Removal of organic content from diesel exhaust particles alters cellular responses of primary human bronchial epithelial cells cultured at an air-liquid interface

Background Exposure to air pollutants, including diesel particulate matter, has been linked to adverse respiratory health effects. Inhaled diesel particulate matter contains adsorbed organic compounds. It is not clear whether the adsorbed organics or the residual components are more deleterious to airway cells. Using a physiologically relevant model, we investigated the role of diesel organic content on mediating cellular responses of primary human bronchial epithelial cells (HBECs) cultured at an air-liquid interface (ALI). Methods Primary HBECs were cultured and differentiated at ALI for at least 28 days. To determine which component is most harmful, we compared primary HBEC responses elicited by residual (with organics removed) diesel emissions (DE) to those elicited by neat (unmodified) DE for 30 and 60 minutes at ALI, with cigarette smoke condensate (CSC) as the positive control, and filtered air as negative control. Cell viability (WST-1 cell proliferation assay), inflammation (TNF-α, IL-6 and IL-8 ELISA) and changes in gene expression (qRT-PCR for HO-1, CYP1A1, TNF-α and IL-8 mRNA) were measured. Results Immunofluorescence and cytological staining confirmed the mucociliary phenotype of primary HBECs differentiated at ALI. Neat DE caused a comparable reduction in cell viability at 30 or 60 min exposures, whereas residual DE caused a greater reduction at 60 min. When corrected for cell viability, cytokine protein secretion for TNF-α, IL-6 and IL-8 were maximal with residual DE at 60 min. mRNA expression for HO-1, CYP1A1, TNF-α and IL-8 was not significantly different between exposures. Conclusion This study provides new insights into epithelial cell responses to diesel emissions using a physiologically relevant aerosol exposure model. Both the organic content and residual components of diesel emissions play an important role in determining bronchial epithelial cell response in vitro. Future studies should be directed at testing potentially useful interventions against the adverse health effects of air pollution exposure.

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.

Mutations in STIL, Encoding a Pericentriolar and Centrosomal Protein, Cause Primary Microcephaly

Primary microcephaly (MCPH) is an autosomal-recessive congenital disorder characterized by smaller-than-normal brain size and mental retardation. MCPH is genetically heterogeneous with six known loci: MCPH1-MCPH6. We report mapping of a novel locus, MCPH7, to chromosome 1p32.3-p33 between markers D1S2797 and D1S417, corresponding to a physical distance of 8.39 Mb. Heterogeneity analysis of 24 families previously excluded from linkage to the six known MCPH loci suggested linkage of five families (20.83%) to the MCPH7 locus. In addition, four families were excluded from linkage to the MCPH7 locus as well as all of the six previously known loci, whereas the remaining 15 families could not be conclusively excluded or included. The combined maximum two-point LOD score for the linked families was 5.96 at marker D1S386 at theta = 0.0. The combined multipoint LOD score was 6.97 between markers D1S2797 and D1S417. Previously, mutations in four genes, MCPH1, CDK5RAP2, ASPM, and CENPJ, that code for centrosomal proteins have been shown to cause this disorder. Three different homozygous mutations in STIL, which codes for a pericentriolar and centrosomal protein, were identified in patients from three of the five families linked to the MCPH7 locus; all are predicted to truncate the STIL protein. Further, another recently ascertained family was homozygous for the same mutation as one of the original families. There was no evidence for a common haplotype. These results suggest that the centrosome and its associated structures are important in the control of neurogenesis in the developing human brain.

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.

The nature of non-equilibrium solidification of undercooled Agsingle bondCu alloys in contact with primary copper dendrites

Liquids of silver-copper alloys with near eutectic compositions embedded in a copper matrix were undercooled. The structural and microstructural investigations of these alloys solidified from undercooled temperature indicated the absence of both the eutectic reaction and diffusionless transformation below the equal free energy curve (T0). Instead the liquid maintained local equilibrium with the copper dendrites continuously until it intersected the extended solidus of the silver rich solid solution.

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.

