Early Success With Retention in Care Among People Living With HIV at Decentralized ART Satellite Sites in Yangon, Myanmar, 2015–2016

Introduction: Myanmar is one of the countries in the Asia-Pacific region hit hardest by the HIV epidemic that is concentrated among urban areas and key populations. In 2014, the National AIDS Programme (NAP) launched a new model of decentralized service delivery with the establishment ART satellite sites with care delivered by HIV peer workers.Methods: ART satellite sites are implemented by non-government organizations to service high burden HIV areas and populations that suffer stigma or find access to public sector services difficult. They provide continuity of HIV care from outreach testing, counseling, linkage to care, and retention in care. Anti-retroviral (ART) initiation occurs at health facilities by specialist physicians. We conducted a retrospective cohort study of people living with HIV (PLHIV) who were initiated on ART from 2015 to 2016 at five ART satellite sites in Yangon, Myanmar to assess outcomes and time from enrolment to ART initiation.Results: Of 1,339 PLHIV on ART treatment in 2015–16, 1,157 (89%) were retained, and 5% were lost from care and 5% reported dead, at the end of March 2018. Attrition rates (death and lost-to-follow-up) were found to be significantly associated with a CD4 count ≤ 50 cells/mm3 and having baseline weight ≤ 50 kg. Median time taken from enrolment to ART initiation was 1.9 months (interquartile range: 1.4–2.5).Conclusion: We report high rates of retention in care of PLHIV in a new model of ART satellite sties in Yangon, Myanmar after 3 years of follow-up. The delays identified in time taken from enrolment to ART initiation need to be explored further and addressed. This initial study supports continuation of plans to scale-up ART satellite sites in Myanmar. To optimize outcomes for patients and the program and accelerate progress to reduce HIV transmission and end the HIV epidemic, operational research needs to be embedded within the response

A small insulinomimetic molecule also improves insulin sensitivity in diabetic mice

Dramatic increase of diabetes over the globe is in tandem with the increase in insulin requirement. This is because destruction and dysfunction of pancreatic β-cells are of common occurrence in both Type1 diabetes and Type2 diabetes, and insulin injection becomes a compulsion. Because of several problems associated with insulin injection, orally active insulin mimetic compounds would be ideal substitute. Here we report a small molecule, a peroxyvanadate compound i.e. DmpzH[VO(O2)2(dmpz)], henceforth referred as dmp, which specifically binds to insulin receptor with considerable affinity (KD-1.17μM) thus activating insulin receptor tyrosine kinase and its downstream signaling molecules resulting increased uptake of [14C] 2 Deoxy-glucose. Oral administration of dmp to streptozotocin treated BALB/c mice lowers blood glucose level and markedly stimulates glucose and fatty acid uptake by skeletal muscle and adipose tissue respectively. In db/db mice, it greatly improves insulin sensitivity through excess expression of PPARγ and its target genes i.e. adiponectin, CD36 and aP2. Study on the underlying mechanism demonstrated that excess expression of Wnt3a decreased PPARγ whereas dmp suppression of Wnt3a gene increased PPARγ expression which subsequently augmented adiponectin. Increased production of adiponectin in db/db mice due to dmp effected lowering of circulatory TG and FFA levels, activates AMPK in skeletal muscle and this stimulates mitochondrial biogenesis and bioenergetics. Decrease of lipid load along with increased mitochondrial activity greatly improves energy homeostasis which has been found to be correlated with the increased insulin sensitivity. The results obtained with dmp, therefore, strongly indicate that dmp could be a potential candidate for insulin replacement therapy

Systematic Errors in Sunyaev-Zeldovich Surveys of Galaxy Cluster Velocities

Galaxy cluster surveys compiled via the Sunyaev-Zeldovich Effect have the potential to place strong constraints on cosmology, and in particular the nature of dark energy. Here we consider cluster velocity surveys using kinetic Sunyaev-Zeldovich measurements. Cluster velocities closely trace the large-scale velocity field independent of cluster mass; we demonstrate that two useful cluster velocity statistics are nearly independent of cluster mass, in marked contrast to cluster number count statistics. On the other hand, cluster velocity determinations from three-band observations of Sunyaev-Zeldovich distortions can require additional cluster data or assumptions, and are complicated by microwave emission from dusty galaxies and radio sources, which may be correlated with clusters. Systematic errors in velocity due to these factors can give substantial biases in determination of dark energy parameters, although large cluster velocity surveys will contain enough information that the errors can be modeled using the data itself, with little degradation in cosmological constraints.Comment: 8 pages, 2 figures. Minor changes in the text to match the accepted version. Conclusions unchange

Gridded and direct Epoch of Reionisation bispectrum estimates using the Murchison Widefield Array

