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We used injury spotters and video footage review to establish the frequency of head impacts, their characteristics, and the subsequent medical assessment during the FIFA Arab Cup 2021

Several sports have published consensus statements on methods and reporting of epidemiological studies concerning injuries and illnesses with football (soccer) producing one of the first guidelines. This football-specific consensus statement was published in 2006 and required an update to align with scientific developments in the field. The International Olympic Committee (IOC) recently released a sports-generic consensus statement outlining methods for recording and reporting epidemiological data on injury and illness in sport and encouraged the development of sport-specific extensions.The Fédération Internationale de Football Association Medical Scientific Advisory Board established a panel of 16 football medicine and/or science experts, two players and one coach. With a foundation in the IOC consensus statement, the panel performed literature reviews on each included subtopic and performed two rounds of voting prior to and during a 2-day consensus meeting. The panel agreed on 40 of 75 pre-meeting and 21 of 44 meeting voting statements, respectively. The methodology and definitions presented in this comprehensive football-specific extension should ensure more consistent study designs, data collection procedures and use of nomenclature in future epidemiological studies of football injuries and illnesses regardless of setting. It should facilitate comparisons across studies and pooling of data.

Football (soccer) is a very popular team sport among African women and girls, with player numbers continuing to rise at all levels of the sport. Whereas the participation in football and associated injuries are on the rise, there are not enough sports and exercise medicine (SEM) personnel to attend to these women football players. While Africa may not currently have enough SEM trained medical doctors and/or physiotherapists, it has relatively higher numbers of other healthcare workers; for example, nurses, who lead healthcare services provision from community to tertiary levels. The objectives of this study will be to develop a task sharing approach to actively recruit and train nurses as pitch side responders in grassroots women’s football in Malawi’s Women’s Football League. This study will be a parallel randomised control trial will recruit 24 teams from the Women’s Football League in Malawi, which will be randomised to either the intervention group or the control group. A cohort of 12 nurses will receive training in basic football medicine; after which they will be attached to a total of 12 women’s football teams (intervention group) during one competitive season. The Football Nurses will be directly report to a physiotherapist or doctor in their district to whom they will refer serious injuries for investigations, or further management. The teams with Football Nurses will be compared to other teams that will not have Football Nurses. We expect to develop a low cost, sustainable and context relevant solution to manage the treatment gap of football injuries/illnesses in underserved communities such as women’s football.Trial registration numberPan African Clinical Trial Registry(PACTR202205481965514).

The dual‐specificity tyrosine‐regulated kinases DYRK1A and DYRK1B play a key role in controlling the quiescence‐proliferation switch in cancer cells. Serum reduction of U87MG 2D cultures or multi‐cellular tumour spheroids induced a quiescent like state characterized by increased DYRK1B and p27, and decreased pRb and cyclin D1. VER‐239353 is a potent, selective inhibitor of the DYRK1A and DYRK1B kinases identified through fragment and structure‐guided drug discovery. Inhibition of DYRK1A/B by VER‐239353 in quiescent U87MG cells increased pRb, DYRK1B and cyclin D1 but also increased the cell cycle inhibitors p21 and p27. This resulted in exit from G0 but subsequent arrest in G1. DYRK1A/B inhibition reduced the proliferation of U87MG cells in 2D and 3D culture with greater effects observed under reduced serum conditions. Paradoxically, the induced re‐expression of cell cycle proteins by DYRK1A/B inhibition further inhibited cell proliferation. Cell growth arrest induced in quiescent cells by DYRK1A/B inhibition was reversible through the addition of growth‐promoting factors. DYRK inhibition‐induced DNA damage and synergized with a CHK1 inhibitor in the U87MG spheroids. In vivo, DYRK1A/B inhibition‐induced tumour stasis in a U87MG tumour xenograft model. These results suggest that further evaluation of VER‐239353 as a treatment for glioblastoma is therefore warranted.

