Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesOver the past decade genome-wide association studies (GWAS) have been applied to aid in the understanding of the biology of traits. The success of this approach is governed by the underlying effect sizes carried by the true risk variants and the corresponding statistical power to observe such effects given the study design and sample size under investigation. Previous ASD GWAS have identified genome-wide significant (GWS) risk loci; however, these studies were of only of low statistical power to identify GWS loci at the lower effect sizes (odds ratio (OR) <1.15).We conducted a large-scale coordinated international collaboration to combine independent genotyping data to improve the statistical power and aid in robust discovery of GWS loci. This study uses genome-wide genotyping data from a discovery sample (7387 ASD cases and 8567 controls) followed by meta-analysis of summary statistics from two replication sets (7783 ASD cases and 11359 controls; and 1369 ASD cases and 137308 controls).We observe a GWS locus at 10q24.32 that overlaps several genes including PITX3, which encodes a transcription factor identified as playing a role in neuronal differentiation and CUEDC2 previously reported to be associated with social skills in an independent population cohort. We also observe overlap with regions previously implicated in schizophrenia which was further supported by a strong genetic correlation between these disorders (Rg = 0.23; P = 9 × 10(-6)). We further combined these Psychiatric Genomics Consortium (PGC) ASD GWAS data with the recent PGC schizophrenia GWAS to identify additional regions which may be important in a common neurodevelopmental phenotype and identified 12 novel GWS loci. These include loci previously implicated in ASD such as FOXP1 at 3p13, ATP2B2 at 3p25.3, and a 'neurodevelopmental hub' on chromosome 8p11.23.This study is an important step in the ongoing endeavour to identify the loci which underpin the common variant signal in ASD. In addition to novel GWS loci, we have identified a significant genetic correlation with schizophrenia and association of ASD with several neurodevelopmental-related genes such as EXT1, ASTN2, MACROD2, and HDAC4.National Institutes of Mental Health (NIMH, USA) ACE Network Autism Genetic Resource Exchange (AGRE) is a program of Autism Speaks (USA) The Autism Genome Project (AGP) from Autism Speaks (USA) Canadian Institutes of Health Research (CIHR), Genome Canada Health Research Board (Ireland) Hilibrand Foundation (USA) Medical Research Council (UK) National Institutes of Health (USA) Ontario Genomics Institute University of Toronto McLaughlin Centre Simons Foundation Johns Hopkins Autism Consortium of Boston NLM Family foundation National Institute of Health grants National Health Medical Research Council Scottish Rite Spunk Fund, Inc. Rebecca and Solomon Baker Fund APEX Foundation National Alliance for Research in Schizophrenia and Affective Disorders (NARSAD) endowment fund of the Nancy Pritzker Laboratory (Stanford) Autism Society of America Janet M. Grace Pervasive Developmental Disorders Fund The Lundbeck Foundation universities and university hospitals of Aarhus and Copenhagen Stanley Foundation Centers for Disease Control and Prevention (CDC) Netherlands Scientific Organization Dutch Brain Foundation VU University Amsterdam Trinity Centre for High Performance Computing through Science Foundation Ireland Autism Genome Project (AGP) from Autism Speak

Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders

Autism spectrum disorder (ASD) risk is influenced by common polygenic and de novo variation. We aimed to clarify the influence of polygenic risk for ASD and to identify subgroups of ASD cases, including those with strongly acting de novo variants, in which polygenic risk is relevant. Using a novel approach called the polygenic transmission disequilibrium test and data from 6,454 families with a child with ASD, we show that polygenic risk for ASD, schizophrenia, and greater educational attainment is over-transmitted to children with ASD. These findings hold independent of proband IQ. We find that polygenic variation contributes additively to risk in ASD cases who carry a strongly acting de novo variant. Lastly, we show that elements of polygenic risk are independent and differ in their relationship with phenotype. These results confirm that the genetic influences on ASD are additive and suggest that they create risk through at least partially distinct etiologic pathways

Consequences Of On-Track Competition In Railways By Use Of Simulations

Institute of Transport and Logistics Studies. Faculty of Economics and Business. The University of Sydne

Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia

Background Over the past decade genome-wide association studies (GWAS) have been applied to aid in the understanding of the biology of traits. The success of this approach is governed by the underlying effect sizes carried by the true risk variants and the corresponding statistical power to observe such effects given the study design and sample size under investigation. Previous ASD GWAS have identified genome-wide significant (GWS) risk loci; however, these studies were of only of low statistical power to identify GWS loci at the lower effect sizes (odds ratio (OR) <1.15). Methods We conducted a large-scale coordinated international collaboration to combine independent genotyping data to improve the statistical power and aid in robust discovery of GWS loci. This study uses genome-wide genotyping data from a discovery sample (7387 ASD cases and 8567 controls) followed by meta-analysis of summary statistics from two replication sets (7783 ASD cases and 11359 controls; and 1369 ASD cases and 137308 controls). Results We observe a GWS locus at 10q24.32 that overlaps several genes including PITX3, which encodes a transcription factor identified as playing a role in neuronal differentiation and CUEDC2 previously reported to be associated with social skills in an independent population cohort. We also observe overlap with regions previously implicated in schizophrenia which was further supported by a strong genetic correlation between these disorders (Rg = 0.23; P=9 ×10−6). We further combined these Psychiatric Genomics Consortium (PGC) ASD GWAS data with the recent PGC schizophrenia GWAS to identify additional regions which may be important in a common neurodevelopmental phenotype and identified 12 novel GWS loci. These include loci previously implicated in ASD such as FOXP1 at 3p13, ATP2B2 at 3p25.3, and a ‘neurodevelopmental hub’ on chromosome 8p11.23. Conclusions This study is an important step in the ongoing endeavour to identify the loci which underpin the common variant signal in ASD. In addition to novel GWS loci, we have identified a significant genetic correlation with schizophrenia and association of ASD with several neurodevelopmental-related genes such as EXT1, ASTN2, MACROD2, and HDAC4

Spirituality in childhood cancer care

N&aacute;dia Nara Rolim Lima,1 V&acirc;nia Barbosa do Nascimento,1 Sionara Melo Figueiredo de Carvalho,1 Modesto Leite Rolim Neto,2 Marcial Moreno Moreira,2 Aline Quental Brasil,2 Francisco Tel&eacute;sforo Celestino Junior,2 Gislene Farias de Oliveira,2 Alberto Olavo Adv&iacute;ncula Reis3 1Health Sciences Postgraduate Program, ABC Region Medical School, Santo Andr&eacute;, S&atilde;o Paulo, Brazil; 2Department of Medicine, Federal University of Cear&aacute;, Barbalha, Cear&aacute;, Brazil; 3Public Health Postgraduate Program, University of S&atilde;o Paulo, S&atilde;o Paulo, Brazil Abstract: To deal with the suffering caused by childhood cancer, patients and their families use different coping strategies, among which, spirituality appears a way of minimizing possible damage. In this context, the purpose of the present study was to analyze the influence of spirituality in childhood cancer care, involving biopsychosocial aspects of the child, the family, and the health care team facing the disease. To accomplish this purpose, a nonsystematic review of literature of articles on national and international electronic databases (Scientific Electronic Library Online [SciELO], PubMed, and Latin American and Caribbean Health Sciences Literature [LILACS]) was conducted using the search terms &ldquo;spirituality,&rdquo; &ldquo;child psychology,&rdquo; &ldquo;child,&rdquo; and &ldquo;cancer,&rdquo; as well as on other available resources. After the search, 20 articles met the eligibility criteria and were included in the final sample. Our review showed that the relation between spirituality and health has lately become a subject of growing interest among researchers, as a positive influence of spirituality in the people&#39;s welfare was noted. Studies that were retrieved using the mentioned search strategy in electronic databases, independently assessed by the authors according to the systematic review, showed that spirituality emerges as a driving force that helps pediatric patients and their families in coping with cancer. Health care workers have been increasingly attentive to this dimension of care. However, it is necessary to improve their knowledge regarding the subject. The search highlighted that spirituality is considered a source of comfort and hope, contributing to a better acceptance of his/her chronic condition by the child with cancer, as well as by the family. Further up-to-date studies facing the subject are, thus, needed. It is also necessary to better train health care practitioners, so as to provide humanized care to the child with cancer. Keywords: spirituality, child, child psychology, neoplasms, cance

