HIV policy in Jamaica: good form and substance but inadequate application and accountability

The HIV epidemic and response in Jamaica was reviewed in April–November 2019 as part of the preparation of a National Strategic Plan for 2020-25. The National HIV Programme, which includes multi-sectoral partners, has made substantial achievements in reducing the spread of HIV in the population. Mortality due to HIV in Jamaica has decreased from 25 deaths/100,000 population in 2004 to 13 deaths/100,000 population in 2016. Jamaica has committed to the UNAIDS fast track strategy for ending the AIDS epidemic, but HIV incidence rates remain too high, (1,600/100,000 in 2018). This paper reviews key national policies that have guided Jamaica’s HIV response. We discuss challenges and gaps in policy application and development that impede Jamaica’s efforts to achieve universal access to HIV prevention, treatment and care services

“Do you think your main partner has other sex partners?” A simple question provides insight into sexual risk in Jamaica

To estimate the association between a simple measure of sexual partner concurrency and sexually transmitted infection (STI) we conducted a cross-sectional population-based household survey (n=1795) and targeted surveys of people at venues where people meet sexual partners (n=1580) to ask about sexual behavior. Persons interviewed at venues were tested for HIV, gonorrhoea, chlamydia, gonorrhea, and trichomoniasis. We compared the association between STI and reporting a partner had other partners. More women than men reported their main partner had other partners. Thirteen percent of all women in the population-based survey and 14.4% in the targeted survey reported having one partner in the past 12 months and that partner had additional partners. STI prevalence was significantly associated with reporting a partner had other partners (36.8% vs 30.2%; prevalence ratio [PR]1.2; 95% CI 1.1,1.4). Construction of complete sexual networks is costly and not routinely feasible. We recommend adding a question to cross-sectional surveys used to monitor sexual behavior about whether the respondent believes his or her partner has other sexual partners. Although subject to bias, the question was useful in Jamaica to identify a group of women with only one sexual partner at increased risk of infection

The Comprehensive Post-Acute Stroke Services (COMPASS) study: design and methods for a cluster-randomized pragmatic trial

Background: Patients discharged home after stroke face significant challenges managing residual neurological deficits, secondary prevention, and pre-existing chronic conditions. Post-discharge care is often fragmented leading to increased healthcare costs, readmissions, and sub-optimal utilization of rehabilitation and community services. The COMprehensive Post-Acute Stroke Services (COMPASS) Study is an ongoing cluster-randomized pragmatic trial to assess the effectiveness of a comprehensive, evidence-based, post-acute care model on patient-centered outcomes. Methods: Forty-one hospitals in North Carolina were randomized (as 40 units) to either implement the COMPASS care model or continue their usual care. The recruitment goal is 6000 patients (3000 per arm). Hospital staff ascertain and enroll patients discharged home with a clinical diagnosis of stroke or transient ischemic attack. Patients discharged from intervention hospitals receive 2-day telephone follow-up; a comprehensive clinic visit within 2 weeks that includes a neurological evaluation, assessments of social and functional determinants of health, and an individualized COMPASS Care PlanTM integrated with a community-specific resource database; and additional follow-up calls at 30 and 60 days post-stroke discharge. This model is consistent with the Centers for Medicare and Medicaid Services transitional care management services provided by physicians or advanced practice providers with support from a nurse to conduct patient assessments and coordinate follow-up services. Patients discharged from usual care hospitals represent the control group and receive the standard of care in place at that hospital. Patient-centered outcomes are collected from telephone surveys administered at 90 days. The primary endpoint is patient-reported functional status as measured by the Stroke Impact Scale 16. Secondary outcomes are: caregiver strain, all-cause readmissions, mortality, healthcare utilization, and medication adherence. The study engages patients, caregivers, and other stakeholders (including policymakers, advocacy groups, payers, and local community coalitions) to advise and support the design, implementation, and sustainability of the COMPASS care model. Discussion: Given the high societal and economic burden of stroke, identifying a care model to improve recovery, independence, and quality of life is critical for stroke survivors and their caregivers. The pragmatic trial design provides a real-world assessment of the COMPASS care model effectiveness and will facilitate rapid implementation into clinical practice if successful