We sought to assess the risk of COVID-19 and seasonal flu including respiratory syncytial (RSV) and influenza viruses during the FIFA Arab Cup 2021 in Qatar with full capacity of spectators. We also, evaluated the post-event attitude toward resumption of mass football events.This was a cross-sectional study in which spectators (age ≥ 18 years) were invited for reverse-transcription PCR testing for COVID-19 and seasonal flu. At the same time, between 7 and 14 days after the event, the participants completed a self-administered questionnaire regarding their concerns during the tournament.The tournament included 16 international football teams from the Arab countries. As per the study protocol, 10,000 spectators were approached and 6,475 participated. Among the participants, 4,195 (65.1%), 2,253 (34.9%) and 27 (0.4%) were vaccinated with 2 doses, vaccinated with 3 doses, and recovered from SARS-Cov-2 infection, respectively. There were 61 (0.9%), 41(0.6%) and 11(0.2%) participants who tested positive for COVID-19, RSV and influenza (A/B), respectively. The average cycle threshold (Ct) value for COVID-19 positive cases was 26.1±7.3. Among those who were electronically approached, 6,102 completed the survey whereas 373 had incomplete survey. Overall, 2069 (33.9%) participants reported symptoms that theoretically could be related to COVID-19, of them 39 had positive PCR test (1.9%). Spectators (94.3%) were optimistic about returning sport events to the pre-pandemic status.There was no significant increase in the daily COVID-19 cases during FIFA Arab Cup 2021 with a full capacity of spectators. Therefore, upcoming mass football events can be held safely.

The serine/threonine kinase DYRK1A has been implicated in regulation of a variety of cellular processes associated with cancer progression, including cell cycle control, DNA damage repair, protection from apoptosis, cell differentiation, and metastasis. In addition, elevated-level DYRK1A activity has been associated with increased severity of symptoms in Down's syndrome. A selective inhibitor of DYRK1A could therefore be of therapeutic benefit. We have used fragment and structure-based discovery methods to identify a highly selective, well-tolerated, brain-penetrant DYRK1A inhibitor which showed in vivo activity in a tumor model. The inhibitor provides a useful tool compound for further exploration of the effect of DYRK1A inhibition in models of disease.

Medical handovers are fundamental to optimal patient care but can be a source of errors in clinical care with important implications on patient welfare and safety.1–4 Care of international athletes presents unique challenges to open and effective communication between medical teams. Handover of complete medical records should occur with athlete consent between medical teams on the transfer of an athlete between clubs. There are currently no specific guidelines or published recommendations advising sports and exercise medicine clinicians about medical handovers. The aim of this editorial is to provide a checklist of recommendations for the handover of elite athlete care between clubs and national medical and sports science teams, with lessons shared from professional football (soccer). Accurate clinical records are key to patient safety and protect patients and clinicians in sports medicine and science. In professional football for instance, there are currently 211 men’s5 and 159 women’s6 FIFA registered international football teams. Squads generally consist of 23 players, resulting in up to 8487 players being available for ‘call up’ to international fixtures. Medical and sports science resources vary widely across clubs, sports, sexes, countries, age groups and Para sports, and information available for handover will vary accordingly, creating challenges to meet …

This study aims to scope available peer-reviewed literature published in a FIFA language to understand the current quantity of research on women's football.Five databases were searched on the 15/12/2019. Studies were included when containing original research published in a peer-reviewed journal around female competitive football of any level, any age and on any subject. Author, journal, title and abstract of all included studies were scoped. Population assessed number of participants, level of play, age level of football and publication theme(s) were extracted.A total of 1,634 articles were scoped. The oldest publication dated back to 1939, whilst a total of 202 studies were gathered from 2019. The publication theme most frequently researched was sports medicine (N = 521) followed by strength and conditioning (N = 331) and sociology (N = 299). The majority of studies has focussed on elite (N = 442), senior (N = 977) players.A continuous growth in research attention has been seen. However, the numbers are not comparable to current research output levels in men's football. This study represents an essential first step in a larger 'research agenda-setting' project to determine research priorities for women's football during the next 10 years.

As we begin 2021, the international family of public policy and administration scholars and practitioners seeks to comprehend the turbulent events of the preceding year. These include the shockwave...

