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Increasingly, globalization and the adoption of a market economy have made innovation fundamental for the success of professional sport organizations. Yet oligarchical league structures, isomorphic and hyper-traditional cultures, and hierarchical organizational structures can enhance or hinder organizational creativity, the beginning stage of the innovation process. Therefore, the purpose of this research is to determine the antecedents of organizational creativity in professional sport organizations. Perception of organizational creativity is theorized to be influenced by employee creativity, work environment, and the social interactions of employees. The results, based on a survey of three professional sport organizations’ front offices, indicated perceptions of a work environment with a clear vision and better work processes were associated with greater perceptions of organizational creativity. The lack of relationships between many of the factors theorized to influence organizational creativity, such as an employee’s advice network, could indicate the sport industry is unique in creativity management. This study is the beginning in understanding the first step of innovation, and the processes that influence employees’ perceptions regarding the ways in which their work environment relate to organizational creativity.

This case study analyzed the innovation processes that led to the adoption of a work-integrated learning program among several sport organizations. A comparative case study analysis was used to deduce the commonly shared determinants between each of the sport organizations. Notably, having an innovation champion was a key determination. As well, lack of resources regarding staffing, the involvement of the managers with the participating higher education institution, the ease of contract design, and access to good candidates for the program were also influential in the innovation process. This study revealed, for sport organizations facing similar issues, that the graduate apprenticeship program could provide benefits. As well for sport management program, it could provide a stronger relationship with regional sport organizations. This research also extends the body of research regarding the underlying mechanisms by which sport organizations innovate generally.

The purpose of this study was to examine the effects of employees’ extra-role behaviors on desired organizational outcomes in sport. An assessment of innovative work behaviors and organizational ci...

Conventional approaches to isolate and characterize nanobodies are laborious. We combine phage display, multivariate enrichment, next-generation sequencing, and a streamlined screening strategy to identify numerous anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nanobodies. We characterize their potency and specificity using neutralization assays and hydrogen/deuterium exchange mass spectrometry (HDX-MS). The most potent nanobodies bind to the receptor binding motif of the receptor binding domain (RBD), and we identify two exceptionally potent members of this category (with monomeric half-maximal inhibitory concentrations around 13 and 16 ng/ml). Other nanobodies bind to a more conserved epitope on the side of the RBD and are able to potently neutralize the SARS-CoV-2 founder virus (42 ng/ml), the Beta variant (B.1.351/501Y.V2) (35 ng/ml), and also cross-neutralize the more distantly related SARS-CoV-1 (0.46 μg/ml). The approach presented here is well suited for the screening of phage libraries to identify functional nanobodies for various biomedical and biochemical applications.

Conventional approaches to isolate and characterize nanobodies are laborious and cumbersome. Here we combine phage display, multivariate enrichment, and novel sequence analysis techniques to annotate an entire nanobody repertoire from an immunized alpaca. We combine this approach with a streamlined screening strategy to identify numerous anti-SARS-CoV-2 nanobodies, and use neutralization assays and Hydrogen/Deuterium exchange coupled to mass spectrometry (HDX-MS) epitope mapping to characterize their potency and specificity. Epitope mapping revealed that the binding site is a key determinant of neutralization potency, rather than affinity alone. The most potent nanobodies bind to the receptor binding motif of the RBD, directly preventing interaction with the host cell receptor ACE2, and we identify two exceptionally potent members of this category (with monomeric IC50s around 13 and 16 ng/ml). Other nanobodies bind to a more conserved epitope on the side of the RBD, and are able to potently neutralize the SARS-CoV-2 founder virus (42 ng/ml), the beta variant (B.1.351/501Y.V2) (35 ng/ml), and also cross-neutralize the more distantly related SARS-CoV-1 (0.46 μg/ml). The approach presented here is well suited for the screening of phage libraries to identify functional nanobodies for various biomedical and biochemical applications.

