Trinity Center for Health science

Dublin, Ireland

Trinity Center for Health science

Dublin, Ireland
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Sakrikar D.,Vanderbilt University | Mazei-Robison M.S.,Vanderbilt University | Mergy M.A.,Vanderbilt University | Richtand N.W.,Vanderbilt University | And 7 more authors.
Journal of Neuroscience | Year: 2012

Attention deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed disorder of school-age children. Although genetic and brain-imaging studies suggest a contribution of altered dopamine (DA) signaling in ADHD, evidence of signaling perturbations contributing to risk is largely circumstantial. The presynaptic, cocaine- and amphetamine (AMPH)-sensitive DA transporter (DAT) constrains DA availability at presynaptic and postsynaptic receptors following vesicular release and is targeted by the most commonly prescribed ADHD therapeutics. Using polymorphism discovery approaches with an ADHD cohort, we identified a hDAT (human DAT) coding variant, R615C, located in the distal C terminus of the transporter, a region previously implicated in constitutive and regulated transporter trafficking. Here, we demonstrate that, whereas wild-type DAT proteins traffic in a highly regulated manner, DAT 615C proteins recycle constitutively and demonstrate insensitivity to the endocytic effects of AMPH and PKC (protein kinase C) activation. The disrupted regulation of DAT 615C parallels a redistribution of the transporter variant away from GM1 ganglioside- and flotillin1-enriched membranes, and is accompanied by altered CaMKII (calcium/calmodulin-dependent protein kinase II) and flotillin-1 interactions. Using C-terminal peptides derived from wild-type DAT and the R615C variant, we establish that the DAT 615C C terminus can act dominantly to precludeAMPHregulation of wild-type DAT. Mutagenesis ofDATC-terminal sequences suggests that phosphorylation of T613 may be important in sorting DAT between constitutive and regulated pathways. Together, our studies support a coupling of DAT microdomain localization with transporter regulation and provide evidence of perturbed DAT activity and DA signaling as a risk determinant for ADHD. © 2012 the authors.

Vellinga A.,Discipline of Bacteriology | Bennett K.,Trinity Center for Health science | Murphy A.W.,Discipline of General Practice | Cormican M.,Discipline of Bacteriology | Cormican M.,University Hospital
Journal of Antimicrobial Chemotherapy | Year: 2012

When studying antimicrobial resistance it is clear that individuals do not exist in isolation and are often clustered into groups. Data within groups are generally not independent, but standard statistical approaches assume independence of observations. When data are clustered (e.g. students in schools, patients in general practices, etc.) multilevel analysis can be used. The overall idea of multilevel analysis is that the clustering is taken into account in the analysis and provides additional information on the interactions between individuals and groups. The lowest level is often the individual and additional levels are formed by clustering in groups (the higher levels). This article introduces the principles behind multilevel modelling. The approach is to provide readers with sufficient information to understand outcomes in which this statistical technique is used, without expecting the reader to be able to perform such an analysis. As multilevel modelling can be seen as an extension of linear regression analysis, this is the starting point of the article. Other concepts and terms are introduced throughout, resulting in the explanation of the accompanying article on antimicrobial prescribing and resistance in Irish general practice (Vellinga A, Tansey S, Hanahoe B et al. J Antimicrob Chemother 2012; 67: 2523-30). © The Author 2012. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

Gleeson I.,Trinity Center for Health science
Journal of Radiotherapy in Practice | Year: 2013

