The genetic architecture of the human cerebral cortex

INTRODUCTION The cerebral cortex underlies our complex cognitive capabilities. Variations in human cortical surface area and thickness are associated with neurological, psychological, and behavioral traits and can be measured in vivo by magnetic resonance imaging (MRI). Studies in model organisms have identified genes that influence cortical structure, but little is known about common genetic variants that affect human cortical structure. RATIONALE To identify genetic variants associated with human cortical structure at both global and regional levels, we conducted a genome-wide association meta-analysis of brain MRI data from 51,665 individuals across 60 cohorts. We analyzed the surface area and average thickness of the whole cortex and 34 cortical regions with known functional specializations. RESULTS We identified 306 nominally genome-wide significant loci (P < 5 × 10−8) associated with cortical structure in a discovery sample of 33,992 participants of European ancestry. Of the 299 loci for which replication data were available, 241 loci influencing surface area and 14 influencing thickness remained significant after replication, with 199 loci passing multiple testing correction (P < 8.3 × 10−10; 187 influencing surface area and 12 influencing thickness). Common genetic variants explained 34% (SE = 3%) of the variation in total surface area and 26% (SE = 2%) in average thickness; surface area and thickness showed a negative genetic correlation (rG = −0.32, SE = 0.05, P = 6.5 × 10−12), which suggests that genetic influences have opposing effects on surface area and thickness. Bioinformatic analyses showed that total surface area is influenced by genetic variants that alter gene regulatory activity in neural progenitor cells during fetal development. By contrast, average thickness is influenced by active regulatory elements in adult brain samples, which may reflect processes that occur after mid-fetal development, such as myelination, branching, or pruning. When considered together, these results support the radial unit hypothesis that different developmental mechanisms promote surface area expansion and increases in thickness. To identify specific genetic influences on individual cortical regions, we controlled for global measures (total surface area or average thickness) in the regional analyses. After multiple testing correction, we identified 175 loci that influence regional surface area and 10 that influence regional thickness. Loci that affect regional surface area cluster near genes involved in the Wnt signaling pathway, which is known to influence areal identity. We observed significant positive genetic correlations and evidence of bidirectional causation of total surface area with both general cognitive functioning and educational attainment. We found additional positive genetic correlations between total surface area and Parkinson’s disease but did not find evidence of causation. Negative genetic correlations were evident between total surface area and insomnia, attention deficit hyperactivity disorder, depressive symptoms, major depressive disorder, and neuroticism. CONCLUSION This large-scale collaborative work enhances our understanding of the genetic architecture of the human cerebral cortex and its regional patterning. The highly polygenic architecture of the cortex suggests that distinct genes are involved in the development of specific cortical areas. Moreover, we find evidence that brain structure is a key phenotype along the causal pathway that leads from genetic variation to differences in general cognitive function

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Health professionals for an ageing society: transforming medical Education. A mixed methods approach

Contains fulltext : 157080.pdf (publisher's version ) (Open Access)RU Radboud Universiteit, 25 mei 2016Promotores : Lagro-Janssen, A.L.M., Olde-Rikkert, M.G.M. Co-promotores : Fluit, C.R.M.G., Lagro, J.185 p

[SDM supports better application of EBM in geriatric patients]

Item does not contain fulltextEvidence based medicine (EBM) is the integration of the best research evidence, clinical expertise and patient values in the decision making process for patient care. However, elderly people are often excluded from participating in scientific studies and they often have multiple morbidities, which complicates the application of EBM. Shared decision making (SDM), a process where clinicians and patients share the best available evidence when faced with the task of making decisions, and where patients are supported to consider options, to achieve appropriate treatment can help to shape EBM for this group of patients.In this article, we provide tools for finding relevant literature for the geriatric patient population and for shaping the SDM process to achieve personalized care

Generalism in medicine: not by chance but by design

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Stap voor stap samen beslissen. Gezamenlijke besluitvorming ook bij kwetsbare patiënten mogelijk.

Contains fulltext : 136861.pdf (publisher's version ) (Open Access

Interdisciplinary education affects student learning: a focus group study.

BACKGROUND: In order to best prepare medical students for their increasingly complex future career, interdisciplinary higher education is swiftly gaining popularity. However, the implementation of interdisciplinary learning in medical education is challenging. The present study deepens the understanding of the challenges and opportunities inherent to the implementation of an interdisciplinary course. We elucidated the attitudes and beliefs of students participating in a newly developed interdisciplinary minor, in which students of medicine (MS) and communication and information sciences (CISS) were involved. METHODS: We conducted four semi-structured focus group interviews, of which two were held before, and two were held after the course. Seven MS and six CISS participated voluntarily. A pre-arranged interview guide was used. The interviews were recorded and afterwards systematically analyzed with the 'constant comparative analysis' technique. RESULTS: The focus group interviews revealed three differences in epistemics between students in terms of 1) curriculum content, 2) educational formats and 3) student's competence perceptions. These factors influenced the way students evaluated themselves, each other and the interdisciplinary course. CONCLUSIONS: We conclude that factors that influence interdisciplinary learning are personal epistemics, individual learning preferences, and the synergy that is achieved throughout interdisciplinary learning. Organizing the dialogue among students of different disciplines could make students aware of inequalities, implicated biases and assigned status of different student groups. These empirical results are crucial to tailor interdisciplinary education to each specific discipline and to take interdisciplinary learning to a higher level of maturity

Attitude change during medical education: Comparing addiction, dementia, and diabetes

Item does not contain fulltextThis dataset contains the data of an observational prospective cohort study. This study evaluates medical students' attitudes towards addiction, dementia, and diabetes. Participants were sixth year medical students of the Radboud University Medical Center (Radboudumc). They were recruited from the training in the Primary and Community Care from February 2016 - January 2017. The attitudes were measured three times during this training, using the Medical Condition Regard scale (MCRS)

Shared decision making with frail older patients: Proposed teaching framework and practice recommendations

Contains fulltext : 177946.pdf (publisher's version ) (Open Access)This study has two aims: The first aim is to identify core competencies for shared decision making (SDM) with frail older persons, and the second is to determine key elements of a teaching framework, based on the authors' recently developed model for SDM with older patients who are frail. To this end the authors conducted a qualitative inquiry among health professionals (n = 53) and older patients who are frail (n = 16). Participants formulated core competencies and educational needs for SDM with older patients who are frail, which were further explored in the literature. This resulted in practice recommendations and a teaching framework with the following key elements: create a knowledge base for all health professionals, offer practical training, facilitate communication, identify discussion partners, engage patients, and collaborate. The authors' teaching framework for SDM with older patients who are frail may be useful for clinicians, educators, and researchers who aim to promote SDM with older patients who are frail