Background: High-speed running is commonly implicated in the genesis of hamstring injury. The success of hamstring injury management is typically quantified by the duration of time loss or reinjury rate. These metrics do not consider any loss in performance after returning to play from hamstring injury. It is not known to what extent high-speed running is altered on return to play after such injury. Hypothesis: Match high-speed running distance will change after returning from hamstring injury. Study Design: Non-randomized cohort. Level of Evidence: Level 3. Methods: Match high-speed running distance in highest level professional football (soccer, Rugby League, Rugby Union, and Australian Rules) were examined for a minimum of 5 games prior and subsequent to hamstring strain injury for individual differences using a linear regression models approach. A total of 22 injuries in 15 players were available for analysis. Results: Preinjury cumulative high-speed running distances were strongly correlated for each individual ( r2 = 0.92-1.0; P < 0.0001). Pre- and postinjury high-speed running data were available for a median of 15 matches (range, 6-15). Variance from the preinjury high-speed running distance was significantly less ( P = 0.0005) than the post injury values suggesting a suppression of high-speed running distance after returning from injury. On return to play, 7 of the 15 players showed a sustained absolute reduction in preinjury high-speed running distance, 7 showed no change, and 1 player (only) showed an increase. Analysis of subsequent (second and third injury) return to play showed no differences to return from the index injury. Conclusion: Return to play was not associated with return to high-speed running performance for nearly half of the players examined, although the same number showed no difference. Persisting deficits in match high-speed running may exist for many players after hamstring strain injury. Clinical Relevance: Returning to play does not mean returning to (high-speed running) performance for nearly half of the high-level professional football players examined in this study. This suggests that successful return to play metrics should be expanded from simple time taken and recurrence to include performance.

ObjectiveTo conduct a scoping review providing an overview of the health conditions occuring in retired male and female professional footballers, with an emphasis on musculoskeletal, mental, neurocognitive, cardiovascular and reproductive health conditions.MethodsIn January 2022, a comprehensive systematic literature search in three databases (MEDLINE via PubMed, SPORTDiscus via EBSCOhost and EMBASE) was conducted for common health conditions among retired male and female professional footballers. Primary research studies (full text available online) which described the incidence or prevalence of a health condition (musculoskeletal, mental, neurocognitive, cardiovascular, reproductive) among retired male and female professional footballers were included for review. Case reports, qualitative research and grey literature were omitted.ResultsIn total, 917 eligible articles were identified from the databases, with 41 meeting the eligibility criteria. Osteoarthritis of the hip, knee and ankle were found to be common among retired professional footballers. Mental health symptoms (eg, anxiety, depression) are experienced by retired male and female professional footballers. The incidence of neurocognitive disease appears to be higher among retired male professional footballers than among matched controls. There is very limited evidence examining the presence of health conditions in retired female professional footballers.ConclusionOsteoarthritis of the lower limb, musculoskeletal pain and mental health symptoms are common among retired professional footballers. Knowledge about the occurrence and timing of musculoskeletal, mental health and neurocognitive conditions among retired professional footballers can be used by a wide range of stakeholders to proactively intervene during and after a player’s career to mitigate risk.

OBJECTIVES: To establish agreement in National team contexts when players transition from club to National team about (i) what medical and physical information to collect, (ii) how to use information (iii) identifying challenges to collection and (iv) collection methods. DESIGN: Delphi survey. METHODS: A series of sequential online questionnaires were sent to heads of medical and performance of the 32 National teams following the FIFA 2018 World Cup. Two separate Delphi's; 'Medical' and 'Physical' were administered. The 'Medical' respondent was the person responsible for player health. 'Physical' referred to the person responsible for physical performance. Content analyses were performed, with subsequent rounds designed according to responses of the previous. Agreement was considered at ≥70%. RESULTS: Twenty-three Medical (72%) and 14 (44%) Physical heads participated in Round 1 (3 rounds total). Seventeen Medical and 12 Physical respondents completed all rounds. Medical information agreed upon injury epidemiology, screening and injury treatment strategies. Physical information included training/match-loads, fatigue, wellness and current exercise programmes. Both Medical and Physical agreed information should be used to plan and individualise player programmes. Additionally medical information should guide coaches' national team selection. Communication, willingness to share and quality/completeness of information were agreed as main challenges. Medical and Physical respondents agreed a standardised reporting form and electronic shared database as best option to collect information. CONCLUSIONS: Our findings highlight the importance of health and performance information exchange between national and club teams. Further, this exchange should be cooperative, symbiotic and a two-way process to assist with improving player health.

