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The assessment of patient reported outcomes and health-related quality of life continue to be rapidly evolving areas of research and this new edition reflects the development within the field from an emerging subject to one that is an essential part of the assessment of clinical trials and other clinical studies.

Animal-derived dietary protein ingestion and physical activity stimulate myofibrillar protein synthesis rates in older adults. We determined whether a non-animal-derived diet can support daily myofibrillar protein synthesis rates to the same extent as an omnivorous diet. Nineteen healthy older adults (aged 66 (sem 1) years; BMI 24 (sem 1) kg/m2; twelve males, seven females) participated in a randomised, parallel-group, controlled trial during which they consumed a 3-d isoenergetic high-protein (1·8 g/kg body mass per d) diet, where the protein was provided from predominantly (71 %) animal (OMNI; n 9; six males, three females) or exclusively vegan (VEG; n 10; six males, four females; mycoprotein providing 57 % of daily protein intake) sources. During the dietary control period, participants conducted a daily bout of unilateral resistance-type leg extension exercise. Before the dietary control period, participants ingested 400 ml of deuterated water, with 50-ml doses consumed daily thereafter. Saliva samples were collected throughout to determine body water 2H enrichments, and muscle samples were collected from rested and exercised muscle to determine daily myofibrillar protein synthesis rates. Deuterated water dosing resulted in body water 2H enrichments of approximately 0·78 (sem 0·03) %. Daily myofibrillar protein synthesis rates were 13 (sem 8) (P = 0·169) and 12 (sem 4) % (P = 0·016) greater in the exercised compared with rested leg (1·59 (sem 0·12) v. 1·77 (sem 0·12) and 1·76 (sem 0·14) v. 1·93 (sem 0·12) %/d) in OMNI and VEG groups, respectively. Daily myofibrillar protein synthesis rates did not differ between OMNI and VEG in either rested or exercised muscle (P > 0·05). Over the course of a 3-d intervention, omnivorous- or vegan-derived dietary protein sources can support equivalent rested and exercised daily myofibrillar protein synthesis rates in healthy older adults consuming a high-protein diet.

Given the way multimodality as a field has expanded, becoming more diverse and complex, it is important to pause to identify exactly which concepts, theories and processes of multimodal analysis are more or less suitable for the needs of critical discourse analysis (CDA) and the wider field of critical discourse studies (CDS). The article argues that the field of multimodality remains fragmented both internally, with a range of divergent core interests, and externally from academic fields that have long dealt with the topics to which it is turning its interest. In this article, looking at some key ideas from visual studies, I reflect on what kind of multimodal approach best aligns with the needs of CDS. I argue for an affordance-based approach and one driven by the social and not by need to model on the basis of language.

Twitter campaigns attacking those who make racist or xenophobic statements are valuable, raising the public profile of opinions that will not tolerate racism in any form. They also indicate how our major institutions are failing to address important matters of social justice. But there is concern that social media, such as Twitter, tends to extremes, moral outrages, lack of nuance and incivility, which shape how issues become represented. In this paper, using Critical Discourse Analysis, we look at three Twitter hashtags calling-out racist behaviour. We ask how racism and anti-racism is represented on these hashtags? We show how these misrepresent fundamental aspects of racism in society, distracting from, what race theorists would argue, is the most important thing these incidents tell us about racism at this present time. The findings have consequences for all such Twitter social justice campaigns.

