Association between a 19 bp deletion polymorphism at the dopamine beta-hydroxylase (DBH) locus and migraine with aura

Migraine is a debilitating neurological disorder, affecting 12% of Caucasian populations. It is well known that migraine has a strong genetic component, although the type and number of genes involved is unclear. Our previous work has investigated dopamine related migraine candidate genes and has reported a significant allelic association with migraine of a microsatellite localised to the promoter region of the dopamine beta-hydroxylase (DBH) gene. The present study performed an association analysis in a larger population of case-controls (275 unrelated Caucasian migraineurs versus 275 controls) examining two different genetic DBH polymorphisms (a functional insertion/deletion promoter and a coding SNP A444G polymorphism). Although no significant association was found for the SNP polymorphism, the results showed a significant association between the insertion/deletion variant and disease (chi(2)=8.92, P=0.011), in particular in migraine with aura (chi(2)=11.53, P=0.003) compared to the control group. Furthermore, the analysis of this polymorphism stratified by gender, revealed that male individuals with the homozygote deletion genotype had three times the risk of developing migraine, compared to females. The DBH insertion/deletion polymorphism is in linkage disequilibrium with the previously reported migraine associated DBH microsatellite and this insertion/deletion polymorphism is functional, which may explain a potential role in susceptibility to migraine.

Dopamine receptor genes and migraine with and without aura : an association study

OBJECTIVE: To investigate the role of the dopamine receptor genes, DRD1, DRD3, and DRD5 in the pathogenesis of migraine. BACKGROUND: Migraine is a chronic debilitating disorder affecting approximately 12% of the white population. The disease shows strong familial aggregation and presumably has a genetic basis, but at present, the type and number of genes involved is unclear. The study of candidate genes can prove useful in the identification of genes involved in complex diseases such as migraine, especially if the contribution of the gene to phenotypic expression is minor. Genes coding for proteins involved in dopamine metabolism have been implicated in a number of neurologic conditions and may play a contributory role in migraine. Hence, genes that code for enzymes and receptors modulating dopaminergic activity are good candidates for investigation of the molecular genetic basis of migraine. METHODS: We tested 275 migraineurs and 275 age- and sex-matched individuals free of migraine. Genotypic results were determined by restriction endonuclease digestion of polymerase chain reaction products to detect DRD1 and DRD3 alleles and by Genescan analysis after polymerase chain reaction using fluorescently labelled oligonucleotide primers for the DRD5 marker. RESULTS: Results of chi-square statistical analyses indicated that the allele distribution for migraine cases compared to controls was not significantly different for any of the three tested gene markers (chi2 = 0.1, P =.74 for DRD1; chi2 = 1.8, P =.18 for DRD3; and chi2 = 20.3, P =.08 for DRD5). CONCLUSIONS: These findings offer no evidence for allelic association between the tested dopamine receptor gene polymorphisms and the more prevalent forms of migraine and, therefore, do not support a role for these genes in the pathogenesis of the disorder.

Mixing higher education teaching and learning with mobile devices and social media

The use of mobile devices and social media technologies are becoming all-pervasive in society: they are both transformative and constant. The high levels of mobile device ownership and increased access to social media technologies enables the potential for ‘anytime, anywhere’ cooperation and collaboration in education. While recent reports into emerging technologies in higher education predict an increase in the use of mobile devices and social media technologies (Horizon Report, 2013), there is a lack of theory-based research to indicate how these technologies can be most effectively harnessed to support and enhance student learning and what the impacts of these technologies are on both students and educators. In response to the need to understand how these technologies can be better embraced within higher education, this study investigated how first year education students used mobile devices and social media technologies. More specifically, the study identified how students spent most of their time when connected online with mobile devices and social media technologies and whether the online connected time engaged them in their learning or whether it was a distraction.