This document presents the recommendations developed by the IOC Medical and Scientific Commission and several international federations (IF) on the protection of athletes competing in the heat. It is based on a working group, meetings, field experience and a Delphi process. The first section presents recommendations for event organisers to monitor environmental conditions before and during an event; to provide sufficient ice, shading and cooling; and to work with the IF to remove regulatory and logistical limitations. The second section summarises recommendations that are directly associated with athletes’ behaviours, which include the role and methods for heat acclimation; the management of hydration; and adaptation to the warm-up and clothing. The third section explains the specific medical management of exertional heat stroke (EHS) from the field of play triage to the prehospital management in a dedicated heat deck, complementing the usual medical services. The fourth section provides an example for developing an environmental heat risk analysis for sport competitions across all IFs. In summary, while EHS is one of the leading life-threatening conditions for athletes, it is preventable and treatable with the proper risk mitigation and medical response. The protection of athletes competing in the heat involves the close cooperation of the local organising committee, the national and international federations, the athletes and their entourages and the medical team., publishedVersion

Background: Knee osteoarthritis (OA) is common amongst retired male professional footballers. There is limited understanding with respect to the interplay between imaging findings, clinical presentation and patient-reported outcome measures (PROMs) in retired professional footballers with knee OA. Objectives: This pilot study aimed to evaluate the extent of radiological and clinical knee OA in a cohort of retired male professional footballers, and to explore the relationship between these findings and knee-related PROMs. Methods: Fifteen retired male professional footballers underwent knee radiographs and were surveyed on their history of clinical OA, severe knee injury and previous knee surgery. The Knee Injury and Osteoarthritis Outcome Score Physical Function Short Form (KOOS-PS) and the Patient-Reported Outcomes Measurement Information System Global Health (PROMIS-GH) were used to assess health outcomes, such as level of function and pain. Results: Radiological knee OA was diagnosed in six out of 15 participants. Seven of the participants had a clinical diagnosis of knee OA. Evidence of clinical and radiological OA was present amongst four participants. Radiological knee OA and clinical OA was significantly associated with a history of severe knee injury and previous knee surgery. Low correlations (ρ

Pancreatic cancer (PanCa) is the third leading cause of cancer-related deaths in the United States with limited therapeutic options available. Gemcitabine (GEM), a deoxycytidine nucleoside analog is currently considered the most effective therapy for PanCa; however, it shows only a marginal survival benefit of 6 months. PanCa cells are addicted to ribosome biogenesis (RiBi) which supports their high rate of growth and proliferation. Therefore, strategically targeting the process of RiBi could be one of the ideal strategies for the prevention and treatment of PanCa. In this study, we for the first-time report that RPA194, a catalytic subunit of RNA Pol I is differentially expressed in normal pancreatic ductal epithelial (NPDE) and cancer cells. We also observed differential expression of RPA194 in various grades of pancreatic tumor tissues and its level was increased in high-grade pancreatic tumor tissues. We tested our hypothesis that targeting RPA194 with a non-toxic pharmacological inhibitor (BMH-21) will inhibit the growth of advanced PanCa. We observed that BMH-21 inhibits the growth and induced apoptosis of PanCa cells in a dose-dependent manner and this inhibition was correlated with the expression of RPA194. We observed proteasomal mediated degradation of RPA194 in PanCa cells. BMH-21 treatment inhibited RPA194 occupancy on rDNA but did not affect other nucleolar proteins (UBF, fibrillarin, nucleolin, and nucleophosmin). Two times the effective concentration of BMH-21 (5 µM) did not show any cytotoxic effect in NPDE cells. However, BMH-21 degraded RPA 194 protein in these cells in a similar manner as in PanCa cells. Therefore, we speculate that other proteins are involved in the selective toxicity of BMH-21 in PanCa cells. These findings were translated to in vivo model systems. We observed that BMH-21 significantly (P Citation Format: Mudassier Ahmad, Carlos Perez, Andrew Massey, Vivek Kashyap, Neeraj Chauhan, Haider Ahsan, Jasmine Jasmine, Manish Tripathi, Subhash Chauhan, Bilal Hafeez. Targeting ribosome biogenesis addition is a novel strategy for pancreatic cancer therapy [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr B035.

