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Regulation increasingly mandates collaborative approaches to increase stakeholder input and streamline approval processes. However, understanding how to maintain stakeholder involvement over the course of a long collaborative process is vital to optimize effectiveness. This paper observes more than 700 stakeholders involved in developing and implementing a dam operating license over 16 years. We use text mining and Bayesian hierarchical modeling to observe meeting attendance and recorded actions in meeting minutes. We find that involvement decreased after the initial planning phase, but steadily increased through license development and implementation. After the regulatory mandate to consult with external stakeholders dissolved, overall attendance declined while attendance stability increased, meaning that the non-mandatory stage involved a smaller cadre of dedicated actors. This indicates that high-performing mandated stakeholder involvement processes rely on a constrained group of conveners to sustain interaction and have less turnover than what might be expected given existing evidence from grassroots involvement; assumptions about group dynamics based on involvement in grassroots processes may lead to improper predictions about who will participate, and how, in processes where stakeholder involvement is mandated.

Environmental impact assessment (EIA) processes are grounded on the assumption that producing information about environmental impacts will yield better environmental decisions. Despite the ubiquity of EIA as a policy tool, there is scant evidence of its environmental, social, or economic impacts. Focusing on Environmental Impact Statements (EIS) prepared for water and energy-related projects under the US National Environmental Policy Act, this analysis addresses two questions: (1) What is the balance of environmental impacts associated with infrastructure decisions?; and (2) How does the content of stakeholder feedback received during the review phase differ from draft EIS content, and does this correspond to any changes in the final EIS? We demonstrate the use of automated text mining approaches to identify the distribution of impacts, measure the content of public comments, and observe whether values reflected in comments are associated with a shift in emphases between the draft and final EIS. EISs are shown to convey evenly distributed focus across multiple impact areas. However, we observe no substantive change in focal emphasis between draft and final issuances. This calls into question assumptions about the role that public participation plays in bringing new information to light or changing the course of action.

How do social networks differ between highly collaborative and less collaborative forms of governance? Drawing on a prior study that characterized the level of collaboration for three federal hydropower relicensing processes, we develop exponential random graph models of meeting attendance and participation networks. We find that the highly collaborative relicensing process had lower overall density and a propensity for relatively fewer and stronger interactions. Reciprocity is highest in the high-collaboration process, indicating that it is characterized by mutual interactions. In the low-collaboration process, patterns of connections between any three members of the network displayed a more unidirectional structure, suggesting asymmetrical interactions between active versus passive members of the network. By linking network structure to collaborative dynamics, this study helps elaborate potential mechanisms of successful collaboration.

Objectives The use of digital technology in surgery is increasing rapidly, with a wide array of new applications from presurgical planning to postsurgical performance assessment. Understanding the clinical and economic value of these technologies is vital for making appropriate health policy and purchasing decisions. We explore the potential value of digital technologies in surgery and produce expert consensus on how to assess this value.Design A modified Delphi and consensus conference approach was adopted. Delphi rounds were used to generate priority topics and consensus statements for discussion.Setting and participants An international panel of 14 experts was assembled, representing relevant stakeholder groups: clinicians, health economists, health technology assessment experts, policy-makers and industry.Primary and secondary outcome measures A scoping questionnaire was used to generate research questions to be answered. A second questionnaire was used to rate the importance of these research questions. A final questionnaire was used to generate statements for discussion during three consensus conferences. After discussion, the panel voted on their level of agreement from 1 to 9; where 1=strongly disagree and 9=strongly agree. Consensus was defined as a mean level of agreement of >7.Results Four priority topics were identified: (1) how data are used in digital surgery, (2) the existing evidence base for digital surgical technologies, (3) how digital technologies may assist surgical training and education and (4) methods for the assessment of these technologies. Seven consensus statements were generated and refined, with the final level of consensus ranging from 7.1 to 8.6.Conclusion Potential benefits of digital technologies in surgery include reducing unwarranted variation in surgical practice, increasing access to surgery and reducing health inequalities. Assessments to consider the value of the entire surgical ecosystem holistically are critical, especially as many digital technologies are likely to interact simultaneously in the operating theatre.

This paper is the first to report successful application of self-pierce riveting (SPR) in thin-walled high pressure die cast (HPDC) aluminium for use in automotive applications. HPDC fabricated AA356x coupons were joined to conventional rolled RC5754 material. A set of industry-relevant joint stacks were created. Priority stacks included cast material as the upper layer. More challenging joints were also fabricated with cast material as the lower layer. Automotive industry key performance indicators were used to assess joint integrity. The key results and recommendations were: • HPDC aluminium was revealed to be able to be joined to rolled aluminium according to vehicle manufacturer automotive standards. • Process boundaries were established for satisfactory SPR joints across a range of material thicknesses and stack types. • SPR joint solutions were proven in the most challenging stacks with cast material as a bottom layer. • Greater variability in the joint key performance indicators was observed in stacks where the cast alloy is the top layer. • Microstructural analysis of both AA356x and RC5754 revealed differences in grain structure and hardness and it is proposed that this accounts for the increased variability. • Strength testing of lap shear joints demonstrated the mechanical effectiveness of an SPR joint including cast material. Under normal vehicle operating conditions, the performance of joints including cast material was equivalent to that of rolled material only joints. Following yielding, joints including cast material suffered a more brittle failure mode leading to differences in performance under crash scenarios.

This manuscript analyzes the issues presented in Executive Order 14036, which aimed to promote competition in the American economy, including specific directives for the alcohol industry. Specifically, this manuscript focuses on the issues regarding distilled spirits regulation and delves into the implications for the distilled spirits sector. The order addresses anti-competitive practices, encouraging regulatory bodies to review and revise existing policies that may hinder fair market practices. This paper explores these issues and provides a historical context of distilled spirits regulation in the United States, examining how past policies have shaped the current landscape. It analyzes the key provisions of Executive Order 14036, highlighting its potential to foster increased competition, innovation, and consumer choice within the distilled spirits market. Lastly, the article provides a call to action for policymakers, academia, and consumers which will aid distilled spirits producers in gaining parity with beer and wine producers.

