• A 10 year (2000--2010) systematic review of interventions to improve quality of care in hospitals

      Conry, Mary C; Humphries, Niamh; Morgan, Karen; McGowan, Yvonne; Montgomery, Anthony; Vedhara, Kavita; Panagopoulou, Efharis; Mc Gee, Hannah (2012-08-24)
      Background Against a backdrop of rising healthcare costs, variability in care provision and an increased emphasis on patient satisfaction, the need for effective interventions to improve quality of care has come to the fore. This is the first ten year (2000–2010) systematic review of interventions which sought to improve quality of care in a hospital setting. This review moves beyond a broad assessment of outcome significance levels and makes recommendations for future effective and accessible interventions. Methods Two researchers independently screened a total of 13,195 English language articles from the databases PsychInfo, Medline, PubMed, EmBase and CinNahl. There were 120 potentially relevant full text articles examined and 20 of those articles met the inclusion criteria. Results Included studies were heterogeneous in terms of approach and scientific rigour and varied in scope from small scale improvements for specific patient groups to large scale quality improvement programmes across multiple settings. Interventions were broadly categorised as either technical (n = 11) or interpersonal (n = 9). Technical interventions were in the main implemented by physicians and concentrated on improving care for patients with heart disease or pneumonia. Interpersonal interventions focused on patient satisfaction and tended to be implemented by nursing staff. Technical interventions had a tendency to achieve more substantial improvements in quality of care. Conclusions The rigorous application of inclusion criteria to studies established that despite the very large volume of literature on quality of care improvements, there is a paucity of hospital interventions with a theoretically based design or implementation. The screening process established that intervention studies to date have largely failed to identify their position along the quality of care spectrum. It is suggested that this lack of theoretical grounding may partly explain the minimal transfer of health research to date into policy. It is recommended that future interventions are established within a theoretical framework and that selected quality of care outcomes are assessed using this framework. Future interventions to improve quality of care will be most effective when they use a collaborative approach, involve multidisciplinary teams, utilise available resources, involve physicians and recognise the unique requirements of each patient group.
    • A 6-gene signature identifies four molecular subgroups of neuroblastoma

      Abel, Frida; Dalevi, Daniel; Nethander, Maria; Jornsten, Rebecka; De Preter, Katleen; Vermuelen, Joelle; Stallings, Raymond; Kogner, Per; Maris, John; Nilsson, Staffan (2011-04-14)
      Abstract Background There are currently three postulated genomic subtypes of the childhood tumour neuroblastoma (NB); Type 1, Type 2A, and Type 2B. The most aggressive forms of NB are characterized by amplification of the oncogene MYCN (MNA) and low expression of the favourable marker NTRK1. Recently, mutations or high expression of the familial predisposition gene Anaplastic Lymphoma Kinase (ALK) was associated to unfavourable biology of sporadic NB. Also, various other genes have been linked to NB pathogenesis. Results The present study explores subgroup discrimination by gene expression profiling using three published microarray studies on NB (47 samples). Four distinct clusters were identified by Principal Components Analysis (PCA) in two separate data sets, which could be verified by an unsupervised hierarchical clustering in a third independent data set (101 NB samples) using a set of 74 discriminative genes. The expression signature of six NB-associated genes ALK, BIRC5, CCND1, MYCN, NTRK1, and PHOX2B, significantly discriminated the four clusters (p < 0.05, one-way ANOVA test). PCA clusters p1, p2, and p3 were found to correspond well to the postulated subtypes 1, 2A, and 2B, respectively. Remarkably, a fourth novel cluster was detected in all three independent data sets. This cluster comprised mainly 11q-deleted MNA-negative tumours with low expression of ALK, BIRC5, and PHOX2B, and was significantly associated with higher tumour stage, poor outcome and poor survival compared to the Type 1-corresponding favourable group (INSS stage 4 and/or dead of disease, p < 0.05, Fisher's exact test). Conclusions Based on expression profiling we have identified four molecular subgroups of neuroblastoma, which can be distinguished by a 6-gene signature. The fourth subgroup has not been described elsewhere, and efforts are currently made to further investigate this group's specific characteristics.
    • A case of bovine raw milk contamination with Listeria monocytogenes

