Evidence for CRHR1 in multiple sclerosis using supervised machine learning and meta-analysis in 12 566 individuals

The primary genetic risk factor in multiple sclerosis (MS) is the HLA-DRB1*1501 allele; however, much of the remaining genetic contribution to MS has yet to be elucidated. Several lines of evidence support a role for neuroendocrine system involvement in autoimmunity which may, in part, be genetically determined. Here, we comprehensively investigated variation within eight candidate hypothalamic-pituitary-adrenal (HPA) axis genes and susceptibility to MS. A total of 326 SNPs were investigated in a discovery dataset of 1343 MS cases and 1379 healthy controls of European ancestry using a multi-analytical strategy. Random Forests, a supervised machine-learning algorithm, identified eight intronic SNPs within the corticotrophin-releasing hormone receptor 1 or CRHR1 locus on 17q21.31 as important predictors of MS. On the basis of univariate analyses, six CRHR1 variants were associated with decreased risk for disease following a conservative correction for multiple tests. Independent replication was observed for CRHR1 in a large meta-analysis comprising 2624 MS cases and 7220 healthy controls of European ancestry. Results from a combined meta-analysis of all 3967 MS cases and 8599 controls provide strong evidence for the involvement of CRHR1 in MS. The strongest association was observed for rs242936 (OR = 0.82, 95% CI = 0.74-0.90, P = 9.7 × 10-5). Replicated CRHR1 variants appear to exist on a single associated haplotype. Further investigation of mechanisms involved in HPA axis regulation and response to stress in MS pathogenesis is warranted. © The Author 2010. Published by Oxford University Press. All rights reserved.

Developing a framework for Six Sigma in financial service institutions : empirical evidence from expert interviews

Six Sigma is considered to be an important management philosophy to obtain satisfied customers. But financial service organisations have been slow to adopt Six Sigma issues so far. Despite the extensive effort that has been invested and benefits that can be obtained, the systematic implementation of Six Sigma in financial service organisations is limited. As a company wide implementation framework is missing so far, this paper tries to fill this gap. Based on theory, a conceptual framework is developed and evaluated by experts from financial institutions. The results show that it is very important to link Six Sigma with the strategic as well as the operations level. Furthermore, although Six Sigma is a very important method for improving quality of processes others such as Lean Management are also used This requires a superior project portfolio management to coordinate resources and projects of Six Sigma with the other methods used. Beside the theoretical contribution, the framework can be used by financial service companies to evaluate their Six Sigma activities. Thus, the framework grounded through literature and empirical data will be a useful guide for sustainable and successful implementation of a Six Sigma initiative in financial service organisations.

Managing specialised knowledge in technopreneurial firms : evidence from Australian SMEs

This paper analyses particularities of the knowledge management process in technopreneurial firms with particular focus on knowledge identification, acquisition, utilisation and integration. Using a qualitative investigation from a sample of Australian SMEs, a number of key observations are derived which show the challenges of managing knowledge and how important knowledge management is as a management tool for R&D and innovation process in technology-oriented SMEs. Findings suggest that knowledge management and integration processes in these firms are very much project focused and mainly based on ad hoc and informal processes and not embedded within the overall organisational routines.

Exercise for breast cancer survivors: bridging the gap between evidence and practice

Evidence supporting the benefits of exercise following the diagnosis of breast cancer is overwhelming and compelling. Exercise reduces the severity and number of treatment-related side effects, optimizes quality of life during and following treatment, and may optimize survival. Yet, exercise does not uniformly form part of the standards of care provided to women following a breast cancer diagnosis. This commentary summarizes the evidence in support of exercise as a form of adjuvant treatment and identifies and discusses potential issues preventing the formal integration of exercise into breast cancer care. Proposed within the commentary is a model of breast cancer care that incorporates exercise prescription as a key component but also integrates the need for surveillance and management for common breast cancer treatment-related morbidities, as well as education. While future research evaluating the potential cost savings through implementation of such amodel is required, a committed, collaborative approach by clinicians, allied health professionals, and researchers will be instrumental in bridging the gap between research and practice.

