Fine mapping and replication of genetic risk Loci in primary sclerosing cholangitis

Background and aims. Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by progressive inflammation and fibrosis of the bile ducts eventually leading to biliary cirrhosis. Recent genetic studies in PSC have identified associations at 2q13, 2q35, 3p21, 4q27, 13q31 and suggestive association at 10p15. The aim of this study was to further characterize and refine the genetic architecture of PSC. Methods. We analyzed previously reported associated SNPs at four of these non-HLA loci and 59 SNPs tagging the IL-2/IL-21 (4q27) and IL2RA (10p15) loci in 992 UK PSC cases and 5162 healthy UK controls. Results. The most associated SNPs identified were rs3197999 (3p21 (MST1), p = 1.9 × 10 -6, OR A vs G = 1.28, 95% CI (1.16-1.42)); rs4147359 (10p15 (IL2RA), p = 2.6 × 10 -4, OR A vs G = 1.20, 95% CI (1.09-1.33)) and rs12511287 (4q27 (IL-2/IL-21), p = 3.0 × 10 -4, OR A vs T = 1.21, 95% CI (1.09-1.35)). In addition, we performed a meta-analysis for selected SNPs using published summary statistics from recent studies. We observed genome-wide significance for rs3197999 (3p21 (MST1), P combined = 3.8 × 10 -12) and rs4147359 (10p15 (IL2RA), P combined = 1.5 × 10 -8). Conclusion. We have for the first time confirmed the association of PSC with genetic variants at 10p15 (IL2RA) locus at genome-wide significance and replicated the associations at MST1 and IL-2/IL-21 loci in a large homogeneous UK population. These results strongly implicate the role of IL-2/IL2RA pathway in PSC and provide further confirmation of MST1 association. © Informa Healthcare.

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis. © 2011 Macmillan Publishers Limited. All rights reserved.

Positive psychological strengths and school engagement in primary school children

A sizeable body of research has investigated the impact of specific character strengths or traits on significant outcomes. Some recent research is beginning to consider the effects of groups of strengths, combined as a higher order variable, and termed covitality. This study investigated the combined influence of four positive character traits: gratitude, optimism, zest and persistence, upon school engagement, within a sample of 112 Australian primary school students. The combined effect of these four traits, in defining covitality as a higher or second order factor within a path analysis, was found to predict relatively higher levels of school engagement and pro-social behaviour.

Telling tales and painting pictures: A narrative inquiry into the professional learning of Northern Territory primary teachers

This thesis narrates the professional learning experiences of seven Northern Territory teachers. It outlines the evolution from traditional professional development in schools to an active, responsive professional learning agenda. With increasing demands on teachers, standardisation and the quest for improved student outcomes, key themes in the re-storied narrative emerge about the definition and role of professional learning in complex conditions, effective teaching, quality programmes, and teacher agency. This thesis contributes to knowledge about the characteristics that teachers value in their professional learning experiences. An Ongoing Professional Enhancement Model (OPE) is proposed, highlighting directions in this field for key stakeholders.

Arsenic trioxide promotes mitochondrial DNA mutation and cell apoptosis in primary APL cells and NB4 cell line

This study aimed to investigate the effects of arsenic trioxide (As2O3) on the mitochondrial DNA (mtDNA) of acute promyelocytic leukemia (APL) cells. The NB4 cell line was treated with 2.0 μmol/L As2O3in vitro, and the primary APL cells were treated with 2.0 μmol/L As2O3in vitro and 0.16 mg kg-1 d-1 As2O3in vivo. The mitochondrial DNA of all the cells above was amplified by PCR, directly sequenced and analyzed by Sequence Navigatore and Factura software. The apoptosis rates were assayed by flow cytometry. Mitochondrial DNA mutation in the D-loop region was found in NB4 and APL cells before As2O3 use, but the mutation spots were remarkably increased after As2O3 treatment, which was positively correlated to the rates of cellular apoptosis, the correlation coefficient: rNB4-As2O3=0.973818, and rAPL-As2O3=0.934703. The mutation types include transition, transversion, codon insertion or deletion, and the mutation spots in all samples were not constant and regular. It is revealed that As2O3 aggravates mtDNA mutation in the D-loop region of acute promyelocytic leukemia cells both in vitro and in vivo. Mitochondrial DNA might be one of the targets of As2O3 in APL treatment.

