Application of the disposition model to breast cancer data

In this paper, we have presented the second level nesting of Bonney's disposition model (Bonney, 1998) and examined the implications of higher level nesting of the disposition model in relation to the dimension of the parameter space. We have also compared the performance of the disposition model with Cox's regression model (Cox, 1972). It has been observed that the disposition model has a very large number of unknown parameters, and is therefore limited by the method of estimation used. In the case of the maximum likelihood method, reasonable estimates are obtained if the number of parameters in the model is at most nine. This corresponds to about four to seven covariates. Since each covariate in Cox's model provides a parameter, it is possible to include more covariates in the regression analysis. On the other hand, as opposed to Cox's model, the disposition model is fitted with parameters to capture aggregation in families, if there should be any. The choice of a particular model should therefore depend on the available data set and the purpose of the statistical analysis. --Second level nesting,Proportional hazards model,Quadratic exponential form,Partial likelihood,Familial aggregation,Second-order methods,Marginal models,Conditional models

Which strategy is better for linkage analysis: single-nucleotide polymorphisms or microsatellites? Evaluation by identity-by-state – identity-by-descent transformation affected sib-pair method on GAW14 data

The central issue for Genetic Analysis Workshop 14 (GAW14) is the question, which is the better strategy for linkage analysis, the use of single-nucleotide polymorphisms (SNPs) or microsatellite markers? To answer this question we analyzed the simulated data using Duffy's SIB-PAIR program, which can incorporate parental genotypes, and our identity-by-state – identity-by-descent (IBS-IBD) transformation method of affected sib-pair linkage analysis which uses the matrix transformation between IBS and IBD. The advantages of our method are as follows: the assumption of Hardy-Weinberg equilibrium is not necessary; the parental genotype information maybe all unknown; both IBS and its related IBD transformation can be used in the linkage analysis; the determinant of the IBS-IBD transformation matrix provides a quantitative measure of the quality of the marker in linkage analysis. With the originally distributed simulated data, we found that 1) for microsatellite markers there are virtually no differences in types I and II error rates when parental genotypes were or were not used; 2) on average, a microsatellite marker has more power than a SNP marker does in linkage detection; 3) if parental genotype information is used, SNP markers show lower type I error rates than microsatellite markers; and 4) if parental genotypes are not available, SNP markers show considerable variation in type I error rates for different methods

Variable training does not lead to better motor learning compared to repetitive training in children with DCD when exposed to video games

Background Little is known about the influence of practice schedules on motor learning and skills transfer in children with and without developmental coordination disorder (DCD). Understanding how practice schedules affect motor learning is necessary for motor skills development and rehabilitation. Aims The study investigated whether active video games (exergames) training delivered under variable practice led to better learning and transfer than repetitive practice. Methods and procedures 111 children aged 6–10 years (M = 8.0, SD = 1.0) with no active exergaming experience were randomized to receive exergames training delivered under variable (Variable Game Group (VGG), n = 56) or repetitive practice schedule (Repetitive Game Group (RGG), n = 55). Half the participants were identified as DCD using the DSM-5 criteria, while the rest were typically developing (TD), age-matched children. Both groups participated in two 20 min sessions per week for 5 weeks. Outcomes and results Both participant groups (TD and DCD) improved equally well on game performance. There was no significant difference in positive transfer to balance tasks between practice schedules (Repetitive and Variable) and participant groups (TD and DCD). Conclusions and implications Children with and without DCD learn balance skills quite well when exposed to exergames. Gains in learning and transfer are similar regardless of the form of practice schedule employed. What this paper adds This is the first paper to compare the effect of practice schedules on learning in children with DCD and those with typical development. No differences in motor learning were found between repetitive and variable practice schedules. When children with and without DCD spend the same amount of time on exergames, they do not show any differences in acquisition of motor skills. Transfer of motor skills is similar in children with and without DCD regardless of differences in practice schedules

Hepatitis C virus (HCV): prevalence in a gynecological urgent care clinic population.

