Effect of parent-delivered action observation therapy on upper limb function in unilateral cerebral palsy: a randomized controlled trial

AIM:To determine whether home-based, parent-delivered therapy comprising action observation (AO) and repeated practice (RP) improves upper limb function more than RP alone in children with unilateral cerebral palsy (UCP).METHOD:Design: single-blinded parallel-group randomized controlled trial with 1:1 allocation comparing AO+RP (intervention) with RP alone (control). Randomization: computer-generated, with allocation concealment by opaque sequentially-numbered envelopes.SETTING: northern England, August 2011 to September 2013.PARTICIPANTS: 70 children with UCP; mean age 5.6 years (SD 2.1), 31 female.INTERVENTION: home-based activities were provided, tailored to interests and abilities.DURATION: 15 minutes/day, 5 days/week for 3 months.ASSESSMENTS: Assisting Hand Assessment (AHA; primary outcome measure), Melbourne Assessment 2 (MA2), and ABILHAND-Kids at baseline, 3 months, and 6 months.RESULTS: Outcome data was available at 3 months for 28 children in the AO+RP group and 31 controls, and at 6 months for 26 and 28 children respectively. There were no between-group differences in AHA, MA2, or ABILHAND-Kids at 3 or 6 months versus baseline (all p>0.05). Combined-group improvements (p<0.001), observed in AHA and MA2 at 3 months, were maintained at 6 months. ABILHAND-Kids also showed improvement at 3 months (p=0.003), maintained at 6 months.INTERPRETATION: Parent-delivered RP (with or without AO) improves upper limb function and could supplement therapist input

Seasonal changes in anthropometric and physical characteristics within English academy rugby league players.

Professional rugby league clubs implement training programmes for the development of anthropometric and physical characteristics within an academy programme. However, research that examines seasonal changes in these characteristics is limited. The purpose of the study was to evaluate the seasonal changes in anthropometric and physical characteristics of academy rugby league players by age category (i.e., under 14, 16, 18, 20). Data were collected on 75 players pre- and postseason over a 6-year period (resulting in a total of 195 assessments). Anthropometric (body mass, sum of 4 skinfolds) and physical (10- and 20-m sprint, vertical jump, Yo-Yo intermittent recovery test and 1 repetition maximum squat, bench press, and prone row) measures were collected. The under 14s and 16s showed greater seasonal improvements in body mass (e.g., under 14s = 7.4 ± 4.3% vs. under 20s = 1.2 ± 3.3%) and vertical jump performance than under 18s and under 20s. In contrast, under 18s and under 20s players showed greater seasonal improvements in Yo-Yo performance and 10-m sprint (e.g., under 14s = 1.3 ± 3.9% vs. under 20s = -1.9 ± 1.2%) in comparison to under 14s and under 16s. Seasonal strength improvements were greater for the under 18s compared with under 20s. This study provides comparative data for seasonal changes in anthropometric and physical characteristics within rugby league players aged 13-20 years. Coaches should be aware that seasonal improvements in speed may not exist within younger age categories, until changes in body mass stabilize and consider monitoring changes in other characteristics (e.g., momentum). Large interplayer variability suggests that player development should be considered on an individual and longitudinal basis

Anthropometric and physical characteristics of english academy rugby league players.

The purpose of the present study was to evaluate the anthropometric and physical characteristics of English academy rugby league players by annual-age category (under 16s-under 20s) and between backs and forwards. Data were collected on 133 academy players over a 6-year period (resulting in a total of 257 assessments). Player assessments comprised of anthropometric (height, body mass, sum of 4 skinfolds) and physical (vertical jump, 10- and 20-m sprint, estimated V[Combining Dot Above]O2max via the yo-yo intermittent recovery test level 1, absolute 1 repetition maximum [1RM], and relative squat, bench press, and prone row) measures. Univariate analysis of variance demonstrated significant (p ≤ 0.05) increases in height, body mass, vertical jump, absolute, and relative strength measures across the 5 annual-age categories (e.g., body mass: under 16s = 75.2 ± 11.1, under 20s = 88.9 ± 8.5 kg; vertical jump: under 16s = 45.7 ± 5.2, under 20s = 52.8 ± 5.4 cm; 1RM bench press: under 16s = 73.9 ± 13.2, under 20s = 114.3 ± 15.3 kg). Independent t-tests identified significant (p ≤ 0.05) differences between backs and forwards for anthropometric (e.g., under 16s body mass: backs = 68.4 ± 8.6, forwards = 80.9 ± 9.7 kg) and physical (e.g., under 19s 20-m sprint: backs = 3.04 ± 0.08, forwards = 3.14 ± 0.12s; under 18s relative squat: backs = 1.65 ± 0.18, forwards = 1.51 ± 0.17 kg·kg) characteristics that were dependent on the age category and measure assessed. Findings highlight that anthropometric and physical characteristics develop across annual-age categories and between backs and forwards in academy rugby league players. These findings provide comparative data for such populations and support the need to monitor player development in junior rugby league players

