Medical expulsive therapy in adults with ureteric colic: a multicentre, randomised, placebo-controlled trial.

BACKGROUND: Meta-analyses of previous randomised controlled trials concluded that the smooth muscle relaxant drugs tamsulosin and nifedipine assisted stone passage for people managed expectantly for ureteric colic, but emphasised the need for high-quality trials with wide inclusion criteria. We aimed to fulfil this need by testing effectiveness of these drugs in a standard clinical care setting. METHODS: For this multicentre, randomised, placebo-controlled trial, we recruited adults (aged 18-65 years) undergoing expectant management for a single ureteric stone identified by CT at 24 UK hospitals. Participants were randomly assigned by a remote randomisation system to tamsulosin 400 µg, nifedipine 30 mg, or placebo taken daily for up to 4 weeks, using an algorithm with centre, stone size (≤5 mm or >5 mm), and stone location (upper, mid, or lower ureter) as minimisation covariates. Participants, clinicians, and trial personnel were masked to treatment assignment. The primary outcome was the proportion of participants who did not need further intervention for stone clearance within 4 weeks of randomisation, analysed in a modified intention-to-treat population defined as all eligible patients for whom we had primary outcome data. This trial is registered with the European Clinical Trials Database, EudraCT number 2010-019469-26, and as an International Standard Randomised Controlled Trial, number 69423238. FINDINGS: Between Jan 11, 2011, and Dec 20, 2013, we randomly assigned 1167 participants, 1136 (97%) of whom were included in the primary analysis (17 were excluded because of ineligibility and 14 participants were lost to follow-up). 303 (80%) of 379 participants in the placebo group did not need further intervention by 4 weeks, compared with 307 (81%) of 378 in the tamsulosin group (adjusted risk difference 1·3% [95% CI -5·7 to 8·3]; p=0·73) and 304 (80%) of 379 in the nifedipine group (0·5% [-5·6 to 6·5]; p=0·88). No difference was noted between active treatment and placebo (p=0·78), or between tamsulosin and nifedipine (p=0·77). Serious adverse events were reported in three participants in the nifedipine group (one had right loin pain, diarrhoea, and vomiting; one had malaise, headache, and chest pain; and one had severe chest pain, difficulty breathing, and left arm pain) and in one participant in the placebo group (headache, dizziness, lightheadedness, and chronic abdominal pain). INTERPRETATION: Tamsulosin 400 µg and nifedipine 30 mg are not effective at decreasing the need for further treatment to achieve stone clearance in 4 weeks for patients with expectantly managed ureteric colic. FUNDING: UK National Institute for Health Research Health Technology Assessment Programme.

Concurrent arm swing-stepping (CASS) can reveal gait start hesitation in Parkinson's patients with low self-efficacy and fear of falling.

BACKGROUND: Movement incoordination, freezing of gait, fear of falling, low self-efficacy, and multi-tasking can all contribute to falls in Parkinson's disease. How these multi-factorial risks interact in individual patients remain poorly understood. METHODS: Concurrent arm swing-stepping is a simple motor test in which subjects are first asked to swing their arms before being instructed to initiate the secondary task of leg stepping-in-place. We postulated that in patients with multiple fall risks, sensorimotor impairments in upper- and lower-limb movement control can render concurrent arm swing-stepping a demanding dual task, thereby triggering gait hesitation. A total of 31 subjects with Parkinson's disease were enrolled in the study. RESULTS: It was found that concurrent arm swing-stepping induced hesitation primarily in Parkinson's disease patients with low fall-related self-efficacy and a fear of falling. By contrast, concurrent arm swing-stepping led to limb incoordination in both patients and in healthy elderly controls. The calculated specificity and sensitivity of the concurrent arm swing-stepping test was 100 and 42 % for hesitation and 12 and 77 % for incoordination. CONCLUSION: These results suggest that the concurrent arm swing-stepping test can be used in conjunction with conventional psychometric assessments to facilitate multi-factorial assessment of potential fall risk.

Training for sustained performance: moving toward long-term musician development.

