Sleep and Cognition in Children with Fetal Alcohol Spectrum Disorders (FASD) and Children with Autism Spectrum Disorders (ASD)

Children with Fetal Alcohol Spectrum Disorders (FASD) and Autism Spectrum Disorders (ASD) experience significantly higher rates of sleep disturbances than their typically developing peers. However, little is known about the association between sleep and the cognitive phenotype in these clinical populations. Structural damage affecting cortical and subcortical connectivity occurs as a result of prenatal alcohol exposure in children with FASD, whilst it is believed an abundance of short-range connectivity explains the phenotypic manifestations of childhood ASD. These underlying neural structural and connectivity differences manifest as cognitive patterns, with some shared and some unique characteristics between FASD and ASD. This is the first study to examine sleep and its association with cognition in individuals with FASD, and to compare sleep in individuals with FASD and ASD. We assessed children aged 6–12 years with a diagnosis of FASD (n = 29), ASD (n = 21), and Typically Developing (TD) children (n = 46) using actigraphy (CamNTech Actiwatch 8), digit span tests of working memory (Weschler Intelligence Scale), tests of nonverbal mental age (MA; Ravens Standard Progressive Matrices), receptive vocabulary (British Picture Vocabulary Scale), and a choice reaction time (CRT) task. Children with FASD and ASD presented with significantly shorter total sleep duration, lower sleep efficiency, and more nocturnal wakings than their TD peers. Sleep was significantly associated with scores on the cognitive tests in all three groups. Our findings support the growing body of work asserting that sleep is significant to cognitive functioning in these neurodevelopmental conditions; however, more research is needed to determine cause and effect

Who applies and who gets admitted to UK graduate entry medicine? - an analysis of UK admission statistics

Background Graduate-entry medicine is a recent development in the UK, intended to expand and broaden access to medical training. After eight years, it is time to evaluate its success in recruitment. Objectives This study aimed to compare the applications and admissions profiles of graduate-entry programmes in the UK to traditional 5 and 6-year courses. Methods Aggregate data on applications and admissions were obtained from the Universities and Colleges Admission Service covering 2003 to 2009. Data were extracted, grouped as appropriate and analysed with the Statistical Package for the Social Sciences. Results Graduate-entry attracts 10,000 applications a year. Women form the majority of applicants and admissions to graduate-entry and traditional medicine programmes. Graduate-entry age profile is older, typically 20's or 30's compared to 18 or 19 years in traditional programmes. Graduate-entry applications and admissions were higher from white and black UK ethnic communities than traditional programmes, and lower from southern and Chinese Asian groups. Graduate-entry has few applications or admissions from Scotland or Northern Ireland. Secondary educational achievement is poorer amongst graduate-entry applicants and admissions than traditional programmes. Conclusions Graduate-entry has succeeded in recruiting substantial additional numbers of older applicants to medicine, in which white and black groups are better represented and Asian groups more poorly represented than in traditional undergraduate programmes

Heterotic Sigma Models with N=2 Space-Time Supersymmetry

We study the non-linear sigma model realization of a heterotic vacuum with N=2 space-time supersymmetry. We examine the requirements of (0,2) + (0,4) world-sheet supersymmetry and show that a geometric vacuum must be described by a principal two-torus bundle over a K3 manifold.Comment: 20 pages, uses xy-pic; v3: typos corrected, reference added, discussion of constraints on Hermitian form modifie

Teaching medical students about children with disabilities in a rural setting in a school

Background: To describe and implement a community paediatric placement in a school setting that teaches undergraduate medical students about intellectual disability that provides benefit to the community and is acceptable to both students and teachers. Methods: Twenty six 4th year undergraduate medical students of the University of Newcastle completed their Paediatric studies based in Tamworth in 2004 & 2005 including an 8 week placement at Bullimbal School for Specific Purposes. The placement involved the students being actively involved in assisting with the delivery of a variety of activities aimed at improving the motor skills of a group of disabled children. De-identified data were obtained from completed evaluation surveys from 75% (21 of 26) of the medical students and from 100% (5 of 5) of the teachers. Results: All students and teachers found the placement was acceptable and enjoyed the placement and felt that it gave the medical students a greater understanding of children with disabilities. 80% (4 of 5) of the teachers involved in the program did not feel that its implementation added to their workload and all were enthusiastic to continue with the program. Conclusion: Medical students can be effectively taught and have a valuable clinical experience in a school setting to learn about children with a disability. This educational innovation has provided a mutual benefit for both the medical students and the school children who participated in the program without impacting on the workloads of teachers

Conformational landscapes of DNA polymerase I and mutator derivatives establish fidelity checkpoints for nucleotide insertion

