http://hdl.handle.net/10197/2639 2013-06-18T23:49:44Z 2013-06-18T23:49:44Z Stavropoulos, Ilias Khaldi, Nora Davey, Norman E. O'Brien, Kevin Martin, Finian Shields, Denis C. http://hdl.handle.net/10197/4242 2013-04-08T15:56:56Z 2012-09-04T00:00:00Z

Protein disorder and short conserved motifs in disordered regions are enriched near the cytoplasmic side of single-pass transmembrane proteins Stavropoulos, Ilias; Khaldi, Nora; Davey, Norman E.; O'Brien, Kevin; Martin, Finian; Shields, Denis C. Intracellular juxtamembrane regions of transmembrane proteins play pivotal roles in cell signalling, mediated by protein-protein interactions. Disordered protein regions, and short conserved motifs within them, are emerging as key determinants of many such interactions. Here, we investigated whether disorder and conserved motifs are enriched in the juxtamembrane area of human single-pass transmembrane proteins. Conserved motifs were defined as short disordered regions that were much more conserved than the adjacent disordered residues. Human single-pass proteins had higher mean disorder in their cytoplasmic segments than their extracellular parts. Some, but not all, of this effect reflected the shorter length of the cytoplasmic tail. A peak of cytoplasmic disorder was seen at around 30 residues from the membrane. We noted a significant increase in the incidence of conserved motifs within the disordered regions at the same location, even after correcting for the extent of disorder. We conclude that elevated disorder within the cytoplasmic tail of many transmembrane proteins is likely to be associated with enrichment for signalling interactions mediated by conserved short motifs.

2012-09-04T00:00:00Z Klimas, Jan Field, Catherine Anne Cullen, Walter O'Gorman, Clodagh S. M. Glynn, Liam G. Keenan, Eamon Saunders, Jean Bury, Gerard Dunne, Colum http://hdl.handle.net/10197/4030 2013-01-14T16:30:54Z 2012-11-01T00:00:00Z

Psychosocial interventions to reduce alcohol consumption in concurrent problem alcohol and illicit drug users. Klimas, Jan; Field, Catherine Anne; Cullen, Walter; O'Gorman, Clodagh S. M.; Glynn, Liam G.; Keenan, Eamon; Saunders, Jean; Bury, Gerard; Dunne, Colum Background: Problem alcohol use is common among illicit drug users and is associated with adverse health outcomes. It is also an important factor in poor prognosis among drug users with hepatitis C virus (HCV) as it impacts on progression to hepatic cirrhosis or opiate overdose in opioid users.Objectives: To assess the effects of psychosocial interventions for problem alcohol use in illicit drug users (principally problem drug users of opiates and stimulants).Search methods: We searched the Cochrane Drugs and Alcohol Group trials register (November 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 11, November 2011), PUBMED (1966 to 2011); EMBASE (1974 to 2011); CINAHL (1982 to 2011); PsycINFO (1872 to 2011) and reference list of articles. We also searched: 1) conference proceedings (online archives only) of the Society for the Study of Addiction (SSA), International Harm Reduction Association (IHRA), International Conference on Alcohol Harm Reduction (ICAHR), and American Association for the Treatment of Opioid Dependence (AATOD); 2) online registers of clinical trials, Current Controlled Trials (CCT), Clinical Trials.org, Center Watch and International Clinical Trials Registry Platform (ICTRP).Selection criteria: Randomised controlled trials comparing psychosocial interventions with another therapy (other psychosocial treatment, including non-pharmacological therapies or placebo) in adult (over the age of 18 years) illicit drug users with concurrent problem alcohol use.Data collection and analysis: Two review authors independently assessed risk of bias and extracted data from included trials.Main results: Four studies, 594 participants, were included. Half of the trials were rated as having high or unclear risk of bias. They considered six different psychosocial interventions grouped into four comparisons: (1) cognitive-behavioural coping skills training versus 12-step facilitation (N = 41), (2) brief intervention versus treatment as usual (N = 110), (3) hepatitis health promotion versus motivational interviewing (N = 256), and (4) brief motivational intervention versus assessment-only group (N = 187). Differences between studies precluded any pooling of data. Findings are described for each trial individually:comparison 1: no significant difference; comparison 2: higher rates of decreased alcohol use at three months (risk ratio (RR) 0.32; 95% confidence interval (CI) 0.19 to 0.54) and nine months (RR 0.16; 95% CI 0.08 to 0.33) in the treatment as usual group; comparison 3 (group and individual format): no significant difference; comparison 4: more people reduced alcohol use (by seven or more days in the past 30 days at 6 months) in the brief motivational intervention compared to controls (RR 1.67; 95% CI 1.08 to 2.60).Authors' conclusions: Very little evidence exists that there is no difference in the effectiveness between different types of interventions and that brief interventions are not superior to assessment only or treatment as usual. No conclusion can be made because of the paucity of the data and the low quality of the retrieved studies.

