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Abstract Context Pre-exercise nutrient availability alters acute metabolic responses to exercise, which could modulate training responsiveness. Objective To assess acute and chronic effects of exercise performed before versus after nutrient ingestion on whole-body and intramuscular lipid utilization and postprandial glucose metabolism. Design (1) Acute, randomized, crossover design (Acute Study); (2) 6-week, randomized, controlled design (Training Study). Setting General community. Participants Men with overweight/obesity (mean ± standard deviation, body mass index: 30.2 ± 3.5 kg⋅m-2 for Acute Study, 30.9 ± 4.5 kg⋅m-2 for Training Study). Interventions Moderate-intensity cycling performed before versus after mixed-macronutrient breakfast (Acute Study) or carbohydrate (Training Study) ingestion. Results Acute Study—exercise before versus after breakfast consumption increased net intramuscular lipid utilization in type I (net change: –3.44 ± 2.63% versus 1.44 ± 4.18% area lipid staining, P < 0.01) and type II fibers (–1.89 ± 2.48% versus 1.83 ± 1.92% area lipid staining, P < 0.05). Training Study—postprandial glycemia was not differentially affected by 6 weeks of exercise training performed before versus after carbohydrate intake (P > 0.05). However, postprandial insulinemia was reduced with exercise training performed before but not after carbohydrate ingestion (P = 0.03). This resulted in increased oral glucose insulin sensitivity (25 ± 38 vs –21 ± 32 mL⋅min-1⋅m-2; P = 0.01), associated with increased lipid utilization during exercise (r = 0.50, P = 0.02). Regular exercise before nutrient provision also augmented remodeling of skeletal muscle phospholipids and protein content of the glucose transport protein GLUT4 (P < 0.05). Conclusions Experiments investigating exercise training and metabolic health should consider nutrient-exercise timing, and exercise performed before versus after nutrient intake (ie, in the fasted state) may exert beneficial effects on lipid utilization and reduce postprandial insulinemia.

\"In letters written between 1937 and 1950 to her American pen pal, a working-class Londoner offers accounts of the Blitz and of wartime deprivations and postwar austerity, interweaving descriptions of terror with talk about theater, clothes, and family outings, providing a unique view of daily life during World War II\"--Provided by publisher.

IntroductionThe number of robotic-assisted hip replacement procedures has expanded globally with the intended aim of improving outcomes. Intraoperative robotic-arm systems add additional costs to total hip replacement (THR) surgery but may improve surgical precision and could contribute to diminished pain and improved function. Additionally, these systems may reduce the need for expensive revision surgery. Surgery with conventional instruments may be just as successful, quick and affordable. There is timely demand for a robust evaluation of this technology.Methods and analysisThe Robotic Arthroplasty Clinical and cost Effectiveness Randomised controlled trial for Hips (RACER-Hip) is a multicentre (minimum of six UK sites), participant–assessor blinded, randomised controlled trial. 378 participants with hip osteoarthritis requiring THR will be randomised (1:1) to receive robotic-assisted THR, or THR using conventional surgical instruments. The primary outcome is the Forgotten Joint Score at 12 months post-randomisation; a patient-reported outcome measure assessing participants’ awareness of their joint when undertaking daily activities. Secondary outcomes will be collected post-operatively (pain, blood loss and opioid usage) and at 3, 6, 12, 24 months, then 5 and 10 years postrandomisation (including function, pain, health-related quality of life, reoperations and satisfaction). Allocation concealment will be accomplished using a computer-based randomisation procedure on the day of surgery. Blinding methods include the use of sham incisions for marker clusters and blinded operation notes. The primary analysis will adhere to the intention-to-treat principle. Results will adhere to Consolidated Standards of Reporting Trials statements.Ethics and disseminationThe trial was approved by an ethics committee (Solihull Research Ethics Committee, 30 June 2021, IRAS: 295831). Participants will provide informed consent before agreeing to participate. Results will be disseminated using peer-reviewed journal publications, presentations at international conferences and through the use of social media. We will develop plans to disseminate to patients and public with our patient partners.Trial registration numberISRCTN13374625.

