The genetics of endurance : frequency of the ACTN3 R577X variant in Ironman World Championship athletes

Objectives To investigate the frequency of the ACTN3 R577X polymorphism in elite endurance triathletes, and whether ACTN3 R577X is significantly associated with performance time. Design Cross-sectional study. Methods Saliva samples, questionnaires, and performance times were collected for 196 elite endurance athletes who participated in the 2008 Kona Ironman championship triathlon. Athletes were of predominantly North American, European, and Australian origin. A one-way analysis of variance was conducted to compare performance times between genotype groups. Multiple linear regression analysis was performed to model the effect of questionnaire variables and genotype on performance time. Genotype and allele frequencies were compared to results from different populations using the chi-square test. Results Performance time did not significantly differ between genotype groups, and age, sex, and continent of origin were significant predictors of finishing time (age and sex: p < 5 × 10−6; continent: p = 0.003) though genotype was not. Genotype and allele frequencies obtained (RR 26.5%, RX 50.0%, XX 23.5%, R 51.5%, X 48.5%) were found to be not significantly different from Australian, Spanish, and Italian endurance athletes (p > 0.05), but were significantly different from Kenyan, Ethiopian, and Finnish endurance athletes (p < 0.01). Conclusions Genotype and allele frequencies agreed with those reported for endurance athletes of similar ethnic origin, supporting previous findings for an association between 577X allele and endurance. However, analysis of performance time suggests that ACTN3 does not alone influence endurance performance, or may have a complex effect on endurance performance due to a speed/endurance trade-off.

Association between maternal depressive symptoms in the early postnatal period and responsiveness in feeding at child age 2 years

Maternal depression is a known risk factor for poor outcomes for children. Pathways to these poor outcomes relate to reduced maternal responsiveness or sensitivity to the child. Impaired responsiveness potentially impacts the feeding relationship and thus may be a risk factor for inappropriate feeding practices. The aim of this study was to examine the longitudinal relationships between self-reported maternal post-natal depressive symptoms at child age 4 months and feeding practices at child age 2 years in a community sample. Participants were Australian first-time mothers allocated to the control group of the NOURISH randomized controlled trial when infants were 4 months old. Complete data from 211 mothers (of 346 allocated) followed up when their children were 2 years of age (51% girls) were available for analysis. The relationship between Edinburgh Postnatal Depression Scale (EPDS) score (child age 4 months) and child feeding practices (child age 2 years) was tested using hierarchical linear regression analysis adjusted for maternal and child characteristics. Higher EPDS score was associated with less responsive feeding practices at child age 2 years: greater pressure [β = 0.18, 95% confidence interval (CI): 0.04–0.32, P = 0.01], restriction (β = 0.14, 95% CI: 0.001–0.28, P = 0.05), instrumental (β = 0.14, 95% CI: 0.005–0.27, P = 0.04) and emotional (β = 0.15, 95% CI: 0.01–0.29, P = 0.03) feeding practices (ΔR2 values: 0.02–0.03, P < 0.05). This study provides evidence for the proposed link between maternal post-natal depressive symptoms and lower responsiveness in child feeding. These findings suggest that the provision of support to mothers experiencing some levels of depressive symptomatology in the early post-natal period may improve responsiveness in the child feeding relationship.

Frequency independence of ultrasound transit time spectroscopy

Recent studies have shown that ultrasound transit time spectroscopy (UTTS) is an alternative method to describe ultrasound wave propagation through complex samples as an array of parallel sonic rays. This technique has the potential to characterize bone properties including volume fraction and may be implemented in clinical systems to predict osteoporotic fracture risk. In contrast to broadband ultrasound attenuation, which is highly frequency dependent, we hypothesise that UTTS is frequency independent. This study measured 1 MHz and 5 MHz broadband ultrasound signals through a set of acrylic step-wedge samples. Digital deconvolution of the signals through water and each sample was applied to derive a transit time spectrum. The resulting spectra at both 1 MHz and 5 MHz were compared to the predicted transit time values. Linear regression analysis yields agreement (R2) of 99.23% and 99.74% at 1 MHz and 5 MHz respectively indicating frequency independence of transit time spectra.

