Prostate cancer detection and characterisation using innovative medical imaging

Prostate cancer is the second most common cancer affecting men worldwide. All prostate cancer however, is not equal: some forms of the disease are inert and do not require intervention; other, more aggressive forms benefit from early detection and treatment. Thus, accurate risk stratification is paramount. Inadequacies in the current diagnostic pathway for prostate cancer lead to incorrect risk assignment. Ways of enhancing the diagnostic pathway and improving risk stratification using novel bio-markers are being actively researched worldwide. This thesis focuses on work carried out at University College London (UCL)/University College London Hospitals (UCLH), investigating imaging as a biomarker in prostate cancer. The development of an enhanced form of ultrasound imaging - Prostate HistoScanning (PHS), and the use of multi-parametric magnetic resonance imaging (mpMRI) for prostate cancer detection and risk stratification are investigated. The main body of work: Prostate Imaging Compared to Transperineal Ultrasound guided biopsy for significant prostate cancer Risk Evaluation; the acronym for this is the PICTURE Study, was designed and carried out at UCLH between 2012 and 2014. This research aimed to establish if imaging has a role in improving prostate cancer detection and, if by utilizing imaging in the form of either multi-parametric MRI (mpMRI) or prostate HistoScanning (PHS), men with a negative test may be spared further prostate biopsy. Additionally, for men with a lesion detected on imaging, could a targeted sampling strategy afford accurate disease detection and risk stratification. Despite initial promising results, prostate HistoScanning was found to have no role in prostate cancer detection. Multiparametric MRI however, demonstrated high performance characteristics for the detection of disease. It shows potential as a useful tool for men in whom diagnostic uncertainty remains following primary biopsy; it is asserted that it should therefore be used to help risk stratify these men. Moreover, mpMRI targeted biopsy provides accurate risk stratification; and is an approach that should be adopted

The Effects of Pregnenolone 16α-Carbonitrile Dosing on Digoxin Pharmacokinetics and Intestinal Absorption in the Rat

The effect of Pgp induction in rats by pregnenolone 16α-carbonitrile (PCN) (3 days, 35 mg/kg/d, p.o.) on digoxin pharmacokinetics and intestinal transport has been assessed. After intravenous or oral digoxin dosing the arterial and hepatic portal vein (oral) AUC(0-24h) were significantly reduced by PCN pre-treatment. Biliary digoxin clearance increased 2-fold following PCN treatment. PCN significantly increased net digoxin secretion (2.05- and 4.5-fold respectively) in ileum and colon but not in duodenum or jejunum. This increased secretion correlated with increased Pgp protein expression in ileum and colon. Both intestinal and biliary excretion therefore contribute to altered digoxin disposition following PCN

Metal-Insulator Transition and Spin Degree of Freedom in Silicon 2D Electron Systems

Magnetotransport in 2DES's formed in Si-MOSFET's and Si/SiGe quantum wells at low temperatures is reported. Metallic temperature dependence of resistivity is observed for the n-Si/SiGe sample even in a parallel magnetic field of 9T, where the spins of electrons are expected to be polarized completely. Correlation between the spin polarization and minima in the diagonal resistivity observed by rotating the samples for various total strength of the magnetic field is also investigated.Comment: 3 pages, RevTeX, 4 eps-figures, conference paper (EP2DS-13

Metal-insulator transition in disordered 2DEG including temperature effects

We calculate self-consistently the mutual dependence of electron correlations and electron-defect scattering for a two dimensional electron gas at finite temperature. We employ an STLS approach to calculate the electron correlations while the electron scattering rate off Coulombic impurities and surface roughness is calculated using self-consistent current-relaxation theory. The methods are combined and self-consistently solved. We discuss a metal-insulator transition for a range of disorder levels and electron densities. Our results are in good agreement with recent experimental observations.Comment: 4 pages, RevTeX + epsf, 5 figure

Texture-Modified Diet for Improving the Management of Oropharyngeal Dysphagia in Nursing Home Residents: An Expert Review.

