• QTrim: a novel tool for the quality trimming of sequence reads generated using the Roche/454 sequencing platform

      Shrestha, Ram K; Lubinsky, Baruch; Bansode, Vijay B; Moinz, Mónica BJ; McCormack, Grace P; Travers, Simon A (2014-01-30)
      Abstract Background Many high throughput sequencing (HTS) approaches, such as the Roche/454 platform, produce sequences in which the quality of the sequence (as measured by a Phred-like quality scores) decreases linearly across a sequence read. Undertaking quality trimming of this data is essential to enable confidence in the results of subsequent downstream analysis. Here, we have developed a novel, highly sensitive and accurate approach (QTrim) for the quality trimming of sequence reads generated using the Roche/454 sequencing platform (or any platform with long reads that outputs Phred-like quality scores). Results The performance of QTrim was evaluated against all other available quality trimming approaches on both poor and high quality 454 sequence data. In all cases, QTrim appears to perform equally as well as the best other approach (PRINSEQ) with these two methods significantly outperforming all other methods. Further analysis of the trimmed data revealed that the novel trimming approach implemented in QTrim ensures that the prevalence of low quality bases in the resulting trimmed data is substantially lower than PRINSEQ or any of the other approaches tested. Conclusions QTrim is a novel, highly sensitive and accurate algorithm for the quality trimming of Roche/454 sequence reads. It is implemented both as an executable program that can be integrated with standalone sequence analysis pipelines and as a web-based application to enable individuals with little or no bioinformatics experience to quality trim their sequence data.
    • A qualitative systematic review of studies using the normalization process theory to research implementation processes

      McEvoy, Rachel; Ballini, Luciana; Maltoni, Susanna; O’Donnell, Catherine A; Mair, Frances S; MacFarlane, Anne (2014-01-02)
      Abstract Background There is a well-recognized need for greater use of theory to address research translational gaps. Normalization Process Theory (NPT) provides a set of sociological tools to understand and explain the social processes through which new or modified practices of thinking, enacting, and organizing work are implemented, embedded, and integrated in healthcare and other organizational settings. This review of NPT offers readers the opportunity to observe how, and in what areas, a particular theoretical approach to implementation is being used. In this article we review the literature on NPT in order to understand what interventions NPT is being used to analyze, how NPT is being operationalized, and the reported benefits, if any, of using NPT. Methods Using a framework analysis approach, we conducted a qualitative systematic review of peer-reviewed literature using NPT. We searched 12 electronic databases and all citations linked to six key NPT development papers. Grey literature/unpublished studies were not sought. Limitations of English language, healthcare setting and year of publication 2006 to June 2012 were set. Results Twenty-nine articles met the inclusion criteria; in the main, NPT is being applied to qualitatively analyze a diverse range of complex interventions, many beyond its original field of e-health and telehealth. The NPT constructs have high stability across settings and, notwithstanding challenges in applying NPT in terms of managing overlaps between constructs, there is evidence that it is a beneficial heuristic device to explain and guide implementation processes. Conclusions NPT offers a generalizable framework that can be applied across contexts with opportunities for incremental knowledge gain over time and an explicit framework for analysis, which can explain and potentially shape implementation processes. This is the first review of NPT in use and it generates an impetus for further and extended use of NPT. We recommend that in future NPT research, authors should explicate their rationale for choosing NPT as their theoretical framework and, where possible, involve multiple stakeholders including service users to enable analysis of implementation from a range of perspectives.
    • A quality framework for health services developed through an inclusive approach

      Markham, Trish; Butler, Michelle; McNamara, Martin; Health Service Executive (HSE) (Journal of Nursing Education and Practice, 2015-03-18)
    • A quality improvement initiative in community mental health in the Republic of Ireland

      Murphy, Lorraine; Wells, John Stephen; Lachman, Peter; Bergin, Michael; Health Service Executive (HSE), Waterford Institute of Technology(WIT), Royal College of Physicians Ireland (RCPI) (Insight Medical Publishing (Imed), 2015)
    • Quality of life of palliative chemotherapy naive patients with advanced adenocarcinoma of the stomach or esophagogastric junction treated with irinotecan combined with 5-fluorouracil and folinic acid: results of a randomised phase III trial.

