Concomitant contraceptive implant and efavirenz use in women living with HIV: perspectives on current evidence and policy implications for family planning and HIV treatment guidelines.

IntroductionPreventing unintended pregnancies is important among all women, including those living with HIV. Increasing numbers of women, including HIV-positive women, choose progestin-containing subdermal implants, which are one of the most effective forms of contraception. However, drug-drug interactions between contraceptive hormones and efavirenz-based antiretroviral therapy (ART) may reduce implant effectiveness. We present four inter-related perspectives on this issue.DiscussionFirst, as a case study, we discuss how limited data prompted country-level guidance against the use of implants among women concomitantly using efavirenz in South Africa and its subsequent negative effects on the use of implants in general. Second, we discuss the existing clinical data on this topic, including the observational study from Kenya showing women using implants plus efavirenz-based ART had three-fold higher rates of pregnancy than women using implants plus nevirapine-based ART. However, the higher rates of pregnancy in the implant plus efavirenz group were still lower than the pregnancy rates among women using common alternative contraceptive methods, such as injectables. Third, we discuss the four pharmacokinetic studies that show 50-70% reductions in plasma progestin concentrations in women concurrently using efavirenz-based ART as compared to women not on any ART. These pharmacokinetic studies provide the biologic basis for the clinical findings. Fourth, we discuss how data on this topic have marked implications for both family planning and HIV programmes and policies globally.ConclusionThis controversy underlines the importance of integrating family planning services into routine HIV care, counselling women appropriately on increased risk of pregnancy with concomitant implant and efavirenz use, and expanding contraceptive method mix for all women. As global access to ART expands, greater research is needed to explore implant effectiveness when used concomitantly with newer ART regimens. Data on how HIV-positive women and their partners choose contraceptives, as well as information from providers on how they present and counsel patients on contraceptive options are needed to help guide policy and service delivery. Lastly, greater collaboration between HIV and reproductive health experts at all levels are needed to develop successful strategies to ensure the best HIV and reproductive health outcomes for women living with HIV

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

The free fractions of circulating docosahexaenoic acid and eicosapentenoic acid as optimal end-point of measure in bioavailability studies on n-3 fatty acids

The high complexity of n-3 fatty acids absorption process, along with the huge amount of endogenous fraction, makes bioavailability studies with these agents very challenging and deserving special consideration. In this paper we report the results of a bioequivalence study between a new formulation of EPA+DHA ethyl esters developed by IBSA Institut Biochimique and reference medicinal product present on the Italian market. Bioequivalence was demonstrated according to the criteria established by the EMA Guideline on the Investigation of Bioequivalence. We found that the free fractions represent a better and more sensitive end-point for bioequivalence investigations on n-3 fatty acids, since: (i) the overall and intra-subject variability of PK parameters was markedly lower compared to the same variability calculated on the total DHA and EPA fractions; (ii) the absorption process was completed within 4h, and the whole PK profile could be drawn within 12-15 h from drug administration

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

SUSY Resonances from UHE neutralinos in Neutrino Telescopes and in the Sky

In the Top-down scenarios, the decay of super-heavy particles (m~10^{12-16}GeV), situated in dark-matter halos not very far from our Galaxy, can explain the ultra-high-energy (UHE) cosmic-ray spectrum beyond the Griesen-Zatasepin-Kuzmin cut-off. In the MSSM, a major component of the UHE cosmic-ray flux at PeV-EeV energies could be given by the lightest neutralino \chi, that is the lightest stable supersymmetric particle. Then, the signal of UHE \chi's on earth might emerge over the interactions of a comparable neutrino component. We compute the event rates for the resonant production of "right" selectrons and "right" squarks in mSUGRA, when UHE neutralinos of energy larger than 10^5 GeV scatter off electrons and quarks in an earth-based detector like IceCube. When the resonant channel dominates in the total \chi-e,\chi-q scattering cross section, the only model parameters affecting the corresponding visible signal rates turn out to be the physical masses of the resonant right-scalar and of the lightest neutralino. We compare the expected number of supersymmetric events with the rates corresponding to the expected Glashow W resonance and to the continuum UHE \nu-N scattering for realistic power-law spectra. We find that the event rate in the leptonic selectron channel is particularly promising, and can reach a few tens for a one-year exposure in IceCube. Finally, we note that UHE neutralinos at much higher energies (up to hundreds ZeV) may produce sneutrino resonances by scattering off relic neutrinos in the Local Group hot dark halo. The consequent \tilde{\nu}-burst into hadronic final states could mimic Z-burst events, although with quite smaller conversion efficiency.Comment: 23 pages, 4 figures; one reference adde

Probing mSUGRA via the Extreme Universe Space Observatory

An analysis is carried out within mSUGRA of the estimated number of events originating from upward moving ultra-high energy neutralinos that could be detected by the Extreme Universe Space Observatory (EUSO). The analysis exploits a recently proposed technique that differentiates ultra-high energy neutralinos from ultra-high energy neutrinos using their different absorption lengths in the Earth's crust. It is shown that for a significant part of the parameter space, where the neutralino is mostly a Bino and with squark mass $\sim 1$ TeV, EUSO could see ultra-high energy neutralino events with essentially no background. In the energy range 10^9 GeV < E < 10^11 GeV, the unprecedented aperture of EUSO makes the telescope sensitive to neutralino fluxes as low as 1.1 \times 10^{-6} (E/GeV)^{-1.3} GeV^{-1} cm^{-2} yr^{-1} sr^{-1}, at the 95% CL. Such a hard spectrum is characteristic of supermassive particles' $N$-body hadronic decay. The case in which the flux of ultra-high energy neutralinos is produced via decay of metastable heavy particles with uniform distribution throughout the universe is analyzed in detail. The normalization of the ratio of the relics' density to their lifetime has been fixed so that the baryon flux produced in the supermassive particle decays contributes to about 1/3 of the events reported by the AGASA Collaboration below 10^{11} GeV, and hence the associated GeV gamma-ray flux is in complete agreement with EGRET data. For this particular case, EUSO will collect between 4 and 5 neutralino events (with 0.3 of background) in ~ 3 yr of running. NASA's planned mission, the Orbiting Wide-angle Light-collectors (OWL), is also briefly discussed in this context.Comment: Some discussion added, final version to be published in Physical Review

Future High Energy Neutrino Telescopes

This talk summarizes the main physics goals and basic methods of telescopes for high energy neutrinos. It reviews the present status of deep underwater telescopes and sketches the ICECUBE project as an example for a cube kilometer detector. It is suggested to develop techniques for radio and acoustic detection hand in hand with big optical arrays. These large arrays should be complemented by medium-size detectors in the Megaton range.Comment: Talk given at the Int.Conf.on Neutrino Physics and Astrophysics, Sudbury 2000, 8 pages, 7 figure