The VISA-A (sedentary) should be used for sedentary patients with Achilles tendinopathy: a modified version of the VISA-A developed and evaluated in accordance with the COSMIN checklist

ObjectiveTo develop and evaluate a modified version of the Victorian Institute of Sport Assessment-Achilles (VISA-A) questionnaire, for use in sedentary patients with Achilles tendinopathy, using the Consensus-based Standards for the selection of health Measurement Instruments recommendations.MethodsTwenty-two sedentary patients with Achilles tendinopathy completed the VISA-A and provided feedback regarding the relevance, comprehensiveness and comprehensibility of each item, response options and instructions. Patient and professional feedback was used to develop the VISA-A (sedentary) questionnaire. Reliability, validity and responsiveness of the VISA-A (sedentary) was evaluated in 51 sedentary patients with Achilles tendinopathy: 47.1% women, mean age 64.8 (SD 11.24).ResultsFactor analysis identified two dimensions (symptoms and activity) for the VISA-A (sedentary). Test-retest reliability was excellent for symptoms (intraclass correlation coefficient, ICC=0.991) and activity (ICC=0.999). Repeatability was 1.647 for symptoms and 0.549 for activity. There was a significant difference between the VISA-A and VISA-A (sedentary) scores both pretreatment and post-treatment. There was stronger correlation between the pretreatment to post-treatment change in the VISA-A (sedentary) scores (r=0.420 for symptoms, r=0.407 for activity) and the global rating of change than the VISA-A scores (r=0.253 for symptoms, r=0.186 for activity).ConclusionThe VISA-A (sedentary) demonstrates adequate reliability, validity and responsiveness in sedentary patients with Achilles tendinopathy. The VISA-A (sedentary) is a more appropriate measure than the VISA-A for this cohort and is recommended for clinical and research purposes

Preventing cardiotoxicity in patients with breast cancer and lymphoma: protocol for a multicentre randomised controlled trial (PROACT)

Introduction: Anthracyclines are included in chemotherapy regimens to treat several different types of cancer and are extremely effective. However, it is recognised that a significant side effect is cardiotoxicity; anthracyclines can cause irreversible damage to cardiac cells and ultimately impaired cardiac function and heart failure, which may only be evident years after exposure. The PROACT trial will establish the effectiveness of the ACE inhibitor enalapril maleate (enalapril) in preventing cardiotoxicity in patients with breast cancer and non-Hodgkin’s lymphoma (NHL) receiving anthracycline-based chemotherapy. Methods and analysis: PROACT is a prospective, randomised, open-label, blinded end-point, superiority trial which will recruit adult patients being treated for breast cancer and NHL at NHS hospitals throughout England. The trial aims to recruit 106 participants, who will be randomised to standard care (high-dose anthracycline-based chemotherapy) plus enalapril (intervention) or standard care alone (control). Patients randomised to the intervention arm will receive enalapril (starting at 2.5 mg two times per day and titrating up to a maximum dose of 10 mg two times per day), commencing treatment at least 2 days prior to starting chemotherapy and finishing 3 weeks after their last anthracycline dose. The primary outcome is the presence or absence of cardiac troponin T release at any time during anthracycline treatment, and 1 month after the last dose of anthracycline. Secondary outcomes will focus on cardiac function measured using echocardiogram assessment, adherence to enalapril and side effects. Ethics and dissemination: A favourable opinion was given following research ethics committee review by West Midlands—Edgbaston REC, Ref: 17/WM/0248. Trial findings will be disseminated through engagement with patients, the oncology and cardiology communities, NHS management and commissioning groups and through peer-reviewed publication

Both tails and the centromere targeting domain of CENP-A are required for centromere establishment

The centromere—defined by the presence of nucleosomes containing the histone H3 variant, CENP-A—is the chromosomal locus required for the accurate segregation of chromosomes during cell division. Although the sequence determinants of human CENP-A required to maintain a centromere were reported, those that are required for early steps in establishing a new centromere are unknown. In this paper, we used gain-of-function histone H3 chimeras containing various regions unique to CENP-A to investigate early events in centromere establishment. We targeted histone H3 chimeras to chromosomally integrated Lac operator sequences by fusing each of the chimeras to the Lac repressor. Using this approach, we found surprising contributions from a small portion of the N-terminal tail and the CENP-A targeting domain in the initial recruitment of two essential constitutive centromere proteins, CENP-C and CENP-T. Our results indicate that the regions of CENP-A required for early events in centromere establishment differ from those that are required for maintaining centromere identity

Fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin with gemtuzumab ozogamicin improves event-free survival in younger patients with newly diagnosed aml and overall survival in patients with npm1 and flt3 mutations

