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Disease-specific quality of life in children with suppurative otitis media, including children with Down Syndrome and Autistic Spectrum Disorder 27 Apr 2017

Acute otitis media (AOM) is a bacterial or viral infection of the middle ear which may accompany an upper respiratory tract infection. AOM can occur at any age, however, it is most common between 3 months and 3 years old. At this age, the Eustachian tube is structurally and functionally immature. Diagnosis of AOM is made by clinical and physical examination with an otoscope. Otoscopic examination can show a bulging, erythematous tympanic membrane with indistinct landmarks and displacement of the light reflex. The treatment for AOM are analgesics such as paracetamol or ibuprofen and many cases resolve spontaneously. Antibiotics are frequently given. Antibiotics relieve symptoms quicker and may reduce the chance of residual hearing loss and labyrinthine or intracranial sequelae. With the emergence of antibiotic resistant organisms, it is recommended that a round of antibiotics be administered only for children at highest risk or for those with recurrent acute otitis media(RAOM). RAOM is defined as four or more episodes of AOM in a 6 month period. The aim of this project is to investigate the impact on the quality of life of children that present with recurrent acute otitis media(RAOM).

Functional characterisation of excitatory neurons 27 Apr 2017

Autism spectrum disorder (ASD) is a complex, neurodevelopmental disorder characterised by deficits in social and communication skills, language delay and repetitive or stereotypical behaviour. A variety of copy number variations have been identified that play a role in ASD, including the Neurexin1 gene (NRXN1) which encodes a family of presynaptic cell adhesion transmembrane proteins, vital for neurotransmission and synapse differentiation. It is widely accepted that neurexin and mutations disturb the balance between excitatory (alpha- and beta-nrxn) and inhibitory (mainly alpha-isoform) synaptic activity that is thought to be critical in the pathology in ASD. The seminal discovery that somatic cells can be reprogrammed to produce induced pluripotent stem cells (IPSCs) has revolutionised biological research and medicine. The ability to differentiate these IPSCs into neural cells offers a tremendous opportunity to study disease modelling associated with impaired neuronal cell biology. In this study we will characterise the functional firing properties of IPSc derived glutaminergic neurons differentiated from normal controls and patients carrying a NRXN1 mutation. Functional properties will be assessed by patch clamp examining voltage gated sodium and potassium channels and action potential firing properties under current clamp conditions. This work will be essential to aiding our understanding of ASD.

Potential role of tumour-secreted exosomes in detection and monitoring of breast cancer 27 Apr 2017

MicroRNAs (miRNA) are short, non-coding sequences of RNA that have been shown to be dysregulated in the circulation of patients with a variety of cancers, including breast cancer. Numerous studies have shown that miRNA-containing exosomes are secreted into the circulation and their miRNA content has been shown to reflect that of secreting cells. As such, exosome-encapsulated miRNAs may represent an ideal biomarker for diseases at an early stage. This study aims to identify clinically relevant exosome-encapsulated microRNAs in the circulation of breast cancer patients that are reflective of disease characteristics. Recent initial studies of ExomiRs in the circulation of breast cancer patients have provided an important proof-of-principle, although have been limited in size and scope, and have not reflected the heterogeneity of the disease. The Discipline of Surgery Biobank currently contains >1200 serum/plasma samples, from which exosomes can be isolated. This is an invaluable resource and is linked to complete clinicopathological, and treatment details of patients. This work will determine the clinical relevance (in circulation) of exosome-encapsulated miRNAs recently identified to be secreted by breast tumours In Vitro and In Vivo by the host laboratory group.