      Hunt, Karen; Drummond, Niall; Murphy, Mary; Butler, Francis; Buckley, Jim; Jordan, Kieran (2012-07-06)
      Abstract During routine sampling of bulk raw milk on a dairy farm, the pathogenic bacteria Listeria monocytogenes was found to be a contaminant, at numbers < 100 cfu/ml. A strain with an indistinguishable pulsed-field gel electrophoresis pattern was isolated from the bulk milk two months later. Environmental swabs taken at the dairy environment were negative for the presence of L. monocytogenes, indicating a possible case of excretion of the L. monocytogenes directly into the milk. Milk samples were collected from the individual cows and analysed, resulting in the identification of L. monocytogenes excretion (at 280 cfu/ml) from one of the 4 mammary quarters of one dairy cow out of 180. When the infected cow was isolated from the herd, no L. monocytogenes was detected from the remaining herd. The pulsed-field gel electrophoresis pattern of the strain from the individual cow was indistinguishable from that originally isolated from the bulk milk. The infected cow did not show any clinical signs of disease, nor did the appearance of the milk have any physical abnormalities. Antibiotic treatment of the infected mammary quarter was found to be ineffective. This study shows that there can be risks associated with direct contamination of raw milk with L. monocytogenes.
    • A child with autoimmune polyendocrinopathy candidiasis and ectodermal dysplasia treated with immunosuppression: a case report

      O’Gorman, Clodagh S; Shulman, Rayzel; Lara-Corrales, Irene; Pope, Elena; Marcon, Margaret; Grasemann, Hartmut; Schneider, Rayfel; Upton, Julia; Sochett, Etienne B; Koltin, Dror; et al. (2013-02-14)
      Abstract Introduction Common features of autoimmune polyendocrinopathy-candidiasis-ectodermal dysplasia include candidiasis, hypoparathyroidism and hypoadrenalism. The initial manifestation of autoimmune polyendocrinopathy-candidiasis-ectodermal dysplasia may be autoimmune hepatitis, keratoconjunctivitis, frequent fever with or without a rash, chronic diarrhea, or different combinations of these with or without oral candidiasis. Case presentation We discuss a profoundly affected 2.9-year-old Caucasian girl of Western European descent with a dramatic response to immunosuppression (initially azathioprine and oral steroids, and then subsequently mycophenolate mofetil monotherapy). At four years of follow-up, her response to mycophenolate mofetil is excellent. Conclusion The clinical features of autoimmune polyendocrinopathy-candidiasis-ectodermal dysplasia may continue for years before some of the more common components appear. In such cases, it may be life-saving to diagnose autoimmune polyendocrinopathy-candidiasis-ectodermal dysplasia and commence therapy with immunosuppressive agents. The response of our patient to immunosuppression with mycophenolate mofetil has been dramatic. It is possible that other patients with this condition might also benefit from immunosuppression.
    • A comparison of Irish set dancing and exercises for people with Parkinson¿s disease: A phase II feasibility study

      Volpe, Daniele; Signorini, Matteo; Marchetto, Anna; Lynch, Timothy; Morris, Meg E (2013-06-04)
      Abstract Background People with idiopathic Parkinson’s disease (PD) frequently have low activity levels, poor mobility and reduced quality of life. Although increased physical activity may improve mobility, balance and wellbeing, adherence to exercises and activity programs over the longer term can be challenging, particularly for older people with progressive neurological conditions such as PD. Physical activities that are engaging and enjoyable, such as dancing, might enhance adherence over the long term. The objective of this study was to evaluate the feasibility of a randomized controlled trial of Irish set dancing compared with routine physiotherapy for people with mild to moderately severe PD. Methods Twenty-four people with idiopathic PD referred for movement rehabilitation were randomized to receive standard physiotherapy exercises or Irish set dancing classes once per week plus a weekly home program for 6 months (12 in each group). The feasibility and safety of the proposed RCT protocol was the main focus of this evaluation. The primary outcome was motor disability measured by the motor component of the UPDRS, which was assessed prior to and after therapy by trained assessors blinded to group assignment. The Timed Up and Go, the Berg Balance Scale and the modified Freezing of Gait Questionnaire were secondary measures. Quality of life of the people with PD was evaluated using the PDQ-39. Results Both the Irish set dancing and physiotherapy exercise program were shown to be feasible and safe. There were no differences between groups in the rate of adverse events such as falls, serious injuries, death or rates of admission to hospital. The physiotherapists who provided usual care remained blind to group allocation, with no change in their standard clinical practice. Compliance and adherence to both the exercise and dance programs were very high and attrition rates were low over the 6 months of therapy. Although improvements were made in both groups, the dance group showed superior results to standard physiotherapy in relation to freezing of gait, balance and motor disability. Conclusions Irish dancing and physiotherapy were both safe and feasible in this sample from Venice, with good adherence over a comparatively long time period of 6 months. A larger multi-centre trial is now warranted to establish whether Irish set dancing is more effective than routine physiotherapy for enhancing mobility, balance and quality of life in people living with idiopathic PD. Trial registration EudraCT number 2012-005769-11
    • A comparison of the efficacy of transplantation of bone marrow derived mesenchymal stem cells and unrestricted somatic stem cells on outcome after acute myocardial infarction

