‘Multi-directional management’: Exploring the challenges of performance in the World Class Programme environment

Driven by the ever-increasing intensity of Olympic competition and the ‘no compromise – no stone unturned’ requirements frequently addressed by HM Government and its main agency, UK Sport, a change in culture across Olympic team landscapes is a common occurrence. With a focus on process, this paper presents reflections from eight current or recently serving UK Olympic sport Performance Directors on their experiences of creating and disseminating their vision for their sport, a vital initial activity of the change initiative. To facilitate a broad overview of this construct, reflections are structured around the vision’s characteristics and foundations, how it is delivered to key stakeholder groups, how it is influenced by these groups, the qualities required to ensure its longevity and its limitations. Emerging from these perceptions, the creation and maintenance of a shared team vision was portrayed as a highly dynamic task requiring the active management of a number of key internal and external stakeholders. Furthermore, the application of ‘dark’ traits and context-specific expertise were considered critical attributes for the activity’s success. Finally, recent calls for research to elucidate the wider culture optimisation process are reinforced

Expressive cartography and the aesthetics of public visualization

Aesthetic visualization projects that incorporate users, community stakeholders, multiple modalities and technologies necessarily emphasize the way that an artistic visualization can be both an artifact and a process — a conceptualization of aesthetic visualization that is useful for thinking about visualization in general. In this paper, the authors propose the concept of expressivity as a move away from the indexical claims of visualization and instead towards an acknowledgement of the entangled nature of social, political, economic, cultural, technological and environmental actants. Through a description of the In The Air, Tonight public visualization project, the authors suggest that by making manifest the connections between these actants, a visualization project, as a form of expressive cartography, can contribute to the visibility of and engagement with important issues (e.g. homelessness) that affect society

Aggregate-strength interaction test suite prioritization

Combinatorial interaction testing is a widely used approach. In testing, it is often assumed that all combinatorial test cases have equal fault detection capability, however it has been shown that the execution order of an interaction test suite's test cases may be critical, especially when the testing resources are limited. To improve testing cost-effectiveness, test cases in the interaction test suite can be prioritized, and one of the best-known categories of prioritization approaches is based on “fixed-strength prioritization”, which prioritizes an interaction test suite by choosing new test cases which have the highest uncovered interaction coverage at a fixed strength (level of interaction among parameters). A drawback of these approaches, however, is that, when selecting each test case, they only consider a fixed strength, not multiple strengths. To overcome this, we propose a new “aggregate-strength prioritization”, to combine interaction coverage at different strengths. Experimental results show that in most cases our method performs better than the test-case-generation, reverse test-case-generation, and random prioritization techniques. The method also usually outperforms “fixed-strength prioritization”, while maintaining a similar time cost

Dimerization and auto-processing induce caspase-11 protease activation within the non-canonical inflammasome

Caspase-11 is a cytosolic sensor and protease that drives innate immune responses to the bacterial cell wall component, LPS. Caspase-11 provides defence against cytosolic Gram-negative bacteria; however, excessive caspase-11 responses contribute to murine endotoxic shock. Upon sensing LPS, caspase-11 assembles a higher order structure called the non-canonical inflammasome that enables the activation of caspase-11 protease function, leading to gasdermin D cleavage and cell death. The mechanism by which caspase-11 acquires protease function is, however, poorly defined. Here, we show that caspase-11 dimerization is necessary and sufficient for eliciting basal caspase-11 protease function, such as the ability to auto-cleave. We further show that during non-canonical inflammasome signalling, caspase-11 self-cleaves at site (D285) within the linker connecting the large and small enzymatic subunits. Self-cleavage at the D285 site is required to generate the fully active caspase-11 protease (proposed here to be p32/p10) that mediates gasdermin D cleavage, macrophage death, and NLRP3-dependent IL-1β production. This study provides a detailed molecular mechanism by which LPS induces caspase-11-driven inflammation and cell death to provide host defence against cytosolic bacterial infection

Novel biodegradable sandwich-structured nanofibrous drug-eluting membranes for repair of infected wounds: an in vitro and in vivo study

