Location of Repository

Assessment of control and performance of biomedical systems

By Katie Harris


Introduction: In biomedical systems repeated measurements are often collected, thus presenting a statistical challenge due to high temporal correlation. This research\ud investigates the potential utility of two distinct statistical methodologies in their application.\ud \ud Application: Two clinically diverse biomedical systems, linked by the common methodological interest of assessing control and performance, are considered. (i) An application to renal anaemia aims to investigate the stability of haemoglobin levels, measured monthly for 13 months within 151 patients, with the ultimate goal of improving\ud patient control; (ii) the second an application concerns cerebral autoregulation (a stable cerebral blood flow over a range of arterial blood pressure), to maintain patient safety during a surgical procedure to prevent stroke. Repeated measurements of cerebral blood flow and arterial blood pressure were collected on 36 patients, yielding a total of 4519 cerebral blood flow and 4574 arterial blood pressure measurements (note that the number of observations vary between patients).\ud \ud Statistical methodology: Functional data analysis and multilevel modelling are utilised in the investigation of these two biomedical systems. Functional data analysis considers observations as a function rather than a highly correlated sequence of measurements. Multilevel modelling assumes that measurements are clustered and that within clusters, measurements are scattered about a trend in an uncorrelated manner.\ud \ud Results: Assessment of control within the renal anaemia system and knowledge of the relationship within the cerebral autoregulation system, has been achieved through\ud the successful application of functional data analysis. Loess curves were used as means of exploring the cerebral blood flow – arterial blood pressure relationship in the cerebral autoregulation application. B-splines and phase plots were used to explore haemoglobin control in the renal anaemia system. Further, multilevel modellingincorporating autoregressive correlation structures appropriately models the dependency amongst model residuals due to temporal correlation. Both functional data analysis and multilevelmodelling have demonstrated their utility in the application to model control in biomedical systems. \ud \ud Conclusions: The novel application of these statistical methodologies has successfully provided contemporary insight into these biomedical systems and shows strong prospects for further applications

Publisher: School of Medicine (Leeds)
Year: 2010
OAI identifier: oai:etheses.whiterose.ac.uk:1116

