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We have developed a novel adaptive multi-infusion advisory system for circulatory management of critically ill patients which co-ordinates infusion adjustments to ensure safe trajectories. This system should reduce patient hospital stay and improve patient outcome by enhancing the quality of patient circulatory control; alleviating the clinical cognitive load, giving staff more time for direct patient...
Patients in intensive care units are often prescribed a combination of sedative and analgesic to manage anxiety and pain relief. Proper sedation management is crucial to patient recovery but few intensive care units routinely employ strategies that tailor drug delivery to ongoing patient needs. The Infuse-Rite has been developed to automate a protocol that eliminates the possibility of excessive sedation...
This paper presents two alternative approaches to characterize the pharmacodynamics of propofol anesthesia in children, using State Entropy as a clinical end point. The first approach is the traditional approach where the pharmacodynamic model is described in terms of an effect-site equilibration rate constant and the Hill equation. In the second approach (the monitor-decoupled approach) the dynamics...
This paper reports a method that aims to quantify the changes of tumour vascular structure as a result of drug treatment. The measures we have investigated to date include: vessel radii, inter-branch lengths, tortuosity and branch angles. We show that the distribution of vessel radii is better modelled as a gamma distribution as opposed to the log-normal distribution asserted by other researchers...
The design of novel antimicrobial peptides (AMPs) is an important problem given the rise of drug-resistant bacteria. However, the large size of the sequence search space, combined with the time required to experimentally test or simulate AMPs at the molecular level makes computational approaches based on sequence analysis attractive. We propose a method for designing novel AMPs based on learning from...
Bacterial infections present an enormous problem causing human suffering and cost burdens to the healthcare systems worldwide. Herein we present several versatile strategies for controlled release of antibacterial agents which include silver ions as well as traditional antibiotics. At the heart of these release platforms is a thin film deposited by plasma polymerization. The use of plasma polymerization...
Strontium is a newly developed drug for decreasing risks of hip or vertebral fractures in postmenopausal women. Experimental studies have suggested that Strontium could enhance new bone formation and decrease the bone resorption. Mesenchymal stem cell (MSC) is an important category of stem cells which possess the osteogenic differentiation potential and could be used in the bone and cartilage tissue...
Tissue engineering of vascular grafts still presents several shortcomings. Aiming to vascular regeneration, we developed a biomimetic multilayered scaffold with a middle pivotal collagen lamina between two functionalized layers of poly-L-lactide by means of electrospinning technique, with oriented drug-delivery capacity for the differentiation of human mesenchymal stem cells seeded therein. Applying...
Targeting wound repair, we developed an electrospun poly-L-lactide fibrous scaffold functionalized with G-CSF, a growth factor which is widely recognized as important in wound healing homeostasis. The scaffold was characterized in terms of morphology, mechanical properties and in vitro capacity to induce organization of co-cultures of murine fibroblasts and keratinocytes into a dermo-epidermal multilayered...
The analgesic effect of morphine is highly individual, calling for objective methods to predict the subjective pain relief. Such methods might be based on alteration of brain response caused by morphine during painful stimuli. The study included 11 healthy volunteers subjectively quantifying perception of painful electrical stimulations in the esophagus. Brain evoked potentials following stimulations...
Contraceptive diaphragms offer a discreet method of pregnancy protection that women can use when needed with no side effects. Incorporating antiretroviral HIV microbicides into such devices may also provide protection against HIV infection. The paper gives a brief outline of the work being conducted by PATH, CONRAD and QUB on the development of a microbicide-releasing SILCS diaphragm. The design,...
Drug bioavailability is a major failing point of new pharmaceuticals i.e. drugs fail to reach their target or fail to stay there long enough for therapeutic effect. Compounding this issue, significant variability exists between patients and how they metabolize and distribute a drug. We present WebPK, a web-based tool for simulation of custom pharmacokinetic models. Model parameters can be entered...
It has been observed that heart rate variability (HRV) diminishes during anesthesia, but the exact mechanisms causing it are not completely understood. The aim of this paper was to study the dynamics of HRV during low dose propofol (N=9) and dexmedetomidine (N=8) anesthesia by using state-of-the-art time-varying methods, and thereby ultimately try to improve the safety of anesthesia. The time-varying...
In this paper we propose an application of local statistical models to the problem of identifying patients with pathologic complete response (PCR) to neoadjuvant chemotherapy. The idea of using local models is to split the input space (with data from PCR and NoPCR patients) and build a model for each partition. After the construction of the models we used bayesian classifiers and logistic regression...
This paper addresses mutational events that give rise to differing response to drugs focusing on Rac1, a protein that has been recognized as a target for drug design for cardiovascular disease due its regulatory role of angiogenesis. Rac1 has been considered with reference to Single Nucleotide Polymorphism (SNP), which has become of great value for personalized medicine. We have considered four variation...
Measuring drug resistance is one of the challenging and essential pharmaceutical activities. It is a laborious and costly laboratory-based experimentation. Various clinical and experimental analyses for measuring drug resistance have been carried out. Results have been obtained for different types of therapeutic agents as a consequence of changes in the amino acids compositions in the sequence (mutation)...
This work aims at examining the influence of lorazepam, an anxiolytic drug with sedative effects, on brain activity and specifically on EEG Fractal Dimension (FD). The main objective is to clarify the reasons for FD increase after drug intake and to establish a relationship between FD and EEG energy bands. 14 healthy subjects that received either 2.5mg of lorazepam (verum case) or placebo (placebo...
An automated methodology for Levodopa-induced dyskinesia (LID) assessment is presented in this paper. The methodology is based on the analysis of the signals recorded from accelerometers and gyroscopes, which are placed on certain positions on the subject's body. The obtained signals are analyzed and several features are extracted. Based on these features a classification technique is used for LID...
This study examines the effects of changing oxygen fractional inspiration ratio (FiO2), and nitrous oxide (N2O) for the improvement of cardiovascular control of mean arterial blood pressure (MAP) and heart rate (HR) in C57BL/6 mice under isoflurane anesthesia (1.5%) for up to 90 minutes post-induction. Heart rate variability (HRV) indices are also quantified under these conditions. The results indicate...
QT prolongation is the only clinically proven, yet insufficient, electrocardiogram (ECG) biomarker for drug-induced cardiac toxicity. The goal of this study is to evaluate whether JT area, i.e., total area of the T-wave, can serve as an ECG biomarker for drug-induced cardiac toxicity using both signal processing and computational modeling approaches. An ECG dataset that contained recordings from patients...
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