Factors associated with common mental disorders during the transition to adulthood : do emerging adults and ‘early starters’ differ? Findings from an Australian birth cohort study

Background: Despite increasing diversity in pathways to adulthood, choices available to young people are influenced by environmental, familial and individual factors, namely access to socioeconomic resources, family support and mental and physical health status. Young people from families with higher socioeconomic position (SEP) are more likely to pursue tertiary education and delay entry to adulthood, whereas those from low socioeconomic backgrounds are less likely to attain higher education or training, and more likely to partner and become parents early. The first group are commonly termed ‘emerging adults’ and the latter group ‘early starters’. Mental health disorders during this transition can seriously disrupt psychological, social and academic development as well as employment prospects. Depression, anxiety and most substance use disorders have early onset during adolescence and early adulthood with approximately three quarters of lifetime psychiatric disorders having emerged by 24 years of age. Aims: This thesis aimed to explore the relationships between mental health, sociodemographic factors and family functioning during the transition to adulthood. Four areas were investigated: 1) The key differences between emerging adults and ‘early starters’, were examined and focused on a series of social, economic, and demographic factors as well as DSM-IV diagnoses; 2) Methodological issues associated with the measurement of depression and anxiety in young adults were explored by comparing a quantitative measure of symptoms of anxiety and depression (Achenbach’s YSR and YASR internalising scales) with DSM-IV diagnosed depression and anxiety. 3) The association between family SEP and DSM-IV depression and anxiety was examined in relation to the different pathways to adulthood. 4) Finally, the association between pregnancy loss, abortion and miscarriage, and DSM-IV diagnoses of common psychiatric disorders was assessed in young women who reported early parenting, experiencing a pregnancy loss, or who had never been pregnant. Methods: Data were taken from the Mater University Study of Pregnancy (MUSP), a large birth cohort started in 1981 in Brisbane, Australia. 7223 mothers and their children were assessed five times, at 6 months, 5, 14 and 21 years after birth. Over 3700 young adults, aged 18 to 23 years, were interviewed at the 21-year phase. Respondents completed an extensive series of self-reported questionnaires and a computerised structured psychiatric interview. Three outcomes were assessed at the 21-year phase. Mental health disorders diagnosed by a computerised structured psychiatric interview (CIDI-Auto), the prevalence of DSM-IV depression, anxiety and substance use disorders within the previous 12-month, during the transition (between ages of 18 and 23 years) or lifetime were examined. The primary outcome “current stage in the transition to adulthood” was developed using a measure conceptually constructed from the literature. The measure was based on important demographic markers, and these defined four independent groups: emerging adults (single with no children and living with parents), and three categories of ‘early starter’, singles (with no children or partner, living independently), those with a partner (married or cohabitating but without children) and parents. Early pregnancy loss was assessed using a measure that also defined four independent groups and was based on pregnancy outcomes in the young women This categorised the young women into those who were never pregnant, women who gave birth to a live child, and women who reported some form of pregnancy loss, either an abortion or a spontaneous miscarriage. A series of analyses were undertaken to test the study aims. Potential confounding and mediating factors were prospectively measured between the child’s birth and the 21-year phase. Binomial and multinomial logistic regression was used to estimate the risk of relevant outcomes, and the associations were reported as odds ratios (OR) and 95% confidence intervals (95%CI). Key findings: The thesis makes a number of important contributions to our understanding of the transition to adulthood, particularly in relation to the mental health consequences associated with different pathways. Firstly, findings from the thesis clearly showed that young people who parented or partnered early fared worse across most of the economic and social factors as well as the common mental disorders when compared to emerging adults. That is, young people who became early parents were also more likely to experience recent anxiety (OR=2.0, 95%CI 1.5-2.8) and depression (OR=1.7, 95%CI 1.1-2.7) than were emerging adults after taking into account a range of confounding factors. Singles and those partnering early also had higher rates of lifetime anxiety and depression than emerging adults. Young people who partnered early, but were without children, had decreased odds of recent depression; this may be due to the protective effect of early marriage against depression. It was also found that young people who form families early had an increased risk of cigarette smoking (parents OR=3.7, 95%CI 2.9-4.8) compared to emerging adults, but not heavy alcohol (parents OR=0.4, 95%CI 0.3-0.6) or recent illicit drug use. The high rates of cigarette smoking and tobacco use disorders in ‘early starters’ were explained by common risk factors related to early adversity and lower SEP. Having a child and early marriage may well function as a ‘turning point’ for some young people, it is not clear whether this is due to a conscious decision to disengage from a previous ‘substance using’ lifestyle or simply that they no longer have the time to devote to such activities because of child caring. In relation to the methodological issues associated with assessing common mental disorders in young adults, it was found that although the Achenbach empirical internalising scales successfully predicted both later DSM-IV depression (YSR OR=2.3, 95%CI 1.7-3.1) and concurrently diagnosed depression (YASR OR=6.9, 95%CI 5.0- 9.5) and anxiety (YASR OR=5.1, 95%CI 3.8- 6.7), the scales discriminated poorly between young people with or without DSM-IV diagnosed mood disorder. Sensitivity values (the proportion of true positives) for the internalising scales were surprisingly low. Only a third of young people with current DSM-IV depression (range for each of the scales was between 34% to 42%) were correctly identified as cases by the YASR internalising scales, and only a quarter with current anxiety disorder (range of 23% to 31%) were correctly identified. Also, use of the DSM-oriented scales increased sensitivity only marginally (for depression between 2-8%, and anxiety between 2-6%) above the standard Achenbach scales. This is despite the fact that the DSM-oriented scales were originally developed to overcome the poor prediction of DSM-IV diagnoses by the Achenbach scales. The internalising scales, both standard and DSM-oriented, were much more effective at identifying young people with comorbid depression and anxiety, with OR’s 10.1 to 21.7 depending on the internalising scale used. SEP is an important predictor of both an early transition to adulthood and the experience of anxiety during that time Family income during adolescence was a strong predictor of early parenting and partnering before age 24 but not early independent living. Compared to families in the upper quintile, young people from families with low income were nearly twice as likely to live with a partner and four times more likely to become parents (OR ranged from 2.6 to 4.0). This association remained after adjusting for current employment and education level. Children raised in low income families were 30% more likely to have an anxiety disorder (OR=1.3, 95%CI 0.9-1.9), but not depression, as young adults when compared to children from wealthier families. Emerging adults and ‘early starters’ from low income families did not differ in their likelihood of having a later anxiety disorder. Young women reporting a pregnancy loss had nearly three times the odds of experiencing a lifetime illicit drug disorder (excluding cannabis) [abortion OR=3.6, 95%CI 2.0-6.7 and miscarriage OR=2.6, 95%CI 1.2-5.4]. Abortion was associated with alcohol use disorder (OR=2.1, 95%CI 1.3- 3.5) and 12-month depression (OR=1.9, 95%CI 1.1- 3.1). These finding suggest that the association identified by Fergusson et al between abortion and later psychiatric disorders in young women may be due to pregnancy loss and not to abortion, per se. Conclusion: Findings from this thesis support the view that young people who parent or partner early have a greater burden of depression and anxiety when compared to emerging adults. As well, young women experiencing pregnancy loss, from either abortion or miscarriage, are more likely to experience depression and anxiety than are those who give birth to a live infant or who have never been pregnant. Depression, anxiety and substance use disorders often go unrecognised and untreated in young people; this is especially true in young people from lower SEP. Early identification of these common mental health disorders is important, as depression and anxiety experienced during the transition to adulthood have been found to seriously disrupt an individual’s social, educational and economic prospects in later life.

