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T cells have the remarkable ability to recognize antigen with great specificity and in turn mount an appropriate and robust immune response. Critical to this process is the initial T cell antigen recognition and subsequent signal transduction events. This antigen recognition can be modulated at the site of TCR interaction with peptide:major histocompatibility (pMHC) or peptide interaction with the MHC molecule. Both events could have a range of effects on T cell fate. Though responses to antigens that bind sub-optimally to TCR, known as altered peptide ligands (APL), have been studied extensively, the impact of disrupting antigen binding to MHC has been highlighted to a lesser extent and is usually considered to result in complete loss of epitope recognition. Here we present a model of viral evasion from CD8 T cell immuno-surveillance by a lymphocytic choriomeningitis virus (LCMV) escape mutant with an epitope for which TCR affinity for pMHC remains high but where the antigenic peptide binds sub optimally to MHC. Despite high TCR affinity for variant epitope, levels of interferon regulatory factor-4 (IRF4) are not sustained in response to the variant indicating differences in perceived TCR signal strength. The CD8+ T cell response to the variant epitope is characterized by early proliferation and up-regulation of activation markers. Interestingly, this response is not maintained and is characterized by a lack in IL-2 and IFNγ production, increased apoptosis and an abrogated glycolytic response. We show that disrupting the stability of peptide in MHC can effectively disrupt TCR signal strength despite unchanged affinity for TCR and can significantly impact the CD8+ T cell response to a viral escape mutant.

The capacity to probe antigen specific T cells within the polyclonal repertoire has been revolutionized by the advent of recombinant peptide:MHC (pMHC) technology. Monomers and multimers of peptide: MHC molecules can enrich for and identify antigen specific T cells to elucidate the contributions of T cell frequency, localization and T cell receptor (TCR) affinity during immune responses. Two-dimensional (2D) measurements of TCR-pMHC interactions are at the forefront of this field because the biological topography is replicated such that TCR and pMHC are membrane anchored on opposing cells, allowing for biologically pertinent measures of TCR antigen specificity and diversity. 2D measurements of TCR-pMHC kinetics have also demonstrated increased fidelity, compared to the 3-dimensional surface plasmon resonance data, and are capable of detecting T cell affinities that are below the detection level of most pMHC multimers. Importantly, 2D techniques provide a platform to evaluate affinity and antigen specificity against multiple protein epitopes within polyclonal T cell populations directly ex vivo from sites of ongoing immune responses. This review will discuss how antigen specific peptide:MHC molecules, with a focus on 2D technologies, can be used as effective tools to evaluate the range of TCR affinities that comprise an immune response and more importantly how the breadth of affinities determine functional outcome against a given exposure to antigen. kin

The National Institute of Health R25 Research Education Program was evaluated in the second year of implementation. Twelve mentors and 20 underrepresented minority students (URMs) scholars from partnerships and collaborations among five colleges and universities were added to the program to provide a more diverse research experience. Findings reveal that 100% of research mentors agree that the approachableness and accessibility of the program coordinator were beneficial in achieving mentorship goals and objectives. In addition, 85% of the students strongly agreed that the presentation of their research findings and the weekly reflection on goals, identification of accomplishments, and obstacles through the individual development plan were very effective. Of the 23 successfully tracked students for 2 years, six URMs (26.09%) obtained a bachelor's degree and were admitted into a graduate program; two were directly admitted to a PhD program in biomedical sciences., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: The study investigated the locomotor and tackle pacing profile and loads of female rugby league players following various between-match turnaround durations. Specifically, the study examined the (1) pacing of locomotor and tackle loads across the time-course of a match and; (2) whole-match and peak locomotor and tackle loads of match-play., Methods: Microtechnology data were collected from elite female rugby league players ( n  = 172) representing all National Rugby League Women's teams ( n  = 6 teams) across two seasons. Players were categorised into backs, adjustables, forwards or interchange players. Data was calculated for the whole-match (m), per minute (m.min -1 ) and peak (running: m.min -1 ; acceleration: m.s -2 ) locomotor and tackle loads (number and efficiency (%)) of match-play. The pacing as well as the locomotor and tackle loads of match-play were examined following short (≤6 days), normal (7 days) or long (≥8 days) turnarounds., Results: The pacing profile of playing positions varied across short, normal and long match turnarounds. Trivial to moderate differences existed in the whole-match, per minute and peak locomotor loads across match turnaround durations (effect size ≤ 1.2)., Conclusions: Following various between-match turnaround durations (i.e., short, normal and long match turnarounds), there were variations in the locomotor and tackle pacing profile and loads whereby, the pacing profile of positional groups was more affected than the load profile. The findings can be used in applied settings to guide the recovery strategies and training plans of female rugby league players to optimise performance and wellbeing across various match turnaround durations.

