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Deployment of distributed energy resources has rapidly increased during the last few years. The uptake of renewable energy and especially photovoltaic (PV) systems are of interest to utilities in remote and rural areas where the use of conventional power generation is costly. Investigating the effects of such PV systems on isolated power systems at different penetration levels is a relevant research topic. This study reports on the data acquisition system deployed in a remote town in Western Australia and presents some of the findings and observations extracted from the captured real data. It highlights the maximum PV output variations and investigates the underlying factors. The impact of the PV systems on the voltage across the network is also analysed in this study. The studies show that inverter tripping events have led to larger PV output variations in shorter intervals while the cloud movements have contributed to variations in longer intervals.

Our study shows the relevance of the interactions between atmospheric chemistry and physics to achieve better weather predictions. We provide evidence of the role that stratospheric ozone plays to improve weather forecasts on several timescales, and highlight the need for seamless models to include realistic prognostic ozone interactive with radiation.Representing realistic feedbacks between ozone, radiation, temperature and dynamics is essential to correctly simulate the behaviour of the stratosphere and its links with tropospheric weather and climate. We have implemented an alternative stratospheric ozone model (Monge-Sanz et al., 2011) in the ECMWF system interactively with radiation, and we have assessed its performance and feedbacks with meteorological fields for different timescales, from medium-range to seasonal. Here we will discuss results from the experiments and analyses conducted in our study (Monge-Sanz et al., 2021), showing the feasibility of this ozone model for a seamless numerical weather prediction approach.We will show that the stratospheric ozone distribution provided by this new prognostic ozone model compares very well with observations even for unusual meteorological conditions. On assessing impacts on meteorological variables, the new ozone model improves the representation of the stratosphere, clearly reducing temperature biases in this region. We will also show the benefits it brings to tropospheric meteorological fields, highlighting the potential of this new ozone description to exploit stratospheric sources of predictability and improve weather predictions over Europe on a range of time scales.Therefore, our results show the value of this prognostic stratospheric ozone model for seamless Earth System Models, as well as for global systems where atmospheric composition is coupled to weather forecasts, like the systems being run within the Copernicus Atmosphere Monitoring Service (CAMS). We will also discuss challenges and possible strategies for the inclusion of chemistry-dynamics feedbacks in seamless Earth System Models. References:Monge-Sanz BM, Chipperfield MP, Cariolle D, Feng W. Results from a new linear O3 scheme with embedded heterogeneous chemistry compared with the parent full-chemistry 3-D CTM. Atmos. Chem. Phys. 11, 1227-1242, 2011.Monge-Sanz, B. M., Bozzo, A., Byrne, N., Chipperfield, M. P., Diamantakis, M., Flemming, J., Gray, L. J., Hogan, R. J., Jones, L., Magnusson, L., Polichtchouk, I., Shepherd, T. G., Wedi, N., and Weisheimer, A.: A stratospheric prognostic ozone for seamless Earth System Models: performance, impacts and future, Atmos. Chem. Phys., accepted, https://doi.org/10.5194/acp-2020-1261, 2021.

Problem-based learning along with other game and player-centred approaches have been promoted as valuable alternatives to more traditional, skill-based, directive, and leader-centric pedagogical approaches. However, as research has shown, they are not unproblematic or straightforward to apply. Heeding to calls for more empirical studies of game-centred approaches in coaching contexts, this study explored the impact of a unique problem-based learning (PBL) informed academy-wide coaching approach to athlete learning and development known as Beat the Game within a top-level rugby union professional club. Drawing on Michel Foucault’s ([1977]. Discipline and punish: The birth of the prison. Vintage) disciplinary framework, we specifically sought to critically examine whether, to what extent, and how a PBL informed academy-wide coaching approach challenges the dominant disciplinary logic of elite sport. Our data, based on observations and semi-structured interviews with three academy coaches and sixteen junior and senior academy players, showed a definitive loosening of disciplinary aspects in both training and game environments accompanied by a shift towards a less leader-centric, linear, and hierarchical understanding of leadership and decision-making. Despite these promising shifts, the application of a PBL-informed coaching approach within this elite development context also presented many challenges, not the least of which resulted from the non-alignment of academy and first team coaching approaches. Our analysis, therefore, indicated the need for more research which focuses on the short-term and long-term impact that such disconnects have on continued progression, performance, physical and mental wellbeing, and job satisfaction and longevity especially given the growing popularity of non-linear pedagogies in youth sporting contexts.

Chromosomal rearrangements of the lysine methyltransferase 2A (KMT2A or MLL) gene are observed in ;10% of all acute leukemias, with particularly high frequency (;80%) in infant acute lymphoblastic leukemia (ALL),1 where, despite aggressive chemotherapy, patients still experience poor outcome and long-term side effects.2 Mixed lineage leukemia (MLL) rearrangements (MLL-r)also indicate particularly poor outcomes for patients with acute myeloid leukemia (AML).3 Mechanistically, MLL-r frequently generates fusion proteins involving partners that function in the super elongation complex,4 the result of which is aberrant recruitment to MLL target genes of the positive transcription elongation factor b (PTEFb), composed of cyclin-dependent kinase 9 (CDK9)as the catalytic subunit.5 CDK9 positively regulates transcription elongation through phosphorylation of serine 2 of RNA polymerase II (RNAPII).6 Given the central role of CDK9 in the leukemic MLL-r gene-expression program,7 and the well-described ability of CDK9 inhibitors to reduce levelsof the short-lived prosurvival protein MCL1,8 a number of CDK9 inhibitors have been selected forclinical trials focusing on acute leukemias, including those with MLL-r.8,9 In MLL-r leukemia, the bromodomain and extraterminal (BET) family member bromodomain-containing 4 (BRD4)10 acts to recruit PTEFb to super enhancers and together with CDK9 drives increased expression of many oncogenes including MYC.11,12 The roles of CDK9 and BRD4 in MLL-r leukemias present a strong case for testing inhibitors of these proteins in combination as a potential treatment of MLL-r acute leukemias. Refereed/Peer-reviewed