OBJECTIVE: To determine the prevalence of hepatitis C virus (HCV) among women seeking urgent gynecological care. METHODS: Women were asked to complete a short self-assessment screening of HCV risk. Those answering yes to any of the screening questions were offered HCV testing and were asked to complete a more detailed questionnaire. RESULTS: Among the 125 women who completed the screening questionnaire, 80% (100) answered yes to one or more of the screening questions. Of the 99 women who underwent testing, six (6.1%) were HCV seropositive; a history of injection drug use was the only finding associated with HCV seropositivity (R.R 9.7: 95% CI 1.90-49.40). CONCLUSIONS: Women seeking urgent outpatient gynecological care, particularly those who are injection drug users, are at a substantial risk of HCV infection. A careful risk assessment should be completed in order to identify women who should be offered HCV testing

Genes, age, and alcoholism: analysis of GAW14 data

A genetic analysis of age of onset of alcoholism was performed on the Collaborative Study on the Genetics of Alcoholism data released for Genetic Analysis Workshop 14. Our study illustrates an application of the log-normal age of onset model in our software Genetic Epidemiology Models (GEMs). The phenotype ALDX1 of alcoholism was studied. The analysis strategy was to first find the markers of the Affymetrix SNP dataset with significant association with age of onset, and then to perform linkage analysis on them. ALDX1 revealed strong evidence of linkage for marker tsc0041591 on chromosome 2 and suggestive linkage for marker tsc0894042 on chromosome 3. The largest separation in mean ages of onset of ALDX1 was 19.76 and 24.41 between male smokers who are carriers of the risk allele of tsc0041591 and the non-carriers, respectively. Hence, male smokers who are carriers of marker tsc0041591 on chromosome 2 have an average onset of ALDX1 almost 5 years earlier than non-carriers

A study of genetic association with electrophysiological measures related to alcoholism: GAW14 data

Recently, alcohol-related traits have been shown to have a genetic component. Here, we study the association of specific genetic measures in one of the three sets of electrophysiological measures in families with alcoholism distributed as part of the Genetic Analysis Workshop 14 data, the NTTH (non-target case of Visual Oddball experiment for 4 electrode placements) phenotypes: ntth1, ntth2, ntth3, and ntth4. We focused on the analysis of the 786 Affymetrix markers on chromosome 4. Our desire was to find at least a partial answer to the question of whether ntth1, ntth2, ntth3, and ntth4 are separately or jointly genetically controlled, so we studied the principal components that explain most of the covariation of the four quantitative traits. The first principal component, which explains 70% of the covariation, showed association but not genetic linkage to two markers: tsc0272102 and tsc0560854. On the other hand, ntth1 appeared to be the trait driving the variation in the second principal component, which showed association and genetic linkage at markers in four regions: tsc0045058, tsc1213381, tsc0055068, and tsc0051777 at map distances 53.26, 85.42, 89.31, and 172.86, respectively. These results show that the partial answer to our starting question for this brief analysis is that the NTTH phenotypes are not jointly genetically controlled. The component ntth1 displays marked genetic linkage

Feasibility and content validity of the PERF-FIT test battery to assess movement skills, agility and power among children in low resource settings