Abstract Prostate cancer (PC) staging with conventional imaging often includes multiparametric magnetic resonance (MR) of the prostate, computed tomography (CT) of the chest, abdomen, and pelvis, and whole-body bone scintigraphy. The recent development of highly sensitive and specific prostate specific membrane antigen (PSMA) positron emission tomography (PET) has suggested that prior imaging techniques may be insufficiently sensitive or specific, particularly when evaluating small pathologic lesions. As PSMA PET/CT is considered to be superior for multiple clinical indications, it is being deployed as the new multidisciplinary standard-of-care. Given this, we performed a cost-effectiveness analysis of [18F]DCFPyL PSMA PET/CT imaging in the evaluation of PC relative to conventional imaging and anti-3-[18F]FACBC (18F-Fluciclovine) PET/CT. We also conducted a single institution review of PSMA PET/CT scans performed primarily for research indications from January 2018 to October 2021. Our snapshot of this period of time in our catchment demonstrated that PSMA PET/CT imaging was disproportionately accessed by men of European ancestry (EA) and those residing in zip codes associated with a higher median household income. The cost-effectiveness analysis demonstrated that [18F]DCFPyL PET/CT should be considered as an alternative to anti-3-[18F]FACBC PET/CT and standard of care imaging for prostate cancer staging. [18F]DCFPyL PET/CT is a new imaging modality to evaluate PC patients with higher sensitivity and specificity in detecting disease than other prostate specific imaging studies. Despite this, access may be inequitable. This discrepancy will need to be addressed proactively as the distribution network of the radiotracer includes both academic and non-academic sites nationwide.

Abstract Sport participation and volunteering can make important contributions to good health. Sporting organisations need volunteers to deliver their participation opportunities and for many years the sector has faced challenges to volunteer recruitment and retention, especially due to the increased bureaucratic and compliance demands in operating community sports clubs. As sporting organisations pivot to adapt to COVID-safe sport we can learn about their experiences to inform volunteer recruitment and retention policies and practices. This research examined volunteer intentions and motivations in coaching and officiating in basketball and explored factors influencing their decision to return to COVID-safe basketball. Data was collected via an online survey that drew on theoretical frameworks of volunteer motivations (i.e. modified Volunteer Functions Inventory VFI) in sport as well as sport policies related to COVID-safe guidelines for return to sport. Data was collected in Victoria Australia during July 2020 before basketball had the chance to return from the first Australian-wide COVID-19 lockdown. Volunteers had positive intentions to return to basketball following COVID-19 restrictions because it was fun, to help others, or because friends/family were involved. Volunteers were most concerned that others will not comply with COVID-safe policies particularly around isolating when feeling unwell (95%), but also reported concerns about the inconveniences of some COVID-safe policies introduced to return to organised sport (e.g. social distancing, density limits, and enforcing rule changes). Understanding these volunteer intentions, motivations and factors influencing the decision to return to COVID-safe basketball can help inform recruitment and retention strategies to support volunteers in sport. Practical implications for sport policy and practice are discussed.

The ability to change direction rapidly is a key fitness quality especially in invasive sports where young players perform approximately 300 changes of direction in a game. There iscurrently limited understanding of how anthropometric characteristics and maturation status influence change of direction ability in adolescent. Therefore, the purpose of this investigation is to assess the influence of anthropometrics and maturation status on change of direction ability in young people. The study involved 706 adolescents (367 girls) aged 14 19-yearold attending the same high school in Northern Italy. Stature, body mass, seated height and leg length were measured to determine the anthropometrics and maturation status of the participants. Repeated change of direction ability (10×5 m shuttle run test), lower limb power and muscle strength were evaluated using field tests from the Eurofit test battery. Maturity offset was calculated separately for boys and girls, in accord with the equation proposed by Mirwald. Preliminary analysis with 10×5 m as a dependent variable and sex and PHV as a fixed factor, suggests a significant difference between sex (p < 0.001; d = 0.35) but not with PHV (p = 0.986; d = 0.000) and interaction PHV×sex (p = 0.836; d = 0.000). Our results suggested that repeated change of direction performance wasinfluenced by anthropometrics, maturation and muscle qualitiesin adolescent boys and girls.

Since March 2020, there have been multiple outside influences negatively impacting the U.S. craft beer industry from COVID-19 to inflation all leading up to increased prices for consumers. However, to date, research has not investigated consumer sentiment toward increased prices and their willingness to continue paying increased prices for beer from various outlets. The current study provides an initial assessment of craft beer consumers’ purchase behaviors for on(own)- and off-premise consumption given the impacts of COVID-19 and the recent economic situation. Past research has indicated that increased prices tend to lead to decreased purchases of beer (and alcohol in general). Results of the current online survey of craft beer drinkers mostly align with past findings, as nearly half of the 350 participants in this study indicated that they had decreased their consumption of craft beer away from home. Relatedly, respondents indicated a relatively low willingness to pay price increases for craft beer consumed on-premise (own-premise) or off-premise.

Sensing and cognition by homeowners and technicians for home maintenance are prime examples of human–building interaction. Damage, decay, and pest infestation present signals that humans interpret and then act upon to remedy and mitigate. The maintenance cognition process has direct effects on sustainability and economic vitality, as well as the health and well-being of building occupants. While home maintenance practices date back to antiquity, they readily submit to augmentation and improvement with modern technologies. This paper describes the use of networked smart technologies embedded with machine learning (ML) and presented in electronic formats to better inform homeowners and occupants about safety and maintenance issues, as well as recommend courses of remedial action. The demonstrated technologies include robotic sensing in confined areas, LiDAR scans of structural shape and deformation, moisture and gas sensing, water leak detection, network embedded ML, and augmented reality interfaces with multi-user teaming capabilities. The sensor information passes through a private local dynamic network to processors with neural network pattern recognition capabilities to abstract the information, which then feeds to humans through augmented reality and conventional smart device interfaces. This networked sensor system serves as a testbed and demonstrator for home maintenance technologies, for what can be termed Home Maintenance 4.0.

