A success story: HIV prevention for injection drug users in Rhode Island

BACKGROUND: New HIV diagnoses related to injection drug use (IDU) have declined in the United States. Access to clean syringes and decreasing HIV transmission among injection drug users have been HIV prevention priorities of the Rhode Island (RI) HIV community. To examine trends in IDU-related new HIV diagnoses in RI, we performed a retrospective analysis of new HIV diagnoses according to HIV risk factor from 1990–2003. RESULTS: There has been an 80% absolute reduction in IDU-related new HIV diagnoses in RI coincident with IDU-specific prevention efforts. CONCLUSION: There has been a greater decline in IDU-related new HIV diagnoses in Rhode Island compared to national data reported by the Centers for Disease Control and Prevention. We hypothesize that this dramatic decline in Rhode Island is related to extensive HIV prevention efforts targeting IDUs. Further research is needed to examine the impact of specific HIV prevention interventions for injection drug users

Quasi-diffusion magnetic resonance imaging (QDI): A fast, high b-value diffusion imaging technique.

To enable application of non-Gaussian diffusion magnetic resonance imaging (dMRI) techniques in large-scale clinical trials and facilitate translation to clinical practice there is a requirement for fast, high contrast, techniques that are sensitive to changes in tissue structure which provide diagnostic signatures at the early stages of disease. Here we describe a new way to compress the acquisition of multi-shell b-value diffusion data, Quasi-Diffusion MRI (QDI), which provides a probe of subvoxel tissue complexity using short acquisition times (1-4 min). We also describe a coherent framework for multi-directional diffusion gradient acquisition and data processing that allows computation of rotationally invariant quasi-diffusion tensor imaging (QDTI) maps. QDI is a quantitative technique that is based on a special case of the Continuous Time Random Walk model of diffusion dynamics and assumes the presence of non-Gaussian diffusion properties within tissue microstructure. QDI parameterises the diffusion signal attenuation according to the rate of decay (i.e. diffusion coefficient, D in mm2 s-1) and the shape of the power law tail (i.e. the fractional exponent, α). QDI provides analogous tissue contrast to Diffusional Kurtosis Imaging (DKI) by calculation of normalised entropy of the parameterised diffusion signal decay curve, Hn, but does so without the limitations of a maximum b-value. We show that QDI generates images with superior tissue contrast to conventional diffusion imaging within clinically acceptable acquisition times of between 84 and 228 s. We show that QDI provides clinically meaningful images in cerebral small vessel disease and brain tumour case studies. Our initial findings suggest that QDI may be added to routine conventional dMRI acquisitions allowing simple application in clinical trials and translation to the clinical arena

Maternal corticotropin-releasing hormone is associated with LEP DNA methylation at birth and in childhood: an epigenome-wide study in Project Viva

BackgroundCorticotropin-releasing hormone (CRH) plays a central role in regulating the secretion of cortisol which controls a wide range of biological processes. Fetuses overexposed to cortisol have increased risks of disease in later life. DNA methylation may be the underlying association between prenatal cortisol exposure and health effects. We investigated associations between maternal CRH levels and epigenome-wide DNA methylation of cord blood in offsprings and evaluated whether these associations persisted into mid-childhood.MethodsWe investigated mother-child pairs enrolled in the prospective Project Viva pre-birth cohort. We measured DNA methylation in 257 umbilical cord blood samples using the HumanMethylation450 Bead Chip. We tested associations of maternal CRH concentration with cord blood cells DNA methylation, adjusting the model for maternal age at enrollment, education, maternal race/ethnicity, maternal smoking status, pre-pregnancy body mass index, parity, gestational age at delivery, child sex, and cell-type composition in cord blood. We further examined the persistence of associations between maternal CRH levels and DNA methylation in children's blood cells collected at mid-childhood (n = 239, age: 6.7-10.3 years) additionally adjusting for the children's age at blood drawn.ResultsMaternal CRH levels are associated with DNA methylation variability in cord blood cells at 96 individual CpG sites (False Discovery Rate <0.05). Among the 96 CpG sites, we identified 3 CpGs located near the LEP gene. Regional analyses confirmed the association between maternal CRH and DNA methylation near LEP. Moreover, higher maternal CRH levels were associated with higher blood-cell DNA methylation of the promoter region of LEP in mid-childhood (P < 0.05, β = 0.64, SE = 0.30).ConclusionIn our cohort, maternal CRH was associated with DNA methylation levels in newborns at multiple loci, notably in the LEP gene promoter. The association between maternal CRH and LEP DNA methylation levels persisted into mid-childhood