Abstract Objectives This paper provides evidence-based and, when appropriate, expert reviewed recommendations for long-stay residents who are prescribed texture-modified diets (TMDs), with the consideration that these residents are at high risk of worsening oropharyngeal dysphagia (OD), malnutrition, dehydration, aspiration pneumonia, and OD-associated mortality, poorer quality of life and high costs. Design Nestlé Health Science funded an initial virtual meeting attended by all authors, in which the unmet needs and subsequent recommendations for OD management were discussed. The opinions, results, and recommendations detailed in this paper are those of the authors, and are independent of funding sources. Setting OD is common in nursing home (NH) residents, and is defined as the inability to initiate and perform safe swallowing. The long-stay NH resident population has specific characteristics marked by a shorter life expectancy relative to community-dwelling older adults, high prevalence of multimorbidity with a high rate of complications, dementia, frailty, disability, and often polypharmacy. As a result, OD is associated with malnutrition, dehydration, aspiration pneumonia, functional decline, and death. Complications of OD can potentially be prevented with the use of TMDs. Results This report presents expert opinion and evidence-informed recommendations for best practice on the nutritional management of OD. It aims to highlight the practice gaps between the evidence-based management of OD and real-world patterns, including inadequate dietary provision and insufficient staff training. In addition, the unmet need for OD screening and improvements in therapeutic diets are explored and discussed. Conclusion There is currently limited empirical evidence to guide practice in OD management. Given the complex and heterogeneous population of long-stay NH residents, some 'best practice' approaches and interventions require extensive efficacy testing before further changes in policy can be implemented

Interface charged impurity scattering in semiconductor MOSFETs and MODFETs: temperature dependent resistivity and 2D "metallic" behavior

We present the results on the anomalous 2D transport behavior by employing Drude-Boltzmann transport theory and taking into account the realistic charge impurity scattering effects. Our results show quantitative agreement with the existing experimental data in several different systems and address the origin of the strong and non-monotonic temperature dependent resistivity.Comment: Presented at SIMD, Dec. 1999 in Hawaii. To be published in Superlattices and Microstructures, May 2000 issu

Phase diagram of the metal-insulator transition in 2D electronic systems

We investigated the interdependence of the effects of disorder and carrier correlations on the metal-insulator transition in two-dimensional electronic systems. We present a quantitative metal-insulator phase diagram. Depending on the carrier density we find two different types of metal-insulator transition - a continuous localization for rs=<8 and a discontinuous transition at higher rs. The critical level of disorder at the transition decreases with decreasing carrier density. At very low carrier densities we find that the system is always insulating. The value of the conductivity at the transition is consistent with recent experimental measurements. The self-consistent method which we have developed includes the effects of both disorder and correlations on the transition, using a density relaxation theory with the Coulomb correlations determined from numerical simulation data.Comment: 4 pages, RevTeX + epsf, 5 figures. New comments on conducting phase and on the conductivity. References updated and correcte

Optimum Small Optical Beam Displacement Measurement

We derive the quantum noise limit for the optical beam displacement of a TEM00 mode. Using a multimodal analysis, we show that the conventional split detection scheme for measuring beam displacement is non-optimal with 80% efficiency. We propose a new displacement measurement scheme that is optimal for small beam displacement. This scheme utilises a homodyne detection setup that has a TEM10 mode local oscillator. We show that although the quantum noise limit to displacement measurement can be surpassed using squeezed light in appropriate spatial modes for both schemes, the TEM10 homodyning scheme out-performs split detection for all values of squeezing.Comment: 13 pages, 7 figure

Superconductivity in correlated disordered two-dimensional electron gas

We calculate the dynamic effective electron-electron interaction potential for a low density disordered two-dimensional electron gas. The disordered response function is used to calculate the effective potential where the scattering rate is taken from typical mobilities from recent experiments. We investigate the development of an effective attractive pair potential for both disordered and disorder free systems with correlations determined from existing numerical simulation data. The effect of disorder and correlations on the superconducting critical temperature Tc is discussed.Comment: 4 pages, RevTeX + epsf, 4 figure