Abstract Background The nasal cannula is considered a trusted and effective means of administering low-flow oxygen and is widely used for neonates and infants requiring oxygen therapy, despite an understanding that oxygen concentrations delivered to patients are variable. Methods In the present study, realistic nasal airway replicas derived from medical scans of children less than 3 months old were used to measure the fraction of oxygen inhaled (FiO2) through nasal cannulas during low-flow oxygen delivery. Parameters influencing variability in FiO2 were evaluated, as was the hypothesis that measured FiO2 values could be predicted using a simple, flow-weighted calculation that assumes ideal mixing of oxygen with entrained room air. Tidal breathing through neonatal and infant nasal airway replicas was controlled using a lung simulator. Parameters for nasal cannula oxygen flow rate, nasal airway geometry, tidal volume, respiratory rate, inhalation/exhalation, or I:E ratio (ti/te), breath waveform, and cannula prong insertion position were varied to determine their effect on measured FiO2. In total, FiO2 was measured for 384 different parameter combinations, with each combination repeated in triplicate. Analysis of variance (ANOVA) was used to assess the influence of parameters on measured FiO2. Results Measured FiO2 was not appreciably affected by the breath waveform shape, the replica geometry, or the cannula position but was significantly influenced by the tidal volume, the inhalation time, and the nasal cannula flow rate. Conclusions The flow-weighted calculation overpredicted FiO2 for measured values above 60%, but an empirical correction to the calculation provided good agreement with measured FiO2 across the full range of experimental data.

Interprofessional healthcare team function is critical to the effective delivery of patient care. Team members must possess teamwork competencies, as team function impacts patient, staff, team, and healthcare organizational outcomes. There is evidence that team training is beneficial; however, consensus on the optimal training content, methods, and evaluation is lacking. This manuscript will focus on training content. Team science and training research indicates that an effective team training program must be founded upon teamwork competencies. The Team FIRST framework asserts there are 10 teamwork competencies essential for healthcare providers: recognizing criticality of teamwork, creating a psychologically safe environment, structured communication, closed-loop communication, asking clarifying questions, sharing unique information, optimizing team mental models, mutual trust, mutual performance monitoring, and reflection/debriefing. The Team FIRST framework was conceptualized to instill these evidence-based teamwork competencies in healthcare professionals to improve interprofessional collaboration. This framework is founded in validated team science research and serves future efforts to develop and pilot educational strategies that educate healthcare workers on these competencies.

Purpose – The purpose of this systematic review is to highlight some of the business model changes restaurants, bars and beverage producers undertook to modify their operations in order to not only stay in business but also to better serve their employees and communities during the COVID-19 crisis. Design/methodology/approach – An analysis was conducted on 200 industry articles and categorized into three major themes: expansion of take-out/delivery, innovative practices, and community outreach/corporate support, each are further subdivided into additional themes. The systematic review is further supported by personal interviews with industry professionals. Findings – This research finds that there were many different approaches used in adjusting business models in response to the dining restrictions put in place due to COVID-19. From these approaches, themes were developed which resulted in uncovering some suggestions such as developing contingency plans, being flexible and creative, eliminating menu items, investing in a communication platform and getting involved with local government. In addition, some practices operators should be mindful of such as selling gift cards and starting a crowdfund. Research limitations/implications – This research provides a systematic analysis of business model changes that occurred due to COVID-19 dining restrictions. Researchers can use this information as a guide for further analysis on a specific theme introduced herein. Practical implications – This research offers several practical implications which will assist the industry should another similar event occur in the future. The systematic analysis describes and documents some suggestions as well as practices to be mindful of in preparing contingency plans for the future. Originality/value – This research documents an unprecedented time for the hospitality industry by examining how restaurant, bar and beverage producers around the country responded to COVID-19 restrictions. Distilling the multitude of information into succinct themes that highlight the business model changes that occurred will aid future research as well as operators.

Abstract Background Malaria is a global health problem for which novel therapeutic compounds are needed. To this end, a recently published novel family of antiplasmodial macrolides, strasseriolides A–D, was herein subjected to in vivo efficacy studies and preclinical evaluation in order to identify the most promising candidate(s) for further development. Methods Preclinical evaluation of strasseriolides A–D was performed by MTT-based cytotoxicity assay in THLE-2 (CRL-2706) liver cells, cardiotoxicity screening using the FluxOR™ potassium assay in hERG expressed HEK cells, LC–MS-based analysis of drug-drug interaction involving CYP3A4, CYP2D6 and CYP2C9 isoforms inhibition and metabolic stability assays in human liver microsomes. Mice in vivo toxicity studies were also accomplished by i.v. administration of the compounds (vehicle: 0.5% HPMC, 0.5% Tween 80, 0.5% Benzyl alcohol) in mice at 25 mg/kg dosage. Plasma were prepared from mice blood samples obtained at different time points (over a 24-h period), and analysed by LC-MS to quantify compounds. The most promising compounds, strasseriolides C and D, were subjected to a preliminary in vivo efficacy study in which transgenic GFP-luciferase expressing Plasmodium berghei strain ANKA-infected Swiss Webster female mice (n = 4–5) were treated 48 h post-infection with an i.p. dosage of strasseriolide C at 50 mg/kg and strasseriolide D at 22 mg/kg for four days after which luciferase activity was quantified on day 5 in an IVIS® Lumina II imager. Results Strasseriolides A–D showed no cytotoxicity, no carditoxicity and no drug-drug interaction problems in vitro with varying intrinsic clearance (CLint). Only strasseriolide B was highly toxic to mice in vivo (even at 1 mg/kg i.v. dosage) and, therefore, discontinued in further in vivo studies. Strasseriolide D showed statistically significant activity in vivo giving rise to lower parasitaemia levels (70% lower) compared to the controls treated with vehicle. Conclusions Animal efficacy and preclinical evaluation of the recently discovered potent antiplasmodial macrolides, strasseriolides A–D, led to the identification of strasseriolide D as the most promising compound for further development. Future studies dealing on structure optimization, formulation and establishment of optimal in vivo dosage explorations of this novel compound class could enhance their clinical potency and allow for progress to later stages of the developmental pipeline.

