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    Neighborhood Built Environment and Transport and Leisure Physical Activity: Findings Using Objective Exposure and Outcome Measures in New Zealand
    Witten, K ; Blakely, T ; Bagheri, N ; Badland, H ; Ivory, V ; Pearce, J ; Mavoa, S ; Hinckson, E ; Schofield, G (US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE, 2012-07)
    BACKGROUND: Evidence of associations between neighborhood built environments and transport-related physical activity (PA) is accumulating, but few studies have investigated associations with leisure-time PA. OBJECTIVE: We investigated associations of five objectively measured characteristics of the neighborhood built environment-destination access, street connectivity, dwelling density, land-use mix and streetscape quality-with residents' self-reported PA (transport, leisure, and walking) and accelerometer-derived measures of PA. METHODS: Using a multicity stratified cluster sampling design, we conducted a cross-sectional survey of 2,033 adults who lived in 48 New Zealand neighborhoods. Multilevel regression modeling, which was adjusted for individual-level (sociodemographic and neighborhood preference) and neighborhood-level (deprivation) confounders, was used to estimate associations of built environment with PA. RESULTS: We found that 1-SD increases in destination access, street connectivity, and dwelling density were associated with any versus no self-reported transport, leisure, or walking PA, with increased odds ranging from 21% [street connectivity with leisure PA, 95% confidence interval (CI): 0%, 47%] to 44% (destination accessibility with walking, 95% CI: 17%, 79%). Among participants who self-reported some PA, a 1-SD increase in street connectivity was associated with a 13% increase in leisure PA (95% CI: 0, 28%). SD increases in destination access, street connectivity, and dwelling density were each associated with 7% increases in accelerometer counts. CONCLUSIONS: Associations of neighborhood destination access, street connectivity, and dwelling density with self-reported and objectively measured PA were moderately strong, indicating the potential to increase PA through changes in neighborhood characteristics.
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    Linking GPS and travel diary data using sequence alignment in a study of children's independent mobility
    Mavoa, S ; Oliver, M ; Witten, K ; Badland, HM (BIOMED CENTRAL LTD, 2011-12-05)
    BACKGROUND: Global positioning systems (GPS) are increasingly being used in health research to determine the location of study participants. Combining GPS data with data collected via travel/activity diaries allows researchers to assess where people travel in conjunction with data about trip purpose and accompaniment. However, linking GPS and diary data is problematic and to date the only method has been to match the two datasets manually, which is time consuming and unlikely to be practical for larger data sets. This paper assesses the feasibility of a new sequence alignment method of linking GPS and travel diary data in comparison with the manual matching method. METHODS: GPS and travel diary data obtained from a study of children's independent mobility were linked using sequence alignment algorithms to test the proof of concept. Travel diaries were assessed for quality by counting the number of errors and inconsistencies in each participant's set of diaries. The success of the sequence alignment method was compared for higher versus lower quality travel diaries, and for accompanied versus unaccompanied trips. Time taken and percentage of trips matched were compared for the sequence alignment method and the manual method. RESULTS: The sequence alignment method matched 61.9% of all trips. Higher quality travel diaries were associated with higher match rates in both the sequence alignment and manual matching methods. The sequence alignment method performed almost as well as the manual method and was an order of magnitude faster. However, the sequence alignment method was less successful at fully matching trips and at matching unaccompanied trips. CONCLUSIONS: Sequence alignment is a promising method of linking GPS and travel diary data in large population datasets, especially if limitations in the trip detection algorithm are addressed.
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    Discharge Patterns of Human Tensor Palatini Motor Units during Sleep Onset
    Nicholas, CL ; Jordan, AS ; Heckel, L ; Worsnop, C ; Bei, B ; Saboisky, JP ; Eckert, DJ ; White, DP ; Malhotra, A ; Trinder, J (OXFORD UNIV PRESS INC, 2012-05-01)
    STUDY OBJECTIVES: Upper airway muscles such as genioglossus (GG) and tensor palatini (TP) reduce activity at sleep onset. In GG reduced muscle activity is primarily due to inspiratory modulated motor units becoming silent, suggesting reduced respiratory pattern generator (RPG) output. However, unlike GG, TP shows minimal respiratory modulation and presumably has few inspiratory modulated motor units and minimal input from the RPG. Thus, we investigated the mechanism by which TP reduces activity at sleep onset. DESIGN: The activity of TP motor units were studied during relaxed wakefulness and over the transition from wakefulness to sleep. SETTING: Sleep laboratory. PARTICIPANTS: Nine young (21.4 ± 3.4 years) males were studied on a total of 11 nights. INTERVENTION: Sleep onset. MEASUREMENTS AND RESULTS: Two TP EMGs (thin, hooked wire electrodes), and sleep and respiratory measures were recorded. One hundred twenty-one sleep onsets were identified (13.4 ± 7.2/subject), resulting in 128 motor units (14.3 ± 13.0/subject); 29% of units were tonic, 43% inspiratory modulated (inspiratory phasic 18%, inspiratory tonic 25%), and 28% expiratory modulated (expiratory phasic 21%, expiratory tonic 7%). There was a reduction in both expiratory and inspiratory modulated units, but not tonic units, at sleep onset. Reduced TP activity was almost entirely due to de-recruitment. CONCLUSIONS: TP showed a similar distribution of motor units as other airway muscles. However, a greater proportion of expiratory modulated motor units were active in TP and these expiratory units, along with inspiratory units, tended to become silent over sleep onset. The data suggest that both expiratory and inspiratory drive components from the RPG are reduced at sleep onset in TP.