      Curran, Desmond; Pozzo, Carmelo; Zaluski, Jerzy; Dank, Magdalena; Barone, Carlo; Valvere, Vahur; Yalcin, Suayib; Peschel, Christian; Wenczl, Miklós; Goker, Erdem; et al. (2009-09)
      PURPOSE: The quality of life (QL) of advanced gastric cancer patients receiving irinotecan, folinic acid and 5-fluorouracil (5-FU) (IF arm) or cisplatin with 5-FU (CF arm) is presented. METHODS: Patients with measurable or evaluable advanced gastric cancer received IF weekly for 6/7 weeks or CF q4 weeks. QL was assessed using the EORTC QLQ-C30 at baseline, subsequently every 8 weeks until progression and thereafter every 3 months until death. The QL data were analysed using several statistical methods including summary measures and pattern-mixture modelling. RESULTS: A total of 333 patients were randomised and treated (IF 170, CF 163). The time-to-progression for IF and CF was 5.0 and 4.2 months (P = 0.088), respectively. The overall compliance rates for QL questionnaire completion were 60 and 56% in the IF and CF arms, respectively. Significant treatment differences were observed for the physical functioning scale (P = 0.024), nausea\vomiting (P = 0.001) and EQ-5D thermometer (P = 0.020) in favour of the IF treatment arm. CONCLUSION: There was a trend in favour of IF over CF in time-to-progression. The IF group also demonstrated a better safety profile than CF and a better QL on a number of multi-item scales, suggesting that IF offers an alternative first-line platinum-free treatment option for advanced gastric cancer.
    • Quantifying size-dependent interactions between fluorescently labeled polystyrene nanoparticles and mammalian cells

      Varela, Juan A; Bexiga, Mariana G; Åberg, Christoffer; Simpson, Jeremy C; Dawson, Kenneth A (2012-09-24)
      Abstract Background Nanoparticles (NPs) are currently used in a wide variety of fields such as technology, medicine and industry. Due to the novelty of these applications and to ensure their success, a precise characterization of the interactions between NPs and cells is essential. Findings The current study explores the uptake of polystyrene NPs by 1321N1 human astrocytoma and A549 human lung carcinoma cell lines. In this work we show for the first time a comparison of the uptake rates of fluorescently labeled carboxylated polystyrene (PS) NPs of different sizes (20, 40 and 100 nm) in two different cell types, keeping the number of NPs per unit volume constant for all sizes. We propose a reliable methodology to control the dose of fluorescently labeled NPs, by counting individual NPs using automated particle detection from 3D confocal microscopy images. The possibility of detecting individual NPs also allowed us to calculate the size of each nanoparticle and compare the fluorescence of single NPs across different sizes, thereby providing a robust platform for normalization of NP internalization experiments as measured by flow cytometry. Conclusions Our findings show that 40 nm NPs are internalized faster than 20 nm or 100 nm particles in both cell lines studied, suggesting that there is a privileged size gap in which the internalization of NPs is higher.
    • Quantifying uncertainty, variability and likelihood for ordinary differential equation models

      Weisse, Andrea Y; Middleton, Richard H; Huisinga, Wilhelm (2010-10-28)
      Abstract Background In many applications, ordinary differential equation (ODE) models are subject to uncertainty or variability in initial conditions and parameters. Both, uncertainty and variability can be quantified in terms of a probability density function on the state and parameter space. Results The partial differential equation that describes the evolution of this probability density function has a form that is particularly amenable to application of the well-known method of characteristics. The value of the density at some point in time is directly accessible by the solution of the original ODE extended by a single extra dimension (for the value of the density). This leads to simple methods for studying uncertainty, variability and likelihood, with significant advantages over more traditional Monte Carlo and related approaches especially when studying regions with low probability. Conclusions While such approaches based on the method of characteristics are common practice in other disciplines, their advantages for the study of biological systems have so far remained unrecognized. Several examples illustrate performance and accuracy of the approach and its limitations.
    • Quantitative examination of the bone health status of older adults with intellectual and developmental disability in Ireland: a cross-sectional nationwide study.