Purpose Lower limb malalignment is a strong predictor of progression in knee osteoarthritis. The purpose of this study is to identify the individual alignment variables that predict progression in early to moderate osteoarthritis of the knee. Method A longitudinal cohort study using data from the Osteoarthritis Initiative. In total, 955 individuals (1329 knees) with early to moderate osteoarthritis (Kellgren-Lawrence grade 1, 2 or 3) were identified. All subjects had full-limb radiographs analysed using the Osteotomy module within Medicad® Classic (Hectec GMBH) to give a series of individual alignment variables relevant to the coronal alignment of the lower limb. Logistic regression models, with generalised estimating equations were used to identify which of these individual alignment variables predict symptom worsening (WOMAC score > 9 points) and or structural progression (joint space narrowing progression in the medial compartment > 0.7mm) over 24 months. Results Individual alignment variable were associated with both valgus and varus alignment (mechanical Lateral Distal Femoral Angle, Medial Proximal Tibial Angle and mechanical Lateral Distal Tibial Angle). Only the Medial Proximal Tibial Angle was significantly associated with structural progression and none of the variables was associated with symptom progression. The odds of joint space narrowing progression in the medial compartment occurring at 24 months increased by 21% for every one degree decrease (more varus) in Medial Proximal Tibial Angle (p < 0.001) Conclusions Our results suggest that the risk of structural progression in the medial compartment is associated with greater varus alignment of the proximal tibia. Level of evidence Level III, retrospective cohort study.

Blowing the whistle on corruption or wrongdoing can facilitate the detection, investigation, and then prosecution of a violation that may have otherwise gone undetected. The purpose of this systematic review was to identify the factors that are associated with intentions to blow the whistle on wrongdoing. We searched Academic Search Premier, CINAHL Complete, Education Research Complete, ERIC, Medline, PsycARTICLES, PsycINFO, Regional Business News, and SPORTDiscus in January 2020. The quality of evidence was assessed using the Cochrane risk of bias tool. Of the 9,136 records identified, 217 studies were included in this systematic review. We identified 8 dimensions, 26 higher-order themes, and 119 lower-order themes. The whistleblowing dimensions were personal factors, organizational factors, cost and benefits, outcome expectancies, the offense, reporting, the wrongdoer, and social factors. Based on the findings, it is apparent that organizations should empower, educate, protect, support, and reward those who blow the whistle, in order to increase the likelihood on individuals blowing the whistle on corruption and wrongdoing. A combined approach may increase whistleblowing intentions, although research is required to test this assertion. From a policy perspective, more consistent protection is required across different countries.

The concept of shared decision-making (SDM) has emerged as a key component in the return to play interface as a hallmark of good practice that is athlete focused and allows greater engagement from the athlete. SDM is an appealing, well-intentioned framework that would seemingly lend itself to effectively being implemented. However, in this editorial, we have identified concerns surrounding the social complexities of elite sports and the difficulties of truly applying this concept in practice. In what follows, we explain the dynamics associated, discuss the importance of context when considering the efficacy of this practice and lastly offer what we see as certain key issues that might impede effective SDM.

As research has shown, former elite athletes often struggle to adapt to aspects of their post-sport lives. This can include the management of their identities, dealing with the uncertainty of their...

This paper has explored how a sociological reading of John Grisham’s short work of fiction Bleachers can shed light on the complexities of the coaching and sports retirement processes. The aim of t...

“Being perfect.” Should it be a coach’s aim? The perfect workout, training program, or practice plan. The perfect set of progressions or cues. It’s an enticing goal, one that can clearly be called ...

Background Subjective monitoring of rate of perceived exertion is common practice in many sports. Typically, the information is used to understand the training load and at times modify forthcoming sessions. Identifying the relationship between the athlete and coach’s interpretation of training would likely further benefit understanding load management. The aim of this systematic review was to evaluate the relationship between coaches’ rating of intended exertion (RIE) and/or rating of observed exertion (ROE) and athletes’ reported rating of perceived exertion (RPE). Methods The review was undertaken in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We conducted a search of Medline, Google Scholar, Science Direct, SPORTDiscus, and Web of Science databases. We assessed the correlation between coach-reported RIE and/or ROE and RPE. Assessment for risk of bias was undertaken using the Quality Appraisal for Reliability Studies (QAREL) checklist. Inclusion criteria were (1) male and/or female individuals, (2) individual and/or team sport active participants, and (3) original research article published in the English language. Results Data from 19 articles were found to meet the eligibility criteria. A random effect meta-analysis based on 11 studies demonstrated a positive association of player vs. coach rating of RIE (r = 0.62 [95% CI 0.5 to 0.7], p < 0.001). The pooled correlation from 7 studies of player vs. coach rating on ROE was r = 0.64 95% CI (0.5 to 0.7), p < 0.001. Conclusion There was a moderate to high association between coach RIE and/or ROE and athlete-reported RPE and this association seems to be influenced by many factors. The suggestions we present in this review are based on imploring practitioners to consider a multi-modal approach and the implications of monitoring when using RPE. Trial Registration CRD42020193387

