Sympathetic inhibition of accommodation after sustained nearwork in subjects with myopia and emmetropia

PURPOSE. The purposes of the present study were to assess the effect of a sympathetic inhibitory pharmacologic agent, timolol maleate, on the magnitude of nearwork-induced transient myopia (NITM) and its decay in different refractive groups for an extended near task duration and to determine the proportion of the young adult population manifesting effective sympathetic access under naturalistic closed-loop viewing conditions. METHODS. Ten subjects with emmetropia and 10 with myopia were tested. They read binocularly for 1 hour at a distance of 35 to 40 cm. NITM was calculated as the difference in distance refractive state after task as compared with before task immediately after reading. All subjects received timolol maleate to block the sympathetic nervous system and betaxolol as a control agent in independent test sessions separated by at least 3 days. Forty minutes after drug instillation, the NITM measurement procedure was repeated. RESULTS. Initial NITM magnitude was larger in subjects with myopia than in subjects with emmetropia before and after timolol instillation. Furthermore, NITM magnitude in subjects with sympathetic access was increased after timolol instillation. In contrast, with the control agent betaxolol, there was no increase. NITM decay duration to baseline was increased after timolol instillation in the subjects with myopia only. Only 15% of the subjects (n = 3 subjects with myopia) demonstrated effective and significant access to sympathetic facility. CONCLUSIONS. Subjects with myopia demonstrated an increase in decay duration with timolol, thus suggesting impaired sympathetic inhibition of accommodation. This may be a precursor for myopia progression in some persons.

Self-testing for cancer:a community survey

Background: Cancer-related self-tests are currently available to buy in pharmacies or over the internet, including tests for faecal occult blood, PSA and haematuria. Self-tests have potential benefits (e.g. convenience) but there are also potential harms (e.g. delays in seeking treatment). The extent of cancer-related self-test use in the UK is not known. This study aimed to determine the prevalence of cancer-related self-test use. Methods: Adults (n = 5,545) in the West Midlands were sent a questionnaire that collected socio-demographic information and data regarding previous and potential future use of 18 different self-tests. Prevalence rates were directly standardised to the England population. The postcode based Index of Multiple Deprivation 2004 was used as aproxy measure of deprivation. Results: 2,925 (54%) usable questionnaires were returned. 1.2% (95% CI 0.83% to 1.66%) of responders reported having used a cancer related self test kit and a further 36% reported that they would consider using one in the future. Logistic regression analyses suggest that increasing age, deprivation category and employment status were associated with cancer-related self-test kit use. Conclusion: We conclude that one in 100 of the adult population have used a cancer-related self-test kit and over a third would consider using one in the future. Self-test kit use could alter perceptions of risk, cause psychological morbidity and impact on the demand for healthcare.

Entrepreneurial intention and entrepreneurial behaviour:a social psychological perspective

Increasing the supply of entrepreneurs reduces unemployment and accelerates economic growth (Acs, 2006; Audretsch, 2007; Santarelli et el. 2009; Campbell, 1996; Carree & Thurik, 1996). The supply of entrepreneurs depends on the entrepreneurial intention and activity of the people (Kruger & Brazeal, 1994). Existing behavioural theories explain that entrepreneurial activity is an attitude driven process which is mediated by intention and regulated by behavioural control. These theories are: Theory of Planned Behaviour (Ajzen, 1991; 2002, 2012); Entrepreneurial Event Model (Shapiro & Shokol, 1982), and Social Cognitive Theory (Bandura, 1977; 1986; 2012). Meta-analysis of existing behavioural theories in different fields found that the theories are more effective to analyse behavioural intention and habitual behaviour, but less effective to analyse long-term and risky behaviour (McEachan et al., 2011). The objective of this dissertation is to improve entrepreneurship behaviour theory to advance our understanding of the determinants of the entrepreneurial intention and activity. To achieve this objective we asked three compelling questions in our research. These are: Firstly, why do differences exist in entrepreneurship among age groups. Secondly, how can we improve the theory to analyse entrepreneurial intention and behaviour? And, thirdly, is there any relationship between counterfactual or regretful thinking and entrepreneurial intention? We address these three questions in Chapters 2, 3 and 4 of the dissertation. Earlier studies have identified that there is an inverse U shaped relationship between age and entrepreneurship (Parker, 2004; Hart et al., 2004). In our study, we explain the reasons for this inverse U shape (Chapter 2). To analyse the reasons we use Cognitive Life Cycle theory and Disuse theory. We assume that the stage in the life cycle of an individual moderates the influence of opportunity identification and skill to start a business. In our study, we analyse the moderation effect in early stage entrepreneurship and in serial entrepreneurship. In Chapter 3, the limitations of existing psychological theories are discussed, and a competency value theory of entrepreneurship (CVTE) is proposed to overcome the limitations and extend existing theories. We use a ‘weighted competency’ variable instead of a ‘perceived behavioural control’ variable for the theory of planned behaviour (TPB) and self-efficacy variable for social cognitive theory. Weighted competency is the perceived competency ranking assigned by an individual for his total competencies to be an entrepreneur. The proposed theory was tested in a pilot survey in the UK and in a national adult population survey in a South Asian Country. The results show a significant relationship between competencies and entrepreneurial intention, and weighted competencies and entrepreneurial behaviour as per CVTE. To improve the theory further, in Chapter 4, we test the relationship between counterfactual thinking and entrepreneurial intention. Studies in cognitive psychology identify that ‘upward counterfactual thinking’ influences intention and behaviour (Epstude & Rose, 2008; Smallman & Roese, 2009). Upward counterfactual thinking is regretful thinking for missed opportunities of a problem. This study addresses the question of how an individual’s regretful thinking affects his or her future entrepreneurial career intention. To do so, we conducted a study among students in a business school in the UK, and we found that counterfactual thinking modifies the influence of attitude and opportunity identification in entrepreneurial career intention.