Anaysia and Caviar are temperate siphoviruses isolated from soil using Gordonia terrae 3612 and Mycobacterium smegmatis mc 2 155, respectively. Anaysia's 52,861-bp genome carries 102 genes, while Caviar's 47,074-bp genome carries 79 genes. Based on gene content similarity, Anaysia and Caviar are assigned to phage clusters A15 and A3, respectively.

The aims of this study were to (a) use a data-based approach to identify positional groups within National Rugby League Women's (NRLW) match-play and (b) quantify the peak locomotor demands of NRLW match-play by positional groups. Microtechnology (Global Navigational Satellite System [GNSS] and integrated inertial sensors; n = 142 files; n = 76 players) and match statistics ( n = 238 files; n = 80 players) were collected from all NRLW teams across the 2019 season. Data-based clustering of match statistics was utilized to identify positional clusters through classifying individual playing positions into distinct positional groups. Moving averages (0.5, 1, 2, 3, 5, and 10 min) of peak running and average acceleration/deceleration demands were calculated via microtechnology data for each player per match. All analysis was undertaken in R (R Foundation for Statistical Computing) with positional differences determined via a linear mixed model and effect sizes (ES). Data-based clustering suggested that, when informed by match statistics, individual playing positions can be clustered into one of three positional groups. Based on the clustering of the individual positions, these groups could be broadly defined as backs (fullback, wing, and center), adjustables (halfback, five-eighth, and hooker), and forwards (prop, second-row, and lock). Backs and adjustables demonstrated greater running (backs: ES 0.51-1.00; p < 0.05; adjustables: ES 0.51-0.74, p < 0.05) and average acceleration/deceleration (backs: ES 0.48-0.87; p < 0.05; adjustables: ES 0.60-0.85, p < 0.05) demands than forwards across all durations. Smaller differences (small to trivial) were noted between backs and adjustables across peak running and average acceleration/deceleration demands. Such findings suggest an emerging need to delineate training programs in situations in which individual playing positions train in positional group based settings. Collectively, this work informs the positional groupings that could be applied when examining NRLW data and supports the development of a framework for specifically training female rugby league players for the demands of the NRLW competition., Competing Interests: At the time of submission JC and SB held employment with the National Rugby League. The National Rugby League provided support in the form of research funding for CC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cummins, Charlton, Paul, Shorter, Buxton, Caia and Murphy.)