Success in the performing arts, like sports, is dependent upon the acquisition and consistent use of a diverse range of skills. In sports, an understanding of safe and effective use of the body is required to facilitate long-term involvement in that activity. In order to assist athletes to attain their performance goals, and ensure healthy and sustained involvement, long-term athlete development (LTAD) models have been devised and adapted by professional sporting bodies throughout the world. LTAD models emphasize the intellectual, emotional, and social development of the athlete, encourage long-term participation in physical activities, and enable participants to improve their overall health and well-being and increase their life-long participation in physical activity. At present there is no such long-term development model for musicians. Yet musicians must cope with a multitude of career-related physical and mental demands, and performance-related injuries and career burnout are rife within the profession. Despite this, musicians' training rarely addresses such issues and musicians are left largely to learn about them through either chance or accrued experience. This paper discusses key concepts and recommendations in LTAD models, together with music-specific research highlighting the need for the development of a comprehensive long-term approach to musicians' training. The results of a survey of existing music training programs are compared to recommendations and the different development stages in LTAD models. Finally, implementation science is introduced as a methodological option for identifying how best to communicate the body of evidence-based knowledge concerning healthy and effective music-making to young student musicians.

It's not a virus! Reconceptualizing and de-pathologizing music performance anxiety.

Music Performance Anxiety (MPA) is one of the most widespread and debilitating challenges facing musicians, affecting significant numbers of performers in terms of both their personal and professional functioning. Although numerous interventions exist to target MPA, its prevalence remains unchanged since the first large-scale studies of the 1980s, indicating that available interventions are having limited impact. This review synthesizes and critiques existing literature in order to investigate possible reasons for the limited efficacy of current approaches to managing MPA. Key concepts discussed include conceptual and methodological challenges surrounding defining MPA, theoretical perspectives on MPA's etiology and manifestation, and the coping strategies and interventions used to manage MPA. MPA has predominantly been investigated pathologically and defined as a negative construct manifesting in unwanted symptoms. Based on this conceptualization, interventions largely seek to manage MPA through ameliorating symptoms. This review discusses possible reasons why this approach has broadly not proved successful, including the issue of relaxation being both unrealistic and counterproductive for peak performance, issues associated with intentionally changing one's state creating resistance thus exacerbating anxiety, and focusing on the presence of, rather than response to, symptoms. Despite 50 years of research, MPA remains an unsolved enigma and continues to adversely impact musicians both on and off the stage. Reconceptualizing MPA as a normal and adaptive response to the pressures of performance may offer a new perspective on it, in terms of its definition, assessment and management, with practical as well as theoretical implications.

The relationship between postural stability and dancer's past and future lower-limb injuries.

In an effort to address dance-related injuries, screening programs are typically employed to assess injury susceptibility. The aim of this study was to explore for potential links between postural stability and dancers' previous lower-limb injuries and susceptibility to future lower-limb injuries. Eighty-five contemporary dance students were recruited at a UK dance conservatoire. Information concerning previous injuries was collected by self-report survey. The participants completed two balance tasks, one static and one dynamic, performed on a RS Scan Footscan pressure pad to calculate postural sway. Injuries in the participant cohort were then tracked for a 10-month period to assess injury susceptibility. The participants exhibited significantly less postural sway when balancing on the left leg than their right, and the women exhibited less postural sway than the men. A one-way ANOVA revealed that participants who had experienced a lower-limb injury in the 12 months prior to testing exhibited more postural sway than participants who had not experienced a lower-limb injury, with some of the differences attaining significance (p <0.05). No significant links were found between either postural sway or previous injury and future injury susceptibility. The results suggest that assessments of postural stability via centre of pressure measurements are a reliable method for assessing dancers' balance ability. While reaffirming the importance of comprehensive, multidisciplinary screening programs, the results also highlight the necessity of developing a greater understanding of both dancers and the environments in which they dance and work to fully ascertain injury susceptibility.

Clinical validation of a next-generation sequencing-based multi-cancer early detection "liquid biopsy" blood test in over 1,000 dogs using an independent testing set: The CANcer Detection in Dogs (CANDiD) study.

