131 Works

The Genetic Structure and Landscape of Ireland Reveals Footprints of History

Edmund Gilbert
Ireland has a fascinating history of ancient kingdoms and more modern migrations. Furthermore, Ireland’s island location at the north-western edge of Europe makes it conducive to genetic homogeneity and isolation. The impact of historical migrations on the island is largely unknown, as is the extent of genetic structure in Ireland, despite successful efforts to characterise such genetic ancestry and structure with uniparental data, and efforts within the neighbouring British Isles.The description of the impact of...

Aldosterone-Mineralocorticoid Receptor: Cell Biology to Translational Medicine

Brian Harvey
This book is an open access dissemination of the EU COST Action ADMIRE in Aldosterone/Mineralocorticoid Receptor (MR) physiology and pathophysiology. Aldosterone is the major hormone regulating blood pressure. Alterations in blood levels of aldosterone and genetic mutations in the MR receptor are major causes of hypertension and comorbidities. Many of the drugs in clinical use, and in development for treating hypertension, target aldosterone and MR actions in the kidney and cardiovascular system. The ADMIRE book...

Bioinspired Star-Shaped Poly(L-Lysine) Polypeptides; 2 Efficient Polymeric Nanocarriers for the Delivery of DNA 3 to Mesenchymal Stem Cells

David Walsh, Robert Murphy, Angela Panarella, Rosanne Raftery, Brenton Cavanagh, Jeremy C. Simpson, Fergal O'Brien, Andreas Heise &
The field of tissue engineering is increasingly recognizing that gene therapy can be employed for modulating in vivo cellular response thereby guiding tissue regeneration. However, the field lacks a versatile and biocompatible gene delivery platform capable of efficiently delivering transgenes to mesenchymal stem cells (MSCs), a cell type often refractory to transfection. Herein, we describe the extensive and systematic exploration of three architectural variations of star-shaped poly(l-lysine) polypeptide (star-PLL) with varying number and length of...

A qualitative exploration of adolescents with severe haemophilia and their caretakers regarding their future transition to adult services

Objective: To qualitatively explore the views of adolescents with severe haemophilia A or haemophilia B and their caretakers such as parents and multidisciplinary staff relating to transition from child to adult services.Methods: Qualitative design using semi-structured interviews based upon the Critical Incident Technique (CIT).Results: Thematic analysis using the CIT approach identified five themes all of which pertained to either the positive or negative aspects of the transition programme for adolescents with severe haemophilia and their...

Design and Development of Multi-Targeted Metallodrugs as Potential Chemotherapeutic Agents

Reece G. Kenny
Cancer remains a major global health burden despite significant advances in treatmentregimens. Current drug treatments, including those involving platinum drugs, havedrawbacks including dose limiting toxic side effects and either acquired or intrinsicdrug resistance. The development of safer and more effective drug treatments remainsa major research focus. The platinum drugs in clinical use primarily target DNA.Our Group previously developed novel multi-targeted platinum(II) complexes capableof not only binding cancer cell DNA but also possessing the ability to...

Evaluation of the compatibility of sildenafil during simulated Y-site and multi-lumen administration in a paediatric intensive care unit

Sildenafil, a phosphodiesterase type-5 inhibitor, is used for the treatment of infants with pulmonary hypertension (PH). Intravenous (IV) sildenafil (Revatio®) is approved for the treatment of PH in adults but is used off-label in paediatrics. The absence of compatibility data between sildenafil and other commonly used IV medications such as adrenaline, noradrenaline, vasopressin, milrinone and heparin necessitates the use of a dedicated IV line for sildenafil. In the critically unwell child, limited IV access can...

Tailoring Activators for the Selective Reactions of Ethyl 2-(Trimethylsilyl)acetate Under Batch and Continuous Flow Conditions

Ian Fox
The use of silicon-based reagents in organic synthesis has received significant attention and has been an ever-growing area of focus in recent years. Since Hosami and Sakurai first described the fluoride-initiated reaction of allytrimethylsilane to aldehydes, there have been several advancements in the field. Alternative sources of silicon activation have been developed such as tBu-P4 and proazaphosphotrane bases as well as work completed by my research group into the tetrabutylammonium controlled addition to aldehydes under...

Identifying delays occurring in out-of-hours FAST calls causing increasing door-to-treatment time

Kyra O'Dwyer
Stroke is one of the leading causes of death and disability worldwide and is a huge economic burden. The management of stroke is time dependant. Shorter times result in reduced mortality and morbidity. National Guidelines in Ireland suggest a door-to-treatment time of one hour or less from presentation to the emergency department. Despite this recommendation, delays are still occurring for patients accessing timely treatment. This quality improvement project was carried out in a busy North...

