Meta-analysis of pharmacogenetic interactions in amyotrophic lateral sclerosis clinical trials

OBJECTIVE: To assess whether genetic subgroups in recent amyotrophic lateral sclerosis (ALS) trials responded to treatment with lithium carbonate, but that the treatment effect was lost in a large cohort of nonresponders. METHODS: Individual participant data were obtained from 3 randomized trials investigating the efficacy of lithium carbonate. We matched clinical data with data regarding the UNC13A and C9orf72 genotype. Our primary outcome was survival at 12 months. On an exploratory basis, we assessed whether the effect of lithium depended on the genotype. RESULTS: Clinical data were available for 518 of the 606 participants. Overall, treatment with lithium carbonate did not improve 12-month survival (hazard ratio [HR] 1.0, 95% confidence interval [CI] 0.7-1.4; p = 0.96). Both the UNC13A and C9orf72 genotype were independent predictors of survival (HR 2.4, 95% CI 1.3-4.3; p = 0.006 and HR 2.5, 95% CI 1.1-5.2; p = 0.032, respectively). The effect of lithium was different for UNC13A carriers (p = 0.027), but not for C9orf72 carriers (p = 0.22). The 12-month survival probability for UNC13A carriers treated with lithium carbonate improved from 40.1% (95% CI 23.2-69.1) to 69.7% (95% CI 50.4-96.3). CONCLUSIONS: This study incorporated genetic data into past ALS trials to determine treatment effects in a genetic post hoc analysis. Our results suggest that we should reorient our strategies toward finding treatments for ALS, start focusing on genotype-targeted treatments, and standardize genotyping in order to optimize randomization and analysis for future clinical trials

Eco-sustainable lightweight automotive part manufacturing: GHGs-free die casting of brake leverage prototype made of AZ91D-1.5CaO magnesium alloy

Employing non-flammable AZ91D-1.5CaO Eco-Magnesium® (Eco-Mg) alloy in the European project CRAL provides the lowest carbon footprint for the magnesium cast process. Non-flammable magnesium AZ91D alloyed with Ca (in the form of CaO) was successfully processed by experimenting specific casting process window to melt the non-flammable magnesium alloy in a stationary furnace with no SF6 cover gas and then poured in the air into a vertical shortinjection displacement press machinery specifically developed in EU CRAL project. Brake leverage made of AZ91-1.5CaO Eco-Mg series alloy was successfully manufactured at Brembo Spa premise, as a real example of Mg cast component alternative to the current component made of forged aluminium alloy. As discussed in the experimental part, a preliminary computer-aided simulation test campaign reduced uncertainty in cast trials. The CRAL EU project with the realization of Mg-SF6 free cast part for brake systems has promoted the drastic reduction of Global Warming Potential (GWP) of the Mg cast process route. The Eco-Mg series is a feasible and affordable casting solution for introducing non-flammable Mg alloys in the automobile sector; today struggled for researching cost-driven lightweight components due to forthcoming CO2 emissions restrictions

In-phantom spectra and dose distributions from a high-energy neutron therapy beam

In radiotherapy with external beams, healthy tissues surrounding the target volumes are inevitably irradiated. In the case of neutron therapy, the estimation of dose to the organs surrounding the target volume is particularly challenging, because of the varying contributions from primary and secondary neutrons and photons of different energies. The neutron doses to tissues surrounding the target volume at the Louvain-la-Neuve (LLN) facility were investigated in this work. At LLN, primary neutrons have a broad spectrum with a mean energy of about 30 MeV. The transport of a 10 x 10 cm(2) beam through a water phantom was simulated by means of the Monte Carlo code MCNPX. Distributions of energy-differential values of neutron fluence, kerma and kerma equivalent were estimated at different locations in a water phantom. The evolution of neutron dose and dose equivalent inside the phantom was deduced. Measurements of absorbed dose and of dose equivalent were then carried out in a water phantom using an ionization chamber and superheated drop detectors (SDDs). On the beam axis, the calculations agreed well with the ionization chamber data, but disagreed significantly from the SDD data due to the detector's under-response to neutrons above 20 MeV. Off the beam axis, the calculated absorbed doses were significantly lower than the ionization chamber readings, since gamma fields were not accounted for. The calculated data are doses from neutron-induced charge particles, and these agreed with the values measured by the photon-insensitive SDDs. When exposed to the degraded spectra off the beam axis, the SDD offered reliable estimates of the neutron dose equivalent. (C) 2002 Elsevier Science B.V. All rights reserved

La formazione in tema di sicurezza delle cure e prevenzione controllo delle infezioni correlate all'assistenza

L'articolo analizza i bisogni formativi nell'ambito della prevenzione e controllo del rischio di infezioni correlate all'assistenza, con particolare riferimento alla formazione pre laurea, specialistica, continua dei professionisti e degli specialisti del settore

Application of work place correction factors to dosemeter results for the assessment of personal doses at nuclear facilitie

Ratios of Hp(10) and H*(10) were determined with reference instruments in a number of workplace fields within the nuclear industry and used to derive workplace-specific correction factors. When commercial survey meter results together with these factors were applied to the results of the locally used personal dosemeters their results improved and became within 0.7 and 1.7 of the reference values or better depending on the response of the survey meter. A similar result was obtained when a correction was determined with a prototype reference instrument for Hp(10) after adjustment of its response. Commercially available survey instruments both for photon and neutron H*(10) measurements agreed with the reference instruments in most cases to within 0.5-1.5. Those conclusions are derived from results reported within the EC supported EVIDOS contract

Evaluation of individual monitoring in mixed neutron/photon fields: mid-term results from the EVIDOS project

EVIDOS is an EC sponsored project that aims at an evaluation and improvement of radiation protection dosimetry in mixed neutron/photon fields. This is performed through spectrometric and dosimetric investigations during different measurement campaigns in representative workplaces of the nuclear industry. The performance of routine and, in particular, novel personal dosemeters and survey instruments is tested in selected workplace fields. Reference values for the dose equivalent quantities, H*(10) and Hp(10) and the effective dose E, are determined using different spectrometers that provide the energy distribution of the neutron fluence and using newly developed devices that determine the energy and directional distribution of the neutron fluence. The EVIDOS project has passed the mid-term, and three measurement campaigns have been performed. This paper will give an overview and some new results from the third campaign that was held in Mol (Belgium), around the research reactor VENUS and in the MOX producing plant of Belgonucléaire