Trends in policies, programs and practices in the Australasian First Year Experience literature 2000-2010. The First Year in Higher Education Research Series on Evidence-based Practice. Number 1

This publication is the first in a series of scholarly reports on research-based practice related to the First Year Experience in Higher Education. This report synthesises evidence about practice-based initiatives and pragmatic approaches in Aotearoa (New Zealand) and Australia that aim to enhance the experience of commencing students in the higher education sector. Trends in policies, programs and practices ... examines the first year experience literature from 2000-2010. It acknowledges the uniqueness of the Australasian socio-political context and its influence on the interests and output of researchers. The review surveyed almost 400 empirical reports and conceptual discussions produced over the decade that dealt with the stakeholders, institutions and the higher education sector in Australasia. The literature is examined through two theoretical constructs or “lenses”: first, a set of first year curriculum design principles and second, the generational approach to describing the maturation of initiatives. These outcomes and suggested directions for further research provide the challenges and the opportunities for FYE adherents, both scholars and practitioners, to grapple with in the next decade.

A capabilities-based approach to obtaining a deeper understanding of information technology governance effectiveness : evidence from IT steering committees

Given the substantial investment in information technology (IT), and the significant impact IT has on organizational success, organizations consume considerable resources to manage acquisition and use of their IT resources. While various arguments proposed suggest which IT governance arrangements may work best, our understanding of the effectiveness of such initiatives is limited. We examine the relationship between the effectiveness of IT steering committee driven IT governance initiatives and firm's IT management and IT infrastructure related capabilities. We further propose that firm's ITrelated capabilities generated through IT governance initiatives should improve its business processes and firm-level performance. We test these relationships empirically by a field survey. Results suggest that firms' effectiveness of IT steering committee driven IT governance initiatives positively relates to the level of their IT-related capabilities. We also found positive relationships between IT-related capabilities and internal process-level performance. Our results also support that improvement in internal process-level performance positively relates to improvement in customer service and firm-level performance.

The relationship between self-reported animal fear and ERP modulation : Evidence for enhanced processing and fear of harmless invertebrates in snake- and spider-fearful individuals

The present study used ERPs to compare processing of fear-relevant (FR) animals (snakes and spiders) and non-fear-relevant (NFR) animals similar in appearance (worms and beetles). EEG was recorded from 18 undergraduate participants (10 females) as they completed two animal-viewing tasks that required simple categorization decisions. Participants were divided on a post hoc basis into low snake/spider fear and high snake/spider fear groups. Overall, FR animals were rated higher on fear and elicited a larger LPC. However, individual differences qualified these effects. Participants in the low fear group showed clear differentiation between FR and NFR animals on subjective ratings of fear and LPC modulation. In contrast, participants in the high fear group did not show such differentiation between FR and NFR animals. These findings suggest that the salience of feared-FR animals may generalize on both a behavioural and electro-cortical level to other animals of similar appearance but of a non-harmful nature.

No evidence for subliminal affective priming with emotional facial expression primes

The present study investigated whether facial expressions of emotion presented outside consciousness awareness will elicit evaluative responses as assessed in affective priming. Participants were asked to evaluate pleasant and unpleasant target words that were preceded by masked or unmasked schematic (Experiment 1) or photographic faces (Experiments 1 and 2) with happy or angry expressions. They were either required to perform the target evaluation only or to perform the target evaluation and to name the emotion expressed by the face prime. Prime-target interval was 300 ms in Experiment 1 and 80 ms in Experiment 2. Naming performance confirmed the effectiveness of the masking procedure. Affective priming was evident after unmasked primes in tasks that required naming of the facial expressions for schematic and photographic faces and after unmasked primes in tasks that did not require naming for photographic faces. No affective priming was found after masked primes. The present study failed to provide evidence for affective priming with masked face primes, however, it indicates that voluntary attention to the primes enhances affective priming.

Behavioural evidence for social preferences

A central topic in economics is the existence of social preferences. Behavioural economics in general has approached the issue from several angles. Controlled experimental settings, surveys, and field experiments are able to show that in a number of economic environments, people usually care about immaterial things such as fairness or equity of allocations. Findings from experimental economics specifically have lead to large increase in theories addressing social preferences. Most (pro)social phenomena are well understood in the experimental settings but very difficult to observe 'in the wild'. One criticism in this regard is that many findings are bound by the artificial environment of the computer lab or survey method used. A further criticism is that the traditional methods also fail to directly attribute the observed behaviour to the mental constructs that are expected to stand behind them. This thesis will first examine the usefulness of sports data to test social preference models in a field environment, thus overcoming limitations of the lab with regards to applicability to other - non-artificial - environments. The second major contribution of this research establishes a new neuroscientific tool - the measurement of the heart rate variability - to observe participants' emotional reactions in a traditional experimental setup.