A Novel BMPR2 Mutation Associated with Pulmonary Arterial Hypertension in an Octogenarian

We describe the case of an 83-year-old man with a family history of pulmonary hypertension (PH) who presented with severe pulmonary arterial hypertension (PAH) and later tested positive for a novel bone morphogenetic protein receptor 2 (BMPR2) gene mutation. To our knowledge, this may be the oldest reported patient with PAH in whom a BMPR2 mutation was initially identified

Term birth weight and ambient air pollutant concentrations during pregnancy, among women living in Monroe County, New York

Increased ambient air pollutant concentrations during pregnancy have been associated with reduced birth weight, but the etiologically relevant pregnancy time window(s) is/are unclear. In 76,500 singleton births in Monroe County, NY (2005–2016), who were 37–42 gestational weeks at delivery, we used generalized linear models to regress term birth weight against mean gestational month pollutant concentrations, adjusting for mean temperature, and maternal, infant, and medical service use characteristics. Overall, there were no clear patterns of term birth weight change associated with increased concentrations of any pollutant across gestational months. However, among Hispanic women only, increases in all pollutants, except O3, in multiple gestational months, were associated with decreased term birth weight. Each 3.25 µg/m3 increase in PM2.5 concentration in the 6th gestational month was associated with a −20.4 g (95% CI = −34.0, −6.8) reduction in term birth weight among Hispanic women, but a 4.1 g (95% CI = −2.5, 10.8) increase among non-Hispanic mothers (p for interaction < 0.001). Although ambient air pollutant concentrations during pregnancy were not associated with reduced term birth weight among women of all ethnicities living in Monroe County, this observed association in Hispanic mothers may be a result of less exposure misclassification and bias (due to closer residential proximity to the monitoring site)

Theropod Fauna from Southern Australia Indicates High Polar Diversity and Climate-Driven Dinosaur Provinciality

The Early Cretaceous fauna of Victoria, Australia, provides unique data on the composition of high latitude southern hemisphere dinosaurs. We describe and review theropod dinosaur postcranial remains from the Aptian–Albian Otway and Strzelecki groups, based on at least 37 isolated bones, and more than 90 teeth from the Flat Rocks locality. Several specimens of medium- and large-bodied individuals (estimated up to ∼8.5 metres long) represent allosauroids. Tyrannosauroids are represented by elements indicating medium body sizes (∼3 metres long), likely including the holotype femur of Timimus hermani, and a single cervical vertebra represents a juvenile spinosaurid. Single specimens representing medium- and small-bodied theropods may be referrable to Ceratosauria, Ornithomimosauria, a basal coelurosaur, and at least three taxa within Maniraptora. Thus, nine theropod taxa may have been present. Alternatively, four distinct dorsal vertebrae indicate a minimum of four taxa. However, because most taxa are known from single bones, it is likely that small-bodied theropod diversity remains underestimated. The high abundance of allosauroids and basal coelurosaurs (including tyrannosauroids and possibly ornithomimosaurs), and the relative rarity of ceratosaurs, is strikingly dissimilar to penecontemporaneous dinosaur faunas of Africa and South America, which represent an arid, lower-latitude biome. Similarities between dinosaur faunas of Victoria and the northern continents concern the proportional representatation of higher clades, and may result from the prevailing temperate–polar climate of Australia, especially at high latitudes in Victoria, which is similar to the predominant warm–temperate climate of Laurasia, but distinct from the arid climate zone that covered extensive areas of Gondwana. Most dinosaur groups probably attained a near-cosmopolitan distribution in the Jurassic, prior to fragmentation of the Pangaean supercontinent, and some aspects of the hallmark ‘Gondwanan’ fauna of South America and Africa may therefore reflect climate-driven provinciality, not vicariant evolution driven by continental fragmentation. However, vicariance may still be detected at lower phylogenetic levels

Endothelin-1 Predicts Hemodynamically Assessed Pulmonary Arterial Hypertension in HIV Infection.