Profiling Frailty in a Population of Older Adults Living With Human Immunodeficiency Virus (HIV) In Ireland

Chiara Reddin
Introduction Due to advances in healthcare in recent years, people living with Human Immunodeficiency Virus (PLWH) are for the first time reaching older age since the HIV epidemic began in the 1980s. It is known that PLWH suffer from premature ageing syndromes, such as frailty, younger than the general population (Bhatia et al., 2012). This presents new challenges for healthcare professionals in facilitating older PLWH to live better for longer into older age and in...

Secondary risk factor management 5-years post ischaemic stroke - The ASPIRE-S2 study

Eva Gaynor
Numerous guidelines have been published outlining evidence-based best
practice in secondary stroke prevention, including optimal target control of risk
factors. Despite these guidelines failure to achieve these recommendations in
clinical practice is common. This study, ASPIRE-S2 is a 5-year follow-up study
of the ASPIRE-S Study (Action on Secondary Prevention Interventions and
Rehabilitation in Stroke). The primary aim of this study was to prospectively
assess secondary prevention profiles of Irish ischaemic stroke patients at 5-
years and compare them to that measured at...

The Prevalence of Frailty in Older Adults Referred to Primary Care Physiotherapy and the Influence of Frailty Screening on the Clinical Practice of Physiotherapists : A Mixed Methods Study

Melissa Boland
IntroductionGlobally, the proportion of the population of older adults (aged 65 and older) is growing rapidly. Frailty is a state of increased vulnerability to poor resolution of homeostasis following a stress and is the most problematic expression of population ageing. Physiotherapy is a heavily utilised social and community care service by older adults in the Republic of Ireland. An increasing number of older adults, with the potential presence of frailty, are likely to present to...

Sleep Disturbance in Patients with Advanced Chronic Kidney Disease or End-Stage Renal Disease

Claire Kennedy
Patients with advanced chronic kidney disease (CKD) or end-stage renaldisease (ESRD) have a large burden of symptoms, with sleepdisturbance, restless legs syndrome and fatigue among the mostprevalent (1). These sleep-related symptoms are considered an absolutepriority for both treatment and research by patients and their caregivers(2). Despite this, clinicians consistently underestimate and overlook thesesymptoms in clinical encounters (3). The impact of RRT modality choiceon such symptoms is not well defined and is poorly communicated topatients choosing...

Improving the utilisation and the awareness of high-sensitivity cardiac troponin test

Reginald Imasuen
Cardiac troponin is one of the biomarkers to diagnose a myocardial infarction and has been in use for many years. There has been many improvements in these biomarkers to aid in the diagnosis of a myocardial infarction. An improvement in troponin sensitivity to be specific. Each new generation of troponin has led to improved diagnostic sensitivity. The new generation of troponin are known as the high-sensitivity troponin. The advantage of the high-sensitivity troponin is the...

Improving Nursing Handovers in a Voluntary Mental Health Facility

Around the globe, ineffective handovers have resulted in grave consequences, leading to handover improvement strategies being introduced, along with guidelines beingformulated in many countries. Despite this, however, few studies focused on improving handovers in a psychiatric setting. This current Quality Improvement Project aims tofill this gap and improve nursing handovers in a mental health facility by 50% over eight months. Using Lean Six Sigma's, Define Measure Analyse Improve Control framework and various quality improvement tools,...

The genomics of transplant-related outcomes and familial renal disease

Caragh Stapleton
Chronic kidney disease (CKD) is a growing global health concern with an age-standardized global prevalence of approximately 10%. Of those with CKD, approximately 2% will go on to require renal replacement therapy within any given 5-year period. Renal transplantation is accepted as the most clinically- and cost-effective treatment for end-stage kidney failure. In this thesis, we set out to examine the impact of common genetic variation on renal transplant function as well as a common...

Exploring the experiences of patients with primary and secondary, non-cancer related, lower limb lymphoedema during the intensive and maintenance phases of Complex Decongestive Therapy and its’ impact on their lives

Mary Costello
IntroductionLymphoedema is an incurable, progressive condition, which results in the swelling of a limb or limbs and impairs mobility (Lymphatic Framework, 2006). The psychosocial impact of lower limb lymphoedema is also devastating as body image and quality of life are greatly affected (Lasinski et al, 2012). Although lymphoedema is a chronic condition, it is manageable through treatment modalities which include manual lymphatic drainage, compression bandaging, compression hosiery, skin care and exercise, otherwise known as Complex...

Progressive Resistance Training in a Post-Acute, Older, Inpatient Population

Sinéad Coleman
Introduction Many older adults are at risk of functional decline following an acute hospital admission. Many of these older adults are pre-sarcopenic or sarcopenic and are extremely vulnerable to a further deterioration of function and dependence in Activities of Daily Living ability. Progressive Resistance Training (PRT) is an intervention that involves exercising a muscle against a load that is progressively increased as the muscle strengthens. PRT has been shown to successfully target both functional decline...

