219 resultados para ACE polymorphism
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Educators are faced with many challenging questions in designing an effective curriculum. What prerequisite knowledge do students have before commencing a new subject? At what level of mastery? What is the spread of capabilities between bare-passing students vs. the top performing group? How does the intended learning specification compare to student performance at the end of a subject? In this paper we present a conceptual model that helps in answering some of these questions. It has the following main capabilities: capturing the learning specification in terms of syllabus topics and outcomes; capturing mastery levels to model progression; capturing the minimal vs. aspirational learning design; capturing confidence and reliability metrics for each of these mappings; and finally, comparing and reflecting on the learning specification against actual student performance. We present a web-based implementation of the model, and validate it by mapping the final exams from four programming subjects against the ACM/IEEE CS2013 topics and outcomes, using Bloom's Taxonomy as the mastery scale. We then import the itemised exam grades from 632 students across the four subjects and compare the demonstrated student performance against the expected learning for each of these. Key contributions of this work are the validated conceptual model for capturing and comparing expected learning vs. demonstrated performance, and a web-based implementation of this model, which is made freely available online as a community resource.
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Background: A random QTL effects model uses a function of probabilities that two alleles in the same or in different animals at a particular genomic position are identical by descent (IBD). Estimates of such IBD probabilities and therefore, modeling and estimating QTL variances, depend on marker polymorphism, strength of linkage and linkage disequilibrium of markers and QTL, and the relatedness of animals in the pedigree. The effect of relatedness of animals in a pedigree on IBD probabilities and their characteristics was examined in a simulation study. Results: The study based on nine multi-generational family structures, similar to a pedigree structure of a real dairy population, distinguished by an increased level of inbreeding from zero to 28 % across the studied population. Highest inbreeding level in the pedigree, connected with highest relatedness, was accompanied by highest IBD probabilities of two alleles at the same locus, and by lower relative variation coefficients. Profiles of correlation coefficients of IBD probabilities along the marked chromosomal segment with those at the true QTL position were steepest when the inbreeding coefficient in the pedigree was highest. Precision of estimated QTL location increased with increasing inbreeding and pedigree relatedness. A method to assess the optimum level of inbreeding for QTL detection is proposed, depending on population parameters. Conclusions: An increased overall relationship in a QTL mapping design has positive effects on precision of QTL position estimates. But the relationship of inbreeding level and the capacity for QTL detection depending on the recombination rate of QTL and adjacent informative marker is not linear. © 2010 Freyer et al., licensee BioMed Central Ltd.
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Population-wide associations between loci due to linkage disequilibrium can be used to map quantitative trait loci (QTL) with high resolution. However, spurious associations between markers and QTL can also arise as a consequence of population stratification. Statistical methods that cannot differentiate between loci associations due to linkage disequilibria from those caused in other ways can render false-positive results. The transmission-disequilibrium test (TDT) is a robust test for detecting QTL. The TDT exploits within-family associations that are not affected by population stratification. However, some TDTs are formulated in a rigid-form, with reduced potential applications. In this study we generalize TDT using mixed linear models to allow greater statistical flexibility. Allelic effects are estimated with two independent parameters: one exploiting the robust within-family information and the other the potentially biased between-family information. A significant difference between these two parameters can be used as evidence for spurious association. This methodology was then used to test the effects of the fourth melanocortin receptor (MC4R) on production traits in the pig. The new analyses supported the previously reported results; i.e., the studied polymorphism is either causal of in very strong linkage disequilibrium with the causal mutation, and provided no evidence for spurious association.
