The CHIME graduate programme in health informatics

In 1999 University College London inaugurated a programme of graduate part-time Health Informatics courses to support the UK National Health Service?s Information for Health strategy. The programme has attracted students from across the UK and abroad, with a diverse range of backgrounds and skills and has proved a challenging and rewarding experience for students and tutors alike. The modular programme aims to provide a thorough grounding in the theory and practice of Health Informatics and addresses important application areas. The guiding principle is that Health Informatics graduates need to understand computers and programming but that, since the majority are not going to become programmers, programming methods should not dominate the curriculum.In the taught phase of the programme students attend college for 3 days a month and complete an assignment each month, based on home study. Students may graduate with a certificate or diploma, or go on to tackle a dissertation leading to an MSc. Research projects have included a patient record system based on speech input, a mathematical model for illustrating to patients the risks associated with smoking, an analysis of Trust staff's preparedness for Information for Health and a patient information leaflet giving advice about drug related information on the Web. As we move towards our fifth intake of students, we are in the process of evaluating our programme and carrying out a follow up study of our graduates? subsequent career pathways

A Novel Unsupervised Method to Identify Genes Important in the Anti-viral Response: Application to Interferon/Ribavirin in Hepatitis C Patients

Background: Treating hepatitis C with interferon/ribavirin results in a varied response in terms of decrease in viral titer and ultimate outcome. Marked responders have a sharp decline in viral titer within a few days of treatment initiation, whereas in other patients there is no effect on the virus (poor responders). Previous studies have shown that combination therapy modifies expression of hundreds of genes in vitro and in vivo. However, identifying which, if any, of these genes have a role in viral clearance remains challenging. Aims: The goal of this paper is to link viral levels with gene expression and thereby identify genes that may be responsible for early decrease in viral titer. Methods: Microarrays were performed on RNA isolated from PBMC of patients undergoing interferon/ribavirin therapy. Samples were collected at pre-treatment (day 0), and 1, 2, 7, 14 and 28 days after initiating treatment. A novel method was applied to identify genes that are linked to a decrease in viral titer during interferon/ribavirin treatment. The method uses the relationship between inter-patient gene expression based proximities and inter-patient viral titer based proximities to define the association between microarray gene expression measurements of each gene and viral-titer measurements. Results: We detected 36 unique genes whose expressions provide a clustering of patients that resembles viral titer based clustering of patients. These genes include IRF7, MX1, OASL and OAS2, viperin and many ISG's of unknown function. Conclusion: The genes identified by this method appear to play a major role in the reduction of hepatitis C virus during the early phase of treatment. The method has broad utility and can be used to analyze response to any group of factors influencing biological outcome such as antiviral drugs or anti-cancer agents where microarray data are available. © 2007 Brodsky et al

Modulation of the endocannabinoid system in viable and non-viable first trimester pregnancies by pregnancy-related hormones

<p>Abstract</p> <p>Background</p> <p>In early pregnancy, increased plasma levels of the endocannabinoid anandamide (AEA) are associated with miscarriage through mechanisms that might affect the developing placenta or maternal decidua.</p> <p>Methods</p> <p>In this study, we compare AEA levels in failed and viable pregnancies with the levels of the trophoblastic hormones (beta-human chorionic gonadotrophin (beta-hCG), progesterone (P4) and (pregnancy-associated placental protein-A (PAPP-A)) essential for early pregnancy success and relate that to the expression of the cannabinoid receptors and enzymes that modulate AEA levels.</p> <p>Results</p> <p>The median plasma AEA level in non-viable pregnancies (1.48 nM; n = 20) was higher than in viable pregnancies (1.21 nM; n = 25; <it>P </it>= 0.013), as were progesterone and beta-hCG levels (41.0 vs 51.5 ng/mL; <it>P </it>= 0.052 for P4 and 28,650 vs 6,560 mIU/L; <it>P </it>= 0.144 for beta-hCG, respectively, but were not statistically significant). Serum PAPP-A levels in the viable group were approximately 6.8 times lower than those in the non-viable group (1.82 vs 12.25 mg/L; <it>P </it>= 0.071), but again these differences were statistically insignificant. In the spontaneous miscarriage group, significant correlations between P4 and beta-hCG, P4 and PAPP-A and AEA and PAPP-A levels were observed. Simultaneously, immunohistochemical distributions of the two main cannabinoid receptors and the AEA-modifying enzymes, fatty acid amide hydrolase (FAAH) and <it>N</it>-acylphosphatidylethanolamine-phospholipase D (NAPE-PLD), changed within both the decidua and trophoblast.</p> <p>Conclusions</p> <p>The association of higher AEA levels with early pregnancy failure and with beta-hCG and PAPP-A, but not with progesterone concentrations suggest that plasma AEA levels and pregnancy failure are linked <it>via </it>a mechanism that may involve trophoblastic beta-hCG, and PAPP-A, but not, progesterone production. Although the trophoblast, decidua and embryo contain receptors for AEA, the main AEA target in early pregnancy failure remains unknown.</p