Suggested articles



  1. A distributed lag model with first order auto-regressive error term for hemoglobin response to erythropoietin in dialysis patients. AMIA Annu Symp
  2. (1948). A humoral mechanism in anoxic erythrocytosis. Acta Physiol Scand.
  3. (2005). A Language and Environment for Statistical Computing. R Foundation for Statistical Computing,
  4. A multilevel modelling solution to mathematical coupling.
  5. A new look at the statistical model identification.
  6. (1978). A practical guide to splines.
  7. A randomized controlled study of the consequences of hemodialysis membrane composition on erythropoietic response.
  8. (2008). An Assessment of Dynamic Autoregulation from Spontaneous Fluctuations of Cerebral Blood Flow Velocity: A Comparison of Two Models, Index of Autoregulation and Mean Flow Index. Anesthesia and Analgesia.
  9. (2005). Anaemia and heart failure: aetiology and treatment. Nephrology Dialysis Transplantation.
  10. (2006). Anaemia in chronic kidney disease: Causes, diagnosis, treatment. Cleveland clinic journal or medicine.
  11. Analyzing Change: A Primer on Multilevel Models with Applications to Nephrology.
  12. Anemia Management and the Delay of Chronic Renal Failure Progression.
  13. (1996). Antihypertensive drugs and cerebral circulation.
  14. (2002). Applied Functional Data Analysis -Methods and Case Studies.
  15. (1998). Assessment of cerebral pressure autoregulation in humans - a review of measurement methods. PhysiolMeas.
  16. (2006). Assessment of control in biomedical systems with specific application to the control of renal anemia in haemodialysis patients. The Yorkshire Kidney Research Fund;
  17. Autoregulatory plateau: does it exist?
  18. (1972). Bayes estimates for the linear model.
  19. Blood pressure and intercranial pressure-volume dynamics in severe head injury: relationship with cerebral blood flow.
  20. Carotid endarterectomy–an evidence-based review: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.
  21. Carotid Endarterectomy.
  22. Cases and observations: illustrative of renal disease accompanied by the secretion of albuminous urine. Guys Hosp Rep.
  23. (2003). Cerebral autoregulation during orthostatic stress in healthy controls and in patients with posturally related syncope. Clin Auton Res.
  24. Cerebral autoregulation dynamics in humans.
  25. (1997). Cerebral autoregulation dynamics in premature newborns.
  26. Cerebral autoregulation in carotid artery occlusive disease assessed from spontaneous blood pressure fluctuations by correlation coefficient index.
  27. Cerebral autoregulation: an overview of current concepts and methodology with special focus on the elderly.
  28. (1990). Cerebral Autoregulation. Cerebrovascular and Brain Metabolism Reviews.
  29. (2010). Cerebral Autoregulationduring Carotid Endarterectomy Under Regional and General Anesthesia. European Journal of Vascular and Endovascular Surgery;
  30. Cerebral blood flow responses to severe orthostaticstressinfitandunfityoungandolderadults.
  31. Cerebral BloodFlowandOxygenConsumptioninMan. TheAmerican physiological society.
  32. Cerebral hemodynamics in symptomatic and asymptomatic patients with severe unilateral carotid stenosis before and after carotid endarterectomy.
  33. Cerebral hyperperfusion following carotid endarterectomy.
  34. (2005). Cerebral hyperperfusion syndrome. The Lancet.
  35. (1994). Cerebral versus systemic hemodynamics during graded orthostatic stress in humans. Circulation.
  36. (1978). Cerebrovascular Disorders.
  37. Cloning and expression of the human erythropoietin gene.
  38. Comparative efficacy of Subcutaneous versus Intravenous dose of erythropoietin in pre-dialysis patients of chronic renal failure. Journal Indian academy of clinical medicine.
  39. (2006). Comparison of Akaike information criteria (AIC) and Bayesian information criteria (BIC) in selection of stock recruitment relationships. Fish Res.
  40. (1992). Comparison of intravenous and subcutaneous recombinant human erythropoietin for anemia in hemodialysis patients with significant comorbid disease.
  41. Comparison of Static and Dynamic Cerebral Autoregulation Measurements.
  42. ComparisonofFourierself-deconvolutionand maximum likelihood restoration for curve fitting. Analytical Chemistry.
  43. Computer decision support systems.
  44. (2003). Confidence intervals by the profile likelihood method, with applications in veterinary epidemiology. Contributed paper at ISVEE X.
  45. Correction of Anemia with epoetin alfa in chronic kidney disease.
  46. Correction ofthe anemia of end-stage renal disease with recombinant human erythropoietin.
  47. (2003). Delayed cerebrovascular autoregulatory response to ergometer exercise in normotensive elderly humans. Cerebrovasc Dis.
