Whole exome re-sequencing implicates CCDC38 and cilia structure and function in resistance to smoking related airflow obstruction

Chronic obstructive pulmonary disease (COPD) is a leading cause of global morbidity and mortality and, whilst smoking remains the single most important risk factor, COPD risk is heritable. Of 26 independent genomic regions showing association with lung function in genome-wide association studies, eleven have been reported to show association with airflow obstruction. Although the main risk factor for COPD is smoking, some individuals are observed to have a high forced expired volume in 1 second (FEV1) despite many years of heavy smoking. We # hypothesised that these ‘‘resistant smokers’’ may harbour variants which protect against lung function decline caused by smoking and provide insight into the genetic determinants of lung health. We undertook whole exome re sequencing of 100 heavy smokers who had healthy lung function given their age, sex, height and smoking history and applied three complementary approaches to explore the genetic architecture of smoking resistance. Firstly, we identified novel functional variants in the ‘‘resistant smokers’’ and looked for enrichment of these novel variants within biological pathways. Secondly, we undertook association testing of all exonic variants individually with two independent control sets. Thirdly, we undertook gene-based association testing of all exonic variants. Our strongest signal of association with smoking resistance for a non-synonymous SNP was for rs10859974 (P = 2.3461024) in CCDC38, a gene which has previously been reported to show association with FEV1/FVC, and we demonstrate moderate expression of CCDC38 in bronchial epithelial cells. We identified an enrichment of novel putatively functional variants in genes related to cilia structure and function in resistant smokers. Ciliary function abnormalities are known to be associated with both smoking and reduced mucociliary clearance in patients with COPD. We suggest that genetic influences on the development or function of cilia in the bronchial epithelium may affect growth of cilia or the extent of damage caused by tobacco smoke

Leadership and style in the French Fifth Republic:Nicolas Sarkozy’s presidency in historical and cultural perspective

This article contributes to the body of the developing theoretical research in leadership and presidential studies by adding analysis of what I have termed ‘comportmental style’ as a factor in leader/follower relations. Within institutionalism and the wider structure/agency debate in political science, one of the challenges as regards the study of leadership is to identify factors that offer scope to or else militate against leaders’ performance. The comportmental style of Nicolas Sarkozy (President of the French Republic 2007–2012), deployed in the context of the – changing – institution of the presidency, was a major factor in his extreme unpopularity, and contributed to his defeat in 2012. What this tells us about the nature of the changing French presidency and the role of style will be discussed in the conclusion

Ethnography and incommensurability in the aftermath of insurgency

Does ethnography in some way enact and perform what it names? If one foregrounds this performative dimension, what exactly does ethnography in the aftermath of insurgency do? The article explores these questions as they emerge in the context of ethnography in the aftermath of insurgency (insurgencia) in Guatemala, and in relation to debates in social and cultural theory. It is argued that ethnography activates—and is responsive to—performative modes of subjectification and desubjectification discussed, inter alia, with reference to notions of ‘the archive’ and ‘testimony’. The article shows that ethnography in the aftermath of insurgency conjures up insurrectionary modalities of action. It establishes realignments and relations, enacts substitutions, and arouses modes of cross-identification between subjects, directly referencing how the insurgency was sustained during the Guatemalan conflict. However, rather than crystallizing or stabilizing an account of the insurgency, ethnography deals specifically with incommensurability and the slips— or gaps—that result from oscillations between representation—as in the multiply populated archive that holds the voices of many speaking subjects—and non-representation—as in the indexical domain of the subjectless archive that is all that there is that can speak

Radiation protection: Factors influencing compliance to referral guidelines in minor chest trauma

Objectives: To test the hypothesis that referral guidelines are not sufficiently known by prescribers and that medico-legal concerns could influence the prescription of radiographs in minor chest trauma. Methods: We submitted a questionnaire including a typical clinical history and questions on reasons for prescribing radiographs of the ribs in minor chest trauma to 112 prescriptors (33 residents, 18 surgeons, 7 internists, 24 general practitioners and 30 ER physicians). All accepted to participate. Comparisons were performed by Fisher's exact test followed by a post-hoc analysis and by a McNemar test. Results: Fifty-eight percent of prescriptors proposed rib radiographs, most (89%) being unaware of the guidelines. Only 11% of them changed their intention to order radiographs after information on referral guidelines and radiation dose (P=0.057). The mean dose delivered by rib radiographs was 38 times higher than that of a chest X-ray. Legal and medico-legal concerns (requirements from insurance policies and avoidance of lawsuits) were the main reasons for requesting radiographs. Conclusion: Unsharpness of guidelines in addition to social and medico-legal issues, rather than medical reasons or the lack of knowledge of the guidelines, strongly influence the prescription of radiographs of the ribs in minor chest trauma. Key Points: • Most prescriptors order radiographs of the ribs in minor chest trauma. • Only few prescriptors are aware of referral guidelines. • Information on guidelines does not change their need for radiographs. • Motivations for ordering radiographs are rather legal than medical, but poor compliance to guidelines could also be explained by their unsharpness. • Radiation dose of rib radiographs was 38 times that of a PA chest radiograph.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Geriatric rehabilitation of stroke patients in nursing homes: a study protocol.

Contains fulltext : 88482.pdf (publisher's version ) (Open Access)BACKGROUND: Geriatric patients are typically underrepresented in studies on the functional outcome of rehabilitation after stroke. Moreover, most geriatric stroke patients do probably not participate in intensive rehabilitation programs as offered by rehabilitation centers. As a result, very few studies have described the successfulness of geriatric stroke rehabilitation in nursing home patients, although it appears that the majority of these patients are being discharged back to the community, rather than being transferred to residential care. Nevertheless, factors associated with the successfulness of stroke rehabilitation in nursing homes or skilled nursing facilities are largely unknown. The primary goal of this study is, therefore, to assess the factors that uniquely contribute to the successfulness of rehabilitation in geriatric stroke patients that undergo rehabilitation in nursing homes. A secondary goal is to investigate whether these factors are similar to those associated with the outcome of stroke rehabilitation in the literature. METHODS/DESIGN: This study is part of the Geriatric Rehabilitation in AMPutation and Stroke (GRAMPS) study in the Netherlands. It is a longitudinal, observational, multicenter study in 15 nursing homes in the Southern part of the Netherlands that aims to include at least 200 patients. All participating nursing homes are selected based on the existence of a specialized rehabilitation unit and the provision of dedicated multidisciplinary care. Patient characteristics, disease characteristics, functional status, cognition, behavior, and caregiver information, are collected within two weeks after admission to the nursing home. The first follow-up is at discharge from the nursing home or one year after inclusion, and focuses on functional status and behavior. Successful rehabilitation is defined as discharge from the nursing home to an independent living situation within one year after admission. The second follow-up is three months after discharge in patients who rehabilitated successfully, and assesses functional status, behavior, and quality of life. All instruments used in this study have shown to be valid and reliable in rehabilitation research or are recommended by the Netherlands Heart Foundation guidelines for stroke rehabilitation.Data will be analyzed using SPSS 16.0. Besides descriptive analyses, both univariate and multivariate analyses will be performed with the purpose of identifying associated factors as well as their unique contribution to determining successful rehabilitation. DISCUSSION: This study will provide more information about geriatric stroke rehabilitation in Dutch nursing homes. To our knowledge, this is the first large study that focuses on the determinants of success of geriatric stroke rehabilitation in nursing home patients