Inter- and intra-individual variation in brain structural-cognition relationships in aging

The sources of inter- and intra-individual variability in age-related cognitive decline remain poorly understood. We examined the association between 20-year trajectories of cognitive decline and multimodal brain structure and morphology in older age. We used the Whitehall II Study, an extensively characterised cohort with 3T brain magnetic resonance images acquired at older age (mean age = 69.52 ± 4.9) and 5 repeated cognitive performance assessments between mid-life (mean age = 53.2 ±4.9 years) and late-life (mean age = 67.7 ± 4.9). Using non-negative matrix factorization, we identified 10 brain components integrating cortical thickness, surface area, fractional anisotropy, and mean and radial diffusivities. We observed two latent variables describing distinct brain-cognition associations. The first describes variations in 5 structural components associated with low mid-life performance across multiple cognitive domains, decline in reasoning, but maintenance of fluency abilities. The second describes variations in 6 structural components associated with low mid-life performance in fluency and memory, but retention of multiple abilities. Expression of latent variables predicts future cognition 3.2 years later (mean age = 70.87 ± 4.9). This data-driven approach highlights brain-cognition relationships wherein individuals degrees of cognitive decline and maintenance across diverse cognitive functions are both positively and negatively associated with markers of cortical structure

Understanding the National Student Survey: investigations in languages, linguistics and area studies

This report is a summary of interviews and focus groups with around 100 students and 50 members of academic staff in departments of languages, linguistics or area studies at nine universities in the UK. In recent years, concerns have been expressed about the ambiguity of some of the statements which students are asked to respond to in the National Student Survey (NSS). This project set out to get a better understanding of how students and staff understand the questions. The interviews and focus groups were carried out by members of academic staff at the nine institutions who each then wrote an individual report of their findings. This summary is designed to enable wider distribution of these findings without identifying individual staff, institutions `or departments

Physiotherapy for sleep disturbance in chronic low back pain: a feasibility randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Sleep disturbance is becoming increasingly recognised as a clinically important symptom in people with chronic low back pain (CLBP, low back pain >12 weeks), associated with physical inactivity and depression. Current research and international clinical guidelines recommend people with CLBP assume a physically active role in their recovery to prevent chronicity, but the high prevalence of sleep disturbance in this population may be unknowingly limiting their ability to participate in exercise-based rehabilitation programmes and contributing to poor outcomes. There is currently no knowledge concerning the effectiveness of physiotherapy on sleep disturbance in people with chronic low back pain and no evidence of the feasibility of conducting randomized controlled trials that comprehensively evaluate sleep as an outcome measure in this population.</p> <p>Methods/Design</p> <p>This study will evaluate the feasibility of a randomised controlled trial (RCT), exploring the effects of three forms of physiotherapy (supervised general exercise programme, individualized walking programme and usual physiotherapy, which will serve as the control group) on sleep quality in people with chronic low back pain. A presenting sample of 60 consenting patients will be recruited in the physiotherapy department of Beaumont Hospital, Dublin, Ireland, and randomly allocated to one of the three groups in a concealed manner. The main outcomes will be sleep quality (self-report and objective measurement), and self-reported functional disability, pain, quality of life, fear avoidance, anxiety and depression, physical activity, and patient satisfaction. Outcome will be evaluated at baseline, 3 months and 6 months. Qualitative telephone interviews will be embedded in the research design to obtain feedback from a sample of participants' about their experiences of sleep monitoring, trial participation and interventions, and to inform the design of a fully powered future RCT. Planned analysis will explore trends in the data, effect sizes and clinically important effects (quantitative data), and thematic analysis (qualitative data).</p> <p>Discussion</p> <p>This study will evaluate the feasibility of a randomised controlled trial exploring the effects of three forms of physiotherapy (supervised general exercise programme, individualized walking programme and usual physiotherapy, which will serve as the control group) on sleep quality in people with chronic low back pain.</p> <p>Trial Registration</p> <p>Current controlled trial ISRCTN54009836</p