8--13 um spectroscopy of YSOs: Evolution of the silicate feature

In order to investigate possible connections between dust processing and disk properties, 8--13 um spectra of 34 young stars, with a range of circumstellar environments and spectral types A to M, were obtained using the Long Wavelength Spectrometer at the W. M. Keck Observatory. The broad 9.7 um amorphous silicate feature which dominates this wavelength regime evolves from absorption in young, embedded sources, to emission in optically revealed stars, and to complete absence in older debris disk systems for both low- and intermediate-mass stars. The peak wavelength and FWHM are centered about 9.7 and ~2.3 um, corresponding to amorphous olivine, with a larger spread in FWHM for embedded sources and in peak wavelength for disks. In a few of our objects that have been previously identified as class I low-mass YSOs, the observed silicate feature is complex, with absorption near 9.5 um and emission peaking around 10 um. Although most of the emission spectra show broad classical features attributed to amorphous silicates, variations in the shape/strength may be linked to dust processing, including grain growth and/or silicate crystallization. We study quantitatively the evidence for evolutionary trends in the 8--13 um spectra through a variety of spectral shape diagnostics. Based on the lack of correlation between these diagnostics and broad-band infrared luminosity characteristics for silicate emission sources, we conclude that although spectral signatures of dust processing are present, they can not be connected clearly to disk evolutionary stage (for optically thick disks) or optical depth (for optically thin disks). The diagnostics of silicate absorption features (other than the central wavelength of the feature), however, are tightly correlated with optical depth.Comment: 27 pages, 13 figures, accepted for publication by ApJ, formatted with emulateapj using revtex4 v4.

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Cell Cycle Genes Are the Evolutionarily Conserved Targets of the E2F4 Transcription Factor

Maintaining quiescent cells in G0 phase is achieved in part through the multiprotein subunit complex known as DREAM, and in human cell lines the transcription factor E2F4 directs this complex to its cell cycle targets. We found that E2F4 binds a highly overlapping set of human genes among three diverse primary tissues and an asynchronous cell line, which suggests that tissue-specific binding partners and chromatin structure have minimal influence on E2F4 targeting. To investigate the conservation of these transcription factor binding events, we identified the mouse genes bound by E2f4 in seven primary mouse tissues and a cell line. E2f4 bound a set of mouse genes that was common among mouse tissues, but largely distinct from the genes bound in human. The evolutionarily conserved set of E2F4 bound genes is highly enriched for functionally relevant regulatory interactions important for maintaining cellular quiescence. In contrast, we found minimal mRNA expression perturbations in this core set of E2f4 bound genes in the liver, kidney, and testes of E2f4 null mice. Thus, the regulatory mechanisms maintaining quiescence are robust even to complete loss of conserved transcription factor binding events

Killer cell immunoglobulin-like receptor 3DL1-mediated recognition of human leukocyte antigen B [Letter]

Members of the killer cell immunoglobulin-like receptor (KIR) family, a large group of polymorphic receptors expressed on natural killer (NK) cells, recognize particular peptide-laden human leukocyte antigen (pHLA) class I molecules and have a pivotal role in innate immune responses1. Allelic variation and extensive polymorphism within the three-domain KIR family (KIR3D, domains D0–D1–D2) affects pHLA binding specificity and is linked to the control of viral replication and the treatment outcome of certain haematological malignancies1, 2, 3. Here we describe the structure of a human KIR3DL1 receptor bound to HLA-B*5701 complexed with a self-peptide. KIR3DL1 clamped around the carboxy-terminal end of the HLA-B*5701 antigen-binding cleft, resulting in two discontinuous footprints on the pHLA. First, the D0 domain, a distinguishing feature of the KIR3D family, extended towards β2-microglobulin and abutted a region of the HLA molecule with limited polymorphism, thereby acting as an ‘innate HLA sensor’ domain. Second, whereas the D2–HLA-B*5701 interface exhibited a high degree of complementarity, the D1–pHLA-B*5701 contacts were suboptimal and accommodated a degree of sequence variation both within the peptide and the polymorphic region of the HLA molecule. Although the two-domain KIR (KIR2D) and KIR3DL1 docked similarly onto HLA-C4, 5 and HLA-B respectively, the corresponding D1-mediated interactions differed markedly, thereby providing insight into the specificity of KIR3DL1 for discrete HLA-A and HLA-B allotypes. Collectively, in association with extensive mutagenesis studies at the KIR3DL1–pHLA-B*5701 interface, we provide a framework for understanding the intricate interplay between peptide variability, KIR3D and HLA polymorphism in determining the specificity requirements of this essential innate interaction that is conserved across primate species