The heterogeneity of tumor evolution from AR-positive, adenocarcinoma to AR-negative, neuroendocrine prostate cancer (NEPC) is not fully characterized. Here the authors generate a mouse model to show that Rb1 loss and MYCN overexpression accelerates the progression to AR-negative NEPC and identify emergence of distinct subpopulations of NEPC cells.

Ada Gjyrezi et al. show that ddPCR can be used to accurately measure androgen receptor variant (AR-V) expression levels in single circulating tumor cells (CTCs) from prostate cancer patients. They show that current methods for isolating CTCs tend to underestimate the prevalence of AR-V and that a specific variant, AR-v567es, could be potentially used as a biomarker for an aggressive subtype of prostate cancer.

Introduction and aim: Non-alcoholic fatty liver disease (NAFLD) is one of the most common diseases in the United States. Metabolic distress (obese diabetes) is the main causative element of NAFLD. While there is no cure for NAFLD, endurance exercise (EEx) has emerged as a therapeutic strategy against NAFLD. However, mechanisms of EXE-induced hepatic protection especially in female subjects remain unidentified. Thus, the aim of the study is to examine molecular mechanisms of EXE-induced hepatic protection against diet-induced NAFLD in female mice. Material and methods: Nine-week-old female C57BL/6J mice were randomly divided into three groups: normal-diet control group (CON, n=11); high-fat diet/high-fructose group (HFD/HF, n=11); and HFD/HF+EEx group (HFD/HF+EEx, n=11). The mice assigned to HFD/HF and HFD/HF+EEx groups were fed with HFD/HF for 12 weeks, after which the mice assigned to the EEx group began treadmill exercise for 12 weeks, with HFD/HF continued. Results: EEx attenuated hepatic steatosis, reduced de novo lipogenesis (reduction in ATP-Citrate- Lyase and diacylglycerol-O-acyltransferase 1), and enhanced mitochondrial biogenesis and fatty-acid activation (oxidative phosphorylation enzymes and Acyl-CoA synthetase1). Also, EEx prevented upregulation of gluconeogenic proteins (glyceraldehyde-3-phosphate dehydrogenase, glucose-6-phosphatase, and phosphoenolpyruvate-carboxykinase1), premature senescence (suppression of p53, p22, and p16, tumor-necrosis-factor-α, and interleukin-1β, and oxidative stress), and autophagy deficiency. Furthermore, EXE reversed apoptosis arrest (cleaved cysteine-dependent-aspartate-directed protease3 and Poly-(ADP-ribose)-polymerase1). Conclusion: EEx-mediated reparations of metabolic and redox imbalance (utilization of pentose phosphate pathway), and autophagy deficiency caused by metabolic distress critically contribute to preventing/delaying severe progression of NAFLD. Also, EEx-induced anti-senescence and cell turnover are crucial protective mechanisms against NAFLD.

Purpose: The isometric mid-thigh pull (IMTP) is commonly used to assess maximal and rapid (i.e., explosive) strength in athlete populations. The conventional IMTP instruction is to pull “as hard and fast as possible” (CON). However, previous studies using other isometric tests indicate that the use of ‘hard’ and ‘fast’ independently can result in different test outcomes. This investigation assessed the impact of a ‘hard’ only (HARD) and ‘fast’ only (FAST) instruction on IMTP kinetics when compared to the conventional combined instruction. Methods: Over three separate testing sessions, 17 National level, male, youth footballers (age: 16.4±1.3yr, mass: 69.7±8.0kg, height: 1.75±0.07m) completed three trials of the IMTP under each instruction. Peak force (N) and rapid force production, measured as impulse (N.s-1) over 50ms, 75ms, 100ms, 150ms, and 200ms were extracted and brought forward for analysis. To determine the presence of a statistical difference between conditions, a repeated measures ANOVA was employed while Cohen’s d effects sizes were used to quantify the magnitude of practical difference between each condition. Results: There was no significant or practically relevant impact of instruction condition on peak force (P > 0.05, d=0.08-0.27), or impulse over any time frame (P > 0.05, d=0.01-0.16). Conclusion: Practitioners can be confident that the conventional IMTP instruction is suitable for continued use in this athlete population.

Purpose: Exploring antecedents of flawed wine purchase intention, this study attempts to assess consumer acceptance leading to the purchase or consumption of a flawed wine product as well as build a profile of flawed wine consumers. Design/Methodology/Approach: A survey, from Amazon Mechanical Turk (Mturk) with 260 valid survey responses collected. ANOVA with post hoc testing was used to analyze the data. Findings: Results reflect that attitude, subjective knowledge, perceived behavioral control, perceived risk, and sensory appeal all significantly influence intent to purchase a flawed wine product. Additionally, environmental attitude significantly influences their intent to purchase wines with flaws and their attitude toward flawed wine. Originality: To date, no research has explored consumer acceptance of flawed wines. This study attempted to fill a gap in the literature and add to the overall body of knowledge regarding flawed wines and consumer understanding/acceptance of flawed wines, as well as generating a profile of potential flawed wine consumers. Research Limitations/Implications: Consumer panel data is not as rich as an experimental study design; however, this work starts an academic conversation on flawed wine and provides a foundation for future research. Practical Implications: The results of this study offer practical opportunities, from educating consumers toward a richer understanding of wine flaws; promotional opportunities for wine producers with a product to be disposed of, enhancing revenue generation; and how sensory appeal and environmental concern are beneficial to furthering the understanding and predictability of consumer intentions to purchase flawed wines.