Using a generic definition of cachexia in patients with kidney disease receiving haemodialysis: a longitudinal (pilot) study

International audienceBACKGROUND: Research indicates that cachexia is common among persons with chronic illnesses and is associated with increased morbidity and mortality. However, there continues to be an absence of a uniformed disease-specific definition for cachexia in chronic kidney disease (CKD) patient populations. OBJECTIVE: The primary objective was to identify cachexia in patients receiving haemodialysis (HD) using a generic definition and then follow up on these patients for 12 months. METHOD: This was a longitudinal study of adult chronic HD patients attending two hospital HD units in the UK. Multiple measures relevant to cachexia, including body mass index (BMI), muscle mass [mid-upper arm muscle circumference (MUAMC)], handgrip strength (HGS), fatigue [Functional Assessment of Chronic Illness Therapy (FACIT)], appetite [Functional Assessment of Anorexia/Cachexia Therapy (FAACT)] and biomarkers [C-reactive protein (CRP), serum albumin, haemoglobin and erythropoietin resistance index (ERI)] were recorded. Baseline analysis included group differences analysed using an independent t-test, dichotomized values using the χ2 test and prevalence were reported using the Statistical Package for the Social Sciences 24 (IBM, Armonk, NY, USA). Longitudinal analysis was conducted using repeated measures analysis. RESULTS: A total of 106 patients (30 females and 76 males) were recruited with a mean age of 67.2 years [standard deviation (SD) 13.18] and dialysis vintage of 4.92 years (SD 6.12). At baseline, 17 patients were identified as cachectic, having had reported weight loss (e.g. \textgreater5% for \textgreater6 months) or BMI \textless20 kg/m2 and three or more clinical characteristics of cachexia. Seventy patients were available for analysis at 12 months (11 cachectic versus 59 not cachectic). The FAACT and urea reduction ratio statistically distinguished cachectic patients (P = 0.001). However, measures of weight, BMI, MUAMC, HGS, CRP, ERI and FACIT tended to worsen in cachectic patients. CONCLUSION: Globally, cachexia is a severe but frequently underrecognized problem. This is the first study to apply the defined characteristics of cachexia to a representative sample of patients receiving HD. Further, more extensive studies are required to establish a phenotype of cachexia in advanced CKD

Management of systemic sclerosis: British Society for Rheumatology guideline scope

This guideline will provide a practical roadmap for management of SSc that builds upon the previous treatment guideline to incorporate advances in evidence-based treatment and increased knowledge about assessment, classification and management. General approaches to management as well as treatment of specific complications will be covered, including lung, cardiac, renal and gastrointestinal tract disease, as well as RP, digital vasculopathy, skin manifestations, calcinosis and impact on quality of life. It will include guidance related to emerging approved therapies for interstitial lung disease and account for National Health Service England prescribing policies and national guidance relevant to SSc. The guideline will be developed using the methods and processes outlined in Creating Clinical Guidelines: Our Protocol. This development process to produce guidance, advice and recommendations for practice has National Institute for Health and Care Excellence accreditation

Management of systemic sclerosis: British Society for Rheumatology guideline scope

This guideline will provide a practical roadmap for management of SSc that builds upon the previous treatment guideline to incorporate advances in evidence-based treatment and increased knowledge about assessment, classification and management. General approaches to management as well as treatment of specific complications will be covered, including lung, cardiac, renal and gastrointestinal tract disease, as well as RP, digital vasculopathy, skin manifestations, calcinosis and impact on quality of life. It will include guidance related to emerging approved therapies for interstitial lung disease and account for National Health Service England prescribing policies and national guidance relevant to SSc. The guideline will be developed using the methods and processes outlined in Creating Clinical Guidelines: Our Protocol. This development process to produce guidance, advice and recommendations for practice has National Institute for Health and Care Excellence accreditation

