Implementation of HIV Self-Testing to Reach Men in Rural uMkhanyakude, KwaZulu-Natal, South Africa. a DO-ART Trial Sub Study

Background: KwaZulu–Natal, South Africa has one of the highest HIV prevalence rates globally. Persons <35 years and men have lower rates of HIV testing. HIV self-testing (HIVST) may overcome many barriers of facility-based HIV testing in order to identify HIV positive young persons and men and link them to care. We investigated whether HIVST distribution was a feasible approach to reach men and assessed the proportion of participants who reported their HIVST results, tested positive and linked to care. / Methods: Teams comprised of a nurse, clinic research assistant, and recruiters distributed HIVST kits in rural uMkhanyakude, KwaZulu-Natal from August—November 2018 with a focus on testing men. Workplaces (farms), social venues, taxi ranks, and homesteads were used as HIVST kit distribution points following community sensitisation through community advisory boards and community leaders. HIVST kits, demonstration of use, and small incentives to report testing outcomes were provided. The Department of Health provided confirmatory testing and HIV care at clinics. / Results: Over 11 weeks in late 2018, we distributed 2,634 HIVST kits of which 2,113 (80%) were distributed to persons aged <35 years, 2,591 (98%) to men and 356 (14%) to first time testers. Of the HIVST distributed, 2,107 (80%) reported their results to the study team, and 157 (7%) tested positive. Of persons who tested positive, 107/130 (82%) reported having a confirmatory test of which 102/107 (95%) were positive and initiated on ART. No emergencies or social harms were reported. / Conclusion: Large scale distribution of HIVST kits targeting men in rural KwaZulu-Natal is feasible and highly effective in reaching men, including those who had not previously tested for HIV. While two-thirds of persons who tested HIV positive initiated ART, additional linkage strategies are needed for those who do not link after HIVST. HIVST should be used as a tool to reach men in order to achieve 95% coverage in the UNAIDS testing and care cascade in KwaZulu-Natal

Impact of N-myc amplification on median survival in children with neuroblastoma

Background: Neuroblastoma is the most common extracranial malignant solid tumor in children under 5 years, and it is characterized by wide clinical and biological heterogeneity. N-myc oncogene amplification is considered to be one of the most important prognostic factors used to evaluate survival in these patients. Objectives: The aim of our study was to determine amplification of the N-myc oncogene using real-time quantitative polymerase chain reaction (PCR) and to show the influence of N-myc amplified tumors on the overall survival rate. Patients and Methods: This study is an analytical historical cohort study of forty children with neuroblastoma admitted to the Shafa Hospital, Iran from 1999 to 2010. Paraffined blocks of tumoral tissue were analyzed for N-myc amplification by a PCR. The degree of N-myc amplification was derived from the ratio of the N-myc oncogene and the single copy reference gene, NAGK. In the statistical analysis, a Kaplan-Meier survival analysis was used. Results: We found a variable degree of N-myc amplification, from 3 to 2 200, in 32 of the 40 neuroblastomas (80%). NMYC amplification was seen more frequently in patients older than 2.5 years (71.9%), stage 4 (65.6%) and female (53.1%). Median survival time in the males was significantly longer than in the females (P = 0.03). The overall median survival for N-myc amplified tumor patients was 20 months, and 30 months for the non amplified tumors. Conclusions: The N-myc amplified tumors may increase the probability of more aggressive behavior and rapid tumor progression, especially in advanced stages of neuroblastoma. This study confirmed the importance of obtaining correct measurements of oncogene amplification in the early evaluation of neuroblastomas in order to target more aggressive therapies in patients with a higher risk of cancer progression

de Branges-Rovnyak spaces: basics and theory

For $S$ a contractive analytic operator-valued function on the unit disk ${\mathbb D}$, de Branges and Rovnyak associate a Hilbert space of analytic functions ${\mathcal H}(S)$ and related extension space ${\mathcal D(S)}$ consisting of pairs of analytic functions on the unit disk ${\mathbb D}$. This survey describes three equivalent formulations (the original geometric de Branges-Rovnyak definition, the Toeplitz operator characterization, and the characterization as a reproducing kernel Hilbert space) of the de Branges-Rovnyak space ${\mathcal H}(S)$, as well as its role as the underlying Hilbert space for the modeling of completely non-isometric Hilbert-space contraction operators. Also examined is the extension of these ideas to handle the modeling of the more general class of completely nonunitary contraction operators, where the more general two-component de Branges-Rovnyak model space ${\mathcal D}(S)$ and associated overlapping spaces play key roles. Connections with other function theory problems and applications are also discussed. More recent applications to a variety of subsequent applications are given in a companion survey article

