The association of range of motion, lower limb strength, and load during jump landings in professional ballet dancers.

This study aimed to investigate the associations between peak plantarflexion ankle joint moments and vertical ground reaction forces (vGRF) during jump landings, and static ankle dorsiflexion range of motion (ROM), three-dimensional ankle excursions, and lower extremity strength in professional ballet dancers. Twenty-seven professional ballet dancers volunteered to participate (men = 14, women = 13). Participants attended one data collection session to measure dorsiflexion ROM and isometric lower extremity strength. Two further sessions were used to establish ankle mechanics and vGRFs during countermovement jump landings in seven foot positions, via a seven-camera motion capture system and piezoelectric force platform. Two linear mixed-effects models were used to investigate associations between the target variables and strength, dorsiflexion ROM, and ankle excursions. Dancer identification, sex, and foot position were entered as random effects. Model fit, when considered independent of random effects, was generally poor with the predictor variables explaining little of the variance of peak plantarflexion ankle joint moments (R2 = 0.02) or vGRF (R2 = 0.01). Model fit improved when random effects were considered (R2 = 0.65 & 0.34). Frontal plane ankle excursion was the only predictor variable with a significant negative association with peak plantarflexion ankle joint moments (p = .016), although coefficient estimates were small. Strength, static ankle dorsiflexion ROM, and three-dimensional ankle excursions are poor predictors of load experienced at a joint and system level in professional ballet dancers. Differences between individuals, sex, and foot position may be better indicators of the load experienced during jump landings.

Plants buffer some of the effects of a pair of cadmium-exposed zebrafish on the un-exposed majority.

Certain individuals have a disproportionate effect on group responses. Characteristics may include susceptibility to pollutants, such as cadmium (Cd), a potent trace metal. Here, we show how a pair of Cd-exposed individuals can impact the behavior of unexposed groups. We used behavioral assessments to characterize the extent of the effects of the Cd-exposed individuals on group boldness, cohesion, foraging, activity, and responses to plants. We found that groups with a pair of Cd-exposed fish remained closer to novel stimuli and plants than did groups with untreated (control) fish. The presence of plants reduced Cd-induced differences in shoal cohesion and delays feeding in male shoals. Shoals with Cd- and water-treated fish were equally active. The results suggest that fish acutely exposed to environmentally relevant Cd concentrations can have profound effects on the un-exposed majority. However, the presence of plants may mitigate the effects of contaminants on some aspects of social behavior.

Jumping Asymmetries and Risk of Injuries in Preprofessional Ballet.

BACKGROUND: Preprofessional ballet dancers are exposed to the risk of injuries, primarily in the lower extremities, with most injuries occurring during jumping and landing activities. Interlimb asymmetry during jumping and landing activities has been associated with the injury risk in adolescent athletes, but this has not been examined in dancers. PURPOSE: To investigate associations between interlimb asymmetry during a double-leg countermovement jump (DL-CMJ) and single-leg jump (SLJ) and the injury risk in adolescent preprofessional ballet dancers. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Adolescent preprofessional ballet dancers (N = 255) performed 3 DL-CMJs and 3 SLJs on force plates during annual screening. Absolute and directional (separate values for left and right limb dominance) asymmetries in a set of kinetic variables during a DL-CMJ and in jump height during an SLJ were calculated. Each variable was characterized as having "high" or "normal" asymmetry according to the percentage of asymmetry (greater than or less than or equal to, respectively, the mean ± 0.5 SD) based on the present sample. Risk ratios (RRs) and 95% CIs were calculated based on the injury incidence in the subsequent academic year. RESULTS: Of the 242 dancers that satisfied the inclusion criteria, 128 injuries were observed in the subsequent academic year. In the whole sample, 3 absolute, 7 left limb-dominant, and 1 right limb-dominant kinetic asymmetry in the eccentric, concentric, and landing phases of the DL-CMJ as well as left limb-dominant jump height asymmetry in the SLJ were associated with a significant (P < .001) increase in the injury risk (RR, 1.28-1.69 [95% CI, 1.02-2.37]). Separating by sex, asymmetries in the eccentric and landing phase of the DL-CMJ were not significant in boys, while in girls, RRs for asymmetries in the eccentric and landing phase of the DL-CMJ increased, and SLJ jump height asymmetry was not significant. CONCLUSION: Higher asymmetries in certain kinetic variables during the DL-CMJ and in jump height during the SLJ were associated with an elevated risk of injuries in elite preprofessional ballet dancers with some sex-specific differences. Associations were mainly identified for high left limb-dominant asymmetry in the takeoff phase, suggesting that the injury risk may be specific to a relative right limb deficit.