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Objective In Parkinson's disease (PD), commonly reported risk factors for malnutrition in other populations commonly occur. Few studies have explored which of these factors are of particular importance in malnutrition in PD. The aim was to identify the determinants of nutritional status in people with Parkinson's disease (PWP). Methods Community-dwelling PWP (>18 years) were recruited (n = 125; 73M/52F; Mdn 70 years). Self-report assessments included Beck's Depression Inventory (BDI), Spielberger Trait Anxiety Inventory (STAI), Scales for Outcomes in Parkinson's disease – Autonomic (SCOPA-AUT), Modified Constipation Assessment Scale (MCAS) and Freezing of Gait Questionnaire (FOG-Q). Information about age, PD duration, medications, co-morbid conditions and living situation was obtained. Addenbrooke's Cognitive Examination (ACE-R), Unified Parkinson's Disease Rating Scale (UPDRS) II and UPDRS III were performed. Nutritional status was assessed using the Subjective Global Assessment (SGA) as part of the scored Patient-Generated Subjective Global Assessment (PG-SGA). Results Nineteen (15%) were malnourished (SGA-B). Median PG-SGA score was 3. More of the malnourished were elderly (84% vs. 71%) and had more severe disease (H&Y: 21% vs. 5%). UPDRS II and UPDRS III scores and levodopa equivalent daily dose (LEDD)/body weight(mg/kg) were significantly higher in the malnourished (Mdn 18 vs. 15; 20 vs. 15; 10.1 vs. 7.6 respectively). Regression analyses revealed older age at diagnosis, higher LEDD/body weight (mg/kg), greater UPDRS III score, lower STAI score and higher BDI score as significant predictors of malnutrition (SGA-B). Living alone and higher BDI and UPDRS III scores were significant predictors of a higher log-adjusted PG-SGA score. Conclusions In this sample of PWP, the rate of malnutrition was higher than that previously reported in the general community. Nutrition screening should occur regularly in those with more severe disease and depression. Community support should be provided to PWP living alone. Dopaminergic medication should be reviewed with body weight changes.
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Entrepreneurial strategies in large firms have been analysed in terms of antecedent conditions, elements and outcomes (Ireland, Covin & Kuratko, 2009), but to date less attention has been given to the strategies used by small and medium enterprises to remain competitive. The purpose of this paper is to increase our knowledge and understanding of the types of strategies and activities that existing small and medium enterprises (SMEs) are using to generate new economic activity to ensure the success of their business. This paper explores findings from a qualitative study of SMEs and identifies entrepreneurial management (Stevenson & Jarillo 1995) in different forms in different sized firms. Findings indicate that small and medium sized enterprises seeking to remain competitive, engage in proactive entrepreneurial strategies that develop and exploit capabilities.
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Principal Topic Counties in Northern Europe, such as Sweden, Finland and Denmark, have comparatively low per capita rates of entrepreneurship as measured by independent new venture start-up rates – as for example measured by the Global Entrepreneurship Monitor (GEM) Total entrepreneurial activity (TEA) rate. However, the latest 2011 GEM data reveals that these same countries have comparatively very high Employee Entrepreneurship Activity (EEA) rates – that is a high rate per capita of employees involved in new product development or new enterprise activities. This observation has prompted us to investigate the role of national culture in driving independent versus employee entrepreneurial activities. Prior research has established that national (and regional) culture plays an important role in forming an “entrepreneurial culture” that encourages (or discourages) independent business start-ups and TEA (e.g. Davidsson, 1995; Beugelsdijk, 2007). However, the relationship of culture and EEA has not received research attention. Moreover, empirical relationships between elements of national culture and independent entrepreneurship have revealed some surprising results. For example, Wildeman et al. (1999) report an unexpected higher share of individual business ownership in countries that have higher uncertainty avoidance, higher power distance and lower individualism according to Hofstede’s dimensions of culture. They speculate that dissatisfaction can be a source of entrepreneurship: in countries with a high power distance, a high uncertainty avoidance and low individualism, there may be relatively more business owners since enterprising individuals cannot satisfy their needs within existing organizations. Yet it remains a rather open question whether entrepreneurial behaviour in existing organisations provides a satisfactory explanation for these empirical findings. Methods We will conduct a cross sectional study of the influence of national culture according to the five / six dimensions of Hofstede (1980; 2001) on both TEA and EEA for the 54 countries that participated in GEM 2011. Since it is well established that the opportunities for entrepreneurship vary substantially with a country’s level of economic development, we intend to conduct separate analyses for the three categories of development – innovation driven economies, efficient driven economies and factor driven economies. We also intend to restrict our assessment of TEA to opportunity driven entrepreneurship, as necessity driven entrepreneurship has a different relationship to the “entrepreneurial culture” that is the focus of our study. We will control for a range of factors such as GDP growth, ease of doing business index and unemployment. Results and Implications Descriptive analyses of the GEM TEA and EEA data reveal clusters of countries that appear to be have similar national culture. We are yet to conduct regression analyses.
