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The Effect of Lens Shape, Zonular Insertion and Finite Element Model on Simulated Shape Change of the Eye Lens
No full textThe process of lens shape change in the eye to alter focussing (accommodation) is still not fully understood. Modelling approaches have been used to complement experimental findings in order to determine how constituents in the accommodative process influence the shape change of the lens. An unexplored factor in modelling is the role of the modelling software on the results of simulated shape change. Finite element models were constructed in both Abaqus and Ansys software using biological parameters from measurements of shape and refractive index of two 35-year-old lenses. The effect of zonular insertion on simulated shape change was tested on both 35-year-old lens models and with both types of software. Comparative analysis of shape change, optical power, and stress distributions showed that lens shape and zonular insertion positions affect the results of simulated shape change and that Abaqus and Ansys show differences in their respective models. The effect of the software package used needs to be taken into account when constructing finite element models and deriving conclusions.</p
Kinome‐Wide Synthetic Lethal Screen Identifies PANK4 as a Modulator of Temozolomide Resistance in Glioblastoma
No full textTemozolomide (TMZ) represents the cornerstone of therapy for glioblastoma (GBM). However, acquisition of resistance limits its therapeutic potential. The human kinome is an undisputable source of druggable targets, still, current knowledge remains confined to a limited fraction of it, with a multitude of under‐investigated proteins yet to be characterized. Here, following a kinome‐wide RNAi screen, pantothenate kinase 4 (PANK4) isuncovered as a modulator of TMZ resistance in GBM. Validation of PANK4 across various TMZ‐resistant GBM cell models, patient‐derived GBM cell lines, tissue samples, as well as in vivo studies, corroborates the potential translational significance of these findings. Moreover, PANK4 expression is induced during TMZ treatment, and its expression is associated with a worse clinical outcome. Furthermore, a Tandem Mass Tag (TMT)‐based quantitative proteomic approach, reveals that PANK4 abrogation leads to a significant downregulation of a host of proteins with central roles in cellular detoxification and cellular response to oxidative stress. More specifically, as cells undergo genotoxic stress during TMZ exposure, PANK4 depletion represents a crucial event that can lead to accumulation of intracellular reactive oxygen species (ROS) and subsequent cell death. Collectively, a previously unreported role for PANK4 in mediating therapeutic resistance to TMZ in GBM is unveiled.</p
Formulated palmitoylethanolamide supplementation improves parameters of cognitive function and BDNF levels in young, healthy adults: a randomised cross-over trial
No full textBackground: Palmitoylethanolamide (PEA) is an endocannabinoid-like lipid mediator which is naturally produced in the body and found in certain foods. The aim of this study was to assess the effect of a bioavailable formulated form of PEA (Levagen+®) on serum BDNF levels and parameters of cognitive function in healthy adults. Methods: A randomised double-blinded placebo-controlled cross-over trial was implemented to measure the effects of a 6-week 700 mg/day course of formulated PEA supplementation versus a placebo. Participants (n = 39) completed pre- and post-assessments of a lab-based cognitive test. Serum samples were collected to measure BDNF concentrations using an immunoassay. Results: A significant increase in serum BDNF levels was found following PEA supplementation compared with the placebo (p = 0. 0057, d = 0.62). The cognition test battery demonstrated improved memory with PEA supplementation through better first success (p = 0.142, d = 0.54) and fewer errors (p = 0.0287; d = −0.47) on the Paired Associates Learning test. Conclusion: This was the first study to report a direct beneficial effect of Levagen+® PEA supplementation on memory improvement as well as corresponding increases in circulating neurotrophic marker levels. This suggests that formulated PEA holds promise as an innovative and practical intervention for cognitive health enhancement
Navigating the Nexus of Relevance in Doctoral Research in Architecture
No full textThe text adeptly contextualizes the discourse surrounding relevance in architectural research, drawing upon the insights gleaned from the dedicated academic conference hosted at Anglia Ruskin University in July 2023.</p
Alexander Campbell's covenantal baptism and its Presbyterian debaters on the American frontier(s) in reformed focus
