Sequential pregnancies among women living with HIV in the United Kingdom and Ireland

This thesis investigates the epidemiology of sequential pregnancies among HIV-positive women in the United Kingdom and Ireland, and explores the health, therapeutic and obstetric management, and pregnancy outcomes, of the women experiencing them. Data from the UK and Ireland’s National Study of HIV in Pregnancy and Childhood (NSHPC) are analysed. This is a well-established, active, comprehensive national surveillance study with over 1500 pregnancies currently reported each year. The findings demonstrate that a substantial and increasing proportion of pregnancies are women’s second or subsequent since their HIV diagnosis (39% in 2009), with a rate of 6.7 (95% CI: 6.5-6.9) per 100 woman-years during 1990-2009. Analyses revealed potential missed opportunities for the timely initiation of antiretroviral therapy (ART) in this group of previously diagnosed women, both within and outside the context of pregnancy. Variations in women’s engagement with HIV and pregnancy-related care are explored. In the contemporary context of effective prevention of mother-to-child transmission (PMTCT) interventions there are unanswered questions around the optimal management of HIV-positive women of childbearing age. Exposure to short-course protease inhibitor-based combination ART for PMTCT did not impact on response to therapy in subsequent pregnancies, supporting current UK recommendations. However, analyses of the immunological status and virological outcomes in second pregnancies to women not on ART at conception suggest that initiating lifelong ART in pregnancy may have benefits for maternal health and the risk of vertical transmission in future pregnancies. Adverse pregnancy and perinatal outcomes are investigated among women’s repeat pregnancies, which were for example, more likely to be conceived on ART than index pregnancies. Finally, patterns in mode of delivery for women’s sequential births are explored. The analyses presented in this thesis inform the evidence-base for the effective management of HIV-positive women in the context of current and potential future pregnancies

Bench to Bedside? Boundary Spanning in Academic Health Science Centres

The problem of mobilising research generated knowledge into practice has received increasing attention from policy makers and scholars internationally. Academic Health Science Centres (AHSCs) are partnerships between universities and hospitals which aim to use research discoveries to improve patient care. Despite their complexity and recent international spread, they have not received much attention from social science. This thesis, as a study of this emergent organisational form, contributes to addressing this gap. It conceptualises the ‘bench to bedside’ knowledge mobilisation process within two English AHSC cases as ‘boundary work’ between the domains of research and clinical practice. By analysing qualitative data collected through semi structured interviews (48), observations (130+ hours) and documentary analysis at micro (research/clinical teams) and meso (organisational) levels, it addressed the research question: What boundary processes mobilise knowledge within Academic Health Science Centres? Epistemic, professional and organisational framings were all important conceptualisations of the research/clinical practice boundary. Epistemic elements motivated knowledge mobilisation, with organisational boundaries often proving least permeable. The most effective boundary work encompassed all three. Networked forms of governance prevailed at the organisational level. Joint fields of practice emerged at the micro level with key (instrumental and symbolic) spanning mechanisms including professional hybrids as boundary spanners (e.g. clinician scientists), and objects (e.g. shared data). The ‘bench to bedside’ heuristic operated as an overarching boundary concept, motivationally powerful yet vague enough to bring together diverse groups. This study is one of few to consider the early development of AHSCs from a social science perspective. It contributes empirically and theoretically to the knowledge mobilisation and boundary literature by focussing analysis on the research and clinical practice boundary (as a space for new practice) and the people and objects that work across it, particularly centring on the under-researched role of organisation in this process

A preliminary life cycle analysis of bioethanol production using seawater in a coastal biorefinery setting

Bioethanol has many environmental and practical benefits as a transportation fuel. It is one of the best alternatives to replace fossil fuels due to its liquid nature, which is similar to the gasoline and diesel fuels traditionally used in transportation. In addition, bioethanol production technology has the capacity for negative carbon emissions, which is vital for solving the current global warming dilemma. However, conventional bioethanol production takes place based on an inland site and relies on freshwater and edible crops (or land suitable for edible crop production) for production, which has led to the food vs. fuel debate. Establishing a coastal marine biorefinery (CMB) system for bioethanol production that is based on coastal sites and relies on marine resources (seawater, marine biomass and marine yeast) could be the ultimate solution. In this paper, we aim to evaluate the environmental impact of using seawater for bioethanol production at coastal locations as a step toward the evaluation of a CMB system. Hence, a life cycle assessment for bioethanol production was conducted using the proposed scenario, named Coastal Seawater, and compared to the conventional scenario, named Inland Freshwater (IF). The impact of each scenario in relation to climate change, water depletion, land use and fossil depletion was studied for comparison. The Coastal Seawater scenario demonstrated an improvement upon the conventional scenario in all the selected impact categories. In particular, the use of seawater in the process had a significant effect on water depletion, showing an impact reduction of 31.2%. Furthermore, reductions were demonstrated in natural land transformation, climate change and fossil depletion of 5.5%, 3.5% and 4.2%, respectively. This indicates the positive impact of using seawater and coastal locations for bioethanol production and encourages research to investigate the CMB system.</jats:p