2012-11-01T00:00:00Z Haslam, Niall J. Whiteford, Nava E. Weber, Gerald Prügel-Bennett, Adam Essex, Jonathan W. Neylon, Cameron http://hdl.handle.net/10197/3945 2012-12-03T15:01:36Z 2008-06-01T00:00:00Z

Optimal Probe Length Varies for Targets with High Sequence Variation: Implications for Probe Library Design for Resequencing Highly Variable Genes Haslam, Niall J.; Whiteford, Nava E.; Weber, Gerald; Prügel-Bennett, Adam; Essex, Jonathan W.; Neylon, Cameron Sequencing by hybridisation is an effective method for obtaining large amounts of DNA sequence information at low cost. The efficiency of SBH depends on the design of the probe library to provide the maximum information for minimum cost. Long probes provide a higher probability of non-repeated sequences but lead to an increase in the number of probes required whereas short probes may not provide unique sequence information due to repeated sequences. We have investigated the effect of probe length, use of reference sequences, and thermal filtering on the design of probe libraries for several highly variable target DNA sequences. Results We designed overlapping probe libraries for a range of highly variable drug target genes based on known sequence information and develop a formal terminology to describe probe library design. We find that for some targets these libraries can provide good coverage of a previously unseen target whereas for others the coverage is less than 30%. The optimal probe length varies from as short at 12 nt to as large as 19 nt and depends on the sequence, its variability, and the stringency of thermal filtering. It cannot be determined from inspection of an example gene sequence. Conclusions Optimal probe length and the optimal number of reference sequences used to design a probe library are highly target specific for highly variable sequencing targets. The optimum design cannot be determined simply by inspection of input sequences or of alignments but only by detailed analysis of the each specific target. For highly variable sequences, shorter probes can in some cases provide better information than longer probes. Probe library design would benefit from a general purpose tool for analysing these issues. The formal terminology developed here and the analysis approaches it is used to describe will contribute to the development of such tools.

2008-06-01T00:00:00Z Haslam, Niall J. Shields, Denis C. http://hdl.handle.net/10197/3944 2012-12-03T14:55:50Z 2012-05-18T00:00:00Z

Profile-based short linear protein motif discovery Haslam, Niall J.; Shields, Denis C. Background: Short linear protein motifs are attracting increasing attention as functionally independent sites, typically 3-10 amino acids in length that are enriched in disordered regions of proteins. Multiple methods have recently been proposed to discover over-represented motifs within a set of proteins based on simple regular expressions. Here, we extend these approaches to profile-based methods, which provide a richer motif representation.Results: The profile motif discovery method MEME performed relatively poorly for motifs in disordered regions of proteins. However, when we applied evolutionary weighting to account for redundancy amongst homologous proteins, and masked out poorly conserved regions of disordered proteins, the performance of MEME is equivalent to that of regular expression methods. However, the two approaches returned different subsets within both a benchmark dataset, and a more realistic discovery dataset.Conclusions: Profile-based motif discovery methods complement regular expression based methods. Whilst profile-based methods are computationally more intensive, they are likely to discover motifs currently overlooked by regular expression methods. 

2012-05-18T00:00:00Z Dinkel, Holger Michael, Sushama Weatheritt, Robert J. Davey, Norman E. Van Roey, Kim Altenberg, Brigitte Toedt, Grischa Uyar, Bora Seiler, Markus Budd, Aidan Jödicke, Lisa Dammert, Marcel A. Schroeter, Christian Hammer, Maria Schmidt, Tobias Jehl, Peter McGuigan, Caroline Dymecka, Magdalena Chica, Claudia Luck, Katja Via, Allegra Chatr-aryamontri, Andrew Haslam, Niall J. Grebnev, Gleb Edwards, Richard J. Steinmetz, Michel O. Meiselbach, Heike Diella, Francesca Gibson, Toby J. http://hdl.handle.net/10197/3943 2012-12-03T14:46:39Z 2012-01-01T00:00:00Z