The fidelity of DNA polymerases depends on conformational changes that promote the rejection of incorrect nucleotides before phosphoryl transfer. Here, we combine single-molecule FRET with the use of DNA polymerase I and various fidelity mutants to highlight mechanisms by which active-site side chains influence the conformational transitions and free-energy landscape that underlie fidelity decisions in DNA synthesis. Ternary complexes of high fidelity derivatives with complementary dNTPs adopt mainly a fully closed conformation, whereas a conformation with a FRET value between those of open and closed is sparsely populated. This intermediate-FRET state, which we attribute to a partially closed conformation, is also predominant in ternary complexes with incorrect nucleotides and, strikingly, in most ternary complexes of low-fidelity derivatives for both correct and incorrect nucleotides. The mutator phenotype of the low-fidelity derivatives correlates well with reduced affinity for complementary dNTPs and highlights the partially closed conformation as a primary checkpoint for nucleotide selection

A model for transition of 5 '-nuclease domain of DNA polymerase I from inert to active modes

Bacteria contain DNA polymerase I (PolI), a single polypeptide chain consisting of similar to 930 residues, possessing DNA-dependent DNA polymerase, 3'-5' proofreading and 5'-3' exonuclease (also known as flap endonuclease) activities. PolI is particularly important in the processing of Okazaki fragments generated during lagging strand replication and must ultimately produce a double-stranded substrate with a nick suitable for DNA ligase to seal. PolI's activities must be highly coordinated both temporally and spatially otherwise uncontrolled 5'-nuclease activity could attack a nick and produce extended gaps leading to potentially lethal double-strand breaks. To investigate the mechanism of how PolI efficiently produces these nicks, we present theoretical studies on the dynamics of two possible scenarios or models. In one the flap DNA substrate can transit from the polymerase active site to the 5'-nuclease active site, with the relative position of the two active sites being kept fixed; while the other is that the 5'-nuclease domain can transit from the inactive mode, with the 5'-nuclease active site distant from the cleavage site on the DNA substrate, to the active mode, where the active site and substrate cleavage site are juxtaposed. The theoretical results based on the former scenario are inconsistent with the available experimental data that indicated that the majority of 5'-nucleolytic processing events are carried out by the same PolI molecule that has just extended the upstream primer terminus. By contrast, the theoretical results on the latter model, which is constructed based on available structural studies, are consistent with the experimental data. We thus conclude that the latter model rather than the former one is reasonable to describe the cooperation of the PolI's polymerase and 5'-3' exonuclease activities. Moreover, predicted results for the latter model are presented

Understanding adolescent and young adult use of family physician services: a cross-sectional analysis of the Canadian Community Health Survey

BACKGROUND: Primary health care is known to have positive effects on population health and may reduce at-risk behavior and health problems in adolescence. Yet little is known about the factors that are associated with adolescent and young adult utilization of family physician services. It is critical to determine the factors associated with utilization to inform effective primary health care policy. We address this gap in the primary health care literature by examining three issues concerning adolescent and young adult family physician use: inequity; the unique developmental stage of adolescence; and the distinction between utilization (users versus non-users) and intensity (high users versus low users). METHODS: We conducted nested logistic regressions for two outcomes: utilization and intensity of family physician services for early adolescence, middle adolescence, and young adulthood using the 2005 Canadian Community Health Survey. RESULTS: Chronic conditions were associated with utilization in early and middle adolescence and intensity in all age groups. Respondents from Quebec had lower odds of utilization. Those without a regular medical doctor had much lower odds of being users. The factors associated with use in early and middle adolescence were in keeping with parental involvement while the factors in young adulthood show the emerging independence of this group. CONCLUSIONS: We highlight key messages not known previously for adolescent and young adult use of family physician services. There is inequity concerning regional variation and for those who do not have a regular medical doctor. There is variation in factors associated with family physician services across the three age groups of adolescence. Health care and health care policies aimed at younger adolescents must consider that parents are still the primary decision-maker while older adolescents are more autonomous. There is variation in the factors associated with the two outcomes of utilization and intensity of services. Factors associated with utilization must be understood when considering the equitability of access to primary health care while factors associated with intensity must be understood when considering appropriate use of resources. The understanding gained from this study can inform health care policy that is responsive to the critical developmental stage of adolescence and young adulthood

Issues facing the future health care workforce: the importance of demand modelling

This article examines issues facing the future health care workforce in Australia in light of factors such as population ageing. It has been argued that population ageing in Australia is affecting the supply of health care professionals as the health workforce ages and at the same time increasing the demand for health care services and the health care workforce