Early incidence of occupational asthma among young bakers, pastry-makers and hairdressers: design of a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Occupational exposures are thought to be responsible for 10-15% of new-onset asthma cases in adults, with disparities across sectors. Because most of the data are derived from registries and cross-sectional studies, little is known about incidence of occupational asthma (OA) during the first years after inception of exposure. This paper describes the design of a study that focuses on this early asthma onset period among young workers in the bakery, pastry making and hairdressing sectors in order to assess early incidence of OA in these "at risk" occupations according to exposure duration, and to identify risk factors of OA incidence.</p> <p>Methods/Design</p> <p>The study population is composed of subjects who graduated between 2001 and 2006 in these sectors where they experience exposure to organic or inorganic allergenic or irritant compounds (with an objective of 150 subjects by year) and 250 young workers with no specific occupational exposure. A phone interview focusing on respiratory and 'Ear-Nose-Throat' (ENT) work-related symptoms screen subjects considered as "possibly OA cases". Subjects are invited to participate in a medical visit to complete clinical and lung function investigations, including fractional exhaled nitric oxide (FE_NO) and carbon monoxide (CO) measurements, and to collect blood samples for IgE (Immunoglobulin E) measurements (total IgE and IgE for work-related and common allergens). Markers of oxidative stress and genetic polymorphisms exploration are also assessed. A random sample of 200 "non-cases" (controls) is also visited, following a nested case-control design.</p> <p>Discussion</p> <p>This study may allow to describ a latent period between inception of exposure and the rise of the prevalence of asthma symptoms, an information that would be useful for the prevention of OA. Such a time frame would be suited for conducting screening campaigns of this emergent asthma at a stage when occupational hygiene measures and adapted therapeutic interventions might be effective.</p> <p>Trial registration</p> <p>Clinical trial registration number is NCT01096537.</p

Keratinocytes as Depository of Ammonium-Inducible Glutamine Synthetase: Age- and Anatomy-Dependent Distribution in Human and Rat Skin

In inner organs, glutamine contributes to proliferation, detoxification and establishment of a mechanical barrier, i.e., functions essential for skin, as well. However, the age-dependent and regional peculiarities of distribution of glutamine synthetase (GS), an enzyme responsible for generation of glutamine, and factors regulating its enzymatic activity in mammalian skin remain undisclosed. To explore this, GS localization was investigated using immunohistochemistry and double-labeling of young and adult human and rat skin sections as well as skin cells in culture. In human and rat skin GS was almost completely co-localized with astrocyte-specific proteins (e.g. GFAP). While GS staining was pronounced in all layers of the epidermis of young human skin, staining was reduced and more differentiated among different layers with age. In stratum basale and in stratum spinosum GS was co-localized with the adherens junction component ß-catenin. Inhibition of, glycogen synthase kinase 3β in cultured keratinocytes and HaCaT cells, however, did not support a direct role of ß-catenin in regulation of GS. Enzymatic and reverse transcriptase polymerase chain reaction studies revealed an unusual mode of regulation of this enzyme in keratinocytes, i.e., GS activity, but not expression, was enhanced about 8–10 fold when the cells were exposed to ammonium ions. Prominent posttranscriptional up-regulation of GS activity in keratinocytes by ammonium ions in conjunction with widespread distribution of GS immunoreactivity throughout the epidermis allows considering the skin as a large reservoir of latent GS. Such a depository of glutamine-generating enzyme seems essential for continuous renewal of epidermal permeability barrier and during pathological processes accompanied by hyperammonemia

Statistical Coupling Between time Point-Processes

International audienceThe observation of physical phenomena often goes through the recording of discrete time series of events, that can be represented with marked point processes. The robust estimation of the correlation between two point processes can, therefore, unveil physical mechanisms underlying the observed phenomena. However, the robust estimation of correlation between two, or more, point-processes is hindered by the signal noise (leading to false and missing point detections), the important density of points, and possible time-shift between coupled points. We propose a statistical framework that uses hypothesis testing to estimate coupling between time pointprocesses. Using simulations, we show that our framework accurately estimates the coupling between two time point-processes even for noisy signal (with false point detections), for high density of points and in the presence of a time shift between coupled points. By applying our statistical framework to the recordings of neuron population activity in mouse visual cortex, we measure the functional coupling between individual neurons, and cluster neurons into functional ensembles

A Robust and Versatile Framework to Compare Spike Detection Methods in Calcium Imaging of Neuronal Activity

International audienceCalcium fluorescence imaging enables real-time activity monitoring of single neurons in living animals. A critical inverse problem resides in the precise inference of spike locations from noisy fluorescence traces, especially in the presence of burst spiking and non-linear fluorescence intensity. Several spike extraction algorithms have been proposed in the recent years, but a robust and objective evaluation of their performance still remains elusive due to the unsupervised nature of the problem. Here we propose a biologically-inspired mathematical framework to reproduce synthetic fluorescence traces from a time-series data of spike-trains. The idea is to create a versatile platform to objectively test the state-ofthe art spike inference methodologies over a large range of experimental parameters. Our solution appears as a complementary but more exhaustive approach to determine the robustness of existing solutions to different nature of signals, imaging artefacts, sensitivity to hyper-parameters and pre-processing steps. We benchmark state-of-the-art algorithms with the proposed simulation platform, and validate the results on an experimental dataset of the Hydra Vulgaris. We hypothesize that, in contrast to the common practice of qualitative evaluation, quantitative measure of algorithm robustness is essential in understanding the suitability of a spike inference algorithm to be used in an automated computational pipeline to decipher the neural code

Toward a conceptual renewal of public management? A state of art of the francophone literature

International audienc

Toward a conceptual renewal of public management? A state of art of the francophone literature

International audienc

Cyclic GMP in the perfused rat heart : Effect of ischaemia, anoxia and nitric oxide synthase inhibitor

Working rat hearts perfused with 5.5 mM glucose were submitted to a 10-min period of no-flow ischaemia or anoxia. Both conditions stimulated glycogenolysis, activated phosphorylase and increased cyclic GMP content, although the time course of these changes differed in anoxia and ischaemia. Changes in cyclic GMP content were not correlated with glycogenolysis or phosphorylase activation. Perfusion with 1 microM L-nitroarginine methylester, an inhibitor of nitric oxide synthase, decreased cGMP concentration under normoxic conditions and abolished the ischaemia-induced increase in cGMP. The inhibitor decreased the coronary flow without affecting the overall working performance of the hearts under normoxic conditions