      Flynn, Aidan; Chen, Xizhe; O'Connell, Enda; O'Brien, Timothy (2012-09-13)
      Abstract Introduction A number of questions remain unanswered in the field of cell therapy for acute myocardial infarction, including what is the optimal cell type, and can therapeutic efficacy be enhanced by conditioning regimens. In this study, we sought to address these questions by directly comparing the effect of bone marrow-derived mesenchymal stem cells and unrestricted somatic stem cells delivered 24 hours post-myocardial infarction and by determining if the therapeutic efficacy of unrestricted somatic stem cells could be enhanced by exposing the cells to guiding factors before cell transplantation. Methods Unrestricted somatic stem cells were guided by exposure to 50 ng/mL basic fibroblast growth factor, 20 ng/mL hepatocyte growth factor and 20 ng/mL bone morphogenetic protein-2 for 24 hours. Using a Sprague-Dawley rat model of acute myocardial infarction, we transplanted cells by intramyocardial injection 24 hours post-myocardial infarction. Cardiac function was serially measured using echocardiography, and histological analyses of infarct morphology, angiogenesis and apoptosis were obtained. Transcriptomic and proteomic changes were assessed using microarray and real-time quantitative PCR. Results When assessed 28 days after the myocardial infarction, the delivery of mesenchymal stem cells 24 hours post-myocardial infarction did not improve ejection fraction (P = 0.19), and did not prevent the decline in ejection fraction observed in the absence of cell therapy (P = 0.17). The administration of unrestricted somatic stem cells also did not improve ejection fraction (P = 0.11), but did prevent a further decline in ejection fraction (P = 0.001). Delivery of guided unrestricted somatic stem cells significantly improved ejection fraction (P = 0.03). Guided unrestricted somatic stem cells restored function to a greater extent than mesenchymal stem cells (P = 0.03). The infarct area (P = 0.2), apoptosis (P = 0.07) and angiogenesis (P = 0.09) did not differ between groups. Microarray analysis revealed that, following pre-implantation guiding, the gene groupings of mitosis, signalling and angiogenesis were highly overrepresented, mediators of apoptosis were overrepresented, and cardiomyocyte-associated genes were not differentially expressed. Conclusions These results suggest that guided unrestricted somatic stem cells have a moderate capacity to repair cardiac damage and that they are more effective than mesenchymal stem cells in restoring cardiac function after a myocardial infarction. The mechanism of the benefit was not fully elucidated in this study, but these observations may be mediated by favorable dysregulation of angiogenic and apoptotic gene groupings.
    • A demographic survey of unwanted horses in Ireland 2005-2010