SARS-CoV-2 Variants of Concern (VOCs) with resistance to neutralizing antibodies are threatening to undermine vaccine efficacy. Vaccination and infection have led to widespread humoral immunity against the pandemic founder (Wu-Hu-1). Against this background, it is critical to assess the outcomes of subsequent immunization with variant antigens. It is not yet clear whether heterotypic boosts would be compromised by original antigenic sin, where pre-existing responses to a prior variant dampen responses to a new one, or whether the memory B cell repertoire would bridge the gap between Wu-Hu-1 and VOCs. We show, in macaques immunized with Wu-Hu-1 spike, that a single dose of adjuvanted beta variant receptor binding domain (RBD) protein broadens neutralizing antibody responses to heterologous VOCs. Passive transfer of plasma sampled after Wu-Hu-1 spike immunization only partially protects K18-hACE2 mice from lethal challenge with a beta variant isolate, whereas plasma sampled following heterotypic RBD boost protects completely against disease., Graphical Abstract, The emergence and spread of antibody-resistant SARS-CoV-2 Variants of Concern (VOCs) threatens to diminish vaccine efficacy. Sheward et al. show, in rhesus macaques and K18-hACE2 mice, that reduced vaccine protection against VOCs can be restored by broadening antibody responses with a third, heterotypic RBD booster immunization.

The emergence of SARS-CoV-2 Variants of Concern (VOCs) with mutations in key neutralizing antibody epitopes threatens to undermine vaccines developed against the pandemic founder variant (Wu-Hu-1). Widespread vaccine rollout and continued transmission are creating a population that has antibody responses of varying potency to Wu-Hu-1. Against this background, it is critical to assess the outcomes of subsequent immunization with variant antigens. It is not yet known whether heterotypic vaccine boosts would be compromised by original antigenic sin, where pre-existing responses to a prior variant dampen responses to a new one, or whether the primed memory B cell repertoire would bridge the gap between Wu-Hu-1 and VOCs. Here, we show that a single adjuvanted dose of receptor binding domain (RBD) protein from VOC 501Y.V2 (B.1.351) drives an extremely potent neutralizing antibody response capable of cross-neutralizing both Wu-Hu-1 and 501Y.V2 in rhesus macaques previously immunized with Wu-Hu-1 spike protein. Passive immunization with plasma sampled following this boost protected K18-hACE2 mice from lethal challenge with a 501Y.V2 clinical isolate, whereas only partial protection was afforded by plasma sampled after two Wu-Hu-1 spike immunizations.

BACKGROUND: We aimed to describe the gender-based disparities in burn injury patterns, care received, and mortality across national income levels. METHODS: In the WHO Global Burn Registry (GBR), we compared patient demographics, injury characteristics, care and outcomes by sex using Chi-square statistics. Logistic regression was used to identify the associations of patient sex with surgical treatment and in-hospital mortality. RESULTS: Among 6,431 burn patients (38% female; 62% male), females less frequently received surgical treatment during index hospitalization (49% vs 56%, p

What is organizational behavior, and why should sport managers study it? This chapter introduces the foundations of organizational behavior as it relates to organizational success in the sports industry. Concepts discussed include positive organizational behavior, institutional theory, and resource dependency. The topics introduced in this chapter will receive substantial discussion throughout the remaining chapters of this book.

Organizational behavior is heavily influenced by internal factors such as organizational culture, size, and access to resources. External factors, including societal influences, politics, and employee identification, further alter how organizations interact with stakeholders, including employees and volunteers. This chapter defines and categorizes sport organizations as unique organizations and deserving of study within the broader management disciplines. As students read through this chapter, they will be introduced to important concepts which will be discussed throughout the remainder of this book.

This chapter presents an underutilized topic in sport management: labor. Within this chapter, we take a broad view of the impacts on labor and how labor impacts sport organization employees. The chapter starts with the history of labor and how it has evolved in America. Much of the content in this section is not specifically sport-related, but it is nonetheless essential to have an understanding of how labor is utilized. We then discuss how the law has shaped labor throughout history. We also explore the debate of collegiate student-athletes as employees and what that would mean for the collegiate sports industry. Lastly, the concept of emotional labor is put forth to demonstrate how not all labor is physical.

