Ultraspinning limits and super-entropic black holes

By employing the new ultraspinning limit we construct novel classes of black holes with non-compact event horizons and finite horizon area and study their thermodynamics. Our ultraspinning limit can be understood as a simple generating technique that consists of three steps: i) transforming the known rotating AdS black hole solution to a special coordinate system that rotates (in a given 2-plane) at infinity ii) boosting this rotation to the speed of light iii) compactifying the corresponding azimuthal direction. In so doing we qualitatively change the structure of the spacetime since it is no longer possible to return to a frame that does not rotate at infinity. The obtained black holes have non-compact horizons with topology of a sphere with two punctures. The entropy of some of these exceeds the maximal bound implied by the reverse isoperimetric inequality, such black holes are super-entropic.Comment: 19 pages, 6 figures; minor corrections as in published version, updated reference

Ultraspinning limits and rotating hyperboloid membranes

We apply the hyperboloid membrane limit to the general Kerr-AdS metrics and their recently studied super-entropic cousins and obtain a new class of rotating black holes, for which the rotational parameters in multiple directions attain their maximal value---equal to the AdS radius. These new solutions have a potential application in the description of holographic fluids with vorticity. They also possess interesting thermodynamic properties: we show that---despite the absence of Misner strings---the Bekenstein--Hawking entropy/area law is still violated, raising a question about the origin of this violation.Comment: 10 pages, 2 figures, REVTeX 4-

Burden of tuberculosis disease among adolescents in a rural cohort in Eastern Uganda

BACKGROUND: The world health organization (WHO) declared tuberculosis (TB) a global emergency, mainly affecting people in sub-Saharan Africa. However there is little data about the burden of TB among adolescents. We estimated the prevalence and incidence of TB and assessed factors associated with TB among adolescents aged 12–18 years in a rural population in Uganda in order to prepare the site for phase III clinical trials with novel TB vaccines among adolescents. METHODS: In a prospective cohort study, we recruited 5000 adolescents and followed them actively, every 6 months, for 1–2 years. Participants suspected of having TB were those who had any of; TB signs and symptoms, history of TB contact or a positive tuberculin skin test (TST) of ≥10 mm. Laboratory investigations included sputum smear microscopy and culture. RESULTS: Of the 5000 participants, eight culture confirmed cases of TB were found at baseline: a prevalence of 160/100,000 (95% confidence interval (CI), 69–315). There were 13 incident TB cases detected in an average of 1.1 person years: an incidence of 235/100,000 person years (95% CI, 125–402). None of the confirmed TB cases were HIV infected. Predictors for prevalent TB disease were: a history of TB contact and a cough ≥ 2 weeks at baseline and being out of school, while the only predictor for incident TB was a positive TST during follow-up. CONCLUSION: The TB incidence among adolescents in this rural part of Uganda seemed too low for a phase III TB vaccine trial. However, the study site demonstrated capability to handle a large number of participants with minimal loss to follow-up and its suitability for future clinical trials. Improved contact tracing in TB program activities is likely to increase TB case detection among adolescents. Future studies should explore possible pockets of higher TB incidence in urban areas and among out of school youth

Toxic Stress and Quality of Life in Early School‐Aged Ugandan Children With and Without Perinatal Human Immunodeficiency Virus Infection

Caregiver’s and child’s self‐reported quality of life (QOL) was defined using standardized questionnaires in a sample (N = 277) of 6–10 years old HIV‐infected, HIV‐exposed uninfected, and HIV‐unexposed uninfected children from Uganda. Psychosocial stress (acute stress and cumulative lifetime adversity) and physiologic stress (dysregulations across 13 biomarkers), perinatal HIV status, and their interaction were related to child QOL via general linear models. Lower child‐ and caregiver‐reported psychosocial stress were dose‐dependently associated with higher QOL (acute stress: mean difference coefficient b = 8.1–14.8, effect size [ES] = 0.46–0.83). Lower allostasis was dose‐dependently associated with higher QOL (b = 6.1–9.7, ES = 0.34–0.54). Given low caregiver acute stress, QOL for HIV‐infected was similar to HIV‐uninfected children; however, given high caregiver acute stress, a QOL disadvantage (b = −7.8, 95% CI: −12.8, −2.8; ES = −0.73) was evident for HIV‐infected versus uninfected children. Testing of caregiver stress reduction interventions is warranted to increase wellbeing in dependent children.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156459/2/cad20355.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156459/1/cad20355_am.pd