      Leadon, D P; O'Toole, Dylan; Duggan, Vivienne E (2012-03-02)
      Abstract Background The Irish Horse Industry expanded during the Celtic Tiger boom years, then contracted in the current economic recession. High value horses were traditionally controlled through sale at public auction, private sales and sales to dealers; these are now also being reduced by decreases in production (> 40%), and increases in retirement, re-homing, euthanasia and disposal through Category 2 plants and abattoirs. The absence or banning of horse abattoirs has been shown to have very significant welfare social and economic consequences in the USA. This study described the currently available data on the demographics of unwanted horses in Ireland from 2005 to 2010. Results The majority of horses euthanised by practicing veterinarians are destroyed on medical grounds but the number euthanised at the request of welfare groups and the state, as well as welfare related calls and the number of horses involved in these calls and subsequent visits is increasing reflecting the increasing involvement of the veterinary profession in equine welfare. Welfare groups have limited resources and do not have a tradition of recording data, but they too have reported increasing calls, visits and numbers of horses per visit. Welfare groups provide significant service to equine welfare and the community. Local Authorities report similar trends. Over 300 horses were found dead or required immediate or subsequent euthanasia following welfare group and local authority visits in 2010, which is of national concern. The majority of local authority interfaces with unwanted horses are with urban (60%) rather than rural (40%) horses. Mortality figures are poor indicators of non-fatal neglect. More horses were admitted into the care of local authorities than welfare groups, reflecting significant state and taxpayer investment in the control of low value horses. Category 2 plants and abattoirs represent a significant state investment in licensing and control in the national interest. Abattoirs provide an increasingly important and essential service for the disposal of unwanted horses. Despite the increase in unwanted horses, Ireland is a minority contributor to the EU slaughter total. Conclusions There is a need for annual demographic data compilation and review of the numbers of unwanted horses and ponies within the horse industry to assist policy makers and legislators.
    • A flexible R package for nonnegative matrix factorization

      Gaujoux, Renaud; Seoighe, Cathal (2010-07-02)
      Abstract Background Nonnegative Matrix Factorization (NMF) is an unsupervised learning technique that has been applied successfully in several fields, including signal processing, face recognition and text mining. Recent applications of NMF in bioinformatics have demonstrated its ability to extract meaningful information from high-dimensional data such as gene expression microarrays. Developments in NMF theory and applications have resulted in a variety of algorithms and methods. However, most NMF implementations have been on commercial platforms, while those that are freely available typically require programming skills. This limits their use by the wider research community. Results Our objective is to provide the bioinformatics community with an open-source, easy-to-use and unified interface to standard NMF algorithms, as well as with a simple framework to help implement and test new NMF methods. For that purpose, we have developed a package for the R/BioConductor platform. The package ports public code to R, and is structured to enable users to easily modify and/or add algorithms. It includes a number of published NMF algorithms and initialization methods and facilitates the combination of these to produce new NMF strategies. Commonly used benchmark data and visualization methods are provided to help in the comparison and interpretation of the results. Conclusions The NMF package helps realize the potential of Nonnegative Matrix Factorization, especially in bioinformatics, providing easy access to methods that have already yielded new insights in many applications. Documentation, source code and sample data are available from CRAN.
    • A Frailty Instrument for primary care: findings from the Survey of Health, Ageing and Retirement in Europe (SHARE)

      Romero-Ortuno, Roman; Walsh, Cathal D; Lawlor, Brian A; Kenny, Rose Anne (2010-08-24)
      Abstract Background A frailty paradigm would be useful in primary care to identify older people at risk, but appropriate metrics at that level are lacking. We created and validated a simple instrument for frailty screening in Europeans aged ≥50. Our study is based on the first wave of the Survey of Health, Ageing and Retirement in Europe (SHARE, http://www.share-project.org), a large population-based survey conducted in 2004-2005 in twelve European countries. Methods Subjects: SHARE Wave 1 respondents (17,304 females and 13,811 males). Measures: five SHARE variables approximating Fried's frailty definition. Analyses (for each gender): 1) estimation of a discreet factor (DFactor) model based on the frailty variables using LatentGOLD®. A single DFactor with three ordered levels or latent classes (i.e. non-frail, pre-frail and frail) was modelled; 2) the latent classes were characterised against a biopsychosocial range of Wave 1 variables; 3) the prospective mortality risk (unadjusted and age-adjusted) for each frailty class was established on those subjects with known mortality status at Wave 2 (2007-2008) (11,384 females and 9,163 males); 4) two web-based calculators were created for easy retrieval of a subject's frailty class given any five measurements. Results Females: the DFactor model included 15,578 cases (standard R 2 = 0.61). All five frailty indicators discriminated well (p < 0.001) between the three classes: non-frail (N = 10,420; 66.9%), pre-frail (N = 4,025; 25.8%), and frail (N = 1,133; 7.3%). Relative to the non-frail class, the age-adjusted Odds Ratio (with 95% Confidence Interval) for mortality at Wave 2 was 2.1 (1.4 - 3.0) in the pre-frail and 4.8 (3.1 - 7.4) in the frail. Males: 12,783 cases (standard R 2 = 0.61, all frailty indicators had p < 0.001): non-frail (N = 10,517; 82.3%), pre-frail (N = 1,871; 14.6%), and frail (N = 395; 3.1%); age-adjusted OR (95% CI) for mortality: 3.0 (2.3 - 4.0) in the pre-frail, 6.9 (4.7 - 10.2) in the frail. Conclusions The SHARE Frailty Instrument has sufficient construct and predictive validity, and is readily and freely accessible via web calculators. To our knowledge, SHARE-FI represents the first European research effort towards a common frailty language at the community level.
    • A functional and transcriptomic analysis of NET1 bioactivity in gastric cancer

