Trends in the Population Prevalence of People Who Inject Drugs in US Metropolitan Areas 1992–2007

Background: People who inject drugs (PWID) have increased risk of morbidity and mortality. We update and present estimates and trends of the prevalence of current PWID and PWID subpopulations in 96 US metropolitan statistical areas (MSAs) for 1992–2007. Current estimates of PWID and PWID subpopulations will help target services and help to understand long-term health trends among PWID populations. Methodology: We calculated the number of PWID in the US annually from 1992–2007 and apportioned estimates to MSAs using multiplier methods. We used four types of data indicating drug injection to allocate national annual totals to MSAs, creating four distinct series of component estimates of PWID in each MSA and year. The four component estimates are averaged to create the best estimate of PWID for each MSA and year. We estimated PWID prevalence rates for three subpopulations defined by gender, age, and race/ethnicity. We evaluated trends using multi-level polynomial models. Results: PWID per 10,000 persons aged 15–64 years varied across MSAs from 31 to 345 in 1992 (median 104.4) to 34 to 324 in 2007 (median 91.5). Trend analysis indicates that this rate declined during the early period and then was relatively stable in 2002–2007. Overall prevalence rates for non-Hispanic black PWID increased in 2005 as compared to other racial/ethnic groups. Hispanic prevalence, in contrast, declined across time. Importantly, results show a worrisome trend in young PWID prevalence since HAART was initiated – the mean prevalence was 90 to 100 per 10,000 youth in 1992–1996, but increased to >120 PWID per 10,000 youth in 2006–2007. Conclusions: Overall, PWID rates remained constant since 2002, but increased for two subpopulations: non-Hispanic black PWID and young PWID. Estimates of PWID are important for planning and evaluating public health programs to reduce harm among PWID and for understanding related trends in social and health outcomes

Metropolitan Social Environments and Pre-HAART/HAART Era Changes in Mortality Rates (per 10,000 Adult Residents) among Injection Drug Users Living with AIDS

Background Among the largest US metropolitan areas, trends in mortality rates for injection drug users (IDUs) with AIDS vary substantially. Ecosocial, risk environment and dialectical theories suggest many metropolitan areas characteristics that might drive this variation. We assess metropolitan area characteristics associated with decline in mortality rates among IDUs living with AIDS (per 10,000 adult MSA residents) after highly active antiretroviral therapy (HAART) was developed. Methods This is an ecological cohort study of 86 large US metropolitan areas from 1993–2006. The proportional rate of decline in mortality among IDUs diagnosed with AIDS (as a proportion of adult residents) from 1993–1995 to 2004–2006 was the outcome of interest. This rate of decline was modeled as a function of MSA-level variables suggested by ecosocial, risk environment and dialectical theories. In multiple regression analyses, we used 1993–1995 mortality rates to (partially) control for pre-HAART epidemic history and study how other independent variables affected the outcomes. Results In multivariable models, pre-HAART to HAART era increases in ‘hard drug’ arrest rates and higher pre-HAART income inequality were associated with lower relative declines in mortality rates. Pre-HAART per capita health expenditure and drug abuse treatment rates, and pre- to HAART-era increases in HIV counseling and testing rates, were weakly associated with greater decline in AIDS mortality. Conclusions Mortality among IDUs living with AIDS might be decreased by reducing metropolitan income inequality, increasing public health expenditures, and perhaps increasing drug abuse treatment and HIV testing services. Given prior evidence that drug-related arrest rates are associated with higher HIV prevalence rates among IDUs and do not seem to decrease IDU population prevalence, changes in laws and policing practices to reduce such arrests while still protecting public order should be considered

Predictors of historical change in drug treatment coverage among people who inject drugs in 90 large metropolitan areas in the USA, 1993–2007

Background Adequate access to effective treatment and medication assisted therapies for opioid dependence has led to improved antiretroviral therapy adherence and decreases in morbidity among people who inject drugs (PWID), and can also address a broad range of social and public health problems. However, even with the success of syringe service programs and opioid substitution programs in European countries (and others) the US remains historically low in terms of coverage and access with regard to these programs. This manuscript investigates predictors of historical change in drug treatment coverage for PWID in 90 US metropolitan statistical areas (MSAs) during 1993–2007, a period in which, overall coverage did not change. Methods Drug treatment coverage was measured as the number of PWID in drug treatment, as calculated by treatment entry and census data, divided by numbers of PWID in each MSA. Variables suggested by the Theory of Community Action (i.e., need, resource availability, institutional opposition, organized support, and service symbiosis) were analyzed using mixed-effects multivariate models within dependent variables lagged in time to study predictors of later change in coverage. Results Mean coverage was low in 1993 (6.7%; SD 3.7), and did not increase by 2007 (6.4%; SD 4.5). Multivariate results indicate that increases in baseline unemployment rate (β = 0.312; pseudo-p < 0.0002) predict significantly higher treatment coverage; baseline poverty rate (β = − 0.486; pseudo-p < 0.0001), and baseline size of public health and social work workforce (β = 0.425; pseudo-p < 0.0001) were predictors of later mean coverage levels, and baseline HIV prevalence among PWID predicted variation in treatment coverage trajectories over time (baseline HIV * Time: β = 0.039; pseudo-p < 0.001). Finally, increases in black/white poverty disparity from baseline predicted significantly higher treatment coverage in MSAs (β = 1.269; pseudo-p < 0.0001). Conclusions While harm reduction programs have historically been contested and difficult to implement in many US communities, and despite efforts to increase treatment coverage for PWID, coverage has not increased. Contrary to our hypothesis, epidemiologic need, seems not to be associated with change in treatment coverage over time. Resource availability and institutional opposition are important predictors of change over time in coverage. These findings suggest that new ways have to be found to increase drug treatment coverage in spite of economic changes and belt-tightening policy changes that will make this difficult

