A genome-wide meta-analysis of palmoplantar pustulosis implicates TH2 responses and cigarette smoking in disease pathogenesis

\ua9 2024 The AuthorsBackground: Palmoplantar pustulosis (PPP) is an inflammatory skin disorder that mostly affects smokers and manifests with painful pustular eruptions on the palms and soles. Although the disease can present with concurrent plaque psoriasis, TNF and IL-17/IL-23 inhibitors show limited efficacy. There is therefore a pressing need to uncover PPP disease drivers and therapeutic targets. Objectives: We sought to identify genetic determinants of PPP and investigate whether cigarette smoking contributes to disease pathogenesis. Methods: We performed a genome-wide association meta-analysis of 3 North-European cohorts (n = 1,456 PPP cases and 402,050 controls). We then used the scGWAS program to investigate the cell-type specificity of the association signals. We also undertook genetic correlation analyses to examine the similarities between PPP and other immune-mediated diseases. Finally, we applied Mendelian randomization to analyze the causal relationship between cigarette smoking and PPP. Results: We found that PPP is not associated with the main genetic determinants of plaque psoriasis. Conversely, we identified genome-wide significant associations with the FCGR3A/FCGR3B and CCHCR1 loci. We also observed 13 suggestive (P < 5 7 10−6) susceptibility regions, including the IL4/IL13 interval. Accordingly, we demonstrated a significant genetic correlation between PPP and TH2-mediated diseases such as atopic dermatitis and ulcerative colitis. We also found that genes mapping to PPP-associated intervals were preferentially expressed in dendritic cells and often implicated in T-cell activation pathways. Finally, we undertook a Mendelian randomization analysis, which supported a causal role of cigarette smoking in PPP. Conclusions: The first genome-wide association study of PPP points to a pathogenic role for deregulated TH2 responses and cigarette smoking

Étude des processus d'interaction laser de fibres naturelles par spectrométrie de masse : application à la validation expérimentale des critères de différenciation du cheveu

Not availableLe cheveu suscite l'intérêt de nombreux scientifiques, car il se comporte comme une bande enregistrant l'imprégnation de l'organisme par divers composes : drogues, médicaments, éléments minéraux... Cependant, comme le montre notre travail bibliographique, l'interprétation des résultats obtenus nécessite une connaissance approfondie du cheveu et des interactions avec son environnement. Les différentes techniques d'analyse du cheveu sont généralement longues à mettre en ?uvre et consommatrices en échantillon. C'est pourquoi, nous avons étudié dans ce mémoire une méthode de caractérisation des cheveux à l'aide des microsondes laser couplées à la spectrométrie de masse : LAMMA et FTMS. En effet, elles permettent une analyse rapide sur seulement quelques millimètres de tige pilaire. Les ions formés lors de l'ablation laser d'un cheveu témoin (irradiance = 5 10 [à la puissance]8 W/cm2, longueur d'onde = 266 nm) ont été caractérisés afin de faciliter l'interprétation des spectres de masse. Pour cela, nous avons travaillé sur des cheveux dopés en éléments minéraux ou lavée pour observer la matrice organique et, effectué des calibrations en haute résolution. Ces analyses montrent que l'empreinte « minérale » est due à l'agrégation des cations minéraux avec les anions organiques majoritaires (CN- et CNO-), tandis que l'empreinte organique est principalement liée à la fragmentation de la chaine polypeptidique des kératines. Enfin, nous exposons le protocole d'expertise discriminante des cheveux, tel qu'il a été développé dans notre laboratoire. Dans ce contexte, nous effectuons des analyses morphologiques et par spectrométrie de masse LAMMA. Nous augmentons ainsi le nombre de critères d'analyses, pour qu'une comparaison deux à deux des résultats de chaque cheveu, puisse exclure ou non l'appartenance à une seule et même personn

Laboratory testing of a flexible boom for ice management

Combatting oil spills in the Arctic is a major challenge. Drilling or producing oil or gas in the marginal ice zone (MIZ) may allow booms to be deployed upstream of an offshore structure to clear the water of ice, thereby enabling conventional oil spill countermeasures to be used. Such a boom would be kept in place by two ice-going service vessels or by moored buoys. SINTEF NHL and NRC have performed a number of small-scale tests with a flexible boom in the NRC ice basin in Ottawa. The purpose of the tests was to measure the effectiveness of using a flexible boom for collecting ice, and to determine the loads associated with collecting the ice. In the tests, various boom configurations were towed against a broken ice field consisting of ice pieces typically 50-100 mm across and 30 mm thick. The ice concentration was usually 10/10, but it was reduced to 8/10 and 5/10 for two tests. The boom was towed at speeds of 20 and 50 mm-s-1. Both the width of the boom and the slackness of the boom were varied over reasonable ranges. Two six-component dynamometers were used to support the boom. Thus, the force components on each end of the boom were measured. Further, two video cameras were used to record the effectiveness of each boom configuration. In this paper, the full results of this test program are presented and the application of the test results to the full-scale situation are discussed. The tests show that, under certain conditions, the use of boom is feasible for ice management in oil-contaminated water.NRC publication: Ye

Initial results of a study into the estimation of the development of frequency lock-in for offshore structures subjected to ice loading

Ice-induced vibrations have to be considered in design of vertically sided offshore structures subjected to loading by sea ice, such as offshore wind turbines and oil- and gas platforms. The interaction between ice and structure may result in high global peak loads and the occurring structural vibrations can contribute significantly to the overall fatigue of the structure. A regime of particular interest is the frequency lock-in regime in which the interaction causes the structure to oscillate at high amplitude with a frequency close to one of its natural frequencies. Assessment of frequency lock-in in the design phase can be done based on simple approaches once for given ice conditions the natural modes to experience frequency lock-in and the range of ice drift velocities for which lock-in develops are known. Determining those modes and velocities is however challenging due to the nonlinear nature of the interaction between ice and structure and limited available reference data. In this paper two methods are applied to determine the structural modes and ice drift velocities required as an input for simplified design approaches. The first method is the application of design standards and estimation formulas available from literature. The second method is the application of a recently developed numerical model for simulation of the interaction. The methods are applied to two existing structures which have experienced frequency lock-in and an offshore wind turbine designed to be employed at a location with mild ice conditions. Results show that the estimation formulas do not match with full-scale observations of the existing structures and can therefore not be applied to obtain input for the simplified design approaches. The second method shows to give simulation results consistent with the full-scale observations. Application to the offshore wind turbine reveals that it is most susceptible to frequency lock-in in the second mode.Offshore EngineeringApplied Mechanic