Digital Commons Network^™

Exploring The Role Of Irf4 In The Sensitivity Of Mantle Cell Lymphoma Cells To Bruton's Tyrosine Kinase Inhibitors, Artjoms Portnojs

Peninsula Medical School Theses

Introduction and aim: Mantle cell lymphoma (MCL) is an aggressive subtype of B-cell lymphoma. Therapy using Bruton’s tyrosine kinase (BTK) inhibitors has improved clinical outcomes but primary and secondary resistance to BTK inhibitor (BTKi) therapy affects more than half of MCL patients. Resistance most often arises through gene mutations in cells protected from BTKi effects within the local tissue microenvironment. This thesis develops previous work by the group identifying IRF4 as a central mediator of resistance to BTK inhibitors in MCL; the thesis aims to understand how resistance develops and to identify mechanisms to prevent or overcome BTKi resistance in …

Mishra L, Francis T, Nooji D, Aggarwal H, Mccoll E, Eachempati P. Current Concepts In Restoring Endodontically Treated Teeth., Lora Mishra, Prashanti Eachempati, Tony Francis, Devi Prasad Nooji, Himanshi Aggarwal, Ewen Mccoll

Peninsula Dental School

Restoration of endodontically treated teeth (ETT) is crucial for long-term success. This article reviews current concepts in restoringETT, which focuses on structural integrity and functional performance. Key factors, including residual tooth structure, ferrule effect and pericervical dentine preservation, are discussed alongside advances in conservative access designs, biomimetic protocols and innovative materials,such as ultra-high molecular weight polyethylene fibres. Decision-making frameworks, including the Restorative Difficulty Evaluation System(RDES), are highlighted to support clinicians in achieving predictable outcomes, ensuring tooth survival and patient satisfaction.CPD/Clinical Relevance: The long-term success of endodontically treated teeth depends on selecting appropriate restorative strategiesthat ensure structural integrity, functional performance and …

Considering Behaviour In Genetic Sampling – A Case Study With Grey Seals, Kathryn Wiltshire

School of Biological and Marine Sciences Theses

Genetic variations are increasingly linked to intra-specific behavioural variations. Advancing our knowledge of behavioural genetics could make screening populations for genetic polymorphisms associated with behavioural variations possible. Genetic-behaviour links have been increasingly discovered in terrestrial mammals, but there are few comparable studies in marine mammals. Developing efficient and cost-effective genetic sampling techniques is essential to allow more studies on behavioural genetics in lesser researched marine mammals. This study explores the potential of a sampling technique, still in its infancy in marine mammal studies, that has potential to cause minimal stress to the animals. Buccal swabs were tested in a group …

An Assessment Of The Dietary Bioavailability Of Tio2 And Inorganically Carbon-Based Nanomaterials In Rainbow Trout, Using The Ex Vivo Gut Sac Technique And A In Chemico Digestibility Assay, Craig Mchardy

School of Biological and Marine Sciences Theses

Abstract. Craig McHardyAn assessment of the dietary bioavailability of TiO2 and inorganically carbon-based nanomaterials in rainbow trout, using the ex vivo gut sac technique and a in chemico digestibility assay.Carbon based engineered nanomaterials (ENMs) are an emerging contaminant within modern society, as such their environmental risk assessment is of high importance. Testing for their persistence, toxicity and bioaccumulation potential is important for regulatory bodies to fully understand the hazard posed. To date, data on the bioaccumulation potential of these ENMs is lacking, especially within fish. A tiered approach to bioaccumulation testing has been posed in which precursory tests such as …

Impact Of Dietary Functional Yeast Additives On Growth Performance And Health Of Selected Key Aquaculture Species, Sheu Odu-Onikosi

School of Biological and Marine Sciences Theses

The aquaculture industry has witnessed remarkable growth in recent decades underscoring its crucial role in global food security. However, this rapid expansion brings challenges, including the need to meet growing fish demand while minimising environmental impacts and managing disease prevalence. Functional feed additives (FFAs) have emerged as sustainable solutions to enhance fish health and performance. Among these, yeast-derived additives have garnered significant attention for their nutritional benefits and proven ability to promote growth and strengthen immune responses in fish.This study evaluates the effects of dietary brewer's yeast-derived additives on fish using a range of in-depth analyses, such as growth performance, …