Engineering based problem solving in the middle school : design and construction with simple machines

Incorporating engineering concepts into middle school curriculum is seen as an effective way to improve students’ problem-solving skills. A selection of findings is reported from a science, technology, engineering and mathematics (STEM)-based unit in which students in the second year (grade 8) of a three-year longitudinal study explored engineering concepts and principles pertaining to the functioning of simple machines. The culminating activity, the focus of this paper, required the students to design, construct, test, and evaluate a trebuchet catapult. We consider findings from one of the schools, a co-educational school, where we traced the design process developments of four student groups from two classes. The students’ descriptions and explanations of the simple machines used in their catapult design are examined, together with how they rated various aspects of their engineering designs. Included in the findings are students’ understanding of how their simple machines were simulated by the resources supplied and how the machines interacted in forming a complex machine. An ability to link physical materials with abstract concepts and an awareness of design constraints on their constructions were apparent, although a desire to create a ‘‘perfect’’ catapult despite limitations in the physical materials rather than a prototype for testing concepts was evident. Feedback from teacher interviews added further insights into the students’ developments as well as the teachers’ professional learning. An evolving framework for introducing engineering education in the pre-secondary years is proposed.

Living the indie life : mapping creative teams in a 48 hour game jam and playing with data

In contemporary game development circles the ‘game making jam’ has become an important rite of passage and baptism event, an exploration space and a central indie lifestyle affirmation and community event. Game jams have recently become a focus for design researchers interested in the creative process. In this paper we tell the story of an established local game jam and our various documentation and data collection methods. We present the beginnings of the current project, which seeks to map the creative teams and their process in the space of the challenge, and which aims to enable participants to be more than the objects of the data collection. A perceived issue is that typical documentation approaches are ‘about’ the event as opposed to ‘made by’ the participants and are thus both at odds with the spirit of the jam as a phenomenon and do not really access the rich playful potential of participant experience. In the data collection and visualisation projects described here, we focus on using collected data to re-include the participants in telling stories about their experiences of the event as a place-based experience. Our goal is to find a means to encourage production of ‘anecdata’ - data based on individual story telling that is subjective, malleable, and resists collection via formal mechanisms - and to enable mimesis, or active narrating, on the part of the participants. We present a concept design for data as game based on the logic of early medieval maps and we reflect on how we could enable participation in the data collection itself.

A critical analysis of business process management education and alignment with industry demand : an Australian perspective

Business Process Management (BPM) is accepted globally as an organizational approach to enhance productivity and drive cost efficiencies. Studies confirm a shortage of BPM skilled professionals with limited opportunities to develop the required BPM expertise. This study investigates this gap starting from a critical analysis of BPM courses offered by Australian universities and training institutions. These courses were analyzed and mapped against a leading BPM capability framework to determine how well current BPM education and training offerings in Australia address the core capabilities required by BPM professionals globally. To determine the BPM skill-sets sought by industry, online recruitment advertisements were collated, analyzed, and mapped against this BPM capability framework. The outcomes provide a detailed overview on the alignment of available BPM education/training and industry demand. These insights are useful for BPM professionals and their employers to build awareness of the BPM capabilities required for a BPM mature organization. Universities and other training institutions will benefit from these results by understanding where demand is, where the gaps are, and what other BPM education providers are supplying. This structured comparison method could continue to provide a common ground for future discussion across university-industry boundaries and continuous alignment of their respective practices.

Visually impaired drivers who use bioptic telescopes : self-assessed driving skills and agreement with on-road driving evaluation

