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Biomedical subjects

Martin Brown

Publications and source records attributed to Martin Brown.

14 recordsLinked to original sources
PubMed2006

Insights into the behaviour of systems biology models from dynamic sensitivity and identifiability analysis: a case study of an NF-kappaB signalling pathway.

Mathematical modelling offers a variety of useful techniques to help in understanding the intrinsic behaviour of complex signal transduction networks. From the system engineering point of view, the dynamics of metabolic and signal transduction models can always be described by nonlinear ordinary differential equations (ODEs) following mass balance principles. Based on the state-space formulation, many methods from the area of automatic control can conveniently be applied to the modelling, analysis and design of cell networks. In the present study, dynamic sensitivity analysis is performed on a model of the IkappaB-NF-kappaB signal pathway system. Univariate analysis of the Euclidean-form overall sensitivities shows that only 8 out of the 64 parameters in the model have major influence on the nuclear NF-kappaB oscillations. The sensitivity matrix is then used to address correlation analysis, identifiability assessment and measurement set selection within the framework of least squares estimation and multivariate analysis. It is shown that certain pairs of parameters are exactly or highly correlated to each other in terms of their effects on the measured variables. The experimental design strategy provides guidance on which proteins should best be considered for measurement such that the unknown parameters can be estimated with the best statistical precision. The whole analysis scheme we describe provides efficient parameter estimation techniques for complex cell networks.

I-kappa B Kinase↗
PubMed2006

Projecting the number of patients with colorectal carcinoma by phases of care in the US: 2000-2020.

OBJECTIVE: This study provides projections of colorectal cancer prevalence by phases of care (initial, monitoring, and last year of life) to the year 2020 and describes the estimation method. METHODS: Cancer prevalence by phase of care was estimated from colorectal cancer incidence and survival from the Surveillance, Epidemiology, and End Results (SEER) Program data, population estimates and projections from the US Census Bureau, and all cause mortality data from the Human Mortality Life Tables. Assumptions of constant incidence and survival were used for projections from 2000 to 2020. Modeled and directly observed patient months by phase of care were compared for 1996 -1998 to provide validation of estimates. RESULTS: Prevalence of colorectal cancer is estimated to increase from 1,002,786 (0.36%) patients to 1,522,348 (0.46%) patients between 2000 and 2020. The estimated number of person-months in the initial and last year of life phases of care will increase 43%, while the monitoring phase of care will increase 54%. Modeled person-months by phase of care were consistent with directly observed measures of person months by phase of care in 1996-1998. CONCLUSIONS: Under assumptions of current cancer control strategies we project that colorectal cancer prevalence will increase more rapidly than the US population, largely due to the aging of the US population. This suggests that considerable resources will be needed in the future for initial, continuing and last year of life treatment of colorectal cancer patients unless notable breakthroughs in primary prevention occur in the future years.

Age Distribution↗
PubMed2006

Caloric restriction and intermittent fasting alter spectral measures of heart rate and blood pressure variability in rats.

Dietary restriction (DR) has been shown to increase life span, delay or prevent age-associated diseases, and improve functional and metabolic cardiovascular risk factors in rodents and other species. To investigate the effects of DR on beat-to-beat heart rate and diastolic blood pressure variability (HRV and DPV) in male Sprague-Dawley rats, we implanted telemetric transmitters and animals were maintained on either intermittent fasting (every other day feeding) or calorie-restricted (40% caloric reduction) diets. Using power spectral analysis, we evaluated the temporal profiles of the low- and high-frequency oscillatory components in heart rate and diastolic blood pressure signals to assess cardiac autonomic activity. Body weight, heart rate, and systolic and diastolic blood pressure were all found to decrease in response to DR. Both methods of DR produced decreases in the low-frequency component of DPV spectra, a marker for sympathetic tone, and the high-frequency component of HRV spectra, a marker for parasympathetic activity, was increased. These parameters required at least 1 month to become maximal, but returned toward baseline values rapidly once rats resumed ad libitum diets. These results suggest an additional cardiovascular benefit of DR that merits further studies of this potential effect in humans.

Animals↗
PubMed2005

How can medical students learn in a self-directed way in the clinical environment? Design-based research.

AIM: This study aimed to establish whether and under what conditions medical students can learn in a self-directed manner in the clinical environment. METHOD: A web-based learning management system brought 66 placement students, in a problem-based learning (PBL) medical curriculum, into closer touch with their clinical learning objectives and ways of achieving them. Free response comments from 16 of them during the 7 weeks they used it, transcripts of group discussions before and after the period of use, and responses from all 66 students to a questionnaire were analysed qualitatively. RESULTS: Students were rarely fully autonomous or subservient. They valued affective and pedagogic support, and relied on teachers to manage their learning environment. With support, they were motivated and able to choose how and when to meet their learning needs. The new system was a useful adjunct. CONCLUSIONS: Self-direction, interpreted literally, was a method of learning that students defaulted to when support and guidance were lacking. They found "supported participation" more valuable. Learning in the clinical environment was a social process with as many differences from, as similarities to, PBL.

