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Chlorinated organophosphate flame retardants in waste fabrics and foams: implications for waste management
Get PDFThe presence of some brominated flame retardants (BFRs) in food contact articles and childcare goods at levels lower than those allowed for flame retardancy is frequently linked to the recycling of flame retardant-treated plastics. In response to this, Low POP Concentration Limits (LPCLs) on the maximum permissible concentrations of some BFRs in waste have been established to ensure that waste plastics exceeding such limits are not recycled, hence limiting further contamination of the recycled plastic stream. Given that chlorinated organophosphate flame retardants (Cl-OPFRs) have similar toxicity and health impacts as BFRs, similar concentration limits are predicted to be adopted in the near future for Cl-OPFRs. This study measured Cl-OPFRs in fabrics and foams of waste furniture, end-life vehicle and childcare items from Ireland, the UK, and Saudi Arabia. Our investigation revealed that tris(1-chloro-2-propyl) phosphate (TCIPP) was the predominant Cl-OPFR detected in furniture and childcare items, while tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) was the predominant Cl-OPFR detected in vehicles and childcare items intended for car use. Cl-OPFR concentrations in the UK and Ireland significantly exceeded those in Saudi Arabia likely because of international differences in fire safety regulations. In addition, this study evaluated the utility of X-ray fluorescence (XRF) as a screening tool for regulatory compliance. Specifically, we measured chlorine (Cl) and phosphorus (P) as a surrogate indicator of the presence of Cl-OPFRs in waste fabric and foam. Our investigation revealed that XRF was not a reliable tool for identifying articles containing levels of Cl-OPFRs exceeding the national limit of 1,000 mg/kg. This is because of the high incidence of false exceedances observed in our analyses in 81 %, 74 %, and 97 % of samples from Ireland, the UK, and Saudi Arabia, respectively, as well as the high positive slopes and y-intercepts of plots of XRF Cl against GC/MS (gas chromatography/mass spectrometry) measurements of Cl-OPFRs. Finally, as human exposure to Cl-OPFRs via inhalation, dust ingestion, and dietary intake is crucial, this study assessed exposure to Cl-OPFRs via dermal contact with upholstered items. Our estimates of adult and toddler exposure to Cl-OPFRs via dermal uptake fall below the relevant health-based limit values
‘A new world spelt out in new men’: faith and Moral Re-Armament, c. 1920-1970
Get PDFThis thesis uses Moral Re-Armament - the evangelical Christian group previously known as The Oxford Group and currently known as Initiatives of Change, which was operational worldwide from the 1920s onward - to demonstrate that religious groups were able to change and adapt to the perceived challenges facing Christianity throughout the twentieth century. By doing so, this thesis directly challenges the assumption made by existing historiographies that a modernising Britain was fundamentally incompatible with faith. Adopting a change-not-decline approach to religion, the thesis brings to the forefront the non-traditional and alternative ways of believing which can be seen in Moral Re-Armament: ways of believing which have typically been dismissed by advocates of the secularisation theory as remnants of a lost religious society, or a desperate last-attempt to uphold the importance of faith in a presumed-to-be secular Britain. By exploring the design and dissemination of Moral Re-Armament’s faith, as well as the intense devotion of its followers, this thesis argues that twentieth century Britain continued to witness meaningful experiences of Christianity which were adapted and made new. Additionally, this thesis addresses the surprising lack of historical attention received by a group
as large as Moral Re-Armament, particularly within its British context, given its importance to the stories we tell about religious belief in twentieth century Britain. Ultimately, what is made clear through an exploration of Moral Re-Armament is the importance of moving away from historical narratives which presume religious decline and consequently ignore the very valid and real expressions of faith which remain
Exploring emoji sentiment roles in Arabic textual content on digital social networks
Get PDFIn today’s digital landscape, emoji have risen as pivotal elements in articulating sentiment, especially within the intricacies of the Arabic language. This thesis examines the various roles that emoji can play in expressing sentiment in Arabic texts, highlighting their relevance both in academic and real-world contexts. Beginning with foundational insights, our investigation retraces the history of emoji as important non-verbal communicative tools in human interaction. Then, we explore the distinct challenges of sentiment analysis in Arabic and refer to a thorough review of previous studies to frame our method, identifying both established techniques and unexplored opportunities. At the heart of our research is the understanding that, depending on the context, an emoji can adopt a wide variety of sentiment roles. These range from acting as an indicator, mitigator, emphasizer, reverser, releaser, or trigger of either negative or positive sentiment. Additionally, there are