Electroporation, the transient increase in the permeability of cell membranes when exposed to a high electric field, is an established in vitro technique and is used to introduce DNA or other molecules into cells. When the trans-membrane voltage induced by an external electric field exceeds a certain threshold (normally 0.2-1 V), a rearrangement of the molecular structure of the membrane occurs, leading to pore formation in the membrane and a considerable increase in the cell membrane permeability to ions, molecules and even macromolecules. This phenomenon is, potentially, the basis for many in vivo applications such as electrochemotherapy and gene therapy, but still lacks a comprehensive theoretical basis. This article reviews the state of current electroporation theories and briefly considers current and potential applications in biology and medicine.

Terahertz (THz) radiation occupies that region of the electromagnetic (EM) spectrum between approximately 0.3 and 20 THz. Recent advances in methods of producing THz radiation have stimulated interest in studying the interaction between radiation and biological molecules and tissue. Given that the photon energies associated with this region of the spectrum are 2.0 x 10(-22) to 1.3 x 10(-20) J, an analysis of the interactions requires an understanding of the permittivity and conductivity of the medium (which describe the bulk motions of the molecules) and the possible transitions between the molecular energy levels. This paper reviews current understanding of the interactions between THz radiation and biological molecules, cells and tissues. At frequencies below approximately 6 THz. the interaction may be understood as a classical EM wave interaction (using the parameters of permittivity and conductivity), whereas at higher frequencies. transitions between different molecular vibrational and rotational energy levels become increasingly important and are more readily understood using a quantum-mechanical framework. The latter is of particular interest in using THz to probe transitions between different vibrational modes of deoxyribonucleic acid. Much additional experimental work is required in order to fully understand the interactions between THz radiation and biological molecules and tissue.

With increasing life expectancies and the desire to maintain active lifestyles well into old age, the impact of the debilitating disease osteoarthritis (OA) and its burden on healthcare services is mounting. Emerging regenerative therapies could deliver significant advances in the effective treatment of OA but rely upon the ability to identify the initial signs of tissue damage and will also benefit from quantitative assessment of tissue repair in vivo. Continued development in the field of quantitative MRI in recent years has seen the emergence of techniques able to probe the earliest biochemical changes linked with the onset of OA. Quantitative MRI measurements including T 1 , T 2 and T 1r relaxometry, diffusion weighted imaging and magnetisation transfer have been studied and linked to the macromolecular structure of cartilage. Delayed gadolinium-enhanced MRI of cartilage, sodium MRI and glycosaminoglycan chemical exchange saturation transfer techniques are sensitive to depletion of cartilage glycosaminoglycans and may allow detection of the earliest stages of OA. We review these current and emerging techniques for the diagnosis of early OA, evaluate the progress that has been made towards their implementation in the clinic and identify future challenges in the field.

Whilst SGA identified a patient group with significantly abnormal body mass, muscle mass and muscle strength, serum albumin did not. Serum albumin is not a useful marker of malnutrition in stable patients on CAPD.

Techniques for the coherent generation and detection of electromagnetic radiation in the far infrared, or terahertz, region of the electromagnetic spectrum have recently developed rapidly and may soon be applied for in vivo medical imaging. Both continuous wave and pulsed imaging systems are under development, with terahertz pulsed imaging being the more common method. Typically a pump and probe technique is used, with picosecond pulses of terahertz radiation generated from femtosecond infrared laser pulses, using an antenna or nonlinear crystal. After interaction with the subject either by transmission or reflection, coherent detection is achieved when the terahertz beam is combined with the probe laser beam. Raster scanning of the subject leads to an image data set comprising a time series representing the pulse at each pixel. A set of parametric images may be calculated, mapping the values of various parameters calculated from the shape of the pulses. A safety analysis has been performed, based on current guidelines for skin exposure to radiation of wavelengths 2.6 μm–20 mm (15 GHz–115 THz), to determine the maximum permissible exposure (MPE) for such a terahertz imaging system. The international guidelines for this range of wavelengths are drawn from two U.S. standards documents. The method for this analysis was taken from the American National Standard for the Safe Use of Lasers (ANSI Z136.1), and to ensure a conservative analysis, parameters were drawn from both this standard and from the IEEE Standard for Safety Levels with Respect to Human Exposure to Radio Frequency Electromagnetic Fields (C95.1). The calculated maximum permissible average beam power was 3 mW, indicating that typical terahertz imaging systems are safe according to the current guidelines. Further developments may however result in systems that will exceed the calculated limit. Furthermore, the published MPEs for pulsed exposures are based on measurements at shorter wavelengths and with pulses of longer duration than those used in terahertz pulsed imaging systems, so the results should be treated with caution.

