Screening for health risks: A social science perspective

Health screening promises to reduce risks to individuals via probabilistic sifting of populations for medical conditions. The categorisation and selection of 'conditions' such as cardiovascular events, dementia and depression for screening itself requires prior interpretive labour which usually remains unexamined. Screening systems can take diverse organisational forms and varying relationships to health status, as when purported disease precursors, for example 'pre-cancerous' polyps, or supposed risk factors, such as high cholesterol themselves, become targets for screening. Screening at best yields small, although not necessarily unworthwhile, net population health gains. It also creates new risks, leaving some individuals worse-off than if they had been left alone. The difficulties associated with attempting to measure small net gains through randomised controlled trials are sometimes underestimated. Despite endemic doubts about its clinical utility, bibliometric analysis of published papers shows that responses to health risks are coming to be increasingly thought about in terms of screening. This shift is superimposed on a strengthening tendency to view health through the lens of risk. It merits further scrutiny as a societal phenomenon

Modelling the behaviour of microbulk Micromegas in Xenon/trimethylamine gas

We model the response of a state of the art micro-hole single-stage charge amplication device (`microbulk' Micromegas) in a gaseous atmosphere consisting of Xenon/trimethylamine at various concentrations and pressures. The amplifying structure, made with photo-lithographic techniques similar to those followed in the fabrication of gas electron multipliers (GEMs), consisted of a 100 um-side equilateral-triangle pattern with 50 um-diameter holes placed at its vertexes. Once the primary electrons are guided into the holes by virtue of an optimized field configuration, avalanches develop along the 50 um-height channels etched out of the original doubly copper-clad polyimide foil. In order to properly account for the strong field gradients at the holes' entrance as well as for the fluctuations of the avalanche process (that ultimately determine the achievable energy resolution), we abandoned the hydrodynamic framework, resorting to a purely microscopic description of the electron trajectories as obtained from elementary cross-sections. We show that achieving a satisfactory description needs additional assumptions about atom-molecule (Penning) transfer reactions and charge recombination to be made

Gaseous time projection chambers for rare event detection: Results from the T-REX project. II. Dark matter

As part of the T-REX project, a number of R&D and prototyping activities have been carried out during the last years to explore the applicability of Micromegas-read gaseous TPCs in rare event searches like double beta decay (DBD), axion research and low-mass WIMP searches. While in the companion paper we focus on DBD, in this paper we focus on the results regarding the search for dark matter candidates, both axions and WIMPs. Small ultra-low background Micromegas detectors are used to image the x-ray signal expected in axion helioscopes like CAST at CERN. Background levels as low as $0.8\times 10^{-6}$ c keV$^{-1}$cm$^{-2}$s$^{-1}$ have already been achieved in CAST while values down to $\sim10^{-7}$ c keV$^{-1}$cm$^{-2}$s$^{-1}$ have been obtained in a test bench placed underground in the Laboratorio Subterr\'aneo de Canfranc. Prospects to consolidate and further reduce these values down to $\sim10^{-8}$ c keV$^{-1}$cm$^{-2}$s$^{-1}$will be described. Such detectors, placed at the focal point of x-ray telescopes in the future IAXO experiment, would allow for 10$^5$ better signal-to-noise ratio than CAST, and search for solar axions with $g_{a\gamma}$ down to few 10$^{12}$ GeV$^{-1}$, well into unexplored axion parameter space. In addition, a scaled-up version of these TPCs, properly shielded and placed underground, can be competitive in the search for low-mass WIMPs. The TREX-DM prototype, with $\sim$0.300 kg of Ar at 10 bar, or alternatively $\sim$0.160 kg of Ne at 10 bar, and energy threshold well below 1 keV, has been built to test this concept. We will describe the main technical solutions developed, as well as the results from the commissioning phase on surface. The anticipated sensitivity of this technique might reach $\sim10^{-44}$ cm$^2$ for low mass ($<10$ GeV) WIMPs, well beyond current experimental limits in this mass range.Comment: Published in JCAP. New version with erratum incorporated (new figure 14

Implications of a defined daily dose fixed database for drug utilization research studies: The case of statins in Portugal