      Bennett, Gayle; Sadlier, Denise; Doran, Peter P; MacMathuna, Padraic; Murray, David W (2011-02-01)
      Abstract Background NET1, a RhoA guanine exchange factor, is up-regulated in gastric cancer (GC) tissue and drives the invasive phenotype of this disease. In this study, we aimed to determine the role of NET1 in GC by monitoring the proliferation, motility and invasion of GC cells in which NET1 has been stably knocked down. Additionally, we aimed to determine NET1-dependent transcriptomic events that occur in GC. Methods An in vitro model of stable knockdown of NET1 was achieved in AGS human gastric adenocarcinoma cells via lentiviral mediated transduction of short-hairpin (sh) RNA targeting NET1. Knockdown was assessed using quantitative PCR. Cell proliferation was assessed using an MTS assay and cell migration was assessed using a wound healing scratch assay. Cell invasion was assessed using a transwell matrigel invasion assay. Gene expression profiles were examined using affymetrix oligonucleotide U133A expression arrays. A student's t test was used to determine changes of statistical significance. Results GC cells were transduced with NET1 shRNA resulting in a 97% reduction in NET1 mRNA (p < 0.0001). NET1 knockdown significantly reduced the invasion and migration of GC cells by 94% (p < 0.05) and 24% (p < 0.001) respectively, while cell proliferation was not significantly altered following NET1 knockdown. Microarray analysis was performed on non-target and knockdown cell lines, treated with and without 10 μM lysophosphatidic acid (LPA) allowing us to identify NET1-dependent, LPA-dependent and NET1-mediated LPA-induced gene transcription. Differential gene expression was confirmed by quantitative PCR. Shortlisted NET1-dependent genes included STAT1, TSPAN1, TGFBi and CCL5 all of which were downregulatd upon NET1 downregulation. Shortlisted LPA-dependent genes included EGFR and PPARD where EGFR was upregulated and PPARD was downregulated upon LPA stimulation. Shortlisted NET1 and LPA dependent genes included IGFR1 and PIP5K3. These LPA induced genes were downregulated in NET1 knockdown cells. Conclusions NET1 plays an important role in GC cell migration and invasion, key aspects of GC progression. Furthermore, the gene expression profile further elucidates the molecular mechanisms underpinning NET1-mediated aggressive GC cell behaviour.
    • A gene expression profile indicative of early stage HER2 targeted therapy response

      O’Neill, Fiona; Madden, Stephen F; Clynes, Martin; Crown, John; Doolan, Padraig; Aherne, Sinéad T; O’Connor, Robert (2013-07-01)
      Abstract Background Efficacious application of HER2-targetting agents requires the identification of novel predictive biomarkers. Lapatinib, afatinib and neratinib are tyrosine kinase inhibitors (TKIs) of HER2 and EGFR growth factor receptors. A panel of breast cancer cell lines was treated with these agents, trastuzumab, gefitinib and cytotoxic therapies and the expression pattern of a specific panel of genes using RT-PCR was investigated as a potential marker of early drug response to HER2-targeting therapies. Results Treatment of HER2 TKI-sensitive SKBR3 and BT474 cell lines with lapatinib, afatinib and neratinib induced an increase in the expression of RB1CC1, ERBB3, FOXO3a and NR3C1. The response directly correlated with the degree of sensitivity. This expression pattern switched from up-regulated to down-regulated in the HER2 expressing, HER2-TKI insensitive cell line MDAMB453. Expression of the CCND1 gene demonstrated an inversely proportional response to drug exposure. A similar expression pattern was observed following the treatment with both neratinib and afatinib. These patterns were retained following exposure to traztuzumab and lapatinib plus capecitabine. In contrast, gefitinib, dasatinib and epirubicin treatment resulted in a completely different expression pattern change. Conclusions In these HER2-expressing cell line models, lapatinib, neratinib, afatinib and trastuzumab treatment generated a characteristic and specific gene expression response, proportionate to the sensitivity of the cell lines to the HER2 inhibitor.Characterisation of the induced changes in expression levels of these genes may therefore give a valuable, very early predictor of the likely extent and specificity of tumour HER2 inhibitor response in patients, potentially guiding more specific use of these agents.
    • A genome-wide screen in human embryonic stem cells reveals novel sites of allele-specific histone modification associated with known disease loci

