151398 research outputs found
Sort by
Epigentics in pulmonary sarcoidosis inflammatory phenotype
No full textAim: Epigenetic modifications are emerging as important in regulating immune and fibrotic processes through gene expression in lung disease. We aim to assess how this can be applied to sarcoidosis.Methods: 79 patents with sarcoidosis underwent methylation analysis of 100ng of genomic DNA extracted from peripheral white blood cells, analysis was carried out using the methylkit package in R.Results: We stratified patients by detection of systemic inflammation (ESR >20 or CRP >7) at time of blood draw. 67 patients had no inflammatory signal. We identified 120 targets with q value > 0.05, focusing on genes which had > 5 log2 fold or < -5 Log2 fold change.Conclusion: Pathway analysis indicated genes with reduced activity were involved in a range of functions related to Sarcoidosis including adaptive immunity, interferon signalling, cell migration, and regulation T cell immunity. Genes with increased activity were involved in Interleukin signalling, and neutrophil degranulation. These genes have functions directly linked to the immune system, tissue remodelling, inflammation, or cell signalling, all of which are central in the pathophysiology of sarcoidosis
Protocol for an umbrella review of systematic reviews evaluating the efficacy of digital health solutions in supporting adult cancer survivorship care
No full textIntroductionThe growing number of people living with, through and beyond cancer poses a new challenge for sustainable survivorship care solutions. Digital health solutions which incorporate various information and communication technologies are reshaping healthcare; offering huge potential to facilitate health promotion, support healthcare efficiencies, improve access to healthcare and positively impact health outcomes. Digital health solutions include websites and mobile applications, health information technologies, telehealth solutions, wearable devices, AI-supported chatbots and other technologically assisted provision of health information, communication and services. The breadth and scope of digital health solutions necessitate a synthesis of evidence on their use in supportive care in cancer. This umbrella review will identify, synthesise, and compare systematic reviews which have evaluated the efficacy or effectiveness of digital solutions for adult cancer survivorship care with a particular focus on surveillance and management of physical effects, psychosocial effects, new cancer/ recurring cancers and supporting health promotion and disease prevention.Methods and analysisAn umbrella review of published systematic reviews will be undertaken to explore the types of digital health solutions used, their efficacy or effectiveness as a form of supportive care, and the barriers and enablers associated with their implementation. The umbrella review will be reported according to the Preferred Reporting Items for Overviews of Reviews (PRIOR) checklist. A search will be conducted across key databases. Records will be assessed independently by two review authors for eligibility against predefined criteria and will undergo two stage title, abstract and full text screening. All systematic reviews that meet the inclusion criteria will be assessed for quality using the AMSTAR 2 checklist with quality assessment and data extraction by two reviewers. The degree of publication overlap of primary studies across the included reviews will also be calculated and a mapping of the evidence will also be presented.Ethics and disseminationAs this research proposes using systematic reviews that are already published, ethical approval is not required. Results from this umbrella review will be published in a peer-reviewed journal where any significant deviations from the protocol will be justified
Diabetes-linked metabolic dysfunction relates with distinct tau phosphorylation patterns, neuroinflammation and cognitive impairment in mouse models of Alzheimer's disease
No full textAlzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β plaques and tau neurofibrillary tangles, with tau pathology being closely linked to cognitive decline. Growing evidence suggests that metabolic dysfunction including type 1 diabetes (T1D) and type 2 diabetes (T2D), as well as prediabetes (PreDM), exacerbate AD by promoting different degrees of insulinopenia, insulin resistance and hyperglycemia which can drive chronic inflammation and oxidative stress across multiple organs. Precisely how these metabolic disturbances influence tau phosphorylation remains unclear. To address this, we studied mouse models of AD, T1D, PreDM, T2D and the combination of AD with all three metabolic alterations, at 26 weeks of age, when pathologies are well established. The fact that we are including models of insulin resistance and insulin deficiency allows us to further explore the specific role of insulin as observed in the clinic. We assessed metabolic status, tau phosphorylation and cytokine levels in the brain cortex and cognitive function using the Morris water maze (MWM) and novel object discrimination (NOD) tests. Our results revealed that AD mice with metabolic disorders exhibited tau hyperphosphorylation, particularly at Ser199, Ser202/Thr205 and Ser404, correlating with metabolic dysfunction, cognitive impairment and inflammatory markers. Notably, AD-T2D mice showed the most severe deficits in MWM and NOD performance, indicating a synergistic cognitive decline. Machine learning analysis by random forest effectively classified AD-metabolic phenotypes, identifying key molecular and metabolic markers of neurodegeneration, mainly blood glucose and plasma insulin. These findings highlight the critical role of metabolic dysfunction in exacerbating tau pathology and accelerating cognitive decline in AD. Targeting metabolic pathways may provide concomitant therapeutic opportunities for AD patients with diabetes. Future research should explore interventions that restore insulin signaling and glucose metabolism to mitigate AD progression, probably by repurposing antidiabetic drugs.</p
Queer Theory “Teaching Queer International Relations Theory: A Conversation on Queer Activism, Politics, and Hope in the International Relations Classroom”
