Effects of Selected Music Environments on Performance of an Endurance Event

The present study was conducted to objectively investigate the effects of music upon human performance during an endurance event. If a regulation of human performance can be established, music could be an invaluable aid for use during physical activity. The purpose of this study was to determine the effects of different types of music upon performance of an endurance event. The following two hypotheses were investigated: 1. There is no significant difference among the five treatments on distance performance of an endurance event. 2. There is no significant difference among the five treatments on heart rate before and during an endurance event

Engaging the disengaged indefinitely, and with no budget: creating a sustainable model for student library ambassadors

University Libraries offer a wide range of services and facilities to help enhance the student learning experience and to aid the transition into learning at University. Often, too few Science and Engineering students fully engage with the services and facilities on offer and therefore do not benefit from the opportunities available to them. Drawing on research highlighting the value of peer support, and the fact that students are far more likely to use their peers as an information source than ‘experts’, Loughborough University Library obtained small project funding in 2010 to employ four Student Ambassadors in a pilot project to improve student engagement with the Library. The successful project demonstrated the potency of the idea in engaging with students, particularly non-users, a large proportion of which are based in the Science and Engineering Faculties. In the absence of continued funding, the challenge, addressed here, is how to make such posts sustainable. Past experience at both Nottingham and Loughborough Universities has proven how difficult it is to recruit students on a voluntary basis to engage with University Libraries. In this paper, an innovative and creative method of recruiting and supporting “Learning Resource Leaders” (LRLs) at Nottingham and Loughborough Universities is discussed. The strategies employed have resulted in the recruitment of four LRLs – two at each institution – supported by an industrial sponsor who provides a package of non-monetary incentives. The paper also describes the techniques used by the LRLs to disseminate information about the resources offered by the University Libraries and to engage with the student cohort

Comparison of gene expression in pre-implantation bovine embryos either injected or transfected with a siRNA targeted against E-cadherin

The ability to create transgenic livestock is a tremendous benefit in scientific research for many disciplines including functional genomics, pharmaceutical synthesis and development of enhanced production animals. Transgenes can either be stably or transiently expressed to alter gene function and obtain a specifically engineered phenotype. To create a transgenic bovine embryo, genetically altered somatic cells must be used in somatic cell nucleus transfer, or early 1-cell embryos (zygotes) must be microinjected with plasmid DNA or small interfering RNA (siRNA). Given the cost and skill associated with both methods, a preliminary investigation exploring alternative delivery techniques of siRNA (transient expression) into bovine zygotes with a nonhomologous Cy3 labeled siRNA (Cy3-siRNA) was first performed. It was discovered that zygotes injected with more than 50 Bmol L-1 of Cy3-siRNA fail to form a blastocoel and that, although bovine zygotes are not susceptible to chemical transfection, the trophectoderm cells of the blastocyst are. Based on this information, bovine E-cadherin gene expression was compared in day 9 blastocysts derived from either injected zygotes (day 1) or transfected blastocysts (day 7) with a Cy3 labeled E-cadherin specific siRNA (Cy3-siEcad) to determine 1) if gene suppression in zygotes injected with 25 Bmol L-1 Cy3-siEcad continues during embryo development up to hatching, and 2) if blastocysts transfected at a ratio of 9:6 with GeneJammer® truly experience gene knock down after siRNA transfection capable of maintaining suppression to day 9. Quantitative PCR indicated blastocysts transfected with Cy3-siEcad had a significant 15.3% decrease (P < 0.05) in E-cadherin mRNA at day 9 compared to the injected zygotes. Protein fluorescence analysis from immunocytochemistry of whole mounted day 9 blastocysts revealed injected zygotes accumulated significantly less E-cadherin protein (67.7%) than the transfected blastocysts (P < 0.05). From these data, it can be concluded that although siRNA injection may be capable of knocking down gene expression for the first 7 days of embryonic development, it does not persist to the hatching stage; however, blastocysts transfected at day 7 do express altered gene expression in the trophectoderm which can continue through embryonic hatching events

The Role of Dispersants in Oil Spill Remediation: Fundamental Concepts, Rationale for Use, Fate, and Transport Issues

ABSTRACTOffering a scientific perspective, this paper provides a rationale for the use of dispersants in oil spill remediation by discussing their formulations and modes of action and connecting their physics and chemistry to a their environmental fates and impacts. With the first use of dispersants at the source of the oil release during the Deepwater Horizon incident, there is a new great need for understanding the efficiency and the environmental impacts of their use. The paper concludes with some cautionary recommendations on dispersant research

The role of dispersants in oil spill remediation : fundamental concepts, rationale for use, fate, and transport issues