      Prendergast, James G D; Tong, Pin; Hay, David C; Farrington, Susan M; Semple, Colin A M (2012-05-19)
      AbstractBackgroundChromatin structure at a given site can differ between chromosome copies in a cell, and such imbalances in chromatin structure have been shown to be important in understanding the molecular mechanisms controlling several disease loci. Human genetic variation, DNA methylation, and disease have been intensely studied, uncovering many sites of allele-specific DNA methylation (ASM). However, little is known about the genome-wide occurrence of sites of allele-specific histone modification (ASHM) and their relationship to human disease. The aim of this study was to investigate the extent and characteristics of sites of ASHM in human embryonic stem cells (hESCs).ResultsUsing a statistically rigorous protocol, we investigated the genomic distribution of ASHM in hESCs, and their relationship to sites of allele-specific expression (ASE) and DNA methylation. We found that, although they were rare, sites of ASHM were substantially enriched at loci displaying ASE. Many were also found at known imprinted regions, hence sites of ASHM are likely to be better markers of imprinted regions than sites of ASM. We also found that sites of ASHM and ASE in hESCs colocalize at risk loci for developmental syndromes mediated by deletions, providing insights into the etiology of these disorders.ConclusionThese results demonstrate the potential importance of ASHM patterns in the interpretation of disease loci, and the protocol described provides a basis for similar studies of ASHM in other cell types to further our understanding of human disease susceptibility.
    • A hypoplastic patella fracture in nail patella syndrome: a case report

      Neill, Shane C O; Murphy, Colin G; McElwain, John P (2012-07-16)
      AbstractIntroductionNail patella syndrome is a rare autosomal dominant hereditary condition, with an incidence of 22 per million in the United Kingdom. The syndrome’s most common features include iliac horns, hypoplastic patella and nail dysplasia.Case presentationWe report the case of a 26-year-old Caucasian man with nail patella syndrome who sustained a fracture of his right hypoplastic patella after a fall. His right knee became swollen and he was unable to extend against gravity immediately post fall. Radiographs revealed a fracture of the lower pole of his right patella with associated complete disruption of the extensor mechanism of the knee. He underwent operative fixation and his post operative course was uneventful. He was further treated post operatively with a full knee cast and graded immobilization. At six months he had regained the full range of motion at the knee joint.ConclusionsTo the best of our knowledge, this is the only case report in the literature describing a patella fracture in an individual with nail patella syndrome. We hypothesize that given the extent of pre-existing knee joint impairment in these individuals, functional outcome may be inferior, suggesting the need for more frequent follow-up.
    • A longitudinal qualitative study examining the factors impacting on the ability of persons with T1DM to assimilate the Dose Adjustment For Normal Eating (DAFNE) principles into daily living and how these factors change over time