Impact of embeddedness in ethnic networks on business growth : evidence from Chinese immigrant entrepreneurs in Australia

Immigrant entrepreneurship, or, self-employment by immigrants (Light & Bonacich, 1988), has been of growing interest to researchers (Hosler, 1996). This is due in part to major immigrant receiving countries, such as Australia, the United States, Canada, the United Kingdom and Western Europe, experiencing a high growth rate in their immigrant populations, leading to a more visible presence of immigrant business in major cities (Woon, 2008). By starting their own businesses, immigrant entrepreneurs may circumvent some of the barriers and disadvantages encountered in looking for a job (Sequeira & Rasheed, 2006). Successful immigrant entrepreneurs will integrate into the economy by creating jobs, providing products and services for members of their own ethnic community and society, as well as introducing new products and services that expand consumers’ choices (Rath & Kloosterman, 2000). Immigrant entrepreneurs tend to start business within their ethnic enclave, as it is an integral part of their social and cultural context and the location where ethnic resources reside (Logan et al., 2002). An ethnic enclave is an interdependent network of social and business relationships that are geographically concentrated with its co-ethnic people (Portes & Bach, 1985).

Genetic evidence for the vital function of osterix in cementogenesis

To date, attempts to regenerate a complete tooth, including the critical periodontal tissues associated with the tooth root, have not been successful. Controversy still exists regarding the origin of the cell source for cellular cementum (epithelial or mesenchymal). This disagreement may be partially due to a lack of understanding of the events leading to the initiation and development of the tooth roots and supportive tissues, such as the cementum. Osterix (OSX) is a transcriptional factor essential for osteogenesis, but its role in cementogenesis has not been addressed. In the present study, we first documented a close relationship between the temporal- and spatial-expression pattern of OSX and the formation of cellular cementum. We then generated 3.6 Col 1-OSX transgenic mice, which displayed accelerated cementum formation vs. WT controls. Importantly, the conditional deletion of OSX in the mesenchymal cells with two different Cre systems (the 2.3 kb Col 1 and an inducible CAG-CreER) led to a sharp reduction in cellular cementum formation (including the cementum mass and mineral deposition rate) and gene expression of dentin matrix protein 1 (DMP1) by cementocytes. However, the deletion of the OSX gene after cellular cementum formed did not alter the properties of the mature cementum as evaluated by backscattered SEM and resin-cast SEM. Transient transfection of Osx in the cementoblasts in vitro significantly inhibited cell proliferation and increased cell differentiation and mineralization. Taken together, these data support 1) the mesenchymal origin of cellular cementum (from PDL progenitor cells); 2) the vital role of OSX in controlling the formation of cellular cementum; and 3) the limited remodeling of cellular cementum in adult mice.

Mapping Services to Support a Patient's Journey through Evidence-Based Care Pathways After a Cardiac Event

Background: There are inequalities in geographical access and delivery of health care services in Australia, particularly for cardiovascular disease (CVD), Australia's major cause of death. Analyses and models that can inform and positively influence strategies to augment services and preventative measures are needed. The Cardiac-ARIA project is using geographical spatial technology (GIS) to develop a national index for each of Australia's 13,000 population centres. The index will describe the spatial distribution of CVD health care services available to support populations at risk, in a timely manner, after a major cardiac event. Methods: In the initial phase of the project, an expert panel of cardiologists and an emergency physician have identified key elements of national and international guidelines for management of acute coronary syndromes, cardiac arrest, life-threatening arrhythmias and acute heart failure, from the time of onset (potentially dial 000) to return from the hospital to the community (cardiac rehabilitation). Results: A systematic search has been undertaken to identify the geographical location of, and type of, cardiac services currently available. This has enabled derivation of a master dataset of necessary services, e.g. telephone networks, ambulance, RFDS, helicopter retrieval services, road networks, hospitals, general practitioners, medical community centres, pathology services, CCUs, catheterisation laboratories, cardio-thoracic surgery units and cardiac rehabilitation services. Conclusion: This unique and innovative project has the potential to deliver a powerful tool to both highlight and combat the burden of disease of CVD in urban and regional Australia.

