Continuous non-destructive monitoring of cell health using impedance based interdigitated electrode structured sensors

This article examines some preliminary tests which were performed in order to evaluate the best electrode configuration (width and spacing) for cell culture analyses. Biochips packaged with indium tin oxide (ITO) interdigitated electrodes (IDEs) were used to perform impedance measurements on A549 cells cultured on the surface of the biochip. Several tests were carried out using a 10 mM solution of Sodium Chloride (NaCl), cell medium and the cell culture itself to characterize some of the configurations already fabricated in the facilities at Tyndall National Institute.

Prediction and prevention of venous thrombosis in pregnancy

Venous thromboembolism (VTE) remains the leading cause of maternal mortality. Reports identified further research is required in obese and women post caesarean section (CS). Risk factors for VTE during pregnancy are periodically absent indicating the need for a simple and effective screening tool for pregnancy. Perturbation of the uteroplacental haemostasis has been implicated in placenta mediated pregnancy complications. This thesis had 4 main aims: 1) To investigate anticoagulant effects following a fixed thromboprophylaxis dose in healthy women post elective CS. 2) To evaluate the calibrated automated thrombogram (CAT) assay as a potential predictive tool for thrombosis in pregnancy. 3) To compare the anticoagulant effects of fixed versus weight adjusted thromboprophylaxis dose in morbidly obese pregnant women. 4) To investigate the LMWH effects on human haemostatic gene and antigen expression in placentae and plasma from the uteroplacental , maternal and fetal circulation. Tissue factor pathway inhibitor (TFPI), thrombin antithrombin (TAT), CAT and anti-Xa levels were analysed. Real-time PCR and ELISA were used to quantify mRNA and protein expression of TFPI and TF in placental tissue. In women post CS, anti-Xa levels do not reflect the full anticoagulant effects of LMWH. LMWH thromboprophylaxis in this healthy cohort of patients appears to have a sustained effect in reducing excess thrombin production post elective CS. The results of this study suggest that predicting VTE in pregnant women using CAT assay is not possible at present time. The prothrombotic state in pregnant morbidly obese women was substantially attenuated by weight adjusted but not at fixed LMWH doses. LMWH may be effective in reducing in- vivo thrombin production in the uteroplacental circulation of thrombophilic women. All these results collectively suggest that at appropriate dosage, LMWH is effective in attenuating excess thrombin generation, in low risk pregnant women post caesarean section or moderate to high risk pregnant women who are morbidly obese or tested positive for thrombophilia. The results of the studies provided data to inform evidence-based practice to improve the outcome for pregnant women at risk of thrombosis.

Pharmacotherapy optimization in older patients by a structured clinical pharmacist assessment and intervention

Introduction: Older individuals are particularly vulnerable to potentially inappropriate prescribing (PIP), drug related problems (DRPs) and adverse drug reactions (ADRs). A number of different interventions have been proposed to address these issues. However to-date there is a paucity of well-designed trials examining the impact of such interventions. Therefore the aims of this work were to: (i) establish a baseline PIP prevalence both nationally and internationally using the STOPP, Beers and PRISCUS criteria, (ii) identify the most comprehensive method of assessing PIP in older individuals, (iii) develop a structured pharmacist intervention supported by a computer decisions support system (CDSS) and (iv) examine the impact of this intervention on prescribing and incidence of ADRs. Results: This work identified high rates of PIP across all three healthcare settings in Ireland, 84.7% in the long term care, 70.7% in secondary care and 43.3% in primary care being reported. This work identified that for a comprehensive assessment of prescribing to be undertaken, an amalgamation of all three criteria should be deployed simultaneously. High prevalences of DRPs and PIP in older hospitalised individuals were identified. With 82.0% and 76.3% of patients reported to have at least one DRP or PIP instance respectively. The structured pharmacist intervention demonstrated a positive impact on prescribing, with a significant reduction MAI scores being reported. It also resulted in the intervention patients’ having a reduced risk of experiencing an ADR when compared to the control patients (absolute risk reduction of 6.8 (95% CI 1.5% - 12.3%)) and the number needed to treat = 15 (95% CI 8 - 68). However the intervention was found to have no significant effect on length of stay or mortality rate. Conclusion: This work shows that PIP is highly prevalent in older individuals across three healthcare settings in Ireland. This work also demonstrates that a structured pharmacist intervention support by a dedicated CDSS can significantly improve the appropriateness of prescribing and reduce the incidence of ADRs in older acutely ill hospitalised individuals.