      Casey, Dympna; Murphy, Kathy; Lawton, Julia; Findlay-White, Florence; Dineen, Sean (2011-08-30)
      Abstract Background The literature reveals that structured education programmes, such as DAFNE, result in many positive outcomes for people with Type 1 diabetes including a decrease in HbA1c levels and reductions in hypoglycaemia. While there is evidence that some of these outcomes are maintained we do not know at present what factors are most important over time. The study aim was to identify the key factors impacting on persons with Type 1 diabetes ability to assimilate the Dose Adjustment For Normal Eating (DAFNE) DAFNE principles into their daily lives and how these factors change over time. Methods This is a longitudinal descriptive qualitative study. Interviews were undertaken with 40 participants who had attended DAFNE in one of 5 study sites across the Island of Ireland, at 6 weeks, 6 and 12 months after completion of the programme. The interviews lasted from 30 to 60 minutes and were transcribed verbatim. Data were analysed in three ways, a within time analysis, a cross sectional analysis for each participant and a thematic analysis which focused on examining changes over time Results Four themes that influenced participants' ability to assimilate DAFNE into their daily lives over time were identified. These were: embedded knowledge, continued responsive support, enduring motivation and being empowered. Support at the 6 month period was found to be crucial to continued motivation. Conclusions Understanding the factors that influence people's ability to assimilate DAFNE principles over time into their daily lives can help health professionals give focused responsive support that helps people with diabetes become more empowered. Understanding that continued support matters, particularly around 6 months, is important as health professionals can influence good management by providing appropriate support and enhancing motivation. Trial registration ISRCTN79759174
    • A method for improved clustering and classification of microscopy images using quantitative co-localization coefficients

      Singan, Vasanth R; Handzic, Kenan; Curran, Kathleen M; Simpson, Jeremy C (2012-06-08)
      AbstractBackgroundThe localization of proteins to specific subcellular structures in eukaryotic cells provides important information with respect to their function. Fluorescence microscopy approaches to determine localization distribution have proved to be an essential tool in the characterization of unknown proteins, and are now particularly pertinent as a result of the wide availability of fluorescently-tagged constructs and antibodies. However, there are currently very few image analysis options able to effectively discriminate proteins with apparently similar distributions in cells, despite this information being important for protein characterization.FindingsWe have developed a novel method for combining two existing image analysis approaches, which results in highly efficient and accurate discrimination of proteins with seemingly similar distributions. We have combined image texture-based analysis with quantitative co-localization coefficients, a method that has traditionally only been used to study the spatial overlap between two populations of molecules. Here we describe and present a novel application for quantitative co-localization, as applied to the study of Rab family small GTP binding proteins localizing to the endomembrane system of cultured cells.ConclusionsWe show how quantitative co-localization can be used alongside texture feature analysis, resulting in improved clustering of microscopy images. The use of co-localization as an additional clustering parameter is non-biased and highly applicable to high-throughput image data sets.
    • A metric space approach to the information channel capacity of spike trains

      Houghton, Conor; Gillespie, James B. (2011-07-18)
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    • A molecular analysis of desiccation tolerance mechanisms in the anhydrobiotic nematode Panagrolaimus superbus using expressed sequenced tags

      Tyson, Trevor; O'Mahony Zamora, Georgina; Wong, Simon; Skelton, Mairin; Daly, Brian; Jones, John T; Mulvihill, Eoin D; Elsworth, Benjamin; Phillips, Mark; Blaxter, Mark; et al. (2012-01-26)
      Abstract Background Some organisms can survive extreme desiccation by entering into a state of suspended animation known as anhydrobiosis. Panagrolaimus superbus is a free-living anhydrobiotic nematode that can survive rapid environmental desiccation. The mechanisms that P. superbus uses to combat the potentially lethal effects of cellular dehydration may include the constitutive and inducible expression of protective molecules, along with behavioural and/or morphological adaptations that slow the rate of cellular water loss. In addition, inducible repair and revival programmes may also be required for successful rehydration and recovery from anhydrobiosis. Results To identify constitutively expressed candidate anhydrobiotic genes we obtained 9,216 ESTs from an unstressed mixed stage population of P. superbus. We derived 4,009 unigenes from these ESTs. These unigene annotations and sequences can be accessed at http://www.nematodes.org/nembase4/species_info.php?species=PSC. We manually annotated a set of 187 constitutively expressed candidate anhydrobiotic genes from P. superbus. Notable among those is a putative lineage expansion of the lea (late embryogenesis abundant) gene family. The most abundantly expressed sequence was a member of the nematode specific sxp/ral-2 family that is highly expressed in parasitic nematodes and secreted onto the surface of the nematodes' cuticles. There were 2,059 novel unigenes (51.7% of the total), 149 of which are predicted to encode intrinsically disordered proteins lacking a fixed tertiary structure. One unigene may encode an exo-β-1,3-glucanase (GHF5 family), most similar to a sequence from Phytophthora infestans. GHF5 enzymes have been reported from several species of plant parasitic nematodes, with horizontal gene transfer (HGT) from bacteria proposed to explain their evolutionary origin. This P. superbus sequence represents another possible HGT event within the Nematoda. The expression of five of the 19 putative stress response genes tested was upregulated in response to desiccation. These were the antioxidants glutathione peroxidase, dj-1 and 1-Cys peroxiredoxin, an shsp sequence and an lea gene. Conclusions P. superbus appears to utilise a strategy of combined constitutive and inducible gene expression in preparation for entry into anhydrobiosis. The apparent lineage expansion of lea genes, together with their constitutive and inducible expression, suggests that LEA3 proteins are important components of the anhydrobiotic protection repertoire of P. superbus.
    • A multi-centre phase IIa clinical study of predictive testing for preeclampsia: improved pregnancy outcomes via early detection (IMPROvED)

