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Separate Methods (separate + methods)

Distribution by Scientific Domains

Medical Sciences	50%
Life Sciences	50%

Selected Abstracts

Quantitative trait linkage analysis by generalized estimating equations: Unification of variance components and Haseman-Elston regression

GENETIC EPIDEMIOLOGY, Issue 4 2004
Wei-Min Chen
Two of the major approaches for linkage analysis with quantitative traits in humans include variance components and Haseman-Elston regression. Previously, these were viewed as quite separate methods. We describe a general model, fit by use of generalized estimating equations (GEE), for which the variance components and Haseman-Elston methods (including many of the extensions to the original Haseman-Elston method) are special cases, corresponding to different choices for a working covariance matrix. We also show that the regression-based test of Sham et al. ([2002] Am. J. Hum. Genet. 71:238,253) is equivalent to a robust score statistic derived from our GEE approach. These results have several important implications. First, this work provides new insight regarding the connection between these methods. Second, asymptotic approximations for power and sample size allow clear comparisons regarding the relative efficiency of the different methods. Third, our general framework suggests important extensions to the Haseman-Elston approach which make more complete use of the data in extended pedigrees and allow a natural incorporation of environmental and other covariates. © 2004 Wiley-Liss, Inc. [source]

The effect of involvement in participatory research on parent researchers in a Sure Start programme

HEALTH & SOCIAL CARE IN THE COMMUNITY, Issue 6 2006
Ann Rowe M Med Sci BA RN RHVArticle first published online: 24 AUG 200
Abstract Involving service users, patients and members of local communities in health and social care research is becoming increasingly common. However, surprisingly little research has been carried out to examine the experiences of such lay researchers. This paper presents the findings of a study to investigate the experiences of a group of parent researchers involved in a community survey within a UK Sure Start programme. The survey was undertaken to provide insight into the early impact of the programme and inform Sure Start programme expansion. Researchers were recruited from the local community and were given an accredited training programme, before working on the development of the research itself. They took a lead role in the development, data collection, analysis and report writing phases of the survey and have been actively involved with the dissemination of findings. In order to gain insight into the experiences of the lay researchers involved in this work, three separate methods were used to collect data: questionnaires before and after the study, a focus group at the end of the data collection phase and by analysis of personal diaries kept by the parent researchers. Findings reported include lay researchers responses to the accredited training programme, the development of new skills and understanding, access and the conduct of interviews and the impact of the work both for Sure Start and the researchers themselves. Some of the strengths and difficulties of participatory research are discussed and comment made on the extent to which lay involvement impacted on the conduct of the survey. [source]

Correction of mucopolysaccharidosis type IIIA somatic and central nervous system pathology by lentiviral-mediated gene transfer

THE JOURNAL OF GENE MEDICINE, Issue 9 2010
Chantelle McIntyre
Abstract Background The hallmark of lysosomal storage disorders (LSDs) is microscopically demonstrable lysosomal distension. In mucopolysaccharidosis type IIIA (MPS IIIA), this occurs as a result of an inherited deficiency of the lysosomal hydrolase sulphamidase. Consequently, heparan sulphate, a highly sulphated glycosaminoglycan, accumulates primarily within the cells of the reticulo-endothelial and monocyte-macrophage systems and, most importantly, neurones. Children affected by MPS IIIA experience a severe, progressive neuropathology that ultimately leads to death at around 15 years of age. Methods MPS IIIA pathology was addressed in a mouse model using two separate methods of therapeutic gene delivery. A lentiviral vector expressing murine sulphamidase was delivered to 6-week-old MPS IIIA affected mice either by intravenous injection, or by intraventricular infusion. Therapeutic outcomes were assessed 7 months after gene transfer. Results After intravenous gene delivery, liver sulphamidase was restored to approximately 30% of wild-type levels. The resultant widespread delivery of enzyme secreted from transduced cells to somatic tissues via the peripheral circulation corrected most somatic pathology. However, unlike an earlier study, central nervous system (CNS) pathology remained unchanged. Conversely, intraventricular gene delivery resulted in widespread sulphamidase gene delivery in (and reduced lysosomal storage throughout) the brain. Improvements in behaviour were observed in these mice, and interestingly, pathological urinary retention was prevented. Conclusions The CNS remains the last major barrier to effective therapy for children affected by LSDs. The blood,brain barrier (BBB) limits the uptake of lysosomal enzymes from the peripheral circulation into the CNS, making direct gene delivery to the brain a reasonable, albeit more challenging, therapeutic option. Future work will further assess the relative advantages of directly targeting the brain with somatic gene delivery with sulphamidase modified to increase the efficiency of transport across the BBB. Copyright © 2010 John Wiley & Sons, Ltd. [source]

Prognosis for patients with thin cutaneous melanoma

CANCER, Issue 6 2003
Long-term survival data from the New South Wales Central Cancer Registry, the Sydney Melanoma Unit
Abstract BACKGROUND Estimates of long-term survival for patients with thin (, 1 mm) primary cutaneous melanomas vary widely. Two separate methods were used to study the survival of patients with melanoma from New South Wales (NSW), Australia, and from the Sydney Melanoma Unit (SMU). METHODS The NSW Central Cancer Registry (NSWCCR) provided data on all patients who were diagnosed with cutaneous melanomas that measured , 1 mm thick between 1983 and 1998, inclusive. Patients with metastases at the time of diagnosis were not included, leaving 18,088 patients for analysis. The SMU data base was analyzed to extract data for all patients with thin melanomas who met the same criteria from 1979 to 1998, inclusive. All patients who had their primary tumors treated definitively elsewhere were excluded, leaving 2746 patients for analysis. Ten-year Kaplan,Meier survival rates were calculated, and significant differences were determined using log-rank analysis. Prognostic factors were evaluated with Cox proportional hazards analysis. RESULTS The NSWCCR analysis revealed a 10-year survival rate of 96.4%. The 10-year survival rate for patients at SMU was 92.7%. Among the patients at SMU who died, the median time to recurrence was 49.8 months, and the median time to death was 65.9 months. The 10-year survival for patients at SMU who had lesions that measured , 0.75 mm was 96.9% compared with 84.3% for patients who had lesions that measured 0.76,1.0 mm. For patients who had ulcerated melanomas measuring , 1 mm thick, the 10-year survival rate was 83%, compared with 92.3% for patients who had nonulcerated melanomas. CONCLUSIONS The results of the current study confirmed the excellent survival rate for patients with thin melanomas. Higher-risk subsets of patients who may warrant consideration for aggressive investigation and treatment are identifiable. Cancer 2003;98:1223,31. © 2003 American Cancer Society. DOI 10.1002/cncr.11624 [source]