Prevention Research Centers: Contributions to Updating the Public Health Workforce Through Training

Because public health is a continually evolving field, it is essential to provide ample training opportunities for public health professionals. As a natural outgrowth of the Centers for Disease Control and Prevention\u27s Prevention Research Centers Program, training courses of many types have been developed for public health practitioners working in the field. This article describes three of the Prevention Research Center training program offerings: Evidence-Based Public Health, Physical Activity and Public Health for Practitioners, and Social Marketing. These courses illustrate the commitment of the Prevention Research Centers Program to helping create a better trained public health workforce, thereby enhancing the likelihood of improving public health

Comparison of \nu\mu-Ar multiplicity distributions observed by MicroBooNE to GENIE model predictions

We measure a large set of observables in inclusive charged current muon neutrino scattering on argon with the MicroBooNE liquid argon time projection chamber operating at Fermilab. We evaluate three neutrino interaction models based on the widely used GENIE event generator using these observables. The measurement uses a data set consisting of neutrino interactions with a final state muon candidate fully contained within the MicroBooNE detector. These data were collected in 2016 with the Fermilab Booster Neutrino Beam, which has an average neutrino energy of 800 MeV, using an exposure corresponding to 5E19 protons-on-target. The analysis employs fully automatic event selection and charged particle track reconstruction and uses a data-driven technique to separate neutrino interactions from cosmic ray background events. We find that GENIE models consistently describe the shapes of a large number of kinematic distributions for fixed observed multiplicity.Comment: 31 pages, 39 figures, 10 table

Variations in adolescents’ motivational characteristics across gender and physical activity patterns: A latent class analysis approach

Abstract Background Neglecting to take account of the underlying context or type of physical activity (PA) that underpins overall involvement has resulted in a limited understanding of adolescents’ PA participation. The purpose of the present research was to identify male and female adolescents’ leisure time PA patterns and examine whether psychological processes derived from self-determination theory differ as a function of the pattern of PA undertaken. Methods Nine hundred ninety-five students (61.2% females, 38.8% males; M age = 13.72 years, SD = 1.25) from eight secondary schools in Dublin, Ireland completed a physical activity recall 7 day diary and measures of intrinsic motivation, competence, relatedness, autonomy and autonomy support. Based on the diary five binary indicators of physical activity were derived reflecting recommended levels of MVPA on a minimum of 3 days, at least three sessions of non-organized physical activity (e.g. jog), team sport, individual sport, and organized non-sport physical activity (e.g. dance). Latent class analysis was used to identify subgroups of adolescents that engaged in similar patterns of physical activity. Profiles of physical activity participation were subsequently compared on motivational characteristics using Kruskal-Wallis tests. Results Latent class analysis revealed six distinct classes for girls (Organized Run/Swim & Dance/Gym; Organized Dance; Leisure Active Team Sport; Active Individual Sport; Walk/Run/Outdoor games; Non-Participation) and five for boys (Leisure Active Gym; Leisure Active Individual Sport; Active Team Sport; Active Mixed Type; Non-Participation). Significant differences were found between the classes. Girls characterized by participation in team or individual sport, and boys represented by team sport participation demonstrated significantly higher self-determined motivational characteristics relative to other profiles of physical activity. Conclusion This research offers a nuanced insight into the underlying type of activities that constitute overall patterns of PA among adolescent boys and girls and further reveals that psychological processes vary dependent on the profile of physical activity undertaken. The findings may be useful for informing interventions aimed at promoting physical activity among young people

HIV-1 persistence following extremely early initiation of antiretroviral therapy (ART) during acute HIV-1 infection: An observational study

