Case Report First Report of Clostridium lavalense Isolated in Human Blood Cultures

An 88-year-old man was admitted to the hospital with worsening malaise, fever, and weakness. Anaerobic blood culture bottles revealed the presence of an anaerobic, Gram-positive sporulated bacillus. Empirical antibiotherapy with intravenous piperacillintazobactam was initiated. The patient defervesced after four days and was switched to oral amoxicillin on his 6th day of antibiotic therapy and later discharged from the hospital. Four months later, he had recovered. The bacterium was initially identified as Clostridium butyricum using anaerobic manual identification panel. 16S rRNA gene sequence and phylogenetic analysis showed the bacterium to be Clostridium lavalense, a recently described species with no previously published case of isolation in human diagnostic samples so far. This is the first report of Clostridium lavalense isolation from human blood cultures. Further studies are needed in order to elucidate the role of Clostridium lavalense in human disease and its virulence factors

The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease

Many common variants have been associated with hematological traits, but identification of causal genes and pathways has proven challenging. We performed a genome-wide association analysis in the UK Biobank and INTERVAL studies, testing 29.5 million genetic variants for association with 36 red cell, white cell, and platelet properties in 173,480 European-ancestry participants. This effort yielded hundreds of low frequency (<5%) and rare (<1%) variants with a strong impact on blood cell phenotypes. Our data highlight general properties of the allelic architecture of complex traits, including the proportion of the heritable component of each blood trait explained by the polygenic signal across different genome regulatory domains. Finally, through Mendelian randomization, we provide evidence of shared genetic pathways linking blood cell indices with complex pathologies, including autoimmune diseases, schizophrenia, and coronary heart disease and evidence suggesting previously reported population associations between blood cell indices and cardiovascular disease may be non-causal.We thank members of the Cambridge BioResource Scientific Advisory Board and Management Committee for their support of our study and the National Institute for Health Research Cambridge Biomedical Research Centre for funding. K.D. is funded as a HSST trainee by NHS Health Education England. M.F. is funded from the BLUEPRINT Grant Code HEALTH-F5-2011-282510 and the BHF Cambridge Centre of Excellence [RE/13/6/30180]. J.R.S. is funded by a MRC CASE Industrial studentship, co-funded by Pfizer. J.D. is a British Heart Foundation Professor, European Research Council Senior Investigator, and National Institute for Health Research (NIHR) Senior Investigator. S.M., S.T, M.H, K.M. and L.D. are supported by the NIHR BioResource-Rare Diseases, which is funded by NIHR. Research in the Ouwehand laboratory is supported by program grants from the NIHR to W.H.O., the European Commission (HEALTH-F2-2012-279233), the British Heart Foundation (BHF) to W.J.A. and D.R. under numbers RP-PG-0310-1002 and RG/09/12/28096 and Bristol Myers-Squibb; the laboratory also receives funding from NHSBT. W.H.O is a NIHR Senior Investigator. The INTERVAL academic coordinating centre receives core support from the UK Medical Research Council (G0800270), the BHF (SP/09/002), the NIHR and Cambridge Biomedical Research Centre, as well as grants from the European Research Council (268834), the European Commission Framework Programme 7 (HEALTH-F2-2012-279233), Merck and Pfizer. DJR and DA were supported by the NIHR Programme ‘Erythropoiesis in Health and Disease’ (Ref. NIHR-RP-PG-0310-1004). N.S. is supported by the Wellcome Trust (Grant Codes WT098051 and WT091310), the EU FP7 (EPIGENESYS Grant Code 257082 and BLUEPRINT Grant Code HEALTH-F5-2011-282510). The INTERVAL study is funded by NHSBT and has been supported by the NIHR-BTRU in Donor Health and Genomics at the University of Cambridge in partnership with NHSBT. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, the Department of Health of England or NHSBT. D.G. is supported by a “la Caixa”-Severo Ochoa pre-doctoral fellowship

Whole Exome Sequencing Reveals the Major Genetic Contributors to Nonsyndromic Tetralogy of Fallot