The 2-pool urea kinetic model has been developed analytically and applied to the description of the observed increase in blood levels of urea following dialysis (urea rebound), assuming that the dialyser urea clearance K less than 0.4X where X is the urea mass transfer coefficient between the intracellular and extracellular pools (volumes V1, V2 respectively). Urea generation was also neglected. Measurements were made in a group of six children suffering from chronic renal failure. From the model X, the efficiency of dialysis, and the equilibrium urea concentration C infinity were estimated in the presence of urea rebound using a blood urea measurement taken 90 min following start of dialysis, in addition to the conventional samples taken immediately pre- and post-dialysis. In three of the patients agreement between the experimental value of X derived from a multi-blood-sample technique post-dialysis, and the model value, was within 10%, for the range V1 = 0.4 W - 0.38 W, V2 = 0.2 W - 0.238 W, (W = patient's weight). Experimental values of X were in the range 93 - 300 ml min-1. Model estimates of C infinity were accurate to within 10%. An approximate technique was also developed which permitted an estimate of C infinity which was independent of V1, V2, K. The results indicated that C infinity was estimated to within 10% of the true equilibrium urea concentration. The error in the estimate of dialysis efficiency based on a single pool model was reduced by at least 50% using the model. The model may be applied clinically to the estimation of dialysis efficiency in the presence of significant urea rebound.

Infertility affects one in six couples at some time in their lives, with 48% of these couples requiring assisted conception techniques in order to achieve a pregnancy. Whilst the overall clinical pregnancy rate per embryo transfer is 23%, this varies widely between clinics. The Human Fertilisation and Embryology Authority has attempted to analyse the results of all units, with weighting of different factors affecting assisted conception, and the published data have invariably led to comparisons between units. However, statistical models need to be developed to eliminate bias for valid comparisons. Neural networks offer a novel approach to pattern recognition. In some instances neural networks can identify a wider range of associations than other statistical techniques due in part to their ability to recognize highly non-linear associations. It was hoped that a neural network approach may be able to predict success for individual couples about to undergo in-vitro fertilization (IVF) treatment. A neural network was constructed using the variables of age, number of eggs recovered, number of embryos transferred and whether there was embryo freezing. Overall the network managed to achieve an accuracy of 59%.

The ability to predict how far a drug will penetrate into the tumour microenvironment within its pharmacokinetic (PK) lifespan would provide valuable information about therapeutic response. As the PK profile is directly related to the route and schedule of drug administration, an in silico tool that can predict the drug administration schedule that results in optimal drug delivery to tumours would streamline clinical trial design. This paper investigates the application of mathematical and computational modelling techniques to help improve our understanding of the fundamental mechanisms underlying drug delivery, and compares the performance of a simple model with more complex approaches. Three models of drug transport are developed, all based on the same drug binding model and parametrized by bespoke in vitro experiments. Their predictions, compared for a 'tumour cord' geometry, are qualitatively and quantitatively similar. We assess the effect of varying the PK profile of the supplied drug, and the binding affinity of the drug to tumour cells, on the concentration of drug reaching cells and the accumulated exposure of cells to drug at arbitrary distances from a supplying blood vessel. This is a contribution towards developing a useful drug transport modelling tool for informing strategies for the treatment of tumour cells which are 'pharmacokinetically resistant' to chemotherapeutic strategies.