3He/4He isotopic ratio characterization of the Polynesian region: the society and upper Cook-Austral chains

We report the result of a systematic survey of the helium isotopic composition for basaltic rocks from the Polynesian region. The database covering the Society chain lists 79 entries deriving from experiments carried out at SIO (Scripps Institution of Oceanography, University of California San Diego, CA, USA) following the procedure of crushing on-line with an 8 minute single step; data for the Cook-Austral islands are taken from the literature. The 3He/4He value distribution shows an intrinsic dispersion s between 1.1 and 1.4 times RA (RA= 3He/4He in Air = 1.3931026) and appears sensibly uniform over the area explored, clearly independent from the variation of age (0 to 20 My) along the dorsal of the Island chains. The difference appearing between the mean value obtained for the Society (R/RA = 6.361) and the Cook-Austral (R/RA = 7.361.4) is not appreciable within the “natural” dispersion. The values obtained are substantially lower than the Pacific MORB (R/RAA8.7 RA). No evident correlation appears in the general picture between the helium data and the other radiogenic isotopes interpreted as tracers for possible heterogeneity in the mantle

Mortality for chronic-degenerative diseases in Tuscany: Ecological study comparing neighboring areas with substantial differences in environmental pollution

Objectives: Environmental pollution is associated with morbidity and mortality for chronic-degenerative diseases. Recent data points out a relationship between proximity to industrial plants and mortality due to neoplasms. The aim of this study has been to compare mortality due to chronic-degenerative diseases in the area of Tuscany (Bassa Val di Cecina), Italy, characterized by the presence of 2 neighboring municipalities similar in terms of size but with substantial differences in industrial activities: Rosignano (the site of chemical, energy production and waste processing industries) and Cecina (with no polluting activity). Material and Methods: Standardized mortality rates for the 2001–2010 decade were calculated; the data of the whole Tuscany was assumed as reference. Environmental levels of pollutants were obtained by databases of the Environmental Protection Agency of Tuscany Region (Agenzia Regionale per la Protezione Ambientale della Toscana – ARPAT). Maximum tolerated pollutant levels set by national laws were assumed as reference. Results: In the whole Bassa Val di Cecina, significantly elevated standardized mortality rates due to mesothelioma, ischemic heart diseases, cerebrovascular diseases and Alzheimer and other degenerative diseases of nervous system were observed. In the municipality of Rosignano, a significant excess of mortality for all these groups of diseases was confirmed. On the contrary, the municipality of Cecina showed only significantly higher mortality rates for ischemic heart diseases. Elevated levels of heavy metals in sea water and of particulate matter which contains particles of diameter ≤ 10 mm (PM10) and ozone in air were detected in Rosignano. Conclusions: This study shows an excess of mortality for chronic-degenerative diseases in the area with elevated concentration of polluting factories. Proximity to industrial plants seems to represent a risk factor for those diseases. Int J Occup Med Environ Health 2017;30(4):641–65

Reduced T-cell repertoire restrictions in abatacept-treated rheumatoid arthritis patients.

BACKGROUND: CD28(neg) T cells, which display functional characteristic of oligoclonally expanded cytotoxic memory T lymphocytes, are believed to be pathologically relevant in rheumatoid arthritis manifestation. The CD28 co-stimulation blockade by abatacept can prevent the generation of CD28(neg) T-cell populations in these patients. METHODS: Samples were obtained before and after 12 months of abatacept therapy. T-cell phenotype and T-cell receptor diversity were evaluated by flow cytometry and complementarity-determining region-3 spectratyping, respectively, while telomerase reverse-transcriptase gene level was measured by real-time PCR. RESULTS: Abatacept induces a decrease of the percentage and number of CD4(+)CD28(neg) T cells and a reduction of T-cell repertoire restrictions; these features are directly correlated. Thymic output and telomerase activity are not modified by the therapy. CONCLUSIONS: Abatacept-induced decrease of peripheral T-cell repertoire restrictions can due to a reduced generation of senescent, chronically stimulated CD4(+)CD28(neg) T cells

Acceptability and Feasibility of a Pharmacist-Led HIV Pre-Exposure Prophylaxis (PrEP) Program in the Midwestern United States

