Association of SNPs in LCP1 and CTIF with hearing in 11 year old children:findings from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort and the G-EAR consortium

BACKGROUND: The genetic basis of hearing loss in humans is relatively poorly understood. In recent years, experimental approaches including laboratory studies of early onset hearing loss in inbred mouse strains, or proteomic analyses of hair cells or hair bundles, have suggested new candidate molecules involved in hearing function. However, the relevance of these genes/gene products to hearing function in humans remains unknown. We investigated whether single nucleotide polymorphisms (SNPs) in the human orthologues of genes of interest arising from the above-mentioned studies correlate with hearing function in children. METHODS: 577 SNPs from 13 genes were each analysed by linear regression against averaged high (3, 4 and 8 kHz) or low frequency (0.5, 1 and 2 kHz) audiometry data from 4970 children in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth-cohort at age eleven years. Genes found to contain SNPs with low p-values were then investigated in 3417 adults in the G-EAR study of hearing. RESULTS: Genotypic data were available in ALSPAC for a total of 577 SNPs from 13 genes of interest. Two SNPs approached sample-wide significance (pre-specified at p = 0.00014): rs12959910 in CBP80/20-dependent translation initiation factor (CTIF) for averaged high frequency hearing (p = 0.00079, β = 0.61 dB per minor allele); and rs10492452 in L-plastin (LCP1) for averaged low frequency hearing (p = 0.00056, β = 0.45 dB). For low frequencies, rs9567638 in LCP1 also enhanced hearing in females (p = 0.0011, β = -1.76 dB; males p = 0.23, β = 0.61 dB, likelihood-ratio test p = 0.006). SNPs in LCP1 and CTIF were then examined against low and high frequency hearing data for adults in G-EAR. Although the ALSPAC results were not replicated, a SNP in LCP1, rs17601960, is in strong LD with rs9967638, and was associated with enhanced low frequency hearing in adult females in G-EAR (p = 0.00084). CONCLUSIONS: There was evidence to suggest that multiple SNPs in CTIF may contribute a small detrimental effect to hearing, and that a sex-specific locus in LCP1 is protective of hearing. No individual SNPs reached sample-wide significance in both ALSPAC and G-EAR. This is the first report of a possible association between LCP1 and hearing function.

Breakfast skipping is associated with cyberbullying and school bullying victimization:a school-based cross-sectional study

Breakfast skipping is a health concern that has well-known negative consequences physically and psychologically. It is therefore important to understand why children skip breakfast. The purpose of this study was to establish whether the experience of bullying and cyberbullying impacts upon breakfast skipping and to further evaluate whether the inability for youths to cope with bullying victimization affects their mental health (depression), and in turn predicts breakfast skipping. Data were obtained from the Eastern Ontario 2011 Youth Risk Behaviour Survey, a cross-sectional regional school-based survey of middle and high school students (11-20 years old) across the five counties of Eastern Ontario, Canada (N = 3035). Self-reported data about children's experiences of bullying victimization, breakfast eating habits, socio-economical status, depression, and other risk behaviours were analysed. Approximately half of the participants (50.4%) reported not eating breakfast on a regular basis: 26.3% and 24.1% reported often (usually eat breakfast three times or more per week) and frequent (usually eat breakfast twice a week or less) breakfast skipping behaviour, respectively. Victims of both cyberbullying and school bullying presented greater likelihood of often (adjusted relative risk ratio (RR) = 1.55; 95% confidence interval (CI) = 1.17-2.06) and frequent (RR = 1.97; 95% CI = 1.28-3.03) breakfast skipping. Mediation analysis further showed that depression fully mediated the relationship between school bullying victimization and frequent breakfast skipping. Moreover, depression partially mediated the associations between both cyberbullying and school bullying with frequent breakfast skipping. These findings highlight the potential interrelationships between cyberbullying, school bullying and depression in predicting unhealthy breakfast skipping behaviour in children. © 2014 Elsevier Ltd.