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This paper addresses the ambiguous relationship of internal, organizationa social capital and external social capital with corporate entrepreneurship performance. Drawing on social construction theory we argue that bricolage can mitigate some of the negative effects associated with social capital by recombining and redefining the purpose of available resources. We investigated our hypotheses through a random sample of 206 corporate entrepreneurship projects. We found that both internal and external social capital have no direct effect on performance of corporate entrepreneurship projects. The results indicate that bricolage mediates the relationship between social capital and performance of corporate entrepreneurship projects. Bricolage thrives in particularly when there is wide availability of social capital internal and external to the organization. The implications are that bricolage is a critical behavior in allowing corporate entrepreneur projects to benefit from resources available through their network of social relations inside and outside the company.
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In this paper, we present initial results of an inductive, longitudinal case study of four firms that applied bricolage behaviors during resource constraints in firm emergence. Building on these cases, we discuss and extend existing research in bricolage theories by investigating how bricolage enables or hinders progress within firm creation. We explore the factors that places limits on the use of bricolage effectiveness during emergence. Specifically, in this paper, we discuss the impact of commitment and attention on bricolage effectiveness and how these influences may shape attempts to further progress and continue despite the resource constraints entrepreneurs often face in venture creation processes.
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There is an army of bottom of the pyramid entrepreneurs (BOPE) who have the potential to transform developing economies, if they can identify and exploit business opportunities. BOPE could have unidentified resources that could lead to the recognition of radical new opportunities. This study paper asks how environmental factors and identification of resources affect Opportunity Recognition by BOP entrepreneurs in developing economies. To investigate this research question we conduct a literature review and plan semi-structured interviews of existing and nascent entrepreneurs in the largest and arguably the poorest country in Africa, the Democratic Republic of the Congo. In this paper we review the context of BOPE and describe the methodology we will use to gather and analyse data. Finally, we describe our access to suitable respondents for this study and how it will be conducted.
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While entrepreneurship research has taken firm formation to be the predominant mode of opportunity exploitation, entrepreneurship can take place through many other types of organizational arrangements. In the present article, we consider one such alternative arrangement, namely the formation of inter-organizational projects (IOPs). We propose a multi-level contingency model that suggests that uncertainty both at the level of the firm and at the level of the environment makes the exploitation of opportunities through IOPs more likely. The model is tested by telephone survey data collected amongst a panel of 1725 SMEs and longitudinal industry data. Our findings provide strong support for the industry-level part of the model, but interestingly, only partial support for the firm level part of the model. This indicates that the effects of uncertainty need to be dissected into different levels of analysis to understand the conditions under which alternative modes of opportunity exploitation can be a prominent entrepreneurial alternative to new firm formation.
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We support Shane and Venkataraman’s (2000) basic idea of an “entrepreneurship nexus” where characteristics of the actor as well as those of the “opportunity” they work on influence action and outcomes in the creation of new economic activities. However, a review of the literature reveals that minimal progress has been made on the core issues pertaining to the nexus idea. We argue that this is rooted in fundamental and insurmountable problems with the “opportunity” construct itself, and demonstrate the state of confusion in the literature caused by inconsistent use of the construct within and across works and authors. As an alternative, we suggest the admittedly subjective notion of New Venture as a more workable alternative. We provide a comprehensive definition and explanation of this construct, and take steps towards improved conceptualization and operationalization of its subdimensions. With some further work on these conceptualizations and operationalizations it will be possible to implement a comprehensive research program that can finally deliver on the promise outlined by Shane and Venkataraman (2000).
