Background

Motor neurone disease (MND) is a devastating illness which leads to muscle weakness and death, usually within 2-3 years of symptom onset. Respiratory insufficiency is a common cause of morbidity, particularly in later stages of MND and respiratory complications are the leading cause of mortality in MND patients. Non Invasive Ventilation (NIV) is the current standard therapy to manage respiratory insufficiency. Some MND patients however do not tolerate NIV due to a number of issues including mask interface problems and claustrophobia. In those that do tolerate NIV, eventually respiratory muscle weakness will progress to a point at which intermittent/overnight NIV is ineffective. The NeuRx RA/4 Diaphragm Pacing System was originally developed for patients with respiratory insufficiency and diaphragm paralysis secondary to stable high spinal cord injuries. The DiPALS study will assess the effect of diaphragm pacing (DP) when used to treat patients with MND and respiratory insufficiency.

Method/Design

108 patients will be recruited to the study at 5 sites in the UK. Patients will be randomised to either receive NIV (current standard care) or receive DP in addition to NIV. Study participants will be required to complete outcome measures at 5 follow up time points (2, 3, 6, 9 and 12 months) plus an additional surgery and 1 week post operative visit for those in the DP group. 12 patients (and their carers) from the DP group will also be asked to complete 2 qualitative interviews.

Discussion

The primary objective of this trial will be to evaluate the effect of Diaphragm Pacing (DP) on survival over the study duration in patients with MND with respiratory muscle weakness. The project is funded by the National Institute for Health Research, Health Technology Assessment (HTA) Programme (project number 09/55/33) and the Motor Neurone Disease Association and the Henry Smith Charity. Trial Registration: Current controlled trials ISRCTN53817913. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the HTA programme, NIHR, NHS or the Department of Health.

The acquisition and analysis of datasets including multi-level omics and physiology from non-model species, sampled from field populations, is a formidable challenge, which so far has prevented the application of systems biology approaches. If successful, these could contribute enormously to improving our understanding of how populations of living organisms adapt to environmental stressors relating to, for example, pollution and climate. Here we describe the first application of a network inference approach integrating transcriptional, metabolic and phenotypic information representative of wild populations of the European flounder fish, sampled at seven estuarine locations in northern Europe with different degrees and profiles of chemical contaminants. We identified network modules, whose activity was predictive of environmental exposure and represented a link between molecular and morphometric indices. These sub-networks represented both known and candidate novel adverse outcome pathways representative of several aspects of human liver pathophysiology such as liver hyperplasia, fibrosis, and hepatocellular carcinoma. At the molecular level these pathways were linked to TNF alpha, TGF beta, PDGF, AGT and VEGF signalling. More generally, this pioneering study has important implications as it can be applied to model molecular mechanisms of compensatory adaptation to a wide range of scenarios in wild populations.

Author Summary

Understanding how living organisms adapt to changes in their natural habitats is of paramount importance particularly in respect to environmental stressors, such as pollution or climate. Computational models integrating the multi-level molecular responses with organism physiology are likely to be indispensable tools to address this challenge. However, because of the difficulties in acquiring and integrating data from non-model species and because of the intrinsic complexity of field studies, such an approach has not yet been attempted. Here we describe the first example of a global network reconstruction linking transcriptional and metabolic responses to physiology in the flatfish, European flounder, a species currently used to monitor coastal waters around Northern Europe. The model we developed has revealed a remarkable similarity between network modules predictive of chemical exposure in the environment and pathways involved in relevant aspects of human pathophysiology. Generally, the approach we have pioneered has important implications as it can be applied to model molecular mechanisms of compensatory adaptation to a wide range of scenarios in wild populations.

Objective

To determine the extent of testing, diagnostic episodes and management of genital Chlamydia trachomatis (CT) infection in UK primary care using a large primary care database.

Methods

The incidence of CT tests, diagnostic episodes, treatments and referrals was measured for all adult patients in the General Practice Research Database between 1990 and 2004.

Results

Rates of CT testing in those aged 12–64 years in 2004 increased to 1439/100 000 patient years (py) in women but only 74/100 000 py in men. Testing rates were highest among 20–24‐year‐old women (5.5% tested in 2004), followed by 25–34‐year‐old women (3.7% tested in 2004). 0.5% of registered 16–24‐year‐old women were diagnosed as having CT infection in 2004. Three‐quarters of patients with a recorded diagnosis of CT had had an appropriate prescription issued in 2004, a proportion that increased from 1990 along with a decrease in referrals to genitourinary medicine. In 2004, general practitioners treated 25.0% of all recorded diagnoses of CT in women and 5.1% of those in men.

Conclusions

Testing for and diagnostic episodes of CT in primary care have increased since 1990. Testing continues disproportionately to target women aged >24 years. Extremely low rates of testing in men, together with high positivity, demonstrate a missed opportunity for diagnosis of CT and contact tracing in general practice.

Background

Asthma management guidelines recommend a stepwise approach to instituting and adjusting anti-inflammatory controller therapy for children with asthma. The objective of this retrospective observational study was to describe prescribing patterns of asthma controller therapies for children in a primary care setting.