  48. Development and exploitation of a clinical decision support system for the management of renal anemia.
  49. Diagnosis and initial management of acute stroke and transient ischaemic attack: summary of NICE guidance.
  50. (1974). Differential equations, dynamical systems and linear algebra;
  51. dos Santos Silva I. Statistical issues in lifecourse epidemiology.
  52. Dose Conversion from Epoetin alfa to Darbepoetin alfa for Patients with Chronic Kidney Disease Receiving Hemodialysis.
  53. Double-blind comparison of full and partial anemia correction in incident hemodialysis patients without symptomatic heart disease.
  54. Dynamic cerebral autoregulation and beat to beat blood pressure control are impaired in acute ischaemic stroke.
  55. Dynamic cerebral autoregulation in carotid stenosis before and after carotid stenting.
  56. Dynamic cerebral autoregulation is unaffected by aging.
  57. Dynamic regulation of middle cerebral artery blood flow velocity in aging and hypertension.
  58. (2008). Early assessment and treatment of people who have had a stroke or transient ischaemic attack (TIA). Information about NICE clinical guideline 68;
  59. Effect of Carotid Endarterectomy or Stenting on Impairment of Dynamic Cerebral Autoregulation.
  60. (2000). Effects of haemoglobin normalization on quality of life and cardiovascular parameters in end-stage renal failure. Nephrol Dial Transplant.
  61. (2008). Erythropoietin stimulating agents in the management of anemia of chronic kidney disease. Patient Preference and Adherence.
  62. (1978). Estimating the Dimension of a Model. The Annals of Statistics.
  63. Failure of autoregulation of cerebral blood flow in neonates studied by pulsed doppler ultrasound of the internal carotid artery.
  64. Flexible Parsimonious Smoothing and Additive Modeling.
  65. Flexible smoothing with B-splines and penalties.
  66. Functional Data Analysis Applied to a Randomized Controlled Clinical Trial in Hemodialysis Patients Describes the Variability of Patient Responses in the Control of Renal Anemia.
  67. (1997). Functional Data Analysis.
  68. Gaussian process functional regression modeling for batch data.
  69. General anesthesia versus local anesthesia for carotid surgery (GALA): a multicentre, randomised controlled trial.
  70. (1997). Guidelines for the use of carotid endarterectomy: current recommendations from the Canadian Neurosurgical Society. Can Med Mssoc.
  71. (2009). Haemoglobin and haematocrit targets for the anemia of chronic kidney disease (Review). The Cochrane Collaboration.
  72. (1999). Hematocrit level and associated mortality in hemodialysis patients.
  73. Hemodynamic effect of carotid endarterectomy.
  74. (1997). Hemodynamic instability after carotid endarterectomy: risk factors and associations with operativecomplications.
  75. (2005). Hemoglobin cycling in hemodialysis patients treated with recombinant human erythropoietin. Kidney Int.
  76. Hemoglobin level variability: Associations with co-morbidity, intercurrent events, and hospitalizations.
  77. (2002). Hierarchical linear models : applications and data analysis methods. Thousand Oaks, CA ; London : Sage Publications;
  78. (2004). Human Anatomy and Physiology.
  79. Impaired dynamic cerebral autoregulation in carotid artery stenosis.
  80. (2000). Increasing the hematocrit has a beneficial effect on quality of life and is safe in selected hemodialysis patients. J Am Soc Nephrol.
  81. Information theory and an extension of the maximum likelihood principle.
  82. Is strokethemost commoncause ofdisability?
  83. (2003). Linearity and non-linearityin cerebral hemodynamics. Med Eng Phys.
  84. Local versus general anesthesia for carotid endarterectomy. Cochrane database of systematic reviews.
  85. Locally Weighted Regression: An approach to Regression analysis by local fitting.
  86. (1991). Logspline Density Estimation. Computational Statistics and Data Analysis.
  87. (2009). Managing the anaemia of chronic kidney disease. Aust Prescr.
  88. Maximum likelihood approaches to variance component estimation and to related problems.
  89. (2002). Mixed Effects Models in S and S-Plus.
  90. (2005). MLwiN version 2.02. Multilevel Models Project, Institute of Education,
  91. Modeling of nonlinear physiological systems with fast and slow dynamics. II. Application to cerebral autoregulation.
  92. (1999). Models for Repeated Measurements.
  93. (1997). Monitoring of autoregulation using laser Doppler flowmetry in patients with head injury.
  94. (1996). Monitoring of cerebral autoregulation in head injured patients.
  95. (1999). Multilevel Analysis: An Introduction to Basic and Advanced Multilevel Modeling.
  96. (2001). Multilevel modelling of health statistics.
  97. (1995). Multilevel statistical models. London: Edward Arnold;