Sport employees engage in behaviors at their workplace every day that impact the organization’s overall success. Those behaviors can be defined as in-role or extra-role behaviors. Extra-role behaviors include organizational citizenship behaviors, as well as creative behaviors. Employee creativity is influenced by domain-relevant skills, intrinsic task motivation, and engagement in creativity-related processes. Those processes can be broken up into three stages: problem identification, information searching and encoding, and idea generation. Other influential mechanisms for managers to encourage creative behaviors include autonomy, time and space, rest, and specific idea generation activities, including juxtapositioning and divergent thinking.

This chapter covers a wide array of motivational theories. It starts with a review of well-known practical perspectives, such as equity theory and expectancy theory. From there, a discussion of Maslow’s hierarchy of needs and Herzberg’s motivational hygiene theory is conducted. A prominent theory of motivation, self-determination theory, is then covered and applied to the sports industry. The chapter finishes by examining contemporary constructs (i.e., authenticity and grit) and their potential application within the sports industry.

As has been widely discussed throughout this book, communication between sport organizations and their employees is a critical but challenging process. We’ve also discussed the importance of organizational culture in defining the organization’s identity, as well as the role person-organization fit plays in helping employees determine if their values are in line with those of their employer. This chapter explores how each of those topics relates to how sport organizations socialize new employees into the organization. Specifically, we’ll examine how organizations communicate with new employees and how new employees search for and perceive information about their workplace. The chapter ends with a brief discussion on psychological contracts between sport employees and sport organizations.

Communication is one of the most challenging yet important tasks that any organization undertakes. Communication allows employees to learn about organizational goals, share ideas, and develop plans. However, organizational messages are only useful if they are received and understood by the intended audience. This chapter explores the communication process, from identifying the intended audience, choosing the proper communication channel, and delivering the message so that it can be understood. This chapter also explores the challenges for lower-tier employees in getting their messages to upper administration.

This chapter covers all aspects of diversity, equity, and inclusion as it relates to sport organizations. There are four major aspects of diversity to consider: ethical, legal, economic, and consumer/participant. First, understanding what diversity and inclusion are provides the foundation for building a better sport organization. The research in sport management indicates diversity and inclusion can be beneficial to the organization. Practical steps and considerations for improving diversity and inclusion in sport organizations are discussed in this chapter. This includes diversity statements, recruitment strategies, hiring process issues, programming, and organizational structure.

Conflict is often seen to be a negative word within organizations. Unchecked, conflict can cause many issues that will tear teams and organizations apart. However, a lack of conflict can be just as detrimental. This chapter differentiates between functional conflict that can benefit an organization and dysfunctional forms of conflict, which can be extremely harmful to an organization’s health. We will then discuss structural and contextual factors that influence conflict within sport organizations. The chapter ends with a discussion about negotiation.

This chapter describes the various forms of personality among individuals and how their personality can contribute to their “fit” with their organization. This chapter discusses various personality frameworks such as the DISC profile, the Big 5, and Myers-Briggs’ perspectives. We also explain how one’s beliefs and value systems guide one’s decision-making processes. The chapter concludes with a review of the concept of “person-environment fit” and its various subcomponents.

Innovation does not happen alone. Building a creative and innovative work team increases the likelihood of successful innovation in sport organizations. When innovation is the goal, these elements need to be considered: leader-member exchange, participative safety, vision and goal clarity, support for innovation, task orientation, diversity of thought, social interaction, and resources, such as time and rewards. Innovation in a sport organization can include positive changes to process or structure, as well as new products. The process of innovation has been theorized as a three-stage process: idea initiation, idea adoption decision, and idea implementation. In that process, identifying and supporting an innovation champion has been shown to increase the likelihood of an idea’s success in an organization.

Emotions are a part of everyone’s life, and the workplace is no different. This chapter will look at both traditional and contemporary perspectives of how humans perceive and generate emotions. Concepts such as emotional intelligence, pride, passion, and well-being are all examined. The chapter also includes a discussion on how emotions are particularly relevant and important in the sport workplace.