Nematode P granules are cytoplasmic RNA–protein biomolecule condensates central to germ cell development. Here the authors show that dimerization of the PGL-1 scaffolding protein is crucial to granule formation and mRNA repression, and that the WAGO-1 Argonaute protein is a cofactor in repressing PGL-1 bound mRNAs.

Agility is a complex skill that is influenced by several physical, technical and cognitive factors. In this position stand, we discuss agility as it relates to invasion sports such as the many football codes. An important concept when conceptualising agility is understanding how it is applied on the field or court. Agility is particularly important in contests between attackers and defenders. For example, an attacker needs to create space or separation from defenders, in order to evade or to maintain possession of the ball. Conversely, defenders may require agility to reduce time and space in relation to the attacker, thereby applying pressure with the intention of achieving a turnover of possession. The movements performed in an agility scenario are diverse, and may involve an isolated deceleration, or a range of actions to produce a lateral displacement of the body at various angles and speeds. To create novel insights into agility, the interactions between predators and prey are explored in the animal world and reveal that successful pursuit (like a defender) or escape (like an attacker) is influenced by the ability to accelerate and attain high speeds, decelerate, and manoeuvre with control at optimum speeds, as well as expressing perceptual and cognitive skills. A plethora of sports literature claiming to discuss agility actually refers to pre-planned change-of-direction (COD) movements, known as COD ability. There are several differences between agility and COD ability, which should be considered when testing and prescribing agility activities. The characteristics of different agility techniques are presented and discussed with consideration to performance and the risk of injury such as anterior cruciate ligament (ACL) rupture, with the aim of creating multiple movement solutions for the athlete. Due to the diversity of agility actions performed in invasion sports, physical development should include tissue strengthening as well as fast and slow stretch-shortening cycle exercises to cater for different speeds and angles of agility movements. The speed and accuracy of decision-making in agility contests (cognitive component) are determined by the athlete’s ability to anticipate opponent’s actions, visually scan the environment, recognise patterns of play, and predict movement strategies based on knowledge of situations. One versus one contests, small-sided games, and video perceptual training can enhance the cognitive component of agility. Finally, there is no single coaching strategy or method that should be used to develop agility. Instead, the appropriate methodology must fit the individual needs of athletes, and therefore a mixed multicomponent approach is needed as part of an agility framework. Training examples to develop agility are presented throughout this position statement.

Coincidence counters play the role of gating events from the background noise in almost every quantum photonics setup. Precise multi-channel and high count-rate coincidence counting tools have become desirable due to an increase in the complexity of quantum photonics experiments. However, timing analyzers are struggling to meet these needs. We are proposing a Field Programmable Gate Array (FPGA) based coincidence counting system which provides 8 operational channels with 8.9 ps root mean square (RMS) resolution (with a bin width of 7.7 ps) and a count-rate of 320 million counts per second (MCPS) (with 40 MCPS per channel). We have successfully tested our design in different quantum photonics scenarios such as the detection of two-photon interference and pseudo-photon-number resolving detection of a coherent state of light where it has shown its capability of working beyond the saturation of detectors. Also, we have introduced a Dual Data Rate Registration TDC, which improved the linearity of the time tagging operation by using both clock edges without increasing the dead-time or using the space excessively. 1.2 LSB in max DNL error, 1.8 LSB in max INL error, 10 ps in FWHM and 3.2 ps in RMS resolution improvements were achieved.

Abstract Background Adenosine-to-inosine (A-to-I) RNA editing, mediated by ADAR1 and ADAR2, occurs at tens of thousands to millions of sites across mammalian transcriptomes. A-to-I editing can change the protein coding potential of a transcript and alter RNA splicing, miRNA biology, RNA secondary structure and formation of other RNA species. In vivo, the editing-dependent protein recoding of GRIA2 is the essential function of ADAR2, while ADAR1 editing prevents innate immune sensing of endogenous RNAs by MDA5 in both human and mouse. However, a significant proportion of A-to-I editing sites can be edited by both ADAR1 and ADAR2, particularly within the brain where both are highly expressed. The physiological function(s) of these shared sites, including those evolutionarily conserved, is largely unknown. Results To generate completely A-to-I editing-deficient mammals, we crossed the viable rescued ADAR1-editing-deficient animals (Adar1 E861A/E861A Ifih1 −/− ) with rescued ADAR2-deficient (Adarb1 −/− Gria2 R/R ) animals. Unexpectedly, the global absence of editing was well tolerated. Adar1 E861A/E861A Ifih1 −/− Adarb1 −/− Gria2 R/R were recovered at Mendelian ratios and age normally. Detailed transcriptome analysis demonstrated that editing was absent in the brains of the compound mutants and that ADAR1 and ADAR2 have similar editing site preferences and patterns. Conclusions We conclude that ADAR1 and ADAR2 are non-redundant and do not compensate for each other’s essential functions in vivo. Physiologically essential A-to-I editing comprises a small subset of the editome, and the majority of editing is dispensable for mammalian homeostasis. Moreover, in vivo biologically essential protein recoding mediated by A-to-I editing is an exception in mammals.

