Practice transformations to optimize the delivery of HIV primary care in community healthcare settings in the United States: A program implementation study.

BackgroundThe United States HIV care workforce is shrinking, which could complicate service delivery to people living with HIV (PLWH). In this study, we examined the impact of practice transformations, defined as efficiencies in structures and delivery of care, on demonstration project sites within the Workforce Capacity Building Initiative, a Health Resources and Services Administration (HRSA) Ryan White HIV/AIDS Program Special Projects of National Significance (SPNS).Methods and findingsData were collected at 14 demonstration project sites in 7 states and the District of Columbia. Organizational assessments were completed at sites once before and 4 times after implementation. They captured 3 transformation approaches: maximizing the HIV care workforce (efforts to increase the number of existing healthcare workforce members involved in the care of PLWH), share-the-care (team-based care giving more responsibility to midlevel providers and staff), and enhancing client engagement in primary HIV care to reduce emergency and inpatient care (e.g., care coordination). We also obtained Ryan White HIV/AIDS Program Services Reports (RSRs) from sites for calendar years (CYs) 2014-2016, corresponding to before, during, and after transformation. The RSR include data on client retention in HIV care, prescription of antiretroviral therapy (ART), and viral suppression. We used generalized estimating equation (GEE) models to analyze changes among sites implementing each practice transformation approach. The demonstration projects had a mean of 18.5 prescribing providers (SD = 23.5). They reported data on more than 13,500 clients per year (mean = 969/site, SD = 1,351). Demographic characteristics remained similar over time. In 2014, a majority of clients were male (71% versus 28% female and 0.2% transgender), with a mean age of 47 (interquartile range [IQR] 37-54). Racial/ethnic characteristics (48% African American, 31% Hispanic/Latino, 14% white) and HIV risk varied (31% men who have sex with men; 31% heterosexual men and women; 7% injection drug use). A substantial minority was on Medicaid (41%). Across sites, there was significant uptake in practices consistent with maximizing the HIV care workforce (18% increase, p < 0.001), share-the-care (25% increase, p < 0.001), and facilitating patient engagement in HIV primary care (13% increase, p < 0.001). There were also significant improvements over time in retention in HIV care (adjusted odds ratio [aOR] = 1.03; 95% confidence interval [CI] 1.02-1.04; p < 0.001), ART prescription levels (aOR = 1.01; 95% CI 1.00-1.01; p < 0.001), and viral suppression (aOR = 1.03; 95% CI 1.02-1.04; p < 0.001). All outcomes improved at sites that implemented transformations to maximize the HIV care workforce or improve client engagement. At sites that implemented share-the-care practices, only retention in care and viral suppression outcomes improved. Study limitations included use of demonstration project sites funded by the Ryan White HIV/AIDS Program (RWHAP), which tend to have better HIV outcomes than other US clinics; varying practice transformation designs; lack of a true control condition; and a potential Hawthorne effect because site teams were aware of the evaluation.ConclusionsIn this study, we found that practice transformations are a potential strategy for addressing anticipated workforce challenges among those providing care to PLWH. They hold the promise of optimizing the use of personnel and ensuring the delivery of care to all in need while potentially enhancing HIV care continuum outcomes

Global risk assessment of cardiovascular disease in resource constrained settings

Cardiovascular disease (CVD) is an emerging problem in Sub-Saharan Africa. Many current guidelines recommend using global risk assessment (GRA) to quantify the risk for developing CVD and to guide treatment and policy. Most GRA tools require lipid measures which are not readily available in resource-constrained settings. Of the 3 most published non-laboratory based tools: Gaziano and Framingham substitute BMI for cholesterol; WHO does not include BMI or cholesterol

EO-1 Data Quality and Sensor Stability with Changing Orbital Precession at the End of a 16 Year Mission

