The importance of modelling heterogeneity in complex disease: application to NIMH Schizophrenia Genetics Initiative data

As for other complex diseases, linkage analyses of schizophrenia (SZ) have produced evidence for numerous chromosomal regions, with inconsistent results reported across studies. The presence of locus heterogeneity appears likely and may reduce the power of linkage analyses if homogeneity is assumed. In addition, when multiple heterogeneous datasets are pooled, inter-sample variation in the proportion of linked families (alpha) may diminish the power of the pooled sample to detect susceptibility loci, in spite of the larger sample size obtained. We compare the significance of linkage findings obtained using allele-sharing LOD scores (LOD(exp))-which assume homogeneity-and heterogeneity LOD scores (HLOD) in European American and African American NIMH SZ families. We also pool these two samples and evaluate the relative power of the LOD(exp) and two different heterogeneity statistics. One of these (HLOD-P) estimates the heterogeneity parameter alpha only in aggregate data, while the second (HLOD-S) determines alpha separately for each sample. In separate and combined data, we show consistently improved performance of HLOD scores over LOD(exp). Notably, genome-wide significant evidence for linkage is obtained at chromosome 10p in the European American sample using a recessive HLOD score. When the two samples are combined, linkage at the 10p locus also achieves genome-wide significance under HLOD-S, but not HLOD-P. Using HLOD-S, improved evidence for linkage was also obtained for a previously reported region on chromosome 15q. In linkage analyses of complex disease, power may be maximised by routinely modelling locus heterogeneity within individual datasets, even when multiple datasets are combined to form larger samples.

Understanding the heterogeneity of entrepreneurship education: going beyond Gartner

This paper seeks to draw attention to the importance of appreciating and using ever-present diversity to achieve increased legitimacy for entrepreneurship education. As such, it aims to draw the reader into a reflective process of discovery as to why entrepreneurship education is important and how such importance can be prolonged. Design/methodology/approach - The paper revisits Gartner's 1985 conceptual framework for understanding the complexity of entrepreneurship. The paper proposes an alternative framework based on the logic of Gartner's framework to advance the understanding of entrepreneurship education. The authors discuss the dimensions of the proposed framework and explain the nature of the dialogic relations contained within. Findings - It is argued that the proposed conceptual framework provides a new way to understand ever-present heterogeneity related to the development and delivery of entrepreneurship education. Practical implications - The paper extends an invitation to the reader to audit their own involvement and proximity to entrepreneurship education. It argues that increased awareness of the value that heterogeneity plays in student learning outcomes and programme branding is directly related to the presence of heterogeneity across the dimensions of the conceptual framework. Originality/value - The paper introduces a simple yet powerlu1 means of understanding what factors contribute to the success or otherwise of developing and delivering entrepreneurship education. The simplicity of the approach suggested provides all entrepreneurship educators with the means to audit all facets of their programme.

Developing a supportive culture for teaching and learning : a university, faculty and school perspective