An evaluation of paediatric medicines reconciliation at hospital discharge into the community

OBJECTIVE: A UK national survey of primary care physicians has indicated that the medication information on hospital discharge summary was incomplete or inaccurate most of the time. Internationally, studies have shown that hospital pharmacist's interventions reduce these discrepancies in the adult population. There have been no published studies on the incidence and severity of the discrepancies of the medication prescribed for children specifically at discharge to date. The objectives of this study were to investigate the incidence, nature and potential clinical severity of medication discrepancies at the point of hospital discharge in a paediatric setting. METHODS: Five weeks prospective review of hospital discharge letters was carried out. Medication discrepancies between the initial doctor's discharge letter and finalised drug chart were identified, pharmacist changes were recorded and their severity was assessed. The setting of the review was at a London, UK paediatric hospital providing local secondary and specialist tertiary care. The outcome measures were: - incidence and the potential clinical severity of medication discrepancies identified by the hospital pharmacist at discharge. KEY FINDINGS: 142 patients (64 female and 78 males, age range 1 month - 18 years) were discharged on 501 medications. The majority of patients were under the care of general surgery and general paediatric teams. One in three discharge letters contained at least one medication discrepancy and required pharmacist interventions to rectify prior to completion. Of these, 1 in 10 had the potential for patient harm if undetected. CONCLUSIONS: Medicines reconciliation by pharmacist at discharge may be a good intervention in preventing medication discrepancies which have the potential to cause moderate harm in paediatric patients.

Health and population effects of rare gene knockouts in adult humans with related parents

Examining complete gene knockouts within a viable organism can inform on gene function. We sequenced the exomes of 3222 British Pakistani-heritage adults with high parental relatedness, discovering 1111 rare-variant homozygous genotypes with predicted loss of gene function (knockouts) in 781 genes. We observed 13.7% fewer than expected homozygous knockout genotypes, implying an average load of 1.6 recessive-lethal-equivalent LOF variants per adult. Linking genetic data to lifelong health records, knockouts were not associated with clinical consultation or prescription rate. In this dataset we identified a healthy PRDM9 knockout mother, and performed phased genome sequencing on her, her child and controls, which showed meiotic recombination sites localized away from PRDM9-dependent hotspots. Thus, natural LOF variants inform upon essential genetic loci, and demonstrate PRDM9 redundancy in humans.

Prophylactic ranitidine treatment in critically ill children - a population pharmacokinetic study

Aims - To characterize the population pharmacokinetics of ranitidine in critically ill children and to determine the influence of various clinical and demographic factors on its disposition. Methods - Data were collected prospectively from 78 paediatric patients (n = 248 plasma samples) who received oral or intravenous ranitidine for prophylaxis against stress ulcers, gastrointestinal bleeding or the treatment of gastro-oesophageal reflux. Plasma samples were analysed using high-performance liquid chromatography, and the data were subjected to population pharmacokinetic analysis using nonlinear mixed-effects modelling. Results - A one-compartment model best described the plasma concentration profile, with an exponential structure for interindividual errors and a proportional structure for intra-individual error. After backward stepwise elimination, the final model showed a significant decrease in objective function value (−12.618; P < 0.001) compared with the weight-corrected base model. Final parameter estimates for the population were 32.1 l h−1 for total clearance and 285 l for volume of distribution, both allometrically modelled for a 70 kg adult. Final estimates for absorption rate constant and bioavailability were 1.31 h−1 and 27.5%, respectively. No significant relationship was found between age and weight-corrected ranitidine pharmacokinetic parameters in the final model, with the covariate for cardiac failure or surgery being shown to reduce clearance significantly by a factor of 0.46. Conclusions - Currently, ranitidine dose recommendations are based on children's weights. However, our findings suggest that a dosing scheme that takes into consideration both weight and cardiac failure/surgery would be more appropriate in order to avoid administration of higher or more frequent doses than necessary.