IntroductionHead and neck cancer (HNC) affects the mouth, throat, salivary glands, voice box, nose or sinuses. Every year, over 12 000 people in the UK are diagnosed with HNC. Neck dissection is a key, surgical component of patient care. However, many people experience postoperative restriction in shoulder and neck movements, pain, fatigue and low mood, with only half ever returning to work.Methods and analysisGetting Recovery Right After Neck Dissection (GRRAND) is a two-arm, multicentre, pragmatic randomised controlled trial. The trial aims to compare clinical and cost-effectiveness of a personalised physiotherapy programme (GRRAND programme) versus usual practice, National Health Service (NHS), postdischarge care.The planned sample size is 390 participants. Participants will be recruited from across UK sites and followed up for 12 months. The primary outcome is the shoulder pain and disability index at 12 months. Economic evaluation will be conducted from a healthcare system and personal social services perspective. Secondary outcome data, including pain, function, health-related quality of life, mental well-being, health resource use and adverse events, will be collected at 6 weeks, 3, 6 and 12 months, with exercise adherence at 6 weeks. A process evaluation will determine how GRRAND is implemented, delivered and received across clinical settings, exploring what works, for whom and under what conditions. Analysis will be on an intention-to-treat basis and reported inline with the Consolidated Standards of Reporting Trials statement.Ethics and disseminationThe trial was approved by the London-Brent Research Ethics Committee (ref: 24/LO/0722) on 15 October 2024. Trial results will be disseminated via peer-reviewed publications, presentations at national and international conferences, in lay summaries and social media. This protocol adheres to the recommended Standard Protocol Items: Recommendations for Interventional Trials checklist.Trial registration numberISRCTN13855775.

IntroductionPain and disability after meniscectomy can be a substantial lifelong problem. There are few treatment options, especially for young people. Non-surgical management (rehabilitation) is an option but increasingly surgeons are performing meniscal allograft transplants (MATs) for these individuals. However, this is still an uncommon procedure, and availability and usage of MAT vary widely both in the UK and internationally. It is not known which treatment option is the most effective and cost-effective.Methods and analysisThe Meniscal Transplant surgery or Optimised Rehabilitation trial is an international, multicentre, randomised controlled trial. The aim is to compare the clinical and cost effectiveness of MAT versus an optimised package of individualised, progressive, rehabilitation that we have called personalised knee therapy (PKT).Participants will be recruited from sites across the UK, Australia, Canada and Belgium. The planned 144 participants provide at least 90% power to detect a 10-point difference in the Knee injury and Osteoarthritis Outcome Score (KOOS4) at 24-months post randomisation (primary outcome). A prospectively planned economic evaluation will be conducted from a healthcare system and personal social services perspective. Secondary outcome data including health utility, occupational status, sports participation, mental well-being, further treatment, and adverse events will be collected at 3, 6, 12, 18, and 24 months. Analysis will be on an intention-to-treat basis and reported in-line with the Consolidated Standards of Reporting Trials statement.Ethics and disseminationThe trial was approved by the London—Bloomsbury Research Ethics Committee on 19 August 2022 (22/LO/0327) and Northern Sydney Local Health District Human Research Ethics Committee, NSW, Australia on the 13 March 2023 (2022/ETH01890).Trial results will be disseminated via peer-reviewed publications, presentations at international conferences, in lay summaries and using social media as appropriate.This protocol adheres to the recommended Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist.Trial registration number ISRCTN87336549.