Unravelling The Ecological Trade-Offs In Behavioural And Physiological Sexual Traits, Alicia Eveson

School of Biological and Marine Sciences Theses

Animals experience temporally and spatially heterogeneous environments throughout their lives. Therefore, individuals that are able to plastically adjust their behaviour to the current environment, are able to maximise their fitness. These behavioural adjustments are particularly important where there are trade-offs between investment in different life-history traits. Trade-offs between reproduction and survival have been widely documented, in addition to a body of evidence for trade-offs between mating related traits. How an individual adjusts their mating behaviour in response to their social and biotic environments are important aspects of selection. Changes in the social environment, including sex ratio or population density changes, …

Factors Controlling Protein Metabolism And Growth In The Common Limpet Patella Vulgata, Ignacio Alvarez-Cienfuegos

School of Biological and Marine Sciences Theses

The intertidal environment is a complex and highly dynamic ecosystem shaped by the interaction of strong abiotic and biotic factors. Organisms living in this habitat present marked physiological and behavioural adaptations to cope with extreme and fluctuating conditions, which make this ecosystem the perfect natural laboratory to analyse the effects of biological interactions and physical stressors in ectotherm protein metabolism and growth in the field. Patella vulgata’s ability to maintain aerobic metabolism out of the water, its homing behaviour, its high abundance, and wide geographical distribution facilitates the study of ectothermic physiological processes in the field. Despite the importance of …

Effects Of Host-Derived Probiotics On The Growth Performance And Health Of Tilapia And Carp, Sherilyn Abarra

School of Biological and Marine Sciences Theses

To address the need for well-characterised probiotic strains for tilapia and carp aquaculture, this study investigated the isolation, characterisation, and application of host-derived candidate probiotics from Nile tilapia (Oreochromis niloticus) and mirror carp (Cyprinus carpio), and their influence on growth, feed utilisation, intestinal integrity and microbiome, and mucosal health of the host.A total of 263 intestinal bacterial isolates were screened in vitro for antagonism against Aeromonas hydrophila and Streptococcus iniae. The top 31 isolates with inhibitory effects underwent screening against three further fish pathogens and were assessed for haemolytic activity and extracellular enzyme production in …

Metabolic And Kinetic Impacts Of The Auxiliary Energy Source In Model Chemolithoheterotrophic Bacteria, Caleb Yarnley

School of Biological and Marine Sciences Theses

Chemolithoheterotrophy describes a type of microbial metabolism by which organisms oxidise an inorganic electron donor to supplement the generation of an electrochemical gradient. This results in higher overall growth yields and maximum specific growth rates as the organism does not need to generate as many reducing equivalents to fuel the respiratory chain and can instead redirect that material into anabolic reactions to generate more biomass. Many aspects of this metabolism remain poorly understood due to the difficulty in observing genuine chemolithoheterotrophy, with significant increases in the maximum specific growth yield (YMAX) and maximum specific growth rate (µMAX) seen in continuous …

Evidence For Alcohol-Mediated Hemolysis And Erythrophagocytosis, Chaowen Zheng, Siyuan Li, Johannes Mueller, Cheng Chen, Huanran Lyu, Guandou Yuan, Ane Zamalloa, Lissette Adofina, Parthi Srinivasan, Krishna Menon, Nigel Heaton, Stephan Immenschuh, Ines Silva, Vanessa Rausch, Seddik Hammad, Steven Dooley, Shilpa Chokshi, Antonio Riva, Songqing He, Sebastian Mueller

Peninsula Medical School

Alcohol-related liver disease (ALD) is the most common liver disease worldwide; however, its underlying molecular mechanisms remain poorly understood. Here, we identify ethanol-mediated hemolysis and erythrophagocytosis as major contributors to ALD pathogenesis using both in vitro and in vivo models, as well as surrogate markers such as heme oxygenase-1 (HO-1) and CD163, a scavenger receptor for hemoglobin-haptoglobin complexes. A key initial observation was the direct optical evidence of serum hemolysis in heavy drinkers, which diminished after one week of alcohol withdrawal. In parallel, soluble CD163 (sCD163) levels declined during alcohol detoxification correlating with liver damage and fibrosis stages. Moreover, red …