ELM--the database of eukaryotic linear motifs Dinkel, Holger; Michael, Sushama; Weatheritt, Robert J.; Davey, Norman E.; Van Roey, Kim; Altenberg, Brigitte; Toedt, Grischa; Uyar, Bora; Seiler, Markus; Budd, Aidan; Jödicke, Lisa; Dammert, Marcel A.; Schroeter, Christian; Hammer, Maria; Schmidt, Tobias; Jehl, Peter; McGuigan, Caroline; Dymecka, Magdalena; Chica, Claudia; Luck, Katja; Via, Allegra; Chatr-aryamontri, Andrew; Haslam, Niall J.; Grebnev, Gleb; Edwards, Richard J.; Steinmetz, Michel O.; Meiselbach, Heike; Diella, Francesca; Gibson, Toby J. Linear motifs are short, evolutionarily plastic components of regulatory proteins and provide low-affinity interaction interfaces. These compact modules play central roles in mediating every aspect of the regulatory functionality of the cell. They are particularly prominent in mediating cell signaling, controlling protein turnover and directing protein localization. Given their importance, our understanding of motifs is surprisingly limited, largely as a result of the difficulty of discovery, both experimentally and computationally. The Eukaryotic Linear Motif (ELM) resource at http://elm.eu.org provides the biological community with a comprehensive database of known experimentally validated motifs, and an exploratory tool to discover putative linear motifs in user-submitted protein sequences. The current update of the ELM database comprises 1800 annotated motif instances representing 170 distinct functional classes, including approximately 500 novel instances and 24 novel classes. Several older motif class entries have been also revisited, improving annotation and adding novel instances. Furthermore, addition of full-text search capabilities, an enhanced interface and simplified batch download has improved the overall accessibility of the ELM data. The motif discovery portion of the ELM resource has added conservation, and structural attributes have been incorporated to aid users to discriminate biologically relevant motifs from stochastically occurring non-functional instances.

2012-01-01T00:00:00Z Riccombeni, Alessandro Butler, Geraldine http://hdl.handle.net/10197/3934 2012-11-28T13:03:00Z 2012-09-01T00:00:00Z

Role of Genomics and RNA-seq in Studies of Fungal Virulence Riccombeni, Alessandro; Butler, Geraldine Since its introduction in the last decade, massive parallel sequencing, or "next-generation sequencing", has revolutionized our access to genomic information, providing accurate data with increasingly higher yields and lower costs with respect to first-generation technology. Massive parallel sequencing of cDNA, or RNA-seq, is progressively replacing array-based technology as the method of choice for transcriptomics. This review describes some of the most recent applications of next-generation sequencing technology to the study of pathogenic fungi, including Candida, Aspergillus and Cryptococcusspecies. Several integrated approaches illustrate the power and accuracy of RNA-seq for studying the biology of human fungal pathogens. In addition, the lack of consistency in data analysis is discussed.

2012-09-01T00:00:00Z Regan, Ciaran M. http://hdl.handle.net/10197/3916 2012-11-26T14:46:08Z 2012-11-01T00:00:00Z

The Addicted Self: A Neuroscientific Perspective Regan, Ciaran M.

2012-11-01T00:00:00Z Moore, David Davis, Michaela Starc, Tina http://hdl.handle.net/10197/3892 2012-11-07T16:56:10Z 2012-05-01T00:00:00Z

Investigating the ability of radiographers to recognise typical non accidental injury fractures in children Moore, David; Davis, Michaela; Starc, Tina Introduction: Child abuse is often underreported by the general population and healthcare professionals for a variety of reasons and, therefore, all avenues to improve the discovery and prevention of child abuse should be explored.  Radiographers are well positioned to identify child abuse and in particular Non Accidental Injuries (N.A.I.); having a wealth of experience in image acquisition and visualisation.  In the Republic of Ireland Health Care professionals are legally required to report suspicious cases as Designated Officers.  Aim: Our aim was to measure radiographers' ability to recognise non-accidental injury fractures in children comparing radiographers from two different European Countries. Method: 22 radiographers working in hospitals in the Republic of Ireland and Slovenia viewed 26 plain radiographic images (13 NAI fractures/13 accidental fractures) and rated their confidence on a scale from 1 to 6 that a fracture was either accidental (1-3) or non-accidental (4-6).  The images were viewed using ViewDex software on a laptop calibrated to DICOM greyscale standard display function.  Viewing conditions were standardised and optimised.  An ROC curve was plotted and sensitivity, specificity and area under the curve (AUC) were calculated for each radiographer. Results: The results demonstrated a difference in values which AUC was statistically significant (P=0.0111)Conclusion:  Further research would be beneficial with more images, full skeletal surveys, and paediatric radiologist(s) as a gold standard for comparison.