Behavioural and morphological evidence for the involvement of glial cell activation in delta opioid receptor function: implications for the development of opioid tolerance

Previous studies have demonstrated that prolonged morphine treatment in vivo induces the translocation of delta opioid receptors (δORs) from intracellular compartments to neuronal plasma membranes and this trafficking event is correlated with an increased functional competence of the receptor. The mechanism underlying this phenomenon is unknown; however chronic morphine treatment has been shown to involve the activation and hypertrophy of spinal glial cells. In the present study we have examined whether activated glia may be associated with the enhanced δOR-mediated antinociception observed following prolonged morphine treatment. Accordingly, animals were treated with morphine with or without concomitant administration of propentofylline, an inhibitor of glial activation that was previously shown to block the development of morphine antinociceptive tolerance. The morphine regimen previously demonstrated to initiate δOR trafficking induced the activation of both astrocytes and microglia in the dorsal spinal cord as indicated by a significant increase in cell volume and cell surface area. Consistent with previous data, morphine-treated rats displayed a significant augmentation in δOR-mediated antinociception. Concomitant spinal administration of propentofylline with morphine significantly attenuated the spinal immune response as well as the morphine-induced enhancement of δOR-mediated effects. These results complement previous reports that glial activation contributes to a state of opioid analgesic tolerance, and also suggest that neuro-glial communication is likely responsible in part for the altered functional competence in δOR-mediated effects following morphine treatment

Influence of management practice on the microbiota of a critically endangered species: a longitudinal study of kākāpō chick faeces and associated nest litter

BACKGROUND: The critically endangered kākāpō is a flightless, nocturnal parrot endemic to Aotearoa New Zealand. Recent efforts to describe the gastrointestinal microbial community of this threatened herbivore revealed a low-diversity microbiota that is often dominated by Escherichia-Shigella bacteria. Given the importance of associated microbial communities to animal health, and increasing appreciation of their potential relevance to threatened species conservation, we sought to better understand the development of this unusual gut microbiota profile. To this end, we conducted a longitudinal analysis of faecal material collected from kākāpō chicks during the 2019 breeding season, in addition to associated nest litter material. RESULTS: Using an experimental approach rarely seen in studies of threatened species microbiota, we evaluated the impact of a regular conservation practice on the developing kākāpō microbiota, namely the removal of faecal material from nests. Artificially removing chick faeces from nests had negligible impact on bacterial community diversity for either chicks or nests (p > 0.05). However, the gut microbiota did change significantly over time as chick age increased (p < 0.01), with an increasing relative abundance of Escherichia-Shigella coli over the study period and similar observations for the associated nest litter microbiota (p < 0.01). Supplementary feeding substantially altered gut bacterial diversity of kākāpō chicks (p < 0.01), characterised by a significant increase in Lactobacillus bacteria. CONCLUSIONS: Overall, chick age and hand rearing conditions had the most marked impact on faecal bacterial communities. Similarly, the surrounding nest litter microbiota changed significantly over time since a kākāpō chick was first placed in the nest, though we found no evidence that removal of faecal material influenced the bacterial communities of either litter or faecal samples. Taken together, these observations will inform ongoing conservation and management of this most enigmatic of bird species

Behçet's syndrome in children and young people in the United Kingdom & Republic of Ireland: a prospective epidemiological study