Patterns of care: Primary research in mental health nursing

The foundation of mental health nursing has historically been grounded in an interpersonal, person-centred process of health care, yet recent evidence suggests that the interactional work of mental health nursing is being eroded. Literature emphasises the importance of person-centred care on consumer outcomes, a model reliant upon the intimate engagement of nurses and consumers. Yet, the arrival of medical interventions in psychiatry has diverted nursing work from the therapeutic nursing role to task-based roles delegated by medicine, distancing nurses from consumers. This study used work sampling methodology to observe the proportion of time nurses working in an inpatient mental health setting engage in specific activities. The observations of this study determined that nurses' time is accounted for 31.65% in direct care, 51.63% in indirect care and 16.71% in service related activities.

Visual demands in modern Australian primary school classrooms

BACKGROUND The visual demands of modern classrooms are poorly understood yet are relevant in determining the levels of visual function required to perform optimally within this environment. METHODS Thirty-three Year 5 and 6 classrooms from eight south-east Queensland schools were included. Classroom activities undertaken during a full school day (9 am to 3 pm) were observed and a range of measurements recorded, including classroom environment (physical dimensions, illumination levels), text size and contrast of learning materials, habitual working distances (distance and estimated for near) and time spent performing various classroom tasks. These measures were used to calculate demand-related minimum criteria for distance and near visual acuity, contrast and sustained use of accommodation and vergence. RESULTS The visual acuity demands for distance and near were 0.33 ± 0.13 and 0.72 ± 0.09 logMAR, respectively (using habitual viewing distances and smallest target sizes) or 0.33 ± 0.09 logMAR assuming a 2.5 times acuity reserve for sustained near tasks. The mean contrast levels of learning materials at distance and near were greater than 70 per cent. Near tasks (47 per cent) dominated the academic tasks performed in the classroom followed by distance (29 per cent), distance to near (15 per cent) and computer-based (nine per cent). On average, children engaged in continuous near fixation for 23 ± 5 minutes at a time and during distance-near tasks performed fixation changes 10 ± 1 times per minute. The mean estimated habitual near working distance was 23 ± 1 cm (4.38 ± 0.24 D accommodative demand) and the vergence demand was 0.86 ± 0.07Δ at distance and 21.94 ± 1.09Δ at near assuming an average pupillary distance of 56 mm. CONCLUSIONS Relatively high levels of visual acuity, contrast demand and sustained accommodative-convergence responses are required to meet the requirements of modern classroom environments. These findings provide an evidence base to inform prescribing guidelines and develop paediatric vision screening protocols and referral criteria.

The development and inter-relationship of metacognitive components among primary school children

Much interest has been expressed in the construct metacognition, the individual's knowledge and control of his own cognitive processes. Recent educational proposals have suggested the training of general metacognitive principles in schools. The exact nature of the construct has, however, remained vague. The aim of the present study was to provide some clarity. In a study of the metacognitive responses of 144 primary school children (aged 7‐11 years) four measures commonly used to assess metacognitive function were examined. First, the content of each measure was examined. Secondly, in an attempt to identify a metacognitive factor, commonality among the measures, both of developmental patterns and statistical relationship, was sought. Whilst a common pattern of development in the children's responses to the four measures was identified, factor analysis failed to provide evidence for a common metacognitive factor and unified construct.