Coherent spinor dynamics in a spin-1 Bose condensate

Collisions in a thermal gas are perceived as random or incoherent as a consequence of the large numbers of initial and final quantum states accessible to the system. In a quantum gas, e.g. a Bose-Einstein condensate or a degenerate Fermi gas, the phase space accessible to low energy collisions is so restricted that collisions be-come coherent and reversible. Here, we report the observation of coherent spin-changing collisions in a gas of spin-1 bosons. Starting with condensates occupying two spin states, a condensate in the third spin state is coherently and reversibly created by atomic collisions. The observed dynamics are analogous to Josephson oscillations in weakly connected superconductors and represent a type of matter-wave four-wave mixing. The spin-dependent scattering length is determined from these oscillations to be -1.45(18) Bohr. Finally, we demonstrate coherent control of the evolution of the system by applying differential phase shifts to the spin states using magnetic fields.Comment: 19 pages, 3 figure

A Qualitative Analysis of Experiential Challenges Associated with Meditation Practice

Although empirical interest in meditation has flourished in recent years, few studies have addressed possible downsides of meditation practice, particularly in community populations. In-depth interviews were conducted with 30 male meditators in London, UK, recruited using principles of maximum variation sampling, and analysed using a modified constant comparison approach. Having originally set out simply to inquire about the impact of various meditation practices (including but not limited to mindfulness) on men’s wellbeing, we uncovered psychological challenges associated with its practice. While meditation was generally reported to be conducive to wellbeing, substantial difficulties accounted for approximately one quarter of the interview data. Our paper focuses specifically on these issues in order to alert health professionals to potential challenges associated with meditation. Four main problems of increasing severity were uncovered: Meditation was a difficult skill to learn and practise; participants encountered troubling thoughts and feelings which were hard to manage; meditation reportedly exacerbated mental health issues, such as depression and anxiety; and in a few cases, meditation was associated with psychotic episodes. Our paper raises important issues around safeguarding those who practise meditation, both within therapeutic settings and in the community

MicroRNA Expression Data Reveals a Signature of Kidney Damage following Ischemia Reperfusion Injury

Ischemia reperfusion injury (IRI) is a leading cause of acute kidney injury, a common problem worldwide associated with significant morbidity and mortality. We have recently examined the role of microRNAs (miRs) in renal IRI using expression profiling. Here we conducted mathematical analyses to determine if differential expression of miRs can be used to define a biomarker of renal IRI. Principal component analysis (PCA) was combined with spherical geometry to determine whether samples that underwent renal injury as a result of IRI can be distinguished from controls based on alterations in miR expression using our data set consisting of time series measuring 571 miRs. Using PCA, we examined whether changes in miR expression in the kidney following IRI have a distinct direction when compared to controls based on the trajectory of the first three principal components (PCs) for our time series. We then used Monte Carlo methods and spherical geometry to assess the statistical significance of these directions. We hypothesized that if IRI and control samples exhibit distinct directions, then miR expression can be used as a biomarker of injury. Our data reveal that the pattern of miR expression in the kidney following IRI has a distinct direction based on the trajectory of the first three PCs and can be distinguished from changes observed in sham controls. Analyses of samples from immunodeficient mice indicated that the changes in miR expression observed following IRI were lymphocyte independent, and therefore represent a kidney intrinsic response to injury. Together, these data strongly support the notion that IRI results in distinct changes in miR expression that can be used as a biomarker of injury

Contribution of microscopy for understanding the mechanism of action against trypanosomatids