Objective: There are many uncertainties surrounding the aetiology, treatment and sequelae of hyperemesis gravidarum (HG). Prioritising research questions could reduce research waste, helping researchers and funders direct attention to those questions which most urgently need addressing. The HG priority setting partnership (PSP) was established to identify and rank the top 25 priority research questions important to both patients and clinicians., Methods: Following the James Lind Alliance (JLA) methodology, an HG PSP steering group was established. Stakeholders representing patients, carers and multidisciplinary professionals completed an online survey to gather uncertainties. Eligible uncertainties related to HG. Uncertainties on nausea and vomiting of pregnancy and those on complementary treatments were not eligible. Questions were verified against the evidence. Two rounds of prioritisation included an online ranking survey and a 1-hour consensus workshop., Results: 1009 participants (938 patients/carers, 118 professionals with overlap between categories) submitted 2899 questions. Questions originated from participants in 26 different countries, and people from 32 countries took part in the first prioritisation stage. 66 unique questions emerged, which were evidence checked according to the agreed protocol. 65 true uncertainties were narrowed via an online ranking survey to 26 unranked uncertainties. The consensus workshop was attended by 19 international patients and clinicians who reached consensus on the top 10 questions for international researchers to address. More patients than professionals took part in the surveys but were equally distributed during the consensus workshop. Participants from low-income and middle-income countries noted that the priorities may be different in their settings., Conclusions: By following the JLA method, a prioritised list of uncertainties relevant to both HG patients and their clinicians has been identified which can inform the international HG research agenda, funders and policy-makers. While it is possible to conduct an international PSP, results from developed countries may not be as relevant in low-income and middle-income countries., Competing Interests: Competing interests: CRD is chair of the charity Pregnancy Sickness Support, which funded the JLA aspect of this project. RG and MO are trustees, KL is an employee and EW is a volunteer for Pregnancy Sickness Support. CRD and CN-P are trustees of the Bikkja Trust which funded the consensus workshop and provided some travel bursaries. CN-P has received consultancy and speaker fees from Alliance Pharma., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Equine Caudal Cervical Morphologic Variation (ECCMV) is a congenital malformation of the caudal cervical spine distinct from the more commonly recognized Cervical Vertebral Stenotic Myelopathy (CVSM). The most common presentation of ECCMV is recognized on the sixth cervical vertebra (C6). In "normal" presentations, the transverse processes on the left and right sides have a caudal lamina projecting ventrally below the caudal vertebral body in a heel shape. With ECCMV, variations occur to the structure of the caudal ventral lamina on one or both sides of C6 and may include the seventh cervical (C7) and first thoracic (T1) vertebrae and ribs, in varying configurations. Whereas the prevalence of ECCMV is not known, it has been recognized for many years and has been reported to occur with relatively high frequency within multiple populations of domesticated horses. To date, there is no documented link between the occurrence of ECCMV and clinical signs. However, based on retrospective studies, multiple authors have recognized the potential impact on performance that this condition may have. Establishing a reliable radiographic protocol for the consistent diagnosis of ECCMV would allow quantitative, scientific evaluation of the problem and support clinicians working in this field. We present a radiographic technique, which has been illustrated by diagnosis of ECCMV in three horses and confirmation of the diagnoses in two cases via postmortem examination.

Introduction: Dog boots are being utilized to improve performance and welfare of dogs exposed to a range of adverse conditions; however, there is a lack of empirical evidence establishing the impact of these on gait characteristics. The aim of this research was to quantify alterations to ground force kinetics associated with the introduction of canine boots., Methods: Six clinically sound beagles were analyzed on two separate occasions using a cross-over study design to enable randomization between barefoot and shod conditions. During each session, dogs were trotted by an experienced handler over an AMTI force plate sampling at 1,000 Hz to quantify stance time, peak vertical force, peak vertical instantaneous loading rate, and vertical impulse., Results: Although there was no significant difference found between footwear conditions for stance time, peak vertical force, and vertical impulse, peak vertical instantaneous loading rate was significantly greater in shod when compared to barefoot., Discussion: Findings suggest that while canine boots may provide environmental protection, increases in loading rate are indicative of alterations in foot strike that may result in overloading of musculoskeletal structures. Therefore, caution must be taken when introducing footwear to ensure an adequate adjustment period., (© 2019. Akadémiai Kiadó Zrt.)

Quantifying the training and competition loads of players in contact team sports can be performed in a variety of ways, including kinematic, perceptual, heart rate or biochemical monitoring methods. Whilst these approaches provide data relevant for team sports practitioners and athletes, their application to a contact team sport setting can sometimes be challenging or illogical. Furthermore, these methods can generate large fragmented datasets, do not provide a single global measure of training load and cannot adequately quantify all key elements of performance in contact team sports. A previous attempt to address these limitations via the estimation of metabolic energy demand (global energy measurement) has been criticised for its inability to fully quantify the energetic costs of team sports, particularly during collisions. This is despite the seemingly unintentional misapplication of the model's principles to settings outside of its intended use. There are other hindrances to the application of such models, which are discussed herein, such as the data-handling procedures of Global Position System manufacturers and the unrealistic expectations of end users. Nevertheless, we propose an alternative energetic approach, based on Global Positioning System-derived data, to improve the assessment of mechanical load in contact team sports. We present a framework for the estimation of mechanical work performed during locomotor and contact events with the capacity to globally quantify the work done during training and matches.

