54 research outputs found
A trial of a job-specific workers' health surveillance program for construction workers: study protocol
<p>Abstract</p> <p>Background</p> <p>Dutch construction workers are offered periodic health examinations. This care can be improved by tailoring this workers health surveillance (WHS) to the demands of the job and adjust the preventive actions to the specific health risks of a worker in a particular job. To improve the quality of the WHS for construction workers and stimulate relevant job-specific preventive actions by the occupational physician, we have developed a job-specific WHS. The job-specific WHS consists of modules assessing both physical and psychological requirements. The selected measurement instruments chosen, are based on their appropriateness to measure the workers' capacity and health requirements. They include a questionnaire and biometrical tests, and physical performance tests that measure physical functional capabilities. Furthermore, our job-specific WHS provides occupational physicians with a protocol to increase the worker-behavioural effectiveness of their counselling and to stimulate job-specific preventive actions. The objective of this paper is to describe and clarify our study to evaluate the behavioural effects of this job-specific WHS on workers and occupational physicians.</p> <p>Methods/Design</p> <p>The ongoing study of bricklayers and supervisors is a nonrandomised trial to compare the outcome of an intervention (job-specific WHS) group (n = 206) with that of a control (WHS) group (n = 206). The study includes a three-month follow-up. The primary outcome measure is the proportion of participants who have undertaken one or more of the preventive actions advised by their occupational physician in the three months after attending the WHS. A process evaluation will be carried out to determine context, reach, dose delivered, dose received, fidelity, and satisfaction. The present study is in accordance with the TREND Statement.</p> <p>Discussion</p> <p>This study will allow an evaluation of the behaviour of both the workers and occupational physician regarding the preventive actions undertaken by them within the scope of a job-specific WHS.</p> <p>Trial registration</p> <p><a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=3012">NTR3012</a></p
Identification of Novel Functional Inhibitors of Acid Sphingomyelinase
We describe a hitherto unknown feature for 27 small drug-like molecules, namely functional inhibition of acid sphingomyelinase (ASM). These entities named FIASMAs (Functional Inhibitors of Acid SphingoMyelinAse), therefore, can be potentially used to treat diseases associated with enhanced activity of ASM, such as Alzheimer's disease, major depression, radiation- and chemotherapy-induced apoptosis and endotoxic shock syndrome. Residual activity of ASM measured in the presence of 10 µM drug concentration shows a bimodal distribution; thus the tested drugs can be classified into two groups with lower and higher inhibitory activity. All FIASMAs share distinct physicochemical properties in showing lipophilic and weakly basic properties. Hierarchical clustering of Tanimoto coefficients revealed that FIASMAs occur among drugs of various chemical scaffolds. Moreover, FIASMAs more frequently violate Lipinski's Rule-of-Five than compounds without effect on ASM. Inhibition of ASM appears to be associated with good permeability across the blood-brain barrier. In the present investigation, we developed a novel structure-property-activity relationship by using a random forest-based binary classification learner. Virtual screening revealed that only six out of 768 (0.78%) compounds of natural products functionally inhibit ASM, whereas this inhibitory activity occurs in 135 out of 2028 (6.66%) drugs licensed for medical use in humans
Prenatal exposures and exposomics of asthma
This review examines the causal investigation of preclinical development of childhood asthma using exposomic tools. We examine the current state of knowledge regarding early-life exposure to non-biogenic indoor air pollution and the developmental modulation of the immune system. We examine how metabolomics technologies could aid not only in the biomarker identification of a particular asthma phenotype, but also the mechanisms underlying the immunopathologic process. Within such a framework, we propose alternate components of exposomic investigation of asthma in which, the exposome represents a reiterative investigative process of targeted biomarker identification, validation through computational systems biology and physical sampling of environmental medi
On the origin of the photocurrent of electrochemically passivated p-InP(100) photoelectrodes