Soliciting additional concerns in the primary care consultation and the utility of a brief communication intervention to aid solicitation: A qualitative study

Objective To investigate the perspectives of general practitioners (GPs) on the practice of soliciting additional concerns (ACs) and the acceptability and utility of two brief interventions (prompts) designed to aid the solicitation. Methods Eighteen GPs participating in a feasibility randomised controlled trial were interviewed. Interviews were semi-structured and audio-recorded. Data were analysed using a Framework Approach. Results Participants perceived eliciting ACs as important for: reducing the need for multiple visits, identifying serious illness early, and increasing patient and GP satisfaction. GPs found the prompts easy to use and some continued their use after the study had ended to aid time management. Others noted similarities between the intervention and their usual practice. Nevertheless, soliciting ACs in every consultation was not unanimously supported. Conclusion The prompts were acceptable to GPs within a trial context, but there was disagreement as to whether ACs should be solicited routinely. Some GPs considered the intervention to aid their prioritisation efficiency within consultations. Practice implications Some GPs will find prompts which encourage ACs to be solicited early in the consultation enable them to better organise priorities and manage time-limited consultations more effectively.

Evaluating the risk of mixtures in the indoor air of primary school classrooms

In school environments, children are constantly exposed to mixtures of airborne substances, derived from a variety of sources, both in the classroom and in the school surroundings. It is important to evaluate the hazardous properties of these mixtures, in order to conduct risk assessments of their impact on chil¬dren’s health. Within this context, through the application of a Maximum Cumulative Ratio approach, this study aimed to explore whether health risks due to indoor air mixtures are driven by a single substance or are due to cumulative exposure to various substances. This methodology requires knowledge of the concentration of substances in the air mixture, together with a health related weighting factor (i.e. reference concentration or lowest concentration of interest), which is necessary to calculate the Hazard Index. Maximum cumulative ratio and Hazard Index values were then used to categorise the mixtures into four groups, based on their hazard potential and therefore, appropriate risk management strategies. Air samples were collected from classrooms in 25 primary schools in Brisbane, Australia. Analysis was conducted based on the measured concentration of these substances in about 300 air samples. The results showed that in 92% of the schools, indoor air mixtures belonged to the ‘low concern’ group and therefore, they did not require any further assessment. In the remaining schools, toxicity was mainly governed by a single substance, with a very small number of schools having a multiple substance mix which required a combined risk assessment. The proposed approach enables the identification of such schools and thus, aides in the efficient health risk management of pollution emissions and air quality in the school environment.

Primary brain tumor patients’ supportive care needs and multidisciplinary rehabilitation, community and psychosocial support services: Awareness, referral and utilization

Primary brain tumors are associated with significant physical, cognitive and psychosocial changes. Although treatment guidelines recommend offering multidisciplinary rehabilitation and support services to address patients’ residual deficits, the extent to which patients access such services is unclear. This study aimed to assess patients’ supportive care needs early after diagnosis, and quantify service awareness, referral and utilization. A population-based sample of 40 adults recently diagnosed with primary brain tumors was recruited through the Queensland Cancer Registry, representing 18.9% of the eligible population of 203 patients. Patients or carer proxies completed surveys of supportive care needs at baseline (approximately three months after diagnosis) and three months later. Descriptive statistics summarized needs and service utilization, and linear regression identified predictors of service use. Unmet supportive care needs were highest at baseline for all domains, and highest for the physical and psychological needs domains at each time point. At follow-up, participants reported awareness of, referral to, and use of 32 informational, support, health professional or practical services. All or almost all participants were aware of at least one informational (100%), health professional (100%), support (97%) or practical service (94%). Participants were most commonly aware of speech therapists (97%), physiotherapists (94%) and diagnostic information from the internet (88%). Clinician referrals were most commonly made to physiotherapists (53%), speech therapists (50%) and diagnostic information booklets (44%), and accordingly, participants most commonly used physiotherapists (56%), diagnostic information booklets (47%), diagnostic information from the internet (47%), and speech therapists (43%). Comparatively low referral to and use of psychosocial services may limit patients’ abilities to cope with their condition and the changes they experience.

What does the review of the Australian Curriculum mean for History in the Primary Years?