In the early 1990's the University of Salford was typical of most pre-1992 Universities in that whilst students provided much of it's income, little attention was paid to pedagogy. As Warren Piper (1994) observed, University teachers were professional in their subject areas but generally did not seek to acquire a pedagogy of HE. This was the case in Alsford. Courses were efficiently run but only a minority of staff were engaged in actively considering learning and teaching issues. Instead staff time was spent on research and commercial activity.----- In the mid-1990's the teaching environment began to change significantly. As well as Dearing, the advent of QAA and teaching quality reviews, Salford was already experiencing changes in the characteristics of its student body. Wideing access was on our agenda before it was so predominant nationally. With increasing numbers and heterogeneity of students as well as these external factors, new challenges were facing the University and teaching domain.----- This paper describes how a culture which values teaching, learning and pedagogic inquiry is being created in the university. It then focuses on parts of this process specific to the Faculty of Business and Informatics, namely the Faculty's Learning and Teaching Research Network and the establishment of the Centre for Construction Education in the School of Construction and Property Management.----- The Faculty of Business and Informatics' Learning and Teaching Research Network aims to raise the profile, quality and volume of pedagogic research across the five schools in the faculty. The initiative is targeted at all academics regardless of previous research experience. We hope to grow and nurture research potential where it exists and to acknowledge and use the existing expertise of subject-based researchers in collaborative ventures. We work on the principle that people are deliged to share what they know but need appreciation and feedback for doing so. A further ain is to surface and celebrate the significant amount of tacit knowledge in the area of pedagogy evidenced by the strength of student and employer feedback in many areas of the faculty's teaching.----- The Faculty embraces generic and core management expertise but also includes applied management disciplines in information systems and construction and property management where internationally leading research activities and networked centres of excellence have been established. Drawing from this experience, and within the context of the Faculty network, a Centre for Construction Education is being established with key international external partners to develop a sustainable business model of an enterprising pedagogic centre that can undertake useful research to underpin teaching in the Faculty whilst offering sustainable business services to allow it to benefit from pump-priming grant funding.----- Internal and external networking are important elements in our plans and ongoing work. Key to this are our links with the LTSN subject centres (BEST and CEBE) and the LTSN generic centre. The paper discusses networking as a concept and gives examples of practices which have proved useful in this context.----- The academic influences on our approach are also examined. Dixon’s (2000) work examining how a range of companies succeed through internal knowledge sharing has provided a range of transferable practices. We also examine the notion of dialogue in this context, defined by Ballantyne (1999) as ‘The interactive human process of reasoning together which comes into being through interactions based on spontaneity or need and is enabled by trust’ Social constructionist principles of Practical Authorship (Shotter, 1993, Pavlica, Holman and Thorpe, 1998)) have also proved useful in developing our perspective on learning and knowledge creation within our community of practice.

Venture idea newness, relatedness and performance in nascent ventures

Principal Topic The study of the origin and characteristics of venture ideas - or ''opportunities'' as they are often called - and their contextual fit are key research goals in entrepreneurship (Davidsson, 2004). We define venture idea as ''the core ideas of an entrepreneur about what to sell, how to sell, whom to sell and how an entrepreneur acquire or produce the product or service which he/she sells'' for the purpose of this study. When realized the venture idea becomes a ''business model''. Even though venture ideas are central to entrepreneurship yet its characteristics and their effect to the entrepreneurial process is mysterious. According to Schumpeter (1934) entrepreneurs could creatively destruct the existing market condition by introducing new product/service, new production methods, new markets, and new sources of supply and reorganization of industries. The introduction, development and use of new ideas are generally called as ''innovation'' (Damanpour & Wischnevsky, 2006) and ''newness'' is a property of innovation and is a relative term which means that the degree of unfamiliarity of venture idea either to a firm or to a market. However Schumpeter's (1934) discusses five different types of newness, indicating that type of newness is an important issue. More recently, Shane and Venkataraman (2000) called for research taking into consideration not only the variation of characteristics of individuals but also heterogeneity of venture ideas, Empirically, Samuelson (2001, 2004) investigated process differences between innovative venture ideas and imitative venture ideas. However, he used only a crude dichotomy regarding the venture idea newness. According to Davidsson, (2004) as entrepreneurs could introduce new economic activities ranging from pure imitation to being new to the entire world market, highlighting that newness is a matter of degree. Dahlqvist (2007) examined the venture idea newness and made and attempt at more refined assessment of the degree and type of newness of venture idea. Building on these predecessors our study refines the assessment of venture idea newness by measuring the degree of venture idea newness (new to the world, new to the market, substantially improved while not entirely new, and imitation) for four different types of newness (product/service, method of production, method of promotion, and customer/target market). We then related type and degree of newness to the pace of progress in nascent venturing process. We hypothesize that newness will slow down the business creation process. Shane & Venkataraman (2000) introduced entrepreneurship as the nexus of opportunities and individuals. In line with this some scholars has investigated the relationship between individuals and opportunities. For example Shane (2000) investigates the relatedness between individuals' prior knowledge and identification of opportunities. Shepherd & DeTinne (2005) identified that there is a positive relationship between potential financial reward and the identification of innovative venture ideas. Sarasvathy's 'Effectuation Theory'' assumes high degree of relatedness with founders' skills, knowledge and resources in the selection of venture ideas. However entrepreneurship literature is scant with analyses of how this relatedness affects to the progress of venturing process. Therefore, we assess the venture ideas' degree of relatedness to prior knowledge and resources, and relate these, too, to the pace of progress in nascent venturing process. We hypothesize that relatedness will increase the speed of business creation. Methodology For this study we will compare early findings from data collected through the Comprehensive Australian Study of Entrepreneurial Emergence (CAUSEE). CAUSEE is a longitudinal study whose primary objective is to uncover the factors that initiate, hinder and facilitate the process of emergence and development of new firms. Data were collected from a representative sample of some 30,000 households in Australia using random digit dialing (RDD) telephone survey interviews. Through the first round of data collection identified 600 entrepreneurs who are currently involved in the business start-up process. The unit of the analysis is the emerging venture, with the respondent acting as its spokesperson. The study methodology allows researchers to identify ventures in early stages of creation and to longitudinally follow their progression through data collection periods over time. Our measures of newness build on previous work by Dahlqvist (2007). Our adapted version was developed over two pre-tests with about 80 participants in each. The measures of relatedness were developed through the two rounds of pre-testing. The pace of progress in the venture creation process is assessed with the help of time-stamped gestation activities; a technique developed in the Panel Study of Entrepreneurial Dynamics (PSED). Results and Implications We hypothesized that venture idea newness slows down the venturing process whereas relatedness facilitates the venturing process. Results of 600 nascent entrepreneurs in Australia indicated that there is marginal support for the hypothesis that relatedness assists the gestation progress. Newness is significant but is the opposite sign to the hypothesized. The results give number of implications for researchers, business founders, consultants and policy makers in terms of better knowledge of the venture creation process.