Telomere length in circulating leukocytes is associated with lung function and disease

Several clinical studies suggest the involvement of premature ageing processes in chronic obstructive pulmonary disease (COPD). Using an epidemiological approach, we studied whether accelerated ageing indicated by telomere length, a marker of biological age, is associated with COPD and asthma, and whether intrinsic age-related processes contribute to the interindividual variability of lung function. Our meta-analysis of 14 studies included 934 COPD cases with 15 846 controls defined according to the Global Lungs Initiative (GLI) criteria (or 1189 COPD cases according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria), 2834 asthma cases with 28 195 controls, and spirometric parameters (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC) of 12 595 individuals. Associations with telomere length were tested by linear regression, adjusting for age, sex and smoking status. We observed negative associations between telomere length and asthma (β= −0.0452, p=0.024) as well as COPD (β= −0.0982, p=0.001), with associations being stronger and more significant when using GLI criteria than those of GOLD. In both diseases, effects were stronger in females than males. The investigation of spirometric indices showed positive associations between telomere length and FEV1 (p=1.07×10−7), FVC (p=2.07×10−5), and FEV1/FVC (p=5.27×10−3). The effect was somewhat weaker in apparently healthy subjects than in COPD or asthma patients. Our results provide indirect evidence for the hypothesis that cellular senescence may contribute to the pathogenesis of COPD and asthma, and that lung function may reflect biological ageing primarily due to intrinsic processes, which are likely to be aggravated in lung diseases.

The effect of LRP5 polymorphisms on bone mineral density is apparent in childhood

Bone mass acquired during childhood is the primary determinant of adult bone mineral density (BMD) and osteoporosis risk. Bone accrual is subject to genetic influences. Activating and inactivating LRP5 gene mutations elicit extreme bone phenotypes, while more common LRP5 polymorphisms are associated with normal variation of BMD. Our aim was to test the hypothesis that LRP5 gene polymorphisms influence bone mass acquisition during childhood. The association between LRP5 gene polymorphisms and bone size and mineralization was examined in 819 unrelated British Caucasian children (n = 429 boys) aged 9 years. Height, weight, pubertal status (where available), total-body and spinal bone area, bone mineral content (BMC), BMD, and area-adjusted BMC (aBMC) were assessed. Dual-energy X-ray absorptiometry (DXA)-gene associations were assessed by linear regression, with adjustment for age, gender, pubertal status, and body size parameters. There were 140, 79, 12, and 2 girls who achieved Tanner stages I-IV, respectively, and 179 and 32 boys who achieved Tanner stages I and II, respectively. The rs2306862 (N740N) coding polymorphism in exon 10 of the LRP5 gene was associated with spinal BMD and aBMC (each P = 0.01) and total-body BMD and aBMC (P = 0.04 and 0.03, respectively). Adjusting for pubertal stage strengthened associations between this polymorphism and spinal BMD and aBMC (P = 0.01 and 0.002, respectively). Individuals homozygous for the T allele had greater spinal BMD and aBMC scores than those homozygous for the C allele. A dose effect was apparent as the mean spinal BMD and aBMC of heterozygous TC individuals were intermediate between those of their TT and CC counterparts. The N740N polymorphism in exon 10 of LRP5 was associated with spinal BMD and aBMC in pre- and early pubertal children. These results indicate that LRP5 influences volumetric bone density in childhood, possibly through effects on trabecular bone formation.

Determinants of the citation rate of medical research publications from a developing country

Background The number of citations received by an article is considered as an objective marker judging the importance and the quality of the research work. The present study aims to study the determinants of citations for research articles published by Sri Lankan authors. Methods Papers were selectively retrieved from the SciVerse Scopus® (Elsevier Properties S.A, USA) database for 10 years from 1st January 1997 to 31st December 2006, of which 50% were selected for inclusion by simple random sampling. The primary outcome measure was citation rate (defined as the number of citations during the 2 subsequent years after publication). Citation data was collected using the SciVerse Scopus® Citation Analyzer and self citations were excluded. A linear regression analysis was performed with ‘number of citations’ as the continuous dependent variable and other independent variables. Result The number of publications has steadily increased during the period of study. Over three quarter of papers were published in international journals. More than half of publications were research studies (55.3%), and most of the research studies were descriptive cross-sectional studies (27.1%). The mean number of citations within 2 years of publication was 1.7 and 52.1% of papers were not cited within the first two years of publication. The mean number of citations for collaborative studies (2.74) was significantly higher than that of non-collaborative studies (0.66). The mean number of citations did not significantly change depending on whether the publication had a positive result (2.08) or not (2.92) and was also not influenced by the presence (2.30) or absence (1.99) of the main study conclusion in the title of the article. In the linear regression model, the journal rank, number of authors, conducting the study abroad, being a research study or systematic review/meta-analysis and having regional and/or international collaboration all significantly increased the number of citations. Conclusion The journal rank, number of authors, conducting the study abroad, being a research study or systematic review/meta-analysis and having regional and/or international collaboration all significantly increased the number of citations. However, the presence of a positive result in the study did not influence the citation rate.