Periprocedural management of direct oral anticoagulants in patients with atrial fibrillation and active cancer.

BACKGROUND: Cancer and atrial fibrillation (AF) are common concurrent disorders. Direct oral anticoagulants (DOACs) are prescribed to prevent stroke in patients with AF. Patients with cancer often undergo invasive procedures for diagnostic or therapeutic purposes, necessitating interruption of anticoagulation. There are limited data to guide best periprocedural anticoagulation management practices in the setting of active cancer. OBJECTIVES: To describe patient characteristics, periprocedural management, and clinical outcomes in DOAC-treated patients with AF according to active cancer status. METHODS: We conducted descriptive and comparative analyses using data from the PAUSE study. Multivariable logistic regression was used to determine whether active cancer status was an independent risk factor for bleeding outcomes. Covariates were selected a priori based on biological rationale and preexisting knowledge. RESULTS: Patients with active cancer were older (P < .001), more likely to be thrombocytopenic (P = .026), have moderate renal dysfunction (P = .005), and more likely to receive low-dose DOAC therapy (P < .001). A greater proportion of patients with active cancer underwent a high-bleed-risk procedure (P < .001), with longer periprocedural DOAC-interruption intervals (P <.001) and lower preprocedural residual DOAC levels (P = .002). Active cancer was an independent predictor for surgical major bleeding (OR = 2.45; 95% CI, 1.08-5.14) after adjusting for study center, procedure category and bleed risk, thrombocytopenia, hypertension, and the use of a P2Y12 inhibitor. CONCLUSIONS: Active cancer status is associated with an increased risk of surgical major bleeding among DOAC-treated patients with AF undergoing interruption of anticoagulation for elective invasive procedures.

Jumping demands during classical ballet class.

Ballet class represents a considerable portion of professional ballet training, yet the external training load demands associated with class-and particularly the jumping demands-have not been investigated. The purpose of this study was to measure the jumping demands of ballet class by sex and rank. Eleven female and eight male elite professional ballet dancers participated in 109 ballet classes taught by 12 different teachers. Jump counts and jump heights were measured during each class. A Poisson generalized linear mixed effects model was used to examine the differences in jump counts between sexes and ranks. Greater jump counts were observed during class in men than in women (153, 95% confidence intervals [CI] [137, 170] vs. 119, 95% CI [109, 131], p = 0.004) and in junior ranking dancers compared with senior ranking dancers (151, 95% CI [138, 165] vs. 121, 95% CI [108, 135], p = 0.006). Female junior and senior ranking dancers jumped at rates of 9.2 ± 2.6 and 8.6 ± 4.7 jumps·min-1 , respectively, while male junior and senior ranking dancers jumped at rates of 9.1 ± 2.6 and 8.7 ± 2.6 jumps·min-1 , respectively. Across all classes, 73% of jumps observed were below 50% of maximum double-legged countermovement jump height. Unlike rehearsals and performances, class offers dancers an opportunity to self-regulate load, and as such, are a useful session to manage jump load, and facilitate gradual return-to-dance pathways. Communication between health care and artistic staff is essential to facilitate load management during class.

Epidemiology and management of ankle sprain injuries over seven seasons in an elite professional ballet company.

