iGWAS: Integrative Genome‐Wide Association Studies of Genetic and Genomic Data for Disease Susceptibility Using Mediation Analysis

Genome‐wide association studies (GWAS) have been a standard practice in identifying single nucleotide polymorphisms (SNPs) for disease susceptibility. We propose a new approach, termed integrative GWAS (iGWAS) that exploits the information of gene expressions to investigate the mechanisms of the association of SNPs with a disease phenotype, and to incorporate the family‐based design for genetic association studies. Specifically, the relations among SNPs, gene expression, and disease are modeled within the mediation analysis framework, which allows us to disentangle the genetic effect on a disease phenotype into two parts: an effect mediated through a gene expression (mediation effect, ME) and an effect through other biological mechanisms or environment‐mediated mechanisms (alternative effect, AE). We develop omnibus tests for the ME and AE that are robust to underlying true disease models. Numerical studies show that the iGWAS approach is able to facilitate discovering genetic association mechanisms, and outperforms the SNP‐only method for testing genetic associations. We conduct a family‐based iGWAS of childhood asthma that integrates genetic and genomic data. The iGWAS approach identifies six novel susceptibility genes (MANEA, MRPL53, LYCAT, ST8SIA4, NDFIP1, and PTCH1) using the omnibus test with false discovery rate less than 1%, whereas no gene using SNP‐only analyses survives with the same cut‐off. The iGWAS analyses further characterize that genetic effects of these genes are mostly mediated through their gene expressions. In summary, the iGWAS approach provides a new analytic framework to investigate the mechanism of genetic etiology, and identifies novel susceptibility genes of childhood asthma that were biologically meaningful.     

医疗纠纷人民调解中责任认定相关问题探析

医学的专业性、复杂性以及医患双方知识信息的差异,加大了医疗纠纷案件的处理难度,无论诉讼、人民调解、行政调解、仲裁等何种解决途径,明晰责任、分析过错均是化解矛盾的关键环节。探讨了医疗纠纷人民调解中责任认定的主要形式及其具备的优势,并对目前该制度存在的问题加以分析。     

Associations Between Spirituality,Mindfulness, and Psychological Symptoms Among Advanced Lung Cancer Patients and Their Spousal Caregivers

ContextPatients with metastatic lung cancer and their spousal caregivers are at high risk of psychological symptoms. Mindfulness may improve psychological symptoms via spiritual well-being (SW); yet, this mediation model has not been examined in a dyadic context.ObjectivesWe examined the mediating role of two dimensions of SW (meaning/peace and faith) in the mindfulness-symptoms link in Stage IV lung cancer patients and their spousal caregivers.MethodsWe examined the actor-partner interdependence model of mediation using multivariate multilevel modeling with 78 couples. Four actor-partner interdependence model of mediation analyses were conducted to examine one predictor (mindfulness) × two mediators (meaning/peace and faith) × two psychological symptoms (depressive symptoms and cancer distress). We also tested four alternative models in which mindfulness mediates the associations between SW and psychological symptoms.ResultsThe alternative model (SW → mindfulness → psychological symptoms) was preferred than the original model (mindfulness → SW → psychological symptoms). For patients, meaning/peace was directly associated with their own psychological symptoms, whereas faith was only indirectly associated with their own psychological symptoms via mindfulness. For spouses, meaning/peace was both directly and indirectly associated with their own psychological symptoms, whereas faith was only directly associated with their own depressive symptoms (but not cancer distress). Moreover, spouses' faith was indirectly associated with patients' psychological symptoms through patients' mindfulness.ConclusionSW is associated with patients' and spouses' psychological symptoms both directly and indirectly through mindfulness. Thus, interventions that target SW, particularly meaning and peace, along with mindfulness may be beneficial to the psychological management of patients facing a terminal disease and their spousal caregivers.     

Mental Well‐Being Mediates the Relationship between Perceived Stress and Perceived Health

The association between stress and health has been well researched in the past; however, comparatively few mediators have been tested to understand the underlying mechanism. With increasing awareness on mental well‐being, this study evaluated the relationship between perceived stress and perceived health and examined mental well‐being as a mediator. Two‐hundred undergraduates aged 21 to 26 years completed the English Perceived Stress Scale, Health Status Questionnaire and Asian Mental Well‐Being Scale that assess perceived stress, perceived health and mental well‐being, respectively. Factor analysis and structural equation modelling on the Perceived Stress Scale replicated the reported two‐factor structure after excluding an insignificant item. Linear multiple regression analyses indicated that perceived stress was negatively associated with perceived health. Results showed that mental well‐being partially mediated the relationship between perceived stress and perceived health, although it is acknowledged that this association could be bidirectional. Findings from the present study suggest that future research could focus on reducing stress and improving mental well‐being to alleviate the effect of stress on health. Copyright © 2013 John Wiley & Sons, Ltd.     

Pulsion et clinique de la déambulation dans un syndrome de type Alzheimer : une lecture lacanienne

AimsThis article addresses the issue of wandering in Alzheimer's disease from a psychoanalytic point of view, taking into account the importance of the spatial dimension in psychic dynamics.MethodAfter having presented wandering from a behavioral point of view, it is discussed from a metapsychological perspective, making use of A. & G. Haddad's concept of the “viatoric drive” and as well as J. Lacan's reflections on “the wandering of the journey” and “the wandering of desire.” The clinical vignette of Mr. M. in a workshop of therapeutic mediation through art helps us illustrate the unconscious psychic movements at play in walking.ResultsThree subjective markers emerge: wandering reveals the subject's difficult in orienting himself in both physical and psychological space, demonstrating a form of excitation that is not supported by the viatoric drive; “the wandering of the journey” makes it possible to relocate the place of the Other in the Imaginary; “the wandering of desire” incites the subject to repetition through the play of the drives.DiscussionNeurodegenerative disease is an obstacle to wandering. Art-therapy workshops can help Alzheimer's patients with the reorganization of wandering, where unconscious knowledge would prevail over the excitation of ambulation, thus suggesting, for the subject, the possibility of a structuring “elsewhere.”ConclusionThinking of mediated workshops as places of creation for the subject opens up the possibility of inhabiting one's wandering, considered as expressions of a journey and of desire.