  98. (1994). Multilevel time series models with applications to Repeated Measures data. Statistics in Medicine.
  99. Normalization of hemoglobin levels in chronic kidney disease and anemia.
  100. On the Estimation and Performance of Subset Autoregressive Integrated Moving Average Models.
  101. Optimal routeof administrationof erythropoietinin chronicrenal failure patients: Intravenous versus subcutaneous.
  102. (1990). Pharmacokinetics and effects of recombinant human erythropoietin after intravenous and subcutaneous injections to healthy volunteers.
  103. (2009). Population-based study of risk and predictors of stroke in the first few hours after a TIA. Neurology.
  104. Pressure-autoregulation, C02 reactivity andasymmetryofhaemodynamicparametersinpatientswithcarotisarterystenotic disease: A clinical appraisal.
  105. Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial.
  106. Properties of sufficiency and statisticaltests.
  107. Purification of human erythropoietin.
  108. Random effects models for longitudinal data.
  109. (1996). Recent insights into the regulation of cerebral circulation.
  110. (1989). Recombinant human erythropoietin in anemic patients with endstage renal disease. Results of a phase III multicenter trial. Ann Intern Med.
  111. Recovery of interblock information when block sizes are unequal.
  112. (2008). Red Blood Cell Lifespan, Erythropoiesis and Hemoglobin Control. Contrib Nephrol.
  113. Red blood cell survival in chronic renal failure.
  114. Robust Locally Weighted Regression and Smoothing Scatterplots.
  115. (1994). Simultaneous transcranial Doppler and arterial blood pressure response to lower body negative pressure.
  116. Spect measurements of regional cerebral perfusion and carbondioxide reactivity: correlation with cerebral collaterals in internal carotid artery occlusive disease.
  117. (1992). Statistical information and the measurement of educational outcomes (editorial).
  118. (2001). Stroke incidence and risk factors in a population based cohort study. London: The Stroke Association;
  119. Structured conversion from thrice weekly to weekly erythropoietic regimens using a computerized decision-support system: A randomized clinical study.
  120. Subcutaneous Compared with Intravenous Epoetin in Patients Receiving Hemodialysis. The New England
  121. Testing for Serial Correlation in Least Squares Regression,
  122. (1994). Testing of cerebral autoregulation in head injury by waveform analysis of blood flow velocity and cerebral perfusion pressure. Acta Neurochir.
  123. (2004). The Analysis of time series - An Introduction. London: Chapman and Hall;
  124. (2008). The Anatomical Basis of Clinical Practice, 40th edition. Edinburgh : Churchill Livingstone;
  125. (2000). The application of multilevel modelling to periodontal research data. Community Dental Health.
  126. (1996). The Burden of Stroke. London: The Stroke Association;
  127. (1996). The differing effects of regional and general anesthesia on cerebral metabolism during carotid endarterectomy. European Journal of Vascular and Endovascular Surgery.
  128. The effect of epoetin dose on hematocrit.
  129. (1998). The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin.
  130. The GALA trial – a summary of the findings.
  131. The goodness of fit of regression formulae and the distribution of regression coefficients.
  132. The New FDA label For Erythropoietin Treatment: How Does It Affect Hemoglobin Target? Kidney International.
  133. (1931). The Smoothing of Time Series.
  134. The use of iron in patients on chronic dialysis: mistakes and misconceptions.
  135. (1989). The use of recombinant human erythropoietin: Effect in end-stage renal disease. Prevention of Chronic Uremia.
  136. Thomas Willis’ famous eponym: the circle of Willis.
  137. (1994). Time Series Analysis, Forecasting and Control.
  138. Transcranial Doppler Monitoring during carotid endarterectomy.
  139. Transfer function analysis for clinical evaluation of dynamic cerebral autoregulation - a comparison between spontaneous and respiratoryinduced oscillations.
  140. Transfer function analysis of dynamic cerebral autoregulation in humans.
  141. (2007). Treating anemia of chronic kidney disease in the primary care setting: cardiovascularoutcomes and management recommendations. Osteopathic Medicine and Primary Care.
  142. (1990). Treatment of the anemia of chronic renal failure with recombinant human erythropoietin. Annu Rev Med.
  143. (1994). Variance components testing in longitudinal mixed effects model.
  144. (2000). WHO Expert committeeon biological standardization technical report series.
  145. (1993). Worldwide prevalence of anaemia

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.