Cancer is the leading cause of death in dogs, yet there are no established screening paradigms for early detection. Liquid biopsy methods that interrogate cancer-derived genomic alterations in cell-free DNA in blood are being adopted for multi-cancer early detection in human medicine and are now available for veterinary use. The CANcer Detection in Dogs (CANDiD) study is an international, multi-center clinical study designed to validate the performance of a novel multi-cancer early detection "liquid biopsy" test developed for noninvasive detection and characterization of cancer in dogs using next-generation sequencing (NGS) of blood-derived DNA; study results are reported here. In total, 1,358 cancer-diagnosed and presumably cancer-free dogs were enrolled in the study, representing the range of breeds, weights, ages, and cancer types seen in routine clinical practice; 1,100 subjects met inclusion criteria for analysis and were used in the validation of the test. Overall, the liquid biopsy test demonstrated a 54.7% (95% CI: 49.3-60.0%) sensitivity and a 98.5% (95% CI: 97.0-99.3%) specificity. For three of the most aggressive canine cancers (lymphoma, hemangiosarcoma, osteosarcoma), the detection rate was 85.4% (95% CI: 78.4-90.9%); and for eight of the most common canine cancers (lymphoma, hemangiosarcoma, osteosarcoma, soft tissue sarcoma, mast cell tumor, mammary gland carcinoma, anal sac adenocarcinoma, malignant melanoma), the detection rate was 61.9% (95% CI: 55.3-68.1%). The test detected cancer signal in patients representing 30 distinct cancer types and provided a Cancer Signal Origin prediction for a subset of patients with hematological malignancies. Furthermore, the test accurately detected cancer signal in four presumably cancer-free subjects before the onset of clinical signs, further supporting the utility of liquid biopsy as an early detection test. Taken together, these findings demonstrate that NGS-based liquid biopsy can offer a novel option for noninvasive multi-cancer detection in dogs.

AutoSNPdb: an annotated single nucleotide polymorphism database for crop plants.

Single nucleotide polymorphisms (SNPs) may be considered the ultimate genetic marker as they represent the finest resolution of a DNA sequence (a single nucleotide), are generally abundant in populations and have a low mutation rate. Analysis of assembled EST sequence data provides a cost-effective means to identify large numbers of SNPs associated with functional genes. We have developed an integrated SNP discovery pipeline, which identifies SNPs from assembled EST sequences. The results are maintained in a custom relational database along with EST source and annotation information. The current database hosts data for the important crops rice, barley and Brassica. Users may rapidly identify polymorphic sequences of interest through BLAST sequence comparison, keyword searches of annotations derived from UniRef90 and GenBank comparisons, GO annotations or in genes corresponding to syntenic regions of reference genomes. In addition, SNPs between specific varieties may be identified for targeted mapping and association studies. SNPs are viewed using a user-friendly graphical interface. The database is freely accessible at http://autosnpdb.qfab.org.au/.

POMHS 9b - antipsychotic prescribing in people with a learning disability.

INTRODUCTION: Prescribing Observatory for Mental Health (POMH-UK) runs national audit-based quality improvement programmes open to all specialist mental health services in the UK to help improve prescribing practice in discrete areas. AIMS: The baseline sample and this re-audit represent the largest audits of antipsychotic prescribing in PWLD that have been conducted to date; and thus provide the most generalisable picture of such prescribing nationally. METHODOLOGY: A case note audit of use of antipsychotic medication in PWLD was conducted using standard data collection tool provided by POMH-UK. Trust wide, 7 clinical teams in Essex and Bedfordshire & Luton, participated in the re-audit. Analysis and benchmarking was conducted centrally by POMH-UK and an individualised Trust report was compiled by POMH-UK for local review and consideration. STANDARDS: The indication for treatment with antipsychotic medication should be documented in the clinical records (Deb 2006). The continuing need for antipsychotic medication should be reviewed at least once a year (Deb 2006). Side effects of antipsychotic medication should be reviewed at least once a year. This review should include assessment for the presence of extrapyramidal side effects (EPS), and screening for the 4 aspects of the metabolic syndrome: obesity, hypertension, impaired glucose tolerance and dyslipidaemia (NICE schizophrenia guideline update CG82, 2009). FINDINGS: Out of three standards measured, Standard One maintained 100% throughout the baseline and re-audit and Standard Two achieved over 90% throughout baseline and re-audit. Standard 3 has improved from baseline to re-audit. Overall, there has been clear improvement in all 3 standards from baseline audit.