Genetic analyses in a sample of individuals with high or low BMD shows association with multiple Wnt pathway genes

INTRODUCTION Although the high heritability of BMD variation has long been established, few genes have been conclusively shown to affect the variation of BMD in the general population. Extreme truncate selection has been proposed as a more powerful alternative to unselected cohort designs in quantitative trait association studies. We sought to test these theoretical predictions in studies of the bone densitometry measures BMD, BMC, and femoral neck area, by investigating their association with members of the Wnt pathway, some of which have previously been shown to be associated with BMD in much larger cohorts, in a moderate-sized extreme truncate selected cohort (absolute value BMD Z-scores = 1.5-4.0; n = 344). MATERIALS AND METHODS Ninety-six tag-single nucleotide polymorphism (SNPs) lying in 13 Wnt signaling pathway genes were selected to tag common genetic variation (minor allele frequency [MAF] > 5% with an r(2) > 0.8) within 5 kb of all exons of 13 Wnt signaling pathway genes. The genes studied included LRP1, LRP5, LRP6, Wnt3a, Wnt7b, Wnt10b, SFRP1, SFRP2, DKK1, DKK2, FZD7, WISP3, and SOST. Three hundred forty-four cases with either high or low BMD were genotyped by Illumina Goldengate microarray SNP genotyping methods. Association was tested either by Cochrane-Armitage test for dichotomous variables or by linear regression for quantitative traits. RESULTS Strong association was shown with LRP5, polymorphisms of which have previously been shown to influence total hip BMD (minimum p = 0.0006). In addition, polymorphisms of the Wnt antagonist, SFRP1, were significantly associated with BMD and BMC (minimum p = 0.00042). Previously reported associations of LRP1, LRP6, and SOST with BMD were confirmed. Two other Wnt pathway genes, Wnt3a and DKK2, also showed nominal association with BMD. CONCLUSIONS This study shows that polymorphisms of multiple members of the Wnt pathway are associated with BMD variation. Furthermore, this study shows in a practical trial that study designs involving extreme truncate selection and moderate sample sizes can robustly identify genes of relevant effect sizes involved in BMD variation in the general population. This has implications for the design of future genome-wide studies of quantitative bone phenotypes relevant to osteoporosis.

Measurement of stenotic carotid arterial compliance with MRI

Arterial compliance has been shown to correlate well with overall cardiovascular outcome and it may also be a potential risk factor for the development of atheromatous disease. This study assesses the utility of 2-D phase contrast Magnetic Resonance (MR) imaging with intra-sequence blood pressure measurement to determine carotid compliance and distensibility. 20 patients underwent 2-D phase contrast MR imaging and also ultrasound-based wall tracking measurements. Values for carotid compliance and distensibility were derived from the two different modalities and compared. Linear regression analysis was utilised to determine the extent of correlation between MR and ultrasound derived parameters. In those variables that could be directly compared, an agreement analysis was undertaken. MR measures of compliance showed a good correlation with measures based on ultrasound wall-tracking (r=0.61, 95% CI 0.34 to 0.81 p=0.0003). Vessels that had undergone carotid endarterectomy previously were significantly less compliant than either diseased or normal contralateral vessels (p=0.04). Agreement studies showed a relatively poor intra-class correlation coefficient (ICC) between diameter-based measures of compliance through either MR or ultrasound (ICC=0.14). MRI based assessment of local carotid compliance appears to be both robust and technically feasible in most subjects. Measures of compliance correlate well with ultrasound-based values and correlate best when cross-sectional area change is used rather than derived diameter changes. If validated by further larger studies, 2-D phase contrast imaging with intra-sequence blood pressure monitoring and off-line radial artery tonometry may provide a useful tool in further assessment of patients with carotid atheroma.

Intuitive interaction in a mixed reality system

Tangible physical systems are more intuitive than Intangible virtual Systems. Mixed reality systems are considered as an alternative to virtual systems, bringing advantages of tangible systems into an interaction. However, past research has mainly focussed on technical aspects of incorporating pervasive-ness and immersive-ness in the virtual systems. This paper reports on an empirical study of intuitive Interaction in a Mixed Reality game system for children and the design aspects that could facilitate intuitive Interaction in such systems. A related samples Friedman’s test showed that the Mixed Reality game system demonstrated more intuitive interactions than non-intuitive Interactions. A linear regression analysis further established that the variation in intuitive Interaction in the Mixed Reality system could be statistically significantly explained primarily by physical affordances offered by the Mixed Reality system and to a lesser extent by the perceived affordances in the system. Design guidelines to develop intuitive Mixed Reality systems are discussed. These guidelines should allow designers to exploit the wonders of advances in technology and at the same time allow users to directly interact with the physical real world. This will allow users to access maximal physical affordances, which are primary contributors to intuitive interaction in Tangible and Mixed Reality systems.