MENOS4 trial: a multicentre randomised controlled trial (RCT) of a breast care nurse delivered cognitive behavioural therapy (CBT) intervention to reduce the impact of hot flushes in women with breast cancer: Study Protocol

BACKGROUND: Women who have been treated for breast cancer may identify vasomotor symptoms, such as hot flushes and night sweats (HFNS), as a serious problem. HFNS are unpleasant to experience and can have a significant impact on daily life, potentially leading to reduced adherence to life saving adjuvant hormonal therapy. It is known that Cognitive Behavioural Therapy (CBT) is effective for the alleviation of hot flushes in both well women and women who have had breast cancer. Most women with breast cancer will see a breast care nurse and there is evidence that nurses can be trained to deliver psychological treatments to a satisfactory level, whilst also maintaining treatment fidelity. The research team will assess whether breast care nurses can effectively deliver a CBT intervention to alleviate hot flushes in women with breast cancer.METHODS: This study is a multi-centre phase III individually randomised controlled trial of group CBT versus usual care to reduce the impact of hot flushes in women with breast cancer. 120-160 women with primary breast cancer experiencing seven or more problematic HFNS a week will be randomised to receive either treatment as usual (TAU) or participation in the group CBT intervention plus TAU (CBT Group). A process evaluation using May's Normalisation Process Theory will be conducted, as well as practical and organisational issues relating to the implementation of the intervention. Fidelity of implementation of the intervention will be conducted by expert assessment. The cost effectiveness of the intervention will also be assessed.DISCUSSION: There is a need for studies that enable effective interventions to be implemented in practice. There is good evidence that CBT is helpful for women with breast cancer who experience HFNS, yet it is not widely available. It is not yet known whether the intervention can be effectively delivered by breast care nurses or implemented in practice. This study will provide information on both whether the intervention can effectively help women with hot flushes and whether and how it can be translated into routine clinical practice.TRIAL REGISTRATION: ISRCTN 12824632 . Registered 25-01-2017.</p

Tree of Sex: A database of sexual systems

The vast majority of eukaryotic organisms reproduce sexually, yet the nature of the sexual system and the mechanism of sex determination often vary remarkably, even among closely related species. Some species of animals and plants change sex across their lifespan, some contain hermaphrodites as well as males and females, some determine sex with highly differentiated chromosomes, while others determine sex according to their environment. Testing evolutionary hypotheses regarding the causes and consequences of this diversity requires interspecific data placed in a phylogenetic context. Such comparative studies have been hampered by the lack of accessible data listing sexual systems and sex determination mechanisms across the eukaryotic tree of life. Here, we describe a database developed to facilitate access to sexual system and sex chromosome information, with data on sexual systems from 11,038 plant, 705 fish, 173 amphibian, 593 non-avian reptilian, 195 avian, 479 mammalian, and 11,556 invertebrate species

Profiling sulfur(VI) fluorides as reactive functionalities for chemical biology tools and expansion of the ligandable proteome