The recent introduction of the Australian Curriculum: History as a timetabled school subject has enhanced the teaching of history in the primary years. Previously, history was integrated with geography, economics and civics and citizenship; however, in the new curriculum students are introduced to history from their first year at school. The review addresses significant concerns about the scope and content in history in an over-crowded primary curriculum (Donnelly & Wiltshire, 2014; APPA, 2014). However, the history curriculum provides a rare opportunity to explore distinctive content and develop agency by investigating personal, local, national and international contexts. This paper examines the recommendations of the review and the implications for history in the primary years.

Tipping points: Teachers' reported reasons for referring primary school children for excessive anxiety

The current study explored the reasons that primary school teachers reported were tipping points for them in deciding whether or not and when to refer a child to the school student support team for excessive anxiety. Twenty teachers in two Queensland primary schools were interviewed. Content analysis of interview transcripts revealed six themes reflecting teachers' perceived reasons for deciding to refer anxious children: 1)impact on learning; 2)atypical child behavior; 3)repeated difficulties that do not improve over time; 4)poor response to strategies; 5)teachers' need for support; and 6)information from parents/carers. Teachers considered different combinations of reasons, and had many different tipping points for making a referral. Both teacher-and system-level influences impacted referral decisions. Implications and future research are discussed.

The changing experiences of primary teachers: Responding to scenarios involving diverse sexualities

Sex education and diverse sexualities are controversial topics within the primary school arena. Concepts of childhood innocence have influenced sex education curriculum, policy development and teaching practices within schools. However, research shows that primary school-aged students are aware of and talk about sexualities. The aim of this research is to reveal the pedagogical experiences of primary school teachers in relation to scenarios inclusive of diverse sexualities. Social constructionist theories of pedagogy and phenomenographic methods are used to provide a detailed analysis of the ways in which primary teacher participants conceptualise their encounters with students who introduce concepts of diverse sexualities. This research reveals that primary students ask questions about diverse sexualities, they use homophobic expressions (often as a daily occurrence), they sometimes reveal homosexual feelings to teachers, some have same-sex parents and some are being raised with knowledge of diverse sexualities. Without comprehensive policy and curriculum support, and appropriate professional learning for teachers, teachers are unable to make well informed pedagogical decisions that promote inclusive education.

Effect of exercise referral schemes in primary care on physical activity and improving health outcomes: Systematic review and meta-analysis

Objective To assess the impact of exercise referral schemes on physical activity and health outcomes. Design Systematic review and meta-analysis. Data sources Medline, Embase, PsycINFO, Cochrane Library, ISI Web of Science, SPORTDiscus, and ongoing trial registries up to October 2009. We also checked study references. Study selection - Design: randomised controlled trials or non-randomised controlled (cluster or individual) studies published in peer review journals. - Population: sedentary individuals with or without medical diagnosis. - Exercise referral schemes defined as: clear referrals by primary care professionals to third party service providers to increase physical activity or exercise, physical activity or exercise programmes tailored to individuals, and initial assessment and monitoring throughout programmes. - Comparators: usual care, no intervention, or alternative exercise referral schemes. Results Eight randomised controlled trials met the inclusion criteria, comparing exercise referral schemes with usual care (six trials), alternative physical activity intervention (two), and an exercise referral scheme plus a self determination theory intervention (one). Compared with usual care, follow-up data for exercise referral schemes showed an increased number of participants who achieved 90-150 minutes of physical activity of at least moderate intensity per week (pooled relative risk 1.16, 95% confidence intervals 1.03 to 1.30) and a reduced level of depression (pooled standardised mean difference −0.82, −1.28 to −0.35). Evidence of a between group difference in physical activity of moderate or vigorous intensity or in other health outcomes was inconsistent at follow-up. We did not find any difference in outcomes between exercise referral schemes and the other two comparator groups. None of the included trials separately reported outcomes in individuals with specific medical diagnoses. Substantial heterogeneity in the quality and nature of the exercise referral schemes across studies might have contributed to the inconsistency in outcome findings. Conclusions Considerable uncertainty remains as to the effectiveness of exercise referral schemes for increasing physical activity, fitness, or health indicators, or whether they are an efficient use of resources for sedentary people with or without a medical diagnosis.