Infants with MLL-rearranged infant acute lymphoblastic leukemia (MLL-r iALL) undergo intense therapy to counter a highly aggressive malignancy with survival rates of only 30–40%. The majority of patients initially show therapy response, but in two-thirds of cases the leukemia returns, typically during treatment. The glucocorticoid drug prednisone is established as a major player in the treatment of leukemia and the in vivo response to prednisone monotreatment is currently the best indicator of risk for MLL-r iALL. We used two different single-cell RNA sequencing technologies to analyze the expression of a prednisone-dependent signature, derived from an independent study, in diagnostic bone marrow and peripheral blood biopsies. This allowed us to classify individual leukemic cells as either resistant or sensitive to treatment and show that quantification of these two groups can be used to better predict the occurrence of future relapse in individual patients. This work also sheds light on the nature of the therapy-resistant subpopulation of relapse-initiating cells. Leukemic cells associated with high relapse risk are characterized by basal activation of glucocorticoid response, smaller size, and a quiescent gene expression program with cell stemness properties. These results improve current risk stratification and elucidate leukemic therapy-resistant subpopulations at diagnosis.

The treatment of children diagnosed with acute lymphoblastic leukemia (ALL) has improved significantly over recent decades, with 5-year event-free survival (EFS) approaching 85% [1]. However, 5-year EFS for infants diagnosed at less than 1 year of age with MLL-rearranged ALL remains less than 40% [2]. MLL-rearranged infant ALL is both clinically and biologically distinct from other childhood ALL subtypes, which is reflected by a unique gene expression profile [3], a remarkably silent mutational landscape [4], and pronounced resistance to currently applied chemotherapeutics [5].

Infants with MLL-rearranged acute lymphoblastic leukemia (ALL) undergo intense therapy to counter a highly aggressive leukemia with survival rates of only 30-40%. The majority of patients initially show therapy response, but in two-thirds of cases the leukemia returns, typically during treatment. Accurate relapse prediction would enable treatment strategies that take relapse risk into account, with potential benefits for all patients. Through analysis of diagnostic bone marrow biopsies, we show that single-cell RNA sequencing can predict future relapse occurrence. By analysing gene modules derived from an independent study of the gene expression response to the key drug prednisone, individual leukemic cells are predicted to be either resistant or sensitive to treatment. Quantification of the proportion of cells classified by single-cell transcriptomics as resistant or sensitive, accurately predicts the occurrence of future relapse in individual patients. Strikingly, the single-cell based classification is even consistent with the order of relapse timing. These results lay the foundation for risk-based treatment of MLL-rearranged infant ALL, through single-cell classification. This work also sheds light on the subpopulation of cells from which leukemic relapse arises. Leukemic cells associated with high relapse risk are characterized by a smaller size and a quiescent gene expression program. These cells have significantly fewer transcripts, thereby also demonstrating why single-cell analyses may outperform bulk mRNA studies for risk stratification. This study indicates that single-cell RNA sequencing will be a valuable tool for risk stratification of MLL-rearranged infant ALL, and shows how clinically relevant information can be derived from single-cell genomics.Key PointsSingle-cell RNA sequencing accurately predicts relapse in MLL-rearranged infant ALLIdentification of cells from which MLL-rearranged infant ALL relapses occur

Comprehensive cataloguing of the acute myeloid leukaemia (AML) genome has revealed a high frequency of mutations and deletions in epigenetic factors that are frequently linked to treatment resistance and poor patient outcome. In this review, we discuss how the epigenetic mechanisms that underpin normal haematopoiesis are subverted in AML, and in particular how these processes are altered in childhood and adolescent leukaemias. We also provide a brief summary of the burgeoning field of epigenetic-based therapies, and how AML treatment might be improved through provision of better conceptual frameworks for understanding the pleiotropic molecular effects of epigenetic disruption.

Deployment of distributed energy resources (DER) has rapidly increased during the last few years. The uptake of renewable energy and especially photovoltaic (PV) systems is of interest to utilities of remote and rural areas where the use of conventional power generation is costly. Investigating the effects of cloud movements on the power system of such areas at different PV penetrations is a relevant research topic. This paper reports on the data acquisition system deployed in a remote town in Western Australia and presents some of the findings and observations extracted from the captured real data. It then highlights the maximum PV output variations to identify the worst-case scenarios that should be considered when determining the maximum PV hosting capacity in that area. The studies show that inverter trip events have led to larger PV output variations in shorter intervals while the cloud movements have contributed to variations in longer intervals.

This article describes the radiation facilities and associated sample preparation, management, and analysis equipment currently in place at the Dalton Cumbrian Facility, a facility which opened in 2011 to support the UK’s nuclear industry. Examples of measurements performed using these facilities are presented to illustrate their versatility and the breadth of research they make possible. Results are presented from research which furthers our understanding of radiation damage to polymeric materials, radiolytic yield of gaseous products in situations relevant to nuclear materials, radiation chemistry in light water reactor cooling systems, material chemistry relevant to immobilization of nuclear waste, and radiation-induced corrosion of fuel cladding elements. Applications of radiation chemistry relevant to health care are also described. Research concerning the mechanisms of radioprotection by dietary carotenoids is reported. An ongoing open-labware project to develop a suite of modular sample handling components suited to radiation research is described, as is the development of a new neutron source able to provide directional beams of neutrons.