Human interfaces to structured documents

This research investigates some of the reasons for the reported difficulties experienced by writers when using editing software designed for structured documents. The overall objective was to determine if there are aspects of the software interfaces which militate against optimal document construction by writers who are not computer experts, and to suggest possible remedies. Studies were undertaken to explore the nature and extent of the difficulties, and to identify which components of the software interfaces are involved. A model of a revised user interface was tested, and some possible adaptations to the interface are proposed which may help overcome the difficulties. The methodology comprised: 1. identification and description of the nature of a ‘structured document’ and what distinguishes it from other types of document used on computers; 2. isolation of the requirements of users of such documents, and the construction a set of personas which describe them; 3. evaluation of other work on the interaction between humans and computers, specifically in software for creating and editing structured documents; 4. estimation of the levels of adoption of the available software for editing structured documents and the reactions of existing users to it, with specific reference to difficulties encountered in using it; 5. examination of the software and identification of any mismatches between the expectations of users and the facilities provided by the software; 6. assessment of any physical or psychological factors in the reported difficulties experienced, and to determine what (if any) changes to the software might affect these. The conclusions are that seven of the twelve modifications tested could contribute to an improvement in usability, effectiveness, and efficiency when writing structured text (new document selection; adding new sections and new lists; identifying key information typographically; the creation of cross-references and bibliographic references; and the inclusion of parts of other documents). The remaining five were seen as more applicable to editing existing material than authoring new text (adding new elements; splitting and joining elements [before and after]; and moving block text).

Novel structured emulsions for delivering of food flavours

Flavour release from food is determined by the binding of flavours to other food ingredients and the partition of flavour molecules among different phases. Food emulsions are used as delivery systems for food flavours, and tailored structuring in emulsions provides novel means to better control flavour release. The current study investigated four structured oil-in-water emulsions with structuring in the oil phase, oil-water interface, and water phase. Oil phase structuring was achieved by the formation of monoglyceride (MG) liquid crystals in the oil droplets (MG structured emulsions). Structured interface was created by the adsorption of a whey protein isolate (WPI)-pectin double layer at the interface (multilayer emulsion). Water phase structured emulsions referred to emulsion filled protein gels (EFP gels), where emulsion droplets were embedded in WPI gel network, and emulsions with maltodextrins (MDs) of different dextrose-equivalent (DE) values. Flavour compounds with different physicochemical properties were added into the emulsions, and flavour release (release rate, headspace concentration and air-emulsion partition coefficient) was described by GC headspace analysis. Emulsion structures, including crystalline structure, particle size, emulsion stability, rheology, texture, and microstructures, were characterized using differential scanning calorimetry and X-ray diffraction, light scattering, multisample analytical centrifuge, rheometry, texture analysis, and confocal laser scanning microscopy, respectively. In MG structured emulsions, MG self-assembled into liquid crystalline structures and stable β-form crystals were formed after 3 days of storage at 25 °C. The inclusion of MG crystals allowed tween 20 stabilized emulsions to present viscoelastic properties, and it made WPI stabilized emulsions more sensitive to the change of pH and NaCl concentrations. Flavour compounds in MG structured emulsions had lower initial headspace concentration and air-emulsion partition coefficients than those in unstructured emulsions. Flavour release can be modulated by changing MG content, oil content and oil type. WPI-pectin multilayer emulsions were stable at pH 5.0, 4.0, and 3.0, but they presented extensive creaming when subjected to salt solutions with NaCl ≥ 150 mM and mixed with artificial salivas. Increase of pH from 5.0 to 7.0 resulted in higher headspace concentration but unchanged release rate, and increase of NaCl concentration led to increased headspace concentration and release rate. The study also showed that salivas could trigger higher release of hydrophobic flavours and lower release of hydrophilic flavours. In EFP gels, increases in protein content and oil content contributed to gels with higher storage modulus and force at breaking. Flavour compounds had significantly reduced release rates and air-emulsion partition coefficients in the gels than the corresponding ungelled emulsions, and the reduction was in line with the increase of protein content. Gels with stronger gel network but lower oil content were prepared, and lower or unaffected release rates of the flavours were observed. In emulsions containing maltodextrins, water was frozen at a much lower temperature, and emulsion stability was greatly improved when subjected to freeze-thawing. Among different MDs, MD DE 6 offered the emulsion the highest stability. Flavours had lower air-emulsion partition coefficients in the emulsions with MDs than those in the emulsion without MD. Moreover, the involvement of MDs in the emulsions allowed most flavours had similar release profiles before and after freeze-thaw treatment. The present study provided information about different structured emulsions as delivery systems for flavour compounds, and on how food structure can be designed to modulate flavour release, which could be helpful in the development of functional foods with improved flavour profile.