Random Breath Testing in Australia: Is there an Optimum Level of Intensity?

Background: Random Breath Testing (RBT) is the main drink driving law enforcement tool used throughout Australia. International comparative research considers Australia to have the most successful RBT program compared to other countries in terms of crash reductions (Erke, Goldenbeld, & Vaa, 2009). This success is attributed to the programs high intensity (Erke et al., 2009). Our review of the extant literature suggests that there is no research evidence that indicates an optimal level of alcohol breath testing. That is, we suggest that no research exists to guide policy regarding whether or not there is a point at which alcohol related crashes reach a point of diminishing returns as a result of either saturated or targeted RBT testing. Aims: In this paper we first provide an examination of RBTs and alcohol related crashes across Australian jurisdictions. We then address the question of whether or not an optimal level of random breath testing exists by examining the relationship between the number of RBTs conducted and the occurrence of alcohol-related crashes over time, across all Australian states. Method: To examine the association between RBT rates and alcohol related crashes and to assess whether an optimal ratio of RBT tests per licenced drivers can be determined we draw on three administrative data sources form each jurisdiction. Where possible data collected spans January 1st 2000 to September 30th 2012. The RBT administrative dataset includes the number of Random Breath Tests (RBTs) conducted per month. The traffic crash administrative dataset contains aggregated monthly count of the number of traffic crashes where an individual’s recorded BAC reaches or exceeds 0.05g/ml of alcohol in blood. The licenced driver data were the monthly number of registered licenced drivers spanning January 2000 to December 2011. Results: The data highlights that the Australian story does not reflective of all States and territories. The stable RBT to licenced driver ratio in Queensland (of 1:1) suggests a stable rate of alcohol related crash data of 5.5 per 100,000 licenced drivers. Yet, in South Australia were a relative stable rate of RBT to licenced driver ratio of 1:2 is maintained the rate of alcohol related traffic crashes is substantially less at 3.7 per 100,000. We use joinpoint regression techniques and varying regression models to fit the data and compare the different patterns between jurisdictions. Discussion: The results of this study provide an updated review and evaluation of RBTs conducted in Australia and examines the association between RBTs and alcohol related traffic crashes. We also present an evidence base to guide policy decisions for RBT operations.

The association between time spent outdoors and myopia using a novel biomarker of outdoor light exposure

PURPOSE: We sought to determine whether conjunctival ultraviolet autofluorescence (UVAF), a biomarker of outdoor light exposure, is associated with myopia. METHODS: We performed a cross-sectional study on Norfolk Island and recruited individuals aged ≥ 15 years. Participants completed a sun-exposure questionnaire and underwent non-cycloplegic autorefraction. Conjunctival UVAF used a specially adapted electronic flash system fitted with UV-transmission filters (transmittance range 300-400 nm, peak 365 nm) as the excitation source. Temporal and nasal conjunctival UVAF was measured in both eyes using computerized photographic analysis with the sum referred to as "total UVAF." RESULTS: In 636 participants, prevalence of myopia decreased with an increasing quartile of total UVAF (P(trend) = 0.002). Median total UVAF was lower in subjects with myopia (spherical equivalent [SE] ≤ -1.0 diopter [D]) than participants without myopia: 16.6 mm(2) versus 28.6 mm(2), P = 0.001. In the multivariable model that adjusted for age, sex, smoking, cataract, height and weight, UVAF was independently associated with myopia (SE ≤ -1.0 D): odds ratio (OR) for total UVAF (per 10 mm(2)) was 0.81, 95% confidence interval (CI) 0.69 to 0.94, P = 0.007. UVAF was also significantly associated with myopia when analysis was restricted to subjects <50 years, and in moderate-severe myopia (SE ≤ -3.0 D). Prevalence of myopia decreased with increasing time outdoors (P(trend) = 0.03), but time outdoors was not associated with myopia on multivariable analysis. CONCLUSIONS: Study authors identified a protective association between increasing UVAF and myopia. The protective association of higher UVAF against myopia was stronger than that of increased levels of time spent outdoors as measured by this study's questionnaire. Future studies should investigate the association between UVAF and incident myopia, and its relationship to myopic progression.

International corporate entrepreneurship among SMEs : a test of Stevenson's notion of entrepreneurial management

Geographical market expansion is included in various definitions of entrepreneurship as it entails the opening up of new markets (for example, Davidsson 2003). Expansion into new international markets and launch of new products in international markets are also consistent with definitions of entrepreneurship which center on the pursuit of opportunities {e.g.\Stevenson, 1983 #922;Gartner, 1993 #931}. Accordingly, the decision by managers of small, internationally active businesses to continue to internationalize can be viewed as an entrepreneurial act. In spite of the fact that both start-ups and existing firms can behave entrepreneurially by expanding into new international markets, the attention of entrepreneurship researchers interested in international activities has largely focused on international new ventures (INVs); that is, business organizations that internationalize from inception (Oviatt, and McDougall 1994; Oviatt, and McDougall 1997). Consequently, pursuit of international opportunities by established small and medium-sized enterprises (SMEs) lacks theoretical understanding and empirical investigation through an entrepreneurship lens. This paper contributes to the body of knowledge at the entrepreneurship-internationalization interface by testing whether Stevenson’s opportunity-based conceptualization of entrepreneurial management (Stevenson 1983; Stevenson and Gumpert 1985; Stevenson and Jarillo 1990) can explain the attainment of continued entrepreneurial outcomes by SMEs operating in foreign markets. We choose Stevenson’s conceptualization as it gauges firm-level characteristics that are theorized to facilitate the pursuit of entrepreneurial opportunities, which arguably is at the heart of SMEs’ continued venturing into international markets.