2012-05-01T00:00:00Z Mooney, Catherine Haslam, Niall J. Pollastri, Gianluca Shields, Denis C. http://hdl.handle.net/10197/3891 2012-11-07T15:27:40Z 2012-10-01T00:00:00Z

Towards the Improved Discovery and Design of Functional Peptides: Common Features of Diverse Classes Permit Generalized Prediction of Bioactivity Mooney, Catherine; Haslam, Niall J.; Pollastri, Gianluca; Shields, Denis C. The conventional wisdom is that certain classes of bioactive peptides have specific structural features that endow their particular functions. Accordingly, predictions of bioactivity have focused on particular subgroups, such as antimicrobial peptides. We hypothesized that bioactive peptides may share more general features, and assessed this by contrasting the predictive power of existing antimicrobial predictors as well as a novel general predictor, PeptideRanker, across different classes of peptides.We observed that existing antimicrobial predictors had reasonable predictive power to identify peptides of certain other classes i.e. toxin and venom peptides. We trained two general predictors of peptide bioactivity, one focused on short peptides (4-20 amino acids) and one focused on long peptides (>20 amino acids). These general predictors had performance that was typically as good as, or better than, that of specific predictors. We noted some striking differences in the features of short peptide and long peptide predictions, in particular, high scoring short peptides favour phenylalanine. This is consistent with the hypothesis that short and long peptides have different functional constraints, perhaps reflecting the difficulty for typical short peptides in supporting independent tertiary structure.We conclude that there are general shared features of bioactive peptides across different functional classes, indicating that computational prediction may accelerate the discovery of novel bioactive peptides and aid in the improved design of existing peptides, across many functional classes. An implementation of the predictive method, PeptideRanker, may be used to identify among a set of peptides those that may be more likely to be bioactive.

2012-10-01T00:00:00Z Haslam, Niall J. Shields, Denis C. http://hdl.handle.net/10197/3789 2012-09-05T15:37:09Z 2012-05-18T00:00:00Z

Profile-based short linear protein motif discovery. Haslam, Niall J.; Shields, Denis C. Background Short linear protein motifs are attracting increasing attention as functionally independent sites, typically 3-10 amino acids in length that are enriched in disordered regions of proteins. Multiple methods have recently been proposed to discover over-represented motifs within a set of proteins based on simple regular expressions. Here, we extend these approaches to profile-based methods, which provide a richer motif representation. Results The profile motif discovery method MEME performed relatively poorly for motifs in disordered regions of proteins. However, when we applied evolutionary weighting to account for redundancy amongst homologous proteins, and masked out poorly conserved regions of disordered proteins, the performance of MEME is equivalent to that of regular expression methods. However, the two approaches returned different subsets within both a benchmark dataset, and a more realistic discovery dataset. Conclusions Profile-based motif discovery methods complement regular expression based methods. Whilst profile-based methods are computationally more intensive, they are likely to discover motifs currently overlooked by regular expression methods.

2012-05-18T00:00:00Z Norris, Roseanne Casey, Fergal FitzGerald, Richard Shields, Denis C. Mooney, Catherine http://hdl.handle.net/10197/3748 2012-08-17T15:22:47Z 2012-08-14T00:00:00Z

Predictive modelling of angiotensin converting enzyme inhibitory dipeptides Norris, Roseanne; Casey, Fergal; FitzGerald, Richard; Shields, Denis C.; Mooney, Catherine The ability of docking to predict angiotensin converting enzyme (ACE) inhibitory dipeptide sequences was assessed using AutoDock Vina. All potential dipeptides and phospho-dipeptides were docked and scored. Peptide intestinal stability was assessed using a prediction amino acid clustering model. Selected dipeptides, having AutoDock Vina scores −8.1 and predicted to be ‘stable’ intestinally, were characterised, using LIGPLOT and for ACE-inhibitory potency. Two newly identified ACE-inhibitory dipeptides, Asp-Trp and Trp-Pro, having Vina scores of −8.3 and −8.6 gave IC50 values of 258 ± 4.23 and 217 ± 15.7 μM, respectively. LIGPLOT analysis indicated no zinc interaction for these dipeptides. Phospho-dipeptides were predicted to have a good affinity for ACE. However, the experimentally determined IC50 results did not correlate since, for example, Trp-pThr and Pro-pTyr, having Vina scores of −8.5 and −8.1, respectively, displayed IC50 values of >500 μM. While docking allowed identification of new ACE inhibitory dipeptides, it may not be a fully reliable predictive tool in all cases.