Purpose. To compare self-assessed driving habits and skills of licensed drivers with central visual loss who use bioptic telescopes to those of age-matched normally sighted drivers, and to examine the association between bioptic drivers' impressions of the quality of their driving and ratings by a “backseat” evaluator. Methods. Participants were licensed bioptic drivers (n = 23) and age-matched normally sighted drivers (n = 23). A questionnaire was administered addressing driving difficulty, space, quality, exposure, and, for bioptic drivers, whether the telescope was helpful in on-road situations. Visual acuity and contrast sensitivity were assessed. Information on ocular diagnosis, telescope characteristics, and bioptic driving experience was collected from the medical record or in interview. On-road driving performance in regular traffic conditions was rated independently by two evaluators. Results. Like normally sighted drivers, bioptic drivers reported no or little difficulty in many driving situations (e.g., left turns, rush hour), but reported more difficulty under poor visibility conditions and in unfamiliar areas (P < 0.05). Driving exposure was reduced in bioptic drivers (driving 250 miles per week on average vs. 410 miles per week for normally sighted drivers, P = 0.02), but driving space was similar to that of normally sighted drivers (P = 0.29). All but one bioptic driver used the telescope in at least one driving task, and 56% used the telescope in three or more tasks. Bioptic drivers' judgments about the quality of their driving were very similar to backseat evaluators' ratings. Conclusions. Bioptic drivers show insight into the overall quality of their driving and areas in which they experience driving difficulty. They report using the bioptic telescope while driving, contrary to previous claims that it is primarily used to pass the vision screening test at licensure.

Perceptions of the built environment and associations with walking among retirement village residents

Housing options, such as retirement villages, that promote and encourage healthy behaviors are needed to accommodate the growing older adult population. To examine how environmental perceptions relate to walking, residents of retirement villages in Perth, Australia, were sampled, and associations between a wide range of village and neighborhood environmental attributes and walking leisurely, briskly, and for transport were examined. Perceived village features associated with walking included aesthetics (odds ratio [OR] = 1.72), personal safety (OR = 0.43), and services and facilities (OR = 0.80), whereas neighborhood attributes included fewer physical barriers (OR = 1.37) and proximate destinations (OR = 1.93). Findings suggest that locating retirement villages in neighborhoods with many local destinations may encourage more walking than providing many services and facilities within villages. Indeed, safe villages rich with amenities were shown to be related to less walking in residents. These findings have implications for the location, design, and layout of retirement villages.

Vascular remodeling in the internal mammary artery graft and association with in situ endothelin-1 and receptor expression

BACKGROUND: The vasoconstricting peptide endothelin-1 (ET-1) has been associated with atherosclerotic cardiovascular disease, vascular smooth muscle cell (VSMC) growth stimulation, and intimal thickening. ET-1 binds 2 receptor subtypes, endothelin A and B, and the ETA receptor mediates vasoconstriction and VSMC growth. This study aims to quantitatively assess arterial remodeling variables and compare them with changes in ET-1, ETA, and ETB expression in the internal mammary artery (IMA). METHODS AND RESULTS: Specimens from 55 coronary artery disease (CAD) patients (45 men, 10 women; mean age 65 years) and 14 control IMA specimens (from 7 men and 7 women; mean age 45 years) were collected. IMA cross sections were assessed by histochemical and immunohistochemical staining methods to quantify the levels of medionecrosis, fibrosis, VSMC growth, ET-1, ETA, ETB, and macrophage infiltration. The percentage area of medionecrosis in the patients was almost double that in the controls (31.85+/-14.52% versus 17.10+/-9.96%, P=0.0006). Total and type 1 collagen was significantly increased compared with controls (65.8+/-18.3% versus 33.7+/-13.7%, P=0.07, and 14.2+/-10.0% versus 4.8+/-2.8%, P=0.01, respectively). Despite ACE and/or statin therapy, ET-1 expression and cell cycling were significantly elevated in the patient IMAs relative to the controls (46.27+/-18.46 versus 8.56+/-8.42, P=0.0001, and 37.29+/-12.88 versus 11.06+/-8.18, P=0.0001, respectively). ETA and ETB staining was elevated in the patient vessels (46.88+/-11.52% versus 18.58+/-7.65%, P=0.0001, and 42.98+/-7.08% versus 34.73+/-5.20%, P=0.0067, respectively). A mild presence of macrophages was noted in all sections. CONCLUSIONS: Elevated distribution of collagen indicative of fibrosis coupled with increased cell cycling and high levels of ET-1 and ETA expression in the absence of chronic inflammation suggests altered IMA VSMC regulation is fundamental to the remodeling process.