Future tools for association mapping in crop plants.

Association mapping currently relies on the identification of genetic markers. Several technologies have been adopted for genetic marker analysis, with single nucleotide polymorphisms (SNPs) being the most popular where a reasonable quantity of genome sequence data are available. We describe several tools we have developed for the discovery, annotation, and visualization of molecular markers for association mapping. These include autoSNPdb for SNP discovery from assembled sequence data; TAGdb for the identification of gene specific paired read Illumina GAII data; CMap3D for the comparison of mapped genetic and physical markers; and BAC and Gene Annotator for the online annotation of genes and genomic sequences.

Emotion Regulation Processes Can Benefit Self-Regulated Learning in Classical Musicians.

Self-regulated learning (SRL) is the degree to which students are metacognitively, motivationally, and behaviourally active participants in their own learning process. It involves the self-regulation of cognitive, behavioural, and affective processes. SRL holds significant potential for enhancing practise and achievement. Although affect is acknowledged as one of the three fundamental processes in SRL, there is limited research investigating it. However, emotions have been found to influence SRL efficiency while emotion regulation (ER) can impact learning outcomes. Thus, this study sought to investigate how ER processes relate to SRL among professional musicians who perform Western classical music. Four forms of regulation (reappraisal, suppression, rumination, repression) were examined in relation to the SRL three-phase model. Professional musicians (N = 334) of 39 nationalities (age: 18-66; [M = 28]; female = 215; male = 119) completed a survey comprising the Self-Regulated Learning in Music Questionnaire, the Emotion Regulation Questionnaire, and demographic items. A significant positive correlation emerged between SRL and reappraisal, and significant negative correlations emerged between SRL and the other three processes. Further multiple linear regression analysis revealed that reappraisal, practise hours, and expertise accounted for 26% of the variance in SRL. Finally, a factorial (2 × 2 × 2) ANOVA yielded significant group differences on ER as a function of gender, expertise, and occupation. Results suggest that reappraisal can enhance the use of SRL in musicians, thus highlighting the potential utility in considering ER as part of SRL. These results suggest that by including training on emotion regulation strategies within musicians' educational institutions and workplaces, efficiency and engagement in SRL can be enhanced. This could produce more effective learning strategies and outcomes, together with higher musical achievements.

Conservatory Musicians' Temporal Organization and Self-Regulation Processes in Preparing for a Music Exam.

Performing at the very highest levels requires rigorous preparation before the important performance. Musicians and especially music students encounter many challenges when preparing themselves for an important musical performance. This study sought to identify and analyze the context-specific temporal organization and self-regulation efforts that music students employ during their preparation period. Conservatory musicians were recruited from an Australian University Conservatorium. Thirteen conservatory musicians aged between 19 and 21 years (M = 19.6; SD = 0.76) participated in the study. All musicians, through an elicitation interview, were asked to recall and reconstruct their preparation period, leading up to a performance exam. Elicitation interviews provided access to music students' experiences by describing their general preparation. The results showed that conservatory musicians go through different phases (Phase 1: Choosing a piece; Phase 2: Piece discovery; Phase 3: Piece interpretation; Phase 4: Performance preparation). Self-regulatory efforts to prepare for a music performance exam vary from one musician to another. Organizational and disorganizational competencies, specific self-regulatory skills, seem not to be exploited by conservatory musicians. Also, during their preparation, most music students prefer technical and musical work than challenges such as playing in front of the public. Emotionally, conservatory musicians go through pleasant and unpleasant emotions depending on the phase of their preparation. Our results show that music students could benefit from advice on how to organize their preparation period well before an important performance takes place. Implications for conservatory musicians and teachers are discussed.

