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Medical devices for the minimally invasive delivery of therapeutic cargo for the prevention of heart failure
No full textTherapeutic advances are increasing the number of patients that survive cardiac disease
such as a myocardial infarction, however, current treatments do not fully stop the
development of heart failure. Advanced therapeutic strategies such as stem cell therapies
have not proved effective in phase III trials likely due to poor retention and survival of
transplanted cells in the infarcted myocardium. This has led to the use of biomaterials
which can deliver cells to the myocardium increasing retention rates up to 80% while also
mechanically supporting the weakened ventricle. Although biomaterials may be an option
for clinical translation, they currently lack effective delivery strategies to the heart and
are limited by the traumatic injection into the myocardium. In this thesis it is shown that
delivering therapeutics to the epicardium using minimally invasive medical device
approaches may be an effective alternative to this problem. Firstly, the SPREADs device
is used as a novel bioresorbable biomaterial carrier that can be delivered to the heart
using a minimally invasive subxiphoid approach. SPREADs could mechanically support
the infarcted ventricle while simultaneously delivering cells in a chronic porcine model of
myocardial infarction. Secondly, the TherEpi device is presented that allows for the
minimally invasive multidose delivery of therapeutics to the epicardium. This thesis
shows that multidose delivery of follastatin like protein 1 (FSTL-1) with TherEpi
significantly improves cardiac function, reduces scar size, prevents ventricular thinning,
and improves angiogenesis in a rodent model of MI in comparison to both single dose
epicardial delivery of FSTL-1 and MI controls. Next, the STAR device is presented
which allows active delivery of therapeutics even with the formation of a fibrous capsule.
STAR can be loaded with a mechanoresponsive tough gel and a bioresponsive ascorbyl
palmitate gel to allow on demand release of drugs in response to mechanical and
biological stimuli. Lastly, a model of chemotherapy induced cardiotoxicity using a h9c2
cell is presented and tested with promising prophylactic cardioprotectants. It is shown
that resveratrol significantly reduced cell death in comparison to clinically approved
dexrazoxane and carvedilol in the h9c2 model of doxorubicin induced cardiotoxicity.
Resveratrol could be used in systems such as TherEpi and STAR for prophylactic
localised delivery for prevention of doxorubicin induced cardiotoxicity. In summary this
thesis prevents novel minimally invasive medical devices for therapeutic delivery.2023-01-2
Volumetric Video in Augmented Reality Applications for Museological Narratives: A user study for the Long Room in the Library of Trinity College Dublin
No full textCross-reality (XR) technologies are quickly establishing themselves as commonplace platforms for presenting objects of historical, scientific, artistic, and cultural interest to the public. In this space, augmented reality (AR) is notably successful in delivering cultural heritage (CH) applications, including architectural and environmental heritage reconstruction, exhibition data management and representation, storytelling, and exhibition curation. Generally, it has been observed that the nature of information delivery in applications created for narrating exhibitions tends to be informative and formal. Here we report on the assessment of a pilot scene for a prototype AR application that attempts to break this mold by employing a humorous and playful mode of communication. This bespoke AR experience harnessed the cutting-edge live-action capture technique of volumetric video (VV) to create a digital tour-guide that playfully embellished the museological experience of the museum visitors. This applied research paper consists of measuring, presenting, and discussing the appeal, interest, and ease of use of this ludic AR storytelling strategy mediated via AR technology in a CH context
Promoting Reflective Writing among Psychiatry Students
No full textED-MEDIA 2011: World Conference on Educational Multimedia, Hypermedia & Telecommunications, Lisbon, Portugal, 27 June - 1 July 2011This paper reports on a study on the use of online learning to teach reflective writing to psychiatry students. The students learnt about reflection and reflective writing using an interactive learning unit and a discussion forum. They posted responses to an article at three levels of reflection. Their learning was assessed using a reflective essay. The majority of students engaged with the discussion forum though some had difficulty in distinguishing the levels of reflection. The students rarely commented on each other’s posts. Modifications will be made for future use based on ongoing research