Assessing Redundancy in DNA Replication Initiation 27 Apr 2017

CDC7 kinase is a key molecular switch for DNA replication. CDC7 kinase is a protein kinase which phosphorylates and activates the mini-chromosome maintenance (MCM) helicase thus triggering DNA replication origin firing. However, recent research has shown that CDC7 kinase inhibition with some ATP competitive inhibitors does not entirely inhibit DNA replication and cell cycle can still proceed, thus have marginal effects on cell proliferation. Importantly the FANCI protein, that is normally involved in DNA repair, has been shown to be involved for the firing of DNA replication origins during replication stress and to regulate CDC7 dependent activation of MCM helicase at "dormant origins" . We will test the hypothesis that CDC7 and FANCI cooperate in the activation origin during normal replication and that the activity of CDC7 inhibitors could be greatly enhanced in FANCI depleted cells. For this we will deplete FANCI from breast derived cells and traet them with different doses of the CDC7 inhibitor XL413. Key goals are 1) reproducible detection of FANCI by western blotting, 2) efficacious depletion of FANCI by siRNA and 3) implementation of DNA replication and cell survival assays.

Diabetes Mellitus, Human Uterine Contractility and Labour 27 Apr 2017

It is well recognised that both maternal obesity in pregnancy, and maternal gestational Diabetes Mellitus (DM) result in a much greater need for caesarean section for delivery of the infant (1-3). There is an emerging view that the human uterine smooth muscle is subjected to some type of metabolic dysregulation in these conditions, but the exact factors involved are unknown. The aim of this project is to examine the effects of a number of biomarkers associated with DM in obese women on the contractility of human pregnant myometrium in vitro. The effects of glucose, Proinsulin C-Peptide, and Insulin, on spontaneous, and agonist (oxytocin)-induced contractions of human myometrium in vitro, obtained in the third trimester of pregnancy, will be examined. The following parameters will be measured, and compared with simultaneously run control experiments: frequency and force of contractions, peak amplitude and integrals of contractile activity over 15-minute periods. The raw data measured will be compared using ANOVA, followed by Tukey's HSD test for post-hoc analysis, with significance taken as a P value

Beyond Transitions 21 Jan 2017

Volunteering Matters will use the grant to support younger people with disabilities in Blaenau Gwent by providing them with skills and empowering them during the transition from education to further education, employment or training. This grant for £5,000 will fund volunteer expenses, mentor training, stationery and telephone costs, promotional materials, evaluation, and administration support.

Amount: £5,000
Funder: The Big Lottery Fund
Recipient: Volunteering Matters
Region: Wales
District: Blaenau Gwent - Blaenau Gwent

Primary cilia and cellular senescence 05 Sep 2017

Somatic cells undergo senescence after a finite number of divisions, indefinitely arresting their proliferation. The mechanisms of cellular senescence are not well understood, although DNA damage signalling is one major cause. We have found that senescent human fibroblasts have increased frequency and length of primary cilia, antenna-like structures that sense and transduce various extracellular signals, notably Hedgehog. Here we propose to test the hypothesis that primary ciliation contributes to cellular senescence. We will use genome editing in primary cells to ablate CEP164, which is required for primary ciliogenesis, and then follow the kinetics of cellular senescence in the knockout population. We also propose to examine cilium-controlled signalling pathways to determine how they are affected during the initiation of senescence programmes. We will perform competitive co-culture experiments between ciliated and non-ciliated populations to define how ciliation capacity directs senescence in mixed populations. Together, the proposed experiments will test a novel cellular mechanism of senescence, a process of great significance in human health and the normal aging process.

Amount: £51,168
Funder: The Wellcome Trust
Recipient: National University of Ireland Galway

Haemocompatibility and biocompatibility of a polyurethane-based polymer for use in prosthetic heart valves 27 Apr 2017

Developing valves with efficient function and long-term durability without the need for anticoagulation therapy, coupled with the ability to be accommodated in many different types of patient, are the principal requirements of replacement heart valves. The current treatment options available do not fit well with these critieria. The overall aim of the project is to develop a biomimetic polymer alternative to pericardium heart valve leaflets with a more repeatable, consistent and predictable production process. Main research objective: To investigate the haemocompatability of the polymer valve. That is, to measure the blood's response to contact with the valve by measuring parameters such as thrombogenicity, activation of coagulation, blood cell countsand platelet activation. Secondary research objective: To carry out a comprehensive collaborative literature review with my supervisor to deisign an experiment that helps us to understand the blood's response to the polymer in a dynamic environment i.e. simulating the in vivo scenario of blood being pumped across the valve and therefore coming in contact with the valve while under stress. Time allowing, we will then carry out this experiment. We hypothesize that the polyurethane-based material will have equivalent haemocompatibility to that of a commercially available aortic heart valve replacement.