      Burke, Éilish; Carroll, Rachael; O'Dwyer, Máire; Walsh, James Bernard; McCallion, Philip; McCarron, Mary (BMJ Open, 2019-04-15)
    • A quest for health: Creating a world of difference in Clondalkin

      Cosgrove, Sharon; Clondalkin Partnership (Clondalkin Partnership, 2003-04)
    • RACK(1) to the future - a historical perspective

      Ron, Dorit; Adams, David R; Baillie, George S; Long, Aideen; O’Connor, Rosemary; Kiely, Patrick A (2013-08-01)
      This perspective summarises the first and long overdue RACK1 meeting held at the University of Limerick, Ireland, May 2013, in which RACK1’s role in the immune system, the heart and the brain were discussed and its contribution to disease states such as cancer, cardiac hypertrophy and addiction were described. RACK1 is a scaffolding protein and a member of the WD repeat family of proteins. These proteins have a unique architectural assembly that facilitates protein anchoring and the stabilisation of protein activity. A large body of evidence is accumulating which is helping to define the versatile role of RACK1 in assembling and dismantling complex signaling pathways from the cell membrane to the nucleus in health and disease. In this commentary, we first provide a historical perspective on RACK1. We also address many of the pertinent and topical questions about this protein such as its role in transcription, epigenetics and translation, its cytoskeletal contribution and the merits of targeting RACK1 in disease.
    • RACK1, A Multifaceted Scaffolding Protein: Structure and Function

      Adams, David R; Ron, Dorit; Kiely, Patrick A (2011-10-06)
      Abstract The Receptor for Activated C Kinase 1 (RACK1) is a member of the tryptophan-aspartate repeat (WD-repeat) family of proteins and shares significant homology to the β subunit of G-proteins (Gβ). RACK1 adopts a seven-bladed β-propeller structure which facilitates protein binding. RACK1 has a significant role to play in shuttling proteins around the cell, anchoring proteins at particular locations and in stabilising protein activity. It interacts with the ribosomal machinery, with several cell surface receptors and with proteins in the nucleus. As a result, RACK1 is a key mediator of various pathways and contributes to numerous aspects of cellular function. Here, we discuss RACK1 gene and structure and its role in specific signaling pathways, and address how posttranslational modifications facilitate subcellular location and translocation of RACK1. This review condenses several recent studies suggesting a role for RACK1 in physiological processes such as development, cell migration, central nervous system (CN) function and circadian rhythm as well as reviewing the role of RACK1 in disease.
    • A randomised controlled trial of a lengthened and multi-disciplinary consultation model in a socially deprived community: a study protocol.

      Whitford, David L; Chan, Wai-Sun; Family and Community Medicine, Royal College of Surgeons in Ireland-Medical University of Bahrain, Adliya, Kingdom of Bahrain. dwhitford@rcsi-mub.com (2007)
      BACKGROUND: There has been little development of the general practice consultation over the years, and many aspects of the present consultation do not serve communities with multiple health and social problems well. Many of the problems presenting to general practitioners in socio-economically disadvantaged areas are not amenable to a purely medical solution, and would particularly benefit from a multidisciplinary approach. Socio-economic deprivation is also associated with those very factors (more psychosocial problems, greater need for health promotion, more chronic diseases, more need for patient enablement) that longer consultations have been shown to address. This paper describes our study protocol, which aims to evaluate whether a lengthened multidisciplinary primary care team consultation with families in a socially deprived area can improve the psychological health of mothers in the families. METHODS/DESIGN: In a randomised controlled trial, families with a history of social problems, substance misuse or depression are randomly allocated to an intervention or control group. The study is based in three general practices in a highly deprived area of North Dublin. Primary health care teams will be trained in conducting a multidisciplinary lengthened consultation. Families in the intervention group will participate in the new style multidisciplinary consultation. Outcomes of families receiving the intervention will be compared to the control group who will receive only usual general practitioner care. The primary outcome is the psychological health of mothers of the families and secondary outcomes include general health status, quality of life measures and health service usage. DISCUSSION: The main aim of this study is to evaluate the effectiveness of a lengthened multidisciplinary team consultation in primary care. The embedded nature of this study in general practices in a highly deprived area ensures generalisability to other deprived communities, but more particularly it promises relevance to primary care. TRIAL REGISTRATION: Current Controlled Trials ISRCTN70578736.
    • A randomised controlled trial of an exercise plus behaviour change intervention in people with multiple sclerosis: the step it up study protocol