The benefits of thermal clothing during winter in patients with heart failure : a pilot randomised controlled trial

Background Many Australian cities experience large winter increases in deaths and hospitalisations. Flu outbreaks are only part of the problem and inadequate protection from cold weather is a key independent risk factor. Better home insulation has been shown to improve health during winter, but no study has examined whether better personal insulation improves health. Data and Methods We ran a randomised controlled trial of thermal clothing versus usual care. Subjects with heart failure (a group vulnerable to cold) were recruited from a public hospital in Brisbane in winter and followed-up at the end of winter. Those randomised to the intervention received two thermal hats and tops and a digital thermometer. The primary outcome was the number of days in hospital, with secondary outcomes of General Practitioner (GP) visits and self-rated health. Results The mean number of days in hospital per 100 winter days was 2.5 in the intervention group and 1.8 in the usual care group, with a mean difference of 0.7 (95% CI: –1.5, 5.4). The intervention group had 0.2 fewer GP visits on average (95% CI: –0.8, 0.3), and a higher self-rated health, mean improvement –0.3 (95% CI: –0.9, 0.3). The thermal tops were generally well used, but even in cold temperatures the hats were only worn by 30% of subjects. Conclusions Thermal clothes are a cheap and simple intervention, but further work needs to be done on increasing compliance and confirming the health and economic benefits of providing thermals to at-risk groups.

The intervening role of Agreeableness in the relationship between trait emotional intelligence and Machiavellianism : reassessing the potential dark side of EI

Previous research into the potential ‘dark’ side of trait emotional intelligence (EI) has repeatedly demonstrated that trait EI is negatively associated with Machiavellianism. In this study, we reassess the potential dark side of trait EI, by testing whether Agreeableness mediates and/or moderates the relationship between trait EI and Machiavellianism. Hypothesized mediation and moderation effects were tested using a large sample of 884 workers who completed several self-report questionnaires. Results provide support for both hypotheses; Agreeableness was found to mediate and moderate the relationship between trait EI and Machiavellianism. Overall, results indicate that individuals high in trait EI tend to have low levels of Machiavellianism because they generally have a positive nature (i.e. are agreeable) and not because they are emotionally competent per se. Results also indicate that individuals high in ‘perceived emotional competence’ have the potential to be high in Machiavellianism, particularly when they are low in Agreeableness.

ACE research vignette 029 : Can entrepreneurship be taught?

This series of research vignettes is aimed at sharing current and interesting research findings from our team of international Entrepreneurship researchers. This vignette, written by Professor Per Davidsson, examines the evidence on whether entrepreneurship education and training leads to more entrepreneurial action and success.

Understanding the impact of legislative changes on child car seating and restraint practices in regional Queensland