Here, we report a comprehensive profiling study of sulfur(VI) fluorides (SVI-F) in the context of multiple chemical biology applications and illustrate that these motifs present an exciting opportunity to develop tools for a wide scope of protein targets. SVI-Fs are reactive functionalities that offer utility for targeting almost any protein, as they can modify multiple residues including Lys, Tyr, His and Ser. A panel of SVI-F functionalities were studied with respect to hydrolytic stability and reactivity with nucleophilic amino acids. Subsequently, the reactivity of SVI-Fs with CAII and kinase proteins was investigated, in the context of both fragment binders and optimized probes. Finally, the performance of the SVI-F panel in chemoproteomic workflows was analyzed. The studies provided an in-depth understanding of the hydrolytic stability, protein reactivity and chemoproteomic utility of SVI-F functionalities that are suitable for direct incorporation into chemical tools. Such insights offer a valuable guide for the prospective design of SVI-F-containing ligands for various chemical biology workflows and demonstrate the wide range of proteins that SVI-Fs can capture, thus highlighting the opportunity for SVI-Fs to expand the liganded proteome

The roles of encoding and retrieval processes in associative and categorical memory illusions

Four experiments investigated the origin of associative and categorical memory illusions by comparing the effects of study and test associations on Deese/Roediger-McDermott (DRM) and categorized lists. Experiments 1 and 2 found that levels of false recognition with both list types were increased by manipulations that facilitated the generation of associates at study (blocked presentation of study lists and explicit instructions to generate associates of studied items). Experiments 3 and 4 showed that manipulations designed to increase test associations (test-induced priming and part-set cuing) did not increase levels of false memory with either list type. These findings indicate that false memories produced by both DRM and categorized lists are influenced by associations activated at study but not by associations activated at test

CONFIRM: a double-blind, placebo controlled phase III clinical trial investigating the effect of nivolumab in patients with relapsed mesothelioma: study protocol for a randomised controlled trial

Background: Mesothelioma is an incurable, apoptosis-resistant cancer caused in most cases by previous exposure to asbestos and is increasing in incidence. It represents a growing health burden but remains under-researched, with limited treatment options. Early promising signals of activity relating to both PD-L1- and PD-1-targeted treatment in mesothelioma implicate a dependency of mesothelioma on this immune checkpoint. There is a need to evaluate checkpoint inhibitors in patients with relapsed mesothelioma where treatment options are limited. Methods: The addition of 12 months of nivolumab (anti-PD1 antibody) to standard practice will be conducted in the UK using a randomised, placebo-controlled phase III trial (the Cancer Research UK CONFIRM trial). A total of 336 patients with pleural or peritoneal mesothelioma who have received at least two prior lines of therapy will be recruited from UK secondary care sites. Patients will be randomised 2:1 (nivolumab:placebo), stratified according to epithelioid/non-epithelioid, to receive either 240 mg nivolumab monotherapy or saline placebo as a 30-min intravenous infusion. Treatment will be for up to 12 months. We will determine whether the use of nivolumab increases overall survival (the primary efficacy endpoint). Secondary endpoints will include progression-free survival, objective response rate, toxicity, quality of life and cost-effectiveness. Analysis will be performed according to the intention-to-treat principle using a Cox regression analysis for the primary endpoint (and for other time-to-event endpoints). Discussion: The outcome of this trial will provide evidence of the potential benefit of the use of nivolumab in the treatment of relapsed mesothelioma. If found to be clinically effective, safe and cost-effective it is likely to become the new standard of care in the UK

Phosphorylation of Exo1 modulates homologous recombination repair of DNA double-strand breaks

DNA double-strand break (DSB) repair via the homologous recombination pathway is a multi-stage process, which results in repair of the DSB without loss of genetic information or fidelity. One essential step in this process is the generation of extended single-stranded DNA (ssDNA) regions at the break site. This ssDNA serves to induce cell cycle checkpoints and is required for Rad51 mediated strand invasion of the sister chromatid. Here, we show that human Exonuclease 1 (Exo1) is required for the normal repair of DSBs by HR. Cells depleted of Exo1 show chromosomal instability and hypersensitivity to ionising radiation (IR) exposure. We find that Exo1 accumulates rapidly at DSBs and is required for the recruitment of RPA and Rad51 to sites of DSBs, suggesting a role for Exo1 in ssDNA generation. Interestingly, the phosphorylation of Exo1 by ATM appears to regulate the activity of Exo1 following resection, allowing optimal Rad51 loading and the completion of HR repair. These data establish a role for Exo1 in resection of DSBs in human cells, highlighting the critical requirement of Exo1 for DSB repair via HR and thus the maintenance of genomic stability