For HIV, the time since infection can be estimated from sequence data for acutely infected samples. One popular approach relies on the star-like nature of phylogenies generated under exponential population growth, and the resulting Poisson distribution of mutations away from the founding variant. However, real-world complications, such as APOBEC hypermutation and multiple-founder transmission, present a challenge to this approach, requiring data curation to remove these signals before reasonable timing estimates may be obtained. Here we suggest a simple alternative approach that derives the timing estimate not from the entire mutational spectrum but from the proportion of sequences that have no mutations. This can be approximated quickly and is robust to phenomena such as multiple founder transmission and APOBEC hypermutation. Our approach is Bayesian, and we adopt a conjugate prior to obtain closed form posterior distributions at negligible computational expense. Using real data and simulations, we show that this approach provides accurate timing estimates and credible intervals without the inconvenience of data curation and is robust to complicating phenomena that can mislead existing approaches or cause them to fail entirely. For immediate use we provide an implementation via Google Sheets, which offers bulk analysis of multiple datasets, as well as more detailed individual-donor analyses. For inclusion in data processing pipelines we provide implementations in three languages: Julia, R, and Python.

The neural circuits responsible for animal behavior remain largely unknown. We summarize new methods and present the circuitry of a large fraction of the brain of the fruit fly Drosophila melanogaster. Improved methods include new procedures to prepare, image, align, segment, find synapses in, and proofread such large data sets. We define cell types, refine computational compartments, and provide an exhaustive atlas of cell examples and types, many of them novel. We provide detailed circuits consisting of neurons and their chemical synapses for most of the central brain. We make the data public and simplify access, reducing the effort needed to answer circuit questions, and provide procedures linking the neurons defined by our analysis with genetic reagents. Biologically, we examine distributions of connection strengths, neural motifs on different scales, electrical consequences of compartmentalization, and evidence that maximizing packing density is an important criterion in the evolution of the fly’s brain., eLife digest Animal brains of all sizes, from the smallest to the largest, work in broadly similar ways. Studying the brain of any one animal in depth can thus reveal the general principles behind the workings of all brains. The fruit fly Drosophila is a popular choice for such research. With about 100,000 neurons – compared to some 86 billion in humans – the fly brain is small enough to study at the level of individual cells. But it nevertheless supports a range of complex behaviors, including navigation, courtship and learning. Thanks to decades of research, scientists now have a good understanding of which parts of the fruit fly brain support particular behaviors. But exactly how they do this is often unclear. This is because previous studies showing the connections between cells only covered small areas of the brain. This is like trying to understand a novel when all you can see is a few isolated paragraphs. To solve this problem, Scheffer, Xu, Januszewski, Lu, Takemura, Hayworth, Huang, Shinomiya et al. prepared the first complete map of the entire central region of the fruit fly brain. The central brain consists of approximately 25,000 neurons and around 20 million connections. To prepare the map – or connectome – the brain was cut into very thin 8nm slices and photographed with an electron microscope. A three-dimensional map of the neurons and connections in the brain was then reconstructed from these images using machine learning algorithms. Finally, Scheffer et al. used the new connectome to obtain further insights into the circuits that support specific fruit fly behaviors. The central brain connectome is freely available online for anyone to access. When used in combination with existing methods, the map will make it easier to understand how the fly brain works, and how and why it can fail to work correctly. Many of these findings will likely apply to larger brains, including our own. In the long run, studying the fly connectome may therefore lead to a better understanding of the human brain and its disorders. Performing a similar analysis on the brain of a small mammal, by scaling up the methods here, will be a likely next step along this path.

The neural circuits responsible for animal behavior remain largely unknown. We summarize new methods and present the circuitry of a large fraction of the brain of the fruit fly Drosophila melanogaster. Improved methods include new procedures to prepare, image, align, segment, find synapses in, and proofread such large data sets. We define cell types, refine computational compartments, and provide an exhaustive atlas of cell examples and types, many of them novel. We provide detailed circuits consisting of neurons and their chemical synapses for most of the central brain. We make the data public and simplify access, reducing the effort needed to answer circuit questions, and provide procedures linking the neurons defined by our analysis with genetic reagents. Biologically, we examine distributions of connection strengths, neural motifs on different scales, electrical consequences of compartmentalization, and evidence that maximizing packing density is an important criterion in the evolution of the fly’s brain.