Extracellular vesicles have been described in non-paracrine cellular interactions in cancer. We report a similar phenomenon in B-cell precursor (BCP) acute lymphoblastic leukaemia (ALL). Using advanced microscopy and high throughput screening, we further characterise a subset of large vesicles (LEVs) identified in cell lines, murine models of human BCP-ALL and clinical samples. Primary ALL blasts and cell lines released heterogeneous anucleate vesicles <6 micron into extracellular fluids. Larger LEVs were enclosed in continuous membranes, contained intact organelles and demonstrated an organised cytoskeleton. An excess of circulating CD19-positive LEVs were observed in diagnostic samples and isolated from mice engrafted with BCP-ALL primary cells. LEVs exhibited dynamic shape change in vitro and were internalised by other leukaemic cell lines leading to phenotypic transformation analogous to the cell of origin. In patient-derived xenografts, LEVs were released by primary ALL cells into extracellular spaces and internalised by murine mesenchymal cells in vivo. Collectively these data highlight the heterogeneity but accessibility of LEVs in clinical samples and their potential to provide a unique insight into the biology of the cell of origin and to their development as novel biomarkers to aid diagnosis and improve therapeutic outcomes.

BackgroundAcute Rehabilitation following Traumatic anterior shoulder dISlocAtioN (ARTISAN) was a large trial comparing the clinical and cost-effectiveness of two rehabilitation interventions in adults with a first-time traumatic shoulder dislocation. Participants were allocated to receive either a single session of advice (ARTISAN) or a single session of advice and a programme of physiotherapy (ARTISAN plus). Trial results illustrated that additional physiotherapy after an initial session was not superior in improving functional outcomes for participants.ObjectivesIn this study, we aim to explore the experiences of a purposive sample of participants from both the ARTISAN and ARTISAN plus groups regarding their rehabilitation journey.DesignThis is a semistructured interview-based study.SettingThe study was conducted in the United Kingdom.ParticipantsThirty-one participants of ARTISAN trial: 16 participants from ARTISAN group and 15 from ARTISAN plus group.Outcome measures and analysisThe study follows the consolidated criteria for reporting qualitative research. The framework analysis was used to synthesise the participants’ experiences. The interviews were coded through NVivo 12.6.1.ResultsThree dominant and interrelated topics emerged from the interview data: (1) feelings about their shoulder rehabilitation outcome, (2) judgement of ARTISAN rehabilitation materials, (3) assessment of shoulder rehabilitation service provision.ConclusionBoth forms of intervention have some merit for some individuals. Thus, it may be appropriate to look at the patients’ preference for offering treatment to them. Recognising and facilitating this will be of benefit to both the patients and healthcare as a whole.