AimsTelephone consultations have been in clinical use since the early 1960s and are increasing in frequency and importance in many areas of medicine. With the advent of the COVID-19 pandemic in 2020, the use of telemedicine consultations increased dramatically alongside utilization of other digital technologies. Despite promise and potential advantages for clinicians (including remote working, improved time management and safety) there are known drawbacks to telephone consultations for psychiatrists. This includes limitations to assessments of mental state and risk, with loss of non-verbal communication often cited as a point in favour of more sophisticated technologies such as video calling. By adopting telephone consultations to a greater extent during the initial months of the COVID-19 pandemic in the Coventry Crisis Resolution and Home Treatment Team (CRHTT), we aimed to assess the patient experience in telehealth, through a patient survey.MethodAfter an initial assessment or follow-up consultation with a medical practitioner from the crisis team, patients were invited to take part in a short questionnaire with a member of the administration staff. This consisted of eight questions on a Likert scale and three open questions for comments. Results were collated and analyzed via Microsoft Excel.ResultMost patients found the telephone consultations satisfactory, with more than 90% returning positive scores in understanding, convenience and overall satisfaction. All patients felt listened to and that their confidentiality was maintained; with all but one respondent willing to engage in further consultations via the telephone. Negative scores were typically returned for practical telephonic problems including poor signal, interference and background noise. In their comments patients expressed largely positive views about their experience with their clinician; analysis revealed key insights into the patient experience, demonstrating the convenience, comfort and flexibility possible with ‘telepsychiatry’.ConclusionPatient experience of telemedicine in a UK psychiatric crisis team is mostly positive, with clear advantages for both patients and clinicians. Our results show telephone consultations can be expanded to new patient assessments alongside follow-ups, enabling the team to reach a greater number of service users. This includes service users who are housebound due to infirmity, required to shield or have significant anxiety about the pandemic.

Purpose: Robust preclinical models of pediatric acute lymphoblastic leukemia (ALL) are essential in prioritizing promising therapies for clinical assessment in high-risk patients. Patient-derived xenograft (PDX) models of ALL provide a clinically relevant platform for assessing novel drugs, with efficacy generally assessed by enumerating circulating human lymphoblasts in mouse peripheral blood (PB) as an indicator of disease burden. While allowing indirect measurement of disease burden in real time, this technique cannot assess treatment effects on internal reservoirs of disease. We explore benefits of bioluminescence imaging (BLI) to evaluate drug responses in ALL PDXs, compared with PB monitoring. BLI-based thresholds of drug response are also explored. Experimental Design: ALL PDXs were lentivirally transduced to stably express luciferase and green fluorescent protein. In vivo PDX responses to an induction-type regimen of vincristine, dexamethasone, and L-asparaginase were assessed by BLI and PB. Residual disease at day 28 after treatment initiation was assessed by flow cytometric analysis of major organs. BLI and PB were subsequently used to evaluate efficacy of the Bcl-2 inhibitor venetoclax. Results: BLI considerably accelerated and enhanced detection of leukemia burden compared with PB and identified sites of residual disease during treatment in a quantitative manner, highlighting limitations in current PB-based scoring criteria. Using BLI alongside enumeration of human lymphoblasts in PB and bone marrow, we were able to redefine response criteria analogous to the clinical setting. Conclusions: BLI substantially improves the stringency of preclinical drug testing in pediatric ALL PDXs, which will likely be important in prioritizing effective agents for clinical assessment. Clin Cancer Res; 23(14); 3744–55. ©2017 AACR.

Wearable GPS tracking devices have become commonplace coaching aids across professional field sports to enhance sports performances and reduce injury rates, despite the implications of the technology being poorly understood. This study looked at how GPS devices are used and the impact constant surveillance has upon the physical, psychological, and emotional health of rugby football workers. The disciplinary analysis of Michel Foucault was used to investigate how British Super League teams use wearable GPS technology, to investigate the dominant 'truth' that promotes surveillance technologies as 'universally beneficial' to athlete sports performance, health and well-being. Data was drawn from semi-structured interviews with three performance analysts/strength and conditioning coaches at three different Super League clubs across the North of England. Participants confessed data generated from wearable GPS is often totally ignored, despite being specifically produced to protect athlete health and wellbeing. When used, GPS data can become a 'disciplinary tool' to normalise and coerce players to comply with potentially unhealthy physical and psychological demands of a professional playing career. Importantly, regardless of how GPS data was used, the employment of wearable GPS devices was constantly and rigorously implemented. The constant surveillance experience by working players, when mismanaged or adopted as a coercive disciplinary tool, magnifies the uncertainty and fear of failure central to the predominant challenges that arise during a working football career. This leads to the acceptance of problematic norms damaging to physical, psychological, and emotional health. If GPS or other surveillance based performance analysis technologies are to be used in sport, coaches need to regulate or re-think their day-to-day use to avoid creating new harms to athlete health and well-being.