Background and purpose Accurate delineation of the target volume and organs at risk (OARs) are vital to ensure systematic errors are small. The use of contrast agents (CAs) in the bladder and rectum may aid contouring and reduce inter and intra-observer variability. The aim of this study was to evaluate the dosimetric effect of the presence of such contrast on the monitor units (MUs), planning target volume (PTV), rectum and bladder. Materials and methods The prostate, seminal vesicles, rectum and bladder were contoured by a single observer on ten patients with bladder and rectal contrast. To evaluate the dosimetric effect of the presence of contrast, the density of the ten patients with contrast in the bladder and rectum was virtually changed to 1 g/cm 3. A four-field 15 MV conformal radiation therapy technique was applied in which dose volume histograms and MUs were compared using computed tomographic (CT) density and the 1 g/cm3 density. Results The presence of contrast resulted in a 0·09% (<1 MU) increase in anterior MUs and decrease of 1% (<1 MU) in the posterior beam MUs. Lateral beams were not affected. The PTV and bladder dose increased slightly without contrast. The rectum showed a maximum change of 0·62% dose among the measured dose values. A maximum dose of 0·3 Gy at the 30% volume was also seen. Conclusions The dosimetric effect of bladder and rectal CAs on MUs, dose to the PTV and OARs in using this technique was very small. This would not be clinically significant, but only if the extreme limits of dose volume constraints were being reached. Copyright © Cambridge University Press 2013.

Vellinga A.,Discipline of General Practice | Murphy A.W.,Discipline of General Practice | Hanahoe B.,University Hospital | Bennett K.,Trinity Center for Health science | Cormican M.,University Hospital
Journal of Antimicrobial Chemotherapy | Year: 2010

Objectives: A retrospective analysis of databases was performed to describe trimethoprim and ciprofloxacin prescribing and resistance in Escherichia coli within general practices in the West of Ireland from 2004 to 2008. Methods: Antimicrobial susceptibility testing was performed by disc diffusion methods according to the CLSI methods and criteria on significant E. coli isolates (colony count .105 cfu/mL) from urine samples submitted from general practice. Data were collected over a 4.5 year period and aggregated at practice level. Data on anti- microbial prescribing of practices were obtained from the national Irish prescribing database, which accounts for ~70% of all medicines prescribed in primary care. A multilevel model (MLwiN) was fitted with trimethoprim/ciprofloxacin resistance rates as outcome and practice prescribing as predictor. Practice and individual routinely collected variables were controlled for in the model. Results: Seventy-two general practices sent between 13 and 720 (median 155) samples that turned out to be E. coli positive. Prescribing at practice level was significantly correlated with the probability of antimicrobial- resistant E. coli with an odds ratio of 1.02 [95% confidence interval (CI) 1.01-1.04] for every additional prescrip- tion of trimethoprim per 1000 patients per month in the practice and 1.08 (1.04-1.11) for ciprofloxacin. Age was a significant risk factor in both models. Higher variation between practices was found for ciprofloxacin as well as a yearly increase in resistance. Comparing a 'mean' practice with 1 prescription per month with one with 10 prescriptions per month showed an increase in predicted probability of a resistant E. coli for the 'mean' patient from 23.9% to 27.5% for trimethoprim and from 3.0% to 5.5% for ciprofloxacin. Conclusions: A higher level of antimicrobial prescribing in a practice is associated with a higher probability of a resistant E. coli for the patient. The variation in antimicrobial resistance levels between practices was relatively higher for ciprofloxacin than for trimethoprim. © The Author 2010.

O'Donovan C.,Trinity Center for Health science | Roche E.F.,Trinity Center for Health science | Hussey J.,Trinity Center for Health science
Pediatric Obesity | Year: 2014