P-Rex1 is a guanine-nucleotide exchange factor (GEF) that activates Rac-type small G proteins in response to the stimulation of a range of receptors, particularly G protein-coupled receptors (GPCRs), to control cytoskeletal dynamics and other Rac-dependent cell responses. P-Rex1 is mainly expressed in leukocytes and neurons. Whereas its roles in leukocytes have been studied extensively, relatively little is known about its functions in neurons. Here, we used CRISPR/Cas9-mediated P-Rex1 deficiency in neuronal PC12 cells that stably overexpress the GPCR S1PR1, a receptor for sphingosine 1-phosphate (S1P), to investigate the role of P-Rex1 in neuronal GPCR signalling and cell responses. We show that P-Rex1 is required for the S1P-stimulated activation of Rac1 and Akt, basal Rac3 activity, and constitutive cAMP production in PC12-S1PR1 cells. The constitutive cAMP production was not due to increased expression levels of major neuronal adenylyl cyclases, suggesting that P-Rex1 may regulate adenylyl cyclase activity. P-Rex1 was required for maintenance of neurite protrusions and spreading in S1P-stimulated PC12-S1PR1 cells, as well as for cell-cycle progression and proliferation. In summary, we identified novel functional roles of P-Rex1 in neuronal Rac, Akt and cAMP signalling, as well as in neuronal cell-cycle progression and proliferation.

This infographic outlines evidence-based recommendations on COVID-19 reverse transcriptase PCR (RT-PCR) testing in elite sport settings, aiming to protect personal and population health, and acknowledging resources and expertise that are often available in elite sport. Public health recommendations vary by country and region, and protocol decisions should be made in consultation with relevant public health authorities. An expert, multidisciplinary group with input from clinical virology, microbiology, public health, infectious diseases and sports medicine provides optimal implementation and interpretation of testing. Interventions to prevent COVID-19 transmission should be implemented consistently1 2 and should include The current gold standard of testing is RT-PCR testing.4–6 The test is highly sensitive and specific to SARS-CoV-2 viral RNA in laboratory conditions.2 Test results should be interpreted on the basis of the pretest probability, previous test …

The kinase DYRK1A is an attractive target for drug discovery programs due to its implication in multiple diseases. Through a fragment screen, we identified a simple biaryl compound that is bound to the DYRK1A ATP site with very high efficiency, although with limited selectivity. Structure-guided optimization cycles enabled us to convert this fragment hit into potent and selective DYRK1A inhibitors. Exploiting the structural differences in DYRK1A and its close homologue DYRK2, we were able to fine-tune the selectivity of our inhibitors. Our best compounds potently inhibited DYRK1A in the cell culture and in vivo and demonstrated drug-like properties. The inhibition of DYRK1A in vivo translated into dose-dependent tumor growth inhibition in a model of ovarian carcinoma.