Thromboxane synthase expression and correlation with VEGF and angiogenesis in non-small cell lung cancer

Background Thromboxane synthase (TXS) metabolizes prostaglandin H2 into thromboxanes, which are biologically active on cancer cells. TXS over-expression has been reported in a range of cancers, and associated with angiogenesis and poor outcome. TXS has been identified as a potential therapeutic target in NSCLC. This study examines a link between TXS expression, angiogenesis, and survival in NSCLC. Methods TXS and VEGF metabolite levels were measured in NSCLC serum samples (n=46) by EIA. TXB2 levels were correlated with VEGF. A 204-patient TMA was stained for TXS, VEGF, and CD-31 expression. Expression was correlated with a range of clinical parameters, including overall survival. TXS expression was correlated with VEGF and CD-31. Stable TXS clones were generated and the effect of overexpression on tumor growth and angiogenesis markers was examined in-vitro and in-vivo (xenograft mouse model). Results Serum TXB2 levels were correlated with VEGF (p<0.05). TXS and VEGF were expressed to a varying degree in NSCLC tissue. TXS was associated with VEGF (p<0.0001) and microvessel density (CD-31; p<0.05). TXS and VEGF expression levels were higher in adenocarcinoma (p<0.0001) and female patients (p<0.05). Stable overexpression of TXS increased VEGF secretion in-vitro. While no significant association with patient survival was observed for either TXS or VEGF in our patient cohort, TXS overexpression significantly (p<0.05) increased tumor growth in-vivo. TXS overexpression was also associated with higher levels of VEGF, microvessel density, and reduced apoptosis in xenograft tumors. Conclusion TXS promotes tumor growth in-vivo in NSCLC, an effect which is at least partly mediated through increased tumor angiogenesis.

“Best for everyone concerned” or “Only as a last resort”? Views of Australian doctors about sterilisation of men and women with intellectual disability

Background  Doctors have the potential to influence opportunities for normative life experiences in the area of sexuality for individuals with intellectual disability (ID). Method  In Study One, 106 doctors completed the Attitudes to Sexuality Questionnaire (Individuals with an Intellectual Disability). In Study Two, 97 doctors completed a modified form of the questionnaire that included additional questions designed to assess their views about sterilisation. Results  Attitudes were less positive about parenting than about other aspects of sexuality, and less sexual freedom was seen as desirable for adults with ID. A surprising number of doctors agreed that sterilisation was a desirable practice. Study Two provided data about the conditions under which sterilisation was endorsed. Most doctors reported they had not been approached to perform sterilisations. Only 12% believed medical practitioners receive sufficient training in the area of disability and sexuality. Conclusions  The findings have implications for training and professional development for doctors.

Assessment of gene expression of intracellular calcium channels, pumps and exchangers with epidermal growth factor-induced epithelial-mesenchymal transition in a breast cancer cell line

Background Epithelial-mesenchymal transition (EMT) is a process implicated in cancer metastasis that involves the conversion of epithelial cells to a more mesenchymal and invasive cell phenotype. In breast cancer cells EMT is associated with altered store-operated calcium influx and changes in calcium signalling mediated by activation of cell surface purinergic receptors. In this study, we investigated whether MDA-MB-468 breast cancer cells induced to undergo EMT exhibit changes in mRNA levels of calcium channels, pumps and exchangers located on intracellular calcium storing organelles, including the Golgi, mitochondria and endoplasmic reticulum (ER). Methods Epidermal growth factor (EGF) was used to induce EMT in MDA-MB-468 breast cancer cells. Serum-deprived cells were treated with EGF (50 ng/mL) for 12 h and gene expression was assessed using quantitative RT-PCR. Results and conclusions These data reveal no significant alterations in mRNA levels of the Golgi calcium pump secretory pathway calcium ATPases (SPCA1 and SPCA2), or the mitochondrial calcium uniporter (MCU) or Na+/Ca2+ exchanger (NCLX). However, EGF-induced EMT was associated with significant alterations in mRNA levels of specific ER calcium channels and pumps, including (sarco)-endoplasmic reticulum calcium ATPases (SERCAs), and inositol 1,4,5-trisphosphate receptor (IP3R) and ryanodine receptor (RYR) calcium channel isoforms. The most prominent change in gene expression between the epithelial and mesenchymal-like states was RYR2, which was enriched 45-fold in EGF-treated MDA-MB-468 cells. These findings indicate that EGF-induced EMT in breast cancer cells may be associated with major alterations in ER calcium homeostasis.

