Generalised Anxiety Disorder – A Twin Study of Genetic Architecture, Genome-Wide Association and Differential Gene Expression

Generalised Anxiety Disorder (GAD) is a common anxiety-related diagnosis, affecting approximately 5% of the adult population. One characteristic of GAD is a high degree of anxiety sensitivity (AS), a personality trait which describes the fear of arousal-related sensations. Here we present a genome-wide association study of AS using a cohort of 730 MZ and DZ female twins. The GWAS showed a significant association for a variant within the RBFOX1 gene. A heritability analysis of the same cohort also confirmed a significant genetic component with h2 of 0.42. Additionally, a subset of the cohort (25 MZ twins discordant for AS) was studied for evidence of differential expression using RNA-seq data. Significant differential expression of two exons with the ITM2B gene within the discordant MZ subset was observed, a finding that was replicated in an independent cohort. While previous research has shown that anxiety has a high comorbidity with a variety of psychiatric and neurodegenerative disorders, our analysis suggests a novel etiology specific to AS

Obstacles on the way to the clinical visualisation of beta cells: looking for the Aeneas of molecular imaging to navigate between Scylla and Charybdis

For more than a decade, researchers have been trying to develop non-invasive imaging techniques for the in vivo measurement of viable pancreatic beta cells. However, in spite of intense research efforts, only one tracer for positron emission tomography (PET) imaging is currently under clinical evaluation. To many diabetologists it may remain unclear why the imaging world struggles to develop an effective method for non-invasive beta cell imaging (BCI), which could be useful for both research and clinical purposes. Here, we provide a concise overview of the obstacles and challenges encountered on the way to such BCI, in both native and transplanted islets. We discuss the major difficulties posed by the anatomical and cell biological features of pancreatic islets, as well as the chemical and physical limits of the main imaging modalities, with special focus on PET, SPECT and MRI. We conclude by indicating new avenues for future research in the field, based on several remarkable recent results

Protein tyrosine phosphatases in glioma biology

Gliomas are a diverse group of brain tumors of glial origin. Most are characterized by diffuse infiltrative growth in the surrounding brain. In combination with their refractive nature to chemotherapy this makes it almost impossible to cure patients using combinations of conventional therapeutic strategies. The drastically increased knowledge about the molecular underpinnings of gliomas during the last decade has elicited high expectations for a more rational and effective therapy for these tumors. Most studies on the molecular pathways involved in glioma biology thus far had a strong focus on growth factor receptor protein tyrosine kinase (PTK) and phosphatidylinositol phosphatase signaling pathways. Except for the tumor suppressor PTEN, much less attention has been paid to the PTK counterparts, the protein tyrosine phosphatase (PTP) superfamily, in gliomas. PTPs are instrumental in the reversible phosphorylation of tyrosine residues and have emerged as important regulators of signaling pathways that are linked to various developmental and disease-related processes. Here, we provide an overview of the current knowledge on PTP involvement in gliomagenesis. So far, the data point to the potential implication of receptor-type (RPTPδ, DEP1, RPTPμ, RPTPζ) and intracellular (PTP1B, TCPTP, SHP2, PTPN13) classical PTPs, dual-specific PTPs (MKP-1, VHP, PRL-3, KAP, PTEN) and the CDC25B and CDC25C PTPs in glioma biology. Like PTKs, these PTPs may represent promising targets for the development of novel diagnostic and therapeutic strategies in the treatment of high-grade gliomas

Reading in one's ethnic language: A study of Greek-Australian high school students

This paper examines reading achievement when the maternal/paternal language has become a de facto second language. The performance of a cohort of Greek-Australian high school students (N=270) on a diagnostic Greek reading test was significantly below that of pupils in second to fourth grades in Greece. The mean item difficulty for Greek-Australian high school students was 0.35 compared with 0.51 for second grade, 0.69 for third grade and 0.80 for fourth grade pupils in Greece. The pattern of responding indicated that the Rasch model fitted the data. The effects of background factors were also examined. Students whose mother or father spoke Greek had statistically significant higher levels of ability than those who spoke Greek and English or English alone. It was also found that the length of the key words (correct responses) had a large effect on the difficulty of the questions; the longer the key word, the more difficult the question was. The implications of the results for assessment of reading in and the acquisition of an ethnic or second language are discussed

Validation of written and video based assessment instruments in physical education

A written paper (WP) and a video-based-paper (VP) were usedto measure the learning outcomes of three experimental teaching units (ETUs) of athletics. The subjects (n=49) were 16 year olds. The ETUs represented three teaching environments; practice, practice and handouts, and classbased sessions. Pre and post-tests were administered for the content of rules, planning tactics and techniques. Rasch model analysis showed that both tests were unidimensional and reliable (R ranged from 0.86 to 0.92). The efficiency of the three experimental teaching units was evaluated by means of paired sample t-tests. The subjects performed better on the posttests (WP: effect size=1.2 and VP: effect size=0.93). The pre-tests and posttests abilities of the subjects were highly correlated (WP: r=0.380 and VP: r=0.322). The subjects of the class-based sessions achieved significantly better scores on all content areas when video based assessments were used. The findings of this study are applicable to athletics

Can we use Rasch measurement in vocational education and training classrooms?

The purpose of this paper is to introduce some of the concepts of Rasch measurement through an example in vocational education. Test data are reported for a typical class size group of 19 students on six criterionreferenced and competency-based assessment tasks. These were part of an objective structured clinical examination for nursing students. The results are then compared with those of a bootstrap replicated sample of 1000 students. The results from the classroom sample are markedly similar to that of the bootstrap. It is argued that Rasch measurement does have application for criterion-referenced assessments but there can be substantive limitations when applying it to the typically small samples representative of most vocational education groups. Rasch measurement is not a mere statistical modelling method but the application of fundamental measurement principles, therefore, there are a number of theoretical issues involved which need to be considered before applying Rasch analysis in any situation