• Living with a brother who has an Autism Spectrum Disorder: a sister's perspective

      Connell, Zara O.; Halloran, Maeve O.; Doody, Owen (British Journal of Learning Disabilities, 2014-09)
    • Long acting reversible contraception

      Daly, Miriam (Nursing in General Practice, 2014-05)
    • Long-term exposure of CdTe quantum dots on PC12 cellular activity and the determination of optimum non-toxic concentrations for biological use

      Prasad, Babu R; Nikolskaya, Natalia; Connolly, David; Smith, Terry J; Byrne, Stephen J; Gerard, Valerie A; Gun'ko, Yurii K; Rochev, Yury (2010-03-25)
      Abstract Background The unique and tuneable photonic properties of Quantum Dots (QDs) have made them potentially useful tools for imaging biological entities. However, QDs though attractive diagnostic and therapeutic tools, have a major disadvantage due to their inherent cytotoxic nature. The cellular interaction, uptake and resultant toxic influence of CdTe QDs (gelatinised and non-gelatinised Thioglycolic acid (TGA) capped) have been investigated with pheochromocytoma 12 (PC12) cells. In conjunction to their analysis by confocal microscopy, the QD - cell interplay was explored as the QD concentrations were varied over extended (up to 72 hours) co-incubation times. Coupled to this investigation, cell viability, DNA quantification and cell proliferation assays were also performed to compare and contrast the various factors leading to cell stress and ultimately death. Results Thioglycolic acid (TGA) stabilised CdTe QDs (gel and non - gel) were co-incubated with PC12 cells and investigated as to how their presence influenced cell behaviour and function. Cell morphology was analysed as the QD concentrations were varied over co-incubations up to 72 hours. The QDs were found to be excellent fluorophores, illuminating the cytoplasm of the cells and no deleterious effects were witnessed at concentrations of ~10-9 M. Three assays were utilised to probe how individual cell functions (viability, DNA quantification and proliferation) were affected by the presence of the QDs at various concentrations and incubation times. Cell response was found to not only be concentration dependant but also influenced by the surface environment of the QDs. Gelatine capping on the surface acts as a barrier towards the leaking of toxic atoms, thus reducing the negative impact of the QDs. Conclusion This study has shown that under the correct conditions, QDs can be routinely used for the imaging of PC12 cells with minimal adverse effects. We have found that PC12 cells are highly susceptible to an increased concentration range of the QDs, while the gelatine coating acts as a barrier towards enhanced toxicity at higher QD concentrations.
    • Long-term risk of stroke after transient ischaemic attack: a hospital-based validation of the ABCD2 rule

      Galvin, Rose; Atanassova, Penka A; Motterlini, Nicola; Fahey, Tom; Dimitrov, Borislav D (2014-05-04)
      Abstract Background The ABCD2 clinical prediction rule is a seven point summation of clinical factors independently predictive of stroke risk. The purpose of this cohort study is to validate the ABCD2 rule in a Bulgarian hospital up to three years after TIA. Methods All consecutive admissions to an emergency department with symptoms of a first TIA were included. Baseline data and clinical examinations including the ABCD2 scores were documented by neurologists. Discrimination and calibration performance was examined using ABCD2 cut-off scores of ≥3, ≥4 and ≥5 points, consistent with the international guidelines. The Hosmer-Lemeshow test was used to examine calibration between the observed and expected outcomes as predicted by ABCD2 score within the logistic regression analysis. Results Eighty-nine patients were enrolled to the study with a mean age of 63 years (+/- 12 years). Fifty-nine percent (n = 53) of the study population was male. Seven strokes (7 · 8%) occurred within the first year and six further strokes within the three-year follow-up period. There was no incident of stroke within the first 90 days after TIA. The rule demonstrated good predictive (OR = 1 · 58, 95% CI 1 · 09-2 · 29) and discriminative performance (AUCROC = 0 · 72, 95% CI 0 · 58-0 · 86), as well as a moderate calibration performance at three years. Conclusion This validation of the ABCD2 rule in a Bulgarian hospital demonstrates that the rule has good predictive and discriminative performance at three years. The ABCD2 is quick to administer and may serve as a useful tool to assist clinicians in the long-term management of individuals with TIA.
    • Long-term survey of a syringe-dispensing machine needle exchange program: answering public concerns