The clinical and cost effectiveness of surgical interventions for stones in the lower pole of the kidney: the percutaneous nephrolithotomy, flexible ureterorenoscopy and extracorporeal shockwave lithotripsy for lower pole kidney stones randomised controlled trial (PUrE RCT) protocol.

INTRODUCTION: Renal stones are common, with a lifetime prevalence of 10% in adults. Global incidence is increasing due to increases in obesity and diabetes, with these patient populations being more likely to suffer renal stone disease. Flank pain from stones (renal colic) is the most common cause of emergency admission to UK urology departments. Stones most commonly develop in the lower pole of the kidney (in ~35% of cases) and here are least likely to pass without intervention. Currently there are three technologies available within the UK National Health Service to remove lower pole kidney stones: extracorporeal shockwave lithotripsy (ESWL), percutaneous nephrolithotomy (PCNL) and flexible ureterorenoscopy (FURS) with laser lithotripsy. Current evidence indicates there is uncertainty regarding the management of lower pole stones, and each treatment has advantages and disadvantages. The aim of this trial is to determine the clinical and cost effectiveness of FURS compared with ESWL or PCNL in the treatment of lower pole kidney stones. METHODS: The PUrE (PCNL, FURS and ESWL for lower pole kidney stones) trial is a multi-centre, randomised controlled trial (RCT) evaluating FURS versus ESWL or PCNL for lower pole kidney stones. Patients aged ≥16 years with a stone(s) in the lower pole of either kidney confirmed by non-contrast computed tomography of the kidney, ureter and bladder (CTKUB) and requiring treatment for a stone ≤10 mm will be randomised to receive FURS or ESWL (RCT1), and those requiring treatment for a stone >10 mm to ≤25 mm will be randomised to receive FURS or PCNL (RCT2). Participants will undergo follow-up by questionnaires every week up to 12 weeks post-intervention and at 12 months post-randomisation. The primary clinical outcome is health status measured by the area under the curve calculated from multiple measurements of the EuroQol five dimensions five-level version (EQ-5D-5L) questionnaire up to 12 weeks post-intervention. The primary economic outcome is the incremental cost per quality-adjusted life year gained at 12 months post-randomisation. DISCUSSION: The PUrE trial aims to provide robust evidence on health status, quality of life, clinical outcomes and resource use to directly inform choice and National Health Service provision of the three treatment options. TRIAL REGISTRATION: ISRCTN: ISRCTN98970319. Registered on 11 November 2015.

Gene conversion in the rice genome.

BACKGROUND: Gene conversion causes a non-reciprocal transfer of genetic information between similar sequences. Gene conversion can both homogenize genes and recruit point mutations thereby shaping the evolution of multigene families. In the rice genome, the large number of duplicated genes increases opportunities for gene conversion. RESULTS: To characterize gene conversion in rice, we have defined 626 multigene families in which 377 gene conversions were detected using the GENECONV program. Over 60% of the conversions we detected were between chromosomes. We found that the inter-chromosomal conversions distributed between chromosome 1 and 5, 2 and 6, and 3 and 5 are more frequent than genome average (Z-test, P < 0.05). The frequencies of gene conversion on the same chromosome decreased with the physical distance between gene conversion partners. Ka/Ks analysis indicates that gene conversion is not tightly linked to natural selection in the rice genome. To assess the contribution of segmental duplication on gene conversion statistics, we determined locations of conversion partners with respect to inter-chromosomal segment duplication. The number of conversions associated with segmentation is less than ten percent. Pseudogenes in the rice genome with low similarity to Arabidopsis genes showed greater likelihood for gene conversion than those with high similarity to Arabidopsis genes. Functional annotations suggest that at least 14 multigene families related to disease or bacteria resistance were involved in conversion events. CONCLUSION: The evolution of gene families in the rice genome may have been accelerated by conversion with pseudogenes. Our analysis suggests a possible role for gene conversion in the evolution of pathogen-response genes.

Identification and characterization of insect-specific proteins by genome data analysis.