Anticoagulation and bleeding risk in patients with COVID-19

BACKGROUND: There is no current standardized approach to anticoagulation in patients with Coronavirus Disease 2019 (COVID-19) while potential bleeding risks remain. Our study characterizes the patterns of anticoagulation use in COVID-19 patients and the risk of related bleeding. METHODS: This is a single center retrospective analysis of 355 adult patients with confirmed diagnosis of COVID-19 from March 1 to May 31, 2020. Chi-square was used to analyze the relationship between degree of anticoagulant dose and bleeding events by site. Multivariable logistic regression was used to look at factors associated with inpatient death. RESULTS: 61% of patients were being treated with prophylactic doses of anticoagulation, while 7% and 29% were being treated with sub-therapeutic and therapeutic anticoagulation (TA) doses respectively. In 44% of patients, we found that the decision to escalate the dose of anticoagulation was based on laboratory values characterizing the severity of COVID-19 such as rising D-dimer levels. There were significantly higher rates of bleeding from non-CNS/non-GI sites (p = 0.039) and from any bleeding site overall (p = 0.019) with TA. TA was associated with significantly higher rates of inpatient death (41.6% vs 15.3% p \u3c 0.0001) compared to those without. All patients who developed CNS hemorrhage died p = 0.011. After multivariable logistic regression, only age OR 1.04 95% CI (1.01 to 1.07) p = 0.008 and therapeutic anticoagulation was associated with inpatient mortality OR 6.16 95% CI (2.96 to 12.83) p ≤ 0.0001. CONCLUSION: The use of TA was significantly associated with increased risk of bleeding. Bleeding in turn exhibited trends towards higher inpatient death among patients with COVID-19. These findings should be interpreted with caution and larger more controlled studies are needed to verify the net effects of anticoagulation in patients with COVID-19

Mobile Health–Supported HIV Self-Testing Strategy Among Urban Refugee and Displaced Youth in Kampala, Uganda: Protocol for a Cluster Randomized Trial (Tushirikiane, Supporting Each Other)

© Carmen Logie, Moses Okumu, Robert Hakiza, Daniel Kibuuka Musoke, Isha Berry, Simon Mwima, Peter Kyambadde, Uwase Mimy Kiera, Miranda Loutet, Stella Neema, Katie Newby, Clara McNamee, Stefan D Baral, Richard Lester, Joshua Musinguzi, Lawrence Mbuagbaw. Originally published in JMIR Research Protocols. This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/)Background: HIV is the leading cause of mortality among youth in sub-Saharan Africa. Uganda hosts over 1.43 million refugees, and more than 83,000 live in Kampala, largely in informal settlements. There is limited information about HIV testing uptake and preferences among urban refugee and displaced youth. HIV self-testing is a promising method for increasing testing uptake. Further, mobile health (mHealth) interventions have been effective in increasing HIV testing uptake and could be particularly useful among youth. Objective: This study aims to evaluate the feasibility and effectiveness of two HIV self-testing implementation strategies (HIV self-testing intervention alone and HIV self-testing combined with an mHealth intervention) in comparison with the HIV testing standard of care in terms of HIV testing outcomes among refugee/displaced youth aged 16 to 24 years in Kampala, Uganda. Methods: A three-arm cluster randomized controlled trial will be implemented across five informal settlements grouped into three sites, based on proximity, and randomization will be performed with a 1:1:1 method. Approximately 450 adolescents (150 per cluster) will be enrolled and followed for 12 months. Data will be collected at the following three time points: baseline enrollment, 8 months after enrollment, and 12 months after enrollment. Primary outcomes (HIV testing frequency, HIV status knowledge, linkage to confirmatory testing, and linkage to HIV care) and secondary outcomes (depression, condom use efficacy, consistent condom use, sexual relationship power, HIV stigma, and adolescent sexual and reproductive health stigma) will be evaluated. Results: The study has been conducted in accordance with CONSORT (Consolidated Standards of Reporting Trials) guidelines. The study has received ethical approval from the University of Toronto (June 14, 2019), Mildmay Uganda (November 11, 2019), and the Uganda National Council for Science and Technology (August 3, 2020). The Tushirikiane trial launched in February 2020, recruiting a total of 452 participants. Data collection was paused for 8 months due to COVID-19. Data collection for wave 2 resumed in November 2020, and as of December 10, 2020, a total of 295 participants have been followed-up. The third, and final, wave of data collection will be conducted between February and March 2021. Conclusions: This study will contribute to the knowledge of differentiated HIV testing implementation strategies for urban refugee and displaced youth living in informal settlements. We will share the findings in peer-reviewed manuscripts and conference presentations.Peer reviewe

The Potential for DPPIV/CD26 usage as a surrogate marker for Antiretroviral Therapy Efficacy in HIV Infected populations