Major depressive disorder and nutritional medicine : a review of monotherapies and adjuvant treatments

A literature review was conducted to examine the evidence for nutritional interventions in depression. It revealed a number of significant conclusions. Interestingly, more positive clinical trials were found to support adjuvant, rather than monotherapeutic, use of nutrients to treat depression. Much evidence exists in the area of adjuvant application of folic acid, S-adenosyl-methionine, omega-3, and L-tryptophan with antidepressants. Current evidence does not support omega-3 as an effective monotherapy to treat depression. However, this may be due, at least in part, to olive oil being used as the control intervention, some studies using docosahexaenoic acid alone or a higher docosahexaenoic acid to eicosapentaenoic acid ratio, and significant heterogeneity regarding depressive populations. Nevertheless, adjunctive prescription of omega-3 with antidepressants, or in people with dietary deficiency, may be beneficial. Inositol lacks evidence as an effective antidepressant and cannot be currently recommended. Evidence on the use of L-trytophan for depression is inconclusive and additional studies utilizing a more robust methodology are required.

The present via the past : an archaelogical approach to analysing the design and use of a contemporary urban village

This research applies an archaeological lens to an inner-city master planned development in order to investigate the tension between the design of space and the use of space. The chosen case study for this thesis is Kelvin Grove Urban Village (KGUV), located in inner city Brisbane, Australia. The site of this urban village has strong links to the past. KGUV draws on both the history of the place in particular along with more general mythologies of village life in its design and subsequent marketing approaches. The design and marketing approach depends upon notions of an imagined past where life in a place shaped like a traditional village was better and more socially sustainable than modern urban spaces. The appropriation of this urban village concept has been criticised as a shallow marketing ploy. The translation and applicability of the urban village model across time and space is therefore contentious. KGUV was considered both in terms of its design and marketing and in terms of a reading of the actual use of this master planned place. Central to this analysis is the figure of the boundary and related themes of social heterogeneity, inclusion and exclusion. The refraction of history in the site is also an important theme. An interpretive archaeological approach was used overall as a novel method to derive this analysis.