Recommendations for the treatment of epilepsy in adult patients in general practice in Belgium: an update

In 2008, a group of Belgian epilepsy experts published recommendations for antiepileptic drug (AED) treatment of epilepsies in adults and children. Selection of compounds was based on the registration and reimbursement status in Belgium, the level of evidence for efficacy, common daily practice and the personal views and experiences of the authors. In November 2011 the validity of these recommendations was reviewed by the same group of Belgian epilepsy experts who contributed to the preparation of the original paper. The recommendations made in 2008 for initial monotherapy in paediatric patients were still considered to be valid, except for the first choice treatment for childhood absence epilepsy. This update therefore focuses on the treatment recommendations for initial monotherapy and add-on treatment in adult patients. Several other relevant aspects of treatment with AEDs are addressed, including considerations for optimal combination of AEDs (rational polytherapy), pharmacokinetic properties, pharmacodynamic and pharmacokinetic interaction profile, adverse effects, comorbidity, treatment of elderly patients, AED treatment during pregnancy, and generic substitution of AEDs

Who does not gain weight? Prevalence and predictors of weight maintenance in young women

OBJECTIVE: To investigate the prevalence and predictors of weight maintenance over time in a large sample of young Australian women. DESIGN: This population study examined baseline and 4 y follow-up data from the cohort of young women participating in the Australian Longitudinal Study on Women\u27s Health. SUBJECTS: A total of 8726 young women aged 18-23 y at baseline. MEASURES: Height, weight and body mass index (BMI); physical activity; time spent sitting; selected eating behaviours (eg dieting, disordered eating, takeaway food consumption); cigarette smoking, alcohol consumption; parity; and sociodemographic characteristics. RESULTS: Only 44% of the women reported their BMI at follow-up to be within 5% of their baseline BMI (maintainers); 41% had gained weight and 15% had lost weight. Weight maintainers were more likely to be in managerial or professional occupations; to have never married; to be currently studying; and not to be mothers. Controlling for sociodemographic factors, weight maintainers were more likely to be in a healthy weight range at baseline, and to report that they spent less time sitting, and consumed less takeaway food, than women who gained weight. CONCLUSIONS: Fewer than half the young women in this community sample maintained their weight over this 4 y period in their early twenties. Findings of widespread weight gain, particularly among those already overweight, suggest that early adulthood, which is a time of significant life changes for many women, may be an important time for implementing strategies to promote maintenance of healthy weight. Strategies which encourage decreased sitting time and less takeaway food consumption may be effective for encouraging weight maintenance at this life stage.<br /

A Novel Estimator for the Rate of Information Transfer by Continuous Signals

The information transfer rate provides an objective and rigorous way to quantify how much information is being transmitted through a communications channel whose input and output consist of time-varying signals. However, current estimators of information content in continuous signals are typically based on assumptions about the system's linearity and signal statistics, or they require prohibitive amounts of data. Here we present a novel information rate estimator without these limitations that is also optimized for computational efficiency. We validate the method with a simulated Gaussian information channel and demonstrate its performance with two example applications. Information transfer between the input and output signals of a nonlinear system is analyzed using a sensory receptor neuron as the model system. Then, a climate data set is analyzed to demonstrate that the method can be applied to a system based on two outputs generated by interrelated random processes. These analyses also demonstrate that the new method offers consistent performance in situations where classical methods fail. In addition to these examples, the method is applicable to a wide range of continuous time series commonly observed in the natural sciences, economics and engineering

The challenges of communicating research evidence in practice: perspectives from UK health visitors and practice nurses