Contribuição de diferentes conteúdos das aulas de educação física no ensino fundamental I para o desenvolvimento das habilidades motoras fundamentais

INTRODUÇÃO E OBJETIVO: Este estudo investigou a contribuição das aulas de educação física (EF) no ensino fundamental I para o desenvolvimento de habilidades motoras fundamentais de crianças de duas escolas públicas da mesma região da cidade de São Paulo, e se a prática de esportes radicais, além das aulas de EF, poderia diferenciar tal desenvolvimento. MÉTODOS: Dezenove crianças (9,5 ± 0,3 anos) que tiveram semanalmente duas aulas de EF formaram o grupo controle (GC) e 22 crianças (9,6 ± 0,5 anos) que tiveram semanalmente duas aulas de EF e três aulas de esportes radicais formaram o grupo experimental (GE). Todas as crianças foram filmadas realizando as habilidades motoras dos subtestes locomotor e controle de objetos do Test of Gross Motor Development (TGMD-2). As filmagens foram analisadas posteriormente e escores brutos foram atribuídos de acordo com a qualidade do movimento observado, e idade motora equivalente também foi estimada para os dois subtestes. RESULTADOS: Os resultados indicaram que as crianças do GE apresentaram escores brutos maiores que as crianças do GC no subteste locomotor e os dois grupos apresentaram escores brutos similares no subteste controle de objetos. Ainda, as crianças do GE apresentaram idade motora equivalente maior que a idade cronológica no subteste locomotor enquanto que as crianças do GC não apresentaram diferença entre as duas idades, e os dois grupos não apresentaram diferenças entre idade motora equivalente e idade cronológica no subteste controle de objetos. CONCLUSÃO: Com base nos resultados, concluímos que aulas de EF nos quatro primeiros anos do ensino fundamental I contribuíram adequadamente para o desenvolvimento de habilidades motoras fundamentais, uma vez que os dois grupos não apresentaram idade motora equivalente inferior à idade cronológica; e que aulas de esportes radicais contribuíram ainda mais para o desenvolvimento de habilidades locomotoras

Early prediction of hypocalcemia after thyroidectomy using parathyroid hormone: an analysis of pooled individual patient data from nine observational studies

BACKGROUND: Monitoring for hypocalcemia after thyroidectomy, using only symptoms and serum calcium levels, can delay the discharge of patients who will remain normocalcemic and can delay the treatment of hypocalcemic patients. STUDY DESIGN: We conducted a systematic search for articles describing use of parathyroid hormone (PTH) assay, checked within hours of completing thyroidectomy, to predict postoperative symptomatic hypocalcemia. Studies were excluded if all patients were treated with postoperative calcium, or if early PTH values were used to alter management of the patient. Individual patient data (perioperative PTH and calcium levels, development of hypocalcemia) were obtained for 457 patients from the corresponding authors of 9 studies and pooled to yield the following results. RESULTS: PTH, checked at three time periods after removal of the thyroid gland (0 to 20 minutes, 1 to 2 hours, and 6 hours), was substantially lower in patients who became hypocalcemic compared with those who remained normocalcemic. The accuracy of PTH in determining hypocalcemia increased with time and was excellent when checked 1 to 6 hours postoperatively. A single PTH threshold (65% decrease compared with preoperative level), checked 6 hours after completing thyroidectomy, had a sensitivity of 96.4% and specificity of 91.4% in detecting postoperative hypocalcemia. CONCLUSIONS: PTH assay, when checked 1 to 6 hours after thyroidectomy, has excellent accuracy in determining which patients will become symptomatically hypocalcemic. Routine use of this assay should be considered because it may allow earlier discharge of the normocalcemic patient and earlier identification of patients requiring treatment of postthyroidectomy hypocalcemia