instances where an emoji simply maintains a neutral effect on the sentiment of the accompanying text. To achieve this, we gathered a large dataset, mainly from Twitter, and developed lexicons of words and emoji tailored for sentiment analysis in Arabic. These lexicons were the basis of our analysis model. By leveraging the insights gained from the emoji-roles sentiment lexicon and combining them with our established knowledge of the sentiment roles associated with specific emoji patterns, we make a significant improvement in the conventional sentiment classifier based on the emoji lexicon. Traditional methods often assign a static sentiment score to an emoji, failing to consider its varying roles in different textual contexts. Our refined approach corrects this oversight. Instead of considering a singular unchanging sentiment score for each emoji, the classifier dynamically retrieves sentiment scores based on the specific role the emoji plays within a given sentence. In conclusion, we compare our method with other Arabic sentiment analysis tools, demonstrating the value of our approach, especially within nuanced linguistic phenomena such as sarcasm and humour. This thesis sets the foundation for future Arabic research in this expanding domain
Energy and Sovereignty: Oil and Decolonisation in Algeria and France, 1956-1975
No full textThis thesis argues that the histories of decolonisation and energy need to be combined in new ways. Through a socio-technical analysis of the hydrocarbon sector, the thesis argues that oil fundamentally reshaped the end of empire and process of decolonisation across France and Algeria.
The analysis adopts the method of ‘following’ oil and gas across France and Algeria. Traversing the conventional watershed of 1962 and Algerian independence, it focuses on the two decades between the discovery of oil in Algeria in the mid-late 1950s and the mid-1970s, when Algeria stood at the forefront of an international struggle for economic independence and a new global economic order, as a result of its successful nationalisation of oil.
The thesis explores the relationship between an assemblage of ‘oil actors,’ spanning the state, private companies, oil workers, and local communities, with a focus on how these actors moulded sovereignty and nation-building. I argue that the social and commercial influence of these actors shaped political agency as well as policy application and outcomes in ways that have been overlooked by a historiography which focuses on oil as an economic prize or elite tool. By analysing the nexus of relations that bound oil actors together, the thesis seeks to shed new light on how these actors mediated, interpreted, and deployed imperial structures and legacies. The account uses these perspectives to rethink the conventional chronology of decolonisation across the Mediterranean
Interrogating hypoxia-mediated CD8 T cell dysfunction in multiple myeloma
Get PDFIntroduction: Multiple myeloma (MM) is an incurable plasma cell malignancy that develops in the bone marrow (BM). The BM is understood to be immunosuppressive and hypoxic, which may limit therapeutic responses to immune-directed therapies. This thesis interrogates whether the hypoxic nature of the BM environment drives CD8 T cell dysfunction.
Methods: CD8 T cells are isolated from healthy human peripheral blood and incubated overnight in normoxia (21% oxygen) or hypoxia (1% oxygen) to allow oxygen level equilibration. Cells are activated by anti-CD3/anti-CD28 antibodies and analysed for immune function, metabolism and signalling. MM patient samples, including blood and BM mononuclear cells, are analysed ex vivo by flow cytometry.
Results: CD8 T cells stimulated in hypoxia demonstrate impaired proliferation, CD25 expression and IFN-gamma production. However, TNF-alpha production, granzyme-B expression and CD107a externalisation are unaffected by hypoxia. A defect in T cell signalling lies at the level of mTOR, with impact on downstream targets. Stable isotope-based metabolic tracing identifies a reduction of activation-induced glycolysis, glucose oxidation and glutaminolysis in hypoxia. Bulk RNA sequencing and flow cytometric analysis identify BNIP3 as a marker of hypoxia and potential mechanisms driving mTOR suppression in hypoxia are explored. Stimulation of CD8 T cells with a BCMAxCD3 bispecific antibody and BCMA-expressing MM cell lines bring these findings into a therapeutic context. CD8 T cells from the BM of MM patients demonstrate impaired proliferation and expression of c-Myc compared to those from the PB.
Conclusion: Hypoxia impairs CD8 T cell signalling, activation and specific effector functions alongside activation-induced metabolic reprogramming. These intrinsic effects correlate with reduced function of MM patient CD8 T cells found in the BM compared to the PB. This work could aid understanding the limitations of response with immune-directed therapies acting within a hypoxic environment
Multimorbidity in pregnancy: Epidemiology and core outcome set
Get PDFBackground: Women are increasingly entering pregnancy with two or more long-term physical or mental health conditions. This can impact on the outcomes for the pregnant women and her offspring. This thesis aims to (i) describe the epidemiology of multimorbidity in pregnancy in the United Kingdom (UK) and (ii) develop a core outcome set for studies of pregnant women with multimorbidity.