The use of dashboards in performance management : evidence from sales managers

The purpose of this paper is to identify and empirically examine the key features, purposes, uses, and benefits of performance dashboards. We find that only about a quarter of the sales managers surveyed1 in Finland used a dashboard, which was lower than previously reported. Dashboards were used for four distinct purposes: (i) monitoring, (ii) problem solving, (iii) rationalizing, and (iv) communication and consistency. There was a high correlation between the different uses of dashboards and user productivity indicating that dashboards were perceived as effective tools in performance management, not just for monitoring one‟s own performance but for other purposes including communication. The quality of the data in dashboards did not seem to be a concern (except for completeness) but it was a critical driver regarding its use. This is the first empirical study on performance dashboards in terms of adoption rates, key features, and benefits. The study highlights the research potential and benefits of dashboards, which could be valuable for future researchers and practitioners.

The two dimensions of virtual and collocated project teams or what project team members WANT and GET : empirical evidence

The current paper compares and investigates the discrepancies in motivational drives of project team members with respect to their project environment in collocated and distributed (virtual) project teams. The set of factors, which in this context are called ‘Sense of Ownership’, is used as a scale to measure these discrepancies using one tailed t tests. These factors are abstracted from theories of motivation, team performance, and team effectiveness and are related to ‘Nature of Work’, ‘Rewards’, and ‘Communication’. It has been observed that ‘virtualness’ does not seem to impact the motivational drives of the project team members or the way the project environments provide or support those motivational drives in collocated and distributed projects. At a more specific level in terms of the motivational drives of the project team (‘WANT’) and the ability of the project environment to provide or support those factors (‘GET’), in collocated project teams, significant discrepancies were observed with respect to financial and non financial rewards, learning opportunities, nature of work and project specific communication, while in distributed teams, significant discrepancies with respect to project centric communication, followed by financial rewards and nature of work. Further, distributed project environments seem to better support the team member motivation than collocated project environments. The study concludes that both the collocated and distributed project environments may not be adequately supporting the motivational drives of its project team members, which may be frustrating to them. However, members working in virtual team environments may be less frustrated than their collocated counterparts as virtual project environments are better aligned with the motivational drives of their team members vis-à-vis the collocated project environments.

Evidence for time dependency of molecular rate estimates

Long-term changes in the genetic composition of a population occur by the fixation of new mutations, a process known as substitution. The rate at which mutations arise in a population and the rate at which they are fixed are expected to be equal under neutral conditions (Kimura, 1968). Between the appearance of a new mutation and its eventual fate of fixation or loss, there will be a period in which it exists as a transient polymorphism in the population (Kimura and Ohta, 1971). If the majority of mutations are deleterious (and nonlethal), the fixation probabilities of these transient polymorphisms are reduced and the mutation rate will exceed the substitution rate (Kimura, 1983). Consequently, different apparent rates may be observed on different time scales of the molecular evolutionary process (Penny, 2005; Penny and Holmes, 2001). The substitution rate of the mitochondrial protein-coding genes of birds and mammals has been traditionally recognized to be about 0.01 substitutions/site/million years (Myr) (Brown et al., 1979; Ho, 2007; Irwin et al., 1991; Shields and Wilson, 1987), with the noncoding D-loop evolving several times more quickly (e.g., Pesole et al., 1992; Quinn, 1992). Over the past decade, there has been mounting evidence that instantaneous mutation rates substantially exceed substitution rates, in a range of organisms (e.g., Denver et al., 2000; Howell et al., 2003; Lambert et al., 2002; Mao et al., 2006; Mumm et al., 1997; Parsons et al., 1997; Santos et al., 2005). The immediate reaction to the first of these findings was that the polymorphisms generated by the elevated mutation rate are short-lived, perhaps extending back only a few hundred years (Gibbons, 1998; Macaulay et al., 1997). That is, purifying selection was thought to remove these polymorphisms very rapidly.