The prognosis for children diagnosed with high-risk acute lymphoblastic leukemia (ALL) remains sub-optimal, and more potent and less toxic treatments are urgently needed. We investigated the efficacy of a novel nicotinamide phosphoribosyltransferase inhibitor, OT-82, against a panel of patient-derived xenografts (PDXs) established from high-risk and poor outcome pediatric ALL cases. OT-82 was well-tolerated and demonstrated impressive single agent in vivo efficacy, achieving significant leukemia growth delay in 95% (20/21) and disease regression in 86% (18/21) of PDXs. In addition, OT-82 enhanced the efficacy of the established drugs cytarabine and dasatinib and, as a single agent, showed similar efficacy as an induction-type regimen combining three drugs used to treat pediatric ALL. OT-82 exerted its anti-leukemic action by depleting NAD(+) and ATP, inhibiting the NAD(+)-requiring DNA damage repair enzyme PARP-1, increasing mitochondrial ROS levels and inducing DNA damage, culminating in apoptosis induction. OT-82 sensitivity was associated with the occurrence of mutations in major DNA damage response genes, while OT-82 resistance was characterized by high expression levels of CD38. In conclusion, our study provides evidence that OT-82, as a single agent, and in combination with established drugs, is a promising new therapeutic strategy for a broad spectrum of high-risk pediatric ALL for which improved therapies are urgently needed.

African Horse Sickness (AHS) is a highly lethal, vector-borne viral disease of equids, endemic to sub-Saharan Africa but with a history of outbreaks into Europe. The pathogenesis of the virus is not fully understood; some studies have shown that certain proteins are linked to virulence, and that the outcome of infection is highly dependent on viral factors. Disease can also manifest with several different presentations in the equine host (fever form, cardiac form, pulmonary form and mixed form) but the mechanism underlying this variation is not fully understood. Pathogenicity and virulence studies of AHSV are difficult to perform in horses for logistical, ethical and financial reasons. As an alternative, Interferon-alpha receptor knockout (IFNAR-/-) mice have previously been used in AHSV vaccinology studies. Full pathology characterization of the AHSV infection in this model is the primary objective of our work, which will address questions regarding pathogenesis of AHSV. Here we present data collected from experimental infection of IFNAR (-/-) mice with a strain of AHSV serotype 4, including: clinical signs; histopathology; immuno-histochemical analysis of immune response to infection; antigen detection in tissues; and transmission electron microscopy of AHSV infected tissues. In addition, we will show data from experimental infection in this animal model comparing the pathogenicity of different AHSV strains. Results obtained indicate AHSV-4 infection is correlated with oedema and pneumonia in the lungs, inflammation in the liver and meningitis plus perivascular cuffing in the cerebrum. Other data shows that different strains of AHSV differ in terms of their pathogenicity and tropism.

Physical examination is an important tool in diagnosing patellofemoral problems. Due to the variety of different pathologies which can be exhibited in the joint, a systematic approach is recommended. The authors recommend a stepwise examination, with the patient examined standing, sitting and supine; in each, both a static and dynamic examination is performed. Systematic examination and accurate documentation of findings aid the choice of further investigations and management strategies.

Existing literature on the work of sports chaplains has focused primarily on practitioner accounts of chaplaincy with elite athletes. While these narratives provide useful descriptions of personal experience and practical application, they are largely devoid of theoretical grounding. This paper seeks to address this imbalance by proposing the need for sports chaplains to have a more critical understanding of sport and its relational dynamics. We begin by problematizing some of the historical assumptions underpinning elite sport, especially in relation to identity formation. We then explore some of the moral dilemmas which may be experienced by Christian athletes who inhabit contemporary sporting contexts. In line with the work of established sociological scholars, we then move to a critical analysis of performance-based identity and how an understanding of sociological concepts and ideas might assist chaplains in their work with elite athletes. The paper concludes by identifying sports chaplains as key figures in the disruption of performance-based identity.

Purpose: High tibial osteotomy (HTO) is a recognised treatment for medial compartment knee arthritis and in recent years has regained popularity. Preoperative planning of wedge opening is based on standing AP radiographs, aiming to deliver the WBL to a desired point. Clinical results can be unpredictable, and this may be due to an inability to deliver the preoperative plan. This study explores the theoretical wedge opening accuracy required to deliver preoperative plans, based on clinical AP radiographs. Methods: A theoretical 2-D model of osteotomy was developed to determine the degree of radiological wedge opening accuracy required to deliver the weight-bearing line to a preoperative target of 62–66 % of the width of the tibial plateau. Results: This model suggests that, to deliver the weight-bearing line to the preoperative target on plane radiographs, the theoretical medial wedge must be opened to an accuracy of ±0.9 mm. Conclusion: Although this study only explores a model of wedge opening based on AP radiographs, with current surgical systems, it is unlikely that the surgeon can achieve this level of accuracy within a real-life surgical setting. Surgical accuracy in HTO is known to be important for both short- and long-term clinical outcomes. This study highlights the need for improved surgical accuracy aids and/or patient stratification to mitigate the effects of surgical errors.

Empirical evidence demonstrates that performing artists are confronted by a variety of ‘bodily crises’ (e.g., injury, attrition of habits induced by ageing) over the course of their careers (Wainwright, Williams, & Turner, 2005). Such crises may present a serious threat to the embodied subject. Unfortunately, many prominent theories of skill acquisition (e.g., Fitts & Posner, 1967) appear to evacuate the body from performance by suggesting that any form of conscious processing (i.e., paying conscious attention to one's action during motor skill execution) will disrupt habitual behaviour. As a result, few researchers have considered how performers might tackle bodily anomalies. In the current paper, we seek to address this issue by discussing a variety of the ‘crises’ that confront the performing body. We start by discussing a number of disciplinary practices that may contribute to these crises. Next, we argue that habitual movements must be open to ‘acts of creativity’ in order to maintain a productive relationship between the performing body and the environment. Then we consider what this ‘creative action’ might involve and discuss a number of approaches (e.g., mindfulness, somaesthetic awareness) that could maintain and improve one's movement proficiency. Here, our argument draws on Dewey's (1922) pragmatist philosophy and his belief that ‘intelligent habit’ was required to help people to improve their movement functioning. Finally, we consider the implications of our argument for current conceptualisations of ‘habitual’ movement and recommend that researchers explore the adaptive and flexible capacity of the performing body.