Analysis of Ras-effector interaction competition in large intestine and colorectal cancer context
No full textCancer is the second leading cause of death globally, and colorectal cancer (CRC) is among the five most common cancers. The small GTPase KRAS is an oncogene that is mutated in ~30% of all CRCs. Pharmacological treatments of CRC are currently unsatisfactory, but much hope rests on network-centric approaches to drug development and cancer treatment. These approaches, however, require a better understanding of how networks downstream of Ras oncoproteins are connected in a particular tissue context–here colon and CRC. Previously we have shown that competition for binding to a ‘hub’ protein, such as Ras, can induce a rewiring of signal transduction networks. In this study, we analysed 56 established and predicted effectors that contain a structural domain with the potential ability to bind to Ras oncoproteins and their link to pathways coordinating intestinal homoeostasis and barrier function. Using protein concentrations in colon tissue and Ras-effector binding affinities, a computational network model was generated that predicted how effectors differentially and competitively bind to Ras in colon context. The model also predicted both qualitative and quantitative changes in Ras-effector complex formations with increased levels of active Ras–to simulate its upregulation in cancer–simply as an emergent property of competition for the same binding interface on the surface of Ras. We also considered how the number of Ras-effector complexes at the membrane can be increased by additional domains present in some effectors that are recruited to the membrane in response to specific conditions (inputs/stimuli/growth factors) in colon context and CRC.Science Foundation Irelan
Biomaterials approach for targeted therapeutics delivery in inflammatory bowel disease
No full textPathogenesis of inflammatory bowel diseases (IBD) is associated with continuous episodes of diffusive gut epithelial inflammation and dysregulated mucosal immune response. IBD (with major forms Crohn’s and ulcerative colitis) is the second most common inflammatory condition, affecting 6.8 million people around the globe. Current conventional oral and injectable delivery strategies are well established in the management and therapy of colonic diseases including IBD. However, disadvantages in terms of the inability to target the drugs directly at the diseased tissue, with limited therapeutic efficacy and a high risk of off-targeted drug associated side-effects make replacement of the conventional strategies desirable. Therefore, advanced drug delivery strategies with site-specificity and local delivery to the inflamed colon are essential for effective treatment of intestinal inflammation locally.
Site-specific delivery of the drugs to inflamed colon regions can prevent the associated drug systemic toxicities while maintaining therapeutic efficacy. Targeting inflammation regions can ideally be accomplished by developing an ideal drug delivery system that targets unique characters of the colitis tissue. In colitis, intestinal epithelium has the dysregulated mucous layer and a high degree of cationic proteins accumulation, which results cationic charge building up at the colitis surface, providing drug carriers with an anionic surface charge as targeting vehicles. A delivery carrier system with an anionic surface charge with mucoadhesive properties could favourably adhere to the cationic charge of the inflamed surfaces and release the payload locally. An inflammation targeted nanocarrier system (IT/NCs) was fabricated via oral delivery for colitis therapy using cyclosporine A (CsA) immunosuppressant drug. Interestingly, the in vitro (charge- modified surfaces), ex vivo (on human healthy vs colitis biopsies) findings confirmed the preferential adhesion on positive (inflamed) surfaces. Further in vivo (DSS and TNBS colitis mice models) therapeutic efficacy study data have shown that the CsA/IT- NCs system is an encouraging therapeutic approach in the management of colitis. Restoration of barrier functionality by mucosal healing strategies has the potential to be a considered approach in colitis therapy. Nevertheless, although attempts have been made to develop anti-inflammatory, immunomodulatory therapies for patients with IBD have been widespread, treatments for the mucosal repair and tissue homeostasis in IBD are still under investigation, and there are a few commercial products available. Mucosal healing, epithelial restitution and symptom management have become vital goals to maintain the remission levels and eventually to stop the IBD progression as well as extra-intestinal manifestations. By identifying the importance of