      Duplessy, Catherine; Reynaud, Emmanuel G (2014-05-22)
      Abstract Background Syringe-dispensing machines (SDM) provide syringes at any time even to hard-to-reach injecting drug users (IDUs). They represent an important harm reduction strategy in large populated urban areas such as Paris. We analyzed the performance of one of the world's largest SDM schemes based in Paris over 12 years to understand its efficiency and its limitations, to answer public and stakeholder concerns and optimize its outputs. Methods Parisian syringe dispensing and exchange machines were monitored as well as their sharp disposals and associated bins over a 12-year period. Moreover, mechanical counting devices were installed on specific syringe-dispensing/exchange machines to record the characteristics of the exchange process. Results Distribution and needle exchange have risen steadily by 202% for the distribution and 2,000% for syringe recovery even without a coin counterpart. However, 2 machines out of 34 generate 50% of the total activity of the scheme. It takes 14 s for an IDU to collect a syringe, while the average user takes 3.76 syringes per session 20 min apart. Interestingly, collection time stops early in the evening (19 h) for the entire night. Conclusions SDMs had an increasing distribution role during daytime as part of the harm reduction strategy in Paris with efficient recycling capacities of used syringes and a limited number of kits collected by IDU. Using counting devices to monitor Syringe Exchange Programs (SEPs) is a very helpful tool to optimize use and answer public and stakeholder concerns.
    • Longitudinal stability of the diurnal rhythm of intraocular pressure in subjects with healthy eyes, ocular hypertension and pigment dispersion syndrome

      Huchzermeyer, Cord; Reulbach, Udo; Horn, Folkert; Lämmer, Robert; Mardin, Christian Y; Jünemann, Anselm GM (2014-10-15)
      Abstract Background The diurnal fluctuation of intraocular pressure may be relevant in glaucoma. The aim of this study was to find out whether the timing of diurnal fluctuation is stable over the years. Methods Long-term IOP data from the Erlangen Glaucoma Registry, consisting of several annual extended diurnal IOP profiles for each patient, was retrospectively analyzed. Normal subjects, patients with ocular hypertension and with pigment dispersion syndrome were included because these subjects had not been treated with antiglaucomatous medications at the time of data acquisition. A cosine curve was fitted to the IOP data and the stability of individual rhythms over the years was tested using the Rayleigh test. To compare the peak times among groups, means were calculated only from subjects with a significant Rayleigh test. Results Of the fifty-two eligible subjects, a total of 364 extended diurnal IOP profiles measured in a sitting position had been collected over a period of 114 ± 39 months. The Rayleigh test indicated intraindividual stability of phase timing only in 19 subjects (36%). In subjects with pigment dispersions syndrome, peak IOP occurred on average two hours and seven minutes later during the day compared with subjects without this condition (p = 0.05). Conclusions Fitting of cosine curves to the clinical IOP profiles was generally feasible, although careful interpretation is warranted due to lack of measurements in supine position and between midnight and 7 am. The interesting observation of a phase lag in eyes with pigment dispersion syndrome warrants confirmation and exploration in future prospective studies. The analysis of the IOP data showed no stable individual rhythm in the long term in a majority of patients.
    • A longitudinal study of tooth erosion in adolescents indicates that this may be a progressive phenomenon, at least on some tooth sites.