Aims Given the discrepancies between PDDs (prescribed daily doses) and DDDs (defined daily doses), we aimed to assess the extent of error in the results of an 18-year population-level study on statin utilization in Portugal. Methods The Portuguese regulatory agency provided data for the period 2000-2018 on statin dispensing (C10AA). The DDDs were gathered from the ATC/DDD database. DDDs were calculated by the DDD year-by-year approach (DDDYEAR) and by the DDD last-year approach (DDDLAST). PDDs were calculated according to the year-by-year approach (PDDYEAR). Statin annual utilization rates per 1000 inhabitants per day were also calculated. Percent errors were calculated for PDDYEAR and DDDYEAR units. Results The DDDYEAR approach revealed decreases in the consumption of atorvastatin, fluvastatin, lovastatin, pravastatin and simvastatin in 2009, when their DDD was modified. Conversely, the results from both DDDLAST and PDDYEAR approaches indicated gradual changes in the actual consumption of all statins in Portugal. Before 2009, atorvastatin, pravastatin and simvastatin utilization was greatly overestimated by DDDYEAR/1000 inhabitants/day. The average dose of lovastatin prescribed in the past 18 years (20 mg) was below the assigned DDDs during the study period, varying from 30 mg to 45 mg. Conversely, the PDD for fluvastatin was above the DDD values (ranging from 40 mg in 2000 to 70 mg in 2016). For atorvastatin, pravastatin and simvastatin, national PDDs were above the assigned DDD until the DDD modification in 2009. Conclusions A more dynamic system, based on national and annually updated DDDs, should be able to reduce discrepancies between DDDs and PDDs and the bias in utilization studies

A Micromegas-based low-background x-ray detector coupled to a slumped-glass telescope for axion research

We report on the design, construction and operation of a low background x-ray detection line composed of a shielded Micromegas (micromesh gaseous structure) detector of the microbulk technique. The detector is made from radiopure materials and is placed at the focal point of a $\sim$~5 cm diameter, 1.3 m focal-length, cone-approximation Wolter I x-ray telescope (XRT) comprised of thermally-formed (or "slumped") glass substrates deposited with multilayer coatings. The system has been conceived as a technological pathfinder for the future International Axion Observatory (IAXO), as it combines two of the techniques (optic and detector) proposed in the conceptual design of the project. It is innovative for two reasons: it is the first time an x-ray optic has been designed and fabricated specifically for axion research, and the first time a Micromegas detector has been operated with an x-ray optic. The line has been installed at one end of the CERN Axion Solar Telescope (CAST) magnet and is currently looking for solar axions. The combination of the XRT and Micromegas detector provides the best signal-to-noise ratio obtained so far by any detection system of the CAST experiment with a background rate of 5.4$\times$10$^{-3}\;$counts per hour in the energy region-of-interest and signal spot area.Comment: 21 pages, 16 figure

Topotecan-vincristine-doxorubicin in stage 4 high risk neuroblastoma patients failing to achieve a complete metastatic response to rapid COJEC : a SIOPEN study

Purpose : Metastatic response to induction therapy for high-risk neuroblastoma is a prognostic factor. In the International Society of Paediatric Oncology Europe Neuroblastoma (SIOPEN) HR-NBL-1 protocol, only patients with metastatic complete response (CR) or partial response (PR) with <= three abnormal skeletal areas on iodine 123-metaiodobenzylguanidine ([I-123] mIBG) scintigraphy and no bone marrow disease proceed to high dose therapy (HDT). In this study, topotecan-vincristine-doxorubicin (TVD) was evaluated in patients failing to achieve these criteria, with the aim of improving the metastatic response rate. Materials and Methods : Patients with metastatic high-risk neuroblastoma who had not achieved the SIOPEN criteria for HDT after induction received two courses of topotecan 1.5 mg/m(2)/day for 5 days, followed by a 48-hour infusion of vincristine, 2 mg/m(2), and doxorubicin, 45 mg/m(2). Results : Sixty-three patients were eligible and evaluable. Following two courses of TVD, four (6.4%) patients had an overall CR, while 28 (44.4%) had a PR with a combined response rate of 50.8% (95% confidence interval [CI], 37.9 to 63.6). Of these, 23 patients achieved a metastatic CR or a PR with <= 3 mIBG skeletal areas and no bone marrow disease (36.5%; 95% CI, 24.7 to 49.6) and were eligible to receive HDT. Toxicity was mostly haematological, affecting 106 of the 126 courses (84.1%; 95% CI, 76.5 to 90.0), and dose reduction was necessary in six patients. Stomatitis was the second most common nonhematological toxicity, occurring in 20 patients (31.7%). Conclusion : TVD was effective in improving the response rate of high-risk neuroblastoma patients after induction with COJEC enabling them to proceed to HDT. However, the long-term benefits of TVD needs to be determined in randomized clinical trials