How Epilepsy Risks Might Be Introduced And Discussed In Clinical Consultations, Rohit Shankar

Peninsula Medical School

AbstractAdverse impacts of epilepsy (e.g., injury, depression, and Sudden Unexpected Death from Epilepsy (SUDEP) can be mitigated by factors that patients may control, such as medication adherence, improved sleep and diet, reduced alcohol and taking care around pregnancy. New guidelines state that risk should be discussed at the time of diagnosis but some clinicians express concern about not wanting to raise anxiety.ObjectiveTo explicate practices by which epilepsy expert clinicians broach discussions of risk in specialist epilepsy clinics.Methods24 recordings of initial telephone appointments at specialist clinics where epilepsy is diagnosed from two specialist outpatient epilepsy services in England were subjected to …

Epidemiology Of Thrombotic Thrombocytopenia Syndrome 2011 To 2022: English Sentinel Network Cohort Studies, José M. Ordóñez-Mena, Debasish Kar, Xuejuan Fan, Filipa Ferreira, Sneha N. Anand, Deborah Layton, David Clifton, Mark Joy, Anshul Thakur, Anu Alessi, Andrew Lee, Lisa Mather, Simon De Lusignan

Peninsula Medical School

Background and Objective: Thrombotic thrombocytopenia syndrome (TTS) is a rare condition following vaccination with adenovirus-vectored coronavirus disease 2019 (COVID-19) vaccines. This retrospective analysis of England primary care data aimed to estimate TTS event rates before, during, and after the COVID-19 pandemic, and following AZD1222 (ChAdOx1-nCoV-19) vaccination. Methods: Primary care data on TTS events were collected using the Oxford-Royal College of General Practitioners Research and Surveillance Centre sentinel network. TTS events were defined as thromboembolism with coincident (± 7 days) thrombocytopenia events using Systematized Nomenclature of Medicine clinical terms (the current Brighton Collaboration definition could not be used in the study …

Consensus-Based Research Priorities For Post-Collision Care In The Western Cape Province Of South Africa, Naseef Abdullah, Tim Nutbeam, Colleen J. Saunders, Craig Wylie, Nigel Lang, Willem Stassen

Peninsula Medical School

Introduction: Road traffic injuries constitute a significant global health burden, causing 1.3 million deaths and 50million injuries annually, with 92 % of fatalities occurring in low-and middle-income countries (LMICs). Despitethis disproportionate impact, research priorities in post-collision care often reflect high-income country contexts,creating a critical misalignment between evidence generation and contextual realities in LMICs.Methods: This mixed-methods study employed a three-phase approach to identify research priorities for postcollision care in the Western Cape, South Africa. Phase 1 consisted of a comprehensive literature review toidentify preliminary thematic areas and research questions. Phase 2 involved a stakeholder engagement workshop using modified nominal group techniques …

Letter-To-The-Editor To The Study By Bartek J Et Al “Multidisciplinary Consensus-Based Statement On The Current Role Of Middle Meningeal Artery Embolization (Mmae) In Chronic Subdural Hematoma (Csdh)” – A Letter From The International Csdh Research Group Committee, Icoric, T.S.R. Jensen, J. Duerinck, D. Holl, C. Iorio-Morin, J. Soleman, E. Edlmann

Peninsula Medical School

No abstract provided.