Temperature variation between neighboring days and mortality: a distributed lag non-linear analysis

Objectives To investigate whether a sudden temperature change between neighboring days has significant impact on mortality. Methods A Poisson generalized linear regression model combined with a distributed lag non-linear models was used to estimate the association of temperature change between neighboring days with mortality in a subtropical Chinese city during 2008–2012. Temperature change was calculated as the current day’s temperature minus the previous day’s temperature. Results A significant effect of temperature change between neighboring days on mortality was observed. Temperature increase was significantly associated with elevated mortality from non-accidental and cardiovascular diseases, while temperature decrease had a protective effect on non-accidental mortality and cardiovascular mortality. Males and people aged 65 years or older appeared to be more vulnerable to the impact of temperature change. Conclusions Temperature increase between neighboring days has a significant adverse impact on mortality. Further health mitigation strategies as a response to climate change should take into account temperature variation between neighboring days.

Contribution of take-out food consumption to socioeconomic differences in fruit and vegetable intake : a mediation analysis

Lower fruit and vegetable intake among socioeconomically disadvantaged groups has been well documented, and may be a consequence of a higher consumption of take-out foods. This study examined whether, and to what extent, take-out food consumption mediated (explained) the association between socioeconomic position and fruit and vegetable intake. A cross-sectional postal survey was conducted among 1500 randomly selected adults aged 25–64 years in Brisbane, Australia in 2009 (response rate = 63.7%, N = 903). A food frequency questionnaire assessed usual daily servings of fruits and vegetables (0 to 6), overall take-out consumption (times/week) and the consumption of 22 specific take-out items (never to ≥once/day). These specific take-out items were grouped into “less healthy” and “healthy” choices and indices were created for each type of choice (0 to 100). Socioeconomic position was ascertained by education. The analyses were performed using linear regression, and a bootstrap re-sampling approach estimated the statistical significance of the mediated effects. Mean daily serves of fruits and vegetables was 1.89 (SD 1.05) and 2.47 (SD 1.12) respectively. The least educated group were more likely to consume fewer serves of fruit (B= –0.39, p<0.001) and vegetables (B= –0.43, p<0.001) compared with the highest educated. The consumption of “less healthy” take-out food partly explained (mediated) education differences in fruit and vegetable intake; however, no mediating effects were observed for overall and “healthy” take-out consumption. Regular consumption of “less healthy” take-out items may contribute to socioeconomic differences in fruit and vegetable intake, possibly by displacing these foods.

Bayesian hierarchical analysis on crash prediction models

Traditional crash prediction models, such as generalized linear regression models, are incapable of taking into account the multilevel data structure, which extensively exists in crash data. Disregarding the possible within-group correlations can lead to the production of models giving unreliable and biased estimates of unknowns. This study innovatively proposes a -level hierarchy, viz. (Geographic region level – Traffic site level – Traffic crash level – Driver-vehicle unit level – Vehicle-occupant level) Time level, to establish a general form of multilevel data structure in traffic safety analysis. To properly model the potential cross-group heterogeneity due to the multilevel data structure, a framework of Bayesian hierarchical models that explicitly specify multilevel structure and correctly yield parameter estimates is introduced and recommended. The proposed method is illustrated in an individual-severity analysis of intersection crashes using the Singapore crash records. This study proved the importance of accounting for the within-group correlations and demonstrated the flexibilities and effectiveness of the Bayesian hierarchical method in modeling multilevel structure of traffic crash data.

A hybrid approach to combining CART and logistic regression for stock ranking

The benefits of applying tree-based methods to the purpose of modelling financial assets as opposed to linear factor analysis are increasingly being understood by market practitioners. Tree-based models such as CART (classification and regression trees) are particularly well suited to analysing stock market data which is noisy and often contains non-linear relationships and high-order interactions. CART was originally developed in the 1980s by medical researchers disheartened by the stringent assumptions applied by traditional regression analysis (Brieman et al. [1984]). In the intervening years, CART has been successfully applied to many areas of finance such as the classification of financial distress of firms (see Frydman, Altman and Kao [1985]), asset allocation (see Sorensen, Mezrich and Miller [1996]), equity style timing (see Kao and Shumaker [1999]) and stock selection (see Sorensen, Miller and Ooi [2000])...