Genome-wide linkage analysis of multiple measures of neuroticism of 2 large cohorts from Australia and the Netherlands

CONTEXT People meeting diagnostic criteria for anxiety or depressive disorders tend to score high on the personality scale of neuroticism. Studying this personality dimension can give insights into the etiology of these important psychiatric disorders. OBJECTIVES To undertake a comprehensive genome-wide linkage study of neuroticism using large study samples that have been measured multiple times and to compare the results between countries for replication and across time within countries for consistency. DESIGN Genome-wide linkage scan. SETTING Twin individuals and their family members from Australia and the Netherlands. PARTICIPANTS Nineteen thousand six hundred thirty-five sibling pairs completed self-report questionnaires for neuroticism up to 5 times over a period of up to 22 years. Five thousand sixty-nine sibling pairs were genotyped with microsatellite markers. METHODS Nonparametric linkage analyses were conducted in MERLIN-REGRESS for the mean neuroticism scores averaged across time. Additional analyses were conducted for the time-specific measures of neuroticism from each country to investigate consistency of linkage results. RESULTS Three chromosomal regions exceeded empirically derived thresholds for suggestive linkage using mean neuroticism scores: 10p 5 Kosambi cM (cM) (Dutch study sample), 14q 103 cM (Dutch study sample), and 18q 117 cM (combined Australian and Dutch study sample), but only 14q retained significance after correction for multiple testing. These regions all showed evidence for linkage in individual time-specific measures of neuroticism and 1 (18q) showed some evidence for replication between countries. Linkage intervals for these regions all overlap with regions identified in other studies of neuroticism or related traits and/or in studies of anxiety in mice. CONCLUSIONS Our results demonstrate the value of the availability of multiple measures over time and add to the optimism reported in recent reviews for replication of linkage regions for neuroticism. These regions are likely to harbor causal variants for neuroticism and its related psychiatric disorders and can inform prioritization of results from genome-wide association studies.

Patterns of entrepreneurial career development: An optimal matching analysis approach

Longitudinal studies of entrepreneurial career development are rare, and current knowledge of self-employment patterns and their relationships with individual difference characteristics is limited. In this study, the authors analyzed employment data from a subsample of 514 participants from the German Socio-Economic Panel study (1984–2008). Results of an optimal matching analysis indicated that a continuous self-employment pattern could be distinguished from four alternative employment patterns (change from employment to self-employment, full-time employees, part-time employees, and farmers). Results of a multinomial logistic regression analysis showed that certain socio-demographic characteristics (i.e., age and gender) and personality characteristics (i.e., conscientiousness and risk-taking propensity) were related to the likelihood of following a continuous self-employment pattern compared to the other employment patterns. Implications for future research on entrepreneurial career development are discussed.

Osteoporosis medication dispensing for older Australian women from 2002 to 2010: Influences of publications, guidelines, marketing activities and policy

Purpose Developments in anti-osteoporosis medications (AOMs) have led to changes in guidelines and policy, which, along with media and marketing strategies, have had an impact upon the prescribing of AOM. The aim was to examine patterns of AOM dispensing in older women (aged 76–81 years at baseline) from 2002 to 2010. Methods Administrative claims data were used to describe AOM dispensing in 4649 participants (born in 1921–1926 and still alive in 2011) in the Australian Longitudinal Study on Women's Health. The patterns were interpreted in the context of changes in guidelines, indications for subsidy, publications (scholarly and general media), and marketing activities. Results Total use of AOM increased from 134 DDD/1000/day in 2002 to 216 DDD/1000/day in 2007 but then decreased to 184 DDD/1000/day in 2010. Alendronate was the most commonly dispensed AOM but decreased from 2007, while use of risedronate (2002 onward), strontium ranelate (2007 onward) and zoledronic acid (2008 onward) increased. Etidronate and hormone replacement therapy (HRT) prescriptions gradually decreased over time. The decline in alendronate dispensing coincided with increases of other bisphosphonates and publicity about potential adverse effects of bisphosphonates, despite relaxing indications for bone density testing and subsidy for AOM. Conclusions Overall dispense of AOM from 2002 reached a peak in 2007 and thereafter declined despite increases in therapeutic options and improved subsidised access. The recent decline in overall AOM dispensing seems to be explained largely by negative publicity rather than specific changes in guidelines and policy.