\u3cp\u3eIII-V semiconductors such as InP are highly efficient light absorbers for photoelectrochemical (PEC) water splitting devices. Yet, their cathodic stability is limited due to photocorrosion and the measured photocurrents do not necessarily originate from H\u3csub\u3e2\u3c/sub\u3e evolution only. We evaluated the PEC stability and activation of model p-InP(100) photocathodes upon photoelectrochemical passivation (i.e. repeated surface oxidation/reduction). The electrode was subjected to a sequence of linear potential scans with or without intermittent passivation steps (repeated passivation and continuous reduction, respectively). The evolution of H\u3csub\u3e2\u3c/sub\u3e and PH\u3csub\u3e3\u3c/sub\u3e gases was monitored by online electrochemical mass spectrometry (OLEMS) and the Faradaic efficiencies of these processes were determined. Repeated passivation led to an increase of the photocurrent in 0.5 M H\u3csub\u3e2\u3c/sub\u3eSO\u3csub\u3e4\u3c/sub\u3e, while continuous reduction did not affect the photocurrent of p-InP(100). Neither H\u3csub\u3e2\u3c/sub\u3e nor PH\u3csub\u3e3\u3c/sub\u3e formation increased to the same extent as the photocurrent during the repeated passivation treatment. Surface analysis of the spent electrodes revealed substantial roughening of the electrode surface by repeated passivation, while continuous reduction left the surface unaltered. On the other hand, photocathodic conditioning performed in 0.5 M HCl led to the expected correlation between photocurrent increase and H\u3csub\u3e2\u3c/sub\u3e formation. Ultimately, the H\u3csub\u3e2\u3c/sub\u3e evolution rates of the photoelectrodes in H\u3csub\u3e2\u3c/sub\u3eSO\u3csub\u3e4\u3c/sub\u3e and HCl are comparable. The much higher photocurrent in H\u3csub\u3e2\u3c/sub\u3eSO\u3csub\u3e4\u3c/sub\u3e is due to competing side-reactions. The results emphasize the need for a detailed evaluation of the Faradaic efficiencies of all the involved processes using a chemical-specific technique like OLEMS. Photo-OLEMS can be beneficial in the study of photoelectrochemical reactions enabling the instantaneous detection of small amounts of reaction by-products.\u3c/p\u3
High-efficiency InP-based photocathode for hydrogen production by interface energetics design and photon management
The solar energy conversion efficiency of photoelectrochemical (PEC) devices is usually limited by poor interface energetics, limiting the onset potential, and light reflection losses. Here, a three-pronged approach to obtain excellent performance of an InP-based photoelectrode for water reduction is presented. First, a buried p-n+ junction is fabricated, which shifts the valence band edge favorably with respect to the hydrogen redox potential. Photoelectron spectroscopy substantiates that the shift of the surface photovoltage is mainly determined by the buried junction. Second, a periodic array of InP nanopillars is created at the surface of the photoelectrode to substantially reduce the optical reflection losses. This device displays an unprecedented photocathodic power-saved efficiency of 15.8% for single junction water reduction. Third, a thin TiO2 protection layer significantly increases the stability of the InP-based photoelectrode. Careful design of the interface energetics based on surface photovoltage spectroscopy allows obtaining a PEC cell with stable record performance in water reduction. The efficiency of photoelectrochemical (PEC) water splitting devices is usually limited by interface energetics mismatch between the semiconductor and the electrolyte and insufficient light absorption. The highest photocathodic power-saved efficiency of 15.8% reported so far for single junction PEC water reduction is obtained through interface energetics design and photon management of an InP-based photoelectrode
Metformin does not affect cancer risk: a cohort study in the U.K. Clinical Practice Research Datalink analyzed like an intention-to-treat trial.
OBJECTIVE: Meta-analyses of epidemiologic studies have suggested that metformin may reduce cancer incidence, but randomized controlled trials did not support this hypothesis. RESEARCH DESIGN AND METHODS: A retrospective cohort study, Clinical Practice Research Datalink, was designed to investigate the association between use of metformin compared with other antidiabetes medications and cancer risk by emulating an intention-to-treat analysis as in a trial. A total of 95,820 participants with type 2 diabetes who started taking metformin and other oral antidiabetes medications within 12 months of their diagnosis (initiators) were followed up for first incident cancer diagnosis without regard to any subsequent changes in pharmacotherapy. Cox proportional hazards models were used to estimate multivariable-adjusted hazard ratios (HR) and 95% CI. RESULTS: A total of 51,484 individuals (54%) were metformin initiators and 18,264 (19%) were sulfonylurea initiators, and 3,805 first incident cancers were diagnosed during a median follow-up time of 5.1 years. Compared with initiators of sulfonylurea, initiators of metformin had a similar incidence of total cancer (HR 0.96; 95% CI 0.89-1.04) and colorectal (HR 0.92; 95% CI 0.76-1.13), prostate (HR 1.02; 95% CI 0.83-1.25), lung (HR 0.85; 95% CI 0.68-1.07), or postmenopausal breast (HR 1.03; 95% CI 0.82-1.31) cancer or any other cancer. CONCLUSIONS: In this large study, individuals with diabetes who used metformin had a similar risk of developing cancer compared with those who used sulfonylureas
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