Host recognition by a polyphagous lepidopteran (Helicoverpa armigera): Primary host plants, host produced volatiles and neurosensory stimulation

An important question in the host-finding behaviour of a polyphagous insect is whether the insect recognizes a suite or template of chemicals that are common to many plants? To answer this question, headspace volatiles of a subset of commonly used host plants (pigeon pea, tobacco, cotton and bean) and nonhost plants (lantana and oleander) of Helicoverpa armigera Hübner (Lepidoptera: Noctuidae) are screened by gas chromatography (GC) linked to a mated female H. armigera electroantennograph (EAG). In the present study, pigeon pea is postulated to be a primary host plant of the insect, for comparison of the EAG responses across the test plants. EAG responses for pigeon pea volatiles are also compared between females of different physiological status (virgin and mated females) and the sexes. Eight electrophysiologically active compounds in pigeon pea headspace are identified in relatively high concentrations using GC linked to mass spectrometry (GC-MS). These comprised three green leaf volatiles [(2E)-hexenal, (3Z)-hexenylacetate and (3Z)-hexenyl-2-methylbutyrate] and five monoterpenes (α-pinene, β-myrcene, limonene, E-β-ocimene and linalool). Other tested host plants have a smaller subset of these electrophysiologically active compounds and even the nonhost plants contain some of these compounds, all at relatively lower concentrations than pigeon pea. The physiological status or sex of the moths has no effect on the responses for these identified compounds. The present study demonstrates how some host plants can be primary targets for moths that are searching for hosts whereas the other host plants are incidental or secondary targets.

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.

School and choice : Anethnography of a primary school with bilingual classes

Based on a one-year ethnographic study of a primary school in Finland with specialised classes in Finnish and English (referred to as bilingual classes by research participants), this research traces patterns of how nationed, raced, classed and gendered differences are produced and gain meaning in school. I examine several aspects of these differences: the ways the teachers and parents make sense of school and of school choice; the repertoires of self put forward by teachers, parents and pupils of the bilingual classes; and the insitutional and classroom practices in Sunny Lane School (pseudonym). My purpose is to examine how the construction of differentness is related to the policy of school choice. I approach this questions from a knowledge problematic, and explore connections and disjunctions between the interpretations of teachers and those of parents, as well as between what teachers and parents expressed or said and the practices they engaged in. My data consists of fieldnotes generated through a one-year period of ethnographic study in Sunny Lane School, and of ethnographic interviews with teachers and parents primarily of the bilingual classes. This data focuses on the initial stages of the bilingual classes, which included the application and testing processes for these classes, and on Grades 1─3. In my analysis, I pursue poststructural feminist theorisations on questions of knowledge, power and subjectivity, which foreground an understanding of the constitutive force of discourse and the performative, partial, and relational nature of knowledge. I begin by situating my ethnographic field in relation to wider developments, namely, the emergence of school choice and the rhetoric of curricular reform and language education in Finland. I move on from there to ask how teachers discuss the introduction of these specialised classes, then trace pupils paths to these classes, their parents goals related to school choice, teachers constructions of the pupils and parents of bilingual classes, and how these shape the ways in which school and classroom practices unfold. School choice, I argue, functioned as a spatial practice, defining who belongs in school and demarcating the position of teachers, parents and pupils in school. Notions of classed and ethnicised differences entered the ways teachers and parents made sense of school choice. Teachers idealised school in terms of social cohesiveness and constructed social cohesion as a task for school to perform. The hopes parents iterated were connected to ensuring their children s futurity, to their perceptions of the advantages of fluency in English, but also to the differences they believed to exist between the social milieus of different schools. Ideals such as openmindedness and cosmopolitanism were also articulated by parents, and these ideals assumed different content for ethnic majority and minority parents. Teachers discussed the introduction of bilingual classes as being a means to ensure the school s future, and emphasised bilingual classes as fitting into the rubric of Finnish comprehensive schooling which, they maintained, is committed to equality. Parents were expected to accommodate their views and adopt the position of the responsible, supportive parent that was suggested to them by teachers. Teachers assumed a posture teachers of appreciating different cultures, while maintaining Finnishness as common ground in school. Discussion on pupils knowledge and experience of other countries took place often in bilingual classes, and various cultural theme events were organized on occasion. In school, pupils are taught to identify themselves in terms of cultural belonging. The rhetoric promoted by teachers was one of inclusiveness, which was also applied to describe the task of qualifying pupils for bilingual classes, qualifying which pupils can belong. Bilingual classes were idealised as taking a neutral, impartial posture toward difference by ethnic majority teachers and parents, and the relationship of school choice to classed advantage, for example, was something teachers, as well as parents, preferred not to discuss. Pupils were addressed by teachers during lessons in ways that assumed self responsibility and diligence, and they assumed the discursive category of being good, competent pupils made available to them. While this allowed them to position themselves favourably in school, their participation in a bilingual class was marked by the pressure to succeed well in school.

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.