The use of narrative text for injury surveillance research : a systematic review

Objective: To summarise the extent to which narrative text fields in administrative health data are used to gather information about the event resulting in presentation to a health care provider for treatment of an injury, and to highlight best practise approaches to conducting narrative text interrogation for injury surveillance purposes.----- Design: Systematic review----- Data sources: Electronic databases searched included CINAHL, Google Scholar, Medline, Proquest, PubMed and PubMed Central.. Snowballing strategies were employed by searching the bibliographies of retrieved references to identify relevant associated articles.----- Selection criteria: Papers were selected if the study used a health-related database and if the study objectives were to a) use text field to identify injury cases or use text fields to extract additional information on injury circumstances not available from coded data or b) use text fields to assess accuracy of coded data fields for injury-related cases or c) describe methods/approaches for extracting injury information from text fields.----- Methods: The papers identified through the search were independently screened by two authors for inclusion, resulting in 41 papers selected for review. Due to heterogeneity between studies metaanalysis was not performed.----- Results: The majority of papers reviewed focused on describing injury epidemiology trends using coded data and text fields to supplement coded data (28 papers), with these studies demonstrating the value of text data for providing more specific information beyond what had been coded to enable case selection or provide circumstantial information. Caveats were expressed in terms of the consistency and completeness of recording of text information resulting in underestimates when using these data. Four coding validation papers were reviewed with these studies showing the utility of text data for validating and checking the accuracy of coded data. Seven studies (9 papers) described methods for interrogating injury text fields for systematic extraction of information, with a combination of manual and semi-automated methods used to refine and develop algorithms for extraction and classification of coded data from text. Quality assurance approaches to assessing the robustness of the methods for extracting text data was only discussed in 8 of the epidemiology papers, and 1 of the coding validation papers. All of the text interrogation methodology papers described systematic approaches to ensuring the quality of the approach.----- Conclusions: Manual review and coding approaches, text search methods, and statistical tools have been utilised to extract data from narrative text and translate it into useable, detailed injury event information. These techniques can and have been applied to administrative datasets to identify specific injury types and add value to previously coded injury datasets. Only a few studies thoroughly described the methods which were used for text mining and less than half of the studies which were reviewed used/described quality assurance methods for ensuring the robustness of the approach. New techniques utilising semi-automated computerised approaches and Bayesian/clustering statistical methods offer the potential to further develop and standardise the analysis of narrative text for injury surveillance.

The utility and challenges of using ICD codes in child maltreatment research : a review of existing literature

Objective: The objectives of this article are to explore the extent to which the International Statistical Classification of Diseases and Related Health Problems (ICD) has been used in child abuse research, to describe how the ICD system has been applied and to assess factors affecting the reliability of ICD coded data in child abuse research.----- Methods: PubMed, CINAHL, PsychInfo and Google Scholar were searched for peer reviewed articles written since 1989 that used ICD as the classification system to identify cases and research child abuse using health databases. Snowballing strategies were also employed by searching the bibliographies of retrieved references to identify relevant associated articles. The papers identified through the search were independently screened by two authors for inclusion, resulting in 47 studies selected for the review. Due to heterogeneity of studies metaanalysis was not performed.----- Results: This paper highlights both utility and limitations of ICD coded data. ICD codes have been widely used to conduct research into child maltreatment in health data systems. The codes appear to be used primarily to determine child maltreatment patterns within identified diagnoses or to identify child maltreatment cases for research.----- Conclusions: A significant impediment to the use of ICD codes in child maltreatment research is the under-ascertainment of child maltreatment by using coded data alone. This is most clearly identified and, to some degree, quantified, in research where data linkage is used. Practice Implications: The importance of improved child maltreatment identification will assist in identifying risk factors and creating programs that can prevent and treat child maltreatment and assist in meeting reporting obligations under the CRC.

Cost effectiveness of antimicrobial catheters in the intensive care unit : Addressing uncertainty in the decision