BACKGROUND: Insects constitute the vast majority of known species with their importance including biodiversity, agricultural, and human health concerns. It is likely that the successful adaptation of the Insecta clade depends on specific components in its proteome that give rise to specialized features. However, proteome determination is an intensive undertaking. Here we present results from a computational method that uses genome analysis to characterize insect and eukaryote proteomes as an approximation complementary to experimental approaches. RESULTS: Homologs in common to Drosophila melanogaster, Anopheles gambiae, Bombyx mori, Tribolium castaneum, and Apis mellifera were compared to the complete genomes of three non-insect eukaryotes (opisthokonts) Homo sapiens, Caenorhabditis elegans and Saccharomyces cerevisiae. This operation yielded 154 groups of orthologous proteins in Drosophila to be insect-specific homologs; 466 groups were determined to be common to eukaryotes (represented by three opisthokonts). ESTs from the hemimetabolous insect Locust migratoria were also considered in order to approximate their corresponding genes in the insect-specific homologs. Stress and stimulus response proteins were found to constitute a higher fraction in the insect-specific homologs than in the homologs common to eukaryotes. CONCLUSION: The significant representation of stress response and stimulus response proteins in proteins determined to be insect-specific, along with specific cuticle and pheromone/odorant binding proteins, suggest that communication and adaptation to environments may distinguish insect evolution relative to other eukaryotes. The tendency for low Ka/Ks ratios in the insect-specific protein set suggests purifying selection pressure. The generally larger number of paralogs in the insect-specific proteins may indicate adaptation to environment changes. Instances in our insect-specific protein set have been arrived at through experiments reported in the literature, supporting the accuracy of our approach.

Perceived Enablers and Barriers to Optimal Health among Music Students: A Qualitative Study in the Music Conservatoire Setting.

Student health and wellbeing within higher education has been documented as poor in relation to the general population. This is a particular problem among students at music conservatoires, who are studying within a unique educational context that is known to generate both physical and psychological challenges. This article examines how conservatoire students experience health and wellbeing within their institutional context, using a framework from health promotion to focus attention on perceived enablers and barriers to optimal health in relation to three levels: lifestyle, support services, and conservatoire environment. In order to respond to the individuality of students' experiences, a qualitative approach was taken based on semi-structured interviews with 20 current or recent conservatoire students in the United Kingdom. Thematic analysis revealed a complex set of enablers and barriers: (i) lifestyle enablers included value placed on the importance of optimal health and wellbeing for musicians and daily practices to enable this; lifestyle barriers included struggling to maintain healthy lifestyles within the context of musical practice and learning; (ii) support enablers included accessible support sources within and beyond the conservatoire; support barriers included a perceived lack of availability or awareness of appropriate support; (iii) environmental enablers included positive and enjoyable experiences of performance as well as strong relationships and communities; environmental barriers included experiences of comparison and competition, pressure and stress, challenges with negative performance feedback, psychological distress, and perceived overwork. The findings reveal a need for health promotion to focus not only on individuals but also on the daily practices and routines of conservatoires. Additionally, they suggest that continued work is required to embed health and wellbeing support as an integral component of conservatoire education, raising awareness so that all students are fully informed of where, and how, to seek the information or help that they may need. Finally, they indicate a need for more radical scrutiny of the cultures of conservatoires and an assessment of how these can be modified to best optimize students' health and wellbeing.

A structured interface to the object-oriented genomics unified schema for XML-formatted data.