BACKGROUND: HIV pre-exposure prophylaxis (PrEP) substantially reduces the risk of HIV acquisition, yet significant barriers exist to its prescription and use. Incorporating pharmacists in the PrEP care process may help increase access to PrEP services. METHODS: Our pharmacist-led PrEP program (P-PrEP) included pharmacists from a university-based HIV clinic, a community pharmacy, and two community-based clinics. Through a collaborative practice agreement, pharmacists conducted PrEP visits with potential candidates for PrEP, according to the recommended CDC guidelines, and authorized emtricitabine-tenofovir disoproxil fumarate prescriptions. Demographics and retention in care over 12 months were summarized and participant satisfaction and pharmacist acceptability with the P-PrEP program were assessed by Likert-scale questionnaires. RESULTS: Sixty patients enrolled in the P-PrEP program between January and June 2017 completing 139 visits. The mean age was 34 years (range 20-61 years) and 88% identified as men who have sex with men, 91.7% were men, 83.3% were white, 80% were commercially insured, and 89.8% had completed some college education or higher. Participant retention at 3, 6, 9, and 12 months was 73%, 58%, 43%, and 28%, respectively. To date, no participant has seroconverted. One hundred percent of the participants who completed the patient satisfaction questionnaire would recommend the P-PrEP program. Pharmacists reported feeling comfortable performing point-of-care testing and rarely reported feeling uncomfortable during PrEP visits (3 occasions - 2.2%) or experiencing workflow disruption (1 occasion - 0.7%). CONCLUSIONS: Implementation of a pharmacist-led PrEP program is feasible and associated with high rates of patient satisfaction and pharmacist acceptability

Effectiveness and Safety of Bictegravir/Emtricitabine/Tenofovir Alafenamide in Patients With HIV-1 Infection and Ongoing Substance Use Disorder: The BASE Study

BACKGROUND: People with human immunodeficiency virus (HIV) and substance use disorder (PWH/SUD) are at higher risk of nonadherence to antiretroviral therapy. Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) exhibits high rates of efficacy with a favorable adverse event profile. The BASE study (NCT03998176) is a phase 4, single-arm study evaluating the effectiveness and safety of B/F/TAF among PWH/SUD. METHODS: Viremic (HIV RNA \u3e1000 copies/mL) PWH/SUD initiated B/F/TAF once daily for 48 weeks (W). The primary endpoint was proportion of participants with HIV RNA/mL at W24. Secondary endpoints were proportion of participants with HIV-1 RNA/mL at W48, safety, B/F/TAF adherence (dried blood spot [DBS] concentrations of emtricitabine triphosphate and tenofovir diphosphate [TFV-DP]), substance use (NIDA-ASSIST), and quality of life (SF-12). RESULTS: Forty-three participants were enrolled; 95% reported methamphetamine use. Median age was 38 (range, 21-62) years; 21% were female, 81% White, 14% Black, and 16% Hispanic. Thirty-two (74%) and 21 (49%) participants had HIV RNA/mL (intention-to-treat) at W24 and W48, respectively. Seven participants (16%) experienced confirmed virologic failure through W48; 1 developed emergent drug resistance (M184V). Fifteen participants (35%) experienced grade ≥3 adverse events. Five participants (12%) reported suicidal ideation; none resulted in discontinuation. Median DBS concentrations were representative of 5-6 doses/week (TFV-DP, 1603 fmol/punches). NIDA-ASSIST scores declined from baseline to W48 with methamphetamine use decreasing most (-7.9 points; -29%), and SF-12 physical/mental scores increased 1.2 and 7.6 points, respectively. CONCLUSIONS: B/F/TAF among a high-risk population of PWH/SUD resulted in an initial 72% viral suppression rate at W24 before dropping to 49% at W48 as retention declined. One participant developed emergent drug resistance (M184V)

Midwest Pharmacists\u27 Familiarity, Experience, and Willingness to Provide Pre-Exposure Prophylaxis (PrEP) for HIV