No full textTeaching Queer International Relations Theory means getting creative, and learning outside of the International Relations classroom. Neither of the chapter's authors teach courses exclusively about Queer Theory, and instead integrate Queer Theory throughout their teaching. For Jamie, research and teaching with a queer lens is motivated by being a queer lesbian committed to a feminist emancipatory practice. For Caitlin, Queer Theory allows her, as a White, straight cis woman, to both challenge the various gendered, sexual, and racial hierarchies and scrutinize the (dis)comforts and privileges she herself embodies, in search of a feminist and queerer vision of global politics. Queer Theory resists definition, and so the authors deliberately do not define it in this chapter. Instead, they offer their lived experiences and visions of what teaching Queer Theory means to them, that is, an approach, politics, and activism that is plural and grounded in the lived experiences of queer folks
Examining how multilingual learners engaged in a science modeling assessment through translanguaging
No full textAssessments that require students to articulate their scientific models in English can be challenging for multilingual learners, who may lack the language proficiency to do so. In response to these increasing language demands, we have developed a digital science modeling assessment task that is adaptable to these students' linguistic and semiotic resources, enabling them to demonstrate their knowledge and skills. A pilot study involving 32 multilingual learners in the United States revealed their ability to use various linguistic resources and multiple language modes to create, describe, and explain their models. The study underscores the importance of assessments that promote translanguaging, allowing students to exhibit their science learning through various representations and catering to the diverse needs of multilingual learners. The findings of this study are likely to influence the design of digital content assessments that enable multilingual learners to utilize translanguaging to demonstrate their knowledge and skills
Cascade error correction attack; exploiting implicit and side channel information leakage
No full textThis work presents a complete mathematical model of a novel cryptanalytic attack that combines the Cascade error correction leakages with the side channel information leakage to construct a more powerful attack than either of these two launched alone. We find that a higher Quantum Bit Error Rate (QBER) leaves Cascade more vulnerable to reliable information being extracted from side channel leakage and as such, reliable complete key recovery. For a key length of 1024bits and QBER of 0.2, on any device where the ratio between the difference of noiseless power consumption levels of an XOR function outputting 0 or 1, and power consumption noise, is greater than 1.7, a full key recovery is expected. For lower QBER, we see that for the ratio of the difference of noiseless power consumption and power consumption noise must higher in order to successfully recover the key
Variants of unknown significance in hyperlipidemia: a diagnostic quandary
No full textA 39-year-old woman was referred to a secondary care lipidology service after she was found to have severe mixed dyslipidemia at a workplace health check. The total cholesterol concentration was 7.8, nonfasting triglyceride 3.0, high-density lipoprotein cholesterol 1.8, low-density lipoprotein (LDL) cholesterol 5.2 [estimated using the Friedewald equation (1)] and non-high-density lipoprotein cholesterol 6.6 mmol/L. She was an ex-smoker and consumed approximately 5 units of alcohol per week (1 unit is equal to 8 g or 10 mL of pure alcohol). Her medical history was remarkable only for treated hypothyroidism; there was no personal history of atherosclerotic cardiovascular disease. Her mother had hypercholesterolemia, but there were no other relevant findings in the family. On examination, her body mass index was 24.0 kg/m2; there was no corneal arcus and no tendon xanthomata or cutaneous manifestations of dyslipidemia. She described intermittent chest pain, although the history was not typical of angina. Further biochemical investigations revealed hemoglobin A1c 35 mmol/mol, TSH 1.10 mIU/L, total bilirubin 4 µmol/L, alkaline phosphatase 57 U/L, aspartate transferase 13 U/L, gamma-glutamyl transferase 19 U/L, alanine aminotransferase 10 U/L, albumin 47 g/L, urea 4.1 mmol/L, and creatinine 56 µmol/L, all within reference ranges. Lipoprotein(a) was 290 nmol/L, deemed to be in the high risk range for cardiovascular disease (2). Ten-year cardiovascular risk was estimated at 1.4% using the QRISK3 calculator (3). This represented a relative risk of 2.0 compared to a healthy woman of her age and ethnicity. Computed tomography coronary angiography revealed a small focus of calcification in the left anterior descending coronary artery but no occlusive coronary artery disease. The Agatson computed tomography coronary artery calcium score was 14.5 (90th percentile for age and sex)
Catalytic production of aviation jet biofuels from biomass: a review
No full textThe aviation sector is a major emitter of fossil fuel-derived carbon dioxide contributing to global warming. For instance, jet fuel consumed by the aviation industry is 1.5–1.7 billion barrels per year, resulting in 705 million metric tons of carbon dioxide emissions. Aircraft manufacturers have set ambitious goals, aiming for carbon-free growth post-2020 and a 50% reduction in greenhouse gas emissions by 2030. This issue can be solved by replacing fossil fuels with biofuels produced from modern biomass, thus meeting the carbon neutral objective. Here, we review the technologies to convert biomass into jet biofuel with focus on reactants, catalysts, and the chemistry of combustion. Reactants include alcohols, oil, esters, fatty acids, gas and sugars. Catalysts include Fischer–Tropsch catalysts, palladium, platinum, ruthenium, nickel, and molybdenum. The utilization of jet biofuels could potentially reduce greenhouse gas emissions by up to 80%. We also discuss economic implications.<br/