Data management systems are fast becoming required components in many biology laboratories as the role of computer-based information grows. Although the need for data management systems is on the rise, their inherent complexities can deter the full and routine use of their computational capabilities. The significant undertaking to implement a capable production system can be reduced in part by adapting an established data management system. In such a way, we are leveraging the Genomics Unified Schema (GUS) developed at the Computational Biology and Informatics Laboratory at the University of Pennsylvania as a foundation for managing and analysing DNA sequence data in centromere research projects around Arabidopsis thaliana and related species. Because GUS provides a core schema that includes support for genome sequences, mRNA and its expression, and annotated chromosomes, it is ideal for synthesising a variety of parameters to analyse these repetitive and highly dynamic portions of the genome. Despite this, production-strength data management frameworks are complex, requiring dedicated efforts to adapt and maintain. The work reported in this article addresses one component of such an effort, namely the pivotal task of marshalling data from various sources into GUS. In order to harness GUS for our project, and motivated by efficiency needs, we developed a structured framework for transferring data into GUS from outside sources. This technology is embodied in a GUS object-layer processor, XMLGUS. XMLGUS facilitates incorporating data into GUS by (i) formulating an XML interface that includes relational database key constraint definitions, (ii) regularising traversal through that XML, (iii) realising automatic processing of the XML with database key constraints and (iv) allowing for special processing of input data within the framework for automated processing. The application of XMLGUS to production pipeline processing for a sequencing project and inputting the Arabidopsis genome into GUS is discussed. XMLGUS is available from the Flora website (http://flora.ittc.ku.edu/).

Use of drug therapy in the management of symptomatic ureteric stones in hospitalised adults: a multicentre, placebo-controlled, randomised controlled trial and cost-effectiveness analysis of a calcium channel blocker (nifedipine) and an alpha-blocker (tamsulosin) (the SUSPEND trial).

BACKGROUND: Ureteric colic, the term used to describe the pain felt when a stone passes down the ureter from the kidney to the bladder, is a frequent reason for people to seek emergency health care. Treatment with the muscle-relaxant drugs tamsulosin hydrochloride (Petyme, TEVA UK Ltd) and nifedipine (Coracten(®), UCB Pharma Ltd) as medical expulsive therapy (MET) is increasingly being used to improve the likelihood of spontaneous stone passage and lessen the need for interventional procedures. However, there remains considerable uncertainty around the effectiveness of these drugs for routine use. OBJECTIVES: To determine whether or not treatment with either tamsulosin 400 µg or nifedipine 30 mg for up to 4 weeks increases the rate of spontaneous stone passage for people with ureteric colic compared with placebo, and whether or not it is cost-effective for the UK NHS. DESIGN: A pragmatic, randomised controlled trial comparing two active drugs, tamsulosin and nifedipine, against placebo. Participants, clinicians and trial staff were blinded to treatment allocation. A cost-utility analysis was performed using data gathered during trial participation. SETTING: Urology departments in 24 UK NHS hospitals. PARTICIPANTS: Adults aged between 18 and 65 years admitted as an emergency with a single ureteric stone measuring ≤ 10 mm, localised by computerised tomography, who were able to take trial medications and complete trial procedures. INTERVENTIONS: Eligible participants were randomised 1 : 1 : 1 to take tamsulosin 400 µg, nifedipine 30 mg or placebo once daily for up to 4 weeks to make the following comparisons: tamsulosin or nifedipine (MET) versus placebo and tamsulosin versus nifedipine. MAIN OUTCOME MEASURES: The primary effectiveness outcome was the proportion of participants who spontaneously passed their stone. This was defined as the lack of need for active intervention for ureteric stones at up to 4 weeks after randomisation. This was determined from 4- and 12-week case-report forms completed by research staff, and from the 4-week participant self-reported questionnaire. The primary economic outcome was the incremental cost per quality-adjusted life-year (QALY) gained over 12 weeks. We estimated costs from NHS sources and calculated QALYs from participant completion of the European Quality of Life-5 Dimensions health status questionnaire 3-level response (EQ-5D-3L™) at baseline, 4 weeks and 12 weeks. RESULTS: Primary outcome analysis included 97% of the 1167 participants randomised (378/391 tamsulosin, 379/387 nifedipine and 379/399 placebo participants). The proportion of participants who spontaneously passed their stone did not differ between MET and placebo [odds ratio (OR) 1.04, 95% confidence interval (CI) 0.77 to 1.43; absolute difference 0.8%, 95% CI -4.1% to 5.7%] or between tamsulosin and nifedipine [OR 1.06, 95% CI 0.74 to 1.53; absolute difference 1%, 95% CI -4.6% to 6.6%]. There was no evidence of a difference in QALYs gained or in cost between the trial groups, which means that the use of MET would be very unlikely to be considered cost-effective. These findings were unchanged by extensive sensitivity analyses around predictors of stone passage, including sex, stone size and stone location. CONCLUSIONS: Tamsulosin and nifedipine did not increase the likelihood of stone passage over 4 weeks for people with ureteric colic, and use of these drugs is very unlikely to be cost-effective for the NHS. Further work is required to investigate the phenomenon of large, high-quality trials showing smaller effect size than meta-analysis of several small, lower-quality studies. TRIAL REGISTRATION: Current Controlled Trials ISRCTN69423238. European Clinical Trials Database (EudraCT) number 2010-019469-26. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 63. See the NIHR Journals Library website for further project information.