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Debate about the relationships between business planning and performance has been active for decades (Bhidé, 2000; Mintzberg, 1994). While results have been inconclusive, this topic still strongly divides the research community (Brinckmann et al., 2010; Chwolka & Raith, 2011; Delmar & Shane, 2004; Frese, 2009; Gruber, 2007; Honig & Karlsson, 2004). Previous research explored the relationships between innovation and the venture creation process (Amason et al., 2006, Dewar & Dutton, 1986; Jennings et al., 2009). However, the relationships between business planning and innovation have mostly been invoked indirectly in the strategy and entrepreneurship literatures through the notion of uncertainty surrounding the development of innovation. Some posited that planning may be irrelevant due to the iterative process, the numerous changes innovation development entails and the need to be flexible (Brews & Hunt, 1999). Others suggested that planning may facilitate the achievement of goals and overcoming of obstacles (Locke and Latham, 2000), guide the venture in its allocation of resources (Delmar and Shane, 2003) and help to foster the communication about the innovation being developed (Liao & Welsh, 2008). However, the nature and extents of the relationships between business planning, innovation and performance are still largely unknown. Moreover, if the reasons why ventures should engage (Frese, 2009) –or not- (Honig, 2004) in business planning have been investigated quite extensively (Brinckmann et al., 2010), the specific value of business planning for nascent firms developing innovation is still unclear. The objective of this paper is to shed some light on these important aspects by investigating the two following questions on a large sample of random nascent firms: 1) how is business planning use over time by new ventures developing different types and degrees of innovation? 2) how do business planning and innovation impact the performance of the nascent firms? Methods & Key propositions This PSED-type study draws its data from the first three waves of the CAUSEE project where 30,105 Australian households were randomly contacted by phone using a methodology to capture emerging firms (Davidsson, Steffens, Gordon, Reynolds, 2008). This screening led to the identification of 594 nascent ventures (i.e., firms that were not operating yet at the time of the identification) that were willing to participate in the study. Comprehensive phone interviews were conducted with these 594 ventures. Likewise, two comprehensive follow-ups were organised 12 months and 24 months later where 80% of the eligible cases of the previous wave completed the interview. The questionnaire contains specific sections investigating business plans such as: presence or absence, degree of formality and updates of the plan. Four types of innovation are measured along three degrees of intensity to produce a comprehensive continuous measure ranging from 0 to 12 (Dahlqvist & Wiklund, 2011). Other sections informing on the gestation activities, industry and different types of experiences will be used as controls to measure the relationships and the impacts of business planning and innovation on the performance of nascent firms overtime. Results from two rounds of pre-testing informed the design of the instrument included in the main survey. The three waves of data are used to first test and compare the use of planning amongst nascent firms by their degrees of innovation and then to examine their impact on performance overtime through regression analyses. Results and Implications Three waves of data collection have been completed. Preliminary results show that on average, innovative firms are more likely to have a business plans than their low innovative counterpart. They are also most likely to update their plan suggesting a more continuous use of the plan over time than previously thought. Further analyses regarding the relationships between business planning, innovation and performance are undergoing. This paper is expected to contribute to the literature on business planning and innovation by measuring quantitatively their impact on nascent firms activities and performance at different stages of their development. In addition, this study will shed a new light on the business planning-performance relationship by disentangling plans, types of nascent firms regarding their innovation degres and their performance over time. Finally, we expect to increase the understanding of the venture creation process by analysing those questions on nascent firms from a large longitudinal sample of randomly selected ventures. We acknowledge the results from this study will be preliminary and will have to be interpreted with caution as the business planning-performance is not a straightforward relationship (Brinckmann et al., 2010). Meanwhile, we believe that this study is important to the field of entrepreneurship as it provides some much needed insights on the processes used by nascent firms during their creation and early operating stages.