No full textThis thesis represents Alexander Campbell (1788-1866), one of Ulster’s most impactful Presbyterian immigrants to America, as an Ulster-Scot who contributed intellectually to America’s religious frontier by debating aspects of Scottish/Ulster-Scottish theology.The thesis represents Campbell in debate over baptism, with other Ulster-Scots, namely Nathan Rice (1807-1877), John Walker (1784-1845), Samuel Ralston (1756-1851), William Maccalla (1788-1859) and Henry Cooke (1788-1868). It maintains that Campbell and his UIster-Scottish compatriots contributed intellectually to the American religious frontier. Importantly, the thesis maintains that there are two features of Campbell’s intellectual contribution. These features are his sacramental theology and his challenge to paedobaptists to develop a New Testament baptismal theology. The thesis contributes to current academic discussion by correcting a misrepresentation alleged by some historians that Ulster-Scots made no intellectual contribution to the American Frontier.The thesis interacts with Campbell’s assertion that he restored New Testament baptism by representing it as a sacrament, not merely as a sign, that is a response of faith. This involved an amalgamation of a Catholic sacramentalism with Protestant Evangelicalism. Essentially, it is salvation by both decisional and baptismal regeneration. In part three, the thesis also interacts with Campbell’s five-point challenge to paedobaptists to construct a New Testament baptismal theology.Part three is crucial for the thesis’s coherence because it demonstrates that Campbell’s intellectual contribution was scholarly by affirming not so much its veracity but its validity as a theological perception with which other perceptions can interact. Accordingly, part three of the thesis shows that Campbell’s ideas have currency, beyond his 19th century situation in life, into the 20th and 21st centuries through a wider discussion with Reformed theologians. Specific evidence of this currency is provided by references to two famous 20th century baptismal debates, together with the 21st century debate known as the Federal Vision.</p
"One never dropped a hat pin!": a mixed methods analysis of the factors influencing mental health and wellbeing in middle-aged and older LGBTI+ people in the UK
No full textThis thesis explores the factors which influence mental health and wellbeing in middle-aged (MA) and older LGBTI+ people living in the UK. Current research on this topic is limited and the study aims to provide new insights which policy makers, local authorities, community organisations and scientists can consider in their commissioning intentions, policy making and research in the fields of economics and healthcare through the lens of theories relating to minority stress and health equity in ageing. Initial questions were formulated into five thematic hypotheses for testing and analysis. The first three investigate the relationship between wellbeing and discrimination, stigma, social support and identity, the fourth investigates specific effects relating to race and ethnicity and wellbeing, and the final thematic hypothesis investigates factors affecting access to health services from this population group. A mixed methods approach was chosen and an exploratory sequential design model adopted, providing the opportunity for an initial qualitative enquiry to take place, in order to (i) identify topics specific to the UK context and test elements of the international literature; and (ii) to validate the conceptual framework and instruments for wider application, via interviews with 24 participants. The second phase took the format of a national online survey which yielded data from 248 respondents.Findings from the qualitative phase identified eight major themes for further exploration: identity, ‘coming out’, opinions of others, social support, stigma and discrimination, positive moderators, mental health aspects, and ‘new’ information not identified in the literature – this final area included early insights into the effect of the COVID-19 pandemic on the wellbeing of LGBTI+ people. The survey offered a sense of magnitude of these phenomena through statistical testing, and yielded further insights on age group differences. The outcomes indicate that, even today, there exists significant stigmatization in being LGBTI+, demonstrated through types and levels of discrimination, further compounded when intersections of age and in some cases, race, are included. Positive associations between social support mechanisms offer a strong mitigating effect, both on the wellbeing of older LGBTI+ people, and on how they access healthcare services.Combining both sets of findings yielded new insights into the wellbeing of LGBTI+ MA/older people, for example, that in some cases, people have better wellbeing as they age. This enabled the conceptual framework to be adapted and a new model to be proposed which contributes to the current knowledge in this field: the Wellbeing Promotion Model. The study also adds to and extends the current academic literature by providing new insights and theoretical perspectives, including the negative associations of economic condition and the COVID-19 pandemic on wellbeing.</p
Aesthetic Dynamics of Experiential Space in Architecture
No full textAesthetic dynamics in architectural experience engages spatial dynamics as well as formal dynamics through embodied simulation. Spatial dynamics can be rendered visible through computational representation, informing and enriching digital tectonics</p
Prevalence and factors associated with depression and anxiety among COVID-19 survivors in Dhaka city
No full textBackground: Coronavirus disease 2019 (COVID-19) is a global public health concern. Evidence shows that depression and anxiety are common among patients with COVID-19 after recovery. About one-third of the total COVID-19 cases in Bangladesh have been reported in Dhaka city. Therefore, the study aimed to evaluate the prevalence of depression and anxiety among COVID-19 survivors in Dhaka city as well as to identify the factors associated with these mental health conditions.