Demographic Profiles Of San Diego And Imperial Counties, Tessa Tinkler, Eo Hanabusa, Laura Deitrick, Connelly Meschen

Nonprofit Sector Issues and Trends

The Demographic Profiles of San Diego and Imperial Counties provides a snapshot of the two counties' vulnerable populations, including low-income communities, youth, immigrants, refugees, individuals experiencing homelessness, and retirement-age adults. While these counties differ in population size by more than an order of magnitude, the backdrop of California's rising cost of living, shifting immigration policies, income and health disparities, and the projections for an increasing aging population present compounding barriers to financial stability and access to services for all ages. Comprehensive data to understand these community needs was more readily available for San Diego County than Imperial County. This report …

Il-1 Signal Inhibition In Alcohol-Related Hepatitis: A Randomized, Double-Blind, Placebo-Controlled Trial Of Canakinumab, Nikhil Vergis, Vishal Patel, Karolina Bogdanowicz, Justyna Czyzewska-Khan, Rosemary Keshinro, Francesca Fiorentino, Emily Day, Paul Middleton, Stephen Atkinson, Thomas Tranah, Mary Cross, Daphne Babalis, Neil Foster, Emma Lord, Alberto Quaglia, Josephine Lloyd, Robert Goldin, William Rosenberg, Richard Parker, Paul Richardson, Steven Masson, Gavin Whitehouse, Cyril Sieberhagan, David Patch, Nikolai Naoumov, Ashwin Dhanda, Ewan Forrest, Mark Thursz

Peninsula Medical School

Background and Aims: Short-term mortality in alcohol-related hepatitis (AH) is high, and no current therapy results in durable benefit. A role for interleukin (IL)-1β has been demonstrated in the pathogenesis of alcohol-induced steatohepatitis. This study explored the safety and efficacy of canakinumab (CAN), a monoclonal antibody targeting IL-1β, in the treatment of patients with AH. Methods: Participants with biopsy-confirmed AH and discriminant function ≥32 but Model for End-Stage Liver Disease ≤27 were randomly allocated 1:1 to receive either CAN 3 mg/kg or placebo (PBO). Liver biopsies were taken before and 28 days after treatment. The primary endpoint was the overall …

Impact Of Social Deprivation Upon The Preoperative Pathway And Early Surgical Outcomes After Pancreatoduodenectomy For Pdac And Non-Pdac Periampullary Cancer In England: The Surg-Panc-Uk Study, Surg-Panc-Uk Study Group On Behalf Of Augis, Thomas W Thorne, Siobhan C Mckay, Samir Pathak, Richard Wilkin, Jenifer Barrie, John Moir, Keith J Roberts, Somaiah Aroori

Peninsula Medical School

BACKGROUND: Socioeconomic deprivation is linked to poorer outcomes in many cancers, however the impact of social deprivation on survival in resectable pancreatic and other peri-ampullary cancers appears mixed. Moreover, no studies consider the impact of social deprivation on diagnostic pathway length.

METHODS: A retrospective observational cohort study of adults with suspected periampullary cancer undergoing pancreaticoduodenectomy in England. Following surgery, patients were stratified by cancer type (PDAC, duodenal cancer, cholangiocarcinoma and ampullary cancer) and the impact of social deprivation (IMD deprivation quintiles) upon short-term survival and diagnostic pathway length analysed.

RESULTS: 648 patients from England with social deprivation data were identified, …

Discussing Poverty Within Primary Care Consultations: Implications For Mental Health Support, F. Thomas, K. Wyatt, K. Berzins, I. Lee, J. Horrell, A. Mcloughlin

Peninsula Medical School

No abstract provided.

A Mapping Review Of Studies Exploring The Barriers And Facilitators To A Dementia Diagnosis Through An Intersectionality Lens, Ben Hicks, Katherine Wheatley, Emma Porter, Nicolas Farina, Sube Banerjee

Peninsula Medical School

BackgroundPromoting a ‘timely’ diagnosis is a global policy directive.AimsThis review adopts an intersectional approach, visually mapping the existing literature to highlight gaps in the evidence base on barriers and facilitators to dementia diagnosis.MethodA systematic approach was undertaken, following the PRISMA guidelines, updating previous reviews. The literature search was conducted on PubMed, PsycINFO, CINAHL Complete and Scopus. In line with mapping review methodology, we report the current state of the literature by describing the number of studies that outline barriers and facilitators to seeking help for a dementia diagnosis, split by social categorisation.ResultsOn the 7 June 2024, a total of 45 …