The mediating effect of task presentation on collaboration and children's acquisition of scientific reasoning

There has been considerable research concerning peer interaction and the acquisition of children's scientific reasoning. This study investigated differences in collaborative activity between pairs of children working around a computer with pairs of children working with physical apparatus and related any differences to the development of children's scientific reasoning. Children aged between 9 and 10 years old (48 boys and 48 girls) were placed into either same ability or mixed ability pairs according to their individual, pre-test performance on a scientific reasoning task. These pairs then worked on either a computer version or a physical version of Inhelder and Piaget's (1958) chemical combination task. Type of presentation was found to mediate the nature and type of collaborative activity. The mixed-ability pairs working around the computer talked proportionally more about the task and management of the task; had proportionally more transactive discussions and used the record more productively than children working with the physical apparatus. Type of presentation was also found to mediated children's learning. Children in same ability pairs who worked with the physical apparatus improved significantly more than same ability pairs who worked around the computer. These findings were partially predicted from a socio-cultural theory and show the importance of tools for mediating collaborative activity and collaborative learning

Diagnosis of non-effusive feline infectious peritonitis by reverse transcriptase quantitative PCR from mesenteric lymph node fine-needle aspirates

The aim of this study was to evaluate a feline coronavirus (FCoV) reverse transcriptase quantitative PCR (RT-qPCR) on fine-needle aspirates (FNAs) from mesenteric lymph nodes (MLNs) collected in sterile saline for the purpose of diagnosing non-effusive feline infectious peritonitis (FIP) in cats. First, the ability of the assay to detect viral RNA in MLN FNA preparations compared with MLN biopsy preparations was assessed in matched samples from eight cats. Second, a panel of MLN FNA samples was collected from a series of cats representing non-effusive FIP cases (n = 20), FCoV-seropositive individuals (n = 8) and FCoV seronegative individuals (n = 18). Disease status of the animals was determined using a combination of gross pathology, histopathology and/or 'FIP profile', consisting of serology, clinical pathology and clinical signs. Viral RNA was detected in 18/20 non-effusive FIP cases; it was not detected in two cases that presented with neurological FIP. Samples from 18 seronegative non-FIP control cats and 7/8 samples from seropositive non-FIP control cats contained no detectable viral RNA. Thus, as a method for diagnosing non-effusive FIP, MLN FNA RT-qPCR had an overall sensitivity of 90.0% and specificity of 96.1%. In cases with a high index of suspicion of disease, RT-qPCR targeting FCoV in MLN FNA can provide important information to support the ante-mortem diagnosis of non-effusive FIP. Importantly, viral RNA can be reliably detected in MLN FNA samples in saline submitted via the national mail service. When applied in combination with biochemistry, haematology and serological tests in cases with a high index of suspicion of disease the results of this assay may be used to support a diagnosis of non-effusive FIP

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility

Several susceptibility loci for classical Hodgkin lymphoma (cHL) have been reported, however much of the heritable risk is unknown. Here, we perform a meta-analysis of two existing genome-wide association studies (GWAS), a new GWAS, and replication totalling 5,314 cases and 16,749 controls. We identify risk loci for all cHL at 6q22.33 (rs9482849, P=1.52 × 10-8) and for nodular sclerosis HL (NSHL) at 3q28 (rs4459895, P=9.43 × 10-17), 6q23.3 (rs6928977, P=4.62 × 10-55 11), 10p14 (rs3781093, P=9.49 × 10-13), 13q34 (rs112998813, P=4.58 × 10-8) and 16p13.13 (rs34972832, P=2.12 × 10-8). Additionally, independent loci within the HLA region are observed for NSHL (rs9269081, HLA-DPB1*03:01, Val86 in HLA-DRB1) and mixed cellularity HL (rs1633096, rs13196329, Val86 in HLA-DRB1). The new and established risk loci localise to areas of active chromatin and show an over-representation of transcription factor binding for determinants of B-cell development and immune response.In the United Kingdom, Bloodwise (LLR; 10021) provided principal funding for the study. Support from Cancer Research UK (C1298/A8362 supported by the Bobby Moore Fund) and the Lymphoma Research Trust is also acknowledged. A.S. is supported by a clinical fellowship from Cancer Research UK. For the UK-GWAS, sample and data acquisition were supported by Breast Cancer Now, the European Union and the Lymphoma Research Trust. The UK-GWAS made use of control genotyping data generated by the WTCCC. For further information, please visit the publishr's website

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

An Extreme-Value Model of Concept Testing

We model concept testing in new product development as a search for the most profitable solution to a design problem. When allocating resources, developers must balance the cost of testing multiple designs against the potential profits that may result. We propose extreme-value theory as a mathematical abstraction of the concept-testing process. We investigate the trade-off between the benefits and costs of parallel concept testing and derive closed-form solutions for the case of profits that follow extreme-value distributions. We analyze the roles of the scale and tail-shape parameters of the profit distribution as well as the cost of testing in determining the optimal number of tests and total budget for the concept phase of NPD. Using an example, we illustrate how to estimate and interpret the scale and tail-shape parameters. We find that the impact of declining concept-testing costs on expected profits, the number of concepts tested, and total spending depend on the scale/cost ratio and tail-shape parameter of the profit distribution.Concept Testing, Prototyping, Extreme-Value Theory, New Product Development, Parallel Testing, Concept Selection, R...D Spending