      Coote, Susan; Gallagher, Stephen; Msetfi, Rachel; Larkin, Aidan; Newell, John; Motl, Robert W; Hayes, Sara (2014-12-21)
    • Randomized controlled trial comparing telephone and mail follow-up for recruitment of participants into a clinical trial of colorectal cancer screening

      Wong, Arthur D; Kirby, John; Guyatt, Gordon H; Moayyedi, Paul; Vora, Parag; You, John J (2013-02-11)
      Abstract Background Investigators often face challenges when recruiting participants into randomized controlled trials (RCTs). Some data suggest that telephone reminders may lead to greater participant enrollment. Methods Patients aged 50 to 70 years from family practice rosters were initially mailed invitations to participate in an RCT of colorectal cancer screening. Patients who did not respond were randomly allocated to follow-up invitations by either telephone or mail four weeks after the initial invitation. The primary outcome was attendance for eligibility screening with the study nurse. Results After mailing invitations to 1,348 patients, 104 patients were initially enrolled in the RCT of colon cancer screening. Of 952 patients who did not respond to the initial mailed invitation, we randomly allocated 480 to follow-up invitation by telephone and 472 to follow-up invitation by mail. Attendance for eligibility screening with the study nurse was more frequent when non-responders were followed-up by telephone (84/480, 17.5%) than by mail (43/472, 9.1%) (relative risk (RR) 1.92, 95% confidence interval (CI) 1.36 to 2.71, P < 0.001). Enrollment into the RCT was also greater among patients followed-up by telephone (59/480, 12.3%) compared to those followed-up by mail (35/472, 7.4%) (RR 1.66, 95% CI 1.11 to 2.47, P=0.01). Conclusions Telephone-based follow-up results in greater enrollment compared to a mail-based method. Our findings should be of interest to investigators conducting RCTs, particularly trials of screening interventions involving asymptomatic participants for which volunteer participation may be challenging. Trial registration Clinicaltrials.gov NCT00865527
    • A randomized controlled trial of the computerized CBT programme, MoodGYM, for public mental health service users waiting for interventions

      Twomey, Conal; O'Reilly, Gary; Byrne, Michael; Bury, Matthew; White, Aisling; Kissane, Sheila; McMahon, Aisling; Clancy, Nicola; School of Psychology, University College Dublin, Ireland (British Journal of Clinical Psychology, 2014-05)
    • Randomized controlled trial to evaluate tooth stain reduction with nicotine replacement gum during a smoking cessation program