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    Genetics of epilepsy The testimony of twins in the molecular era
    Vadlamudi, L ; Milne, RL ; Lawrence, K ; Heron, SE ; Eckhaus, J ; Keay, D ; Connellan, M ; Torn-Broers, Y ; Howell, RA ; Mulley, JC ; Scheffer, IE ; Dibbens, LM ; Hopper, JL ; Berkovic, SF (LIPPINCOTT WILLIAMS & WILKINS, 2014-09-16)
    OBJECTIVE: Analysis of twins with epilepsy to explore the genetic architecture of specific epilepsies, to evaluate the applicability of the 2010 International League Against Epilepsy (ILAE) organization of epilepsy syndromes, and to integrate molecular genetics with phenotypic analyses. METHODS: A total of 558 twin pairs suspected to have epilepsy were ascertained from twin registries (69%) or referral (31%). Casewise concordance estimates were calculated for epilepsy syndromes. Epilepsies were then grouped according to the 2010 ILAE organizational scheme. Molecular genetic information was utilized where applicable. RESULTS: Of 558 twin pairs, 418 had confirmed seizures. A total of 534 twin individuals were affected. There were higher twin concordance estimates for monozygotic (MZ) than for dizygotic (DZ) twins for idiopathic generalized epilepsies (MZ = 0.77; DZ = 0.35), genetic epilepsy with febrile seizures plus (MZ = 0.85; DZ = 0.25), and focal epilepsies (MZ = 0.40; DZ = 0.03). Utilizing the 2010 ILAE scheme, the twin data clearly demonstrated genetic influences in the syndromes designated as genetic. Of the 384 tested twin individuals, 10.9% had mutations of large effect in known epilepsy genes or carried validated susceptibility alleles. CONCLUSIONS: Twin studies confirm clear genetic influences for specific epilepsies. Analysis of the twin sample using the 2010 ILAE scheme strongly supported the validity of grouping the "genetic" syndromes together and shows this organizational scheme to be a more flexible and biologically meaningful system than previous classifications. Successful selected molecular testing applied to this cohort is the prelude to future large-scale next-generation sequencing of epilepsy research cohorts. Insights into genetic architecture provided by twin studies provide essential data for optimizing such approaches.
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    Rotavirus inhibits IFN-induced STAT nuclear translocation by a mechanism that acts after STAT binding to importin-α
    Holloway, G ; Dang, VT ; Jans, DA ; Coulson, BS (SOC GENERAL MICROBIOLOGY, 2014-08)
    The importance of innate immunity to rotaviruses is exemplified by the range of strategies evolved by rotaviruses to interfere with the IFN response. We showed previously that rotaviruses block gene expression induced by type I and II IFNs, through a mechanism allowing activation of signal transducer and activator of transcription (STAT) 1 and STAT2 but preventing their nuclear accumulation. This normally occurs through activated STAT1/2 dimerization, enabling an interaction with importin α5 that mediates transport into the nucleus. In rotavirus-infected cells, STAT1/2 inhibition may limit the antiviral actions of IFN produced early in infection. Here we further analysed the block to STAT1/2 nuclear accumulation, showing that activated STAT1 accumulates in the cytoplasm in rotavirus-infected cells. STAT1/2 nuclear accumulation was inhibited by rotavirus even in the presence of the nuclear export inhibitor Leptomycin B, demonstrating that enhanced nuclear export is not involved in STAT1/2 cytoplasmic retention. The ability to inhibit STAT nuclear translocation was completely conserved amongst the group A rotaviruses tested, including a divergent avian strain. Analysis of mutant rotaviruses indicated that residues after amino acid 47 of NSP1 are dispensable for STAT inhibition. Furthermore, expression of any of the 12 Rhesus monkey rotavirus proteins did not inhibit IFN-stimulated STAT1 nuclear translocation. Finally, co-immunoprecipitation experiments from transfected epithelial cells showed that STAT1/2 binds importin α5 normally following rotavirus infection. These findings demonstrate that rotavirus probably employs a novel strategy to inhibit IFN-induced STAT signalling, which acts after STAT activation and binding to the nuclear import machinery.
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    The Impact of Family History of Allergy on Risk of Food Allergy: A Population-Based Study of Infants
    Koplin, JJ ; Allen, KJ ; Gurrin, LC ; Peters, RL ; Lowe, AJ ; Tang, MLK ; Dharmage, SC (MDPI AG, 2013-11)
    The apparent rapid increase in IgE-mediated food allergy and its implications are now widely recognized, but little is known about the relationship between family history (an indirect measure of genetic risk) and the risk of food allergy. In a population-based study of 5,276 one year old infants (HealthNuts), the prevalence of oral food challenge-confirmed food allergy was measured. Associations between family history of allergic disease and food allergy in infants were examined using multiple logistic regression. Food allergy was diagnosed in 534 infants. Compared to those with no family history of allergic disease, children meeting the current definition of "high risk" for allergic disease (one immediate family member with a history of any allergic disease) showed only a modest increase (OR 1.4, 95% CI 1.1-1.7) in food allergy, while having two or more allergic family members was more strongly predictive of food allergy in the child (OR 1.8, 95% CI 1.5-2.3). There were also differences in the associations between family history and egg and peanut allergy in the child. Re-defining "high risk" as two or more allergic family members may be more useful for identification of groups with a significantly increased risk of food allergy both clinically and within research studies.