Effect of NRXN1 gene deletion on neurite outgrowth and cell fate in human induced pluripotent stem cells derived from ASD patients 27 Apr 2017

Autism is a devastating neurodevelopmental disorder with unmet clinical needs. Multiple genetic factors are involved, and NRXN1 is one of the most common rare but significant factors. Professor Shen at NUIG has been granted a SFI Investigator’s award to investigate autism using induced pluripotent stems cells (iPSCs). They have derived iPSCs from controls and autistic patients with NRXN1 deletions, and differentiate iPSCs into astrocytes and neurons. RNA sequencing data from 100 days of differentiated cultures demonstrated a disturbed balance of neurons and astrocytes in patients' samples. This project will therefore investigate if NRXN1 deletion affects early birth of cell types. I will perform lineage differentiation protocol to directionally differentiate iPSCs into cortical lineage. I will compare proliferation in neural stem cells, and quantify their rates between patients and controls. I will investigate astrocyte/neuronal lineage determination using Tuj1 and GFAP markers. Autism symptoms appear early postnatally which correlates with development of neuronal network, and preliminary data showed dysregulation of MAPK and GSK3beta in patient neural stem cells, which play important roles in neurite outgrowth. I will therefore also investigate neuritogenesis during early neuronal differentiation. This internship is anticipated to provide evidence into how NRXN1 deletion may affect autism-related early brain development.

A study of the utility of a computerised version of the MBT in assessing cognition in a population with mixed neuropsychiatric presentations. 27 Apr 2017

This study aims to explore the usefulness of MBTc (computerised version of the months backwards test) at detecting delirium. A major challenge in accurately detecting delirium is the lack of a reliable and convenient tool that can be used in everyday practice (O’Hanlon et al 2013). Despite the ease of use of the verbal Months Backwards Test, there are inconsistencies in how it is administered e.g. how to deal with errors and the use of prompts. A novel computerised version of the months backwards test has been developed at the University of Limerick and its performance has been examined in a population of hospitalised elderly patients and cognitively intact young people. The MBTc test had a high correlation with the verbal version of the test and demonstrated excellent sensitivity for detecting cognitive impairment in elderly patients. It is thought the enhanced standardisation of administration of the computerised version of the test will improve reliability of clinical detection of these symptoms. Participants will also be asked to complete other psychiatry tests e.g. Serial Sevens and WORLD backwards. Patients’ perspectives of the various tests will be sought. The above investigations will form part of a standard Consultation Liaison Psychiatry assessment.

Grant to Royal British Legion: Colston Bassett, Owthorpe and Cotgrave Branch 04 Aug 2017

Any grant will support veterans who need help with improving their lives at a difficult time or in challenging circumstances.

Grant to Volunteering Matters 11 May 2017

£135,000 over three years (3 x £45,000) for the salary, project delivery and support costs of an Inclusion Worker engaging young disabled people in volunteering.