      Whelton, Helen; Kingston, Rose; O’Mullane, Denis; Nilsson, Frederick (2012-06-13)
      AbstractBackgroundIn addition to its general and periodontal health effects smoking causes tooth staining. Smoking cessation support interventions with an added stain removal or tooth whitening effect may increase motivation to quit smoking. Oral health professionals are well placed to provide smoking cessation advice and support to patients. The objective of the present study was to evaluate the effect of Nicorette® Freshmint Gum used in a smoking cessation programme administered in a dental setting, on extrinsic stain and tooth shade among smokers.MethodsAn evaluator-blinded, randomized, 12-week parallel-group controlled trial was conducted among 200 daily smokers motivated to quit smoking. Participants were randomised to use either the Nicorette® Freshmint Gum or Nicorette® Microtab (tablet). Tooth staining and shade were rated using the modified Lobene Stain Index and the Vita® Shade Guide at baseline, weeks 2, 6 and 12. To maintain consistency with other whitening studies, the primary end-point was the mean change in stain index between baseline and week 6. Secondary variables included changes in stain measurements and tooth shade at the other time points the number of gums or tablets used per day and throughout the trial period; and the number of cigarettes smoked per day. Treatments were compared using analysis of covariance (ANCOVA), using treatment and nicotine dependence as factors and the corresponding baseline measurement as a covariate. Each comparison (modified intention-to-treat) was tested at the 0.05 level, two-sided. Within-treatment changes from baseline were compared using a paired t-test.ResultsAt week 6, the gum-group experienced a reduction in mean stain scores whilst the tablet-group experienced an increase with mean changes of -0.14 and +0.12 respectively, (p = 0.005, ANCOVA). The change in mean tooth shade scores was statistically significantly greater in the gum-group than in the tablet group at 2 (p = 0.015), 6 (p = 0.011) and 12 weeks (p = 0.003) with greater lightening in the gum-group at each examination period.ConclusionThese results support the efficacy of the tested nicotine replacement gum in stain reduction and shade lightening. These findings may help dentists to motivate those wishing to quit smoking using a nicotine replacement gum.Trial registrationNCT01440985
    • Rapamycin regulates autophagy and cell adhesion in induced pluripotent stem cells

      Sotthibundhu, Areechun; McDonagh, Katya; von Kriegsheim, Alexander; Garcia-Munoz, Amaya; Klawiter, Agnieszka; Thompson, Kerry; Chauhan, Kapil D; Krawczyk, Janusz; McInerney, Veronica; Dockery, Peter; et al. (2016-11-15)
      Abstract Background Cellular reprogramming is a stressful process, which requires cells to engulf somatic features and produce and maintain stemness machineries. Autophagy is a process to degrade unwanted proteins and is required for the derivation of induced pluripotent stem cells (iPSCs). However, the role of autophagy during iPSC maintenance remains undefined. Methods Human iPSCs were investigated by microscopy, immunofluorescence, and immunoblotting to detect autophagy machinery. Cells were treated with rapamycin to activate autophagy and with bafilomycin to block autophagy during iPSC maintenance. High concentrations of rapamycin treatment unexpectedly resulted in spontaneous formation of round floating spheres of uniform size, which were analyzed for differentiation into three germ layers. Mass spectrometry was deployed to reveal altered protein expression and pathways associated with rapamycin treatment. Results We demonstrate that human iPSCs express high basal levels of autophagy, including key components of APMKα, ULK1/2, BECLIN-1, ATG13, ATG101, ATG12, ATG3, ATG5, and LC3B. Block of autophagy by bafilomycin induces iPSC death and rapamycin attenuates the bafilomycin effect. Rapamycin treatment upregulates autophagy in iPSCs in a dose/time-dependent manner. High concentration of rapamycin reduces NANOG expression and induces spontaneous formation of round and uniformly sized embryoid bodies (EBs) with accelerated differentiation into three germ layers. Mass spectrometry analysis identifies actin cytoskeleton and adherens junctions as the major targets of rapamycin in mediating iPSC detachment and differentiation. Conclusions High levels of basal autophagy activity are present during iPSC derivation and maintenance. Rapamycin alters expression of actin cytoskeleton and adherens junctions, induces uniform EB formation, and accelerates differentiation. IPSCs are sensitive to enzyme dissociation and require a lengthy differentiation time. The shape and size of EBs also play a role in the heterogeneity of end cell products. This research therefore highlights the potential of rapamycin in producing uniform EBs and in shortening iPSC differentiation duration.
    • Rapamycin regulates autophagy and cell adhesion in induced pluripotent stem cells