AA6010 in the F temper was investigated using a Gleeble 3800 test rig across a range of temperatures (350–550 °C) and strain rates (1 × 10−1 s−1 1 × 101 s−1) to identify optimal forming conditions. Post-forming electron back-scattered diffraction analysis was conducted to identify the mechanisms responsible for the material formability. Optimal forming conditions were observed to be 500 °C and a strain rate of 1 × 10−1 s−1, with clear evidence of dynamic recrystallisation observed, this being the dominant mechanism responsible for the increased formability. Peak yield strength of 335 MPa was achieved using a rapid aging treatment of 205 °C for one hour.

Introduction Chronic low back pain disorders (CLBDs) present a substantial societal burden; however, optimal treatment remains debated. To date, pairwise and network meta-analyses have evaluated individual treatment modes, yet a comparison of a wide range of common treatments is required to evaluate their relative effectiveness. Using network meta-analysis, we aim to evaluate the effectiveness of treatments (acupuncture, education or advice, electrophysical agents, exercise, manual therapies/manipulation, massage, the McKenzie method, pharmacotherapy, psychological therapies, surgery, epidural injections, percutaneous treatments, traction, physical therapy, multidisciplinary pain management, placebo, ‘usual care’ and/or no treatment) on pain intensity, disability and/or mental health in patients with CLBDs.Methods and analysis Six electronic databases and reference lists of 285 prior systematic reviews were searched. Eligible studies will be randomised controlled/clinical trials (including cross-over and cluster designs) that examine individual treatments or treatment combinations in adult patients with CLBDs. Studies must be published in English, German or Chinese as a full-journal publication in a peer-reviewed journal. A narrative approach will be used to synthesise and report qualitative and quantitative data, and, where feasible, network meta-analyses will be performed. Reporting of the review will be informed by Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidance, including the network meta-analysis extension (PRISMA-NMA). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach for network meta-analysis will be implemented for assessing the quality of the findings.Ethics and dissemination Ethical approval is not required for this systematic review of the published data. Findings will be disseminated via peer-reviewed publication.PROSPERO registration number PROSPERO registration number CRD42020182039.

When scientists act unethically, their actions can cause harm to participants, undermine knowledge creation, and discredit the scientific community. Responsible Conduct of Research (RCR) training is one of the main ways institutions try to prevent scientists from acting unethically. However, this only addresses the problem if scientists value the training, and if the problem stems from ignorance. This study looks at what scientists think causes unethical behavior in science, with the hopes of improving RCR training by shaping it based on the views of the targeted audience ( n = 14 scientists). Previous studies have surveyed scientists about what they believe causes unethical behavior using pre-defined response items. This study uses a qualitative research methodology to elicit scientists’ beliefs without predefining the range of responses. The data for this phenomenographic study were collected from interviews which presented ethical case studies and asked subjects how they would respond to those situations. Categories and subcategories were created to organize their reasonings. This work will inform the development of future methods for preventing unethical behavior in research.

Complex training where a high-load conditioning stimulus (CS) is performed prior to a biomechanically similar plyometric movement has been demonstrated to acutely enhance the performance of the plyometric movement in a phenomenon called post-activation performance enhancement (PAPE). Despite the positive influence PAPE can have on power production, the abundance of research has only investigated PAPE locally while comparing biomechanically similar movements. The purpose of this study was to determine if a heavy barbell bench press could elicit PAPE in a lower body plyometric movement. Eight (n = 8) resistance-trained males performed one set of countermovement jumps (CMJs) before (pre-CS) and three sets of CMJs after (post-CS) a heavy bench press set. Changes in muscle activation, jump height, work, power output, and rate of force development (RFD) during the early (E-RFD) and late (L-RFD) stages were compared between pre-CS and post-CS. The level of significance was set at p < .05. There were no significant differences in muscle activation, jump height, work, power output, or E-RFD (p > .05). There was a significant increase in L-RFD between pre-CS and the final set of jumps post-CS (p = .01). These results suggest that an upper body CS may not influence PAPE in the lower body. However, pairing a high-load upper body exercise with a lower body plyometric does not seem disadvantageous, and could be implemented as a strategy to maximize workout time efficiency with proper fatigue management incorporation.

Human cytomegalovirus (CMV) utilizes different glycoproteins to enter into fibroblast and epithelial cells. A trimer of glycoproteins H, L, and O (gH/gL/gO) is required for entry into all cells, whereas a pentamer of gH/gL/UL128/UL130/UL131A is selectively required for infection of epithelial, endothelial, and some myeloid-lineage cells, but not of fibroblasts. Both complexes are of considerable interest for vaccine and immunotherapeutic development but present a conundrum: gH/gL-specific antibodies have moderate potency yet neutralize CMV entry into all cell types, whereas pentamer-specific antibodies are more potent but do not block fibroblast infection. Which cell types and neutralizing activities are important for protective efficacy in vivo remain unclear. Here, we present evidence that certain CMV strains have evolved polymorphisms in gO to evade trimer-specific neutralizing antibodies. Using luciferase-tagged variants of strain TB40/E in which the native gO is replaced by gOs from other strains, we tested the effects of gO polymorphisms on neutralization by monoclonal antibodies (mAbs) targeting four independent epitopes in gH/gL that are common to both trimer and pentamer. Neutralization of fibroblast entry by three mAbs displayed a range of potencies that depended on the gO type, a fourth mAb failed to neutralize fibroblast entry regardless of the gO type, while neutralization of epithelial cell entry by all four mAbs was potent and independent of the gO type. Thus, specific polymorphisms in gO protect the virus from mAb neutralization in the context of fibroblast but not epithelial cell entry. No influence of gO type was observed for protection against CMV hyperimmune globulin or CMV-seropositive human sera, suggesting that antibodies targeting protected gH/gL epitopes represent a minority of the polyclonal neutralizing repertoire induced by natural infection.