Validity of accelerometry in ambulatory children and adolescents with cerebral palsy

To evaluate the validity of the ActiGraph accelerometer for the measurement of physical activity intensity in children and adolescents with cerebral palsy (CP) using oxygen uptake (VO 2) as the criterion measure. Thirty children and adolescents with CP (mean age 12.6 ± 2.0 years) wore an ActiGraph 7164 and a Cosmed K4b 2 portable indirect calorimeter during four activities; quiet sitting, comfortable paced walking, brisk paced walking and fast paced walking. VO 2 was converted to METs and activity energy expenditure and classiWed as sedentary, light or moderate-to-vigorous intensity according to the conventions for children. Mean ActiGraph counts min -1 were classiWed as sedentary, light or moderate-to-vigorous (MVPA) intensity using four diVerent sets of cut-points. VO 2 and counts min¡1 increased signiWcantly with increases in walking speed (P < 0.001). Receiver operating characteristic (ROC) curve analysis indicated that, of the four sets of cut-points evaluated, the Evenson et al. (J Sports Sci 26(14):1557-1565, 2008) cut-points had the highest classiWcation accuracy for sedentary (92%) and MVPA (91%), as well as the second highest classiWcation accuracy for light intensity physical activity (67%). A ROC curve analysis of data from our participants yielded a CP-speciWc cut-point for MVPA that was lower than the Evenson cut-point (2,012 vs. 2,296 counts min¡1), however, the diVerence in classiWcation accuracy was not statistically signiWcant 94% (95% CI = 88.2-97.7%) vs. 91% (95% CI = 83.5-96.5%). In conclusion, among children and adolescents with CP, the ActiGraph is able to diVerentiate between diVerent intensities of walking. The use of the Evenson cut-points will permit the estimation of time spent in MVPA and allows comparisons to be made between activity measured in typically developing adolescents and adolescents with CP. © 2011 Springer-Verlag.

Confirmatory factor analysis of the baby eating behaviour questionnaire and associations with infant weight, gender and feeding mode in an Australian sample

The aim of this study was to evaluate the factor structure of the Baby Eating Behaviour Questionnaire (BEBQ) in an Australian community sample of mother-infant dyads. A secondary aim was to explore the relationship between the BEBQ subscales and infant gender, weight and current feeding mode. Confirmatory factor analysis (CFA) utilising structural equation modelling examined the hypothesised 4-factor model of the BEBQ. Only mothers (N=467) who completed all items on the BEBQ (infant age: M=17 weeks, SD=3 weeks) were included in the analysis. The original 4-factor model did not provide an acceptable fit to the data due to poor performance of the Satiety responsiveness factor. Removal of this factor (3 items) resulted in a well-fitting 3-factor model. Cronbach’s α was acceptable for the Enjoyment of food (α=0.73), Food responsiveness (α=0.78) and Slowness in eating (α=0.68) subscales but low for the Satiety responsiveness (α=0.56) subscale. Enjoyment of food was associated with higher infant weight whereas Slowness in eating and Satiety responsiveness were both associated with lower infant weight. Differences on all four subscales as a function of feeding mode were observed. This study is the first to use CFA to evaluate the hypothesised factor structure of the BEBQ. Findings support further development work on the Satiety responsiveness subscale in particular, but confirm the utility of the Enjoyment of food, Food responsiveness and Slowness in eating subscales.