What is already known about this subject Active video games (AVGs) are being marketed as exercise tools. AVG play can result in light-to-moderate intensity physical activity. What this study adds A comparison correcting for body size between the energy expended by children with obesity and those of a healthy weight playing AVGs. An examination of several variables related to the energy cost of AVG play including steps taken and rate of perceived exertion. There may be some differences in how children with obesity and children of a healthy weight play AVGs. Background Increasing physical activity and reducing sedentary behaviour form a large part of the treatment of paediatric obesity. However, many children today spend prolonged periods of time playing sedentary video games. Active video games (AVGs) represent a novel and child friendly form of physical activity. Objectives To measure the energy cost of playing two AVGs in children with obesity and healthy age- and gender-matched children. Methods The energy cost of gaming and heart rates achieved during gaming conditions were compared between groups. Results AVG play can result in light-to-moderate intensity physical activity (2.7-5.4metabolic equivalents). When corrected for fat-free mass those with obesity expended significantly less energy than healthy weight peers playing Nintendo Wii Fit Free Jogging (P=0.017). No significant difference was seen between groups in the energy cost of playing Boxing. Conclusion Certain AVGs, particularly those that require lower limb movement, could be used to increase total energy expenditure, replace more sedentary activities, or achieve moderate intensity physical activity among children with obesity. There seems to be some differences in how children with obesity and children of a healthy weight play AVGs. This could result in those with obesity expending less energy than their lean peers during AVG play. © 2013 The Authors. Pediatric Obesity © 2013 International Association for the Study of Obesity.

Mikulich O.,Trinity Center for Health science | Callaly E.,Trinity Center for Health science | Bennett K.,Trinity Center for Health science | O'Riordan D.,Jamess Hospital
Acute Medicine | Year: 2011

Background: A weekend emergency medical admission has been associated with a higher mortality. We have examined all weekend admissions to St James' Hospital, Dublin between 2002 and 2009. Methods: We divided admissions by weekday or weekend (Saturday or Sunday) presentation. We utilised a multivariate logistic model, to determine whether a weekend admission was independently predictive of 30 day outcome. Results: There were 49337 episodes recorded in 25883 patients; 30-day inhospital mortality at the weekend (9.9% vs. 9.0%) had an unadjusted Odds Ratio of 1.11 (95% CI 0.99, 1.23: p=0.057). In the full risk (unlike the univariate) model, a weekend admission was not independently predictive (OR 1.05; 95% CI: 0.88, 1.24). The case-mix for a weekend admission differed; with more neurological diagnoses (22.8% vs 20.4% : p = 0.001) and less gastrointestinal disease (18.3% vs 21.1% : p = 0.001). A biochemistry only illness severity score predicted a higher mortality for weekend admissions. Conclusion: Patients admitted at the weekend had an approximate 11% increased 30-day in-hospital mortality, compared with a weekday admission. However, admission at the weekend was not independently predictive in a risk model that included Illness Severity (age and biochemical markers) and co-morbidity. Sicker patients, with a worse outcome, are admitted over the weekend; these considerations should inform the allocation of healthcare resources. © 2011 Rila Publications Ltd.

Hamshere M.L.,University of Cardiff | Stergiakouli E.,University of Cardiff | Langley K.,University of Cardiff | Martin J.,University of Cardiff | And 7 more authors.
British Journal of Psychiatry | Year: 2013

Background: There is recent evidence of some degree of shared genetic susceptibility between adult schizophrenia and childhood attention-deficit hyperactivity disorder (ADHD) for rare chromosomal variants. Aims: To determine whether there is overlap between common alleles conferring risk of schizophrenia in adults with those that do so for ADHD in children. Method: We used recently published Psychiatric Genome-wide Association Study (GWAS) Consortium (PGC) adult schizophrenia data to define alleles over-represented in people with schizophrenia and tested whether those alleles were more common in 727 children with ADHD than in 2067 controls. Results: Schizophrenia risk alleles discriminated ADHD cases from controls (P = 1.04×10-4, R 2 = 0.45%); stronger discrimination was given by alleles that were risk alleles for both adult schizophrenia and adult bipolar disorder (also derived from a PGC data-set) (P = 9.98×10-6, R2 = 0.59%). Conclusions: This increasing evidence for a small, but significant, shared genetic susceptibility between adult schizophrenia and childhood ADHD highlights the importance of research work across traditional diagnostic boundaries.