Road crashes contribute to a significant amount of child mortality and morbidity in Australia. In fact, passenger injuries contribute to the majority of child crash road trauma. A number of factors contribute to child injury and death in motor vehicles, including inappropriate seating position, inappropriate choice of restraint, and incorrect installation and use of child restraints. Prior to March 2010, child restraint legislation in Queensland only required children twelve months and younger to be seated in a properly adjusted and fastened child restraint. This legislation left older infants and young children potentially suboptimally protected. From March 2010, new legislation specified seating position and type of child restraint required, depending on the age of the child. This research was underpinned by the Health Belief Model (HBM), which explores health related behaviour, behaviour change, environmental factors influencing behaviour change (including legislative changes) and is flexible enough to be used in relation to parents' health practices for their children, rather than parent health directly. This thesis investigates the extent to which the changes to child restraint legislation have led parents in regional areas of Queensland to use appropriate restraint practices for their children and determines the extent to which the constructs of the HBM, parental perceptions, barriers and environmental factors contribute to the appropriateness of child seating and restraint use. Study One included three sets of observations taken in two regional cities of Queensland prior to the legislative amendment, during an educative period of six months, and after the enactment of the legislation. Each child's seating position and restraint type were recorded. Results showed that the proportion of children observed occupying the front seat decreased by 15.6 per cent with the announcement the legislation. There was no decrease in front seat use at the enactment of the legislation. The proportion of children observed using dedicated child restraints increased by 8.8 per cent with the announcement of the legislation when there was one child in the vehicle. Further, there was a 10.1 per cent increase in the proportion of children observed using a seat belt that fit with the announcement when there was one child in the vehicle and with the enactment of the legislation regardless of the number of children in the vehicle (21.8 per cent for one child, 39.7 per cent for two children and 40.2 per cent for three or more children). Study Two comprised initial intercept interviews, later followed up by telephone, with parents with children aged eight years and younger at the announcement and telephone interviews at the enactment of the legislation in one regional city in Queensland. Parents reported their child restraint practices, and opinions, knowledge and understanding of the requirements of the new legislation. Parent responses were analysed in terms of the constructs in the HBM. When asked which seating position their child 'usually' used, parents reported child front seat use was nil (0.0 per cent) and did not change with the enactment of the legislative amendment. However, when parents were asked whether they allowed children to use the front seat at some point within the six months prior to the interview, reported child front seat use was 7 (5.4 per cent) children at T2 and 10 (9.6 per cent) at T3. Reported use of age-appropriate child restraints did not increase with the enactment of the legislation (p = 0.77, ns). Parents reported restraint practices were classed as either appropriate or inappropriate. Parents who reported appropriate restraint practices were those whose children were sitting in optimal restraints and seating positions for their age according to the requirements of the legislation. Parents who reported inappropriate restraint practices were those who had one or more children who were suboptimally restrained or seated for their age according to the requirements of the legislation. Neither parents' perceptions about their susceptibility of being in a crash nor the likelihood of severity of child injury if involved in a crash yielded significant differences in the appropriateness of reported parent restraint practices over time with the enactment of the legislation. A trend in the data suggested parents perceived a benefit to using appropriate restraint practices was to avoid fines and demerit points. Over 75 per cent of parents who agreed that child restraints provide better protection for children than an adult seat belt reported appropriately seating and restraining their children (2 (1) = 8.093, p<.05). The self-efficacy measure regarding parents' confidence in installing a child restraint showed a significant association with appropriate parental restraint practices (2 (1) = 7.036, p<.05). Results suggested that some parents may have misinterpreted the announcement of the legislative amendment as the announcement of the enforcement of the legislation instead. Some parents who correctly reported details of the legislation did not report appropriate child restraint practices. This finding shows that parents' knowledge of the legislative amendment does not necessarily have an impact on their behaviour to appropriately seat and restrain children. The results of these studies have important implications for road safety and the prevention of road-related injury and death to children in Queensland. Firstly, parents reported feeling unsure of how to install restraints, which suggests that there may be children travelling in restraints that have not been installed correctly, putting them at risk. Interventions to alert and encourage parents to seek advice when unsure about the correct installation of child restraints could be considered. Secondly, some parents in this study although they were using the most appropriate restraint for their children, reported using a type that was not the most appropriate restraint for the child's age according to the legislation. This suggests that intervention may be effective in helping parents make a more accurate choice of the most appropriate type of restraint to use with children, especially as the child ages and child restraint requirements change. Further research could be conducted to ascertain the most effective methods of informing and motivating parents to use the most appropriate restraints and seating positions for their children, as these results show a concerning disparity between reported restraint practices and those that were observed.

PV string per-module maximum power point enabling converters

Many grid connected PV installations consist of a single series string of PV modules and a single DC-AC inverter. This efficiency of this topology can be enhanced with additional low power, low cost per panel converter modules. Most current flows directly in the series string which ensures high efficiency. However parallel Cúk or buck-boost DC-DC converters connected across each adjacent pair of modules now support any desired current difference between series connected PV modules. Each converter “shuffles” the desired difference in PV module currents between two modules and so on up the string. Spice simulations show that even with poor efficiency, these modules can make a significant improvement to the overall power which can be recovered from partially shaded PV strings.