2012-08-14T00:00:00Z Klimas, Jan Field, Catherine Anne Anderson, Rolande Barry, Joseph Bedford, Declan Bourke, Margaret Corrigan, Gerard Doyle, Joseph Flanagan, Jean Gallagher, Hugh Geoghegan, Noreen Harkin, Kieran Keenan, Eamon Lambert, John McAuliffe, Ruaidhri McCann, Mary Ellen McCormick, Aiden O'Driscoll, Denis O'Gara, Colin Perry, Nicola Smyth, Bobby P. Weldon, Fiona Cullen, Walter Bury, Gerard Lyons, Suzi http://hdl.handle.net/10197/3618 2012-05-22T14:42:46Z 2012-03-09T00:00:00Z

Problem alcohol use among problem drug users : development of clinical guidelines for general practice Klimas, Jan; Field, Catherine Anne; Anderson, Rolande; Barry, Joseph; Bedford, Declan; Bourke, Margaret; Corrigan, Gerard; Doyle, Joseph; Flanagan, Jean; Gallagher, Hugh; Geoghegan, Noreen; Harkin, Kieran; Keenan, Eamon; Lambert, John; McAuliffe, Ruaidhri; McCann, Mary Ellen; McCormick, Aiden; O'Driscoll, Denis; O'Gara, Colin; Perry, Nicola; Smyth, Bobby P.; Weldon, Fiona; Cullen, Walter; Bury, Gerard; Lyons, Suzi Introduction: Problem alcohol use is common and associated with considerable adverse health and social outcomes among patients who attend GPs in Ireland and other European countries for opioid substitution treatment. This paper aims to describe the development and content of clinical guidelines for the management of problem alcohol use among current or former opioid users attending general practice for methadone treatment. Methods: The guidelines were developed in several stages: i) identification of key stakeholders; ii) development of evidence-based draft guidelines, and iii)determination of a modified ‘Delphi-facilitated’ consensus among the group members. These guidelines were informed by a review of scientific evidence and a qualitative study, results of which will be presented also at this conference. Results: The guidelines incorporate advice for GPs on all aspects of care of this problem, including i) definition of problem alcohol use among problem drug users, ii) screening / identification of problem alcohol use, iii) interventions for treatment and management of problem alcohol use, iv) referral to secondary services and v) role of GPs in the management of persistent problem alcohol use and on-going care. Conclusions: General practice has an important role to play in the care of problem alcohol use among problem drug users, especially patients who attend for methadone treatment. Further research on strategies to inform the implementation of this study is a priority. Abstract for presentation at AUDGPI Annual Scientific Meeting, Dublin, Ireland, 9th March 2012

2012-03-09T00:00:00Z Field, Catherine Anne Klimas, Jan Cullen, Walter Barry, Joe Bury, Gerard Keenan, Eamon Lyons, Suzi Smyth, Bobby P. http://hdl.handle.net/10197/3578 2012-04-17T15:04:23Z 2012-03-09T00:00:00Z

The management of problem alcohol use among drug users in primary care : exploring patients’ experience of screening and treatment Field, Catherine Anne; Klimas, Jan; Cullen, Walter; Barry, Joe; Bury, Gerard; Keenan, Eamon; Lyons, Suzi; Smyth, Bobby P. Problem alcohol use is common among drug using patients who attend GPs in Ireland (35%) and other European countries. It is associated with adverse health outcomes including physical, psychological and social implications. These include various forms of liver disease exacerbated by the high prevalence of Hepatitis C among IDUs (62-81% in Ireland), fatal/non-fatal opiate overdose, mood anxiety, personality disorders, poor emotional health and wellbeing, early cessation of drug treatment, poor treatment outcomes and an increase in anti-social behaviour. Evidence has demonstrated the role of primary care in screening and treatment for problem alcohol use and the importance of a stepped approach to alcohol treatment. This study examined patients’ experience of being screened and treated for problem alcohol use, the barriers and enablers to addressing these issues and their views on how these therapeutic interventions can be improved. Abstract for paper presented at AUDGPI 2012, The Association of University Departments of General Practice in Ireland Annual Scientific Meeting Hosted By Department of General Practice The Royal College of surgeons in Ireland, Dublin, Ireland, 9th March 2012