The aim of this study was to consider the retirement experiences of British male professional association footballers by utilising Foucault’s analysis of discipline discussed in Discipline and Punish: The Birth of the Prison. Specifically, we drew upon Foucault to consider how, through the various techniques and instruments of discipline, the professional football context produces ‘docile footballing bodies’ and how this might influence a player’s experiences in retirement. We gathered our empirical material using a Foucauldian-informed interview framework with 25 former professional male football players between the ages of 21 and 34. Our analysis suggested that retirement from football was both a challenge and a relief for our participants, and that their extended period of time within football’s strong disciplinary apparatus significantly influenced how they experienced their retirement.

Increased storage of carbon in the oceans has been proposed as a mechanism to explain lower concentrations of atmospheric carbon dioxide during ice ages; however, unequivocal signatures of this storage have not been found1. In seawater, the dissolved gases oxygen and carbon dioxide are linked via the production and decay of organic material, with reconstructions of low oxygen concentrations in the past indicating an increase in biologically mediated carbon storage. Marine sediment proxy records have suggested that oxygen concentrations in the deep ocean were indeed lower during the last ice age, but that near-surface and intermediate waters of the Pacific Ocean—a large fraction of which are poorly oxygenated at present—were generally better oxygenated during the glacial1–3. This vertical opposition could suggest a minimal net basin-integrated change in carbon storage. Here we apply a dual-proxy approach, incorporating qualitative upper-water-column and quantitative bottom-water oxygen reconstructions4,5, to constrain changes in the vertical extent of low-oxygen waters in the eastern tropical Pacific since the last ice age. Our tandem proxy reconstructions provide evidence of a downward expansion of oxygen depletion in the eastern Pacific during the last glacial, with no indication of greater oxygenation in the upper reaches of the water column. We extrapolate our quantitative deep-water oxygen reconstructions to show that the respired carbon reservoir of the glacial Pacific was substantially increased, establishing it as an important component of the coupled mechanism that led to low levels of atmospheric carbon dioxide during the glacial. A downward expansion of oxygen depletion in the eastern Pacific Ocean during the last ice age suggests an increase in the respired carbon reservoir, contributing to the lower levels of atmospheric carbon dioxide during this period.

Background Surgical training has been subject to significant upheaval in recent years with an increasingly rigorous assessment regimen for trainees. The assessment of surgical trainers is less well evolved by comparison. Recent proposals from the Royal College of Surgeons of England recommend “professionalising the trainers.” However, they do not suggest any accepted or validated methods of trainer assessment, nor do they indicate how these might be implemented and monitored in a real-world training program to determine their effect on trainee outcomes. Aim To determine what is known about the attributes of successful surgical trainers. Methods We conducted a systematic review of the scientific literature using the preferred reporting items for systematic reviews and meta-analyses and Cochrane guidelines of the Medline database using specific search criteria. The qualitative analysis involved grouping trainer attributes together into “themes” within 4 “super-themes.” Each theme needed to be mentioned by a minimum of 5 studies. Results After review of the full study texts a total of 14 studies met the inclusion criteria. Thirteen studies involved the views of trainees, whereas only 1 study solely assessed the views of trainers. There was a wide variety of study designs and types of participants. The attribute themes are listed in brackets after each super-theme: “character” (approachability, patience, enthusiasm, encouraging/supportiveness), “procedural” (willingness to let trainee operate, balance between supervision and independence), “teamwork and communication” (sets educational aims and objectives, ability to use appropriate feedback, communication skills, and time availability to train) and “clinical” (capable, good relationships with patients, and the health care team). Conclusions This detailed review describes several perceived important themes for the positive attributes of surgical trainers. The identification of these key attributes is only of value if their presence is confirmed by effective and feasible evaluation, and if the possession of such attributes in trainers is proven to have a positive effect on training. In times of reduced training opportunities, exploring the topics raised by this review through future education research is warranted.

Researchers taking advantage of recent advancements in neural networks have made leaps in many fields such as image recognition, natural language processing, and speech recognition. However, little work has been done with neural networks in the field of binary analysis. Recently, researchers have used neural networks to recognize function boundaries in binaries, using only the bytes of the programs as features. In this paper, we extend their work to detect the bytes of bogus basic blocks added in the dead branches of opaque predicates. We perform a case study using the bogus control flow transformation offered by Obfuscator-LLVM. We detect the bytes of bogus basic blocks with a 94% F1 score. This information can be used to prune code for static reverse engineering. We believe this line of research will yield optimized triage, reverse engineering tools, and malware detection based on obfuscation identification using neural networks.

This chapter centres on the lives of disabled children and ‘Looked After Children’, many of whom are disabled. We ask: Can disabled children’s childhood studies (DCCS) be useful towards thinking about other forms of non-normative childhood? We focus on three areas: (i) surveillance and intimacy; (ii) pathology and psychologisation; and (iii) vulnerability and future. We conclude that DCCS offers new perspectives on the lives of Looked After Children and that it is a framework that can be used to think through other ‘non-normative’ childhoods.