Offering a scientific perspective, this paper provides a rationale for the use of dispersants in oil spill remediation by discussing their formulations and modes of action and connecting their physics and chemistry to a their environmental fates and impacts. With the first use of dispersants at the source of the oil release during the Deepwater Horizon incident, there is a new great need for understanding the efficiency and the environmental impacts of their use. The paper concludes with some cautionary recommendations on dispersant research.Author Posting. © The Oceanography Society, 2016. This article is posted here by permission of The Oceanography Society for personal use, not for redistribution. The definitive version was published in Oceanography 29, no. 3 (2016): 108–117, doi:10.5670/oceanog.2016.75

Identification of a selective G1-phase benzimidazolone inhibitor by a senescence-targeted virtual screen using artificial neural networks

Cellular senescence is a barrier to tumorigenesis in normal cells and tumour cells undergo senescence responses to genotoxic stimuli, which is a potential target phenotype for cancer therapy. However, in this setting, mixed-mode responses are common with apoptosis the dominant effect. Hence, more selective senescence inducers are required. Here we report a machine learning-based in silico screen to identify potential senescence agonists. We built profiles of differentially affected biological process networks from expression data obtained under induced telomere dysfunction conditions in colorectal cancer cells and matched these to a panel of 17 protein targets with confirmatory screening data in PubChem. We trained a neural network using 3517 compounds identified as active or inactive against these targets. The resulting classification model was used to screen a virtual library of ~2M lead-like compounds. 147 virtual hits were acquired for validation in growth inhibition and senescence-associated β-galactosidase (SA-β-gal) assays. Among the found hits a benzimidazolone compound, CB-20903630, had low micromolar IC50 for growth inhibition of HCT116 cells and selectively induced SA-β-gal activity in the entire treated cell population without cytotoxicity or apoptosis induction. Growth suppression was mediated by G1 blockade involving increased p21 expression and suppressed cyclin B1, CDK1 and CDC25C. Additionally, the compound inhibited growth of multicellular spheroids and caused severe retardation of population kinetics in long term treatments. Preliminary structure-activity and structure clustering analyses are reported and expression analysis of CB-20903630 against other cell cycle suppressor compounds suggested a PI3K/AKT-inhibitor-like profile in normal cells, with different pathways affected in cancer cells

What are the experiences of seeking, receiving and providing FGM-related healthcare?: perspectives of health professionals and women/girls who have undergone FGM: protocol for a systematic review of qualitative evidence

Introduction: Female Genital Mutilation (FGM) is an issue of global concern. High levels of migration mean that healthcare systems in higher-income western countries are increasingly being challenged to respond to the care needs of affected communities. Research has identified significant challenges in the provision of, and access to, FGM-related healthcare. There is a lack of confidence and competence among health professionals in providing appropriate care, suggesting an urgent need for evidence-based service development in this area. This study will involve two systematic reviews of qualitative evidence to explore the experiences, needs, barriers and facilitators to seeking and providing FGM-related healthcare in high income (OECD) countries, from the perspectives of: (1) women and girls who have undergone FGM and (2) health professionals. Review methods: Twelve databases including MEDLINE, EMBASE, PsycINFO, ASSIA, Web of Science, ERIC, CINAHL, and POPLINE will be searched with no limits on publication year. Relevant grey literature will be identified from digital sources and professional networks. Two reviewers will independently screen, select and critically appraise the studies. Study quality will be assessed using the JBI-QARI appraisal tool. Findings will be extracted into NVivo software. Synthesis will involve inductive thematic analysis, including in-depth reading, line by line coding of the findings, development of descriptive themes and re-coding to higher level analytical themes. Confidence in the review findings will be assessed using the GRADE-CERQual approach. Findings will be integrated into a comprehensive set of recommendations for research, policy and practice. Dissemination: The syntheses will be reported as per the ENTREQ statement. Two reviews will be published in peer-reviewed journals and an integrated report disseminated at stakeholder engagement events

Dependence on RAD52 and RAD1 for anticancer drug resistance mediated by inactivation of mismatch repair genes

AbstractMismatch repair (MMR) proteins repair mispaired DNA bases and have an important role in maintaining the integrity of the genome [1]. Loss of MMR has been correlated with resistance to a variety of DNA-damaging agents, including many anticancer drugs [2]. How loss of MMR leads to resistance is not understood, but is proposed to be due to loss of futile MMR activity and/or replication stalling [3,4]. We report that inactivation of MMR genes (MLH1, MLH2, MSH2, MSH3, MSH6, but not PMS1) in isogenic strains of Saccharomyces cerevisiae led to increased resistance to the anticancer drugs cisplatin, carboplatin and doxorubicin, but had no effect on sensitivity to ultraviolet C (UVC) radiation. Sensitivity to cisplatin and doxorubicin was increased in mlh1 mutant strains when the MLH1 gene was reintroduced, demonstrating a direct involvement of MMR proteins in sensitivity to these DNA-damaging agents. Inactivation of MLH1, MLH2 or MSH2 had no significant effect, however, on drug sensitivities in the rad52 or rad1 mutant strains that are defective in mitotic recombination and removing unpaired DNA single strands. We propose a model whereby MMR proteins – in addition to their role in DNA-damage recognition – decrease adduct tolerance during DNA replication by modulating the levels of recombination-dependent bypass. This hypothesis is supported by the finding that, in human ovarian tumour cells, loss of hMLH1 correlated with acquisition of cisplatin resistance and increased cisplatin-induced sister chromatid exchange, both of which were reversed by restoration of hMLH1 expression

Induction of labour versus expectant management for nulliparous women over 35 years of age: a multi-centre prospective, randomised controlled trial.

