Performance of the Two Aerogel Cherenkov Detectors of the JLab Hall A Hadron Spectrometer

We report on the design and commissioning of two silica aerogel Cherenkov detectors with different refractive indices. In particular, extraordinary performance in terms of the number of detected photoelectrons was achieved through an appropriate choice of PMT type and reflector, along with some design considerations. After four years of operation, the number of detected photoelectrons was found to be noticeably reduced in both detectors as a result of contamination, yellowing, of the aerogel material. Along with the details of the set-up, we illustrate the characteristics of the detectors during different time periods and the probable causes of the contamination. In particular we show that the replacement of the contaminated aerogel and parts of the reflecting material has almost restored the initial performance of the detectors.Comment: 18 pages, 9 Figures, 4 Tables, 44 Reference

Effectiveness of dolutegravir-based regimens as either first-line or switch antiretroviral therapy: data from the Icona cohort

Introduction: Concerns about dolutegravir (DTG) tolerability in the real-life setting have recently arisen. We aimed to estimate the risk of treatment discontinuation and virological failure of DTG-based regimens from a large cohort of HIV-infected individuals. Methods: We performed a multicentre, observational study including all antiretroviral therapy (ART)-naïve and virologically suppressed treatment-experienced (TE) patients from the Icona (Italian Cohort Naïve Antiretrovirals) cohort who started, for the first time, a DTG-based regimen from January 2015 to December 2017. We estimated the cumulative risk of DTG discontinuation regardless of the reason and for toxicity, and of virological failure using Kaplan–Meier curves. We used Cox regression model to investigate predictors of DTG discontinuation. Results: About 1679 individuals (932 ART-naïve, 747 TE) were included. The one- and two-year probabilities (95% CI) of DTG discontinuation were 6.7% (4.9 to 8.4) and 11.5% (8.7 to 14.3) for ART-naïve and 6.6% (4.6 to 8.6) and 7.6% (5.4 to 9.8) for TE subjects. In both ART-naïve and TE patients, discontinuations of DTG were mainly driven by toxicity with an estimated risk (95% CI) of 4.0% (2.6 to 5.4) and 2.5% (1.3 to 3.6) by one year and 5.6% (3.8 to 7.5) and 4.0% (2.4 to 5.6) by two years respectively. Neuropsychiatric events were the main reason for stopping DTG in both ART-naïve (2.1%) and TE (1.7%) patients. In ART-naïve, a concomitant AIDS diagnosis predicted the risk of discontinuing DTG for any reason (adjusted relative hazard (aRH) = 3.38, p = 0.001), whereas starting DTG in combination with abacavir (ABC) was associated with a higher risk of discontinuing because of toxicity (aRH = 3.30, p = 0.009). TE patients starting a DTG-based dual therapy compared to a triple therapy had a lower risk of discontinuation for any reason (adjusted hazard ratio (aHR) = 2.50, p = 0.037 for ABC-based triple-therapies, aHR = 3.56, p = 0.012 for tenofovir-based) and for toxicity (aHR = 5.26, p = 0.030 for ABC-based, aHR = 6.60, p = 0.024 for tenofovir-based). The one- and two-year probabilities (95% CI) of virological failure were 1.2% (0.3 to 2.0) and 4.6% (2.7 to 6.5) in the ART naïve group and 2.2% (1.0 to 3.3) and 2.9% (1.5 to 4.3) in the TE group. Conclusions: In this large cohort, DTG showed excellent efficacy and optimal tolerability both as first-line and switching ART. The low risk of treatment-limiting toxicities in ART-naïve as well as in treated individuals reassures on the use of DTG in everyday clinical practice

Life satisfaction and confidence in national institutions: evidence from South America

A number of South American countries experienced turbulent democratic, political and economic upheaval over the last 40 years in the form of coup d’états in the 1970s, tumultuous elections, and repeated severe economic crises, some of which happened fairly recently. Starting in 2010, a number of court proceedings across the region have made past military coup d’états the focus of national conversations. South American citizens may, therefore, have lost confidence in national institutions that have repeatedly disappointed their trust and expectations; a situation with potentially detrimental effects on their well-being. Using eight waves of the Gallup World Poll collected between 2009 and 2016 across ten South American countries, we investigate to what extent people’s confidence in financial institutions, the honesty of elections, the military, the judicial system, the national government and the police is associated with people’s current and expectation of future life satisfaction. We find that people who report confidence in these six institutions rate their current and expected life satisfaction, on average, to be higher than those who lack these types of institutional confidence, even after controlling for demographic factors and macroeconomic indicators. In addition, we investigate changes over time for all six measures of confidence in institutions as well as for current and expectation of future life satisfaction. Our results suggest that governments’ investments in well-functioning institutions may contribute positively to subjective well-being in a society. However, our analysis is correlational and we thus cannot rule out reverse causality

Disability quotas: past or future policy?