Tourism Destination Preferences: A Longitudinal Analysis of Consumer Decision Sets

There have only been a small number of applications of consumer decision set theory to holiday destination choice, and these studies have tended to rely on a single cross sectional snapshot of research participants’ stated preferences. Very little has been reported on the relationship between stated destination preferences and actual travel, or changes in decision set composition over time. The paper presents a rare longitudinal examination of destination decision sets, in the context of short break holidays by car in Queensland, Australia. Two questionnaires were administered, three months apart. The first identified destination preferences while the second examined actual travel and revisited destination preferences. In relation to the conference theme, there was very little change in consumer preferences towards the competitive set of destinations over the three month period. A key implication for the destination of interest, which, in an attempt to change market perceptions, launched a new brand campaign during the period of the project, is that a long term investment in a consistent brand message will be required to change market perceptions. The results go some way to support the proposition that the positioning of a destination into a consumer’s decision set represents a source of competitive advantage.

Longitudinal Student Evaluations of a Postgraduate Unit Using Importance-Performance Analysis

The Australian tourism tertiary education sector operates in a competitive and dynamic environment, which necessitates a market orientation to be successful. Academic staff and management in the sector must regularly assess the perceptions of prospective and current students, and monitor the satisfaction levels of current students. This study is concerned with the setting and monitoring of satisfaction levels of current students, reporting the results of three longitudinal investigations of student satisfaction in a postgraduate unit. The study also addresses a limitation of a university’s generic teaching evaluation instrument. Importance-performance analysis (IPA) has been recommended as a simple but effective tool for overcoming the deficiencies of many student evaluation studies, which have generally measured only attribute importance or importance at the end of a semester. IPA was used to compare student expectations of the unit at the beginning of semester with their perceptions of performance ten weeks later. The first stage documented key benchmarks for which amendments to the unit based on student feedback could be evaluated during subsequent teaching periods.

Impact response and parametric studies of reinforced concrete circular columns

This paper presents a detailed description of the influence of critical parameters that govern the vulnerability of columns under lateral impact loads. Numerical simulations are conducted by using the Finite Element program LS-DYNA, incorporating steel reinforcement, material models and strain rate effects. A simplified method based on impact pulse generated from full scale impact tests is used for impact reconstruction and effects of the various pulse loading parameters are investigated under low to medium velocity impacts. A constitutive material model which can simulate failures under tri-axial state of stresses is used for concrete. Confinement effects are also introduced to the numerical simulation and columns of Grade 30 to 50 concrete under pure axial loading are analysed in detail. This research confirmed that the vulnerability of the axially loaded columns can be mitigated by reducing the slenderness ratio and concrete grade, and by choosing the design option with a minimal amount of longitudinal steel. Additionally, it is evident that approximately a 50% increase in impact capacity can be gained for columns in medium rise buildings by enhancing the confinement effects alone. Results also indicated that the ductility as well as the mode of failure under impact can be changed with the volumetric ratio of lateral steel. Moreover, to increase the impact capacity of the vulnerable columns, a higher confining stress is required. The general provisions of current design codes do not sufficiently cover this aspect and hence this research will provide additional guidelines to overcome the inadequacies of code provisions.