The Earth Observing One (EO-1) satellite has completed 16 years of Earth observations in early 2017. What started as a technology mission to test various new advancements turned into a science and application mission that extended many years beyond the satellites planned life expectancy. EO-1s primary instruments are spectral imagers: Hyperion, the only civilian full spectrum spectrometer (430-2400 nm) in orbit; and the Advanced Land Imager (ALI), the prototype for Landsat-8s pushbroom imaging technology. Both Hyperion and ALI instruments have continued to perform well, but in February 2011 the satellite ran out of the fuel necessary to maintain orbit, which initiated a change in precession rate that led to increasingly earlier equatorial crossing times during its last five years. The change from EO-1s original orbit, when it was formation flying with Landsat-7 at a 10:01am equatorial overpass time, to earlier overpass times results in image acquisitions with increasing solar zenith angles (SZAs). In this study, we take several approaches to characterize data quality as SZAs increased. Our results show that for both EO-1 sensors, atmospherically corrected reflectance products are within 5 to 10 of mean pre-drift products. No marked trend in decreasing quality in ALI or Hyperion is apparent through 2016, and these data remain a high quality resource through the end of the mission

PGC-1 alpha induced mitochondrial biogenesis in stromal cells underpins mitochondrial transfer to melanoma

INTRODUCTION: Progress in the knowledge of metabolic interactions between cancer and its microenvironment is ongoing and may lead to novel therapeutic approaches. Until recently, melanoma was considered a glycolytic tumour due to mutations in mitochondrial-DNA, however, these malignant cells can regain OXPHOS capacity via the transfer of mitochondrial-DNA, a process that supports their proliferation in-vitro and in-vivo. Here we study how melanoma cells acquire mitochondria and how this process is facilitated from the tumour microenvironment. METHODS: Primary melanoma cells, and MSCs derived from patients were obtained. Genes’ expression and DNA quantification was analysed using Real-time PCR. MSC migration, melanoma proliferation and tumour volume, in a xenograft subcutaneous mouse model, were monitored through bioluminescent live animal imaging. RESULTS: Human melanoma cells attract bone marrow-derived stromal cells (MSCs) to the primary tumour site where they stimulate mitochondrial biogenesis in the MSCs through upregulation of PGC1a. Mitochondria are transferred to the melanoma cells via direct contact with the MSCs. Moreover, inhibition of MSC-derived PGC1a was able to prevent mitochondrial transfer and improve NSG melanoma mouse tumour burden. CONCLUSION: MSC mitochondrial biogenesis stimulated by melanoma cells is prerequisite for mitochondrial transfer and subsequent tumour growth, where targeting this pathway may provide an effective novel therapeutic approach in melanoma

A search for supernova-like optical counterparts to ASKAP-localised Fast Radio Bursts

Fast radio bursts (FRBs) are millisecond-scale radio pulses, which originate in distant galaxies and are produced by unknown sources. The mystery remains partially because of the typical difficulty in localising FRBs to host galaxies. Accurate localisations delivered by the Commensal Real-time ASKAP Fast Transients (CRAFT) survey now provide an opportunity to study the host galaxies and potential transient counterparts of FRBs at a large range of wavelengths. In this work, we investigate whether the first three FRBs accurately localised by CRAFT have supernova-like transient counterparts. We obtained two sets of imaging epochs with the Very Large Telescope for three host galaxies, one soon after the burst detection and one several months later. After subtracting these images no optical counterparts were identified in the associated FRB host galaxies, so we instead place limits on the brightness of any potential optical transients. A Monte Carlo approach, in which supernova light curves were modelled and their base properties randomised, was used to estimate the probability of a supernova associated with each FRB going undetected. We conclude that Type Ia and IIn supernovae are unlikely to accompany every apparently non-repeating FRB.Comment: 7 pages, 3 figures. Accepted to Astronomy & Astrophysics on 03 June 202

A Combination of Two Human Monoclonal Antibodies Limits Fetal Damage by Zika Virus in Macaques

Human infection by Zika virus (ZIKV) during pregnancy can lead to vertical transmission and fetal aberrations, including microcephaly. Prophylactic administration of antibodies can diminish or prevent ZIKV infection in animal models, but whether passive immunization can protect nonhuman primates and their fetuses during pregnancy has not been determined. Z004 and Z021 are neutralizing monoclonal antibodies to domain III of the envelope (EDIII) of ZIKV. Together the two antibodies protect nonpregnant macaques against infection even after Fc modifications to prevent antibody-dependent enhancement in vitro (ADE) and extend their half-lives. Here we report on prophylactic co-administration of the Fc-modified antibodies to pregnant rhesus macaques challenged 3 times with ZIKV during first and second trimester. The two antibodies did not entirely eliminate maternal viremia but limited vertical transmission protecting the fetus from neurologic damage. Thus, maternal passive immunization with two antibodies to EDIII can shield primate fetuses from the harmful effects of ZIKV