Coffey M.,Trinity Center for Health Science | Vaandering A.,Cliniques Universitaires Saint Luc
Radiotherapy and Oncology | Year: 2010

PET/CT imaging modalities have been shown to be useful in the diagnosis, staging, and monitoring of malignant diseases. Its inclusion into the treatment planning process is now central to modern radiotherapy practice. However, it is essential to be cognisant of the factors that are necessary in order to ensure that the acquired images are consistent with the requirements for both treatment planning and treatment delivery. Essential parameters required in image acquisition for radiotherapy planning and treatment include consistencies of table tops and the use of laser light for patient set-up. But they also include the accurate definition of the patient's initial positioning and the use of proper immobilization devices in the radiotherapy department. While determining this optimum set-up, patient psychological factors and limitations that may be due to the subsequent use of PET/CT for planning purposes need to be taken into account. Furthermore, patient set-up data need to be properly recorded and transmitted to the imaging departments. To ensure the consistency of patient set-up, the radiation therapist should ideally be directly involved in informing and positioning the patient on the PET/CT. However, a proper exchange of patient-related information can also be achieved by a close liaison between the two departments and by the use of clear detailed protocols per type of patient set-up and/or per localization of tumour site. © 2010 European Society for Therapeutic Radiology and Oncology and European Association of Nuclear Medicine. Published by Elsevier Ireland Ltd. All rights reserved.

Machold C.,Trinity Center for Health science
Irish medical journal | Year: 2012

Social Networking Sites (SNSs) have grown substantially, posing new hazards to teenagers. This study aimed to determine general patterns of Internet usage among Irish teenagers aged 11-16 years, and to identify potential hazards, including; bullying, inappropriate contact, overuse, addiction and invasion of users' privacy. A cross-sectional study design was employed to survey students at three Irish secondary schools, with a sample of 474 completing a questionnaire. 202 (44%) (n = 460) accessed the Internet using a shared home computer. Two hours or less were spent online daily by 285(62%), of whom 450 (98%) were unsupervised. 306 (72%) (n = 425) reported frequent usage of SNSs, 403 (95%) of whom were Facebook users. 42 (10%) males and 51 (12%) females experienced bullying online, while 114 (27%) reported inappropriate contact from others. Concerning overuse and the risk of addiction, 140 (33%) felt they accessed SNSs too often. These patterns among Irish teenagers suggest that SNS usage poses significant dangers, which are going largely unaddressed.

Vellinga A.,National University of Ireland | Tansey S.,University Hospital | Hanahoe B.,University Hospital | Bennett K.,Trinity Center for Health science | And 3 more authors.
Journal of Antimicrobial Chemotherapy | Year: 2012

Objectives: Individual and group level factors associated with the probability of antimicrobial resistance of uropathogenic Escherichia coli were analysed in a multilevel model. Methods: Adult patients consulting with a suspected urinary tract infection (UTI) in 22 general practices over a 9 month period supplied a urine sample for laboratory analysis. Cases were patients with a UTI associated with a resistant E. coli. Previous antimicrobial exposure and other patient characteristics were recorded from the medical files. Results: Six hundred and thirty-three patients with an E. coli UTI and a full record for all variables were included. Of the E. coli isolates, 36% were resistant to trimethoprim and 12% to ciprofloxacin. A multilevel logistic regression model was fitted. The odds that E. coli was resistant increased with increasing number of prescriptions over the previous year for trimethoprim from 1.4 (0.8-2.2) for one previous prescription to 4.7 (1.9-12.4) for two and 6.4 (2.0-25.4) for three or more. For ciprofloxacin the ORs were 2.7 (1.2-5.6) for one and 6.5 (2.9-14.8) for two or more. The probability that uropathogenic E. coli was resistant showed important variation between practices and a difference of 17% for trimethoprim and 33% for ciprofloxacin was observed for an imaginary patient moving from a practice with low to a practice with high probability. This difference could not be explained by practice prescribing or practice resistance levels. Conclusions: Previous antimicrobial use and the practice visited affect the risk that a patient with a UTI will be diagnosed with an E. coli resistant to this agent, which was particularly important for ciprofloxacin. © The Author 2012. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

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