Enhancing students' self-concepts and related constructs: A critical longitudinal analysis capitalising on and combining promising enhancement techniques for educational settings

Enhancing children's self-concepts is widely accepted as a critical educational outcome of schooling and is postulated as a mediating variable that facilitates the attainment of other desired outcomes such as improved academic achievement. Despite considerable advances in self-concept research, there has been limited progress in devising teacher-administered enhancement interventions. This is unfortunate as teachers are crucial change agents during important developmental periods when self-concept is formed. The primary aim of the present investigation is to build on the promising features of previous self-concept enhancement studies by: (a) combining two exciting research directions developed by Burnett and Craven to develop a potentially powerful cognitive-based intervention; (b) incorporating recent developments in theory and measurement to ensure that the multidimensionality of self-concept is accounted for in the research design; (c) fully investigating the effects of a potentially strong cognitive intervention on reading, mathematics, school and learning self-concepts by using a large sample size and a sophisticated research design; (d) evaluating the effects of the intervention on affective and cognitive subcomponents of reading, mathematics, school and learning self-concepts over time to test for differential effects of the intervention; (e) modifying and extending current procedures to maximise the successful implementation of a teacher-mediated intervention in a naturalistic setting by incorporating sophisticated teacher training as suggested by Hattie (1992) and including an assessment of the efficacy of implementation; and (f) examining the durability of effects associated with the intervention.

Panel studies of new venture creation : a review and suggestions for future research

We review all journal articles based on “PSED-type” research, i.e., longitudinal, empirical studies of large probability samples of on-going, business start-up efforts. We conclude that the research stream has yielded interesting findings; sometimes by confirming prior research with a less bias-prone methodology and at other times by challenging whether prior conclusions are valid for the early stages of venture development. Most importantly, the research has addressed new, process-related research questions that prior research has shunned or been unable to study in a rigorous manner. The research has revealed an enormous and fascinating variability in new venture creation that also makes it challenging to arrive at broadly valid generalizations. An analysis of the findings across studies as well as an examination of those studies that have been relatively more successful at explaining outcomes give good guidance regarding what is required in order to achieve strong and credible results. We compile and present such advice to users of existing data sets and designers of new projects in the following areas: Statistically representative and/or theoretically relevant sampling; Level of analysis issues; Dealing with process heterogeneity; Dealing with other heterogeneity issues, and Choice and interpretation of dependent variables.

Panel studies of new venture creation: a methods-focused review and suggestions for future research

Longitudinal panel studies of large, random samples of business start-ups captured at the pre-operational stage allow researchers to address core issues for entrepreneurship research, namely, the processes of creation of new business ventures as well as their antecedents and outcomes. Here, we perform a methods-orientated review of all 83 journal articles that have used this type of data set, our purpose being to assist users of current data sets as well as designers of new projects in making the best use of this innovative research approach. Our review reveals a number of methods issues that are largely particular to this type of research. We conclude that amidst exemplary contributions, much of the reviewed research has not adequately managed these methods challenges, nor has it made use of the full potential of this new research approach. Specifically, we identify and suggest remedies for context-specific and interrelated methods challenges relating to sample definition, choice of level of analysis, operationalization and conceptualization, use of longitudinal data and dealing with various types of problematic heterogeneity. In addition, we note that future research can make further strides towards full utilization of the advantages of the research approach through better matching (from either direction) between theories and the phenomena captured in the data, and by addressing some under-explored research questions for which the approach may be particularly fruitful.

Neuroprotective effects of low-dose lithium in individuals at ultra-high risk for psychosis. A longitudinal MRI/MRS study

Objectives: To investigate if low-dose lithium may counteract the microstructural and metabolic brain changes proposed to occur in individuals at ultra-high risk (UHR) for psychosis. Methods: Hippocampal T2 relaxation time (HT2RT) and proton magnetic resonance spectroscopy (1H-MRS) measurements were performed prior to initiation and following three months of treatment in 11 UHR patients receiving low-dose lithium and 10 UHR patients receiving treatment as usual (TAU). HT2RT and 1H-MRS percentage change scores between scans were compared using one-way ANOVA and correlated with behavioural change scores. Results: Low-dose lithium significantly reduced HT2RT compared to TAU (p=0.018). No significant group by time effects were seen for any brain metabolites as measured with 1H-MRS, although myo-inositol, creatine, choline-containing compounds and NAA increased in the group receiving low-dose lithium and decreased or remained unchanged in subjects receiving TAU. Conclusions: This pilot study suggests that low-dose lithium may protect the microstructure of the hippocampus in UHR states as reflected by significantly decreasing HT2RT. Larger scale replication studies in UHR states using T2 relaxation time as a proxy for emerging brain pathology seem a feasible mean to test neuroprotective strategies such as low-dose lithium as potential treatments to delay or even prevent the progression to full-blown disorder.