Purpose To determine the optimal induction chemotherapy regimen for younger adults with newly diagnosed AML without known adverse risk cytogenetics. Patients and Methods One thousand thirty-three patients were randomly assigned to intensified (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin [FLAG-Ida]) or standard (daunorubicin and Ara-C [DA]) induction chemotherapy, with one or two doses of gemtuzumab ozogamicin (GO). The primary end point was overall survival (OS). Results There was no difference in remission rate after two courses between FLAG-Ida + GO and DA + GO (complete remission [CR] + CR with incomplete hematologic recovery 93% v 91%) or in day 60 mortality (4.3% v 4.6%). There was no difference in OS (66% v 63%; P = .41); however, the risk of relapse was lower with FLAG-Ida + GO (24% v 41%; P < .001) and 3-year event-free survival was higher (57% v 45%; P < .001). In patients with an NPM1 mutation (30%), 3-year OS was significantly higher with FLAG-Ida + GO (82% v 64%; P = .005). NPM1 measurable residual disease (MRD) clearance was also greater, with 88% versus 77% becoming MRD-negative in peripheral blood after cycle 2 (P = .02). Three-year OS was also higher in patients with a FLT3 mutation (64% v 54%; P = .047). Fewer transplants were performed in patients receiving FLAG-Ida + GO (238 v 278; P = .02). There was no difference in outcome according to the number of GO doses, although NPM1 MRD clearance was higher with two doses in the DA arm. Patients with core binding factor AML treated with DA and one dose of GO had a 3-year OS of 96% with no survival benefit from FLAG-Ida + GO. Conclusion Overall, FLAG-Ida + GO significantly reduced relapse without improving OS. However, exploratory analyses show that patients with NPM1 and FLT3 mutations had substantial improvements in OS. By contrast, in patients with core binding factor AML, outcomes were excellent with DA + GO with no FLAG-Ida benefit

Tritium doped polyaniline as a β-irradiation source

M.S.Jiří Janat

The VISA-A (sedentary) should be used for sedentary patients with Achilles tendinopathy: a modified version of the VISA-A developed and evaluated in accordance with the COSMIN checklist

Objective To develop and evaluate a modified version of the Victorian Institute of Sport Assessment-Achilles (VISA-A) questionnaire, for use in sedentary patients with Achilles tendinopathy, using the Consensus-based Standards for the selection of health Measurement Instruments recommendations. Methods Twenty-two sedentary patients with Achilles tendinopathy completed the VISA-A and provided feedback regarding the relevance, comprehensiveness and comprehensibility of each item, response options and instructions. Patient and professional feedback was used to develop the VISA-A (sedentary) questionnaire. Reliability, validity and responsiveness of the VISA-A (sedentary) was evaluated in 51 sedentary patients with Achilles tendinopathy: 47.1% women, mean age 64.8 (SD 11.24). Results Factor analysis identified two dimensions (symptoms and activity) for the VISA-A (sedentary). Test–retest reliability was excellent for symptoms (intraclass correlation coefficient, ICC=0.991) and activity (ICC=0.999). Repeatability was 1.647 for symptoms and 0.549 for activity. There was a significant difference between the VISA-A and VISA-A (sedentary) scores both pretreatment and post-treatment. There was stronger correlation between the pretreatment to post-treatment change in the VISA-A (sedentary) scores (r=0.420 for symptoms, r=0.407 for activity) and the global rating of change than the VISA-A scores (r=0.253 for symptoms, r=0.186 for activity). Conclusion The VISA-A (sedentary) demonstrates adequate reliability, validity and responsiveness in sedentary patients with Achilles tendinopathy. The VISA-A (sedentary) is a more appropriate measure than the VISA-A for this cohort and is recommended for clinical and research purposes.</p

Manned sample return mission to Phobos: A technology demonstration for human exploration of Mars

In order to reduce the knowledge gap associated with long-duration human exploration of Mars, a manned precursor mission destined for one of the Martian moons is currently considered a feasible option for testing and demonstrating critical technologies within the Martian system. The 2013 Caltech Space Challenge, a student mission design competition held at the California Institute of Technology, addressed the interest in human precursor missions. Two teams of 16 students, with varying backgrounds and nationalities, were allocated five days to design a mission to land at least one human on a Martian moon and return them, along with a sample, safely to Earth with a launch date no later than January 1, 2041. This paper provides an overview of Technology Advancing Phobos Exploration and Return (TAPER-1), the manned Phobos sample return mission devised by Team Explorer. As the first manned mission to the Martian system, TAPER-1 is designed as an opposition class mission to Phobos, carrying four astronauts, with a launch date in April 2033, and a nominal time of flight of 456 days. In addition, this paper demonstrates the feasibility and value of exposing students to the process of rapid mission design