Methods: A cross-sectional study was carried out among a total of 384 COVID-19 survivors aged 18 years or older. Data collection was done through face-to-face and telephone interviews using a semi-structured questionnaire. Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder (GAD-7) scales were used to assess depression and anxiety, respectively. Binary logistic regression analysis was performed to identify the predictors of depression and anxiety among patients recovered from COVID-19.
Results: The overall prevalence of depression and anxiety was 26.0% and 23.2%, respectively among COVID-19 survivors. The respondents who were ≥60 years were 2.62 and 3.02 times more likely to report depressive and anxiety symptoms, respectively than those aged 18 to 39 years. Hospitalised patients recovered from COVID-19 had a 2.18 times higher chance of developing anxiety than their non-hospitalised counterparts. COVID-19 recovered patients with comorbidities were at 3.35 and 2.97 times higher risk of depression and anxiety, respectively compared to those without comorbidities. Similarly, the respondents who had already passed a period of 15 days to 3 months after recovery showed 3.06 and 1.85 times higher odds of depression and anxiety, respectively than those who had already passed a period of above 3 to 6 months after recovery.
Conclusion: The study reported a high prevalence of depression and anxiety among COVID-19 survivors living in Dhaka city. The findings suggest the need for appropriate interventions to reduce mental health complications in COVID-19 survivors.</p
The effect of limited access to antenatal care on pregnancy experiences and outcomes among undocumented migrant women in Europe: a systematic review
No full textWomen who are undocumented migrants in Europe encounter a variety of challenges while trying to access health services, including restricted access to antenatal care (ANC) despite the importance of ANC to the well-being of mothers and their infants. This study's aim was to examine the effect that limited access to antenatal care has on the pregnancy experiences and outcomes of undocumented migrant (UM) women in Europe. Systematic searches were done on PubMed, Ovid MEDLINE, Ovid EMBASE, EBSCO CINAHL Plus, and BioMed Central. From the search results, only primary research articles that reported on the pregnancy outcomes and experiences of undocumented migrants were selected. A meta-analysis was not possible because this review included information from both qualitative and quantitative studies. The data that was taken from the included publications was organised, analysed, using the Microsoft Excel programme, and then meta-synthesised. Twelve papers from seven different European nations—Belgium, France, Sweden, Denmark, Norway, Finland, and England—were included in this systematic review. Eight of the studies aimed to explore the access to and utilization of ANC by undocumented migrant women and the related pregnancy outcomes. Two of the included studies examined the pregnancy experiences of UMs and two examined the perinatal risks associated with living as a migrant with no legal status. Although heterogeneous in their specific findings most of the studies showed undocumented immigrants are more likely to experience unfavourable pregnancy outcomes and experience greater anxiety and worries due to a variety of factors than documented migrants and registered citizens. This review's conclusions demonstrate the pressing need for policy modifications and healthcare reforms in Europe to address the problems associated with undocumented migrants’ restricted access to antenatal care. It also highlights the urgent need for structural changes that will give this vulnerable population's health and well-being a higher priority. It is not just an issue of health equality but also a humanitarian obligation to address the many obstacles and difficulties undocumented migrant women endure during pregnancy
The vagus nerve mediates the physiological but not pharmacological effects of PYY3-36 on food intake
No full textPeptide YY (PYY3-36) is a post-prandially released gut hormone with potent appetite-reducing activity, the mechanism of action of which is not fully understood. Unravelling how this system physiologically regulates food intake may help unlock its therapeutic potential, whilst minimising unwanted effects. Here we demonstrate that germline and post-natal targeted knockdown of the PYY3-36 preferring receptor (neuropeptide Y (NPY) Y2 receptor (Y2R)) in the afferent vagus nerve is required for the appetite inhibitory effects of physiologically-released PYY3-36, but not peripherally administered pharmacological doses. Post-natal knockdown of the Y2R results in a transient body weight phenotype that is not evident in the germline model. Loss of vagal Y2R signalling also results in altered meal patterning associated with accelerated gastric emptying. These results are important for the design of PYY-based anti-obesity agents.</p
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