The effect of probiotics and zinc supplementation on the immune response to oral rotavirus vaccine: A randomized, factorial design, placebo-controlled study among Indian infants.

BACKGROUND: Strategies are needed to improve oral rotavirus vaccine (RV), which provides suboptimal protection in developing countries. Probiotics and zinc supplementation could improve RV immunogenicity by altering the intestinal microbiota and immune function. METHODS: Infants 5weeks old living in urban Vellore, India were enrolled in a randomized, double-blind, placebo-controlled trial with a 4-arm factorial design to assess the effects of daily zinc (5mg), probiotic (1010Lactobacillus rhamnosus GG) or placebo on the immunogenicity of two doses of RV (Rotarix®, GlaxoSmithKline Biologicals) given at 6 and 10weeks of age. Infants were eligible for participation if healthy, available for the study duration and without prior receipt of RV or oral poliovirus vaccine other than the birth dose. The primary outcome was seroconversion to rotavirus at 14weeks of age based on detection of VP6-specific IgA at ?20U/ml in previously seronegative infants or a fourfold rise in concentration. RESULTS: The study took place during July 2012 to February 2013. 620 infants were randomized equally between study arms and 551 (88.9%) completed per protocol. Seroconversion was recorded in 54/137 (39.4%), 42/136 (30.9%), 40/143 (28.0%), and 37/135 (27.4%) infants receiving (1) probiotic and zinc, (2) probiotic and placebo, (3) placebo and zinc, (4) two placebos. Seroconversion showed a modest improvement among infants receiving probiotic (difference between groups 1, 2 and 3, 4 was 7.5% (97.5% Confidence Interval (CI): -1.4%, 16.2%), p=0.066) but not zinc (difference between groups 1, 3 and 2, 4 was 4.4% (97.5% CI: -4.4%, 13.2%), p=0.272). 16 serious adverse events were recorded, none related to study interventions. CONCLUSIONS: Zinc or probiotic supplementation did not significantly improve the low immunogenicity of rotavirus vaccine given to infants in a poor urban community in India. A modest effect of combined supplementation deserves further investigation. TRIAL REGISTRATION: The trial was registered in India (CTRI/2012/05/002677)

Genome-Wide Association Study Using Extreme Truncate Selection Identifies Novel Genes Affecting Bone Mineral Density and Fracture Risk

Osteoporotic fracture is a major cause of morbidity and mortality worldwide. Low bone mineral density (BMD) is a major predisposing factor to fracture and is known to be highly heritable. Site-, gender-, and age-specific genetic effects on BMD are thought to be significant, but have largely not been considered in the design of genome-wide association studies (GWAS) of BMD to date. We report here a GWAS using a novel study design focusing on women of a specific age (postmenopausal women, age 55–85 years), with either extreme high or low hip BMD (age- and gender-adjusted BMD z-scores of +1.5 to +4.0, n = 1055, or −4.0 to −1.5, n = 900), with replication in cohorts of women drawn from the general population (n = 20,898). The study replicates 21 of 26 known BMD–associated genes. Additionally, we report suggestive association of a further six new genetic associations in or around the genes CLCN7, GALNT3, IBSP, LTBP3, RSPO3, and SOX4, with replication in two independent datasets. A novel mouse model with a loss-of-function mutation in GALNT3 is also reported, which has high bone mass, supporting the involvement of this gene in BMD determination. In addition to identifying further genes associated with BMD, this study confirms the efficiency of extreme-truncate selection designs for quantitative trait association studies