An exploratory study to evaluate whether medical nutrition therapy can improve dietary intake in hospital patients who eat poorly

Background and aims The Australasian Nutrition Care Day Survey (ANCDS) reported two-in-five patients consume ≤50% of the offered food in Australian and New Zealand hospitals. After controlling for confounders (nutritional status, age, disease type and severity), the ANCDS also established an independent association between poor food intake and increased in-hospital mortality. This study aimed to evaluate if medical nutrition therapy (MNT) could improve dietary intake in hospital patients eating poorly. Methods An exploratory pilot study was conducted in the respiratory, neurology and orthopaedic wards of an Australian hospital. At baseline, percentage food intake (0%, 25%, 50%, 75%, and 100%) was evaluated for each main meal and snack for a 24-hour period in patients hospitalised for ≥2 days and not under dietetic review. Patients consuming ≤50% of offered meals due to nutrition-impact symptoms were referred to ward dietitians for MNT. Food intake was re-evaluated on the seventh day following recruitment (post-MNT). Results 184 patients were observed over four weeks; 32 patients were referred for MNT. Although baseline and post-MNT data for 20 participants (68±17years, 65% females) indicated a significant increase in median energy and protein intake post-MNT (3600kJ/day, 40g/day) versus baseline (2250kJ/day, 25g/day) (p<0.05), the increased intake met only 50% of dietary requirements. Persistent nutrition impact symptoms affected intake. Conclusion In this pilot study whilst dietary intake improved, it remained inadequate to meet participants’ estimated requirements due to ongoing nutrition-impact symptoms. Appropriate medical management and early enteral feeding could be a possible solution for such patients.

Inadequate management of medicines by the older-aged living in a retirement village

BACKGROUND: A comparison of the management of medicines by the older-aged living in freehold (fully owned) and rental homes in retirement villages has suggested that the older-aged living in rental, but not freehold, retirement villages may require help to manage their medicines. OBJECTIVE: The objective of this study was to investigate the management of medicines by the older-aged living independently in a leasehold (partly owned) home in retirement village to determine whether they also need help in managing their medicines. METHOD: Semi-structured interviews were conducted with 22 older-aged residents living in a leasehold retirement village. MAIN OUTCOME MEASURE: The main outcome measure was the perception of present and ongoing adherence. RESULTS: Amongst participants in the leasehold retirement village, with an average age of 82.9 years, the perceptions of present and ongoing adherence indicated that only 55 % of older-aged participants were adherent at the time of the study, and not likely to have problems with adherence within the next 6-12 months. Participants from the leasehold retirement village had a good understanding of 58 % of their illnesses. A mean of 9.8 medicines per person were prescribed. Cardiovascular medicines were the most commonly prescribed at 86 %. CONCLUSION: The older-aged living in leasehold retirement villages may require extra assistance/resources to manage their medicines.

Does it matter whether friends, parents, or peers drink walk? Identifying which normative influences predict young pedestrian's decisions to walk while intoxicated

Drink walking, that is walking in a public place while intoxicated, is associated with increased risk of injury and fatality. Young people and males are especially prone to engaging in this behaviour, yet little is known about the factors associated with individual’s decisions to drink walk. The present research explores the role of different normative influences (friendship group norm, parent group norm, university peer group norm) and perceived risk, within an extended theory of planned behaviour (TPB) framework, in predicting young people’s self-reported drink walking intentions. One hundred and eighteen young people (aged 17-25 years) completed a survey including sociodemographic measures and extended TPB measures related to drink walking. Overall the extended TPB explained 72.8% of the variance in young people’s intentions to drink walk in the next six months with attitude, perceived behavioural control, friendship group norm, and gender (male) emerging as significant predictors. Males, as compared with females, had higher intentions to drink walk and lower perceptions of risk regarding drink walking. Together, these findings provide a clearer indication of the salient normative influences and gender differences in young pedestrian’s decisions to walk while intoxicated. Such findings can be used to inform future interventions designed to reduce injuries and fatalities associated with drink walking.

The effects and interactions of GABAergic and dopaminergic agents in the prevention of form deprivation myopia by brief periods of normal vision

Intravitreal injections of GABA antagonists, dopamine agonists and brief periods of normal vision have been shown separately to inhibit form-deprivation myopia (FDM). Our study had three aims: (i) establish whether GABAergic agents modify the myopia protective effect of normal vision, (ii) investigate the receptor sub-type specificity of any observed effect, and (iii) consider an interaction with the dopamine (DA) system. Prior to the period of normal vision GABAergic agents were applied either (i) individually, (ii) in combination with other GABAergic agents (an agonist with an antagonist), or (iii) in combination with DA agonists and antagonists. Water injections were given to groups not receiving drug treatments so that all experimental eyes received intravitreal injections. As shown previously, constant form-deprivation resulted in high myopia and when diffusers were removed for 2 h per day the period of normal vision greatly reduced the FDM that developed. GABA agonists inhibited the protective effect of normal vision whereas antagonists had the opposite effect. GABAA/C agonists and D2 DA antagonists when used in combination were additive in suppressing the protective effect of normal vision. A D2 DA agonist restored some of the protective effect of normal vision that was inhibited by a GABA agonist (muscimol). The protective effect of normal vision against form-deprivation is modifiable by both the GABAergic and DAergic pathways.