&lt;p&gt;Background: Health practitioners play a pivotal role in providing patients with up-to-date evidence and health information. Evidence-based practice and patient-centred care are transforming the delivery of healthcare in the UK. Health practitioners are increasingly balancing the need to provide evidence-based information against that of facilitating patient choice, which may not always concur with the evidence base. There is limited research exploring how health practitioners working in the UK, and particularly those more autonomous practitioners such as health visitors and practice nurses working in community practice settings, negotiate this challenge. This research provides a descriptive account of how health visitors and practice nurses negotiate the challenges of communicating health information and research evidence in practice.&lt;/p&gt; &lt;p&gt;Methods: A total of eighteen in-depth telephone interviews were conducted in the UK between September 2008 and May 2009. The participants comprised nine health visitors and nine practice nurses, recruited via adverts on a nursing website, posters at a practitioner conference and through recommendation. Thematic analysis, with a focus on constant comparative method, was used to analyse the data.&lt;/p&gt; &lt;p&gt;Results: The data were grouped into three main themes: communicating evidence to the critically-minded patient; confidence in communicating evidence; and maintaining the integrity of the patient-practitioner relationship. These findings highlight some of the daily challenges that health visitors and practice nurses face with regard to the complex and dynamic nature of evidence and the changing attitudes and expectations of patients. The findings also highlight the tensions that exist between differing philosophies of evidence-based practice and patient-centred care, which can make communicating about evidence a daunting task.&lt;/p&gt; &lt;p&gt;Conclusions: If health practitioners are to be effective at communicating research evidence, we suggest that more research and resources need to be focused on contextual factors, such as how research evidence is negotiated, appraised and communicated within the dynamic patient-practitioner relationship.&lt;/p&gt

International Veterinary Epilepsy Task Force Consensus Proposal: Outcome of therapeutic interventions in canine and feline epilepsy

Common criteria for the diagnosis of drug resistance and the assessment of outcome are needed urgently as a prerequisite for standardized evaluation and reporting of individual therapeutic responses in canine epilepsy. Thus, we provide a proposal for the definition of drug resistance and partial therapeutic success in canine patients with epilepsy. This consensus statement also suggests a list of factors and aspects of outcome, which should be considered in addition to the impact on seizures. Moreover, these expert recommendations discuss criteria which determine the validity and informative value of a therapeutic trial in an individual patient and also suggest the application of individual outcome criteria. Agreement on common guidelines does not only render a basis for future optimization of individual patient management, but is also a presupposition for the design and implementation of clinical studies with highly standardized inclusion and exclusion criteria. Respective standardization will improve the comparability of findings from different studies and renders an improved basis for multicenter studies. Therefore, this proposal provides an in-depth discussion of the implications of outcome criteria for clinical studies. In particular ethical aspects and the different options for study design and application of individual patient-centered outcome criteria are considered

Sequencing and association analysis of the type 1 diabetes - linked region on chromosome 10p12-q11

Background: In an effort to locate susceptibility genes for type I diabetes (TID) several genome-wide linkage scans have been undertaken. A chromosomal region designated IDDM10 retained genome-wide significance in a combined analysis of the main linkage scans. Here, we studied sequence polymorphisms in 23 Mb on chromosome 10p12-q11, including the putative IDDM10 region, to identify genes associated with TID. Results: Initially, we resequenced the functional candidate genes, CREM and SDF1, located in this region, genotyped 13 tag single nucleotide polymorphisms (SNPs) and found no association with TID. We then undertook analysis of the whole 23 Mb region. We constructed and sequenced a contig tile path from two bacterial artificial clone libraries. By comparison with a clone library from an unrelated person used in the Human Genome Project, we identified 12,058 SNPs. We genotyped 303 SNPs and 25 polymorphic microsatellite markers in 765 multiplex TID families and followed up 22 associated polymorphisms in up to 2,857 families. We found nominal evidence of association in six loci (P = 0.05-0.0026), located near the PAPDI gene. Therefore, we resequenced 38.8 kb in this region, found 147 SNPs and genotyped 84 of them in the TID families. We also tested 13 polymorphisms in the PAPDI gene and in five other loci in 1,612 TID patients and 1,828 controls from the UK. Overall, only the D10S193 microsatellite marker located 28 kb downstream of PAPDI showed nominal evidence of association in both TID families and in the case-control sample (P = 0.037 and 0.03, respectively). Conclusion: We conclude that polymorphisms in the CREM and SDFI genes have no major effect on TID. The weak TID association that we detected in the association scan near the PAPDI gene may be either false or due to a small genuine effect, and cannot explain linkage at the IDDM10 region