments established both cell-intrinsic and cell-extrinsic effects of IRF-1 on the expansion of CD8+ T cells. Thus, IRF-1 restricts WNV infection by modulating the expression of innate antiviral effector molecules while shaping the antigen-specific CD8+ T cell response
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