Background: Numerous movement skills and physical fitness tests have been developed for children in high-income countries. However, adaptation of these tests to low-resource settings has been slow and norms are still unavailable for children living in low-income communities. The aim of this paper was to describe the development and validation of the Performance and Fitness (PERF-FIT) test battery, a new test to assess motor skill-related physical fitness in children in low-resource settings. Method: The PERF-FIT test was developed in a stepwise manner. This involved defining the relevant domains of the construct of interest and selecting and evaluating test items. The Content Validity Index (CVI) was used to estimate content validity. Following development of the PERF-FIT test, a preliminary study was performed to validate items and to examine the feasibility of implementing the test in a low-resource community. Structural validity was also determined based on data from eighty (n = 80) children (aged 7-12 years) using principal component analysis. Results: The CVI for the throw and catch item was 0.86 and 1.00 for the other nine items, leading to a total CVI score of 0.99. The hierarchical sequence of the item series was demonstrated by highly significant (p < 0.001) linear trends, confirming the increase in difficulty of subsequent items. Principal component analysis revealed three factors; the first component is represented by locomotor skills that require static and dynamic balance, the second component by throwing and catching items and the third component by agility and power items. These findings suggest that it is feasible to implement the PERF-FIT in low-resource settings. Conclusion: The PERF-FIT test battery is easy to administer and may be suitable for measuring skill-related physical fitness in in low-resource settings. It has excellent content validity and good structural validity. After minor adaptions, further studies should be conducted to establish normative values, evaluate reliability, and document criterion and cross-cultural validity of this test

Application of the pMHC array to characterise tumour antigen specific T cell populations in leukaemia patients at disease diagnosis

Immunotherapy treatments for cancer are becoming increasingly successful, however to further improve our understanding of the T-cell recognition involved in effective responses and to encourage moves towards the development of personalised treatments for leukaemia immunotherapy, precise antigenic targets in individual patients have been identified. Cellular arrays using peptide-MHC (pMHC) tetramers allow the simultaneous detection of different antigen specific T-cell populations naturally circulating in patients and normal donors. We have developed the pMHC array to detect CD8+ T-cell populations in leukaemia patients that recognise epitopes within viral antigens (cytomegalovirus (CMV) and influenza (Flu)) and leukaemia antigens (including Per Arnt Sim domain 1 (PASD1), MelanA, Wilms’ Tumour (WT1) and tyrosinase). We show that the pMHC array is at least as sensitive as flow cytometry and has the potential to rapidly identify more than 40 specific T-cell populations in a small sample of T-cells (0.8–1.4 x 106). Fourteen of the twenty-six acute myeloid leukaemia (AML) patients analysed had T cells that recognised tumour antigen epitopes, and eight of these recognised PASD1 epitopes. Other tumour epitopes recognised were MelanA (n = 3), tyrosinase (n = 3) and WT1126-134 (n = 1). One of the seven acute lymphocytic leukaemia (ALL) patients analysed had T cells that recognised the MUC1950-958 epitope. In the future the pMHC array may be used provide point of care T-cell analyses, predict patient response to conventional therapy and direct personalised immunotherapy for patients

Supporting citizen inquiry: an investigation of Moon rock

Citizen inquiry is an innovative way for non-professionals to engage in practical scientific activities, in which they take the role of self-regulated scientists in informal learning contexts. This type of activity has similarities to inquiry-based learning and to citizen science, but also important differences. To understand the challenges of supporting citizen inquiry, a prototype system and activity has been developed: the Moon Rock Explorer. Based on the nQuire Toolkit, this offers people without geology expertise an open investigation into authentic specimens of Moon rock, using a Virtual Microscope. The Moon Rock Explorer inquiry has been evaluated in an informal learning context with PhD students from the Open University. Results of the evaluation raise issues related to motivation and interaction between inquiry participants. They also provide evidence that the integration of scientific tools was successful and that the nQuire Toolkit is suitable to deploy and enact citizen inquiries

Political Regimes and Sovereign Credit Risk in Europe, 1750-1913

This article uses a new panel data set to perform a statistical analysis of political regimes and sovereign credit risk in Europe from 1750 to 1913. Old Regime polities typically suffered from fiscal fragmentation and absolutist rule. By the start of World War I, however, many such countries had centralized institutions and limited government. Panel regressions indicate that centralized and?or limited regimes were associated with significant improvements in credit risk relative to fragmented and absolutist ones. Structural break tests also reveal close relationships between major turning points in yield series and political transformations