A feasibility study to evaluate a purposeful walk intervention with a distance goal using a commercially available activity monitor in elderly people post total hip replacement surgery

INTRODUCTION: Total hip replacement (THR) is performed in an increasing number of individuals around the world and while improvements in pain reduction and long-term enhancement of muscle strength are well documented, the improvement in daily activity does not follow the same trend. This study aimed to determine the feasibility of a 5-week intervention where a personalised outdoor walking distance is monitored using a commercial activity monitor (Fitbit Charge 4). METHOD: Data was collected on gait and activities of daily living using patient reported outcome measures. Following the completion of the intervention period, participants took part in a semi-structured interview to voice their opinion on the use of the activity monitor, their experiences, and any challenges in order to assess the feasibility of the intervention. All quantitative data were presented descriptively, using appropriate summary statistics. Interviews were analysed using thematic analysis. RESULTS: Five participants who had undergone total hip replacement surgery within the postoperative period of 3 to 6 months were recruited from the local community. CONCLUSION: The findings suggest that the intervention was feasible and that it encouraged all participants to increase their daily activity. Therefore, it can be concluded that a follow-up effectiveness trial is warranted

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

Oilseed rape (Brassica napus) as a resource for farmland insect pollinators: quantifying floral traits in conventional varieties and breeding systems

This is the final version of the article. Available from the publisher via the DOI in this record.Oilseed rape (OSR; Brassica napus L.) is a major crop in temperate regions and provides an important source ofnutrition to many of the yield-enhancing insect flower visitors that consume floral nectar. The manipulation ofmechanisms that control various crop plant traits for the benefit of pollinators has been suggested in the bid toincrease food security, but little is known about inherent floral trait expression in contemporary OSR varieties orthe breeding systems used in OSR breeding programmes. We studied a range of floral traits in glasshouse-grown, certified conventional varieties of winter OSR to test for variation among and within breeding systems.We measured 24-h nectar secretion rate, amount, concentration and ratio of nectar sugars per flower, and sizesand number of flowers produced per plant from 24 varieties of OSR representing open-pollinated (OP), genicmale sterility (GMS) hybrid and cytoplasmic male sterility (CMS) hybrid breeding systems. Sugar concentrationwas consistent among and within the breeding systems; however, GMS hybrids produced more nectar and moresugar per flower than CMS hybrid or OP varieties. With the exception of ratio of fructose/glucose in OP vari-eties, we found that nectar traits were consistent within all the breeding systems. When scaled, GMS hybridsproduced 1.73 times more nectar resource per plant than OP varieties. Nectar production and amount of nectarsugar in OSR plants were independent of number and size of flowers. Our data show that floral traits of glass-house-grown OSR differed among breeding systems, suggesting that manipulation and enhancement of nectarrewards for insect flower visitors, including pollinators, could be included in future OSR breeding programmes.This work was fundedby the BBSRC, including support from an Insect Pollinators Ini-tiative grant awarded to GAW (BB/I000968/1) that was jointlyfunded by the BBSRC, NERC, the Wellcome Trust, Defra, andthe Scottish Government. Support was also received from HighWycombe Beekeepers’ Association. Rothamsted Researchreceives strategic funding from the Biotechnology and BiologicalSciences Research Council (BBSRC) of the UK

Testosterone replacement in young male cancer survivors: A 6-month double-blind randomised placebo-controlled trial

Background Young male cancer survivors have lower testosterone levels, higher fat mass, and worse quality of life (QoL) than age-matched healthy controls. Low testosterone in cancer survivors can be due to orchidectomy or effects of chemotherapy and radiotherapy. We have undertaken a double-blind, placebo-controlled, 6-month trial of testosterone replacement in young male cancer survivors with borderline low testosterone (7–12 nmol/l). Methods and findings This was a multicentre United Kingdom study conducted in secondary care hospital outpatients. Male survivors of testicular cancer, lymphoma, and leukaemia aged 25–50 years with morning total serum testosterone 7–12 nmol/l were recruited. A total of 136 men were randomised between July 2012 and February 2015 (42.6% aged 25–37 years, 57.4% 38–50 years, 88% testicular cancer, 10% lymphoma, matched for body mass index [BMI]). Participants were randomised 1:1 to receive testosterone (Tostran 2% gel) or placebo for 26 weeks. A dose titration was performed after 2 weeks. The coprimary end points were trunk fat mass and SF36 Physical Functioning score (SF36-PF) at 26 weeks by intention to treat. At 26 weeks, testosterone treatment compared with placebo was associated with decreased trunk fat mass (−0.9 kg, 95% CI −1.6 to −0.3, p = 0.0073), decreased whole-body fat mass (−1.8 kg, 95% CI −2.9 to −0.7, p = 0.0016), and increased lean body mass (1.5 kg, 95% CI 0.9–2.1, p < 0.001). Decrease in fat mass was greatest in those with a high truncal fat mass at baseline. There was no treatment effect on SF36-PF or any other QoL scores. Testosterone treatment was well tolerated. The limitations of our study were as follows: a relatively short duration of treatment, only three cancer groups included, and no hard end point data such as cardiovascular events. Conclusions In young male cancer survivors with low-normal morning total serum testosterone, replacement with testosterone is associated with an improvement in body composition. Trial registration ISRCTN: 70274195, EudraCT: 2011-000677-31