      Nunn, June; Special Care Dentistry, Public and Child Dental Health, Dublin Dental School and Hospital, Lincoln Place, Dublin 2, Ireland. (2009-12)
    • Longitudinal testing of hippocampal plasticity reveals the onset and maintenance of endogenous human Aß-induced synaptic dysfunction in individual freely behaving pre-plaque transgenic rats: rapid reversal by anti-Aß agents

      Qi, Yingjie; Klyubin, Igor; Harney, Sarah C; Hu, NengWei; Cullen, William K; Grant, Marianne K; Steffen, Julia; Wilson, Edward N; Do Carmo, Sonia; Remy, Stefan; et al. (2014-12-24)
      Abstract Long before synaptic loss occurs in Alzheimer’s disease significant harbingers of disease may be detected at the functional level. Here we examined if synaptic long-term potentiation is selectively disrupted prior to extracellular deposition of Aß in a very complete model of Alzheimer’s disease amyloidosis, the McGill-R-Thy1-APP transgenic rat. Longitudinal studies in freely behaving animals revealed an age-dependent, relatively rapid-onset and persistent inhibition of long-term potentiation without a change in baseline synaptic transmission in the CA1 area of the hippocampus. Thus the ability of a standard 200 Hz conditioning protocol to induce significant NMDA receptor-dependent short- and long-term potentiation was lost at about 3.5 months of age and this deficit persisted for at least another 2–3 months, when plaques start to appear. Consistent with in vitro evidence for a causal role of a selective reduction in NMDA receptor-mediated synaptic currents, the deficit in synaptic plasticity in vivo was associated with a reduction in the synaptic burst response to the conditioning stimulation and was overcome using stronger 400 Hz stimulation. Moreover, intracerebroventricular treatment for 3 days with an N-terminally directed monoclonal anti- human Aß antibody, McSA1, transiently reversed the impairment of synaptic plasticity. Similar brief treatment with the BACE1 inhibitor LY2886721 or the γ-secretase inhibitor MRK-560 was found to have a comparable short-lived ameliorative effect when tracked in individual rats. These findings provide strong evidence that endogenously generated human Aß selectively disrupts the induction of long-term potentiation in a manner that enables potential therapeutic options to be assessed longitudinally at the pre-plaque stage of Alzheimer’s disease amyloidosis.
    • Looked after children in dublin and their mental health needs

      McNicholas, F; O'Connor, N; Bandyopadhyay, G (Irish Medical Journal, 2011-04)
    • Low-intensity internet-delivered treatment for generalized anxiety symptoms in routine care: protocol for a randomized controlled trial

      Richards, Derek; Timulak, Ladislav; Doherty, Gavin; Sharry, John; McLoughlin, Orla; Rashleigh, Chuck; Colla, Amy; Joyce, Ciara (2014-04-27)
      Abstract Background Worldwide prevalence of generalized anxiety disorder (GAD) is considered high; in Europe lifetime prevalence has been estimated at 4.3 to 5.9%. High levels of anxiety disorders have been reported in university students, affecting 25 to 30% of the population. Young adults are some of the most vulnerable for the onset of mental health disorders and any stressors may act as a catalyst for their onset. The absence of resources can often mean that many do not seek treatment. Other factors that impede access to resources include such things as a lack of trained professionals, personal stigma, and waiting lists. Anxiety disorders can be treated successfully; indeed brief forms of cognitive-behavior therapy have been recommended. One potential avenue for research and development is that of delivering low-intensity interventions online for students with GAD. Therefore, the current study seeks to investigate the potential effectiveness for a low-intensity online CBT-based treatment for GAD in a service-based setting; implemented as one step in a stepped-care model. Methods/Design The research is a service-based effectiveness study utilizing a randomized waiting-list controlled design. The active intervention consists of six weekly modules of online CBT. Participants are assigned a supporter who provides weekly post-session feedback on progress and exercises. Participants will complete the GAD-7 as the primary outcome measure. Secondary outcomes include pathological worry, depression and measures of well-being. At three-months follow-up data will be collected using the GAD-7, BDI-II, PSWQ, ED-Q5 and WSAS. Post-session data will be collected on significant in-session events in treatment (HAT). A satisfaction with treatment measure will be administered post-treatment (SAT). Discussion The study will be a contribution to the potential for a low-intensity internet-delivered program implemented in a service-based setting; implemented as one step in a stepped-care model. The study will be a contribution to the already established work in online treatments for anxiety worldwide. The study will assess the utility of an innovative digital health solution (SilverCloud) to deliver such interventions. Trial registration Current Controlled Trials ISRCTN16303842.
    • LPS-induced release of IL-6 from glia modulates production of IL-1beta in a JAK2-dependent manner