We apply two methods to estimate the 21~cm bispectrum from data taken within the Epoch of Reionisation (EoR) project of the Murchison Widefield Array (MWA). Using data acquired with the Phase II compact array allows a direct bispectrum estimate to be undertaken on the multiple redundantly-spaced triangles of antenna tiles, as well as an estimate based on data gridded to the $uv$-plane. The direct and gridded bispectrum estimators are applied to 21 hours of high-band (167--197~MHz; $z$=6.2--7.5) data from the 2016 and 2017 observing seasons. Analytic predictions for the bispectrum bias and variance for point source foregrounds are derived. We compare the output of these approaches, the foreground contribution to the signal, and future prospects for measuring the bispectra with redundant and non-redundant arrays. We find that some triangle configurations yield bispectrum estimates that are consistent with the expected noise level after 10 hours, while equilateral configurations are strongly foreground-dominated. Careful choice of triangle configurations may be made to reduce foreground bias that hinders power spectrum estimators, and the 21~cm bispectrum may be accessible in less time than the 21~cm power spectrum for some wave modes, with detections in hundreds of hours.Comment: 19 pages, 10 figures, accepted for publication in PAS

Measurement of nuclear modification factors of gamma(1S)), gamma(2S), and gamma(3S) mesons in PbPb collisions at root s(NN)=5.02 TeV

The cross sections for ϒ(1S), ϒ(2S), and ϒ(3S) production in lead-lead (PbPb) and proton-proton (pp) collisions at √sNN = 5.02 TeV have been measured using the CMS detector at the LHC. The nuclear modification factors, RAA, derived from the PbPb-to-pp ratio of yields for each state, are studied as functions of meson rapidity and transverse momentum, as well as PbPb collision centrality. The yields of all three states are found to be significantly suppressed, and compatible with a sequential ordering of the suppression, RAA(ϒ(1S)) > RAA(ϒ(2S)) > RAA(ϒ(3S)). The suppression of ϒ(1S) is larger than that seen at √sNN = 2.76 TeV, although the two are compatible within uncertainties. The upper limit on the RAA of ϒ(3S) integrated over pT, rapidity and centrality is 0.096 at 95% confidence level, which is the strongest suppression observed for a quarkonium state in heavy ion collisions to date. © 2019 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Funded by SCOAP3.Peer reviewe

The Spectrum of Chromobacterium violaceum Infections from a Single Geographic Location.

Chromobacterium violaceum is a bacterium associated with soil and water exposure in tropical regions and causes rare and serious clinical infections that are often fatal. We reviewed the demographic and clinical details of 28 patients with C. violaceum detected over 15 years from 2000 to 2015, from the Top End of the Northern Territory. Of these patients, 18 had infections attributable toC. violaceum Patients with infections were more commonly male (55.6%), and in the 16- to 60-year (61.1%) age group. Skin and soft tissue infections (50%), predominantly involving the limbs, were the major clinical manifestation. Water, mud exposure, and trauma were all noted as precipitating circumstances and comorbidities were present in 61.1% of the patients with infections. Of the 28 patients, 10 (35.8%) had C. violaceum isolated as an incidental finding or as asymptomatic colonization; these 10 patients did not require or receive therapy for C. violaceum bacterial infections. There were no relapsing infections in this group.Chromobacterium violaceum remains a serious infection, with seven patients (25%) in our series requiring intensive care management. However, the mortality rate (7.1%) in our series was far lower than previously described. This case series of C. violaceum infections from a single geographic area provides additional information of the characteristics of infection with this pathogen

Shifting the paradigm: using disease outbreaks to build resilient health systems

Disease outbreaks and health emergencies can push health systems to a breaking point, especially fragile systems. Building resilient and responsive health systems is an imperative for the global health community and there is an important opportunity to address health systems strengthening activities during outbreak response. The resources dedicated to outbreaks create organisational infrastructure, capacity and networks that can be leveraged to simultaneously strengthen health systems. It is necessary to shift the current paradigm of managing outbreaks to include health system strengthening as a critical component of the response. We identify 10 activities that could be implemented during health emergencies to achieve this goal

NF-κB mediates lipid-induced fetuin-A expression in hepatocytes that impairs adipocyte function effecting insulin resistance

Fetuin-A, a hepatic secretory protein, has recently been implicated in insulin resistance and Type 2 diabetes. It is an endogenous inhibitor of insulin receptor tyrosine kinase. However, regulation of fetuin-A synthesis in relation to insulin resistance is unclear. In the present paper, we report that both non-esterified (‘free’) fatty acids and fetuin-A coexist at high levels in the serum of db/db mice, indicating an association between them. For an in-depth study, we incubated palmitate with HepG2 cells and rat primary hepatocytes, and found enhanced fetuin-A secretion to more than 4-fold over the control. Interestingly, cell lysates from these incubations showed overexpression and activity of NF-κB (nuclear factor κB). In NF-κB-knockout HepG2 cells, palmitate failed to increase fetuin-A secretion, whereas forced expression of NF-κB released fetuin-A massively in the absence of palmitate. Moreover, palmitate stimulated NF-κB binding to the fetuin-A promoter resulting in increased reporter activity. These results suggest NF-κB to be the mediator of the palmitate effect. Palmitate-induced robust expression of fetuin-A indicates the occurrence of additional targets, and we found that fetuin-A severely impaired adipocyte function leading to insulin resistance. Our results reveal a new dimension of lipid-induced insulin resistance and open another contemporary target for therapeutic intervention in Type 2 diabetes