Comparing the Outcomes of Tubularized Incised Plate Urethroplasty and Dorsal Inlay Graft Urethroplasty in Children with Hypospadias: A Systematic Review and Meta-Analysis

Background: Due to their simplicity and excellent outcomes, the tubularized incised plate urethroplasty (TIPU) and the dorsal inlay graft urethroplasty (DIGU) are two of the most commonly used techniques for hypospadias repair in children. However, there is a lack of consensus on which technique offers more favourable results and less added morbidity to the patient. Aims: This study aimed to systematically compare the reported outcomes of the TIPU and DIGU techniques in an effort to...

The Assessment of Myocardial Performance and the Impact of Pathological Processes on Cardiac Adaptation in the Neonatal Population using Functional Echocardiography

Colm Breatnach
Introduction: Functional echocardiography is a rapidly expanding field in both research and clinical settings. Newer techniques facilitate comprehensive and objective assessments of myocardial performance not previously possible. Although work has been done to assess feasibility and obtain reference values for several new modalities in normal term and preterm infants, data is still lacking in several important disease states. Objectives: We aim to study the impact of several important conditions on neonatal myocardial function over the...

Development of an ultrasound triggered, thermally responsive hydrogel as an on-demand delivery system for bone repair

Bones can physiologically regenerate themselves. In the case of non-unionfractures and certain pathological conditions, however, regeneration issuboptimal, too slow, or does not occur. The clinical ‘gold standard’,autografting, can result in numerous complications including infection, chronicpain and donor site morbidity. Current commercial bone graft substitutes haveshown limited success and an effective ‘off-the-shelf’ solution is required. Theobjective of this study was to develop an ultrasonic-thermally responsivehydrogel for bone regeneration and to investigate its potential for on-demanddelivery of...

Progressive Resistance Training in an Older Post-acute Inpatient Population

IntroductionMany older adults are at risk of functional decline following an acute hospital admission. Many of these older adults are pre-sarcopenic or sarcopenic and are extremely vulnerable to a further deterioration of function and dependence in Activities of Daily Living ability. Progressive Resistance Training (PRT) is an intervention that involves exercising a muscle against a load that is progressively increased as the muscle strengthens. PRT has been shown to successfully target both functional decline and...

The role of α2 agonists in paediatric critical care sedation

John Hayden
Background There are two α2 agonists used in sedation in paediatric critical care in Ireland. Firstly, the older medication clonidine and secondly the newer, more selective, α2 agonist dexmedetomidine. Neither agent is licensed for use in paediatrics despite both being in routine clinical use. Not being licensed in children has meant both medications bypassed formal efficacy and safety studies in children during their development. This thesis aimed to address current knowledge deficits and provide an...

miR330-3p Dysregulation Plays a Critical Role in Disrupting the Endothelial Barrier During Staphylococcus aureus Infection

Rebecca L. Watkin
Sepsis is a life-threatening condition defined as an extreme inflammatory host response to infection. One of the most commonly isolated causative microorganisms from sepsis patients is the Gram-positive bacteria Staphylococcus aureus (S. aureus). Upon entry to the bloodstream, S. aureus locates and adheres to the inner lining of the blood vessels, the endothelium, and triggers the typical characteristics of sepsis such as a sustained and dysregulated immune response, hyper-coagulation and endothelial dysfunction. These manifestations are...

miR330-3p Dysregulation Plays a Critical Role in Disrupting the Endothelial Barrier During Staphylococcus aureus Infection

Rebecca L. Watkin
Sepsis is a life-threatening condition defined as an extreme inflammatory host response to infection. One of the most commonly isolated causative microorganisms from sepsis patients is the Gram-positive bacteria Staphylococcus aureus (S. aureus). Upon entry to the bloodstream, S. aureus locates and adheres to the inner lining of the blood vessels, the endothelium, and triggers the typical characteristics of sepsis such as a sustained and dysregulated immune response, hyper-coagulation and endothelial dysfunction. These manifestations are...

Identification of driver mutations and tumour evolution in HER2 positive breast cancer

Peter O'Donovan
This thesis describes the results of a variant calling project using data from the TCHL (Trastuzumab, Carboplatin, and Docetaxel, with Lapatinib) breast cancer whole exome sequencing project. Using a data processing pipeline based on the GATK (Genome Analysis Tool Kit) Best Practices Pipeline, variants were called on a total of 34 tumour samples from 25 patients. This included 20 patients where only a pre-treatment sample was taken from that patient, and 5 patients where samples...

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