The role of input noise in transcriptional regulation

Even under constant external conditions, the expression levels of genes fluctuate. Much emphasis has been placed on the components of this noise that are due to randomness in transcription and translation; here we analyze the role of noise associated with the inputs to transcriptional regulation, the random arrival and binding of transcription factors to their target sites along the genome. This noise sets a fundamental physical limit to the reliability of genetic control, and has clear signatures, but we show that these are easily obscured by experimental limitations and even by conventional methods for plotting the variance vs. mean expression level. We argue that simple, global models of noise dominated by transcription and translation are inconsistent with the embedding of gene expression in a network of regulatory interactions. Analysis of recent experiments on transcriptional control in the early Drosophila embryo shows that these results are quantitatively consistent with the predicted signatures of input noise, and we discuss the experiments needed to test the importance of input noise more generally.Comment: 11 pages, 5 figures minor correction

A novel isolator-based system promotes viability of human embryos during laboratory processing

In vitro fertilisation (IVF) and related technologies are arguably the most challenging of all cell culture applications. The starting material is a single cell from which one aims to produce an embryo capable of establishing a pregnancy eventually leading to a live birth. Laboratory processing during IVF treatment requires open manipulations of gametes and embryos, which typically involves exposure to ambient conditions. To reduce the risk of cellular stress, we have developed a totally enclosed system of interlinked isolator-based workstations designed to maintain oocytes and embryos in a physiological environment throughout the IVF process. Comparison of clinical and laboratory data before and after the introduction of the new system revealed that significantly more embryos developed to the blastocyst stage in the enclosed isolator-based system compared with conventional open-fronted laminar flow hoods. Moreover, blastocysts produced in the isolator-based system contained significantly more cells and their development was accelerated. Consistent with this, the introduction of the enclosed system was accompanied by a significant increase in the clinical pregnancy rate and in the proportion of embryos implanting following transfer to the uterus. The data indicate that protection from ambient conditions promotes improved development of human embryos. Importantly, we found that it was entirely feasible to conduct all IVF-related procedures in the isolator-based workstations

Effect of promoter architecture on the cell-to-cell variability in gene expression

According to recent experimental evidence, the architecture of a promoter, defined as the number, strength and regulatory role of the operators that control the promoter, plays a major role in determining the level of cell-to-cell variability in gene expression. These quantitative experiments call for a corresponding modeling effort that addresses the question of how changes in promoter architecture affect noise in gene expression in a systematic rather than case-by-case fashion. In this article, we make such a systematic investigation, based on a simple microscopic model of gene regulation that incorporates stochastic effects. In particular, we show how operator strength and operator multiplicity affect this variability. We examine different modes of transcription factor binding to complex promoters (cooperative, independent, simultaneous) and how each of these affects the level of variability in transcription product from cell-to-cell. We propose that direct comparison between in vivo single-cell experiments and theoretical predictions for the moments of the probability distribution of mRNA number per cell can discriminate between different kinetic models of gene regulation.Comment: 35 pages, 6 figures, Submitte

Three Spin Spiky Strings in beta-deformed Background

We study rigidly rotating strings in $\beta$-deformed $AdS_5\times S^5$ background with one spin along AdS$_5$ and two angular momenta along $S^5$. We find the spiky string solutions and present the dispersion relation among various charges in this background. We further generalize the result to the case of four angular momenta along $AdS_5 \times S_{\gamma}^5$.Comment: 12 pages, minor corrections, added references, to appear in JHE

A Genome-Wide Analysis of Promoter-Mediated Phenotypic Noise in Escherichia coli

Gene expression is subject to random perturbations that lead to fluctuations in the rate of protein production. As a consequence, for any given protein, genetically identical organisms living in a constant environment will contain different amounts of that particular protein, resulting in different phenotypes. This phenomenon is known as “phenotypic noise.” In bacterial systems, previous studies have shown that, for specific genes, both transcriptional and translational processes affect phenotypic noise. Here, we focus on how the promoter regions of genes affect noise and ask whether levels of promoter-mediated noise are correlated with genes' functional attributes, using data for over 60% of all promoters in Escherichia coli. We find that essential genes and genes with a high degree of evolutionary conservation have promoters that confer low levels of noise. We also find that the level of noise cannot be attributed to the evolutionary time that different genes have spent in the genome of E. coli. In contrast to previous results in eukaryotes, we find no association between promoter-mediated noise and gene expression plasticity. These results are consistent with the hypothesis that, in bacteria, natural selection can act to reduce gene expression noise and that some of this noise is controlled through the sequence of the promoter region alon

Kinetic modelling of competition and depletion of shared miRNAs by competing endogenous RNAs

Non-conding RNAs play a key role in the post-transcriptional regulation of mRNA translation and turnover in eukaryotes. miRNAs, in particular, interact with their target RNAs through protein-mediated, sequence-specific binding, giving rise to extended and highly heterogeneous miRNA-RNA interaction networks. Within such networks, competition to bind miRNAs can generate an effective positive coupling between their targets. Competing endogenous RNAs (ceRNAs) can in turn regulate each other through miRNA-mediated crosstalk. Albeit potentially weak, ceRNA interactions can occur both dynamically, affecting e.g. the regulatory clock, and at stationarity, in which case ceRNA networks as a whole can be implicated in the composition of the cell's proteome. Many features of ceRNA interactions, including the conditions under which they become significant, can be unraveled by mathematical and in silico models. We review the understanding of the ceRNA effect obtained within such frameworks, focusing on the methods employed to quantify it, its role in the processing of gene expression noise, and how network topology can determine its reach.Comment: review article, 29 pages, 7 figure