2012-03-09T00:00:00Z Field, Catherine Anne Klimas, Jan Barry, Joe Bury, Gerard Keenan, Eamon Lyons, Suzi Smyth, Bobby P. Cullen, Walter http://hdl.handle.net/10197/3472 2012-04-17T15:02:44Z 2011-01-20T00:00:00Z

Exploring healthcare professionals experience and attitudes towards screening for and treatment of problem alcohol use among drug users attending primary care Field, Catherine Anne; Klimas, Jan; Barry, Joe; Bury, Gerard; Keenan, Eamon; Lyons, Suzi; Smyth, Bobby P.; Cullen, Walter Problem alcohol use (PAU) is common among drug users (DUs) prevalence rates vary from 13-76%, in a recent Irish study of patients on methadone 35% had an AUDIT score indicating PAU. PAU is associated with adverse health outcomes including physical, psychological and social implications. Despite the crucial role of primary care in screening and treatment for problematic alcohol use and the importance of a stepped approach to alcohol treatment, supported by the evidence, little data reporting intervention interventions which address this issue in DUs attending primary care has been reported. This study has examined healthcare professionals’ experience of and attitudes towards screening and treatment for PAU among drug users in primary care. Twelve GPs and practice nurses who were recruited through the central treatment list participated in this study. Qualitative interviews exploring their experiences of and attitudes towards management of PAU in DUs attending primary care were conducted according to a semi structured interview guide. The topic guide was informed by the results of a literature review completed in the previous phase of our research project. Interviews were audio-recorded and subsequently transcribed by external transcribers. For the purpose of this presentation, we have analysed only sections of the interviews concerning strategies that could facilitate implementation of alcohol interventions in primary care settings. Thematic analysis was utilized to analyse these interview sections. Analysis of the selected interview sections revealed that Doctors and Nurses would prefer additional staff to be available in order to support successful implementation of alcohol screening and brief intervention within their practices. They rated this strategy as the most helpful from a list of strategies provided by the interviewers. The results of this preliminary analysis pointed to the importance of professionals trained in the delivery of brief interventions as a necessary adjunct to the optimal provision of drug treatment in general practice. This finding supports the evidence showing that implementation of evidence based interventions to vulnerable populations attending primary care needs to be preceded by identification of potential obstacles at the implementation onset. Further implications of our findings for clinical practice and policy planning will be discussed in the presentation. Paper presented at the ADEGS/AUDGPI Scientific Meeting (Annual Conference of University Departments of General Practice in Ireland), Thursday 20th & Friday 21st January 2011

2011-01-20T00:00:00Z Field, Catherine Anne Klimas, Jan Barry, Joe Bury, Gerard Keenan, Eamon Lyons, Suzi Smyth, Bobby P. Cullen, Walter http://hdl.handle.net/10197/3429 2013-06-02T03:00:08Z 2012-06-01T00:00:00Z

Alcohol screening and brief intervention among drug users in primary care : a discussion paper Field, Catherine Anne; Klimas, Jan; Barry, Joe; Bury, Gerard; Keenan, Eamon; Lyons, Suzi; Smyth, Bobby P.; Cullen, Walter Background problem alcohol use is common among problem drug users (PDU) and associated with adverse health outcomes. Primary care has an important role in the overall stepped approach to alcohol treatment, especially screening and brief intervention (SBI). Aim To discuss three themes that emerged from an exploration of the literature on SBI for problem alcohol use in drug users attending primary care. Methods material for this discussion paper was gathered from three biomedical databases (PubMed, PsycINFO and Cochrane library), conference proceedings and online resources of professional organisations or national health agencies. Themes discussed in this paper are: (a) the potential of primary care for delivery of alcohol SBIs to PDUs, (b) screening methods and (c) application of brief interventions to PDUs. Although SBI improves health outcomes associated with problem alcohol use in the general population, further research is needed among high-risk patient groups, especially PDUs.

