24 research outputs found

    Assessing the Effects of Responsible Leadership and Ethical Conflict on Behavioral Intention

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    [[abstract]]This study develops a research model that elaborates how responsible leadership and ethical conflict influence employees from the perspectives of role theory and attachment theory. Its empirical results reveal that turnover intention indirectly relates to ethical conflict and responsible leadership via the mediating mechanisms of organizational identification and organizational uncertainty. At the same time, helping intention indirectly relates to ethical conflict and responsible leadership only through organizational identification. Finally, the managerial implications for international business and research limitations based on the empirical results are discussed.[[notice]]補正完

    Optimised and Rapid Pre-clinical Screening in the SOD1G93A Transgenic Mouse Model of Amyotrophic Lateral Sclerosis (ALS)

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    The human SOD1G93A transgenic mouse has been used extensively since its development in 1994 as a model for amyotrophic lateral sclerosis (ALS). In that time, a great many insights into the toxicity of mutant SOD1 have been gained using this and other mutant SOD transgenic mouse models. They all demonstrate a selective toxicity towards motor neurons and in some cases features of the pathology seen in the human disease. These models have two major drawbacks. Firstly the generation of robust preclinical data in these models has been highlighted as an area for concern. Secondly, the amount of time required for a single preclinical experiment in these models (3–4 months) is a hurdle to the development of new therapies. We have developed an inbred C57BL/6 mouse line from the original mixed background (SJLxC57BL/6) SOD1G93A transgenic line and show here that the disease course is remarkably consistent and much less prone to background noise, enabling reduced numbers of mice for testing of therapeutics. Secondly we have identified very early readouts showing a large decline in motor function compared to normal mice. This loss of motor function has allowed us to develop an early, sensitive and rapid screening protocol for the initial phases of denervation of muscle fibers, observed in this model. We describe multiple, quantitative readouts of motor function that can be used to interrogate this early mechanism. Such an approach will increase throughput for reduced costs, whilst reducing the severity of the experimental procedures involved

    Digital assessment of working memory and processing speed in everyday life: Feasibility, validation, and lessons-learned

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    Objectives Cognitive functioning is often impaired in mental and neurological conditions and might fluctuate throughout the day. An existing experience-sampling tool was upgraded to assess individual's cognition in everyday life. The objectives were to test the feasibility and validity of two momentary cognition tasks. Methods The momentary Visuospatial Working Memory Task (mVSWMT) and momentary Digit Symbol Substitution Task (mDSST) were add-ons to an experience sampling method (ESM) smartphone app. Healthy adults (n = 49) between 19 and 73 years of age performed the tasks within an ESM questionnaire 8 times a day, over 6 consecutive days. Feasibility was determined through completion rate and participant experience. Validity was assessed through contextualization of cognitive performance within intrapersonal and situational factors in everyday life. Findings Participants experienced the tasks as pleasant, felt motivated, and the completion rate was high (71%). Social context, age, and distraction influenced cognitive performance in everyday life. The mVSWMT was too difficult as only 37% of recalls were correct and thus requires adjustments (i.e. fixed time between encoding and recall; more trials per moment). The mDSST speed outcome seems the most sensitive outcome measure to capture between- and within-person variance. Conclusions Short momentary cognition tasks for repeated assessment are feasible and hold promise, but more research is needed to improve validity and applicability in different samples. Recommendations for teams engaging in the field include matching task design with traditional neuropsychological tests and involving a multidisciplinary team as well as users. Special attention for individual needs can improve motivation and prevent frustration. Finally, tests should be attractive and competitive to stimulate engagement, but still reflect actual cognitive functioning

    Founder mutations among the Dutch

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    Founder mutations among the Dutch. Zeegers MP, van Poppel F, Vlietinck R, Spruijt L, Ostrer H. Department of Epidemiology, Maastricht University, PO Box 616, 6200 MD, Maastricht, The Netherlands. Many genetic disorders demonstrate mutations that can be traced to a founder, sometimes a person who can be identified. These founder mutations have generated considerable interest, because they facilitate studies of prevalence and penetrance and can be used to quantify the degree of homogeneity within a population. This paper reports on founder mutations among the Dutch and relates their occurrence to the history and demography of the Netherlands. International migration, regional and religious endogamy, and rapid population growth played key roles in shaping the Dutch population. In the first millenniums BC and AD, the Netherlands were invaded by Celts, Romans, Huns, and Germans. In more recent times, large numbers of Huguenots and Germans migrated into the Netherlands. Population growth within the Netherlands was slow until the 19th century, when a period of rapid population growth started. Today, the Dutch population numbers 16 million inhabitants. Several different classes of founder mutations have been identified among the Dutch. Some mutations occur among people who represent genetic isolates within this country. These include mutations for benign familial cholestasis, diabetes mellitus, type I, infantile neuronal ceroid lipofuscinosis, L-DOPA responsive dystonia, and triphalangeal thumb. Although not related to a specific isolate, other founder mutations were identified only within the Netherlands, including those predisposing for hereditary breast-ovarian cancer, familial hypercholesterolemia, frontotemporal dementia, hereditary paragangliomas, juvenile neuronal ceroid lipofuscinosis, malignant melanoma, protein C deficiency, and San Filippo disease. Many of these show a regional distribution, suggesting dissemination from a founder. Some mutations that occur among the Dutch are shared with other European populations and others have been transmitted by Dutch emigres to their descendents in North America and South Africa. The occurrence of short chromosomal regions that have remained identical by descent has resulted in relatively limited genetic heterogeneity for many genetic conditions among the Dutch. These observations demonstrate the opportunity for gene discovery for other diseases and traits in the Netherlands
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