139 research outputs found

    Adoption of technology enabled care to support the management of children and teenagers in rheumatology services: a protocol for a mixed-methods systematic review

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    Introduction COVID-19 catalysed a rapid move to provide care away from the hospital using online communication platforms. Technology enabled care (TEC) continues to be an important driver in progressing future healthcare services. Due to the complex and chronic nature of conditions seen within paediatric rheumatology, TEC may lead to better outcomes. Despite some growth in published literature into the adoption of TEC in paediatric rheumatology, there is limited synthesis. The aim of this review is to provide a comprehensive understanding and evaluation of the adoption of TEC by patients in paediatric rheumatology services, to establish best practices. Methods and analysis This proposed mixed-methods systematic review will be conducted by searching a wide variety of healthcare databases, grey literature resources and associated charities and societies, for articles reported in English language. Data extraction will include population demographics, technology intervention, factors affecting adoption of intervention and consequent study outcomes. A parallel-results convergent synthesis design is planned, with independent syntheses of quantitative and qualitative data, followed by comparison of the findings of each synthesis using a narrative approach. Normalisation process theory will be used to identify, characterise and explain implementation factors. The quality of included articles will be assessed using the Mixed Methods Appraisal Tool for research papers and the Authority, Accuracy, Coverage, Objectivity, Date, Significance checklist for grey literature. Overall confidence in quality and strength of evidence will be assessed using the Confidence in the Evidence from Reviews of Qualitative Research tool. Ethics and dissemination Ethical approval is not required due to the nature of this mixed-methods systematic review. The findings will be disseminated via a peer-reviewed journal, relevant conferences and any other methods (eg, via NHS Trust or NIHR YouTube channels) as advised by paediatric rheumatology patients

    Sex-Dependent Effects of Cardiometabolic Health and APOE4 on Brain Age: A Longitudinal Cohort Study.

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    The aging population is growing faster than all other demographic strata. With older age comes a greater risk of health conditions such as obesity and high blood pressure (BP). These cardiometabolic risk factors (CMRs) exhibit prominent sex differences in midlife and aging, yet their influence on brain health in females vs males is largely unexplored. In this study, we investigated sex differences in relationships between BP, body mass index (BMI), and brain age over time and tested for interactions with APOE ε4 genotype (APOE4), a known genetic risk factor of Alzheimer disease. The sample included participants from 2 United Kingdom-based longitudinal birth cohorts, the Lothian Birth Cohort (1936) and Insight 46 (1946). Participants with MRI data from at least 1 time point were included to evaluate sex differences in associations between CMRs and brain age. The open-access software package brainageR 2.1 was used to estimate brain age for each participant. Linear mixed-effects models were used to assess the relationships between brain age, BMI, BP, and APOE4 status (i.e., carrier vs noncarrier) in males and females over time. The combined sample comprised 1,120 participants (48% female) with a mean age (SD) of 73 (0.72) years in the Lothian Birth Cohort and 71 (0.68) years in Insight 46 at the time point 1 assessment. Approximately 30% of participants were APOE4 carriers. Higher systolic and diastolic BP was significantly associated with older brain age in females only (β = 0.43-0.56, p < 0.05). Among males, higher BMI was associated with older brain age across time points and APOE4 groups (β = 0.72-0.77, p < 0.05). In females, higher BMI was linked to older brain age among APOE4 noncarriers (β = 0.68-0.99, p < 0.05), whereas higher BMI was linked to younger brain age among carriers, particularly at the last time point (β = -1.75, p < 0.05). This study indicates sex-dependent and time-dependent relationships between CMRs, APOE4 status, and brain age. Our findings highlight the necessity of sex-stratified analyses to elucidate the role of CMRs in individual aging trajectories, providing a basis for developing personalized preventive interventions