Background: Human Immunodeficiency Virus (HIV) viral load and CD4+ cell counts are the most commonly used markers for monitoring efficacy of anti-retroviral therapy (ART) in HIV infected individuals. The high cost of viral load monitoring limits its usage in resource limited countries, often leaving the use of CD4+ T cell counts as the only alternative. Though cheaper and more readily available, CD4+ cell counts as a measure of detecting treatment failure, is an unreliable predictor of disease progression. Hence, there is a need for more sensitive alternative, but less costly techniques for detecting treatment failure which can be used in resource limited settings. Objective: To evaluate the feasibility of using plasma CD26/Dipeptidyl peptidase IV (DPPIV) as a novel marker for clinical evaluation of treatment efficacy in HIV infected children. Method: Blood samples collected from HIV+ children (n=76) before and after initiation on ART, were assessed for HIV RNA (viral load), CD4+ T-cell count and DPPIV/CD26 levels. Viral load levels were analyzed using Roche Amplicor HIV-1 Monitor Test kit; CD4+ T-Cell Counts were analyzed using BD FACS Calibur flow cytometer while DPPIV/CD 26 levels were analyzed using Human DPPIV/CD26 Quantikine ELISA kit (R&D Systems, Minneapolis MN). Results: The plasma DPPIV/CD26 levels increased significantly in children after ART initiation (p = 0.017), while the viral load levels declined after ART initiation with subsequent CD4+ cell counts increase. The DPPIV/CD 26 increase positively correlated with viral load decrease while negatively correlating to the CD4+ cell count increase. Conclusion: These findings demonstrate an inverse relationship between DPPIV/CD26 levels and HIV viral load and the direct proportionality of CD4+ Cell counts and DPPIV/CD26 levels, suggesting potential for use of DPPIV/CD26 as a surrogate marker for evaluating HIV disease progression in children receiving anti-retroviral therapy. Key words: CD26/Dipeptidyl peptidase IV (DPPIV), ELISA, Surrogate marker, Viral Load, CD4 Count, antiretroviral

A challenging response to a Lassa fever outbreak in a non endemic area of Sierra Leone in 2019 with export of cases to The Netherlands.

INTRODUCTION: On November 20, 2019, the Sierra Leone International Health Regulations (IHR) National Focal Point was notified of an exported case of Lassa fever in The Netherlands, by a Dutch doctor who previously practiced in a rural hospital in Sierra Leone. This report describes the extent of the outbreak, possible sources of infection, and the outbreak response measures taken. METHODS: Response measures implemented to control the outbreak included coordination across multiple countries and cities, outbreak investigation, active case finding, contact tracing and monitoring, laboratory investigation, and isolation and treatment of cases. RESULTS: We report a hospital-associated outbreak that resulted in 3 confirmed cases (health workers) and 2 probable cases (patients). The case fatality rate was 60%, whereas the secondary attack rate was 14%. Two cases involved exportations to The Netherlands. Failure to detect the index case and poor adherence to infection prevention and control (IPC) protocols contributed to disease spread. Pregnancy status and nonspecific signs and symptoms of the index case contributed to failure in early case detection. CONCLUSIONS: Rapid activation of national and subnational incident management systems resulted in rapid outbreak control. We recommend regular training for clinicians on surveillance and IPC protocols and strengthening in-country Lassa virus diagnostic capacity

Implementation of Electronic Adherence Monitors and Associated Interventions for Routine HIV Antiretroviral Therapy in Uganda: Promising Findings

BackgroundHigh, sustained adherence is critical for achieving the individual and public health benefits of HIV antiretroviral therapy (ART). Electronic monitors provide detailed adherence information and can enable real-time interventions; however, their use to date has largely been confined to research. This pilot study (NCT03825952) sought to understand feasibility and acceptability a relatively low-cost version of this technology and associated interventions for routine ART delivery in sub-Saharan Africa.MethodsWe provided two ART clinics in rural, southwestern Uganda with electronic adherence monitors for data-informed counseling as well as optional SMS messages to clients and/or social supporters (daily or triggered by missed or delayed doses) and/or an alarm. Clinic and ART client experiences were observed for 3 months per client, including time and motion studies. Qualitative interviews among clients, clinicians, and healthcare administrators were informed by the Consolidated Framework for Implementation Research.ResultsFifty-one ART clients were enrolled; 57% were male and the median age was 34 years. Choice of associated intervention varied among participants. The median number of visits during follow-up was two per client. Counselors reviewed the adherence data with 90% of clients at least once; 67% reviewed data at all visits. Average adherence was 94%; four clients had adherence gaps >1 week. Acceptability was high; all but one client found the monitor "very useful” and all found SMS “very useful.” Clinic visits among clients with the intervention lasted 4 min longer on average than those in standard care. The monitors and daily SMS generally functioned well, although excess SMS were triggered, primarily due to cellular network delays. Overall, participants felt the technology improved adherence, clinic experiences, and clinician-client relationships. Few worried about stigma and privacy. Cost was a concern for implementation, particularly at scale.ConclusionWe successfully implemented a relatively low-cost electronic ART adherence monitor and associated interventions for routine care in rural Uganda. Feasibility and acceptability were generally high, and individuals were identified who could benefit from adherence support. Future work should involve longitudinal follow-up of diverse populations, clinical outcomes, and detailed cost-effectiveness analysis to help drive policy decisions around the uptake of this technology for routine clinical care.Clinical Trial Registrationidentifier: NCT03825952

Pooled Individual Data Analysis of 5 Randomized Trials of Infant Nevirapine Prophylaxis to Prevent Breast-Milk HIV-1 Transmission

Background. In resource-limited settings, mothers infected with human immunodeficiency virus type 1 (HIV-1) face a difficult choice: breastfeed their infants but risk transmitting HIV-1 or not breastfeed their infants and risk the infants dying of other infectious diseases or malnutrition. Recent results from observational studies and randomized clinical trials indicate daily administration of nevirapine to the infant can prevent breast-milk HIV-1 transmission