Transmission electron microscopy (TEM) has proved to be a useful tool to study the ultrastructural alterations and the target organelles of new antitrypanosomatid drugs. Thus, it has been observed that sesquiterpene lactones induce diverse ultrastructural alterations in both T. cruzi and Leishmania spp., such as cytoplasmic vacuolization, appearance of multilamellar structures, condensation of nuclear DNA, and, in some cases, an important accumulation of lipid vacuoles. This accumulation could be related to apoptotic events. Some of the sesquiterpene lactones (e.g., psilostachyin) have also been demonstrated to cause an intense mitochondrial swelling accompanied by a visible kinetoplast deformation as well as the appearance of multivesicular bodies. This mitochondrial swelling could be related to the generation of oxidative stress and associated to alterations in the ergosterol metabolism. The appearance of multilamellar structures and multiple kinetoplasts and flagella induced by the sesquiterpene lactone psilostachyin C indicates that this compound would act at the parasite cell cycle level, in an intermediate stage between kinetoplast segregation and nuclear division. In turn, the diterpene lactone icetexane has proved to induce the external membrane budding on T. cruzi together with an apparent disorganization of the pericellar cytoskeleton. Thus, ultrastructural TEM studies allow elucidating the possible mechanisms and the subsequent identification of molecular targets for the action of natural compounds on trypanosomatids.Fil: Lozano, Esteban Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Spina Zapata, Renata María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Barrera, Patricia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Tonn, Carlos Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; ArgentinaFil: Sosa Escudero, Miguel Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentin

Community-based antiretroviral therapy versus standard clinic-based services for HIV in South Africa and Uganda (DO ART): a randomised trial

Background: Community-based delivery of antiretroviral therapy (ART) for HIV, including ART initiation, clinical and laboratory monitoring, and refills, could reduce barriers to treatment and improve viral suppression, reducing the gap in access to care for individuals who have detectable HIV viral load, including men who are less likely than women to be virally suppressed. We aimed to test the effect of community-based ART delivery on viral suppression among people living with HIV not on ART. / Methods: We did a household-randomised, unblinded trial (DO ART) of delivery of ART in the community compared with the clinic in rural and peri-urban settings in KwaZulu-Natal, South Africa and the Sheema District, Uganda. After community-based HIV testing, people living with HIV were randomly assigned (1:1:1) with mobile phone software to community-based ART initiation with quarterly monitoring and ART refills through mobile vans; ART initiation at the clinic followed by mobile van monitoring and refills (hybrid approach); or standard clinic ART initiation and refills. The primary outcome was HIV viral suppression at 12 months. If the difference in viral suppression was not superior between study groups, an a-priori test for non-inferiority was done to test for a relative risk (RR) of more than 0·95. The cost per person virally suppressed was a co-primary outcome of the study. This study is registered with ClinicalTrials.gov, NCT02929992. / Findings: Between May 26, 2016, and March 28, 2019, of 2479 assessed for eligibility, 1315 people living with HIV and not on ART with detectable viral load at baseline were randomly assigned; 666 (51%) were men. Retention at the month 12 visit was 95% (n=1253). At 12 months, community-based ART increased viral suppression compared with the clinic group (306 [74%] vs 269 [63%], RR 1·18, 95% CI 1·07–1·29; psuperiority=0·0005) and the hybrid approach was non-inferior (282 [68%] vs 269 [63%], RR 1·08, 0·98–1·19; pnon-inferiority=0·0049). Community-based ART increased viral suppression among men (73%, RR 1·34, 95% CI 1·16–1·55; psuperiority<0·0001) as did the hybrid approach (66%, RR 1·19, 1·02–1·40; psuperiority=0·026), compared with clinic-based ART (54%). Viral suppression was similar for men (n=156 [73%]) and women (n=150 [75%]) in the community-based ART group. With efficient scale-up, community-based ART could cost US$275–452 per person reaching viral suppression. Community-based ART was considered safe, with few adverse events. / Interpretation: In high and medium HIV prevalence settings in South Africa and Uganda, community-based delivery of ART significantly increased viral suppression compared with clinic-based ART, particularly among men, eliminating disparities in viral suppression by gender. Community-based ART should be implemented and evaluated in different contexts for people with detectable viral load. / Funding: The Bill & Melinda Gates Foundation; the University of Washington and Fred Hutch Center for AIDS Research; the Wellcome Trust; the University of Washington Royalty Research Fund; and the University of Washington King K Holmes Endowed Professorship in STDs and AIDS