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This study used next generation sequencing technologies to investigate growth in a cultured crustacean. The objective was to identify and characterise specific gene loci that contribute important phenotypic variation to growth as well as to develop a large set of SNP markers in candidate genes for assessing correlations between specific mutations and individual growth performance. The genomic dataset generated provides a fundamental resource for application in future crustacean stock improvement programs. Ultimately, the data can be applied to development of culture lines with improved growth performance.
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We employed a Hidden-Markov-Model (HMM) algorithm in loss of heterozygosity (LOH) analysis of high-density single nucleotide polymorphism (SNP) array data from Non-Hodgkin’s lymphoma (NHL) entities, follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL). This revealed a high frequency of LOH over the chromosomal region 11p11.2, containing the gene encoding the protein tyrosine phosphatase receptor type J (PTPRJ). Although PTPRJ regulates components of key survival pathways in B-cells (i.e., BCR, MAPK, and PI3K signaling), its role in B-cell development is poorly understood. LOH of PTPRJ has been described in several types of cancer but not in any hematological malignancy. Interestingly, FL cases with LOH exhibited down-regulation of PTPRJ, in contrast no significant variation of expression was shown in DLBCLs. In addition, sequence screening in Exons 5 and 13 of PTPRJ identified the G973A (rs2270993), T1054C (rs2270992), A1182C (rs1566734), and G2971C (rs4752904) coding SNPs (cSNPs). The A1182 allele was significantly more frequent in FLs and in NHLs with LOH. Significant over-representation of the C1054 (rs2270992) and the C2971 (rs4752904) alleles were also observed in LOH cases. A haplotype analysis also revealed a significant lower frequency of haplotype GTCG in NHL cases, but it was only detected in cases with retention. Conversely, haplotype GCAC was over-representated in cases with LOH. Altogether, these results indicate that the inactivation of PTPRJ may be a common lymphomagenic mechanism in these NHL subtypes and that haplotypes in PTPRJ gene may play a role in susceptibility to NHL, by affecting activation of PTPRJ in these B-cell lymphomas.
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Multiple sclerosis (MS) is a common chronic inflammatory disease of the central nervous system. Susceptibility to the disease is affected by both environmental and genetic factors. Genetic factors include haplotypes in the histocompatibility complex (MHC) and over 50 non-MHC loci reported by genome-wide association studies. Amongst these, we previously reported polymorphisms in chromosome 12q13-14 with a protective effect in individuals of European descent. This locus spans 288 kb and contains 17 genes, including several candidate genes which have potentially significant pathogenic and therapeutic implications. In this study, we aimed to fine-map this locus. We have implemented a two-phase study: a variant discovery phase where we have used next-generation sequencing and two target-enrichment strategies [long-range polymerase chain reaction (PCR) and Nimblegen's solution phase hybridization capture] in pools of 25 samples; and a genotyping phase where we genotyped 712 variants in 3577 healthy controls and 3269 MS patients. This study confirmed the association (rs2069502, P = 9.9 × 10−11, OR = 0.787) and narrowed down the locus of association to an 86.5 kb region. Although the study was unable to pinpoint the key-associated variant, we have identified a 42 (genotyped and imputed) single-nucleotide polymorphism haplotype block likely to harbour the causal variant. No evidence of association at previously reported low-frequency variants in CYP27B1 was observed. As part of the study we compared variant discovery performance using two target-enrichment strategies. We concluded that our pools enriched with Nimblegen's solution phase hybridization capture had better sensitivity to detect true variants than the pools enriched with long-range PCR, whilst specificity was better in the long-range PCR-enriched pools compared with solution phase hybridization capture enriched pools; this result has important implications for the design of future fine-mapping studies.