The effect of age, gender and driver status on pedestrians' intentions to cross the road in risky situations

The theory of planned behaviour (TPB) has been used successfully in the past to account for pedestrians' intentions to cross the road in risky situations. However, accident statistics show age and gender differences in the likelihood of adult pedestrian accidents. This study extends earlier work by examining the relative importance of the model components as predictors of intention to cross for four different adult age groups, men, women, drivers and nondrivers. The groups did not differ in the extent to which they differentiated between two situations of varying perceived risk. The model fit was good, but accounted for less of the variance in intention for the youngest group (17-24) than for other age groups. Differences between the age groups in intention to cross seemed to be due to differences in perceived value of crossing rather than differences in perceived risk. Women were less likely to intend to cross than men and perceived more risk, and there were important age, gender and driver status differences in the importance of the TPB variables as predictors of intention. A key implication of these findings is that road safety interventions need to be designed differently for different groups. © 2006 Elsevier Ltd. All rights reserved.

Spatial and temporal dependencies of cross-orientation suppression in human vision.

A well-known property of orientation-tuned neurons in the visual cortex is that they are suppressed by the superposition of an orthogonal mask. This phenomenon has been explained in terms of physiological constraints (synaptic depression), engineering solutions for components with poor dynamic range (contrast normalization) and fundamental coding strategies for natural images (redundancy reduction). A common but often tacit assumption is that the suppressive process is equally potent at different spatial and temporal scales of analysis. To determine whether it is so, we measured psychophysical cross-orientation masking (XOM) functions for flickering horizontal Gabor stimuli over wide ranges of spatio-temporal frequency and contrast. We found that orthogonal masks raised contrast detection thresholds substantially at low spatial frequencies and high temporal frequencies (high speeds), and that small and unexpected levels of facilitation were evident elsewhere. The data were well fit by a functional model of contrast gain control, where (i) the weight of suppression increased with the ratio of temporal to spatial frequency and (ii) the weight of facilitatory modulation was the same for all conditions, but outcompeted by suppression at higher contrasts. These results (i) provide new constraints for models of primary visual cortex, (ii) associate XOM and facilitation with the transient magno- and sustained parvostreams, respectively, and (iii) reconcile earlier conflicting psychophysical reports on XOM.

Lack of association between glucocorticoid use and presence of the metabolic syndrome in patients with rheumatoid arthritis:a cross-sectional study

Introduction - Rheumatoid arthritis (RA) associates with excessive cardiovascular morbidity and mortality, attributed to both traditional and novel cardiovascular risk factors. The metabolic syndrome, a cluster of classical cardiovascular risk factors, including hypertension, obesity, glucose intolerance, and dyslipidaemia, is highly prevalent in RA. Reports suggest that long-term glucocorticoid (GC) use may exacerbate individual cardiovascular risk factors, but there have been no studies in RA to assess whether it associates with the metabolic syndrome. We examined whether GC exposure associates with the presence of metabolic syndrome in patients with RA. Methods - RA patients (n = 398) with detailed clinical and laboratory assessments were categorised into three groups according to GC exposure: no/limited (<3 months) exposure (NE), low-dose (<7.5 mg/day) long-term exposure (LE), and medium-dose (greater than or equal to 7.5 mg to 30 mg/day) long-term exposure (ME). The metabolic syndrome was defined using the National Cholesterol Education Programme III guidelines. The association of GC exposure with the metabolic syndrome was evaluated using binary logistic regression. Results - The metabolic syndrome was present in 40.1% of this population and its prevalence did not differ significantly between the GC exposure groups (NE 37.9% versus LE 40.7% versus ME 50%, P = 0.241). Binary logistic regression did not demonstrate any increased odds for the metabolic syndrome when comparing ME with LE (odds ratio = 1.64, 95% confidence interval 0.92 to 2.92, P = 0.094) and remained non significant after adjusting for multiple potential confounders. Conclusions - Long-term GC exposure does not appear to associate with a higher prevalence of the metabolic syndrome in patients with RA. The components of the metabolic syndrome may already be extensively modified by other processes in RA (including chronic inflammation and treatments other than GCs), leaving little scope for additive effects of GCs.