      Minogue, Aedín M; Barrett, James P; Lynch, Marina A (2012-06-14)
      AbstractBackgroundCompelling evidence has implicated neuroinflammation in the pathogenesis of a number of neurodegenerative conditions. Chronic activation of both astrocytes and microglia leads to excessive secretion of proinflammatory molecules such as TNFα, IL-6 and IL-1β with potentially deleterious consequences for neuronal viability. Many signaling pathways involving the mitogen-activated protein kinases (MAPKs), nuclear factor κB (NFκB) complex and the Janus kinases (JAKs)/signal transducers and activators of transcription (STAT)-1 have been implicated in the secretion of proinflammatory cytokines from glia. We sought to identify signaling kinases responsible for cytokine production and to delineate the complex interactions which govern time-related responses to lipopolysaccharide (LPS).MethodsWe examined the time-related changes in certain signaling events and the release of proinflammatory cytokines from LPS-stimulated co-cultures of astrocytes and microglia isolated from neonatal rats.ResultsTNFα was detected in the supernatant approximately 1 to 2 hours after LPS treatment while IL-1β and IL-6 were detected after 2 to 3 and 4 to 6 hours, respectively. Interestingly, activation of NFκB signaling preceded release of all cytokines while phosphorylation of STAT1 was evident only after 2 hours, indicating that activation of JAK/STAT may be important in the up-regulation of IL-6 production. Additionally, incubation of glia with TNFα induced both phosphorylation of JAK2 and STAT1 and the interaction of JAK2 with the TNFα receptor (TNFR1). Co-treatment of glia with LPS and recombinant IL-6 protein attenuated the LPS-induced release of both TNFα and IL-1β while potentiating the effect of LPS on suppressor of cytokine signaling (SOCS)3 expression and IL-10 release.ConclusionsThese data indicate that TNFα may regulate IL-6 production through activation of JAK/STAT signaling and that the subsequent production of IL-6 may impact on the release of TNFα, IL-1β and IL-10.
    • Lung cancer--perceptual barriers to cure.

      Kent, B D; Lane, S J (2010-09)
    • Lung involvement at presentation predicts disease activity and permanent organ damage at 6, 12 and 24 months follow - up in ANCA - associated vasculitis

      Hassan, Tidi M; Hassan, Astrid S; Igoe, Ann; Logan, Mark; Gunaratnam, Cedric; McElvaney, Noel G; O’Neill, Shane J; Department of Respiratory, Beaumont Hospital, Beaumont Road, Dublin 9, Ireland (2014-05-27)
      Abstract Background Antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (AAV) may present with pulmonary involvement ranging from mild to life-threatening disease such as diffuse alveolar hemorrhage. There is a paucity of information regarding morbidity outcomes for AAV subjects presenting with lung involvement. This study determines the relationship between disease activity and damage in these subjects using the Birmingham Vasculitis Activity Score v 3 (BVAS 3) and Vasculitis Damage Index (VDI) respectively. Results 151 patients with AAV were included with 59 presenting initially with pulmonary involvement. The initial BVAS scores recorded at time of diagnosis were positively correlated with the final VDI scores at 24 months (p < 0.0001, rs = 0.5871). No differences between BVAS and VDI scores were seen for both groups, however in the lung-involvement group only, BVAS scores were significantly higher at 6, 12 and 24 months whilst the VDI scores were significantly higher at 12 and 24 months. Subjects presenting with pulmonary involvement had an increased likelihood for cardiovascular (OR 1.31, 95% CI 0.89, 1.54; p = 0.032) and renal (OR 1.32, 95% CI 1.22, 1.39; p = 0.005) involvement. Subjects presenting with lung involvement with granulomatosis with polyangiitis and microscopic polyangiitis had 24-month VDI scores that were significantly higher (p = 0.027, p = 0.045), and more likely to develop pulmonary fibrosis (OR 1.79, 95% CI 1.48, 2.12; p < 0.001). Conclusion AAV subjects with lung involvement at presentation had a higher disease activity and damage scores at 6, 12 and 24 months follow-up representing a considerable burden of disease despite improvement in overall survival due to the introduction of immunosuppressive therapy.
    • Magnetic core-shell nanoparticles for drug delivery by nebulization

