No effect of arm exercise on diaphragmatic fatigue or ventilatory constraint in Paralympic athletes with cervical spinal cord injury

Cervical spinal cord injury (CSCI) results in a decrease in the capacity of the lungs and chest wall for pressure, volume, and airflow generation. We asked whether such impairments might increase the potential for exercise-induced diaphragmatic fatigue and mechanical ventilatory constraint in this population. Seven Paralympic wheelchair rugby players (mean ± SD peak oxygen uptake = 16.9 ± 4.9 ml·kg–1·min–1) with traumatic CSCI (C5–C7) performed arm-crank exercise to the limit of tolerance at 90% of their predetermined peak work rate. Diaphragm function was assessed before and 15 and 30 min after exercise by measuring the twitch transdiaphragmatic pressure (Pdi,tw) response to bilateral anterolateral magnetic stimulation of the phrenic nerves. Ventilatory constraint was assessed by measuring the tidal flow volume responses to exercise in relation to the maximal flow volume envelope. Pdi,tw was not different from baseline at any time after exercise (unpotentiated Pdi,tw = 19.3 ± 5.6 cmH2O at baseline, 19.8 ± 5.0 cmH2O at 15 min after exercise, and 19.4 ± 5.7 cmH2O at 30 min after exercise; P = 0.16). During exercise, there was a sudden, sustained rise in operating lung volumes and an eightfold increase in the work of breathing. However, only two subjects showed expiratory flow limitation, and there was substantial capacity to increase both flow and volume (<50% of maximal breathing reserve). In conclusion, highly trained athletes with CSCI do not develop exercise-induced diaphragmatic fatigue and rarely reach mechanical ventilatory constraint

Wide-pulse electrical stimulation to an intrinsic foot muscle induces acute functional changes in forefoot-rearfoot coupling behaviour during walking.

Interventions for strengthening intrinsic foot muscles may be beneficial for rehabilitation from overuse injuries. In this study the acute effects of high-frequency, low-intensity wide-pulse electrical stimulation (WPS) over an intrinsic muscle on subsequent foot function during walking was assessed in healthy participants. WPS was delivered to the m. abductor hallucis (m.AH) of the non-dominant foot during relaxed standing. 3-dimensional forefoot (FF)--rearfoot (RF) coordination was quantified with a vector coding technique within separate periods of the stance phase to study WPS functional effects on foot motion. 4 types of coordinative strategies between the FF and RF were interpreted and compared PRE-to-POST-WPS for both the experimental and control feet. Bilateral electromyography (EMG) from m.AH was analysed during the intervention period for evidence of acute neuromuscular adaptation. The results showed that WPS significantly modulated FF-RF coordination during mid-stance, indicative of a more stable foot. Specifically, a statistically significant increase in FF eversion with concomitant RF inversion in the frontal plane and RF-dominated adduction in the transverse plane was observed. Subject-specific increases in post-stimulus m.AH EMG activation were observed but this was not reflected in an overall group effect. It is concluded that the structural integrity of the foot during walking is enhanced following an acute session of WPS and that this mechanical effect is most likely due to stimulation induced post-tetanic potentiation of synaptic transmission

Giving voters what they want? Party orientation perceptions and preferences in the British electorate

Some of the most important propositions in the political marketing literature hinge on assumptions about the electorate. In particular, voters are presumed to react in different ways to different orientations or postures. Yet there are theoretical reasons for questioning some of these assumptions, and certainly they have seldom been empirically tested. Here, we focus on one prominent example of political marketing research: Lees-Marshment’s orientations’ model. We investigate how the public reacts to product and market orientation, whether they see a trade-off between the two (a point in dispute among political marketing scholars), and whether partisans differ from non-partisan voters by being more inclined to value product over market orientation. Evidence from two mass sample surveys of the British public (both conducted online by YouGov) demonstrates important heterogeneity within the electorate, casts doubt on the core assumptions underlying some political marketing arguments and raises broader questions about what voters are looking for in a party

What Does It Take to Make it to the Polling Station? The Effects of Campaign Activities on Electoral Participation

This study explores the extent to which campaign visibility facilitates electoral participation, using data from first- and second-order elections in Britain. Our contribution to the existing literature is threefold. First, we assess whether the effects of campaign effort are conditioned by marginality, finding that campaign mobilisation gets out the vote regardless of the competitiveness of the race. Second, we look at the relative ability of different campaign activities to stimulate turnout, detecting significant differences. Third, we show that the effects of campaign effort on electoral participation are rather similar in first- and second-order elections. These findings suggest that a greater level of electoral information provided by campaign activities does reduce the costs of voting. Local campaigns play a key role in bringing voters to the polls in marginal and non-marginal races, and at general elections as much as at second-order elections

Inclusion of KI67 significantly improves performance of the PREDICT prognostication and prediction model for early breast cancer.

BACKGROUND: PREDICT (http://www.predict.nhs.uk) is a prognostication and treatment benefit tool for early breast cancer (EBC). The aim of this study was to incorporate the prognostic effect of KI67 status in a new version (v3), and compare performance with the Predict model that includes HER2 status (v2). METHODS: The validation study was based on 1,726 patients with EBC treated in Nottingham between 1989 and 1998. KI67 positivity for PREDICT is defined as >10% of tumour cells staining positive. ROC curves were constructed for Predict models with (v3) and without (v2) KI67 input. Comparison was made using the method of DeLong. RESULTS: In 1274 ER+ patients the predicted number of events at 10 years increased from 196 for v2 to 204 for v3 compared to 221 observed. The area under the ROC curve (AUC) improved from 0.7611 to 0.7676 (p=0.005) in ER+ patients and from 0.7546 to 0.7595 (p=0.0008) in all 1726 patients (ER+ and ER-). CONCLUSION: Addition of KI67 to PREDICT has led to a statistically significant improvement in the model performance for ER+ patients and will aid clinical decision making in these patients. Further studies should determine whether other markers including gene expression profiling provide additional prognostic information to that provided by PREDICT.SEARCH was funded through a programme grant from Cancer Research UK (C490/A10124) and this work is supported by the UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge.This is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/1471-2407-14-90