Aims The aim of this to study was to compare the previously unreported long-term survival outcome of the Oxford medial unicompartmental knee arthroplasty (UKA) performed by trainee surgeons and consultants. Patients and Methods We therefore identified a previously unreported cohort of 1084 knees in 947 patients who had a UKA inserted for anteromedial knee arthritis by consultants and surgeons in training, at a tertiary arthroplasty centre and performed survival analysis on the group with revision as the endpoint. Results The ten-year cumulative survival rate for revision or exchange of any part of the prosthetic components was 93.2% (95% confidence interval (CI) 86.1 to 100, number at risk 45). Consultant surgeons had a nine-year cumulative survival rate of 93.9% (95% CI 90.2 to 97.6, number at risk 16). Trainee surgeons had a cumulative nine-year survival rate of 93.0% (95% CI 90.3 to 95.7, number at risk 35). Although there was no differences in implant survival between consultants and trainees (p = 0.30), there was a difference in failure pattern whereby all re-operations performed for bearing dislocation (n = 7), occurred in the trainee group. This accounted for 0.6% of the entire cohort and 15% of the re-operations. Conclusion This is the largest single series of the Oxford UKA ever reported and demonstrates that good results can be achieved by a heterogeneous group of surgeons, including trainees, if performed within a high-volume centre with considerable experience with the procedure. Cite this article: Bone Joint J 2016;(10 Suppl B):22–7.

Background Since 2011, the knee service at the Nuffield Orthopaedic Centre has been offering a neutralising medial opening wedge high tibial osteotomy (HTO) to a specific group of patients with genu varum and early knee osteoarthritis. An observation was made concerning this group of patients and the presence of CAM deformity at the hip. The aim of this study is to establish whether or not any association exists between the OA phenotype shared by our HTO group and the incidence of CAM deformity at the hip. Methods A cross-sectional study was designed to estimate the prevalence of CAM-type lesions across different groups of individuals. Our HTO group (n = 30) was compared to a prearthroplasty group (n = 20) and control group (n = 20). A total of 70 subjects were identified across the different groups all of whom had long-leg radiographs (LLRs) available for analysis. LLRs were analysed using an in house developed Matlab®-based (Matlab R2009b; MathWorks) software package for hip measurements and MediCAD® (Hectec GmbH, Germany) for lower limb alignment measurements. Results The HTO group had a significantly higher prevalence of CAM lesions (57%) than both the pre-arthroplasty (40%) and control (30%) groups. This difference was maintained when results were adjusted for potential confounding factors (age, gender and laterality). Across the groups, individuals with tibia vara were more likely to have CAM-deformity of the hip (p= 0.021). Conclusions Patients with symptomatic early knee OA and varus deformity of the knee have a high prevalence of CAM deformity in the hip.

In this article, we present a poststructuralist reading of Claire’s (a pseudonym) experiences of receiving video-based coaching in elite level field hockey. Data were gathered through a series of in-depth interviews that formed part of a recursive and iterative data collection and analysis process. Interpreting Claire’s stories through a neo-Foucauldian application of Mathiesen’s synopticon revealed how the presence of a video camera mediated Claire’s practice and imposed a critical gaze, one that became collectively and institutionally consumed. We argue that the thoughts presented in this paper have significant implications for coach practice and education and that, as a result, there is a need for further critical inquiry into coaches’ uses of video-based technology.

Care of infants ( We have used scRNA-seq to analyze the response to treatment of leukemic cells in bone marrow biopsies of seven MLLr-iALL patients, expressing either the oncogenic MLL-AF4 or MLL-ENL fusion gene, at the time of initial diagnosis. Three of these patients successfully underwent treatment and remained disease-free during 7 years of follow-up, while in the remaining four cases the disease returned within a year from diagnosis. All samples were subjected to scRNA-seq by FACS index sorting with the aim of identifying differences between early relapsers and long-term survivors. Quantification of the proportion of cells classified by single cell transcriptomics, categorized as either chemo-resistant or chemo-sensitive, accurately predicts the occurrence of future relapse in individual patients. Strikingly, the single cell-based classification is even consistent with the order of relapse timing. Additionally, leukemic cells associated with high relapse risk are typified by a small phenotype, which coincides with an apparent quiescent gene expression pattern. This study clearly and, to the best of our knowledge, for the first time shows how disease classification and treatment management can directly benefit from single cell genomics. It demonstrates how classification based on a pivotal functional characteristic of single cells can be performed, despite individual patient variation. Our results shed light on the subpopulation from which leukemic relapse originates, and opens up opportunities for strong, risk-based strategies for future MLLr-iALL treatment regimens. Disclosures Pieters: medac: Consultancy; jazz farmaceuticals: Consultancy.

In this Letter, ‘δ18C’ should have been ‘δ13C’ in Fig. 3b, and the x axis should extend to 50 kyr rather than 40 kyr. This figure has been corrected online.

The use of surveillance technologies as tools to encourage performance enhancement has become an accepted component of elite coaching. Those from the communities of sports physiology, psychology and biomechanics who promote the application of surveillance technologies have reported multiple benefits for the athlete. Conversely, several socio-cultural studies have suggested that surveillance technologies can lead to an oppressive mechanism of control over the athlete, significantly altering the role and responsibilities of the contemporary coach. In this critical commentary we use a post-structural position and adopt Foucault’s disciplinary analysis to contribute to the ongoing debate surrounding the use of surveillance technology in sport. Specifically, we achieve this by labelling surveillance technologies in sport as what Foucault (1977) might call, instruments of discipline, and by explaining the impact they have upon the working coach and the skilled athlete. We present some suggestions surrounding how to most appropriately utilise surveillance technologies in a sports coaching context and conclude by warning against a binary consideration of the use of technology as either good or bad.