A longitudinal assessment of chronic wound fluid to detect biochemical indicators of healing

Chronic venous leg ulcers are a detrimental health issue plaguing our society, resulting in long term pain, immobility and decreased quality of life for a large proportion of sufferers. The frequency of these chronic wounds has led current research to focus on the wound environment to provide important information regarding the prolonged, fluctuated or static healing patterns of these wounds. Disruption to the normal wound healing process results in release of multiple factors in the wound environment that could correlate to wound chronicity. These biochemical factors can often be detected through non-invasively sampling chronic wound fluid (CWF) from the site of injury. Of note, whilst there are numerous studies comparing acute and chronic wound fluids, there have not been any reports in the literature employing a longitudinal study in order to track biochemical changes in wound fluid as patients transition from a non-healing to healed state. Initially the objective of this study was to identify biochemical changes in CWF associated with wound healing using a proteomic approach. The proteomic approach incorporated a multi-dimensional liquid chromatography fractionation technique coupled with mass spectrometry (MS) to enable identification of proteins present in lower concentrations in CWF. Not surprisingly, many of the proteins identified in wound fluid were acute phase proteins normally expressed during the inflammatory phase of healing. However, the number of proteins positively identified by MS was quite low. This was attributed to the diverse range in concentration of protein species in CWF making it challenging to detect the diagnostically relevant low molecular weight proteins. In view of this, SELDI-TOF MS was also explored as a means to target low molecular weight proteins in sequential patient CWF samples during the course of healing. Unfortunately, the results generated did not yield any peaks of interest that were altered as wounds transitioned to a healed state. During the course of proteomic assessment of CWF, it became evident that a fraction of non-proteinaceous compounds strongly absorbed at 280 nm. Subsequent analyses confirmed that most of these compounds were in fact part of the purine catabolic pathway, possessing distinctive aromatic rings and which results in high absorbance at 254 nm. The accumulation of these purinogenic compounds in CWF suggests that the wound bed is poorly oxygenated resulting in a switch to anaerobic metabolism and consequently ATP breakdown. In addition, the presence of the terminal purine catabolite, uric acid (UA), indicates that the enzyme xanthine oxidoreductase (XOR) catalyses the reaction of hypoxanthine to xanthine and finally to UA. More importantly, the studies provide evidence for the first time of the exogenous presence of XOR in CWF. XOR is the only enzyme in humans capable of catalysing the production of UA in conjunction with a burst of the highly reactive superoxide radical and other oxidants like H2O2. Excessive release of these free radicals in the wound environment can cause cellular damage disrupting the normal wound healing process. In view of this, a sensitive and specific assay was established for monitoring low concentrations of these catabolites in CWF. This procedure involved combining high performance liquid chromatography (HPLC) with tandem mass spectrometry and multiple reaction monitoring (MRM). This application was selective, using specific MRM transitions and HPLC separations for each analyte, making it ideal for the detection and quantitation of purine catabolites in CWF. The results demonstrated that elevated levels of UA were detected in wound fluid obtained from patients with clinically worse ulcers. This suggests that XOR is active in the wound site generating significant amounts of reactive oxygen species (ROS). In addition, analysis of the amount of purine precursors in wound fluid revealed elevated levels of purine precursors in wound fluid from patients with less severe ulcers. Taken together, the results generated in this thesis suggest that monitoring changes of purine catabolites in CWF is likely to provide valuable information regarding the healing patterns of chronic venous leg ulcers. XOR catalysis of purine precursors not only provides a method for monitoring the onset, prognosis and progress of chronic venous leg ulcers, but also provides a potential therapeutic target by inhibiting XOR, thus blocking UA and ROS production. Targeting a combination of these purinogenic compounds and XOR could lead to the development of novel point of care diagnostic tests. Therefore, further investigation of these processes during wound healing will be worthwhile and may assist in elucidating the pathogenesis of this disease state, which in turn may lead to the development of new diagnostics and therapies that target these processes.