Jumps occur frequently in basketball and can be executed from a single-leg take-off following a run-up or bilaterally from a standing start. Understanding the type of jumps performed in competition and how different muscular qualities influence their performance, informs training prescription. Firstly, to quantify the occurrence of different jump types performed in competition an analysis of 15 semi-professional basketball games was undertaken. Secondly, to understand the influence of muscular qualities on performance of different jump types, Semi-professional male basketball players (N=17) performed jump tests; standing vertical jump, running vertical jumps with a double leg take-off (RVJ2) and a single leg take-off (RVJ1) and tests of lower-body speed-strength; reactive strength index (RSI) from a drop jump, counter movement jump (CMJ) and squat jump. A stationary approach was employed for 69%, a running approach for 26% and a one-step approach for 5%. RVJ1 displayed non-significant (P=0.07) moderate correlation with jump height attained from the CMJ (r=0.439) and a very large (r =.806) significant (P

Background: Safe and effective patient care depends on the teamwork of multidisciplinary healthcare professionals. Unfortunately, the field currently lacks an evidence-based framework for effective teamwork that can be incorporated into medical education and practice across health professions. We introduce a comprehensive framework for team effectiveness. Common challenges to teamwork in healthcare are identified along with evidence-based strategies for overcoming them.Methods: The framework was developed in four steps: 1) grounding in the existing team science literature, 2) semi-structured interviews (N = 13), 3) thematic analysis and initial framework development, and 4) revision of the framework through input from healthcare professionals representative of different functions across the healthcare system (N = 13). A diagnostic tool consisting of one survey item per team competency was developed to complement the framework. The survey was then administered to healthcare teams across clinical and administrative functions (N = 10 teams, 96 individuals), and results were compiled and then used to conduct debriefs with individual team members and teams. A set of common teamwork challenges were identified using the survey and qualitative data. Qualitative data was analyzed to explore the unique ways these challenges manifest in both clinical and administrative teams.Results: The five most common challenges that face healthcare teams relate to accountability, conflict management, decision-making, reflecting on progress, and coaching. These challenges were similar across both clinical and administrative team types. Based on the authors' collective experience designing and implementing Team Development Interventions (TDIs), strategies for managing each challenge are provided.Conclusions: The proposed framework is unique in two ways. First, it's generally applicable across the many types of teams that contribute to the quality and safety of patient care. Second, the levels of the framework build upon each other to contribute to the development of the ideal team states. The framework and accompanying strategies can provide guidance for where and how to target developmental efforts.

The University of Manchester Library has established a key role in facilitating scholarly discourse through its mediated open access (OA) services, but has little track record in intentionally taking OA research outputs to non-academic audiences. This article outlines recent exploratory steps the Library has taken to convince researchers to fully exploit this part of the scholarly communication chain. Driving developments within this service category is a belief that despite the recent rise in OA, the full public benefit of research outputs is often not being realized as many papers are written in inaccessibly technical language. Recognizing our unique position to help authors reach broader audiences with simpler expressions of their work, we have evolved our existing managed OA services to systematically share plain-English summaries of OA papers via Twitter. In parallel, we have taken steps to ensure that our commercial analytics tools work harder to identify and reach the networked communities that form around academic disciplines in the hope that these simpler expressions of research will be more likely to diffuse beyond these networks.

Inhibition of sclerostin with sclerostin antibody (Scl-Ab) results in stimulation of bone formation on cancellous (Cn), endocortical (Ec), and periosteal (Ps) surfaces in rodents and non-human primates. With long-term dosing of Scl-Ab, the increase in bone formation is not sustained, attenuating first on Cn surfaces and later on Ec and Ps surfaces. In Cn bone, the attenuation in bone formation (self-regulation) is associated with transcriptional changes in the osteocyte (OCy) that would limit mitogenesis and are sustained with continued dosing. The expression changes in Cn OCy occur coincident with a decrease in osteoprogenitor (OP) numbers that may directly or indirectly be a consequence of the transcriptional changes in the OCy to limit OP proliferation. To characterize the Scl-Ab–mediated changes in cortical (Ct) bone and compare these changes to Cn bone, densitometric, histomorphometric, and transcriptional analyses were performed on femur diaphyses from aged ovariectomized rats. Animals were administered 50 mg/kg/wk of Scl-Ab or vehicle for up to 6 months (183 days), followed by a treatment-free period (up to 126 days). Scl-Ab increased Ct mass and area through day 183, which declined slightly when treatment was discontinued. Ps and Ec bone formation was sustained through the dosing on both Ct surfaces, with evidence of a decline in bone formation only at day 183 on the Ec surface. This is in contrast to Cn bone, where reduced bone formation was observed after day 29. TaqMan analysis of 60 genes with functional roles in the bone using mRNA isolated from laser capture micro-dissection samples enriched for Ec osteoblasts and Ct OCy suggest a pattern of gene expression in Ct bone that differed from Cn, especially in the OCy, and that corresponded to observed differences in the timing of phenotypic changes. Notable with Scl-Ab treatment was a “transcriptional switch” in Ct OCy at day 183, coincident with the initial decline in bone formation on the endocortex. A consistent sustained increase of expression for most genes in response to Scl-Ab was observed from day 8 through day 85 at the times of maximal bone formation on both Ct surfaces; however, at day 183, this increase was reversed, with expression of these genes generally returning to control values or decreasing compared to vehicle. Genes exhibiting this pattern included Wnt inhibitors Sost and Dkk1, though both had been up-regulated until the end of dosing in Cn OCy. Changes in cell cycle genes such as Cdkn1a and Ndrg1 in Ct OCy suggested up-regulation of p53 signaling, as observed in Cn OCy; however, unlike in Cn bone, p53 signaling was not associated with decreased bone formation and was absent at day 183, when bone formation began to decline on the Ec surface. These data demonstrate involvement of similar molecular pathways in Ct and Cn bone in response to Scl-Ab but with a different temporal relationship to bone formation and suggest that the specific mechanism underlying self-regulation of Scl-Ab–induced bone formation may be different between Cn and Ct bone. Keywords: Osteoporosis, Therapeutics, Anabolics, Wnt signaling, Bone