Dave Wei-Chih Chen1,2, Jun-Yi Liao3, Shih-Jung Liu2, Err-Cheng Chan41Department of Orthopedic Surgery, Chang Gung Memorial Hospital, 2Department of Mechanical Engineering, 3Graduate Institute of Medical Mechatronics, 4School of Medical Technology, Chang Gung University, Kwei-San, Tao-Yuan, TaiwanBackground: The purpose of this study was to develop novel sandwich-structured nanofibrous membranes to provide sustained-release delivery of vancomycin, gentamicin, and lidocaine for repair of infected wounds.Methods: To prepare the biodegradable membranes, poly(D, L)-lactide-co-glycolide (PLGA), collagen, and various pharmaceuticals, including vancomycin, gentamicin, and lidocaine, were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol. They were electrospun into sandwich-structured membranes with PLGA/collagen as the surface layers and PLGA/drugs as the core. An elution method and a high-pressure liquid chromatography assay were used to characterize in vivo and in vitro drug release from the membranes. In addition, repair of infected wounds in rats was studied. Histological examination of epithelialization and granulation at the wound site was also performed.Results: The biodegradable nanofibrous membranes released large amounts of vancomycin and gentamicin (well above the minimum inhibition concentration) and lidocaine in vivo for more than 3 weeks. A bacterial inhibition test was carried out to determine the relative activity of the antibiotics released. The bioactivity ranged from 40% to 100%. The nanofibrous membranes were functionally active in treating infected wounds, and were very effective as accelerators in early-stage wound healing.Conclusion: Using the electrospinning technique, we will be able to manufacture biodegradable, biomimetic, nanofibrous, extracellular membranes for long-term delivery of various drugs.Keywords: nanofibrous, sandwich-structured, drug-eluting membranes, electrospinning, release characteristics, repair, wound infectio

Regenerable DNA-Functionalized Hydrogels for Ultrasensitive, Instrument-Free Mercury(II) Detection and Removal in Water

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of the American Chemical Society, copyright © American Chemical Society after peer review and technical editing by publisher. To access the final edited and published work see Dave, N., Chan, M. Y., Huang, P.-J. J., Smith, B. D., & Liu, J. (2010). Regenerable DNA-Functionalized Hydrogels for Ultrasensitive, Instrument-Free Mercury(II) Detection and Removal in Water. Journal of the American Chemical Society, 132(36), 12668–12673. https://doi.org/10.1021/ja106098jMercury is a highly toxic environmental pollutant with bioaccumulative properties. Therefore, new materials are required to not only detect but also effectively remove mercury from environmental sources such as water. We herein describe a polyacrylamide hydrogel-based sensor functionalized with a thymine-rich DNA that can simultaneously detect and remove mercury from water. Detection is achieved by selective binding of Hg2+ between two thymine bases, inducing a hairpin structure where, upon addition of SYBR Green I dye, green fluorescence is observed. In the absence of Hg2+, however, addition of the dye results in yellow fluorescence. Using the naked eye, the detection limit in a 50 mL water sample is 10 nM Hg2+. This sensor can be regenerated using a simple acid treatment and can remove Hg2+ from water at a rate of ∼1 h−1. This sensor was also used to detect and remove Hg2+ from samples of Lake Ontario water spiked with mercury. In addition, these hydrogel-based sensors are resistant to nuclease and can be rehydrated from dried gels for storage and DNA protection. Similar methods can be used to functionalize hydrogels with other nucleic acids, proteins, and small molecules for environmental and biomedical applications.University of Waterloo || Natural Sciences and Engineering Research Council |

Perceptions on competence by design in urology

Introduction: The Royal College of Physicians and Surgeons of Canada has begun implementing Competence by Design (CBD). However, it is unclear how much urology trainees and faculty know about CBD, their attitudes towards this change, and their willingness to embrace and participate in this new model of training. Methods: This cross-sectional study was conducted through an online survey, which was administered to all trainees and faculty at Canadian urology programs prior to the implementation of CBD. The final survey consisted of eight demographic questions, 17 five-point Likert items, one visual analog scale question, 11 multiple-choice questions, and two open-ended questions. Results: A total of 74 participants (38 faculty and 36 trainees) across 12 universities responded, with a completion rate of 82.4%. This corresponded to an overall response rate of 20.5%. Overall, there was a lack of resounding enthusiasm towards this shift to CBD in urology. Although both trainees and faculty had overall positive perceptions of CBD on assessment, teaching, and readiness, most agreed that this transition will be costly and associated with increased requirements for time, funding, and administrative support. Furthermore, there were significant concerns regarding the lack of valid assessment tools and evidence for the validity of entrustable professional activities. Conclusions: While this survey has demonstrated an appreciation for the benefits of CBD, challenges are equally anticipated. CBD in urology will be a fertile research area; this study has identified several important educational questions regarding the model\u27s effectiveness and consequences, thus, providing collaborative opportunities among all Canadian programs