Introduction: Some types of antimicrobial-coated central venous catheters (A-CVC) have been shown to be cost-effective in preventing catheter-related bloodstream infection (CR-BSI). However, not all types have been evaluated, and there are concerns over the quality and usefulness of these earlier studies. There is uncertainty amongst clinicians over which, if any, antimicrobial-coated central venous catheters to use. We re-evaluated the cost-effectiveness of all commercially available antimicrobialcoated central venous catheters for prevention of catheter-related bloodstream infection in adult intensive care unit (ICU) patients. Methods: We used a Markov decision model to compare the cost-effectiveness of antimicrobial-coated central venous catheters relative to uncoated catheters. Four catheter types were evaluated; minocycline and rifampicin (MR)-coated catheters; silver, platinum and carbon (SPC)-impregnated catheters; and two chlorhexidine and silver sulfadiazine-coated catheters, one coated on the external surface (CH/SSD (ext)) and the other coated on both surfaces (CH/SSD (int/ext)). The incremental cost per qualityadjusted life-year gained and the expected net monetary benefits were estimated for each. Uncertainty arising from data estimates, data quality and heterogeneity was explored in sensitivity analyses. Results: The baseline analysis, with no consideration of uncertainty, indicated all four types of antimicrobial-coated central venous catheters were cost-saving relative to uncoated catheters. Minocycline and rifampicin-coated catheters prevented 15 infections per 1,000 catheters and generated the greatest health benefits, 1.6 quality-adjusted life-years, and cost-savings, AUD $130,289. After considering uncertainty in the current evidence, the minocycline and rifampicin-coated catheters returned the highest incremental monetary net benefits of $948 per catheter; but there was a 62% probability of error in this conclusion. Although the minocycline and rifampicin-coated catheters had the highest monetary net benefits across multiple scenarios, the decision was always associated with high uncertainty. Conclusions: Current evidence suggests that the cost-effectiveness of using antimicrobial-coated central venous catheters within the ICU is highly uncertain. Policies to prevent catheter-related bloodstream infection amongst ICU patients should consider the cost-effectiveness of competing interventions in the light of this uncertainty. Decision makers would do well to consider the current gaps in knowledge and the complexity of producing good quality evidence in this area.

The impact of health information technology on the quality of medical and health care : a systematic review

Objective: To systematically review the published evidence of the impact of health information technology (HIT) on the quality of medical and health care specifically clinicians’ adherence to evidence-based guidelines and the corresponding impact this had on patient clinical outcomes. In order to be as inclusive as possible the research examined literature discussing the use of health information technologies and systems in both medical care such as clinical and surgical, and other health care such as allied health and preventive services.----- Design: Systematic review----- Data Sources: Relevant literature was systematically searched on English language studies indexed in MEDLINE and CINAHL(1998 to 2008), Cochrane Library, PubMed, Database of Abstracts of Review of Effectiveness (DARE), Google scholar and other relevant electronic databases. A search for eligible studies (matching the inclusion criteria) was also performed by searching relevant conference proceedings available through internet and electronic databases, as well as using reference lists identified from cited papers.----- Selection criteria: Studies were included in the review if they examined the impact of Electronic Health Record (EHR), Computerised Provider Order-Entry (CPOE), or Decision Support System (DS); and if the primary outcomes of the studies were focused on the level of compliance with evidence-based guidelines among clinicians. Measures could be either changes in clinical processes resulting from a change of the providers’ behaviour or specific patient outcomes that demonstrated the effectiveness of a particular treatment given by providers. ----- Methods: Studies were reviewed and summarised in tabular and text form. Due to heterogeneity between studies, meta-analysis was not performed.----- Results: Out of 17 studies that assessed the impact of health information technology on health care practitioners’ performance, 14 studies revealed a positive improvement in relation to their compliance with evidence-based guidelines. The primary domain of improvement was evident from preventive care and drug ordering studies. Results from the studies that included an assessment for patient outcomes however, were insufficient to detect either clinically or statistically important improvements as only a small proportion of these studies found benefits. For instance, only 3 studies had shown positive improvement, while 5 studies revealed either no change or adverse outcomes.----- Conclusion: Although the number of included studies was relatively small for reaching a conclusive statement about the effectiveness of health information technologies and systems on clinical care, the results demonstrated consistency with other systematic reviews previously undertaken. Widescale use of HIT has been shown to increase clinician’s adherence to guidelines in this review. Therefore, it presents ongoing opportunities to maximise the uptake of research evidence into practice for health care organisations, policy makers and stakeholders.

Management of comorbidity

Comorbidity of substance use disorders and mental disorders is very common, and there is substantial heterogeneity within subgroups in terms of both their characteristics and the nature of causal relationships between the disorders. Assessment and management strategies need to deal with both the size of the problem across the community and its severe impact in some subgroups, including those with psychosis. At this stage, the research base from which we can derive recommendations is very narrow, but it does offer a foundation for preliminary conclusions. This chapter reviews the current evidence and makes some suggestions for assessment and for both psychological and pharmacological management.