The neural circuits responsible for behavior remain largely unknown. Previous efforts have reconstructed the complete circuits of small animals, with hundreds of neurons, and selected circuits for larger animals. Here we (the FlyEM project at Janelia and collaborators at Google) summarize new methods and present the complete circuitry of a large fraction of the brain of a much more complex animal, the fruit fly Drosophila melanogaster. Improved methods include new procedures to prepare, image, align, segment, find synapses, and proofread such large data sets; new methods that define cell types based on connectivity in addition to morphology; and new methods to simplify access to a large and evolving data set. From the resulting data we derive a better definition of computational compartments and their connections; an exhaustive atlas of cell examples and types, many of them novel; detailed circuits for most of the central brain; and exploration of the statistics and structure of different brain compartments, and the brain as a whole. We make the data public, with a web site and resources specifically designed to make it easy to explore, for all levels of expertise from the expert to the merely curious. The public availability of these data, and the simplified means to access it, dramatically reduces the effort needed to answer typical circuit questions, such as the identity of upstream and downstream neural partners, the circuitry of brain regions, and to link the neurons defined by our analysis with genetic reagents that can be used to study their functions.Note: In the next few weeks, we will release a series of papers with more involved discussions. One paper will detail the hemibrain reconstruction with more extensive analysis and interpretation made possible by this dense connectome. Another paper will explore the central complex, a brain region involved in navigation, motor control, and sleep. A final paper will present insights from the mushroom body, a center of multimodal associative learning in the fly brain.

During the first 24 h of embryonic development the zebrafish embryo undergoes a remarkable change from a single cell to a highly developed body. An initial period of very rapid cleavages is followed by the complex morphogenetic movements of gastrulation in which the initial body of the embryo forms on one side of the yolk, with the future tissues of the internal organs in the innermost cell layers and the future epidermal cells in the outer cell layer. Following gastrulation are the somite forming stages, in which the complete anterior-posterior axis of the embryo is established, with a well-developed head, trunk, and tail. This chapter describes the general changes occurring within the embryo during the early cleavage, blastula, gastrula, and somitogenesis stages of zebrafish development.

PURPOSE: Vascular damage and inflammation are limiting toxic effects of lung cancer radiotherapy, which lead to pneumonitis and pulmonary fibrosis. We have demonstrated that soy isoflavones (SIF) mitigate these toxic effects at late time points after radiation. However, the process by which SIF impacts the onset of radiation-induced inflammation remains to be elucidated. We have now investigated early events of radiation-induced inflammation and identified cellular and molecular signaling patterns by endothelial cells that could be modified by SIF to control vascular damage and the initiation of lung inflammation. MATERIALS AND METHODS: Histopathological, cellular and molecular studies were performed on mouse lungs from C57Bl/6 mice treated with 10Gy of thoracic radiation (XRT) in conjunction with daily oral SIF treatment given prior and after radiation. Parallel studies were performed in-vitro using EA.hy926 endothelial cell line with SIF and radiation. Immunohistochemistry, western blots analysis, and flow cytometry were performed on lung tissue or EA.hy926 cells to analyze endothelial cells, their patterns of cell death or survival, and signaling molecules involved in inflammatory events. RESULTS: Histopathological differences in inflammatory infiltrates and vascular injury in lungs, including vascular endothelial cells, were observed with SIF treatment at early time points post-XRT. XRT-induced expression of proinflammatory adhesion molecule ICAM-1 cells was reduced by SIF in-vitro and in-vivo in endothelial cells. Molecular changes in endothelial cells with SIF treatment in conjunction with XRT included increased DNA damage, reduced cell viability and cyclin B1, and inhibition of nuclear translocation of NF-κB. Analysis of cell death showed that SIF treatment promoted apoptotic endothelial cell death and decreased XRT-induced type III cell death. In-vitro molecular studies indicated that SIF+XRT increased apoptotic caspase-9 activation and production of IFNβ while reducing the release of inflammatory HMGB-1 and IL-1α, the cleavage of pyroptotic gasdermin D, and the release of active IL-1β, which are all events associated with type III cell death. CONCLUSIONS: SIF+XRT caused changes in patterns of endothelial cell death and survival, proinflammatory molecule release, and adhesion molecule expression at early time points post-XRT associated with early reduction of immune cell recruitment. These findings suggest that SIF could mediate its radioprotective effects in irradiated lungs by limiting excessive immune cell homing via vascular endothelium into damaged lung tissue and curtailing the overall inflammatory response to radiation.