      Verma, Navin Kumar; Crosbie-Staunton, Kieran; Satti, Amro; Gallagher, Shane; Ryan, Katie B; Doody, Timothy; McAtamney, Colm; MacLoughlin, Ronan; Galvin, Paul; Burke, Conor S; et al. (2013-01-23)
      AbstractBackgroundAerosolized therapeutics hold great potential for effective treatment of various diseases including lung cancer. In this context, there is an urgent need to develop novel nanocarriers suitable for drug delivery by nebulization. To address this need, we synthesized and characterized a biocompatible drug delivery vehicle following surface coating of Fe3O4 magnetic nanoparticles (MNPs) with a polymer poly(lactic-co-glycolic acid) (PLGA). The polymeric shell of these engineered nanoparticles was loaded with a potential anti-cancer drug quercetin and their suitability for targeting lung cancer cells via nebulization was evaluated.ResultsAverage particle size of the developed MNPs and PLGA-MNPs as measured by electron microscopy was 9.6 and 53.2 nm, whereas their hydrodynamic swelling as determined using dynamic light scattering was 54.3 nm and 293.4 nm respectively. Utilizing a series of standardized biological tests incorporating a cell-based automated image acquisition and analysis procedure in combination with real-time impedance sensing, we confirmed that the developed MNP-based nanocarrier system was biocompatible, as no cytotoxicity was observed when up to 100 mug/ml PLGA-MNP was applied to the cultured human lung epithelial cells. Moreover, the PLGA-MNP preparation was well-tolerated in vivo in mice when applied intranasally as measured by glutathione and IL-6 secretion assays after 1, 4, or 7 days post-treatment. To imitate aerosol formation for drug delivery to the lungs, we applied quercitin loaded PLGA-MNPs to the human lung carcinoma cell line A549 following a single round of nebulization. The drug-loaded PLGA-MNPs significantly reduced the number of viable A549 cells, which was comparable when applied either by nebulization or by direct pipetting.ConclusionWe have developed a magnetic core-shell nanoparticle-based nanocarrier system and evaluated the feasibility of its drug delivery capability via aerosol administration. This study has implications for targeted delivery of therapeutics and poorly soluble medicinal compounds via inhalation route.
    • Magnetic resonance myocardial perfusion imaging in the diagnosis of functionally significant obstructive coronary artery disease: a systematic review protocol