The Dutch Konik is valued from a genetic conservation perspective and also for its role in preservation of natural landscapes. The primary management objective for the captive breeding of this primitive horse is to maintain its genetic purity, whilst also maintaining the nature reserves on which they graze. Breeding selection has traditionally been based on phenotypic characteristics consistent with the breed description, and the selection of animals for removal from the breeding program is problematic at times due to high uniformity within the breed, particularly in height at the wither, colour (mouse to grey dun) and presence of primitive markings. With the objective of identifying an additional non-invasive selection criterion with potential uniqueness to the Dutch Konik, this study investigates the anatomic parameters of the distal equine limb, with a specific focus on the relative lengths of the individual splint bones. Post-mortem dissections performed on distal limbs of Dutch Konik ( n = 47) and modern domesticated horses ( n = 120) revealed significant differences in relation to the length and symmetry of the 2nd and 4th Metacarpals and Metatarsals. Distal limb characteristics with apparent uniqueness to the Dutch Konik are described which could be an important tool in the selection and preservation of the breed., Competing Interests: The authors declare no conflict of interest.

The purpose of this study was to apply a time-motion model to estimate and describe the energy expenditure and metabolic power demands of playing positions in elite rugby league match-play, utilizing Global Positioning System (GPS) devices. 18 elite rugby league players participated in this study. Players' positional groups included: outside backs (n=59 files, n=4 players), adjustables (n=74 files, n=4 players), wide-running (n=104 files, n=7 players) and hit-up forwards (n=36 files, n=3 players). Outside backs expended the greatest total energy (40.1±5.0 kJ·kg(-1)) per match, equivalent to 8.1%, 26.6% and 61.9% greater energy than adjustables, wide-running and hit-up forwards, respectively. Adjustables attained an anaerobic index 7.3% higher than wide-running forwards, 19.7% higher than hit-up forwards (p=0.001) and 43.2% higher than outside backs (p<0.001). Wide-running forwards achieved an anaerobic index (0.34±0.04) 11% and 32.8% higher than hit-up forwards (p=0.001) and outside backs (p<0.001), respectively. Mean power of adjustables (10.0±0.9 W·kg(-1)) was significantly higher than all other groups (outside backs: 28.8%, 7.8±1.0; hit-up: 12.4%, 8.9±0.6; and wide-running: 8.7%, 9.2±0.7 forwards) (p<0.001). Energetics indices indicated differing metabolic demands for all positional groups, suggesting position-specific conditioning drills are required to replicate the energetic demands of match-play., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: The purpose of this research was to develop and validate an instrument to measure shifting or self-altering strategies among African American women., Method: A 13-item instrument was developed to measure aspects of shifting phenomena based on the empirical literature, feedback from focus groups, and cultural experts. The initial validation study, using principal axis analysis, was conducted with a national sample of 318 African American women. A second independent national sample of 190 African American women provided data for a confirmatory factor analysis., Results: Results indicated that the inventory was composed of the following 3 factors: Strong Black Woman, Awareness of Shifting Behavior, and Sensitivity to the Perceptions of Blacks., Conclusions: A structural model was developed based on the Multicultural Assessment-Intervention Process (MAIP) framework that allowed for the exploration of the shifting construct. Implications for future research are discussed., ((c) 2016 APA, all rights reserved).)

Purpose: To investigate temporal variation in running intensity across and within halves and evaluate the agreement between match-analysis indices used to identify fluctuations in running intensity in rugby sevens., Methods: Data from a 15-Hz global positioning system (GPS) were collected from 12 elite rugby sevens players during the IRB World Sevens Series (N = 21 full games). Kinematic (eg, relative distance [RD]) and energetic (eg, metabolic power [MP]) match-analysis indices were determined from velocity-time curves and used to investigate between-halves variations. Mean MP and RD were used to identify peak 2-minute periods of play. Adjacent 2-minute periods (prepeak and postpeak) were compared with peak periods to identify changes in intensity. MP and RD were expressed relative to maximal oxygen uptake (VO2max) and speed at VO2max, respectively, and compared in their ability to describe the intensity of peak periods and their temporal occurrence., Results: Small to moderate reductions were present for kinematic (RD; 8.9%) and energetic (MP; 6%) indices between halves. Peak periods (RD = 130 m/min, MP =13 W/kg) were higher (P < .001) than the match average (RD = 94 m/min, MP = 9.5 W/kg) and the prepeak and postpeak periods (P < .001). RD underestimated the intensity of peak periods compared with MP (bias 16%, limits of agreement [LoA] ± 6%). Peak periods identified by RD and MP were temporally dissociated (bias 21 s, LoA ± 212 s)., Conclusions: The findings suggest that running intensity varies between and within halves; however, the index used will influence both the magnitude and the temporal identification of peak periods.