Effect of text type on near work-induced contrast adaptation in myopic and emmetropic young adults

Purpose Contrast adaptation has been speculated to be an error signal for emmetropization. Myopic children exhibit higher contrast adaptation than emmetropic children. This study aimed to determine whether contrast adaptation varies with the type of text viewed by emmetropic and myopic young adults. Methods Baseline contrast sensitivity was determined in 25 emmetropic and 25 spectacle-corrected myopic young adults for 0.5, 1.2, 2.7, 4.4, and 6.2 cycles per degree (cpd) horizontal sine wave gratings. The adults spent periods looking at a 6.2 cpd high-contrast horizontal grating and reading lines of English and Chinese text (these texts comprised 1.2 cpd row and 6 cpd stroke frequencies). The effects of these near tasks on contrast sensitivity were determined, with decreases in sensitivity indicating contrast adaptation. Results Contrast adaptation was affected by the near task (F2,672 = 43.0; P < 0.001). Adaptation was greater for the grating task (0.13 ± 0.17 log unit, averaged across all frequencies) than reading tasks, but there was no significant difference between the two reading tasks (English 0.05 ± 0.13 log unit versus Chinese 0.04 ± 0.13 log unit). The myopic group showed significantly greater adaptation (by 0.04, 0.04, and 0.05 log units for English, Chinese, and grating tasks, respectively) than the emmetropic group (F1,48 = 5.0; P = 0.03). Conclusions In young adults, reading Chinese text induced similar contrast adaptation as reading English text. Myopes exhibited greater contrast adaptation than emmetropes. Contrast adaptation, independent of text type, might be associated with myopia development.

Crizotinib versus chemotherapy in advanced ALK-positive lung cancer

BACKGROUND: In single-group studies, chromosomal rearrangements of the anaplastic lymphoma kinase gene (ALK ) have been associated with marked clinical responses to crizotinib, an oral tyrosine kinase inhibitor targeting ALK. Whether crizotinib is superior to standard chemotherapy with respect to efficacy is unknown. METHODS: We conducted a phase 3, open-label trial comparing crizotinib with chemotherapy in 347 patients with locally advanced or metastatic ALK-positive lung cancer who had received one prior platinum-based regimen. Patients were randomly assigned to receive oral treatment with crizotinib (250 mg) twice daily or intravenous chemotherapy with either pemetrexed (500 mg per square meter of body-surface area) or docetaxel (75 mg per square meter) every 3 weeks. Patients in the chemotherapy group who had disease progression were permitted to cross over to crizotinib as part of a separate study. The primary end point was progression-free survival. RESULTS: The median progression-free survival was 7.7 months in the crizotinib group and 3.0 months in the chemotherapy group (hazard ratio for progression or death with crizotinib, 0.49; 95% confidence interval [CI], 0.37 to 0.64; P<0.001). The response rates were 65% (95% CI, 58 to 72) with crizotinib, as compared with 20% (95% CI, 14 to 26) with chemotherapy (P<0.001). An interim analysis of overall survival showed no significant improvement with crizotinib as compared with chemotherapy (hazard ratio for death in the crizotinib group, 1.02; 95% CI, 0.68 to 1.54; P=0.54). Common adverse events associated with crizotinib were visual disorder, gastrointestinal side effects, and elevated liver aminotransferase levels, whereas common adverse events with chemotherapy were fatigue, alopecia, and dyspnea. Patients reported greater reductions in symptoms of lung cancer and greater improvement in global quality of life with crizotinib than with chemotherapy. CONCLUSIONS: Crizotinib is superior to standard chemotherapy in patients with previously treated, advanced non-small-cell lung cancer with ALK rearrangement. (Funded by Pfizer; ClinicalTrials.gov number, NCT00932893.) Copyright © 2013 Massachusetts Medical Society.