      Pharithi, Rebabonye B; Meela, Martinus; Kropmans, Thomas; Ward, Frank; Conway, Michael; Newell, Michael (2014-05-26)
      Abstract Background Cardiac magnetic resonance (CMR) myocardial perfusion imaging has been suggested as a non-invasive alternative to pressure wire guided fractional flow reserve (FFR) in detecting haemodynamically significant obstructive coronary artery disease (CAD). The objective of this systematic review is to determine the diagnostic accuracy of CMR and to compare it to FFR. Methods/design A systematic review of diagnostic test accuracy of CMR and FFR will be conducted. Relevant English-language articles published before November 2013 in Medline, PubMed, EMBASE, Google scholar, Scopus and Cochrane databases will be identified. Relevant referenced articles from those selected will also be analysed. Articles describing diagnostic studies that compared CMR to FFR in patients with known or suspected coronary artery disease will be included. Two investigators will independently screen, assess quality and extract data from the selected articles. The Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool will be used to assess methodological quality. STATA 13 (the xtmelogit command) software will be used to calculate bivariate random effects models and estimate pooled sensitivity and specificity with 95% confidence intervals. Forests plots and summary receiver operating characteristics curves will also be generated. Sub-group pooled analyses using image quality of CMR (in terms of magnetic flux density - Tesla) and basis of analyses (coronary arterial territory vs. patients basis) at different FFR cutoffs (≤0.75 and ≤0.8) will also be performed. Discussion This systematic review will help to determine if CMR is an adequate alternative to FFR in the diagnosis of significant and obstructive CAD. We will also be able to assess diagnostic accuracy of specific types of CMR scan at different FFR cutoffs. Systematic review registration This systematic review had been registered at PROSPERO and the registration number is CRD42013006180.
    • The magnitude and characteristics of the population of cancer survivors: using population-based estimates of cancer prevalence to inform service planning for survivorship care

      Sharp, Linda; Deady, Sandra; Gallagher, Pamela; Molcho, Michal; Pearce, Alison; Alforque Thomas, Audrey; Timmons, Aileen; Comber, Harry (2014-10-15)
      Abstract Background Rising cancer incidence and survival mean that the number of cancer survivors is growing. Accumulating evidence suggests many survivors have long-term medical and supportive care needs, and that these needs vary by survivors’ socio-demographic and clinical characteristics. To illustrate how cancer registry data may be useful in survivorship care service planning, we generated population-based estimates of cancer prevalence in Ireland and described socio-demographic and clinical characteristics of the survivor population. Methods Details of people diagnosed with invasive cancer (ICD10 C00-C96) during 1994–2011, and who were still alive on 31/12/2011, were abstracted from the National Cancer Registry, and tabulated by cancer site, sex, current age, marital status, initial treatment, and time since diagnosis. Associations were investigated using chi-square tests. Results After excluding non-melanoma skin cancers, 17-year cancer prevalence in Ireland was 112,610 (females: 58,054 (52%) males: 54,556 (48%)). The four most prevalent cancers among females were breast (26,066), colorectum (6,598), melanoma (4,593) and uterus (3,505) and among males were prostate (23,966), colorectum (8,207), lymphoma (3,236) and melanoma (2,774). At the end of 2011, 39% of female survivors were aged <60 and 35% were ≥70 compared to 25% and 46% of males (p < 0.001). More than half of survivors of bladder, colorectal and prostate cancer were ≥70. Cancers with the highest percentages of younger (<40) survivors were: testis (50%); leukaemia (females: 28%; males: 22%); cervix (20%); and lymphoma (females: 19%; males: 20%). Fewer female (57%) than male (64%) survivors were married but the percentage single was similar (17-18%). More female (25%) than male survivors (18%; p < 0.001) were ≥10 years from diagnosis. Overall, 69% of survivors had undergone cancer-directed surgery, and 39%, 32% and 18% had received radiotherapy, chemotherapy and hormone therapy, respectively. These frequencies were higher among females than males (surgery: 82%, 54%; radiotherapy: 42%, 35%; chemotherapy: 40%, 22%; hormone therapy: 23%, 13%). Conclusions These results reveal the socio-demographic and clinical heterogeneity of the survivor population, and highlight groups which may have specific medical and supportive care needs. These types of population-based estimates may help decision-makers, planners and service providers to develop follow-up and after-care services to effectively meet survivors’ needs.
    • Major Trauma Audit National Report 2016

      National Office of Clinical Audit (National Office of Clinical Audit, 2018)
    • Malignant neuroendocrine tumour of the appendix in childhood with loco-regional lymph node invasion

      Lyons, Rebecca F; Irfan, Muhammad; Waldron, Ronan; Bambury, Niamh; Bennani, Fadel; Nemeth, Tamas; Khan, Waqar; Barry, Kevin (2015-05-29)
      Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1006600359152743