Project description:BackgroundWe have shown previously in multivariable analysis that black men had 19% lower risk of death than white men with metastatic castration-resistant prostate cancer (mCRPC) treated with a docetaxel and prednisone (DP)-based regimen. The primary goal of this analysis was to compare progression-free survival (PFS), biochemical PFS, ≥50% decline in prostate-specific antigen (PSA) from baseline and objective response rate (ORR) in white, black and Asian men with mCRPC treated with a DP-based regimen.Patients and methodsIndividual patient data from 8820 mCRPC men randomized on nine phase III trials to a DP-containing regimen were combined. Race used in the analysis was based on self-report. End points were PFS, biochemical PSA, ≥50% decline in PSA from baseline and ORR. The proportional hazards and the logistic regression models were employed to assess the prognostic importance of race in predicting outcomes adjusting for established prognostic factors.ResultsOf 8820 patients, 7528 (85%) were white, 500 (6%) were black, 424 were Asian (5%) and 368 (4%) had race unspecified. Median PFS were 8.3 [95% confidence interval (CI) 8.2-8.5], 8.2 (95% CI 7.4-8.8) and 8.3 (95% CI 7.6-8.8) months in white, black and Asian men, respectively. Median PSA PFS were 9.9 (95% CI 9.7-10.4), 8.5 (95% CI 8.0-10.3) and 11.1 (95% CI 9.9-12.5) months in white, black and Asian men, respectively.ConclusionsWe observed no differences in clinical outcomes by race and ethnic groups in men with mCRPC enrolled on these phase III clinical trials with DP.
Project description:English national guidelines regarding dementia assessment and management recommend consideration of cultural and linguistic diversity when assessing people with cognitive complaints. To date there has been no assessment of adherence to these guidelines. We aimed to assess whether current services provided in memory assessment services (MAS) adhere to national policy, in their approach to the assessment and management of individuals with memory problems from minority ethnic backgrounds. We sent a survey to 213 memory services in England and Wales. Twenty MAS from seven regions responded to the survey. We found that 80% (16) provided translated resources, 70% (14) used cognitive assessment tools that are culturally sensitive and appropriate, and 65% (13) showed good use of sufficiently skilled and knowledgeable interpreters. Communication barriers, particularly language, were raised as a potential obstacle to diagnosing minority ethnic patients. Memory clinics appear to reflect national policy for the assessment and management of memory problems in minority ethnic patients. However, only a minority of services responded and they may be more engaged in considering these populations. We need wider knowledge of practice to explore how guidelines support healthcare professional's assessment of patients from minority ethnic groups in memory service diagnostic procedures.
Project description:Objectiveto identify perceptions of, and associations with, active ageing among ethnically diverse and homogeneous samples of older people in Britain.Design and settingcross-sectional and longitudinal surveys of older people living at home in Britain.Measuresactive ageing, health, psych-social, socio-economic circumstances, and indicators of quality of life.Resultsrespondents defined active ageing as having health, fitness, and exercise; psychological factors; social roles and activities; independence, neighbourhood and enablers. The ethnically diverse sample respondents were less likely to define active ageing as having physical health and fitness, and were less likely to rate themselves as ageing actively, than more homogeneous sample respondents. The lay-based measure of quality of life used was independently and consistently associated with self-rated active ageing in each sampleConclusionPolicy models of active ageing were reflected in lay views, although the latter had a more multidimensional focus. Lay definitions of active ageing were also more dynamic, compared with definitions of quality of life and successful ageing. Differences in self-rated active ageing and perceptions of this concept by ethnic group need further exploration.
Project description:A major challenge in molecular biology is interrogating the human transcriptome on a genome wide scale when only a limited amount of biological sample is available for analysis. Current methodologies using microarray technologies for simultaneously monitoring mRNA transcription levels require nanogram amounts of total RNA. To overcome the sample size limitation of current technologies, we have developed a method to probe the global gene expression in biological samples as small as 150 cells, or the equivalent of approximately 300 pg total RNA. The new method employs microfluidic devices for the purification of total RNA from mammalian cells and ultra-sensitive whole transcriptome amplification techniques. We verified that the RNA integrity is preserved through the isolation process, accomplished highly reproducible whole transcriptome analysis, and established high correlation between repeated isolations of 150 cells and the same cell culture sample. We validated the technology by demonstrating that the combined microfluidic and amplification protocol is capable of identifying biological pathways perturbed by stimulation, which are consistent with the information recognized in bulk-isolated samples.
Project description:Cellular signaling networks have evolved to enable swift and accurate responses, even in the face of genetic or environmental perturbation. Thus, genetic screens may not identify all the genes that regulate different biological processes. Moreover, although classical screening approaches have succeeded in providing parts lists of the essential components of signaling networks, they typically do not provide much insight into the hierarchical and functional relations that exist among these components. We describe a high-throughput screen in which we used RNA interference to systematically inhibit two genes simultaneously in 17,724 combinations to identify regulators of Drosophila JUN NH(2)-terminal kinase (JNK). Using both genetic and phosphoproteomics data, we then implemented an integrative network algorithm to construct a JNK phosphorylation network, which provides structural and mechanistic insights into the systems architecture of JNK signaling.
Project description:The need to apply modern technologies to analyze DNA from diverse clinical samples often stumbles on suboptimal sample quality. We developed a simple approach to assess DNA fragmentation in minute clinical samples of widely different origin and the likelihood of success of degradation-tolerant whole genome amplification (restriction and circularization-aided rolling circle amplification, RCA-RCA) and subsequent polymerase chain reaction (PCR). A multiplex PCR amplification of four glyceraldehyde-3-phosphate dehydrogenase amplicons of varying sizes was performed using genomic DNA from clinical samples, followed by size discrimination on agarose gel or fluorescent denaturing high-performance liquid chromatography (dHPLC). RCA-RCA followed by real-time PCR was also performed, for correlation. Even minimal quantities of longer PCR fragments ( approximately 300 to 400 bp), visible via high-sensitivity fluorescent dHPLC or agarose gel, were essential for the success of RCA-RCA and subsequent PCR-based assays. dHPLC gave a more accurate correlation between DNA fragmentation and sample quality than agarose gel electrophoresis. Multiplex-PCR-dHPLC predicted correctly the likelihood of assay success in formalin-fixed, paraffin-embedded samples fixed under controlled conditions and of different ages, in laser capture microdissection samples, in tissue print micropeels, and plasma-circulating DNA. Estimates of the percent information retained relative to snap-frozen DNA are derived for real-time PCR analysis. The assay is rapid and convenient and can be used widely to characterize DNA from any clinical sample of unknown quality.