The COVID-19 pandemic has had, and will have, profound effects on every person on earth. Measures advocated by the WHO and put in place by national governments, businesses and individuals will save millions of lives, but current movement restrictions (ie, various degrees of lockdown) cannot continue indefinitely. The activity restrictions imposed by governments are designed to reduce human-to-human transmission; they buy time and allow international collaboration between governments and internally to build and allocate the resources and systems to 1. Test: every suspected case where testing is merited and available while having effective prevention strategies in place. 2. Trace: follow up all confirmed cases of COVID-19 and contact trace every relevant contact to identify and cut off transmission. 3. Treat: manage all cases effectively, with adequate intensive care unit capacity, ventilators and staff. Rightly, professional sport has been placed on hold during the COVID-19 pandemic. The WHO (#BeActive) and many governments continue to promote certain types of moderate physical activity for the benefits it confers on the immune system and physical and mental health.1–4 Sport has health, social and economic benefits for individuals and society, and when the COVID-19 pandemic is better ‘controlled’, it may be appropriate to reintroduce community sport and professional sport. In this editorial, we opine on what needs to be in place for professional sport to recommence. The relaxation of movement/activity/business restrictions is likely to happen over a gradual period, and time frames will differ across nations and even within nations. The following is expected5

Football stakeholders have been advised to exercise caution when determining when to reintroduce professional football due to the risks of COVID-19 overburdening health services and also concerns regarding potential negative health sequelae for players who contract the disease.1 There are considerable economic, social and wider incentives attached to resuming professional football. Should this occur prematurely it would present significant ethical and medical challenges to medical teams. Robust risk assessment and mitigation procedures would facilitate professional football to return in some format despite the ongoing pandemic,2 but they will not eliminate risk completely. This article considers the evolving science pertinent to professional footballers in the context of COVID-19, with the overarching purpose to ensure the health and safety of players, staff, their families and the general public. The primary focus of this article is on strategies to reduce the risk of human-to-human transmission during football activity, aspects of which will be relevant to other sports. Specific risk factors including the contact nature of football and travel demands can increase transmission of COVID-19. Medical teams will be expected to implement interventions which mitigate this risk. The following coreprinciples (figures 1 …

ObjectivesThe purpose of this study was to explore the leadership experiences of elite football team physicians during the COVID-19 pandemic.MethodsA pilot-study based on a cross-sectional design by means of an electronic survey was conducted. The survey relied on 25 questions divided into distinct sections including among others professional and academic experience, leadership experiences and perspectives.ResultsA total of 57 physicians (91% male; mean age: 43 years) gave their electronic informed consent and completed the survey. All participants agreed that the demands of their role had increased during the COVID-19 pandemic. Fifty-two (92%) participants reported that they felt they were expected to take more of a leadership role during the COVID-19 pandemic. Eighteen (35%) reported feeling under pressure to make clinical decisions which were not in keeping with best clinical practice. Additional roles, duties and demands expected of team doctors during the COVID-19 pandemic were subdivided into communication, decision-making, logistical, and public health demands.ConclusionThe findings from this pilot study suggest that the way in which team physicians at professional football clubs operate has altered since the onset of the COVID-19 pandemic, with greater demands placed on leadership skills including decision-making, communication and ethical stewardship. This has potential implications for sporting organisations, clinical practice and research.

Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States with limited therapeutic approaches. Dysregulation of the ribosome biogenesis process was observed in various cancer including pancreatic cancer. Therefore, strategically targeting ribosome biogenesis could be a novel approach for pancreatic cancer treatment. One such approach is to target ribosome biogenesis is via small molecule inhibitors of RNA Polymerase I as these inhibitors have shown promising anti-cancer activity in pre-clinical and clinical studies. We observed differential constitutive expression of various ribosomal proteins including RPA-194 in human PanCa cells when compared with normal HPDE cells. Therefore, we hypothesized that targeting RNA pol I will inhibit the growth of pancreatic cancer. In this study, we for the first time evaluated the therapeutic effect of a novel RNA polymerase I inhibitor (BMH-21) against PanCa in pre-clinical model systems. BMH-21 significantly inhibited the ribosome biogenesis process in various pancreatic cancer cells (Panc-1, AsPC1, BxPC3, MiaPaCa-2) as determined by inhibition of rRNA synthesis and POL I occupancy on rDNA. BMH-21 treatment of pancreatic cancer cells significantly degraded RPA194 protein as determined by Western blot and confocal microscopy analysis. BMH-21 treatment (0.25-5µM) showed differential IC50 in various pancreatic cancer cells which were correlated with the expression of its target proteins RPA194 and RPA135 expression. In our flow cytometry experiment, we observed a significant G0/G1 cell cycle arrest and increase Annexin V and Annexin V7-AAD positive cells in BMH-21 treated pancreatic cancer cells as compared to the vehicle treatment group suggesting its apoptosis-inducing potential in pancreatic cancer cells. BMH-21 treatment inhibited growth and metastatic phenotypes of various PanCa cells as analyzed by various functional assays (colony formation and atomic force microscopy analyses). We also evaluated the effect of BMH-21 on various kinases, which regulate ribosome biogenesis. Interestingly, we observed BMH-21 significantly (P Citation Format: Carlos Perez, Mudassier Ahmad, Andrew Massey, Asif Shahriar, Emmanuel Anning, Vivek Kashyap, Neeraj Chauhan, Anupam Dhasmana, Manish Tripathi, Subhash Chauhan, Bilal Hafeez. Targeting ribosome biogenesis is a novel strategy to suppress the growth of pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3950.