Objectives: When the COVID-19 pandemic caused mandatory closures of physical therapy offices and gyms in the winter and spring of 2020, many patients who had undergone ACL reconstruction (ACLR) over the previous months experienced unexpected interruptions in their rehabilitation process. The purpose of this study was to compare the sport testing, patient reported outcomes, and mental health scores between ACLR patients whose postoperative physical therapy may have been disrupted by the COVID-19 pandemic versus a control cohort of ACLR patients who completed their physical therapy the year prior to the pandemic. With the barriers created by COVID-19, we aimed to understand the relationship between access to physical therapy and objective/subjective patient outcomes as well as mental health scores. Methods: A retrospective study of prospectively collected data as well as prospective collection of patient questionnaires was performed. The control group was patients who underwent ACLR from November 2018 to March 2019 while the experimental “COVID” group consisted of patients who underwent ACLR from November 2019 through March 2020. Patients with concomitant meniscal injury were included, but any revision surgery or multiligamentous knee injury was excluded. Patients must have completed sport testing at 6-7 months postoperatively to be enrolled. Retrospective chart data including surgery specific data, patient specific demographic data, sport testing outcomes including thigh girth, quadriceps and hamstring index, Y-balance, Keiser leg press were reviewed. Patient reported outcome measures were collected through our institutional registry including IKDC, Lysholm, Tegner, SF-12 physical (PCS) and mental (MCS) component summaries, WOMAC and patient satisfaction. Finally, prospectively collected data included the ACL-RSI questionnaire as well as a study-specific questionnaire administered to the experimental population to assess the effect of the pandemic closures on their access to postoperative rehabilitation. Primary analysis compared sport testing outcomes at 6-7 months postoperative between the control group and the COVID group. Secondary analyses compared patient reported outcomes and patient satisfaction between groups. Subgroup analyses included comparisons within the COVID group based on ACL-RSI scores as well as access to PT and self-directed therapy during the pandemic. Results: A total of 50 patients with median age 34.5 years (52% female) were enrolled in the study, 25 in the control group and 25 in the COVID experimental group. Baseline demographics, surgery specific details and preoperative outcomes scores were similar between the groups, with the exception of a higher number of meniscal repairs performed in the COVID group (48% vs. 24%, p = 0.032). Median follow-up for sport testing was 7 months, and no statistically significant differences were seen between the two groups when comparing quadriceps index, hamstring index, Keiser power, Keiser reaction, y-balance, or girth testing (Table 1). Notably, more patients reached full flexion (≥140 degrees) in the control group than the COVID group (96% vs. 76%, p=0.05). Additionally, no differences were seen with regards to patient reported outcomes between the two groups.Subgroup analyses were then performed on the COVID group only. 48% of patients missed in-person physical therapy appointments due to the pandemic, while 68% of patients were able to perform self-directed physical therapy with the largest proportion reporting a frequency of 3-5x a week or higher. Interestingly, missing in-person physical therapy appointments was not statistically significantly associated with worsened postoperative sport testing, patient reported outcome or ACL-RSI scores. Meanwhile, those who participated in frequent (>3x per week) self-directed physical therapy reported improved ACL-RSI scores overall when compared to those patients only participating <2x per week, however only the risk appraisal subscore of the ACL-RSI was statistically significant (median 83 vs 38, p=0.03). Conclusions: Patients who underwent ACLR in the 4 months prior to the 2020 COVID-19 pandemic demonstrated a high rate of decreased access to physical therapy, but did not have significantly worsened sport testing, subjective outcome measures or mental health scores compared to a matched population undergoing ACLR in the same 4 months of 2019. Even when controlling for patients who specifically reported missing physical therapy appointments during the pandemic, no differences were seen. Participation in higher frequency of self-directed therapy led to improved ACL-RSI scores at 1- year postoperatively. These results may suggest that the bourgeoning availability of online and virtual therapy resources necessitated by the pandemic may have long-lasting value in supplementing postoperative rehabilitation, especially for those patients with limited access to in-person therapy due to time, distance, financial or insurance constraints. Additionally, these results have implications for any ongoing ACLR study that may have concerns about data validity in those patients whose perioperative period coincided with the COVID-19 pandemic. Table 1. Comparison of Experimental versus Control groups with respect to physical rehabilitation return to sport assessments.

This thesis aims to show that the concept of style ought to be given greater significance in understanding depiction. I argue that if we want to understand pictorial representations we must remember that how they depict is crucial to understanding not only why they depict what they do, but also why we have the particular kind of experience that they engender. I develop and defend an account of artistic style that has its basis in the claim that individual style is the way in which an artist does something, where this way of doing something is highly personal. With this in place I explore and critically evaluate previous attempts at understanding pictorial representation, in particular the popular Resemblance View, further clarifying the phenomenon of seeing-in along the way. I then modify and develop an account of depiction which has its basis in the work of Flint Schier and Dominic Lopes, who argue for an ‘Aspect-Recognition’ theory of depiction. The Aspect-Recognition theory, I contend, can give us the beginnings of a story about depiction, but while it is pointing in the right direction, I show it is still inadequate. I then use the concept of style that I have developed and build upon the Aspect-Recognition theory to provide a better account; one that not only has explanatory force but also does justice to pictorial diversity and the phenomenology of pictorial experience. Finally, I put this view to work in resolving familiar problems in the philosophy of depiction, namely pictorial misrepresentation and pictorial indeterminacy. These remain the most persistent difficulties for other theories of depiction. Thus my view not only better describes the nature of pictorial experience more generally but is also much better equipped to make sense of curious phenomena in pictorial representation.