    Emission spectra and intrinsic optical bistability in a two-level medium

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    Scattering of resonant radiation in a dense two-level medium is studied theoretically with account for local field effects and renormalization of the resonance frequency. Intrinsic optical bistability is viewed as switching between different spectral patterns of fluorescent light controlled by the incident field strength. Response spectra are calculated analytically for the entire hysteresis loop of atomic excitation. The equations to describe the non-linear interaction of an atomic ensemble with light are derived from the Bogolubov-Born-Green-Kirkwood-Yvon hierarchy for reduced single particle density matrices of atoms and quantized field modes and their correlation operators. The spectral power of scattered light with separated coherent and incoherent constituents is obtained straightforwardly within the hierarchy. The formula obtained for emission spectra can be used to distinguish between possible mechanisms suggested to produce intrinsic bistability.Comment: 18 pages, 5 figure

    Adaptation to AI therapy in breast cancer can induce dynamic alterations in ER activity resulting in estrogen independent metastatic tumours

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    PURPOSE: Acquired resistance to aromatase inhibitor therapy is a major clinical problem in the treatment of breast cancer. The detailed mechanisms of how tumour cells develop this resistance remain unclear. Here, the adapted function of ER to an estrogen-depleted environment following AI treatment is reported. EXPERIMENTAL DESIGN: Global ER-ChIPseq analysis of AI resistant cells identified steroid-independent ER target genes. Matched patient tumour samples, collected before and after AI treatment, were used to assess ER activity. RESULTS: Maintained ER activity was observed in patient tumours following neoadjuvant AI therapy. Genome-wide ER-DNA binding analysis in AI resistant cell lines identified a subset of classic ligand dependent ER target genes which develop steroid independence. Kaplan Meier analysis revealed a significant association between tumours which fail to decrease this steroid independent ER target gene set in response to neoadjuvant AI therapy, and poor disease-free and overall survival (n=72 matched patient tumour samples, p=0.00339 and 0.00155 respectively). The adaptive ER response to AI treatment was highlighted by the ER/AIB1 target gene, early growth response 3 (EGR3). Elevated levels of EGR3 were detected in endocrine resistant local disease recurrent patient tumours in comparison to matched primary tissue. However, evidence from distant metastatic tumours demonstrates that the ER signalling network may undergo further adaptations with disease progression as estrogen-independent ER target gene expression is routinely lost in established metastatic tumours. CONCLUSIONS: Overall, these data provide evidence of a dynamic ER response to endocrine treatment which may provide vital clues for overcoming the clinical issue of therapy resistance

    Ergonomics and sustainability: Towards and embrace of complexity and emergence

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    Technology offers a promising route to a sustainable future, and ergonomics can serve a vital role. The argument of this article is that the lasting success of sustainability initiatives in ergonomics hinges on an examination of ergonomics' own epistemology and ethics. The epistemology of ergonomics is fundamentally empiricist and positivist. This places practical constraints on its ability to address important issues such as sustainability, emergence and complexity. The implicit ethical position of ergonomics is one of neutrality, and its positivist epistemology generally puts value-laden questions outside the parameters of what it sees as scientific practice. We argue, by contrast, that a discipline that deals with both technology and human beings cannot avoid engaging with questions of complexity and emergence and seeking innovative ways of addressing these issues.No Full Tex

    Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation.

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    Thyroid dysfunction is an important public health problem, which affects 10% of the general population and increases the risk of cardiovascular morbidity and mortality. Many aspects of thyroid hormone regulation have only partly been elucidated, including its transport, metabolism, and genetic determinants. Here we report a large meta-analysis of genome-wide association studies for thyroid function and dysfunction, testing 8 million genetic variants in up to 72,167 individuals. One-hundred-and-nine independent genetic variants are associated with these traits. A genetic risk score, calculated to assess their combined effects on clinical end points, shows significant associations with increased risk of both overt (Graves' disease) and subclinical thyroid disease, as well as clinical complications. By functional follow-up on selected signals, we identify a novel thyroid hormone transporter (SLC17A4) and a metabolizing enzyme (AADAT). Together, these results provide new knowledge about thyroid hormone physiology and disease, opening new possibilities for therapeutic targets
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