      Sotthibundhu, Areechun; McDonagh, Katya; von Kriegsheim, Alexander; Garcia-Munoz, Amaya; Klawiter, Agnieszka; Thompson, Kerry; Chauhan, Kapil D; Krawczyk, Janusz; McInerney, Veronica; Dockery, Peter; et al. (2016-11-15)
      Abstract Background Cellular reprogramming is a stressful process, which requires cells to engulf somatic features and produce and maintain stemness machineries. Autophagy is a process to degrade unwanted proteins and is required for the derivation of induced pluripotent stem cells (iPSCs). However, the role of autophagy during iPSC maintenance remains undefined. Methods Human iPSCs were investigated by microscopy, immunofluorescence, and immunoblotting to detect autophagy machinery. Cells were treated with rapamycin to activate autophagy and with bafilomycin to block autophagy during iPSC maintenance. High concentrations of rapamycin treatment unexpectedly resulted in spontaneous formation of round floating spheres of uniform size, which were analyzed for differentiation into three germ layers. Mass spectrometry was deployed to reveal altered protein expression and pathways associated with rapamycin treatment. Results We demonstrate that human iPSCs express high basal levels of autophagy, including key components of APMKα, ULK1/2, BECLIN-1, ATG13, ATG101, ATG12, ATG3, ATG5, and LC3B. Block of autophagy by bafilomycin induces iPSC death and rapamycin attenuates the bafilomycin effect. Rapamycin treatment upregulates autophagy in iPSCs in a dose/time-dependent manner. High concentration of rapamycin reduces NANOG expression and induces spontaneous formation of round and uniformly sized embryoid bodies (EBs) with accelerated differentiation into three germ layers. Mass spectrometry analysis identifies actin cytoskeleton and adherens junctions as the major targets of rapamycin in mediating iPSC detachment and differentiation. Conclusions High levels of basal autophagy activity are present during iPSC derivation and maintenance. Rapamycin alters expression of actin cytoskeleton and adherens junctions, induces uniform EB formation, and accelerates differentiation. IPSCs are sensitive to enzyme dissociation and require a lengthy differentiation time. The shape and size of EBs also play a role in the heterogeneity of end cell products. This research therefore highlights the potential of rapamycin in producing uniform EBs and in shortening iPSC differentiation duration.
    • A rapid evidence review on the effectiveness of institutional health partnerships

      Kelly, Ema; Doyle, Vicki; Weakliam, David; Schönemann, Yvonne (2015-12-14)
      Abstract Background Institutional Health Partnerships are long-term, institution to institution partnerships between high income and low and middle income countries which seek to build capacity and strengthen health institutions in order to improve health service delivery and outcomes. Funding for Institutional Health Partnerships has increased in recent years. This paper outlines a rapid evidence review on the effectiveness of this modality. Methods A rapid evidence review of published and grey literature was conducted. Content relating to the effectiveness of working in partnership and methods and frameworks used were extracted and analysed. The results of this analysis were used to structure a discussion regarding the next steps to strengthen the evidence base for the effectiveness of institutional health partnerships. Results The evidence review, including citation mapping, returned 27 published papers and 17 grey literature documents that met all of the inclusion criteria. Most of the literature did not meet the high standards of formal academic rigour and there was no original research amongst this literature that specifically addressed the effectiveness of institutional health partnerships. This was not surprising given institutional health partnerships do not lend themselves easily to case control studies and randomised control trials due to their high level of diversity and operation in complex social systems. There was, however, a body of practice based knowledge and experience. Conclusions Evidence for the effectiveness of Institutional Health Partnerships is thin both in terms of quantity and academic rigour. There is a need to better define and differentiate Institutional Health Partnerships in order to measure and compare effectiveness across such a diverse group. Effectiveness needs to be measured at the level of individual partnerships, the bodies that facilitate partnership programmes and the level of health service delivery. There is a need to develop indicators and frameworks that specifically address the benefits and values of partnership working and how these relate to effectiveness. These indicators need to be content neutral of specific interventions which are already measured through routine project monitoring and evaluation. This will allow the development of methodological pathways to assess the effectiveness of institutional health partnerships. Until more primary research is conducted or published there is little benefit in further systematic reviews.