Sclerostin antibody (Scl-Ab) stimulates bone formation, which with long-term treatment, attenuates over time. The cellular and molecular mechanisms responsible for the attenuation of bone formation are not well understood, but in aged ovariectomized (OVX) rats, the reduction in vertebral cancellous bone formation is preceded by a reduction in osteoprogenitor (OP) number and significant induction of signaling pathways known to suppress mitogenesis and cell cycle progression in the osteocyte (OCy) (Taylor et al., 2016). To determine if the reduction in OP number is associated with a decrease in proliferation, aged OVX rats were administered vehicle or Scl-Ab for 9 or 29 days and implanted with continuous-delivery 5-bromo-2′-deoxyuridine (BrdU) mini-osmotic pumps 5 days prior to necropsy. The total number of BrdU-labeled osteoblasts (OB) was quantified in vertebral cancellous bone to indirectly assess the effects of Scl-Ab treatment on OP proliferation at the time of activation of modeling-based bone formation at day 9 and at the time of maximal mineralizing surface, initial decrease in OP number, and transcriptional changes in the OCy at day 29. Compared with vehicle, Scl-Ab resulted in an increase in the total number of BrdU-positive OB (+260%) at day 9 that decreased with continued treatment (+50%) at day 29. These differences in proliferation occurred at time points when the increase in total OB number was significant and similar in magnitude. These findings suggest that reduced OP proliferation contributes to the decrease in OP numbers, an effect that would limit the OB pool and contribute to the attenuation of bone formation that occurs with long-term Scl-Ab treatment. Keywords: Osteoporosis, Anabolics, Cell signaling, Osteoprogenitors, Wnt signaling, Bone

Ninety-six parents in a preschool and pediatric clinic participated in a randomized study of a brief parenting intervention. The Attitudes Toward Spanking (ATS) scale was measured at baseline, and, on average, 4 months postintervention. Higher ATS scores are correlated with increased use of physical punishment. In the intervention group, there was a 2.7-point decrease in the ATS score at follow-up compared with baseline (P = 0.01). There was no decrease in the ATS in the control group. Brief interventions may shift parental attitudes toward using less physical punishment and have implications for improving anticipatory guidance within primary care and early education. [ABSTRACT FROM AUTHOR]

Abstract Background Adenosine-to-inosine (A-to-I) editing of dsRNA by ADAR proteins is a pervasive epitranscriptome feature. Tens of thousands of A-to-I editing events are defined in the mouse, yet the functional impact of most is unknown. Editing causing protein recoding is the essential function of ADAR2, but an essential role for recoding by ADAR1 has not been demonstrated. ADAR1 has been proposed to have editing-dependent and editing-independent functions. The relative contribution of these in vivo has not been clearly defined. A critical function of ADAR1 is editing of endogenous RNA to prevent activation of the dsRNA sensor MDA5 (Ifih1). Outside of this, how ADAR1 editing contributes to normal development and homeostasis is uncertain. Results We describe the consequences of ADAR1 editing deficiency on murine homeostasis. Adar1 E861A/E861A Ifih1 -/- mice are strikingly normal, including their lifespan. There is a mild, non-pathogenic innate immune activation signature in the Adar1 E861A/E861A Ifih1 -/- mice. Assessing A-to-I editing across adult tissues demonstrates that outside of the brain, ADAR1 performs the majority of editing and that ADAR2 cannot compensate in its absence. Direct comparison of the Adar1 -/- and Adar1 E861A/E861A alleles demonstrates a high degree of concordance on both Ifih1 +/+ and Ifih1 -/- backgrounds, suggesting no substantial contribution from ADAR1 editing-independent functions. Conclusions These analyses demonstrate that the lifetime absence of ADAR1-editing is well tolerated in the absence of MDA5. We conclude that protein recoding arising from ADAR1-mediated editing is not essential for organismal homeostasis. Additionally, the phenotypes associated with loss of ADAR1 are the result of RNA editing and MDA5-dependent functions.

There is a long tradition at the Royal Botanic Gardens, Kew (RBG, Kew) of cultivating and displaying exotic plants from all over the globe, and the largest Victorian glasshouse, the Temperate House, traditionally showcases plants from temperate regions. The Temperate House Restoration Project was undertaken at RBG, Kew from 2012 to 2018. Over 1,000 species of plants were removed, propagated and replanted for this project, and this article describes the propagation of some of the most difficult to reproduce plant material. Four plant groups or species are presented: Erica verticillata P.J.Bergius, Quercus insignis M.Martens Galeotti, Pinus roxburghii Sargent and Banksia spp. L. This is in order to illustrate the variety of options available for propagating challenging species with attention to their ecology, biology and growing requirements. Also provided are background information, reasons why these plants are considered difficult to multiply in cultivation, how plant material was sourced and the methods employed which led to successful propagation of the material at RBG, Kew. Propagation of the plants was heavily reliant on the horticultural expertise of those involved, and this expertise ensured that most of the original plant material was rejuvenated and new collections with scientific significance were added to the restored Temperate House.

Cerebral malaria (CM) is a clinical syndrome involving irreversible and lethal signs of brain injury associated to infection by parasites of the genus Plasmodium. The pathogenesis of CM derives from infection-induced proinflammatory cytokines associated with cytoadherence of parasitized red blood cells to brain microvasculature. Glycoconjugates are very abundant in the surface of Plasmodium spp., and are critical mediators of parasite virulence in host–pathogen interactions. Herein, we show that 6-Diazo-5-oxo-L-norleucine (DON) therapeutically used for blocking hexosamine biosynthetic pathway leads to recovery in experimental murine cerebral malaria. DON-induced protection was associated with decreased parasitism, which severely reduced Plasmodium transmission to mosquitoes. These findings point to a potential use of DON in combination therapies against malaria.