Methods

Data from the UK General Practice Research Database were examined for children with recorded asthma or recurrent wheezing who, from September 2006 through February 2007, were ≤ 14 years old at the time of a first asthma controller prescription after ≥ 6 months without a controller prescription. We evaluated demographic characteristics, asthma duration, comorbidities, asthma-related health care resource use, and prescribed daily dose of controller medication. In addition, physicians for 635 randomly selected patients completed a survey retrospectively classifying asthma severity at the prescription date and describing therapy and health care utilization for 6 prior months.

Results

We identified 10,004 children, 5942 (59.4%) of them boys, of mean (SD) age of 8.0 (3.8) years. Asthma controller prescriptions were for inhaled corticosteroid (ICS) monotherapy for 9059 (90.6%) children; ICS plus long-acting β2-agonist (LABA) for 698 (7.0%); leukotriene antagonist monotherapy for 91 (0.9%); ICS plus leukotriene antagonist for 55 (0.6%); and other therapy for 101 (1.0%), including 45 (0.45%) children who were prescribed LABA as monotherapy. High doses of ICS (> 400 μg) were prescribed for 44/2140 (2.1%) children < 5 years old and for 420/7452 (5.6%) children ≥ 5 years. Physicians reported asthma severity as intermittent for 346/635 (55%) patients and as mild, moderate, and severe persistent for 159 (25%), 71 (11%), and 11 (2%), respectively (severity data missing for 48 [8%]). The baseline characteristics and controller therapy prescriptions of the survey cohort were similar to those of the full cohort.

Conclusions

Physician classifications of asthma severity did not always correspond to guideline recommendations, as leukotriene receptor antagonists were rarely used and high-dose ICS or add-on LABA was prescribed even in intermittent and mild disease. In UK primary care, monotherapy with ICS is the most common controller therapy at all levels of asthma severity.

Background

In this commentary we present the findings from an international consortium on fish toxicogenomics sponsored by the U.K. Natural Environment Research Council (Fish Toxicogenomics—Moving into Regulation and Monitoring, held 21–23 April 2008 at the Pacific Environmental Science Centre, Vancouver, BC, Canada).

Objectives

The consortium from government agencies, academia, and industry addressed three topics: progress in ecotoxicogenomics, regulatory perspectives on roadblocks for practical implementation of toxicogenomics into risk assessment, and dealing with variability in data sets.

Discussion

Participants noted that examples of successful application of omic technologies have been identified, but critical studies are needed to relate molecular changes to ecological adverse outcome. Participants made recommendations for the management of technical and biological variation. They also stressed the need for enhanced interdisciplinary training and communication as well as considerable investment into the generation and curation of appropriate reference omic data.

Conclusions

The participants concluded that, although there are hurdles to pass on the road to regulatory acceptance, omics technologies are already useful for elucidating modes of action of toxicants and can contribute to the risk assessment process as part of a weight-of-evidence approach.

Functional genomics technologies have been widely adopted in the biological research of both model and non-model species. An efficient functional annotation of DNA or protein sequences is a major requirement for the successful application of these approaches as functional information on gene products is often the key to the interpretation of experimental results. Therefore, there is an increasing need for bioinformatics resources which are able to cope with large amount of sequence data, produce valuable annotation results and are easily accessible to laboratories where functional genomics projects are being undertaken. We present the Blast2GO suite as an integrated and biologist-oriented solution for the high-throughput and automatic functional annotation of DNA or protein sequences based on the Gene Ontology vocabulary. The most outstanding Blast2GO features are: (i) the combination of various annotation strategies and tools controlling type and intensity of annotation, (ii) the numerous graphical features such as the interactive GO-graph visualization for gene-set function profiling or descriptive charts, (iii) the general sequence management features and (iv) high-throughput capabilities. We used the Blast2GO framework to carry out a detailed analysis of annotation behaviour through homology transfer and its impact in functional genomics research. Our aim is to offer biologists useful information to take into account when addressing the task of functionally characterizing their sequence data.

Previous studies have found beneficial effects of aromatherapy massage for agitation in people with dementia, for pain relief and for poor sleep. Children with autism often have sleep difficulties, and it was thought that aromatherapy massage might enable more rapid sleep onset, less sleep disruption and longer sleep duration. Twelve children with autism and learning difficulties (2 girls and 10 boys aged between 12 years 2 months to 15 years 7 months) in a residential school participated in a within subjects repeated measures design: 3 nights when the children were given aromatherapy massage with lavender oil were compared with 14 nights when it was not given. The children were checked every 30 min throughout the night to determine the time taken for the children to settle to sleep, the number of awakenings and the sleep duration. One boy's data were not analyzed owing to lengthy absence. Repeated measures analysis revealed no differences in any of the sleep measures between the nights when the children were given aromatherapy massage and nights when the children were not given aromatherapy massage. The results suggest that the use of aromatherapy massage with lavender oil has no beneficial effect on the sleep patterns of children with autism attending a residential school. It is possible that there are greater effects in the home environment or with longer-term interventions.

SNOMED CT text files are encoded using UTF-8 to allow worldwide distribution and use of the terminology. Incorporating such UTF-8 encoded text into a system not currently using UTF-8 is simplified when the specific range of characters in the imported data is known. This poster describes the superset of ASCII found in the SNOMED CT US/UK Edition January 2003 release.