BACKGROUND: British women are increasingly delaying childbirth. The proportion giving birth over the age of 35 rose from 12% in 1996 to 20% in 2006. Women over this age are at a higher risk of perinatal death, and antepartum stillbirth accounts for 61% of all such deaths. Women over 40 years old have a similar stillbirth risk at 39 weeks as women who are between 25 and 29 years old have at 41 weeks.Many obstetricians respond to this by suggesting labour induction at term to forestall some of the risk. In a national survey of obstetricians 37% already induce women aged 40-44 years. A substantial minority of parents support such a policy, but others do not on the grounds that it might increase the risk of Caesarean section. However trials of induction in other high-risk scenarios have not shown any increase in Caesarean sections, rather the reverse. If induction for women over 35 did not increase Caesareans, or even reduced them, it would plausibly improve perinatal outcome and be an acceptable intervention. We therefore plan to perform a trial to test the effect of such an induction policy on Caesarean section rates.This trial is funded by the NHS Research for Patient Benefit (RfPB) Programme. DESIGN: The 35/39 trial is a multi-centre, prospective, randomised controlled trial. It is being run in twenty UK centres and we aim to recruit 630 nulliparous women (315 per group) aged over 35 years of age, over two years. Women will be randomly allocated to one of two groups: Induction of labour between 39⁰/⁷ and 39⁶/⁷ weeks gestation. Expectant management i.e. awaiting spontaneous onset of labour unless a situation develops necessitating either induction of labour or Caesarean Section.The primary purpose of this trial is to establish what effect a policy of induction of labour at 39 weeks for nulliparous women of advanced maternal age has on the rate of Caesarean section deliveries. The secondary aim is to act as a pilot study for a trial to answer the question, does induction of labour in this group of women improve perinatal outcomes? Randomisation will occur at 36⁰/⁷-39⁶/⁷ weeks gestation via a computerised randomisation programme at the Clinical Trials Unit, University of Nottingham. There will be no blinding to treatment allocation. DISCUSSION: The 35/39 trial is powered to detect an effect of induction of labour on the risk of caesarean section, it is underpowered to determine whether it improves perinatal outcome. The current study will also act as a pilot for a larger study to address this question. TRIAL REGISTRATION: ISRCTN11517275.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma (DIAPHRAGM) study:Protocol of a prospective, multicentre, observational study

Introduction: Malignant pleural mesothelioma (MPM) is an asbestos-related cancer, which is difficult to diagnose. Thoracoscopy is frequently required but is not widely available. An accurate, non-invasive diagnostic biomarker would allow early specialist referral, limit diagnostic delays and maximise clinical trial access. Current markers offer insufficient sensitivity and are not routinely used. The SOMAmer proteomic classifier and fibulin-3 have recently demonstrated sensitivity and specificity exceeding 90% in retrospective studies. DIAPHRAGM (Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma) is a suitably powered, multicentre, prospective observational study designed to determine whether these markers provide clinically useful diagnostic and prognostic information. Methods and analysis: Serum and plasma (for SOMAscan and fibulin-3, respectively) will be collected at presentation, prior to pleural biopsy/pleurodesis, from 83 to 120 patients with MPM, at least 480 patients with non-MPM pleural disease and 109 asbestos-exposed controls. Final numbers of MPM/non-MPM cases will depend on the incidence of MPM in the study population (estimated at 13–20%). Identical sampling and storage protocols will be used in 22 recruiting centres and histological confirmation sought in all cases. Markers will be measured using the SOMAscan proteomic assay (SomaLogic) and a commercially available fibulin-3 ELISA (USCN Life Science). The SE in the estimated sensitivity and specificity will be &lt;5% for each marker and their performance will be compared with serum mesothelin. Blood levels will be compared with paired pleural fluid levels and MPM tumour volume (using MRI) in a nested substudy. The prognostic value of each marker will be assessed and a large bioresource created. Ethics and dissemination: The study has been approved by the West of Scotland Research Ethics Committee (Ref: 13/WS/0240). A Trial Management Group meets on a monthly basis. Results will be published in peer-reviewed journals, presented at international meetings and disseminated to patient groups. Trial registration number: ISRCTN10079972, Pre-results