Methods: The epidemiological study used an observational study design utilising routine health records in the UK. This included primary care records (Clinical Practice Research Datalink [CPRD, UK] and Secure Anonymised Information Linkage [SAIL, Wales]); and secondary care records with linked community prescriptions (Scottish Morbidity Records [SMR]).The study population was pregnant women and the exposure was pre-existing multimorbidity (2 or more long-term conditions). Multimorbidity was operationalised by 79 long-term conditions selected by a multidisciplinary team. Logistic regression was performed to examine the association of maternal multimorbidity with sociodemographic factors.
The core outcome set development consisted of four stages: (i) systematic literature search, (ii) focus groups with stakeholders in the UK, (iii) international Delphi surveys, and (iv) virtual consensus meetings.
Results: Amongst women pregnant in 2018 in the UK, the prevalence of multimorbidity was 44.2% (95% CI 43.7–44.7%), 46.2% (45.6–46.8%) and 19.8% (18.8– 20.8%) in CPRD, SAIL and SMR respectively. When limited to health conditions that were active in the year before pregnancy, the prevalence of multimorbidity was still high (24.2% [23.8–24.6%], 23.5% [23.0–24.0%] and 17.0% [16.0 to 17.9%] in the respective datasets). Logistic regression showed that pregnant women with multimorbidity were more likely to be older (CPRD England, adjusted OR 1.81 [95% CI 1.04–3.17] 45–49 years vs 15–19 years), multigravid (1.68 [1.50–1.89] gravidity ≥ five vs one), have raised body mass index (1.59 [1.44–1.76], body mass index 30+ vs body mass index 18.5–24.9) and smoked preconception (1.61 [1.46–1.77) vs non-smoker).
For the core outcome set development study, 26 studies were included in the systematic literature search (2017 to 2021) reporting 185 outcomes. Three virtual focus groups (n=22) were conducted from December 2021 to March 2022 in the United Kingdom. Thematic analysis of the focus groups added 28 outcomes. Two hundred and nine stakeholders completed the first Delphi survey. One hundred and sixteen stakeholders completed the second Delphi survey where 45 outcomes reached Consensus In (≥70% of all participants rating an outcome as Critically Important). After two rounds of consensus meetings (first meeting n=13, second meeting n=17), the final core outcome set included 11 outcomes: The five maternal outcomes were: maternal death, severe maternal morbidity, change in existing long-term conditions (physical and mental), quality and experience of care, and development of new mental health conditions. The six child outcomes were: survival of baby, gestational age at birth, neurodevelopmental conditions/impairment, quality of life, birth weight, and separation of baby from mother for health care needs.
Conclusion: Multimorbidity is highly prevalent in pregnant women in the United Kingdom. We developed a core outcome set to guide future studies for pregnant women with multimorbidity. The next step would be to quantify the association between maternal multimorbidity and outcomes for the women, the pregnancy, and their offspring
AMIGO3 gene expression and function during oligodendrocyte differentiation in the central nervous system
Get PDFDemyelination causes disruption to neuronal signalling and occurs in many neurodegenerative diseases or in response to brain injury. There are no cures available for demyelinating diseases, including multiple sclerosis (MS), the most common autoimmune inflammatory disease in the central nervous system (CNS). Current approaches to treat MS focus on anti-inflammatory drugs, which prevent demyelination progression and reduce clinical relapses, but do not allow repair or replacement myelin. A natural repair process called remyelination can occur following demyelination. Remyelination can help to repair demyelinating plaques and protect axons from degeneration, but endogenous remyelination is inefficient and fails with ageing and disease progression, Improving remyelination is therefore an important for the focus for the development of MS therapies. Studies of animal models have to led to the discovery of new therapeutic targets which can promote endogenous remyelination. An example is the leucine rich repeat protein (LRRP) leucine rich repeat and immunoglobulin-like domain containing protein 1 (LINGO1). Inhibition of LINGO1 promoted remyelination in several animal models of demyelination, but clinical inhabitation of LINGO1 showed unsuccessful results in clinical trials. We considered the idea that the LINGO1 clinical trials failed due to compensation from another LRRP, amphoterin-induced gene and open reading fram-3 (AMIGO3). AMIGO3 is upregulated more rapidly than LINGO1 after spinal cord injury (SCI) in animal models, and also increases in expression rapidly after axotomy in culture of dorsal root ganglion neurons and retinal ganglion cells. Importantly, AMIGO3 expression is rapidly increased in the CNS during postnatal development when myelinating oligodendrocyte (OL) are generated, and decreases again quickly after myelination begins. AMIGO3 may therefore act a regulator of OL differentiation, and its inhibition could be an alternative therapeutic target for demyelinating diseases.