Amount: £135,000
Funder: City Bridge Trust
Recipient: Volunteering Matters
Region: London
District: Hackney London Boro

Microanatomy of the thumb carpometacarpal (1CMC) joint. 27 Apr 2017

The 1CMCjoint is the joint in the hand most affected by osteoarthritis.However there is only limited information available on its microscopic structure, and the studies which have been performed are difficult to compare as they all utilise different techniques(CT, MRI, SEM).In work as yet unpublished (Wilkins) it demonstrated the feasibility of obtaining joints and imaging them by eSEM to give high resolution surface maps of the articular surfaces, comparable to those obtained in standard SEM.This project was commenced to attempt to integrate and correlate information from several of these techniques. The joints were then reprocessed for routine paraffin histology and the appearance of the joint surface correlated with the morphology of the articular cartilage and subchondral bone in histological sections.This is the first time that direct correlation of the joint surface with joint histology has been demonstrated.This project aims to extend these studies to include micro CT in the examination sequence.Radiographic and CT imaging are clinically useful in assessing joint disease. On successful completion this will enable direct correlation of clinically relevant imaging data with high resolution views of the joint surface and the cartilage bone interface.

Vitamin D in Irish Children with Type 1 Diabetes : A Cross-sectional Study 27 Apr 2017

Vitamin D can be found in the form of cholecalciferol1 (vitamin D3) or ergocalciferol (vitamin D2) which can be obtained from food or dietary supplements. Recent studies revealed that vitamin D plays an important role in the prevention of various chronic diseases including cardiovascular diseases2, cancers such as colorectal and prostate cancers and diabetes mellitus in children3. Low vitamin D levels in children are a widespread problem across the world. The prevalence reported in healthy European children varies widely between 8% and 95%4. Vitamin D deficiencies can be a result of several factors such as inadequate exposure to the sun and disorders that hampers vitamin D absorption to name a few. Vitamin D deficiencies has also been associated with risks of cancer, increased risk of preeclampsia in pregnant women and an increased risk of type 1 diabetes in children and adolescents5. Hence, the aim of this study is to report the vitamin D levels of a cohort of Irish children with Type 1 Diabetes attending a clinic in the west of Ireland, to establish the frequency of low vitamin D levels in that cohort (insufficiency and deficiency) and to compare them to recent study reports from other countries worldwide.

Knowledge, Attitude and Behaviours of Medical Students Towards Sexual Health 27 Apr 2017

Sexual health is a key component to a holistic approach to health frequently overlooked as quite a taboo subject. Medical students as future healthcare professionals and advocates of a healthy lifestyle, it is therefore critical that they understand the importance of their own sexual health and that of their future parents. As part of my research project I plan to investigate the knowledge attitudes and behaviours of undergraduate medical students around sexual health. Notably focussing on the areas of contraception, STI’s, sexual activity and how students feel their knowledge in these areas has been influenced by the medical curriculum. As well as this identifying where possible influential factors such as social, cultural, personal, economic and educational. This study will be carried out following extensive literary reviews in the areas, before compiling a questionnaire for distribution in a cross-sectional survey of undergraduate medical students. The results obtained will be entered into SPSS for cleaning and analyses. This data can then be used a comparison against both national and international based studies. Highlighting any new data. Finally dissemination of findings, via Wellcome Trust research report, conference presentation and peer reviewed journal article.

Assessment of Biomarkers of Reperfusion Injury Relating to Effectiveness of Stroke Treatments 27 Apr 2017

The research aims to quantitatively assess biomarkers of reperfusion injury after induction of focal cerebral ischaemia in rats by occluding the middle cerebral artery, subsequently reperfusing it for 2 or 4 hours. The brain sections of the rats are then analysed to look at the extent of haemorrhage with the dysfunction of the blood brain barrier which causes biomarkers to be released. The results can then be used to measure which biomarker indicate greater reperfusion injury as well as the effectiveness of different reperfusion strategies in stroke.

ANCHOR Project 30 Nov 2017

Supporting the ANCHOR programme - a young persons intervention around early intervention and prevention.

Amount: £15,164
Funder: Suffolk Community Foundation
Recipient: Volunteering Matters

Grant to Chatteris Branch, Royal British Legion 09 Mar 2017

George Clare VC: A town commemorates

The Loop 01 Nov 2017

To deliver 3 Progress Group programmes to help improve peoples mental wellbeing.

Amount: £1,910
Funder: Suffolk Community Foundation
Recipient: Volunteering Matters