      Navaratnam, Kate; Alfirevic, Zarko; Baker, Philip N; Gluud, Christian; Grüttner, Berthold; Kublickiene, Karolina; Zeeman, Gerda; Kenny, Louise C (2013-12-07)
      Abstract Background 5% of first time pregnancies are complicated by pre-eclampsia, the leading cause of maternal death in Europe. No clinically useful screening test exists; consequentially clinicians are unable to offer targeted surveillance or preventative strategies. IMPROvED Consortium members have pioneered a personalised medicine approach to identifying blood-borne biomarkers through recent technological advancements, involving mapping of the blood metabolome and proteome. The key objective is to develop a sensitive, specific, high-throughput and economically viable early pregnancy screening test for pre-eclampsia. Methods/Design We report the design of a multicentre, phase IIa clinical study aiming to recruit 5000 low risk primiparous women to assess and refine innovative prototype tests based on emerging metabolomic and proteomic technologies. Participation involves maternal phlebotomy at 15 and 20 weeks’ gestation, with optional testing and biobanking at 11 and 34 weeks. Blood samples will be analysed using two innovative, proprietary prototype platforms; one metabolomic based and one proteomic based, both of which outperform current biomarker based screening tests at comparable gestations. Analytical and clinical data will be collated and analysed via the Copenhagen Trials Unit. Discussion The IMPROvED study is expected to refine proteomic and metabolomic panels, combined with clinical parameters, and evaluate clinical applicability as an early pregnancy predictive test for pre-eclampsia. If ‘at risk’ patients can be identified, this will allow stratified care with personalised fetal and maternal surveillance, early diagnosis, timely intervention, and significant health economic savings. The IMPROvED biobank will be accessible to the European scientific community for high quality research into the cause and prevention of adverse pregnancy outcome. Trial registration Trial registration number NCT01891240 The IMPROvED project is funded by the seventh framework programme for Research and Technological development of the EU. http://www.fp7-improved.eu/
    • A multidisciplinary primary care team consultation in a socio-economically deprived community: An exploratory randomised controlled trial

      Chan, Wai-Sun; Whitford, David L; Conroy, Ronan; Gibney, David; Hollywood, Brid (2011-01-24)
      Abstract Background Psychosocial problems in socioeconomically deprived communities are not always amenable to traditional medical approaches. Mothers living in these areas are a particularly vulnerable group. The objective of this study was to evaluate the effectiveness of a lengthened multi-disciplinary team consultation in primary care in reducing anxiety and depression in mothers. Methods This was a prospective randomised controlled trial of a multidisciplinary team consultation against normal care. 94 mothers were recruited from three general practices from an area of extreme socio-economic deprivation. Mothers randomised into the intervention group attended a multidisciplinary consultation with up to four case-specific health care professionals. Consultations addressed medical, psychological and social problems and lasted up to one hour. Conventional primary care continued to be available to the intervention families. Control group families received normal primary care services. The outcomes measured were anxiety and depression as using the Hospital Anxiety and Depression Scale (HADS), health status using SF36v2, and quality of life using the abbreviated Schedule for the Evaluation of Individual Quality of Life (SEIQoL-DW) at baseline, 6 months and 12 months. Results Ordered logistic regression was used to analyse the data. There was no significant difference found between intervention and control groups after 6 months and 12 months in all of the measured outcomes. Conclusions The new lengthened multi-disciplinary team consultation did not have any impact on the mental health, general health, and quality of life of mothers after 6 and 12 months. Other methods of primary health care delivery in socio-economically deprived communities need to be evaluated.