This article considers the issues associated with the use of quota systems for the employment of workers with a disability. It examines the use and experiences of such quotas in Italy, Russia and the United Kingdom. Italy has a long established quota for the employment of such workers, whilst the modern Russian system it is a more recent innovation. In contrast the UK abandoned its quotas in the 1990s. We draw on the experiences of the three countries to consider generally whether the use of quotas is either an acceptable means of encouraging employers to take on disabled workers, or is necessary to achieve this objective

Cost effectiveness of first-line oral therapies for pulmonary arterial hypertension: A modelling study

Background: In recent years, a significant number of costly oral therapies have become available for the treatment of pulmonary arterial hypertension (PAH). Funding decisions for these therapies requires weighing up their effectiveness and costs. Objective: The aim of this study was to assess the cost effectiveness of monotherapy with oral PAH-specific therapies versus supportive care as initial therapy for patients with functional class (FC) II and III PAH in Canada. Methods: A cost-utility analysis, from the perspective of a healthcare system and based on a Markov model, was designed to estimate the costs and quality-adjusted life-years (QALYs) associated with bosentan, ambrisentan, riociguat, tadalafil, sildenafil and supportive care for PAH in treatment-naïve patients. Separate analyses were conducted for cohorts of patients commencing therapy at FC II and III PAH. Transition probabilities, based on the relative risk of improving and worsening in FC with treatment versus placebo, were derived from a recent network meta-analysis. Utility values and costs were obtained from published data and clinical expert opinion. Extensive sensitivity analyses were conducted. Results: Analysis suggests that sildenafil is the most cost-effective therapy for PAH in patients with FC II or III. Sildenafil was both the least costly and most effective therapy, thereby dominating all other treatments. Tadalafil was also less costly and more effective than supportive care in FC II and III; however, sildenafil was dominant over tadalafil. Even given the uncertainty within the clinical inputs, the probabilistic sensitivity analysis showed that apart from sildenafil and tadalafil, the other PAH therapies had negligible probability of being the most cost effective. Conclusion: The results show that initiation of therapy with sildenafil is likely the most cost-effective strategy in PAH patients with either FC II or III disease.This research was supported by funds from the Canadian Agency for Drugs and Technologies in Health (CADTH)

Investigation of fennel protein extracts by shot-gun Fourier transform ion cyclotron resonance mass spectrometry

A rapid shot-gun method by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) is proposed for the characterization of fennel proteins. After enzymatic digestion with trypsin, few microliters of extract were analyzed by direct infusion in positive ion mode. A custom-made non-redundant fennel-specific proteome database was derived from the well-known NCBI database; additional proteins belonging to recognized allergenic sources (celery, carrot, parsley, birch, and mugwort) were also included in our database, since patients hypersensitive to these plants could also suffer from fennel allergy. The peptide sequence of each protein from that derived list was theoretically sequenced to produce calculated m/z lists of possible m/z ions after tryptic digestions. Then, by using a home-made Matlab algorithm, those lists were matched with the experimental FT-ICR mass spectrum of the fennel peptide mixture. Finally, Peptide Mass Fingerprint searches confirmed the presence of the matched proteins inside the fennel extract with a total of 70 proteins (61 fennel specific and 9 allergenic proteins)

Sustainable solutions for removing aged wax-based coatings from cultural heritage. Exploiting hydrophobic deep eutectic solvents (DESs)

This study describes the investigation on the use of hydrophobic Deep Eutectic Solvents (DESs) for the removal of nonpolar coatings from works of art to replace toxic solvents. Beeswax and two microcrystalline waxes (R21 and Renaissances) have been selected as reference nonpolar coatings since they are commonly present in their aged state on metal and stone artifacts. The interaction between the DESs and three waxes has been evaluated through contact angle measurements, solubility tests, and cleaning tests carried out by implementing a method that is ordinarily used by restorers. Tests have been conducted on mockups consisting of microscope glass slides covered by wax. The effective removal of the wax-based coating from the mockups has been assessed through spectrocolorimetry and multispectral imaging under visible (VIS) and ultraviolet light (UV) at 365 nm by loading the waxes with a fluorescent marker (Rhodamine 6G). Fourier Transform Infrared (FT-IR) spectroscopy in the Attenuated Total Reflectance (ATR) mode was performed to assess the presence of both the wax and the solvent on the swabs used for the cleaning tests, confirming the actual interaction among the solvent and the solute. The experimental process proved DESs’ potential of being used as green solvents for cleaning treatments on Cultural Heritage