OBJECTIVES: To define the incidence and prevalence of Behçet's syndrome (BS) in children and young people (CYP) up to the age of 16 years in the United Kingdom (UK) and Republic of Ireland (ROI). METHODS: A prospective epidemiological study was undertaken with the support of the British Paediatric Surveillance Unit (BPSU) and the British Society of Paediatric Dermatologists (BSPD). Consultants reported anonymised cases of BS seen. A follow-up study at one year examined progression of disease and treatment. RESULTS: Over a two-year period, 56 cases met International Criteria for Behçet's Disease. For children under 16 years of age, the two-year period prevalence estimate was 4.2 per million (95% CI 3.2-5.4) and the incidence was 0.96 per million person years (95% CI 0.66-1.41). Mucocutaneous disease was the most common phenotype (56/100%), with ocular (10/56; 17.9%), neurological (2/56; 3.6%) and vascular involvement (3/56; 5.4%) being less common. Median age at onset was 6.34 years and at diagnosis was 11.72 years. There were slightly more female than male children reported (32/56; 55.6%). The majority of cases (85.7%) were white Caucasian. Apart from genital ulcers, which were more common in females, there were no significant differences in frequency of manifestations between male or females, nor between ethnicities. Over 83% of cases had three or more non-primary care healthcare professionals involved in their care. CONCLUSION: BS is extremely rare in CYP in the UK and ROI and most have mucocutaneous disease. Healthcare needs are complex, and coordinated care is key

Hepatitis C treatment: where are we now?

Chronic hepatitis C infection affects millions of people worldwide and confers significant morbidity and mortality. Effective treatment is needed to prevent disease progression and associated complications. Previous treatment options were limited to interferon and ribavirin regimens, which gave low cure rates and were associated with unpleasant side effects. The era of direct acting antiviral (DAA) therapies began with the development of the first-generation of NS3/4A protease inhibitors (PI) in 2011. They vastly improved outcomes for patients, particularly those with genotype 1 infection, the most prevalent genotype globally. Since then a multitude of DAAs have been licensed for use and outcomes for patients have improved further, with fewer side effects and cure rates approaching 100%. Recent regimens are interferon-free, and in many cases, ribavirin-free and involve a combination of DAA agents. This review summarises the treatment options currently available and discusses potential barriers that may delay the global eradication of hepatitis C

Characterizing visual fields in RPGR related retinitis pigmentosa using octopus static-automated perimetry

Purpose: Peripheral visual fields have not been as well defined by static automated perimetry as kinetic perimetry in RPGR-related retinitis pigmentosa. This study explores the pattern and sensitivities of peripheral visual fields, which may provide an important end point when assessing interventional clinical trials. Methods: A retrospective observational cross-sectional study of 10 genetically confirmed RPGR subjects was performed. Visual fields were obtained using the Octopus 900 perimeter. Interocular symmetry and repeatability were quantified. Visual fields were subdivided into central and peripheral subfields for analysis. Results: Mean patient age was 32 years old (20 to 49 years old). Average mean sensitivity was 7 dB (SD = 3.67 dB) and 6.8 dB (SD = 3.4 dB) for the right and left eyes, respectively, demonstrating interocular symmetry. Coefficient of repeatability for overall mean sensitivity: <2 dB. Nine out of 10 subjects had a preserved inferotemporal subfield, whose mean sensitivity was highly correlated to the central field (r2 = 0.78, P = 0.002 and r2 = 0.72, P = 0.002 for the right and left eyes, respectively). Within the central field, sensitivities were greater in the temporal than the nasal half (t-test, P = 0.01 and P = 0.03 for the right and left eyes, respectively). Conclusions: Octopus static-automated perimeter demonstrates good repeatability. Interocular symmetry permits use of the noninterventional eye as an internal control. In this cohort, the inferotemporal and central visual fields are preserved into later disease stages likely mapping to populations of surviving cones. Translational Relevance: A consistently preserved inferotemporal island of vision highly correlated to that of the central visual field may have significance as a possible future therapeutic site

Pharmacokinetic and pharmacodynamic modelling after subcutaneous, intravenous and buccal administration of a high-concentration formulation of buprenorphine in conscious cats

The aim of this study was to describe the joint pharmacokinetic-pharmacodynamic model and evaluate thermal antinociception of a high-concentration formulation of buprenorphine (Simbadol™) in cats