The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

High Rates of Prescribing Antimicrobials for Prophylaxis in Children and Neonates: Results From the Antibiotic Resistance and Prescribing in European Children Point Prevalence Survey

Background. This study was conducted to assess the variation in prescription practices for systemic antimicrobial agents used for prophylaxis among pediatric patients hospitalized in 41 countries worldwide. Methods. Using the standardized Antibiotic Resistance and Prescribing in European Children Point Prevalence Survey protocol, a cross-sectional point-prevalence survey was conducted at 226 pediatric hospitals in 41 countries from October 1 to November 30, 2012. Results. Overall, 17 693 pediatric patients were surveyed and 36.7% of them received antibiotics (n = 6499). Of 6818 inpatient children, 2242 (32.9%) received at least 1 antimicrobial for prophylactic use. Of 11 899 prescriptions for antimicrobials, 3400 (28.6%) were provided for prophylactic use. Prophylaxis for medical diseases was the indication in 73.4% of cases (2495 of 3400), whereas 26.6% of prescriptions were for surgical diseases (905 of 3400). In approximately half the cases (48.7% [1656 of 3400]), a combination of 2 or more antimicrobials was prescribed. The use of broad-spectrum antibiotics (BSAs), which included tetracyclines, macrolides, lincosamides, and sulfonamides/trimethoprim, was high (51.8% [1761 of 3400]). Broad-spectrum antibiotic use for medical prophylaxis was more common in Asia (risk ratio [RR], 1.322; 95% confidence interval [CI], 1.202-1.653) and more restricted in Australia (RR, 0.619; 95% CI, 0.521-0.736). Prescription of BSA for surgical prophylaxis also varied according to United Nations region. Finally, a high percentage of surgical patients (79.7% [721 of 905]) received their prophylaxis for longer than 1 day. Conclusions. A high proportion of hospitalized children received prophylactic BSAs. This represents a clear target for quality improvement. Collectively speaking, it is critical to reduce total prophylactic prescribing, BSA use, and prolonged prescription