The unseen host galaxy and high dispersion measure of a precisely-localised Fast Radio Burst suggests a high-redshift origin

FRB 20210912A is a fast radio burst (FRB), detected and localised to sub-arcsecond precision by the Australian Square Kilometre Array Pathfinder. No host galaxy has been identified for this burst despite the high precision of its localisation and deep optical and infrared follow-up, to 5-$\sigma$ limits of $R=26.7$ mag and $K_\mathrm{s}=24.9$ mag with the Very Large Telescope. The combination of precise radio localisation and deep optical imaging has almost always resulted in the secure identification of a host galaxy, and this is the first case in which the line-of-sight is not obscured by the Galactic disk. The dispersion measure of this burst, $\mathrm{DM_{FRB}}=1233.696\pm0.006~\mathrm{pc}\ \mathrm{cm}^{-3}$, allows for a large source redshift of $z>1$ according to the Macquart relation. It could thus be that the host galaxy is consistent with the known population of FRB hosts, but is too distant to detect in our observations ($z>0.7$ for a host like that of the first repeating FRB source, FRB 20121102A); that it is more nearby with a significant excess in $\mathrm{DM_{host}}$, and thus dimmer than any known FRB host; or, least likely, that the FRB is truly hostless. We consider each possibility, making use of the population of known FRB hosts to frame each scenario. The fact of the missing host has ramifications for the FRB field: even with high-precision localisation and deep follow-up, some FRB hosts may be difficult to detect, with more distant hosts being the less likely to be found. This has implications for FRB cosmology, in which high-redshift detections are valuable.Comment: 14 pages, 6 figures. Revised based on referee's comments and accepted to MNRA

VisANT 3.0: new modules for pathway visualization, editing, prediction and construction

With the integration of the KEGG and Predictome databases as well as two search engines for coexpressed genes/proteins using data sets obtained from the Stanford Microarray Database (SMD) and Gene Expression Omnibus (GEO) database, VisANT 3.0 supports exploratory pathway analysis, which includes multi-scale visualization of multiple pathways, editing and annotating pathways using a KEGG compatible visual notation and visualization of expression data in the context of pathways. Expression levels are represented either by color intensity or by nodes with an embedded expression profile. Multiple experiments can be navigated or animated. Known KEGG pathways can be enriched by querying either coexpressed components of known pathway members or proteins with known physical interactions. Predicted pathways for genes/proteins with unknown functions can be inferred from coexpression or physical interaction data. Pathways produced in VisANT can be saved as computer-readable XML format (VisML), graphic images or high-resolution Scalable Vector Graphics (SVG). Pathways in the format of VisML can be securely shared within an interested group or published online using a simple Web link. VisANT is freely available at http://visant.bu.edu

VisANT 3.0: new modules for pathway visualization, editing, prediction and construction

With the integration of the KEGG and Predictome databases as well as two search engines for coexpressed genes/proteins using data sets obtained from the Stanford Microarray Database (SMD) and Gene Expression Omnibus (GEO) database, VisANT 3.0 supports exploratory pathway analysis, which includes multi-scale visualization of multiple pathways, editing and annotating pathways using a KEGG compatible visual notation and visualization of expression data in the context of pathways. Expression levels are represented either by color intensity or by nodes with an embedded expression profile. Multiple experiments can be navigated or animated. Known KEGG pathways can be enriched by querying either coexpressed components of known pathway members or proteins with known physical interactions. Predicted pathways for genes/proteins with unknown functions can be inferred from coexpression or physical interaction data. Pathways produced in VisANT can be saved as computer-readable XML format (VisML), graphic images or high-resolution Scalable Vector Graphics (SVG). Pathways in the format of VisML can be securely shared within an interested group or published online using a simple Web link. VisANT is freely available at http://visant.bu.edu