Hyaluronan (HA) in the mucosal, epithelial matrix component of the intestinal wall, the project also investigated the role of HA-Enema as a non-drug-based device in enhancing the barrier functionalities in colitis. In vitro studies showed that HA-Enema system has shown to decrease inflammation and permeability. Further in vivo DSS colitis mice study revealed that the rectal HA-Enema instillation, which applied as a cementing barrier modulated the intestinal barrier by providing potent anti-inflammatory, permeability reduction response to colitis. The research adds to the current knowledge in inflammation-specific colon-targeted drug delivery strategies, which can also be applied with different small/large molecules delivery in colon-associated disease therapies. In addition, biophysical dysregulated colon wall protecting barrier strategy developed in this project could benefit several patients suffering from colitis.2024-01-2
Sarcopenia, diet, physical activity and obesity in European middle-aged and older adults: the lifeage study
No full textThe revised European consensus defined sarcopenia as a progressive and generalized skeletal muscle disorder that is associated with an increased likelihood of adverse outcomes including falls,
fractures, physical disability and mortality. The aim of this study was to determine the prevalence of
sarcopenia and analyse the influence of diet, physical activity (PA) and obesity index as risk factors
of each criteria of sarcopenia. A total of 629 European middle-aged and older adults were enrolled
in this cross-sectional study. Anthropometrics were assessed. Self-reported PA and adherence to
the Mediterranean diet were evaluated with the Global Physical Activity Questionnaire (GPAQ)
and Prevention with Mediterranean Diet questionnaire (PREDIMED), respectively. The functional
assessment included handgrip strength, lower body muscle strength, gait speed and agility/dynamic
balance. Of the participants, 4.84% to 7.33% showed probable sarcopenia. Sarcopenia was confirmed
in 1.16% to 2.93% of participants. Severe sarcopenia was shown by 0.86% to 1.49% of participants.
Male; age group ≤65 years; lower body mass index (BMI); high levels of vigorous PA; and the
consumption of more than one portion per day of red meat, hamburgers, sausages or cold cuts
and/or preferential consumption of rabbit, chicken or turkey instead of beef, pork, hamburgers or
sausages (OR = 0.126–0.454; all p < 0.013) resulted as protective factors, and more time of sedentary
time (OR = 1.608–2.368; p = 0.032–0.041) resulted as a risk factor for some criteria of sarcopenia.
In conclusion, age, diet, PA, and obesity can affect the risk of having low muscle strength, low muscle
mass or low functional performance, factors connected with sarcopenia
Diagnostic and predictive accuracy of the clinical frailty scale among hospitalised older medical patients: a systematic review and meta-analysis protocol
No full textIntroduction Frailty is a common condition affecting older adults and is associated with increased mortality and adverse outcomes. Identification of older adults at risk of adverse outcomes is central to subsequent resource planning and targeted interventions. This systematic review and meta-analysis will examine the: (1) diagnostic accuracy of the Clinical Frailty Scale (CFS) in identifying hospitalised adults ≥65 years with frailty and a medical diagnosis compared with the reference standard Frailty Index or Frailty Phenotype and (2) predictive value of the CFS in determining those at increased risk of subsequent adverse outcomes
Stanley Cavell and Film: Scepticism and Self-Reliance at the Cinema, by Catherine Wheatley
No full textThe Pamela Davies Collection: Continuity supervision in British widescreen and colour cinema
No full textFilm continuity supervision is a craft historically dominated by women. Yet, several years since Melanie Williams’s pathbreaking article on David Lean’s continuity supervisors, scholarship on this deeply gendered area of film production expertise remains lacking. In response, this dossier contribution will introduce Pamela Davies’ film continuity stills, catalogued by the author at the Bill Douglas Cinema Museum during an AHRC-funded placement (2018–2019). Davies secured the desired consistency of dialogue, cinematic staging and special effects in British cinema from 1948 to 1985, beginning with the post-war cycle of historical drama in widescreen and colour. Taking a multi-faceted archival approach, I discuss how photographs in the collection snapshot Davies at work and the stills photographers who collaborated with her during a transformative period in British cinema. Examining the stills in their material, craft and commercial contexts will raise new questions about continuity work and make the collection more accessible for researchers