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Paul Clarke

Publications and source records attributed to Paul Clarke.

24 records · Page 2Linked to original sources

Proteomic profiling of urinary proteins in renal cancer by surface enhanced laser desorption ionization and neural-network analysis: identification of key issues affecting potential clinical utility.

Recent advances in proteomic profiling technologies, such as surface enhanced laser desorption ionization mass spectrometry, have allowed preliminary profiling and identification of tumor markers in biological fluids in several cancer types and establishment of clinically useful diagnostic computational models. There are currently no routinely used circulating tumor markers for renal cancer, which is often detected incidentally and is frequently advanced at the time of presentation with over half of patients having local or distant tumor spread. We have investigated the clinical utility of surface enhanced laser desorption ionization profiling of urine samples in conjunction with neural-network analysis to either detect renal cancer or to identify proteins of potential use as markers, using samples from a total of 218 individuals, and examined critical technical factors affecting the potential utility of this approach. Samples from patients before undergoing nephrectomy for clear cell renal cell carcinoma (RCC; n = 48), normal volunteers (n = 38), and outpatients attending with benign diseases of the urogenital tract (n = 20) were used to successfully train neural-network models based on either presence/absence of peaks or peak intensity values, resulting in sensitivity and specificity values of 98.3-100%. Using an initial "blind" group of samples from 12 patients with RCC, 11 healthy controls, and 9 patients with benign diseases to test the models, sensitivities and specificities of 81.8-83.3% were achieved. The robustness of the approach was subsequently evaluated with a group of 80 samples analyzed "blind" 10 months later, (36 patients with RCC, 31 healthy volunteers, and 13 patients with benign urological conditions). However, sensitivities and specificities declined markedly, ranging from 41.0% to 76.6%. Possible contributing factors including sample stability, changing laser performance, and chip variability were examined, which may be important for the long-term robustness of such approaches, and this study highlights the need for rigorous evaluation of such factors in future studies.

Adult↗

An investigation into expectation-led interviewer effects in health surveys.

Many large-scale health surveys use interviewers to obtain standardised information about the health of the general population. To improve response rates and data quality, the researchers/designers usually brief the interviewers to familiarise them with the survey procedures and stimulate their interest in the survey. However, it is possible that interviewers, having been exposed to researchers' expectations, may inadvertently influence respondents to produce outcomes consistent with those expectations. Such expectations are referred to here as 'expectation-led interviewer effects'. In this paper, the design and results from an experiment to test for expectation-led interviewer effects are described. The experiment involved conducting two health surveys, called the 'experimental' and the 'control', which were identical in every way except that researchers made a reference to a supposed link between childhood and adult health at the experimental survey briefing. The testing procedure was designed prior to data collection to preclude accusations of data dredging and to ensure that the type I error probability was less than 5 percent. No consistent evidence of expectation-led interviewer effects was found, bar a statistically significant effect for health questions requiring the recall of detailed quantitative information. This effect was small, however.

Adult↗

Making sense of symptom checklists: a latent class approach to the first 9 years of the British Household Panel Survey.

BACKGROUND: In health inequalities research there is a growing impetus to examine the development of inequalities in health over time. However, many of the sources of longitudinal data in Britain are not designed specifically for health research. Typically, health status is assessed by self-reported problems and the use of symptom checklists. METHODS: The British Household Panel Survey (BHPS) is an annual survey of approximately 5500 private households containing 9000 men and women, which began in 1991. Each year, the BHPS contains a checklist of 13 health problems and symptoms. The findings presented here are based on adult participants aged 16 years and over in 1991. Using eight waves of data from the BHPS, we use latent class analysis (LCA) to model latent health status from a set of observed binary variables. Individuals are assigned to a latent health class on the basis of LCA estimated probabilities of class membership given their response patterns and the estimated unconditional class frequencies. The predictive value of latent health class membership is assessed for self-reported health status and functioning, health and welfare service use, and mortality 1 year later. RESULTS: The LCA supported a suitable four-class model of health status representing good health, psychosomatic health problems, physical health problems and comorbid health problems. Members of the good latent health class were predicted to have better self-reported health and functioning, less health and welfare service use, and lower risk of mortality 1 year later than members of the three problem health classes. Those with comorbid health problems were predicted to have particularly poor outcomes. CONCLUSIONS: A latent class approach to modelling self-reported health problems and symptoms has allowed for both quantitative and qualitative dimensions of health status to be captured. This may motivate better informed models of health by users of general population surveys.

Chi-Square Distribution↗

A comparison of transient-evoked otoacoustic emissions and automated auditory brainstem responses for pre-discharge neonatal hearing screening.

The aim of this study was to compare two hearing-screening methods in well newborn infants within the postnatal ward environment prior to discharge. Eighty-one newborn infants underwent one-step hearing screening by measurement of automated auditory brainstem responses (aABRs), using the ALGO-3 screener. These were compared with a further cohort of 81 neonates who underwent two-step screening using transient-evoked otoacoustic emissions (TEOAEs) followed by aABR. The pass rate was 78/81 (96.3%) for the one-step screen, 74/81 (91.4%) for the two-step screen, and 54/81 (66.7%) for TEOAE alone. There was no significant difference between cohorts in time required to complete the screening protocol. We conclude that pre-discharge hearing screening of newborn infants on the postnatal ward is feasible and acceptable. Use of TEOAE alone for pre-discharge screening is associated with an excessively high false-positive rate. At our institution, one-step screening resulted in a lower referral rate compared with a two-step approach. The performance of aABR screening may be affected by prior TEOAE screening.

Age Factors↗

Multiple measures of socio-economic position and psychosocial health: proximal and distal measures.

BACKGROUND: The aim of this paper is to compare three models for exploring the links between different measures of adult socioeconomic position (SEP)-education, occupation, income-and psychosocial health. Model I is a basic univariate regression model with psychosocial health as the outcome and a measure of SEP as the predictor. Model II is a multiple regression model with psychosocial health as the outcome with all three measures of SEP allocated the same temporal position as predictors. Model III treats education, a distal measure of SEP, as antecedent to the proximal measures of SEP in the prediction equations linking SEP to health. METHODS: Participants were drawn from the Whitehall II study, a prospective cohort study of British civil servants. Data analysed here are from Phase 5 (1997-1999) of data collection, 7830 individuals in all. The measures of SEP and psychosocial health were assessed via a self-administered questionnaire. RESULTS: The three models can lead to completely different conclusions. Model III, our preferred model, shows education to have a stronger indirect effect on psychosocial health when compared to its direct effect. The indirect effect is due to the effect of education on proximal measures of social position, occupation, and income in this case. CONCLUSIONS: Results reported here support the hypothesis that a comparison of the relative importance of the different measures of social position in predicting health is meaningless if the causal relationships among these measures are not accounted for.

Adult↗