The current standard treatment for patients with high-risk neuroblastoma includes initial induction chemotherapy with a 21-day interval between induction treatments. We aimed to assess whether an intensive chemotherapy protocol that had a 10-day interval between treatments would improve event-free survival (EFS) in patients aged 1 year or over with high-risk neuroblastoma. Between Oct 30, 1990, and March 18, 1999, patients with stage 4 neuroblastoma who had not received previous chemotherapy were enrolled from 29 centres in Europe. Patients were randomly assigned to rapid treatment (cisplatin [C], vincristine [O], carboplatin [J], etoposide [E], and cyclophosphamide [C], known as COJEC) or standard treatment (vincristine [O], cisplatin [P], etoposide [E], and cyclophosphamide [C], ie, OPEC, alternated with vincristine [O], carboplatin [J], etoposide [E], and cyclophosphamide [C], ie, OJEC). Both regimens used the same total cumulative doses of each drug (except vincristine), but the dose intensity of the rapid regimen was 1·8-times higher than that of the standard regimen. The standard regimen was given every 21 days if patients showed haematological recovery, whereas the rapid regimen was given every 10 days irrespective of haematological recovery. Response to chemotherapy was assessed according to the conventional International Neuroblastoma Response Criteria (INRC). In responders, surgical excision of the primary tumour was attempted, followed by myeloablation (with 200 mg/m 2 of melphalan) and haemopoietic stem-cell rescue. Primary endpoints were 3-year, 5-year, and 10-year EFS. Data were analysed by intention to treat. This trial is registered on the clinical trials site of the US National Cancer Institute website, number NCT00365755, and also as EU-20592 and CCLG-NB-1990-11. 262 patients, of median age 2·95 years (range 1·03–20·97), were randomly assigned—132 patients to standard and 130 patients to rapid treatment. 111 patients in the standard group and 109 patients in the rapid group completed chemotherapy. Chemotherapy doses were recorded for 123 patients in the standard group and 126 patients in the rapid group. 97 of 123 (79%) patients in the standard group and 84 of 126 (67%) patients in the rapid group received at least 90% of the scheduled chemotherapy, and the relative dose intensity was 1·94 compared with the standard regimen. 3-year EFS was 24·2% for patients in the standard group and 31·0% for those in the rapid group (hazard ratio [HR] 0·86 [95% CI 0·66–1·14], p=0·30. 5-year EFS was 18·2% in the standard group and 30·2% in the rapid group, representing a difference of 12·0% (1·8 to 22·3), p=0·022. 10-year EFS was 18·2% in the standard group and 27·1% in the rapid group, representing a difference of 8·9% (−1·2 to 19·0), p=0·085. Myeloablation was given a median of 55 days earlier in patients assigned rapid treatment than those assigned standard treatment. Infective complications (numbers of patients with febrile neutropenia and septicaemia, and if given, time on antibiotic and antifungal treatment) and time in hospital were greater with rapid treatment. Occurrence of fungal infection was the same in both regimens. Dose intensity can be increased with a rapid induction regimen in patients with high-risk neuroblastoma. There was no significant difference in OS between the rapid and standard regimens at 5 years and 10 years. However, an increasing difference in EFS after 3 years suggests that the efficacy of the rapid regimen is better than the standard regimen. A rapid induction regimen enables myeloablation to be given much earlier, which might contribute to a better outcome.

Research shows that racism and xenophobia soared during the Covid-19 pandemic and this was certainly the case with the Roma in Romania. In this article, using critical discourse analysis, we analyse comments left below a television news clip posted on YouTube early in the crisis. This gives us valuable access to the way racism and xenophobia are linguistically expressed in social media, particularly in this Romanian context. It yields insights into how more overt forms of racism can sit alongside others which are less so, all united by a sense of shared embittered victimhood on behalf of Romanian citizens. We show how this takes place as the affordances of social media allow for a collective expression of frustration and mobilisation, reflecting on how social media may increase exposure to more extreme forms of racism. (Critical discourse analysis, Covid-19, online racism, Roma, social media, white victimhood)