The cessation of amateur and recreational sport has had significant implications globally, impacting economic, social and health facets of population well-being. As a result, there is pressure to resume sport at all levels. The ongoing prevalence of SARS-CoV-2 and subsequent ‘second waves’ require urgent best practice guidelines to be developed to return recreational (non-elite) sports as quickly as possible while prioritising the well-being of the participants and support staff.This guidance document describes the need for such advice and the process of collating available evidence. Expert opinion is integrated into this document to provide uniform and pragmatic recommendations, thereby optimising on-field and field-side safety for all involved persons, including coaches, first responders and participants.The nature of SARS-CoV-2 transmission means that the use of some procedures performed during emergency care and resuscitation could potentially be hazardous, necessitating the need for guidance on the use of personal protective equipment, the allocation of predetermined areas to manage potentially infective cases and the governance and audit of the process.

Activating stimulator of interferon genes to turn immunologically refractive cold tumor hot is an exciting therapeutic approach to increase the clinical responsiveness of some human cancers to immune checkpoint inhibitors. DNA damaging drugs and PARP inhibitors are two types of agents that have demonstrated this potential. Inhibitors of Chk1 or Wee1 induce DNA damage in cancer cells in predominantly the S-phase population. Increased cytoplasmic single-stranded and double-stranded DNA (dsDNA) from this DNA damage resulted in increased tank-binding kinase 1 (TBK1) phosphorylation in a range of cancer cell lines. However, despite robust increases in pTBK1, no downstream consequences of TBK1 phosphorylation were observed (namely no increase in pIRF3/7, interferon regulatory factor (IRF)-dependent gene expression or a type I IFN response). In combination with cytotoxic chemotherapy such as gemcitabine or camptothecin (CPT), Chk1 inhibition increased cytoplasmic dsDNA compared with the cytotoxic alone but attenuated the cytotoxic chemotherapy-induced increase in IRF1 protein and STAT1 phosphorylation through inhibition of nuclear RelB translocation. Despite increased cytoplasmic DNA and TBK1 activation, inhibition of Chk1, ataxia telangiectasia and Rad3-related protein, or Wee1 failed to activate a type I IFN response. We discuss the potential underlying mechanisms for this lack of IRF-dependent gene response and how this might influence the clinical strategies of combining Chk1 or Wee1 inhibitors with immune checkpoint inhibitors.

The principal lesson of this chapter is that politics is the driving force for change, not managerial or technocratic efficiency drivers; managerialism is a tool of control. This has profound consequences for issues of accountability. The chapter focuses on the contours of accountability within the context of the contemporary UK reform agendas through an exploration of the different theoretical perspectives and the use of case studies, considering issues such as blame-gaming, culpability avoidance and how network-based approaches to reform pose difficulties for transparent lines of accountability. It reminds us that states and their public administration systems are comprised of individuals who are also members of institutions. Institutions cannot possess a human personality, but consist of people all with a persona, and it is this that institutions are designed and constructed to influence, to control and to serve, often simultaneously. In this chapter, literature on policy networks and accountability is examined in order to bring such challenges to the fore in the context of public value debates in Britain.