Point-of-care ultrasonography for the diagnosis of testicular torsion: A practical resident curriculum

Background: Prompt Doppler ultrasonography to aid in diagnosis is often key to managing testicular torsion, but there may be delays in access; a faster, more widely available alternative is point-of-care ultrasonography (POCUS). The purpose of this study was to develop and evaluate a scrotal POCUS curriculum for urology and emergency medicine residents. Methods: Content experts in urology, emergency medicine and diagnostic imaging collaborated in a modified Delphi method to design a practical didactic curriculum for scrotal POCUS for the identification of testicular torsion. Training included 3 online video teaching modules and a 1-hour hands-on teaching session with standardized adult patients. We evaluated participants\u27 competency in scrotal POCUS using a validated scale. We assessed participants\u27 knowledge, comfort and confidence in performing scrotal POCUS before and after the intervention and at 3 months. Results: Twenty-four urology (n = 12) and emergency medicine (n = 12) residents participated in the curriculum. After hands-on practice, 23 participants (96%) were deemed competent at scrotal POCUS. Pre-post testing showed significant improvement in knowledge (mean score 63% v. 80%, p \u3c 0.001), comfort (mean Likert score 0.6 v. 3.6, p \u3c 0.001) and confidence (mean Likert score 1.0 v. 2.1, p \u3c 0.001) after the intervention. These effects were maintained at the 3-month assessment. Conclusion: The scrotal POCUS curriculum was effective and acceptable to both urology and emergency medicine residents. The findings suggest that scrotal POCUS can be learned effectively through a short hands-on session and didactic instruction

Maternal Benzodiazepines and Z-Drugs Use during Pregnancy and Adverse Birth and Neurodevelopmental Outcomes in Offspring:A Population-Based Cohort Study

Introduction: The use of benzodiazepines and/or z-drugs in women of childbearing age has increased. Objective: The aim of the study was to evaluate whether gestational benzodiazepine and/or z-drug exposure is associated with adverse birth and neurodevelopmental outcomes. Methods: A population-based cohort including mother-child pairs from 2001 to 2018 in Hong Kong was analysed to compare gestationally exposed and nonexposed children on the risk of preterm birth, small for gestational age, autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD) through logistic/Cox proportional hazards regression with a 95% confidence interval (CI). Sibling-matched analyses and negative control analyses were applied. Results: When comparing gestationally exposed with gestationally nonexposed children, the weighted odds ratio (wOR) was 1.10 (95% CI = 0.97-1.25) for preterm birth and 1.03 (95% CI = 0.76-1.39) for small for gestational age, while the weighted hazard ratio (wHR) was 1.40 (95% CI = 1.13-1.73) for ASD and 1.15 (95% CI = 0.94-1.40) for ADHD. Sibling-matched analyses showed no association between gestationally exposed children and their gestationally nonexposed siblings for all outcomes (preterm birth: wOR = 0.84, 95% CI = 0.66-1.06; small for gestational age: wOR = 1.02, 95% CI = 0.50-2.09; ASD: wHR = 1.10, 95% CI = 0.70-1.72; ADHD: wHR = 1.04, 95% CI = 0.57-1.90). Similarly, no significant differences were observed when comparing children whose mothers took benzodiazepines and/or z-drugs during pregnancy to children whose mothers took benzodiazepines and/or z-drugs before but not during pregnancy for all outcomes. Conclusions: The findings do not support a causal relationship between gestational benzodiazepines and/or z-drugs exposure and preterm birth, small for gestational age, ASD, or ADHD. Clinicians and pregnant women should carefully balance the known risks of benzodiazepines and/or z-drugs use against those of untreated anxiety and sleep problems.</p