Considering the above, the first aim of this project was to study the function of AMIGO3 using in vitro models of OL differentiation. For this work, a primary mixed glial culture system was developed to study OL differentiation during early stage of CNS development. Using this system we found that AMIGO3 is downregulated in mixed glial cultures during OL differentiation. We also found that downregulation of AMIGO3 expression by siRNA resulted in the upregulation of OL maturation. On the other hand, increased AMIGO3 levels produced by treatment with recombinant AMIGO3 reduced OL maturation, and activated RhoA GTP activity, a molecule involved in AMIGO3 intracellular signalling. These findings suggest that AMIGO3 downregulates OL differentiation via RhoA GTP signalling.
AMIGO3 is known to engage in homotypic interactions, thus expression on different glial cells could allow cell to cell signalling. Also, AMIGO3 is expressed in cells of the OL lineage and astrocytes, thus AMIGO3 expression in non-OL glia could provide a signal to regulate OL differentiation. Considering this idea, the second aim in this thesis was to compare the expression of AMIGO3 and LINGO1 in primary cultures of astrocytes and microglia. Using Western blot and immunocytochemistry we found strong expression of AMIGO3 proteins in astrocytes, but not in microglia. Surprisingly, we also found that astrocytes express LINGO1 proteins. This work shows that astrocytes, but not microglia, are an abundant source of both AMIGO3 and LINGO1, which together could influence OL differentiation and myelin formation and repair
The production, circulation, and reception of sexual knowledges in published advice literature in Britain and Ireland, 1918-1987
Get PDFThis thesis investigates the markets, networks, mediating institutions and individuals behind the production, circulation, and reception of popular sexual knowledges in published advice literature in Britain, the Irish Free State, and the Republic of Ireland between 1918 and 1987. It uses archives of publishers, authors, libraries, and bookshops to trace these processes. I argue that taking these processes and those involved in them at all stages seriously opens up possibilities for understanding the polyvocal, uneven, and complicated story of the development of sexual culture. I show that advice literature occupied a ‘grey zone’ in sexual culture physically located in public spaces such as retail and library locations, raising questions about who had access to which knowledges, where, and what this could mean both culturally and for understandings of the self.
My methodology brings book and publishing histories into conversation with cultural histories of sex and sexuality. In doing so, it demonstrates the hitherto unrecognised significance of publishers, their relationships with ‘sex experts’, and the markets and institutions within, through, and between which advice books and related ephemera circulated for the production and movement of ideas about sex, bodies, and desires. Piecing together a patchwork of correspondence in publishing, institutional, and individual archives, this thesis ultimately complicates teleological narratives of ‘sexual revolution’ in the twentieth century by arguing that the process of knowledge production was layered and iterative. Through this, I place significance on the interwar period as a pivotal moment in the development of sexual culture, pushing back against narratives of encompassing, transformative change in the latter half of the century
The representation of victimhood, agape and eros in selected interwar and post-1990 First World War prose fiction
Get PDFMy thesis assesses the cross-cultural literary treatments of the trope of innocent victimhood that became apparent in commemorations between 2014 and 2018 of the centenary of the First World War in Germany, Turkey, Armenia, France and Britain. These literary treatments challenge the notion, promoted by national centenary commemorations, that participants in the conflict were innocent victims of tragic circumstances. Although these centenary commemorations were set in specific national contexts, their transnational common denominator is their silence concerning the predicaments of victims of state-induced injustices and on the question of human agency during the conflict. This thesis examines innocent victimhood in fictional First World War texts in which the victims of state-induced injustice take center stage. The four war-related injustices are anti-Semitic discrimination, ethnic cleansing, military injustice, and inhumane psychiatric treatment. The trope of innocent victimhood is examined in four separate chapters. In each case, one interwar novel is compared to thematically related post-1990 texts. The novels originate from a wide range of cultural backgrounds.