Background: It is unknown if extremely early initiation of antiretroviral therapy (ART) may lead to long-term ART-free HIV remission or cure. As a result, we studied 2 individuals recruited from a pre-exposure prophylaxis (PrEP) program who started prophylactic ART an estimated 10 days (Participant A; 54-year-old male) and 12 days (Participant B; 31-year-old male) after infection with peak plasma HIV RNA of 220 copies/mL and 3,343 copies/mL, respectively. Extensive testing of blood and tissue for HIV persistence was performed, and PrEP Participant A underwent analytical treatment interruption (ATI) following 32 weeks of continuous ART. Methods and findings Colorectal and lymph node tissues, bone marrow, cerebral spinal fluid (CSF), plasma, and very large numbers of peripheral blood mononuclear cells (PBMCs) were obtained longitudinally from both participants and were studied for HIV persistence in several laboratories using molecular and culture-based detection methods, including a murine viral outgrowth assay (mVOA). Both participants initiated PrEP with tenofovir/emtricitabine during very early Fiebig stage I (detectable plasma HIV-1 RNA, antibody negative) followed by 4-drug ART intensification. Following peak viral loads, both participants experienced full suppression of HIV-1 plasma viremia. Over the following 2 years, no further HIV could be detected in blood or tissue from PrEP Participant A despite extensive sampling from ileum, rectum, lymph nodes, bone marrow, CSF, circulating CD4+ T cell subsets, and plasma. No HIV was detected from tissues obtained from PrEP Participant B, but low-level HIV RNA or DNA was intermittently detected from various CD4+ T cell subsets. Over 500 million CD4+ T cells were assayed from both participants in a humanized mouse outgrowth assay. Three of 8 mice infused with CD4+ T cells from PrEP Participant B developed viremia (50 million input cells/surviving mouse), but only 1 of 10 mice infused with CD4+ T cells from PrEP Participant A (53 million input cells/mouse) experienced very low level viremia (201 copies/mL); sequence confirmation was unsuccessful. PrEP Participant A stopped ART and remained aviremic for 7.4 months, rebounding with HIV RNA of 36 copies/mL that rose to 59,805 copies/mL 6 days later. ART was restarted promptly. Rebound plasma HIV sequences were identical to those obtained during acute infection by single-genome sequencing. Mathematical modeling predicted that the latent reservoir size was approximately 200 cells prior to ATI and that only around 1% of individuals with a similar HIV burden may achieve lifelong ART-free remission. Furthermore, we observed that lymphocytes expressing the tumor marker CD30 increased in frequency weeks to months prior to detectable HIV-1 RNA in plasma. This study was limited by the small sample size, which was a result of the rarity of individuals presenting during hyperacute infection. Conclusions: We report HIV relapse despite initiation of ART at one of the earliest stages of acute HIV infection possible. Near complete or complete loss of detectable HIV in blood and tissues did not lead to indefinite ART-free HIV remission. However, the small numbers of latently infected cells in individuals treated during hyperacute infection may be associated with prolonged ART-free remission

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Research Summary: Courageous, Collaborative Leadership

While courageous, collaborative leadership has not been formally recognized as a “model” by those who study educational leadership, there is a wealth of information about collaborative (i.e., participatory) leadership and a growing corpus of literature focused on courageous leadership. As in the development of the ideas connected to collaborative leadership, the world of business is taking the lead in delineating what courageous leadership means. Some of this literature has even surfaced in the realm of religious studies (Hybels, 2002). Simply defined, courageousness in leadership addresses the necessity to step outside the box and take chances to help the organization establish appropriate and defensible goals. It also clearly places those who are leaders in a position to confront adversity. Collaborative leadership refers to inclusiveness— teachers, staff, administrators, parents, and other stakeholders—in decision making related to organizational goals. Research in both of the areas of courageousness and collaboration should advance a fuller understanding of what courageous, collaborative leadership is. Since courageous, collaborative leadership is by its very nature effective leadership, this research summary will also briefly review the literature regarding effective leadership

Prevention Research Centers: Contributions to Updating the Public Health Workforce Through Training

Because public health is a continually evolving field, it is essential to provide ample training opportunities for public health professionals. As a natural outgrowth of the Centers for Disease Control and Prevention’s Prevention Research Centers Program, training courses of many types have been developed for public health practitioners working in the field. This article describes three of the Prevention Research Center training program offerings: Evidence-Based Public Health, Physical Activity and Public Health for Practitioners, and Social Marketing. These courses illustrate the commitment of the Prevention Research Centers Program to helping create a better trained public health workforce, thereby enhancing the likelihood of improving public health