118 research outputs found

    Etude par spectrométrie Mössbauer d'alliages Fe-Si-B amorphes

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    Amorphous Fe100-x-ySi yBx alloys have been studied by Môssbauer Spectroscopy. The fitting methods and some possible origins of the asymmetric broadenings of the peaks are discussed. A comparison of the hyperfine field distributions in alloys with and without silicon suggests that iron and silicon are located in similar sites (for the studied y values, y ≤ 9) while boron occupies interstitial sites with ≃ 9 iron atoms nearest neighbours. Crystallisation steps and mechanisms have been studied in Fe82Si3B15 and Fe76Si9B15 alloys. They differ from those found in Fe-B alloys because metastable borides are not observed.Des alliages amorphes Fe100-x- ySiyBx ont été étudiés par spectrométrie Môssbauer. Les méthodes de calcul et les origines possibles des dissymétries des spectres sont discutées. La comparaison des distributions de champ hyperfin des alliages avec et sans silicium suggère que le silicium et le fer occupent des sites semblables (pour les valeurs de y étudiées, y ≤ 9) alors que le bore occupe une position interstitielle avec ≃ 9 atomes de fer proches voisins. Les alliages Fe-B sont fortement stabilisés par le silicium. Les étapes et les mécanismes de cristallisation d'alliages Fe82Si3B 15 et Fe76Si9B15 ont été précisés. Ils diffèrent de ceux observés dans les alliages Fe-B car il ne se forme pas de borures métastables

    Acting Intuition into Sense: How Film Crews Make Sense with Embodied Ways of Knowing

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    This study contributes to a holistic understanding of sensemaking by going beyond the mind–body dualism. To do so, we focus analytically on a phenomenon that operates at the nexus of mind and body: intuition. By observing four film crews, we unpack how people act their intuition into sense – that is, how they transform, through action, an initial sense (intuition) that is tacit, intimate, and complex into one that is publicly displayed, simpler, and ordered (i.e., a developed sense). Our model identifies two sensemaking trajectories, each of which involves several bodily actions (e.g., displaying feelings, working hands-on, speaking assertively). These actions enable intuition to express a facet of itself and acquire new properties. This study makes three important contributions. First, it develops the holistic-relational character of sensemaking by locating it in the relations among multiple loci (cognition, language, body, and materiality) rather than in each one disjunctively. Second, it theorizes embodied sensemaking as a transformative process entailing a rich repertoire of bodily actions. Third, it extends sensemaking research by attending to the physicality and materiality of language in embodied sensemaking

    Intuition: Myth or a Decision-making Tool?

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    Faced with today’s ill-structured business environment of fast-paced change and rising uncertainty, organizations have been searching for management tools that will perform satisfactorily under such ambiguous conditions. In the arena of managerial decision making, one of the approaches being assessed is the use of intuition. Based on our definition of intuition as a non-sequential information-processing mode, which comprises both cognitive and affective elements and results in direct knowing without any use of conscious reasoning, we develop a testable model of integrated analytical and intuitive decision making and propose ways to measure the use of intuition

    Clinical course and prognosis of musculoskeletal pain in patients referred for physiotherapy: does pain site matter?

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    Background: Danish patients with musculoskeletal disorders are commonly referred for primary care physiotherapy treatment but little is known about their general health status, pain diagnoses, clinical course and prognosis. The objectives of this study were to 1) describe the clinical course of patients with musculoskeletal disorders referred to physiotherapy, 2) identify predictors associated with a satisfactory outcome, and 3) determine the influence of the primary pain site diagnosis relative to those predictors. Methods: This was a prospective cohort study of patients (n = 2,706) newly referred because of musculoskeletal pain to 30 physiotherapy practices from January 2012 to May 2012. Data were collected via a web-based questionnaire 1–2 days prior to the first physiotherapy consultation and at 6 weeks, 3 and 6 months, from clinical records (including primary musculoskeletal symptom diagnosis based on the ICPC-2 classification system), and from national registry data. The main outcome was the Patient Acceptable Symptom State. Potential predictors were analysed using backwards step-wise selection during longitudinal Generalised Estimating Equation regression modelling. To assess the influence of pain site on these associations, primary pain site diagnosis was added to the model. Results: Of the patients included, 66% were female and the mean age was 48 (SD 15). The percentage of patients reporting their symptoms as acceptable was 32% at 6 weeks, 43% at 3 months and 52% at 6 months. A higher probability of satisfactory outcome was associated with place of residence, being retired, no compensation claim, less frequent pain, shorter duration of pain, lower levels of disability and fear avoidance, better mental health and being a non-smoker. Primary pain site diagnosis had little influence on these associations, and was not predictive of a satisfactory outcome. Conclusion: Only half of the patients rated their symptoms as acceptable at 6 months. Although satisfactory outcome was difficult to predict at an individual patient level, there were a number of prognostic factors that were associated with this outcome. These factors should be considered when developing generic prediction tools to assess the probability of satisfactory outcome in musculoskeletal physiotherapy patients, because the site of pain did not affect that prognostic association

    The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

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    Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

    The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

    Get PDF
    Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM (-/-) patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

    AD51B in Familial Breast Cancer

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    Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11–1.19, P = 8.88 x 10−16) and among familial cases (OR: 1.24, 95% CI: 1.16–1.32, P = 6.19 x 10−11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk

    The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

    Get PDF
    Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

    Double lockdown: the effects of digital exclusion on undocumented immigrants during the COVID-19 pandemic

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    The COVID-19 pandemic shifted many activities online. However, there is little research on the digital inclusion of undocumented immigrants and their experience of the pandemic in the United States. We conducted 32 interviews with undocumented Latino immigrants in the United States to examine how digital technologies mediated their experiences of the pandemic. We find that undocumented immigrants (1) face barriers to telehealth services, (2) are at high risk of COVID-19 misinformation, (3) experience difficulties in assessing privacy risks, and (4) experienced heterogeneous outcomes of technology use during the pandemic. Our analysis shows that digital technologies both supported and further marginalized undocumented immigrants during the pandemic. Future research on the digital inclusion of vulnerable populations should pay particular attention to the interaction between their underlying vulnerabilities, on one hand, and attitudes, uses, and outcomes associated with technology, on the other

    Double lockdown: the effects of digital exclusion on undocumented immigrants during the COVID-19 pandemic

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    <jats:p> The COVID-19 pandemic shifted many activities online. However, there is little research on the digital inclusion of undocumented immigrants and their experience of the pandemic in the United States. We conducted 32 interviews with undocumented Latino immigrants in the United States to examine how digital technologies mediated their experiences of the pandemic. We find that undocumented immigrants (1) face barriers to telehealth services, (2) are at high risk of COVID-19 misinformation, (3) experience difficulties in assessing privacy risks, and (4) experienced heterogeneous outcomes of technology use during the pandemic. Our analysis shows that digital technologies both supported and further marginalized undocumented immigrants during the pandemic. Future research on the digital inclusion of vulnerable populations should pay particular attention to the interaction between their underlying vulnerabilities, on one hand, and attitudes, uses, and outcomes associated with technology, on the other. </jats:p&gt
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