Purpose Longitudinal cohort studies of knee OA aetiology use MRI to assess meniscal extrusion within the same knee at sequential time points. A validated method of assessment is required to ensure that extrusion is measured at the same location within the knee at each time point. Absolute perpendicular extrusion from the tibial edge can be assessed using the reference standard of segmentation of the tibia and medial meniscus. This is labour intensive and unsuitable for large cohorts. Two methods are commonly used as proxy measurements. Firstly, the apex of the medial tibial spine is used to identify a reproducible MRI coronal slice, from which extrusion is measured. Secondly, the coronal MRI slice of the knee demonstrating the greatest extrusion is used. The purpose of this study was to validate these two methods against the reference standard and to determine the most appropriate method to use in longitudinal cohort studies. We hypothesised that there is no difference in absolute meniscal extrusion measurements between methods. Methods Twenty high-resolution knee MRI scans were obtained in asymptomatic subjects. The tibia and medial meniscus were manually segmented. A custom MATLAB program was used to determine the difference in medial meniscal extrusion of the knee using the reference standard compared to the two other methods. Results Assessing extrusion using the single coronal MRI slice demonstrating the greatest extrusion overestimates the true extrusion of the medial meniscus. It incorrectly places the greatest meniscal extrusion at the anterior part of the tibia. Assessing extrusion using a consistent anatomical landmark, such as the medial tibial spine, most reliably corresponds to the reference of segmentation and measurement of true perpendicular extrusion from the tibial edge. Clinicians and researchers should consider this when assessing meniscal extrusion in the knee, and how it changes over time. Conclusion This study suggests measuring meniscal extrusion on the coronal MRI slice corresponding to the apex of the medial tibial spine as this correlates most closely with the true perpendicular extrusion measurements obtained from manually segmented models.

BCR-ABL1+ B progenitor acute lymphoblastic leukemia (Ph+ B-ALL) is an aggressive disease that frequently responds poorly to currently available therapies. Alterations in IKZF1, which encodes the lymphoid transcription factor Ikaros, are present in over 80% of Ph+ ALL and are associated with a stem cell–like phenotype, aberrant adhesion molecule expression and signaling, leukemic cell adhesion to the bone marrow stem cell niche, and poor outcome. Here, we show that FAK1 is upregulated in Ph+ B-ALL with further overexpression in IKZF1-altered cells and that the FAK inhibitor VS-4718 potently inhibits aberrant FAK signaling and leukemic cell adhesion, potentiating responsiveness to tyrosine kinase inhibitors, inducing cure in vivo. Thus, targeting FAK with VS-4718 is an attractive approach to overcome the deleterious effects of FAK overexpression in Ph+ B-ALL, particularly in abrogating the adhesive phenotype induced by Ikaros alterations, and warrants evaluation in clinical trials for Ph+ B-ALL, regardless of IKZF1 status.

Oxygen depletion in the upper ocean is commonly associated with poor ventilation and storage of respired carbon, potentially linked to atmospheric CO2 levels. Iodine to calcium ratios (I/Ca) in recent planktonic foraminifera suggest that values less than ∼2.5 μmol mol−1 indicate the presence of O2-depleted water. Here we apply this proxy to estimate past dissolved oxygen concentrations in the near surface waters of the currently well-oxygenated Southern Ocean, which played a critical role in carbon sequestration during glacial times. A down-core planktonic I/Ca record from south of the Antarctic Polar Front (APF) suggests that minimum O2 concentrations in the upper ocean fell below 70 μmol kg−1 during the last two glacial periods, indicating persistent glacial O2 depletion at the heart of the carbon engine of the Earth's climate system. These new estimates of past ocean oxygenation variability may assist in resolving mechanisms responsible for the much-debated ice-age atmospheric CO2 decline., Oxygen depletion in the ocean interior may be closely linked to atmospheric CO2 level, yet robust proxies are scarce. Here, using foraminiferal I/Ca as a proxy for oxygenation changes, the authors show that oxygen depletion in the upper waters of the high latitude Southern Ocean occurred during glacials.

Acute lymphoblastic leukemia (ALL) in children exemplifies how multi-agent chemotherapy has improved the outcome for patients. Refinements in treatment protocols and improvements in supportive care for this most common pediatric malignancy have led to a cure rate that now approaches 90%. However, certain pediatric ALL subgroups remain relatively intractable to treatment and many patients who relapse face a similarly dismal outcome. Moreover, survivors of pediatric ALL suffer the long-term sequelae of their intensive treatment throughout their lives. Therefore, the development of drugs to treat relapsed/refractory pediatric ALL, as well as those that more specifically target leukemia cells, remains a high priority. As pediatric malignancies represent a minority of the overall cancer burden, it is not surprising that they are generally underrepresented in drug development efforts. The identification of novel therapies relies largely on the reappropriation of drugs developed for adult malignancies. However, despite the large number of experimental agents available, clinical evaluation of novel drugs for pediatric ALL is hindered by limited patient numbers and the availability of effective established drugs. The Pediatric Preclinical Testing Program (PPTP) was established in 2005 to provide a mechanism by which novel therapeutics could be evaluated against xenograft and cell line models of the most common childhood malignancies, including ALL, to prioritize those with the greatest activity for clinical evaluation. In this article, we review the results of >50 novel agents and combinations tested against the PPTP ALL xenografts, highlighting comparisons between PPTP results and clinical data where possible.