I argue that in First World War prose fiction dealing with state-induced injustice, the cross-cultural recurring pattern that emerges is the nexus between the fictional protagonists’ feelings of guilt and love, which are discussed in relation to the portrayal of victimhood in the texts. In each of the novels under examination, guilt and love complicate the trope of innocent victimhood that marks the official commemorative discourses. The presence of these two feelings allows these protagonists to retain a considerable amount of human agency despite being victims of injustices. The notion of guilt has not received sufficient attention by literary critics of First World War fiction so far. The thesis shows that two kinds of love, selfless agape, based on a sense of solidarity with other victims of injustice, and self-centred eros, based on romantic love and family relations, emerge in the texts. The thesis demonstrates that, in the world of First World War fictional prose, human agency is portrayed in all its complexity. Drawing on Primo Levi’s concept of ‘vast grey zones of conscience’, my thesis describes how the clear-cut distinction between victims and perpetrators is blurred by the portrayal of the protagonists’ guilt in the context of the state-induced crimes committed against them. I argue that by highlighting the issue of responsibility for actions and decisions taken by victims of injustice, literature can provide an important corrective to the over-simplified public perceptions that participants in the conflict were innocent victims
Control of trunk muscle force in individuals with low back pain: new insights revealed by high-density surface electromyography
Get PDFLow back pain (LBP) is a leading cause of disability worldwide, with chronic non-specific LBP (CLBP) accounting for most cases. It is well-recognised that individuals with LBP exhibit different movement patterns compared to those without pain. Extensive research has examined motor adaptations in individuals with CLBP, highlighting alterations in trunk muscle strength, muscle activity, movement patterns, and proprioceptive acuity. Recent studies have also shown that musculoskeletal pain, including CLBP, can impair muscle force control. However, the concept of force or torque steadiness as a motor adaptation in people with CLBP has been relatively understudied and therefore requires further investigation. This thesis presents research that focuses on enhancing our understanding of motor adaptations in people with CLBP, specifically in relation to changes in the control of trunk muscle force/torque steadiness and the potential underlying neuromuscular mechanisms. To achieve this, it examines the relationship between trunk high-density electromyography (HDsEMG) signals and torque using cross-correlation and coherence analyses, and principal component analysis (PCA) to improve these estimations. The first study examined the control of trunk muscle force and EMG-torque relationships during isometric trunk extension contractions, revealing that individuals with CLBP have poorer control compared to pain-free individuals. People with CLBP performed the contractions with altered recruitment strategies, including a higher contribution of more cranial regions of the lumbar erector spinae (ES) to the resultant torque and a failure to increase the contribution of the lumbar ES to the resultant torque with an increase in load. The second study extended these findings to dynamic trunk flexion/extension concentric and eccentric contractions, showing that the control of trunk muscle force is also impaired during these movements alongside altered recruitment patterns. These involved a higher contribution of the thoracolumbar ES to torque, as observed in the first study during trunk extension contractions, and increased abdominal muscle activity, with the centre of activation being more cranial and a higher contribution of this musculature to the resultant torque (particularly the external oblique muscle) during trunk flexion. In contrast, the third study, which investigated the effects of acute low-back soreness induced by delayed onset of muscle soreness (DOMS) on trunk muscle function, recruitment behaviour, movement patterns, and underlying neuromuscular mechanisms, showed that DOMS did not impair trunk force control. However, EMG-torque relationships and kinematics were altered in a contraction-dependent manner. During eccentric contractions, a decrease in the thoracolumbar ES contribution to the resultant torque was observed, and individuals showed increased lumbar flexion during the more demanding contractions. During concentric contractions, a reduction in thoracolumbar range of motion in the sagittal plane was observed, suggesting the maintenance of a more neutral lumbar spine posture, but no alterations in HDsEMG-torque relationships were observed in the presence of DOMS. These findings suggest that pain-free individuals could adapt their motor strategies and maintain muscle performance despite DOMS. The fourth study was a systematic review and meta-analysis that explored the influence of clinical and experimental musculoskeletal pain on the control of muscle force. The findings of this review suggested that the persistent, multidimensional nature of clinical musculoskeletal pain is related to more pronounced impairments in force control compared to the temporary nature of experimental pain, particularly for the trunk. The results of this thesis underscore the importance of evaluating torque steadiness in individuals with CLBP. The findings indicate that people with CLBP exhibit impaired force control and altered trunk muscle recruitment strategies. Future research should explore the value of torque steadiness training and HDsEMG-based biofeedback for enhancing torque steadiness performance in this patient population. These interventions could lead to better-targeted therapies that address the specific neuromuscular deficits associated with CLBP
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