Computational Analysis of Gene Identification with SAGE.

SAGE is one of the few techniques capable of uniformly probing gene expression at a genome level irrespective of mRNA abundance and without a priori knowledge of the transcripts present. However, individual SAGE tags can match many sequences in the reference database, complicating gene identification. We perform a baseline evaluation of gene identification with SAGE using UniGene Human as the reference database by analyzing 1) the distributions of tags for various length tag sets formed for UniGene Human and 2) the tag-to-sequence mapping using a SAGE tag set consisting of 37,522 tags derived from human myeloid cells. The extensive multiplicity of the dbEST component of UniGene significantly detracts from gains that might be expected by extending tags within the scope of the SAGE protocol. In order to achieve reasonable sequence specificity for gene identification with the content of the commonly used UniGene sequence collection, tags on the order of hundreds of bases in length are required. One way to produce tags of such lengths is with GLGI, which extends SAGE tags to the 3' end of cDNA. We show that the longer sequences produced by GLGI relieve significantly the multiple match condition. In the myeloid sample, we also found a correlation between multiple match severity and high copy number. We extrapolate these findings, providing insights into the use of UniGene Human as a reference for gene identification.

Developing a dancer wellness program employing developmental evaluation.

Wellness programs are being increasingly employed with performing artists. Given their aim of reducing injuries, injury tracking is commonly employed as an outcome measure. Evaluating the development and process of a wellness program can also enhance its effectiveness. Developmental evaluation offers one methodological framework within which to conduct such investigations. This paper reports on a 2-year process involving feedback from professional ballet dancers, management and artistic staff, and healthcare providers at a ballet company in order to develop a dancer screening and wellness program. Following a consultation phase, an initial program composed of an expanded medical team and annual injury prevention screen was proposed. Alongside implementation with 30 professional ballet dancers, formal and informal feedback was sought from stakeholders and members across all levels of the ballet company to facilitate ongoing development, evaluation, and revision of the wellness program. The use of a process informed by developmental evaluation helped identify strengths and limitations within the screening process. The collective expertise of the assessors was used to modify the components and process of the screen to strive for ecological appropriateness. The process also fostered buy-in from all involved. Participant feedback helped refine the medical team available to the dancers and influenced the treatment and referral pathways via which dancers are able to access each member of the medical team. Furthermore, reflective discussions with artistic and management staff brought to light potential interactions between repertoire programming, fitness, and injury patterns. This prompted a reconsideration of how artists are trained and supported. Evaluation methods that focus on experiences and insight gained during program development stand to result in more efficient screening programs and health-promotion models and, ultimately, healthier performing artists.

The value of health screening in music schools and conservatoires.

Interest in musicians' health and well-being is growing, reflected by increasing numbers of investigations into the physicality and psychology of musical performance. Within sport and dance, screening and profiling programmes, especially of the musculoskeletal system, have furthered understanding on not only physical and psychological capabilities and demands but also musculoskeletal injury mechanisms and susceptibility. This article engages with questions relating to the development and delivery of musician-specific health screening programmes. Effective screening can offer a variety of benefits for musicians, providing informed recommendations for sustaining performance-related fitness across educational and professional contexts. Employing an interdisciplinary approach when developing screening programmes is essential, as is the ecological appropriateness of the measures used. The implications inherent in delivering and sustaining successful screening programmes in schools and conservatoires are discussed.