Background . Vision problems in homeless children can decrease educational achievement and quality of life. Purpose . To estimate the prevalence and specific diagnoses of vision problems in children in an urban homeless shelter. Methods . A prospective series of 107 homeless children and teenagers who underwent screening with a vision questionnaire, eye chart screening (if mature enough) and if vision problem suspected, evaluation by a pediatric ophthalmologist. Glasses and other therapeutic interventions were provided if necessary. Results . The prevalence of vision problems in this population was 25%. Common diagnoses included astigmatism, amblyopia, anisometropia, myopia, and hyperopia. Glasses were required and provided for 24 children (22%). Conclusions . Vision problems in homeless children are common and frequently correctable with ophthalmic intervention. Evaluation by pediatric ophthalmologist is crucial for accurate diagnoses and treatment. Our system of screening and evaluation is feasible, efficacious, and reproducible in other homeless care situations.

The vertebrate embryo undergoes a series of dramatic morphological changes as the body extends to form the complete anterior-posterior axis during the somite-forming stages. The molecular mechanisms regulating these complex processes are still largely unknown. We show that the Hippo pathway transcriptional coactivators Yap1 and Wwtr1 are specifically localized to the presumptive epidermis and notochord, and play a critical and unexpected role in posterior body extension by regulating Fibronectin assembly underneath the presumptive epidermis and surrounding the notochord. We further find that Yap1 and Wwtr1, also via Fibronectin, have an essential role in the epidermal morphogenesis necessary to form the initial dorsal and ventral fins, a process previously thought to involve bending of an epithelial sheet, but which we now show involves concerted active cell movement. Our results reveal how the Hippo pathway transcriptional program, localized to two specific tissues, acts to control essential morphological events in the vertebrate embryo.

Disability sport programs, events, and organizations have grown rapidly since the first organized competition, the Stoke Mandeville Games in 1948, yet Paralympic-style sport has struggled to find an audience. People without physical disabilities often perceive people with physical disabilities as incompetent. In societies where there is more acceptance of people with physical disabilities, there still may be feelings of discomfort, fear, or rejection regarding people with physical disabilities. The media is regarded as one of the most influential structures in forming and developing the perceptions, opinions, and attitudes of the public. Media serve as an intermediary between the end user and the information or knowledge being transmitted. The most dominant narrative surrounding disability sport and its athletes is one of the supercrip. Priming has a significant impact on the ways in which viewers watch Paralympic-style sport, their reasons for wanting to watch more of it, and their attitudes toward people with disabilities.

© 2016 Taylor & Francis. Volunteer tourism is the fastest growing segment of the alternative tourism market and often a key feature of sport-for-development organizational models. The growing commercialization of this alternative tourism threatens efforts to build a sustainable model of long-term positive outcomes for both the host community and guest volunteers. The purpose of this study was to evaluate the motivations and impacts that a long-term international experience with a sport-for-development initiative had on volunteers from the United States. The authors spent five weeks in Granada and conducted semi-structured interviews with key personnel including out-going yearlong volunteer interns, incoming yearlong volunteer interns, and local Nicaraguan full-time staff. Guided by the volunteer motivational literature, data analysis illustrated three key findings. The most prominent theme involved the motivation of going abroad to gain a cultural experience, in particular to increase global understanding and provide social gains. In addition, our results illustrate the motivations of one's career and professional goals, and the ability to give back to a foreign culture through the use of sport. This demonstrates the potential for sport-for-development organizations to successfully incorporate volunteer tourism into a sustainable model based on specific volunteer recruitment and structure of their experiences.