This study compared differences between ballistic jump squat (B) and nonballistic back squat (NB) force, velocity, power, and relative acceleration duration, and the effect that the method used to identify the positive lifting phase had on these parameters. Ground reaction force and barbell kinematics were recorded from 30 resistance trained men during B and NB performance with 45% 1RM. Force, velocity, and power was averaged over positive lifting phases identified using the traditional peak barbell displacement (PD) and positive impulse method. No significant differences were found between B and NB mean force, and mean power, but B mean velocity was 14% greater than the NB equivalent. Positive impulse mean force was 24% greater than PD mean force, and B relative acceleration duration was 8.6% greater than the NB equivalent when PD was used to identify the end of the positive lifting phase. These results challenge common perceptions of B superiority for power development.

Hair disorders cause psychological distress but are generally poorly controlled; more effective treatments are required. Despite the long-standing use of minoxidil for balding, its mechanism is unclear; suggestions include action on vasculature or follicle cells. Similar drugs also stimulate hair, implicating ATP-sensitive potassium (K(ATP)) channels. To investigate whether K(ATP) channels are present in human follicles, we used organ culture, molecular biological, and immunohistological approaches. Minoxidil and tolbutamide, a K(ATP) channel blocker, opposed each other's effects on the growing phase (anagen) of scalp follicles cultured in media with and without insulin. Reverse transcriptase-polymerase chain reaction identified K(ATP) channel component gene expression including regulatory sulfonylurea receptors (SUR) SUR1 and SUR2B but not SUR2A and pore-forming subunits (Kir) Kir6.1 and Kir6.2. When hair bulb tissues were examined separately, epithelial matrix expressed SUR1 and Kir6.2, whereas both dermal papilla and sheath exhibited SUR2B and Kir6.1. Immunohistochemistry demonstrated similar protein distributions. Thus, human follicles respond biologically to K(ATP) channel regulators in culture and express genes and proteins for two K(ATP) channels, Kir6.2/SUR1 and Kir6.1/SUR2B; minoxidil only stimulates SUR2 channels. These findings indicate that human follicular dermal papillae contain K(ATP) channels that can respond to minoxidil and that tolbutamide may suppress hair growth clinically; novel drugs designed specifically for these channels could treat hair disorders.

This is an exploratory qualitative study of the experience of identity in late adolescent African-American women. Using a semi-structured interview, 17 18- to 22-year-old community college students were interviewed about how they see their identity and about the personal salience of various identity domains-race, gender, sexual orientation, relationships, career, religious beliefs, and political beliefs. It was found that these seven ego identity domains varied in importance, with racial identity as the most salient, while the domains of gender, relationships, and career were also important sources of identity. A sense of "strength" also emerged as an important element of self-definition. Particular attention is paid to the intersection of racial and gender identity for these African-American women who must evolve a sense of self within the context of a society that devalues Blacks and women.

The author reflects on the emotional impact of the O.J. Simpson trial and verdict and contends that the issues and concerns generated by the trial are mental health issues. The lack of leadership of mental health professionals in helping people to deal with their reactions to these events is noted. From this experience, seven lessons for mental health professionals are proposed. In particular, a call is made for mental health practitioners who are committed to cultural diversity to become more involved in understanding and responding to racially charged, community-rupturing events like the Simpson trial and verdict.

In an effort to develop an Afro-centric intrapsychic evaluation tool, the Community Mental Health Council, Inc., Altered States of Consciousness Research Team, developed a structured interview used to quantify and qualify the 17 states of consciousness(1) that occurred in black control, precare, and aftercare subjects. Differences were noted in the three groups as to the incidence, prevalence, and quality of the various states of consciousness. It was also noted that the profile obtained from the interviews yielded a sharp clinical picture of the subjects' total intrapsychic propensities.

Coma, commonly known as "being unconscious" or "out cold," is a state of consciousness characterized by a total inability to perceive incoming stimuli. A retrospective phenomenologic study found that 10 of 36 control, 19 of 36 precare, and 20 of 36 aftercare subjects (49 of 108, or 45.4 percent) had experienced coma at least once during their lives. The implications of these findings are discussed.

Sleep paralysis is a state of consciousness experienced while waking from sleep or falling asleep. It is characterized by an experience of being unable to move for several seconds or minutes. This study represents the first survey to measure the incidence of this disorder in a black population of healthy subjects and psychiatric patients.