2012-06-01T00:00:00Z Mooney, Catherine Pollastri, Gianluca Shields, Denis C. Haslam, Niall J. http://hdl.handle.net/10197/3395 2013-01-25T14:34:36Z 2012-01-06T00:00:00Z

Prediction of short linear protein binding regions Mooney, Catherine; Pollastri, Gianluca; Shields, Denis C.; Haslam, Niall J. Short linear motifs in proteins (typically 3–12 residues in length) play key roles in protein–protein interactions by frequently binding specifically to peptide binding domains within interacting proteins. Their tendency to be found in disordered segments of proteins has meant that they have often been overlooked. Here we present SLiMPred (short linear motif predictor), the first general de novo method designed to computationally predict such regions in protein primary sequences independent of experimentally defined homologs and interactors. The method applies machine learning techniques to predict new motifs based on annotated instances from the Eukaryotic Linear Motif database, as well as structural, biophysical, and biochemical features derived from the protein primary sequence. We have integrated these data sources and benchmarked the predictive accuracy of the method, and found that it performs equivalently to a predictor of protein binding regions in disordered regions, in addition to having predictive power for other classes of motif sites such as polyproline II helix motifs and short linear motifs lying in ordered regions. It will be useful in predicting peptides involved in potential protein associations and will aid in the functional characterization of proteins, especially of proteins lacking experimental information on structures and interactions. We conclude that, despite the diversity of motif sequences and structures, SLiMPred is a valuable tool for prioritizing potential interaction motifs in proteins.

2012-01-06T00:00:00Z Klimas, Jan Field, Catherine Anne Cullen, Walter O'Gorman, Clodagh S. M. Glynn, Liam G. Keenan, Eamon Saunders, Jean Bury, Gerard Dunne, Colum http://hdl.handle.net/10197/3348 2011-11-25T12:40:20Z 2011-08-10T00:00:00Z

Psychosocial interventions for problem alcohol use in illicit drug users (Protocol) Klimas, Jan; Field, Catherine Anne; Cullen, Walter; O'Gorman, Clodagh S. M.; Glynn, Liam G.; Keenan, Eamon; Saunders, Jean; Bury, Gerard; Dunne, Colum This is the protocol for a review and there is no abstract. The objectives are as follows:To determine the effectiveness of psychosocial interventions targeting problem alcohol use versus other treatments in illicit drug users.

2011-08-10T00:00:00Z Klimas, Jan Field, Catherine Anne Barry, Joe Bury, Gerard Keenan, Eamon Lyons, Suzi Smyth, Bobby P. Cullen, Walter http://hdl.handle.net/10197/3347 2012-10-10T16:36:42Z 2012-01-01T00:00:00Z

Commentary on ‘The research translation problem : Alcohol screening and brief intervention in primary care – Real world evidence supports theory’ Klimas, Jan; Field, Catherine Anne; Barry, Joe; Bury, Gerard; Keenan, Eamon; Lyons, Suzi; Smyth, Bobby P.; Cullen, Walter

2012-01-01T00:00:00Z Farmer, Aoife Davis, Michaela http://hdl.handle.net/10197/3319 2011-11-22T14:29:40Z 2009-12-01T00:00:00Z

A small scale qualitative study to investigate the interaction between psychiatric patients and diagnostic radiographers in one Irish hospital Farmer, Aoife; Davis, Michaela Abstract Background: A substantial number of patients with psychiatric illnesses present to the Imaging Department across the Irish Republic each year. Patients who have a psychiatric illness may present difficulties for the radiographer during a radiographic examination. These difficulties may include communication difficulties, and an increased prevalence to become violent due to their illness. Aims: To investigate if radiographers feel confident interacting with psychiatric patients. To ascertain if radiographers need more training in this area of patient interaction. Method: A qualitative approach was used drawing upon six radiographers working in a regional hospital with a psychiatric unit attached. The radiographers were interviewed individually and the results were thematically analysed. Results: The results indicated that the level of the radiographers own confidence in relation to interacting with psychiatric patients was influenced by the number of years since qualification. The majority of radiographers in the study displayed a poor knowledge of psychiatric conditions and how they affect patients. Conclusion: Based upon this small study, the results suggest that newly qualified radiographers do not feel confident in their own abilities when interacting with psychiatric patients and would welcome and benefit from specific training with regards to strategies to deal with psychiatric patients. The radiographers reported that particular areas whichmay be improved upon are more information on psychiatric illnesses, manifestations of different types of psychiatric illness and the subsequent effect on patients. A larger study encompassing the whole of the Republic of Ireland would be valuable as a precursor to a European comparative study in order to investigate this phenomenon at a deeper level. Additionally it is recommended that further research is conducted within a wider European context on student radiographers and lecturers teaching on undergraduate radiography courses to ascertain if this topic is addressed at undergraduate level.