BackgroundHIV infection is an independent risk factor for PAH, but the underlying pathogenesis remains unclear. ET-1 is a robust vasoconstrictor and key mediator of pulmonary vascular homeostasis. Higher levels of ET-1 predict disease severity and mortality in other forms of PAH, and endothelin receptor antagonists are central to treatment, including in HIV-associated PAH. The direct relationship between ET-1 and PAH in HIV-infected individuals is not well described.MethodsWe measured ET-1 and estimated pulmonary artery systolic pressure (PASP) with transthoracic echocardiography (TTE) in 106 HIV-infected individuals. Participants with a PASP ≥ 30 mmHg (n = 65) underwent right heart catheterization (RHC) to definitively diagnose PAH. We conducted multivariable analysis to identify factors associated with PAH.ResultsAmong 106 HIV-infected participants, 80% were male, the median age was 52 years and 77% were on antiretroviral therapy. ET-1 was significantly associated with higher values of PASP [14% per 0.1 pg/mL increase in ET-1, p = 0.05] and PASP ≥ 30 mmHg [PR (prevalence ratio) = 1.24, p = 0.012] on TTE after multivariable adjustment for PAH risk factors. Similarly, among the 65 individuals who underwent RHC, ET-1 was significantly associated with higher values of mean pulmonary artery pressure and PAH (34%, p = 0.003 and PR = 2.43, p = 0.032, respectively) in the multivariable analyses.ConclusionsHigher levels of ET-1 are independently associated with HIV-associated PAH as hemodynamically assessed by RHC. Our findings suggest that excessive ET-1 production in the setting of HIV infection impairs pulmonary endothelial function and contributes to the development of PAH

A Dust Trap in the Young Multiple System HD 34700

This is the author accepted manuscript. The final version is available from the American Astronomical Society via the DOI in this recordMillimeter observations of disks around young stars reveal substructures indicative of gas pressure traps that may aid grain growth and planet formation. We present Submillimeter Array observations of HD 34700- two Herbig Ae stars in a close binary system (Aa/Ab, ∼0.25 AU), surrounded by a disk presenting a large cavity and spiral arms seen in scattered light, and two distant, lower mass companions. These observations include 1.3 mm continuum emission and the 12CO 2-1 line at ∼ 0. 005 (178 AU) resolution. They resolve a prominent azimuthal asymmetry in the continuum, and Keplerian rotation of a circumbinary disk in the 12CO line. The asymmetry is located at a radius of 155+11 −7 AU, consistent with the edge of the scattered light cavity, being resolved in both radius (72+14 −15 AU) and azimuth (FWHM = 64◦+8 −7 ). The strong asymmetry in millimeter continuum emission could be evidence for a dust trap, together with the more symmetric morphology of 12CO emission and small grains. We hypothesize an unseen circumbinary companion, responsible for the cavity in scattered light and creating a vortex at the cavity edge that manifests in dust trapping. The disk mass has limitations imposed by the detection of 12CO and non-detection of 13CO. We discuss its consequences for the potential past gravitational instability of this system, likely accounting for the rapid formation of a circumbinary companion. We also report the discovery of resolved continuum emission associated with HD 34700B (projected separation ∼ 1850AU), which we explain through a circumstellar disk.National Science Foundation (NSF

Investigating the Relative Gas and Small Dust Grain Surface Heights in Protoplanetary Disks

This is the author accepted manuscript. The final version is available from the American Astronomical Society via the DOI in this recordThis work has made use of data from the European Space Agency (ESA) mission Gaia (https://www.cosmos.esa.int/gaia), processed by the Gaia Data Processing and Analysis Disk Height Consortium (DPAC, https://www.cosmos.esa.int/web/ gaia/dpac/consortium).Dust evolution in protoplanetary disks from small dust grains to pebbles is key to the planet formation process. The gas in protoplanetary disks should influence the vertical distribution of small dust grains (∼1 µm) in the disk. Utilizing archival near-infrared polarized light and millimeter observations, we can measure the scale height and the flare parameter β of the small dust grain scattering surface and 12CO gas emission surface for three protoplanetary disks IM Lup, HD 163296, and HD 97048 (CU Cha). For two systems, IM Lup and HD 163296, the 12CO gas and small dust grains at small radii from the star have similar heights but at larger radii (>100 au) the dust grain scattering surface height is lower than the 12CO gas emission surface height. In the case of HD 97048, the small dust grain scattering surface has similar heights to the 12CO gas emission surface at all radii. We ran a protoplanetary disk radiative transfer model of a generic protoplanetary disk with TORUS and showed that there is no difference between the observed scattering surface and 12CO emission surface. We also performed analytical modeling of the system and found that gas-to-dust ratios larger than 100 could explain the observed difference in IM Lup and HD 163296. This is the first direct comparison of observations of gas and small dust grain heights distribution in protoplanetary disks. Future observations of gas emission and near-infrared scattered light instruments are needed to look for similar trends in other protoplanetary disks.National Science Foundation (NSF