Next-generation plasmids for transgenesis in zebrafish and beyond

Transgenesis is an essential technique for any genetic model. Tol2-based transgenesis paired with Gateway-compatible vector collections has transformed zebrafish transgenesis with an accessible, modular system. Here, we established several next-generation transgenesis tools for zebrafish and other species to expand and enhance transgenic applications. To facilitate gene-regulatory element testing, we generated Gateway middle entry vectors harboring the small mouse beta-globin minimal promoter coupled to several fluorophores, CreERT2, and Gal4. To extend the color spectrum for transgenic applications, we established middle entry vectors encoding the bright, blue-fluorescent protein mCerulean and mApple as an alternative red fluorophore. We present a series of p2A peptide-based 3' vectors with different fluorophores and subcellular localizations to co-label cells expressing proteins of interest. Lastly, we established Tol2 destination vectors carrying the zebrafish exorh promoter driving different fluorophores as a pineal gland-specific transgenesis marker active prior to hatching and through adulthood. exorh-based reporters and transgenesis markers also drive specific pineal gland expression in the eye-less cavefish (Astyanax). Together, our vectors provide versatile reagents for transgenesis applications in zebrafish, cavefish, and other models

A Systematic Literature Review with Meta-Analyses of Within- and Between-Day Differences in Objectively Measured Physical Activity in School-Aged Children

Background: Targeting specific time periods of the day or week may enhance physical activity (PA) interventions in youth. The most prudent time segments to target are currently unclear.  Objectives: To systematically review the literature describing differences in young people’s objectively measured PA on weekdays vs. weekends, in school vs. out of school, weekends vs. out of school and lesson time vs. break time.  Methods: Electronic databases were searched for English-language, cross-sectional studies of school-aged children (4–18 years) reporting time-segment-specific accelerometer-measured PA from 01/1990 to 01/2013. We meta-analysed standardised mean differences (SMD) between time segments for mean accelerometer counts per minute (TPA) and minutes in moderate-to-vigorous PA (MVPA). SMD is reported in units of standard deviation; 0.2, 0.5 and 0.8 represent small, moderate and large effects. Heterogeneity was explored using meta-regression (potential effect modifiers: age, sex and study setting).  Results: Of the 54 included studies, 37 were eligible for meta-analyses. Children were more active on weekdays than weekends [pooled SMD (95 % CI) TPA 0.14 (0.08; 0.20), MVPA 0.42 (0.35; 0.49)]. On school days, TPA was lower in school than out of school; however, marginally more MVPA was accumulated in school [TPA −0.24 (−0.40; −0.08), MVPA 0.17 (−0.03; 0.38)]. TPA was slightly lower on weekends than out of school on school days, but a greater absolute volume of MVPA was performed on weekends [TPA −0.10 (−0.19; −0.01), MVPA 1.02 (0.82; 1.23)]. Heterogeneity between studies was high (I2 73.3–96.3 %), with 20.3–53.1 % of variance between studies attributable to potential moderating factors.  Conclusions: School-aged children are more active on weekdays than weekend days. The outcome measure influences the conclusions for other comparisons. Findings support the tailoring of intervention strategies to specific time periods

An organelle-specific protein landscape identifies novel diseases and molecular mechanisms

Contains fulltext : 158967.pdf (publisher's version ) (Open Access)Cellular organelles provide opportunities to relate biological mechanisms to disease. Here we use affinity proteomics, genetics and cell biology to interrogate cilia: poorly understood organelles, where defects cause genetic diseases. Two hundred and seventeen tagged human ciliary proteins create a final landscape of 1,319 proteins, 4,905 interactions and 52 complexes. Reverse tagging, repetition of purifications and statistical analyses, produce a high-resolution network that reveals organelle-specific interactions and complexes not apparent in larger studies, and links vesicle transport, the cytoskeleton, signalling and ubiquitination to ciliary signalling and proteostasis. We observe sub-complexes in exocyst and intraflagellar transport complexes, which we validate biochemically, and by probing structurally predicted, disruptive, genetic variants from ciliary disease patients. The landscape suggests other genetic diseases could be ciliary including 3M syndrome. We show that 3M genes are involved in ciliogenesis, and that patient fibroblasts lack cilia. Overall, this organelle-specific targeting strategy shows considerable promise for Systems Medicine