Rationale: Familial recurrence studies provide strong evidence for a genetic component to the predisposition to sporadic, nonsyndromic Tetralogy of Fallot (TOF), the most common cyanotic congenital heart disease phenotype. Rare genetic variants have been identified as important contributors to the risk of congenital heart disease, but relatively small numbers of TOF cases have been studied to date. Objective: We used whole exome sequencing to assess the prevalence of unique, deleterious variants in the largest cohort of nonsyndromic TOF patients reported to date. Methods and Results: Eight hundred twenty-nine TOF patients underwent whole exome sequencing. The presence of unique, deleterious variants was determined; defined by their absence in the Genome Aggregation Database and a scaled combined annotation-dependent depletion score of ≥20. The clustering of variants in 2 genes, NOTCH1 and FLT4, surpassed thresholds for genome-wide significance (assigned as P<5×10−8) after correction for multiple comparisons. NOTCH1 was most frequently found to harbor unique, deleterious variants. Thirty-one changes were observed in 37 probands (4.5%; 95% CI, 3.2%–6.1%) and included 7 loss-of-function variants 22 missense variants and 2 in-frame indels. Sanger sequencing of the unaffected parents of 7 cases identified 5 de novo variants. Three NOTCH1 variants (p.G200R, p.C607Y, and p.N1875S) were subjected to functional evaluation, and 2 showed a reduction in Jagged1-induced NOTCH signaling. FLT4 variants were found in 2.4% (95% CI, 1.6%–3.8%) of TOF patients, with 21 patients harboring 22 unique, deleterious variants. The variants identified were distinct to those that cause the congenital lymphoedema syndrome Milroy disease. In addition to NOTCH1, FLT4 and the well-established TOF gene, TBX1, we identified potential association with variants in several other candidates, including RYR1, ZFPM1, CAMTA2, DLX6, and PCM1. Conclusions: The NOTCH1 locus is the most frequent site of genetic variants predisposing to nonsyndromic TOF, followed by FLT4. Together, variants in these genes are found in almost 7% of TOF patients

Étude du phénomène d'échecs et d'abandons en chimie générale : rapport statistique /

Bibliogr.: f. 85-8

Une recherche-action pour développer le pouvoir d’agir de communautés au regard du soutien à domicile : quels sont les obstacles et les implications ?

Les savoirs des personnes aînées doivent être entendus au cours d’un projet social inclusif visant le développement de leur pouvoir d’agir. Pour atteindre ce but au regard du soutien à domicile des personnes aînées, une recherche-action a été menée dans trois communautés. Les chercheurs ont soutenu les participants lors du processus visant l’identification des forces, des ressources et des défis, ainsi que le choix d’une intervention et sa mise en oeuvre. Les interventions choisies concernent l’entretien extérieur, le transport communautaire et l’habitation. Des obstacles sont survenus au cours du processus quant à la durée de l’étude, à l’échéancier prévu, à la complexité des interventions choisies et à l’implication des participants. Des implications pour la recherche découlent des résultats de l’étude et des obstacles rencontrés. Elles concernent le recrutement et l’intégration des participants, le soutien, l’ouverture et la souplesse, les rapports de pouvoir et l’adaptation du processus aux caractéristiques des participants.Seniors’ knowledge was to be expanded through an inclusive social project to develop their power to act. To reach this goal with respect to home support for seniors, a research-action project was carried out in three communities. Researchers supported participants during a process of identifying their strengths, resources and challenges, and of then choosing and implementing an intervention. The interventions chosen had to do with outdoor maintenance, community transit and housing. Obstacles appeared during the process involving the length of the study, the planned timeline, the complexity of the chosen interventions and participant involvement. Research implications arise from the study results and the obstacles encountered with participant recruitment and integration, support, openness and flexibility, relationships of power and adapting the process to the characteristics of participants

LE DÉVELOPPEMENT DU POUVOIR D’AGIR EN CONTEXTE DE SOUTIEN À DOMICILE DES PERSONNES AGÉES : EXAMEN DE LA PORTÉE DES CONNAISSANCES

Le développement du pouvoir d’agir est un moyen d’émancipation des individus. Il se réalise lorsque ceux-ci identifient ce qui est important pour eux, leurs obstacles et leurs ressources, construisent les conditions de soutien et les alliances nécessaires pour atteindre leurs objectifs et s’expriment sur l’expérience de changement. Cette démarche serait utile lors de l’accompagnement des aînés ayant besoin de soutien à domicile. Un examen de la portée des connaissances concernant le développement du pouvoir d’agir en contexte de soutien à domicile a été réalisé afin de comprendre comment cette démarche est conçue et appliquée. Le cadre méthodologique d’Arksey et O’Malley (2005) a été utilisé. Parmi 648 articles retracés dans sept bases de données, neuf études se sont avérées pertinentes. Il ressort de cette démarche que peu de chercheurs s’intéressent explicitement au développement du pouvoir d’agir dans un tel contexte. Toutefois, il apparaît utile de se préoccuper des besoins des aînés, de leurs ressources, des obstacles auxquels ils sont confrontés et de ce qu’ils ont compris de l’expérience de changement. Devant ces constats, des études supplémentaires, réalisées à ce sujet en collaboration avec la population concernée, s’avèrent nécessaires.Empowerment is a means by which individuals can emancipate. It occurs when individuals identify what is important to them, their challenges and their resources; build the conditions of support and alliances necessary to achieve their goals; and express themselves on their experience of change. This approach would be useful when accompanying seniors who need home support. A scoping review on this topic was conducted. Arksey and O’Malley’s (2005) methodological framework was used to understand how this approach is designed and applied in the context of home support. Of 648 articles found in seven databases, nine proved relevant. It emerged from the studies reviewed that few researchers explored empowerment in this context. However, it also emerged that it is important to consider the needs of seniors, their resources, the barriers they face, and their own understanding of their experience of change. The findings suggest that more research is needed to improve the effectiveness of interventions and that such research should be conducted in collaboration with the target population