Transfer RNA-derived small RNAs in the cancer transcriptome

The cellular lifetime includes stages such as differentiation, proliferation, division, senescence and apoptosis.These stages are driven by a strictly ordered process of transcription dynamics. Molecular disruption to RNA polymerase assembly, chromatin remodelling and transcription factor binding through to RNA editing, splicing, post-transcriptional regulation and ribosome scanning can result in significant costs arising from genome instability. Cancer development is one example of when such disruption takes place. RNA silencing is a term used to describe the effects of post-transcriptional gene silencing mediated by a diverse set of small RNA molecules. Small RNAs are crucial for regulating gene expression and microguarding genome integrity.RNA silencing studies predominantly focus on small RNAs such as microRNAs, short-interfering RNAs and piwi-interacting RNAs. We describe an emerging renewal of inter-est in a‘larger’small RNA, the transfer RNA (tRNA).Precisely generated tRNA-derived small RNAs, named tRNA halves (tiRNAs) and tRNA fragments (tRFs), have been reported to be abundant with dysregulation associated with cancer. Transfection of tiRNAs inhibits protein translation by displacing eukaryotic initiation factors from messenger RNA (mRNA) and inaugurating stress granule formation.Knockdown of an overexpressed tRF inhibits cancer cell proliferation. Recovery of lacking tRFs prevents cancer metastasis. The dual oncogenic and tumour-suppressive role is typical of functional small RNAs. We review recent reports on tiRNA and tRF discovery and biogenesis, identification and analysis from next-generation sequencing data and a mechanistic animal study to demonstrate their physiological role in cancer biology. We propose tRNA-derived small RNA-mediated RNA silencing is an innate defence mechanism to prevent oncogenic translation. We expect that cancer cells are percipient to their ablated control of transcription and attempt to prevent loss of genome control through RNA silencing

Collective defence and behavioural homogeneity during simulated territorial intrusions in banded mongooses (Mungos mungo)

This is the final version. Available on open access from Wiley via the DOI in this recordConflicts between stable social groups (“intergroup conflicts”) can be damaging and exert a strong influence on within-group social behaviour. The success of groups during intergroup conflict may depend on the ability of individual group members to converge upon collective defence behaviour, such as approaching or attacking. In principle, collective defence can be achieved via a united front, in which each individual responds in the same way to an intergroup threat. We tested the impact of simulated intergroup conflicts on collective defence and individual behaviour in banded mongooses (Mungos mungo), a cooperatively breeding mammal in which intergroup conflict is particularly common and costly. We presented focal groups with scent markings, call playbacks and caged live animals from rival groups and compared their responses to these stimuli with their responses to own-group control stimuli. A greater proportion of group members approached the stimulus and acted defensively in response to rival stimuli as compared to controls, consistent with a unified collective defence response. However, counter to our expectation, groups exhibited lower behavioural homogeneity when presented with rival stimuli as compared to controls. A closer examination of the behaviours competitors used revealed that lower homogeneity was driven by a greater use, and diversity, of defensive behaviours relevant to repelling simulated rivals. Finally, group size affected responses: as group size increased, the proportion of members approaching the stimulus and behavioural homogeneity decreased. Our results lend support to the hypothesis that intergroup conflict leads to coordinated collective defence behaviour during the immediate threat of an intergroup conflict. However, collective defence need not mean that all group members execute the same behaviours.Natural Environment Research Council (NERC)European Research Council (ERC)Human Frontiers Science Progra

User centered ecological interface design (UCEID): A novel method applied to the problem of safe and user-friendly interaction between drivers and autonomous vehicles

© Springer International Publishing AG 2018. User Centered Ecological Interface Design (UCEID) is a novel Human Factors method that integrates relationships between Ecological Interface Design (EID) and inclusive Human Centered Design. It combines existing methodology from the Cognitive Work Analysis (CWA) framework [1–3] and Inclusive User Centered Design [4, 5]. This paper offers a practical guide to UCEID by providing a high-level summary for practitioners using the example of vehicle to driver handover in a BASt Level 3 autonomous vehicle

Psychometric precision in phenotype definition is a useful step in molecular genetic investigation of psychiatric disorders

Affective disorders are highly heritable, but few genetic risk variants have been consistently replicated in molecular genetic association studies. The common method of defining psychiatric phenotypes in molecular genetic research is either a summation of symptom scores or binary threshold score representing the risk of diagnosis. Psychometric latent variable methods can improve the precision of psychiatric phenotypes, especially when the data structure is not straightforward. Using data from the British 1946 birth cohort, we compared summary scores with psychometric modeling based on the General Health Questionnaire (GHQ-28) scale for affective symptoms in an association analysis of 27 candidate genes (249 single-nucleotide polymorphisms (SNPs)). The psychometric method utilized a bi-factor model that partitioned the phenotype variances into five orthogonal latent variable factors, in accordance with the multidimensional data structure of the GHQ-28 involving somatic, social, anxiety and depression domains. Results showed that, compared with the summation approach, the affective symptoms defined by the bi-factor psychometric model had a higher number of associated SNPs of larger effect sizes. These results suggest that psychometrically defined mental health phenotypes can reflect the dimensions of complex phenotypes better than summation scores, and therefore offer a useful approach in genetic association investigations