2009-12-01T00:00:00Z D'Helft, Catherine Brennan, Patrick Davis, Michaela http://hdl.handle.net/10197/3276 2011-10-28T14:05:01Z 2010-01-01T00:00:00Z

Role of the different imaging modalities in the diagnosis and staging of equine navicular syndrome. A review D'Helft, Catherine; Brennan, Patrick; Davis, Michaela Equine navicular syndrome (ENS) is a common ailment responsible for up to one-third of all chronic forelimb lameness. The current presentation, based on literature reviews and veterinary and radiology opinions, offers a brief overview of the current status of imaging the equine navicular syndrome. Conventional radiography, ultrasound, computed tomography, scintigraphy and magnetic resonance imaging are considered since all appear to have some purpose in the diagnosis and staging, relating to the complexity of the syndrome. Appropriate imaging evaluation, following physical examination can yield useful information, not only helping to define the extent of the disease but also facilitating the identification of the most appropriate treatments

2010-01-01T00:00:00Z Puri, Prem Gosemann, Jan-Hendrik Darlow, John Barton, David E. http://hdl.handle.net/10197/3231 2012-08-08T11:49:48Z 2011-10-01T00:00:00Z

Genetics of vesicoureteral reflux Puri, Prem; Gosemann, Jan-Hendrik; Darlow, John; Barton, David E. Primary vesicoureteral reflux (VUR) is the most common urological anomaly in children, affecting 1–2% of the pediatric population and 30–40% of children presenting with urinary tract infections (UTIs). Refluxassociated nephropathy is a major cause of childhood hypertension and chronic renal failure. The hereditary and familial nature of VUR is well recognized and several studies have reported that siblings of children with VUR have a higher incidence of reflux than the general pediatric population. Familial clustering of VUR implies that genetic factors have an important role in its pathogenesis, but no single major locus or gene for VUR has yet been identified and most researchers now acknowledge that VUR is genetically heterogeneous. Improvements in genome-scan techniques and continuously increasing knowledge of the genetic basis of VUR should help us to further understand its pathogenesis.

2011-10-01T00:00:00Z Davey, Norman E. Haslam, Niall J. Shields, Denis C. Edwards, Richard J. http://hdl.handle.net/10197/3180 2013-01-14T17:18:17Z 2011-05-26T00:00:00Z

SLiMSearch 2.0 : biological context for short linear motifs in proteins Davey, Norman E.; Haslam, Niall J.; Shields, Denis C.; Edwards, Richard J. Short, linear motifs (SLiMs) play a critical role in many biological processes. The SLiMSearch 2.0 (Short, Linear Motif Search) web server allows researchers to identify occurrences of a user-defined SLiM in a proteome, using conservation and protein disorder context statistics to rank occurrences. User-friendly output and visualizations of motif context allow the user to quickly gain insight into the validity of a putatively functional motif occurrence. For each motif occurrence, overlapping UniProt features and annotated SLiMs are displayed. Visualization also includes annotated multiple sequence alignments surrounding each occurrence, showing conservation and protein disorder statistics in addition to known and predicted SLiMs, protein domains and known post-translational modifications. In addition, enrichment of Gene Ontology terms and protein interaction partners are provided as indicators of possible motif function. All web server results are available for download. Users can search motifs against the human proteome or a subset thereof defined by Uniprot accession numbers or GO term. The SLiMSearch server is available at: http://bioware.ucd.ie/slimsearch2.html.

2011-05-26T00:00:00Z Duffy, Fergal J. Verniere, Mélanie Devocelle, Marc Bernard, Elise Shields, Denis C. Chubb, Anthony J. http://hdl.handle.net/10197/2987 2012-03-20T17:05:11Z 2011-03-24T00:00:00Z

CycloPs : generating virtual libraries of cyclized and constrained peptides including nonnatural amino acids Duffy, Fergal J.; Verniere, Mélanie; Devocelle, Marc; Bernard, Elise; Shields, Denis C.; Chubb, Anthony J. We introduce CycloPs, software for the generation of virtual libraries of constrained peptides including natural and nonnatural commercially available amino acids. The software is written in the cross-platform Python programming language, and features include generating virtual libraries in one-dimensional SMILES and three-dimensional SDF formats, suitable for virtual screening. The stand-alone software is capable of filtering the virtual libraries using empirical measurements, including peptide synthesizability by standard peptide synthesis techniques, stability, and the druglike properties of the peptide. The software and accompanying Web interface is designed to enable the rapid generation of large, structurally diverse, synthesizable virtual libraries of constrained peptides quickly and conveniently, for use in virtual screening experiments. The stand-alone software, and the Web interface for evaluating these empirical properties of a single peptide, are available at http://bioware.ucd.ie.

2011-03-24T00:00:00Z