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients

Risk and resilience in cognitive ageing

Whilst advancing age is, on average, associated with declining cognitive abilities, the course of cognitive ageing is highly variable at the individual level. The overall aim of this thesis was to improve understanding of risk and protective factors associated with variability in cognitive ageing. I first explored the effect of Alzheimer’s risk gene ‘APOE’ on cognition in healthy adults, and by reviewing the extensive literature, I showed that APOE genotype can have diverse cognitive consequences via multiple neurobiological mechanisms, each with applications to distinct aspects of cognitive ageing and Alzheimer’s disease (AD). I also investigated subjective memory impairment (SMI), which like APOE is associated with increased AD risk, but is also commonly reported by healthy older adults. By presenting a clinical case of persistent SMI, and reviewing evidence for the long-term relevance of brain characteristics in SMI, I reported that MRI can detect early differences in brain structure that herald subsequent cognitive impairment, valuable in clinical settings to identify the most at-risk SMI cases. I also investigated protective factors that preserve cognitive ability in some older adults, particularly whether the brain supports this superior cognitive ageing in multiple ways, via some older adults maintaining more ‘youthful’ brains, and others harnessing additional functional resources to ‘adapt’ to the challenge of brain ageing. Using structural and functional brain metrics alone, I identified multiple patterns of brain ageing predicted to be associated with superior cognitive ageing, and compared cross-sectional and longitudinal cognitive performance, as well as multi-modal MRI metrics acquired at multiple time points between groups. Across these analyses, I found convergent evidence that maintenance of more ‘youthful’ brain structure and function is associated with prior and continued superior cognitive and brain outcomes, particularly in grey and white matter structure, so promotion of this brain profile should be a goal of interventions. High frontal resting- state connectivity in older adults with poorer brain structure was not associated with the predicted cognitive performance benefit, when compared to those with lower structural and functional brain characteristics. Overall, this thesis provides novel insights into risk and protective factors related to variability in cognitive ageing, upon which further use of sensitive cognitive and imaging measures, and unique populations such as the oldest-old, can expand to inform markers and interventions to maximise cognitive abilities in later life.</p

Beyond sorrow and swords: gender in the Old Norse Volsung legend and its British rewritings

This thesis explores male and female identity in Old Norse and British iterations of the V&ouml;lsung legend, focusing on the Poetic Edda and V&ouml;lsunga saga, William Morris's The Story of Sigurd the Volsung and the Fall of the Niblungs, J. R. R. Tolkien's The Legend of Sigurd and Gudr&uacute;n, and Melvin Burgess’s Bloodtide and Bloodsong. Using poststructuralist theories of gender and posthumanism to analyse representations of gender in these texts, it argues that, in the Old Norse versions of this legend, female identity is closely connected to the control of representations of narrative events, whereas male identity is subject to this control but becomes more overtly fluid in the depiction of shape-shifting. The thesis goes beyond previous critical analyses of gender in these texts which observe an active/ passive binary, or focus on female monstrosity and lament, and male heroism. Unlike most examinations of adaptations of this legend which focus on the medieval or Victorian material, this thesis provides a detailed exploration of The Story of Sigurd the Volsung and the Fall of the Niblungs in conjunction with its Old Norse sources. In doing so, it establishes the silencing of female characters by Morris's rewriting, and the foregrounding of male identity through a focus on the body, performance and the built environment. This thesis also considers both the Old Norse texts and Morris's poem alongside later, critically neglected, British versions of the legend to explore the ways in which narrative form influences the representation of the multiplicity of gender in The Legend of Sigurd and Gudr&uacute;n, and the importance of a posthuman conception of identity in Bloodtide and Bloodsong. The thesis argues that the Old Norse sources do not stand aside from their later interpretations as something complete and originary, but are themselves supplemented by the rewritings of Morris, Tolkien and Burgess; it is, therefore, necessary to foreground our knowledge of all these iterations of the narrative to offer a fuller understanding of gender in the Old Norse V&ouml;lsung legend and its British rewritings.This thesis is not currently available via ORA