Cross-orientation masking is speed invariant between ocular pathways but speed dependent within them

In human (D. H. Baker, T. S. Meese, & R. J. Summers, 2007b) and in cat (B. Li, M. R. Peterson, J. K. Thompson, T. Duong, & R. D. Freeman, 2005; F. Sengpiel & V. Vorobyov, 2005) there are at least two routes to cross-orientation suppression (XOS): a broadband, non-adaptable, monocular (within-eye) pathway and a more narrowband, adaptable interocular (between the eyes) pathway. We further characterized these two routes psychophysically by measuring the weight of suppression across spatio-temporal frequency for cross-oriented pairs of superimposed flickering Gabor patches. Masking functions were normalized to unmasked detection thresholds and fitted by a two-stage model of contrast gain control (T. S. Meese, M. A. Georgeson, & D. H. Baker, 2006) that was developed to accommodate XOS. The weight of monocular suppression was a power function of the scalar quantity ‘speed’ (temporal-frequency/spatial-frequency). This weight can be expressed as the ratio of non-oriented magno- and parvo-like mechanisms, permitting a fast-acting, early locus, as befits the urgency for action associated with high retinal speeds. In contrast, dichoptic-masking functions superimposed. Overall, this (i) provides further evidence for dissociation between the two forms of XOS in humans, and (ii) indicates that the monocular and interocular varieties of XOS are space/time scale-dependent and scale-invariant, respectively. This suggests an image-processing role for interocular XOS that is tailored to natural image statistics—very different from that of the scale-dependent (speed-dependent) monocular variety.

Moving on from nascent entrepreneurship:measuring cross-national differences in the transition to new business ownership

Nascent entrepreneurship and new business ownership are subsequent stages in the entrepreneurial process. We illustrate how information from the largest internationally harmonized database on entrepreneurship, the Global Entrepreneurship Monitor project, can be used to approximate the entrepreneurial process. We make a methodological contribution by computing the ratio of new business ownership to nascent entrepreneurship in a way that reflects the transition from nascent to new business ownership and provides cross-nationally comparable information on the efficiency of the entrepreneurial process for 48 countries. We report evidence for the validity of the transition ratio by benchmarking it against transition rates obtained from longitudinal studies and by correlating it with commonly used entrepreneurship indicators and macro-level economic indices. The transition ratio enables future cross-national research on the entrepreneurial process by providing a reliable and valid indicator for one key transition in this process. © 2012 Springer Science+Business Media New York.

An empirical investigation on firm-level performance of cross border mergers and acquisitions

This empirical study investigates the performance of cross border M&A. The first stage is to identify the determinants of making cross border M&A complete. One focus here is to extend the existing empirical evidence in the field of cross border M&A and exploit the likelihood of M&A from a different perspective. Given the determinants of cross border M&A completions, the second stage is to investigate the effects of cross border M&A on post-acquisition firm performance for both targets and acquirers. The thesis exploits a hitherto unused data base, which consists of those firms that are rumoured to be undertaking M&A, and then follow the deal to completion or abandonment. This approach highlights a number of limitations to the previous literature, which relies on statistical methodology to identify potential but non-existent mergers. This thesis changes some conventional understanding for M&A activity. Cross border M&A activity is underpinned by various motives such as synergy, management discipline, and acquisition of complementary resources. Traditionally, it is believed that these motives will boost the international M&A activity and improve firm performance after takeovers. However, this thesis shows that such factors based on these motives as acquirer’s profitability and liquidity and target’s intangible resource actually deter the completion of cross border M&A in the period of 2002-2011. The overall finding suggests that the cross border M&A is the efficiency-seeking activity rather than the resource-seeking activity. Furthermore, compared with firms in takeover rumours, the completion of M&A lowers firm performance. More specifically, the difficulties in transfer of competitive advantages and integration of strategic assets lead to low firm performance in terms of productivity. Besides, firms cannot realise the synergistic effect and managerial disciplinary effect once a cross border M&A is completed, which suggests a low post-acquisition profitability level.