INTRODUCTION: Pharmacist provision of pre-exposure prophylaxis (PrEP) through collaborative practice agreements with physicians could expand access to people at risk for HIV. We characterized pharmacists\u27 familiarity with and willingness to provide PrEP services in Nebraska and Iowa. METHODS: An invitation to complete an 18-question survey was emailed to 1,140 pharmacists in Nebraska and Iowa in June and July of 2016. Descriptive analyses and Pearson chi-square tests were used to determine to what extent demographics, familiarity and experience were associated with respondent willingness to provide PrEP. Wilcoxon rank-sum tests compared ages and years of experience between groups of respondents. RESULTS: One hundred forty pharmacists (12.3%) responded. Less than half were familiar with the use of PrEP (42%) or the CDC guidelines for its use (25%). Respondents who were older (p = .015) and in practice longer (p = .005) were less likely to be familiar with PrEP. Overall, 54% indicated they were fairly or very likely to provide PrEP services as part of a collaborative practice agreement and after additional training. While familiarity with PrEP use or guidelines did not affect respondents\u27 willingness to provide PrEP, respondents were more likely to provide PrEP with prior experience counseling HIV-infected patients on antiretroviral therapy (OR 2.43; p = 0.023) or PrEP (OR 4.67; p = 0.013), and with prior HIV-related continuing education (OR 2.77; p = 0.032). CONCLUSIONS: Pharmacist respondents in Nebraska and Iowa had limited familiarity and experience with PrEP, but most indicated willingness to provide PrEP through collaborative practice agreements after additional training. Provision of PrEP-focused continuing education may lead to increased willingness to participate in PrEP programs

A Pharmacist-Led Medication Switch Protocol in an Academic HIV Clinic: Patient Knowledge and Satisfaction

BACKGROUND: Tenofovir alafenamide (TAF) is associated with less renal and bone toxicity compared with tenofovir disoproxil (TDF). TAF\u27s recent FDA approval has spurred HIV providers to consider switching antiretroviral therapy (ART) regimens containing TDF to TAF to minimize long term risks. Patient views on the process of such medication switches have not been explored. METHODS: Patients taking elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) following the Food and Drug Administration\u27s (FDA) approval of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) received medication education from an HIV pharmacist prior to switching to the tenofovir alafenamide (TAF) formulation. Patients were asked to complete a cross-sectional survey assessing satisfaction with the switch process and knowledge about the new medication 4 to 8 weeks post-switch. RESULTS: Sixty five patients completed the switch and 57 (88%) completed a follow-up survey. Most (86%) reported understanding why the switch was made, while 91% correctly identified that TAF is associated with reduced renal toxicity, and 73% correctly identified that TAF is associated with reduced bone toxicity. No statistically significant difference was found in satisfaction with or understanding of why the medication switch was made when assessed by sex, age, race, or education, but there was a trend toward significance in the distribution of answers based on education level with those with a high school diploma, General Educational Development (GED) or less being more likely to be satisfied with the medication switch (p = 0.074). CONCLUSIONS: Education from an ambulatory clinic-based HIV pharmacist resulted in high rates of patient satisfaction and understanding of the switch from TDF to TAF-containing ART

Observing Ultra High Energy Cosmic Particles from Space: SEUSO, the Super Extreme Universe Space Observatory Mission

The experimental search for ultra high energy cosmic messengers, from $E\sim 10^{19}$ eV to beyond $E\sim 10^{20}$ eV, at the very end of the known energy spectrum, constitutes an extraordinary opportunity to explore a largely unknown aspect of our universe. Key scientific goals are the identification of the sources of ultra high energy particles, the measurement of their spectra and the study of galactic and local intergalactic magnetic fields. Ultra high energy particles might, also, carry evidence of unknown physics or of exotic particles relics of the early universe. To meet this challenge a significant increase in the integrated exposure is required. This implies a new class of experiments with larger acceptances and good understanding of the systematic uncertainties. Space based observatories can reach the instantaneous aperture and the integrated exposure necessary to systematically explore the ultra high energy universe. In this paper, after briefly summarising the science case of the mission, we describe the scientific goals and requirements of the SEUSO concept. We then introduce the SEUSO observational approach and describe the main instrument and mission features. We conclude discussing the expected performance of the mission