Computer-Assisted Instruction↗
PubMed2004

A technology using feedback to manage experience based learning.

The aim was to establish how ICT could apply feedback principles to experience based learning. Based on a survey of student and staff requirements, we developed a personalized educational technology ('iSUS') that: (1) Made students clear what they should learn; (2) Helped them meet appropriate real patients; (3) Encouraged reflective feedback; (4) Calculated benchmarks from accumulated feedback; (5) Compared individual students' feedback against those benchmarks; (6) Matched clinical activities to curriculum objectives; (7) Gave feedback to teachers and course leads. Bench testing proved the system usable. During seven weeks of real time use, a whole year group of 111 students feedback on 1183 learning episodes. Five hundred and forty-one (46%) of feedback episodes were self initiated. We have successfully prototyped an application of feedback principles to experience based learning that students seem to find useful.

Computer-Assisted Instruction↗
PubMed2004

Race/ethnicity and the intensity of medical monitoring under 'watchful waiting' for prostate cancer.

BACKGROUND: Previous studies have found that racial/ethnic minority patients with prostate cancer are more frequently managed with "watchful waiting." Little, however, is known about the medical care received among men managed with watchful waiting. We examine the type and intensity of medical monitoring received by African American, Hispanic, and white patients with prostate cancer managed with "watchful waiting" in fee-for-service systems. METHODS: Surveillance Epidemiology and End Results-Medicare data for men diagnosed with prostate cancer 1994-1996 were used in this study. Men were determined to have initially received watchful waiting if they did not receive surgery, radiation, or hormone treatment within the first 7 months of diagnosis. Crosstabulations, multivariate logistic, and Cox regressions were used to examine the association between clinical and sociodemographic variables and the receipt of a primary care, urology visit, prostate-specific antigen test, or bone scan. RESULTS: In general, Hispanic and African American men received less medical monitoring and had longer median times from diagnosis to receipt of a medical monitoring visit or procedure than white men. Furthermore, nearly 6% of African American, 5% of Hispanic, and 1% of white men did not have any medical monitoring visits or procedures during the 60-month follow-up period (P<0.001). Differences in observed clinical or sociodemographic characteristics did not explain variations in medical monitoring. CONCLUSION: Regular medical monitoring is considered by most medical authorities to be a necessary component of management with watchful waiting. The disproportionately low receipt of medical monitoring visits and procedures observed for African American and Hispanic men managed with watchful waiting in this study suggest that there are racial/ethnic disparities in the receipt of appropriate prostate cancer management.

Black or African American↗
PubMed2002

Measuring costs: administrative claims data, clinical trials, and beyond.

BACKGROUND: Accurate estimation of medical care costs raises a host of issues, both practical and methodological. OBJECTIVES: This article reviews methods for estimating the long-term medical care costs associated with a cancer diagnosis. METHODS: The authors consider data from administrative claims databases and describe the analytic challenges posed by these increasingly common resources. They present a number of statistical methods that are valid under censoring and describe methods for estimating mean costs and controlling for covariates. In addition, the authors compare two different approaches for estimating the cancer-related costs; namely, the portion of the long-term costs that may be attributed to the disease. Examples from economic studies of breast and colorectal cancer are presented. RESULTS: In an analysis of data on colorectal cancer costs from the SEER-Medicare database, the two methods used to estimate expected long-term costs (one model based, one not model-based) yielded similar results. However, in calculating expected cancer-related costs, a method that included future medical costs among controls yielded quite different results from the method that did not include these future costs. CONCLUSIONS: Statistical methods for analyzing long-term medical costs under censoring are available and appropriate in many applications where total or disease-related costs are of interest. Several of these approaches are nonparametric and therefore may be expected to be robust against the non-standard features that are often encountered when analyzing medical cost data.

Clinical Trials as Topic↗
PubMedDate not supplied

Optimisation of the predictive ability of artificial neural network (ANN) models: a comparison of three ANN programs and four classes of training algorithm.

The purpose of this study was to determine whether artificial neural network (ANN) programs implementing different backpropagation algorithms and default settings are capable of generating equivalent highly predictive models. Three ANN packages were used: INForm, CAD/Chem and MATLAB. Twenty variants of gradient descent, conjugate gradient, quasi-Newton and Bayesian regularization algorithms were used to train networks containing a single hidden layer of 3-12 nodes. All INForm and CAD/Chem models trained satisfactorily for tensile strength, disintegration time and percentage dissolution at 15, 30, 45 and 60 min. Similarly, acceptable training was obtained for MATLAB models using Bayesian regularization. Training of MATLAB models with other algorithms was erratic. This effect was attributed to a tendency for the MATLAB implementation of the algorithms to attenuate training in local minima of the error surface. Predictive models for tablet capping and friability could not be generated. The most predictive models from each ANN package varied with respect to the optimum network architecture and training algorithm. No significant differences were found in the predictive ability of these models. It is concluded that comparable models are obtainable from different ANN programs provided that both the network architecture and training algorithm are optimised. A broad strategy for optimisation of the predictive ability of an ANN model is proposed.

Algorithms↗