A longitudinal study of change in preservice teachers’ personal epistemologies

There is strong evidence to show that beliefs about knowing and knowledge held by individuals (personal epistemologies) influence preservice teachers’ learning strategies and learning outcomes (Muis, 2004). However, we know very little about how preservice teachers’ personal epistemologies change as they progress through their teacher education programs. This study investigated changes in personal epistemology and beliefs about learning for a group of preservice teachers as they progressed through the four years of a Bachelor of Education degree. Preservice teachers completed the Epistemological Beliefs Survey (EBS, Kardash & Wood, 2000) when they commenced their course (Time 1) when they were in the 3rd year of their course (Time 2) and then again in the final year of their degree (Time 3). Findings indicated that there were significant changes in preservice teachers’ personal epistemologies between course entry and the final year of their course across all but one of the dimensions measured. Results are discussed in terms of the implications for teaching and teacher education.

Parenting satisfaction and self-efficacy : a longitudinal study of mothers of children with Down Syndrome

Continuities and changes in parenting sense of competence were examined for mothers of children with Down syndrome from early childhood to adolescence. The sample comprised 25 mothers whose child with Down syndrome was aged 4-6 years in the first phase of the study, and 11-15 years at the second time point. Maternal satisfaction with parenting increased over time, but there were no changes in parenting self-efficacy. Scores on these measures were no different from those reported in a normative sample of mothers of typically developing children, suggesting that the challenges of parenting a child with Down syndrome do not impact significantly on parenting sense of competence during the early childhood and adolescent periods. There were some significant relationships of maternal sense of competence with child characteristics and self-reported parenting style, mostly in the expected direction.

Four years on – are the Gazelles still running? A longitudinal study of firm performance after a period of rapid growth

Gazelles, or very rapidly growing firms, are important because they contribute disproportionately to economic growth. There is a concern that some of these firms pursue growth too aggressively resulting in lower subsequent performance. We investigate the relationship between growth and subsequent profitability for gazelle firms, and how this is moderated by firm strategy. Previous empirical research regarding the growth-profitability relationship for firms in general is rather inconclusive, with only one study specifically investigating gazelle firms. Likewise, there are theoretical arguments both for and against growth leading to profitability that equally apply to gazelle firms. Further, while contingency theory might suggest the relationship depends on the firm’s strategy, earlier studies have not investigated this relationship. We address these questions using longitudinal data (seven years) for a sample of 964 Danish Gazelle firms. Our study finds a clear positive relationship between growth and subsequent profitability among gazelle firms. Moreover, this relationship is stronger for firms pursuing a broad market strategy rather than a focus or niche strategy. An important managerial implication is that the growth strategy should be clearly integrated with the general strategic orientation of the firm.

Evaluation of the GHR car following model for traffic safety studies

Traffic safety studies mandate more than what existing micro-simulation models can offer as they postulate that every driver exhibits a safe behaviour. All the microscopic traffic simulation models are consisting of a car-following model and the Gazis–Herman–Rothery (GHR) car-following model is a widely used model. This paper highlights the limitations of the GHR car-following model capability to model longitudinal driving behaviour for safety study purposes. This study reviews and compares different version of the GHR model. To empower the GHR model on precise metrics reproduction a new set of car-following model parameters is offered to simulate unsafe vehicle conflicts. NGSIM vehicle trajectory data is used to evaluate the new model and short following headways and Time to Collision are employed to assess critical safety events within traffic flow. Risky events are extracted from available NGSIM data to evaluate the modified model against the generic versions of the GHR model. The results from simulation tests illustrate that the proposed model does predict the safety metrics better than the generic GHR model. Additionally it can potentially facilitate assessing and predicting traffic facilities’ safety using microscopic simulation. The new model can predict Near-miss rear-end crashes.