Linkage and heritability analysis of migraine symptom groupings: A comparison of three different clustering methods on twin data

Migraine is a painful disorder for which the etiology remains obscure. Diagnosis is largely based on International Headache Society criteria. However, no feature occurs in all patients who meet these criteria, and no single symptom is required for diagnosis. Consequently, this definition may not accurately reflect the phenotypic heterogeneity or genetic basis of the disorder. Such phenotypic uncertainty is typical for complex genetic disorders and has encouraged interest in multivariate statistical methods for classifying disease phenotypes. We applied three popular statistical phenotyping methods—latent class analysis, grade of membership and grade of membership “fuzzy” clustering (Fanny)—to migraine symptom data, and compared heritability and genome-wide linkage results obtained using each approach. Our results demonstrate that different methodologies produce different clustering structures and non-negligible differences in subsequent analyses. We therefore urge caution in the use of any single approach and suggest that multiple phenotyping methods be used.

Computer profiling for forensic purposes

Computer forensics is the process of gathering and analysing evidence from computer systems to aid in the investigation of a crime. Typically, such investigations are undertaken by human forensic examiners using purpose-built software to discover evidence from a computer disk. This process is a manual one, and the time it takes for a forensic examiner to conduct such an investigation is proportional to the storage capacity of the computer's disk drives. The heterogeneity and complexity of various data formats stored on modern computer systems compounds the problems posed by the sheer volume of data. The decision to undertake a computer forensic examination of a computer system is a decision to commit significant quantities of a human examiner's time. Where there is no prior knowledge of the information contained on a computer system, this commitment of time and energy occurs with little idea of the potential benefit to the investigation. The key contribution of this research is the design and development of an automated process to describe a computer system and its activity for the purposes of a computer forensic investigation. The term proposed for this process is computer profiling. A model of a computer system and its activity has been developed over the course of this research. Using this model a computer system, which is the subj ect of investigation, can be automatically described in terms useful to a forensic investigator. The computer profiling process IS resilient to attempts to disguise malicious computer activity. This resilience is achieved by detecting inconsistencies in the information used to infer the apparent activity of the computer. The practicality of the computer profiling process has been demonstrated by a proof-of concept software implementation. The model and the prototype implementation utilising the model were tested with data from real computer systems. The resilience of the process to attempts to disguise malicious activity has also been demonstrated with practical experiments conducted with the same prototype software implementation.

An analysis of the determinants of job satisfaction when individuals' baseline satisfaction levels may differ.

A growing literature seeks to explain differences in individuals' self-reported satisfaction with their jobs. The evidence so far has mainly been based on cross-sectional data and when panel data have been used, individual unobserved heterogeneity has been modelled as an ordered probit model with random effects. This article makes use of longitudinal data for Denmark, taken from the waves 1995-1999 of the European Community Household Panel, and estimates fixed effects ordered logit models using the estimation methods proposed by Ferrer-i-Carbonel and Frijters (2004) and Das and van Soest (1999). For comparison and testing purposes a random effects ordered probit is also estimated. Estimations are carried out separately on the samples of men and women for individuals' overall satisfaction with the jobs they hold. We find that using the fixed effects approach (that clearly rejects the random effects specification), considerably reduces the number of key explanatory variables. The impact of central economic factors is the same as in previous studies, though. Moreover, the determinants of job satisfaction differ considerably between the genders, in particular once individual fixed effects are allowed for.

Difference and dispersion : educational research in a postmodern context

Difference and Dispersion is the fourth in a series of annual research papers produced by doctoral students from The Graduate School of Education, The University of Queensland, following their presentation at the School’s annual Postgraduate Research Conference in Education. The work featured herein celebrates the diversity of cultural and disciplinary backgrounds of education researchers who come from as far afield as Germany, Hong Kong, China, Nigeria, Russia, Singapore, Thailand and of course different parts of Australia. In keeping with a postmodern epistemology, ‘difference’ and ‘dispersion’ are key themes in apprehending the multiplicity of their research topics, methodologies, methods and speaking/writing positions. From widely differing contexts and situations, these writers address the consequences, implications and possibilities for education at the beginning of the third millennium. Their interest ranges from location-specific issues in schools and classrooms, change in learning contexts and processes, educational discourses and relations of power in diverse geographical settings, and the differing articulations of the local and the global in situated policy contexts. Conceived and developed in a spirit of ongoing dialogue with and insight to alternative views and visions of education and society, this edited collection exemplifies the quality in diversity and the high levels of scholarship and supervision at one of Australia’s finest Graduate Schools of Education.