Identification of common genetic risk variants for autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.Peer reviewe

Primary immunodeficiency disease at Red Cross War Memorial Children's Hospital

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Comparison of diagnostic criteria of tuberculous meningitis in human immunodeficiency virus-infected and uninfected children

INTRODUCTION: Tuberculous (TB) meningitis is sometimes difficult to diagnose in young children. The decision to start anti-TB treatment of TB meningitis is usually made on clinical grounds and results of special investigations, such as cerebrospinal fluid examination and cranial computerized tomography (CT), because bacteriologic yield is low and the results delayed. AIM: To determine whether the clinical, laboratory, and radiologic criteria used in the diagnosis of TB meningitis in human immunodeficiency virus (HIV)-uninfected children apply to HIV-infected children. METHODS: Retrospective, case-control study. Clinical, laboratory, and radiologic features of TB meningitis were compared in 34 HIV-infected and 56 HIV-uninfected patients matched for age and stage of TB meningitis. RESULTS: All clinical differences found between the 2 groups at admission were related to the underlying HIV disease. Neurologic presentation and cerebrospinal fluid findings at admission did not differ significantly between the 2 groups. Significantly more HIV-infected than HIV-uninfected children had evidence of TB on chest radiography. The classic CT signs of TB meningitis (obstructive hydrocephalus and basal enhancement) were significantly less prominent in the HIV-infected group (P < 005). CONCLUSION: The diagnostic criteria for clinical diagnosis of TB meningitis apply to HIV-infected children. However, cranial CT findings in this group may be misleading and delay the diagnosis of TB meningitis. Copyright © 2005 by Lippincott Williams & Wilkins.Articl

Two natural heuristics for 3D packing with practical loading constraints

In this paper, we describe two heuristics for the Single Vehicle Loading Problem (SVLP), which can handle practical constraints that are frequently encountered in the freight transportation industry, such as the servicing order of clients; item fragility; and the stability of the goods. The two heuristics, Deepest-Bottom-Left-Fill and Maximum Touching Area, are 3D extensions of natural heuristics that have previously only been applied to 2D packing problems. We employ these heuristics as part of a two-phase tabu search algorithm for the Three-Dimensional Loading Capacitated Vehicle Routing Problem (3L-CVRP), where the task is to serve all customers using a homogeneous fleet of vehicles at minimum traveling cost. The resultant algorithm produces mostly superior solutions to existing approaches, and appears to scale better with problem size. © 2010 Springer-Verlag Berlin Heidelberg