Factors associated with high anticholinergic burden in aging adults with intellectual disabilities:a cross-sectional study

Background: Anticholinergic (AC) medications are associated with cognitive and functional decline in older people, with risk of adverse outcomes increasing with increasing AC exposure. Older people with intellectual disabilities are at increased risk of high AC exposure owing to higher prevalence of multimorbidity, particularly psychiatric morbidities. Objectives: The aims of this study were to determine individual’s AC exposure using the AC cognitive burden (ACB) scale, identify therapeutic classes contributing to burden and determine clinical and demographic factors associated with two levels of AC exposure (ACB score 1–4, ACB 5+). Methods: Cross-sectional (self-report/proxy report)medication data were drawn from Wave 1 of the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing, a study on ageing of 753nationally representative people with ID aged over40 randomly selected from the National Intellectual Disability Database. Medication data were available for 736 (98%). Each individual’s cumulative AC exposure was calculated using the ACB. Multinomiallogistic regression was performed identifying clinical and demographic factors associated with ACB score1–4, and ACB 5+. Results: In the eligible population of 736 participants(mean (±SD) age 54.1 (±8.8) years,55% female), 522(70.9%) were exposed to an ACB medicine (ACB 1+); 214 (29%) had an ACB score of 5+; mean total ACB score= 4.5 (±3.0). Antipsychotics accounted for35.6% of the cumulative ACB score. Age over 65yearswas associated with increased likelihood of both levels of AC exposure (ACB 1–4—adjusted OR 3.28; 95%CI 1.49–7.25, ACB 5+—adjusted OR 3.08; 95%CI1.21–7.63) and having a mental health condition(ACB 1–4—adjusted OR 9.79; 95%CI 5.63–17.02, ACB 5+—adjusted OR 23.74; 95%CI 12.29–45.83). Conclusions: Using a simple cumulative measure proved an effective means to capture total burden and established that AC exposure was high and associated with older age and mental health morbidity. This highlights need for comprehensive medication reviews for older people with intellectual disabilities.

Association of anticholinergic burden with adverse effects in older people with intellectual disabilities:an observational cross-sectional study

BACKGROUND: No studies to date have investigated cumulative anticholinergic exposure and its effects in adults with intellectual disabilities. AIMS: To determine the cumulative exposure to anticholinergics and the factors associated with high exposure. METHOD: A modified Anticholinergic Cognitive Burden (ACB) scale score was calculated for a representative cohort of 736 people over 40 years old with intellectual disabilities, and associations with demographic and clinical factors assessed. RESULTS: Age over 65 years was associated with higher exposure (ACB 1-4 odds ratio (OR) = 3.28, 95% CI 1.49-7.28, ACB 5+ OR = 3.08, 95% CI 1.20-7.63), as was a mental health condition (ACB 1-4 OR = 9.79, 95% CI 5.63-17.02, ACB 5+ OR = 23.74, 95% CI 12.29-45.83). Daytime drowsiness was associated with higher ACB (P<0.001) and chronic constipation reported more frequently (26.6% ACB 5+ v. 7.5% ACB 0, P<0.001). CONCLUSIONS: Older people with intellectual disabilities and with mental health conditions were exposed to high anticholinergic burden. This was associated with daytime dozing and constipation.

Public support for business innovation in Mexico:a cross-sectional analysis

This paper explores the impact of government support in Mexico on the likelihood of firms achieving functional and/or inter-sectoral upgrading in global value chains (GVC). Employing a unique dataset, regression analysis was undertaken to estimate the predicted probabilities of firms upgrading in GVCs considering their regional location. The results suggest that firms located in Mexico City are more likely to achieve functional upgrading vis-à-vis northern firms. Additionally, the presence of an R&D laboratory is crucial if firms are to engage in upgrading. There was no evidence that government support affects the likelihood of firms achieving functional and/or inter-sectoral upgrading.