Over half of childhood intracranial ependymomas occur in children younger than 5 years. As an adjuvant treatment, radiotherapy can be effective, but has the potential to damage the child's developing nervous system at a crucial time—with a resultant reduction in IQ and cognitive impairment, endocrinopathy, and risk of second malignancy. We aimed to assess the role of a primary chemotherapy strategy in avoiding or delaying radiotherapy in children younger than 3 years with intracranial ependymoma. Between December, 1992, and April, 2003, we enrolled 89 children with ependymoma who were aged 3 years or younger at diagnosis, of whom nine had metastatic disease on pre-operative imaging. After maximal surgical resection, children received alternating blocks of myelosuppressive and non-myelosuppressive chemotherapy every 14 days for an intended duration of 1 year. Radiotherapy was withheld unless local imaging (ie, from the child's treatment centre) showed progressive disease. 50 of the 80 patients with non-metastatic disease progressed, 34 of whom were irradiated for progression. The 5-year cumulative incidence of freedom from radiotherapy for the 80 non-metastatic patients was 42% (95% CI 32–53). With a median follow-up of 6 years (range 1·5–11·3), overall survival for the non-metastatic patients at 3 years was 79·3% (95% CI 68·5–86·8) and at 5 years 63·4% (51·2–73·4). The corresponding values for event-free survival were 47·6% (36·2–58·1) and 41·8% (30·7–52·6). There was no significant difference in event-free or overall survival between complete and incomplete surgical resection, nor did survival differ according to histological grade, age at diagnosis, or site of disease. In 47 of 59 (80%) patients who progressed, relapse resulted from local control only. The median time to progression for the 59 patients who progressed was 1·6 years (range 0·1–10·2 years). The median age at irradiation of the whole group was 3·6 years (range 1·5–11·9). For the 80 non-metastatic patients, the 23 who achieved the highest relative dose intensity of chemotherapy had the highest post-chemotherapy 5-year overall survival of 76% (95% CI 46·6–91·2), compared with 52% (33·3–68·1) for the 32 patients who achieved the lowest relative dose intensity of chemotherapy. This protocol avoided or delayed radiotherapy in a substantial proportion of children younger than 3 years without compromising survival. These results suggest, therefore, that primary chemotherapy strategies have an important role in the treatment of very young children with intracranial ependymoma.

Increasing skeletal muscle carnitine content can manipulate fuel metabolism and improve exercise performance. Intravenous insulin infusion during hypercarnitinemia increases plasma carnitine clearance and Na+‐dependent muscle carnitine accretion, likely via stimulating Na+/K+ ATPase pump activity. We hypothesized that the ingestion of high‐dose caffeine, also known to stimulate Na+/K+ ATPase activity, would stimulate plasma carnitine clearance during hypercarnitinemia in humans. In a randomized placebo‐controlled study, six healthy young adults (aged 24 ± 5 years, height 175 ± 8 cm, and weight 70 ± 13 kg) underwent three 5‐h laboratory visits involving the primed continuous intravenous infusion of l‐carnitine (CARN and CARN + CAFF) or saline (CAFF) in parallel with ingestion of caffeine (CARN + CAFF and CAFF) or placebo (CARN) at 0, 2, 3, and 4 h. Regular blood samples were collected to determine concentrations of blood Na+ and K+, and plasma carnitine and caffeine, concentrations. Caffeine ingestion (i.e., CAFF and CARN + CAFF conditions) and l‐carnitine infusion (i.e., CARN and CARN + CAFF) elevated steady‐state plasma caffeine (to ~7 μg·mL−1) and carnitine (to ~400 μmol·L−1) concentrations, respectively, throughout the 5 h infusions. Plasma carnitine concentration was ~15% lower in CARN + CAFF compared with CARN during the final 90 min of the infusion (at 210 min, 356 ± 96 vs. 412 ± 94 μmol·L−1; p = 0.0080: at 240 min, 350 ± 91 vs. 406 ± 102 μmol·L−1; p = 0.0079: and at 300 min, 357 ± 91 vs. 413 ± 110 μmol·L−1; p = 0.0073, respectively). Blood Na+ concentrations were greater in CAFF and CARN + CAFF compared with CARN. Ingestion of high‐dose caffeine stimulates plasma carnitine clearance during hypercarnitinemia, likely via increased Na+/K+ ATPase activity. Carnitine co‐ingestion with caffeine may represent a novel muscle carnitine loading strategy in humans, and therefore manipulate skeletal muscle fuel metabolism and improve exercise performance.