The current study explored the role of psychological contract fulfilment on innovative work behaviours of employees in sport-based small business enterprises (SBEs). Building on literature from sport and non-sport organisational contexts, a model positing a direct linear relationship between psychological contract fulfilment and innovative work behaviours was proposed. Affective commitment and organisational citizenship behaviours were included in the model as partial mediators. The model was tested using a sample of 216 employees from affiliated minor league baseball franchises. Results supported a model where organisational citizenship fully mediated the relationship between psychological contract fulfilments and innovate work behaviours. Affective commitment was predicted by psychological contract fulfilment but was not significantly related to the other variables in the model.

Background: Pediatric severe hemophilia A patients with high titer inhibitors are often reported to have inadequate control of acute bleeding episodes because they do not respond to bypassing agents as predictably as with FVIII therapy for non-inhibitor patients. Thromboelastography (TEG) is a global assay of hemostasis that has promising benefits for use in clinical care for hemophilia patients. Aims: This study was performed to determine in pediatric inhibitor patients: 1) if baseline TEG, specifically R or reaction time that corresponds to time to thrombin generation and clot formation, is stable over time in individual inhibitor patients; 2) if there are any predictors of baseline TEG R time; 3) to determine response to recombinant activated factor VII (rFVIIa, NovoSeven, NovoNordisk, Copenhagen, Denmark); and 4) to determine predictors of TEG R time following rFVIIa. Methods: This analysis was conducted within a consented single institution prospective inceptional cohort study. Clinical data regarding healthy volunteers with no personal or family history of a bleeding or clotting disorder and pediatric hemophilia patients with and without inhibitors (assayed by Nijmegen modification of the Bethesda assay (BU)) were extracted from research records and electronic medical records. For this study, TEGs were performed in kaolin citrated samples with added TPA (final concentration 450 ng/mL). Descriptive data were presented as mean and SD. This report analyzed TEG R times, indicating time to clot formation and initial thrombin generation. Baseline TEGs were obtained at least five half-lives after the last infusion of each clotting factor or bypassing agent received. Post treatment TEGs were performed on patients 1 hour following a therapeutic treatment with rFVIIa. Results: R times on TEGs were obtained on 24 healthy adults, 23 healthy children, 15 children with severe hemophilia A without an inhibitor, and 12 children with severe hemophilia A and an inhibitor. 32 samples were obtained in the 12 children with inhibitors, with 1 to 11 samples from each child. Paired samples were obtained at baseline prior to and 1 hour following a dose (90-270 mg/kg) of rFVIIa. Mean TEG R times were 8.3 minutes (SD 1.4) for healthy adults, 7.7 minutes (SD 1.5) for healthy children, 20.2 minutes (SD 9.4) for children with severe hemophilia A and 102.1 minutes (SD 44.4) for children with severe hemophilia A and inhibitors. Healthy children did not differ from healthy adults (p=0.43), but children with hemophilia with inhibitors differed from healthy controls (p=0.046) and trended toward differences from children with hemophilia without inhibitors (p=0.08, however limited in sample number). Baseline R values in children with inhibitors did not correlate with age (r=-0.19) or inhibitor titer (r=0.23). Children studied on multiple occasions showed variability over time. TEG 1 hour following rFVIIa in a baseline state showed a mean R time of 25.1 minutes (SD 7.1). Post rFVIIa R time did not correlate with age (r=0.21) or inhibitor titer (r=-0.14), but showed considerable correlation with baseline TEG R time (Figure 1, r =0.65, p=0.013). Following infusion of rFVIIa, TEG R times of children with inhibitors never achieved the normal range. However, when rFVIIa was studied following multiple infusions without a washout, the mean TEG R was moderately, but non-significantly shorter at 20.6 minutes (SD 5.6). Conclusions: TEG R times in young children with severe hemophilia A with inhibitors are greatly prolonged compared to healthy children or adults, and moderately longer than that in children with severe hemophilia A without inhibitors. Baseline TEG R varies over time and cannot be predicted by age or inhibitor titer. Baseline TEG R time may be an important predictor of response to bypassing therapy and serial monitoring over time may be clinically useful to guide therapy. During the course of multiple infusions, moderately improved TEG R responses were determined compared with first infusions. This may, in part, explain our previously reported observation of longer duration of rFVIIa dosing in young children with inhibitors. Future studies employing TEG to help optimize response to bypassing agents are needed. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.