OBJECTIVES: To investigate the epidemiology and management of ankle ligament sprains over seven seasons in a professional ballet company. DESIGN: Descriptive epidemiology study. METHODS: Medical attention injury, time-loss injury, and exposure data pertaining to 140 professional ballet dancers were prospectively recorded by Chartered Physiotherapists over seven seasons (2015/16-2021/22); a period including the COVID-19 global pandemic. RESULTS: Sixty-nine ankle sprains (46 time-loss) in 45 dancers (32 %) were recorded: 51 sprains were classified as grade I, 15 were classified as grade II, and three were classified as grade III; 53 sprains affected only one ligament, whilst 16 were multi-ligament sprains. For time-loss injuries, median time-loss durations varied by grading (I - 31 days, II - 54 days, and III - 147 days) and the number of ligaments affected (one - 31 days, two - 54 days, three - 134 days, four - 137 days), with time-loss ranging from 1 to 188 days. Of the 46 time-loss ankle sprains, eight were mild, nine were moderate, and 29 were severe. The incidence rate (injuries·1000 h-1) of medical attention ankle sprains was 0.073 (95 % CI: 0.046 to 0.117) in male dancers and 0.101 (95 % CI: 0.069 to 0.148) in female dancers, and the incidence of time-loss ankle sprains was 0.044 (95 % CI: 0.024 to 0.080) in male dancers and 0.064 (95 % CI: 0.040 to 0.103) in female dancers. No significant effect of sex was observed on either medical attention (p = .304) or time-loss (p = .327) ankle sprain incidence rates. Ten percent of dancers sustained multiple sprains across the seven seasons. Fifty and 39 % of ankle sprains in female and male dancers, respectively, were preceded by a history of ankle sprains. Jumping and landing (30 sprains) and non-dance movements (16 sprains) were the most common inciting movements. Bone bruising and synovitis were the most common concurrent pathologies. CONCLUSIONS: Ankle sprains placed a considerable burden on the ballet company studied. These time-loss durations specified by number and grade of ligament sprain, injury history, and secondary pathologies can guide return-to-dance rehabilitation pathways.

Thrombin generation, bleeding and hemostasis in humans: Protocol for a scoping review of the literature.

INTRODUCTION: Hemostasis and bleeding are difficult to measure. Thrombin generation assays (TGAs) can measure both procoagulant and anticoagulant contributions to coagulation. TGAs might prove useful for the study of bleeding disorders. There has been much progress in TGA methodology over the past two decades, but its clinical significance is uncertain. We will undertake a scoping review of the literature to synthesize available information on the application of TGAs towards the study of bleeding and hemostasis, TGA methodologies being used and to summarize available literature on associations between TGA parameters, bleeding and hemostatic outcomes. METHODS AND ANALYSIS: MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) will be searched in collaboration with an information specialist. Title/abstract and full-text screening will be carried out independently and in duplicate; eligible study types will include randomized controlled trials, non-randomized studies, systematic reviews, and case series reporting TGA results and bleeding/hemostatic outcomes among humans. Mapping the information identified will be carried out with results presented using qualitative data analytical techniques. ETHICS AND DISSEMINATION: This scoping review will use published, publicly available information. Research ethics approval will not be required. We will disseminate our findings using conference presentations, peer-reviewed publications, social media, and engagement with knowledge users. This review will outline knowledge gaps concerning TGAs, better delineate its applicability as a clinically relevant assay for bleeding. and seek to identify ongoing barriers to its widespread adoption in clinical research, and eventually, in the clinical setting. TRAIL REGULATIONS: Registration ID with Open Science Framework: osf.io/zp4ge.

A Pair of Cadmium-exposed Zebrafish Affect Boldness and Landmark use in the Un-exposed Majority.

Some individuals have a disproportionate effect on group responses. These individuals may possess distinct attributes that differentiate them from others. These characteristics may include susceptibility to contaminant exposure such as cadmium, a potent trace metal present in water and food. Here, we tested whether a pair of cadmium-exposed individuals could exert an impact on the behavior of the unexposed majority. We used behavioral assessments to characterize the extent of the effects of the cadmium-exposed pair on group boldness, cohesion, activity and responses to landmarks. We found that groups with a pair of cadmium-exposed fish approached and remained closer to novel stimuli and landmarks than did groups with pairs of fish treated with uncontaminated water (control). Shoals with cadmium and water treated fish exhibited similar levels of cohesion and activity. The results suggest that fish acutely exposed to environmentally-relevant cadmium concentrations can have profound effects on the un-exposed majority.

High-throughput differential scanning fluorimetry (DSF) and cellular thermal shift assays (CETSA): Shifting from manual to automated screening.

Biophysical affinity screening is increasingly being adopted as a high-throughput hit finding technique in drug discovery. Automation is highly beneficial to high-throughput screening (HTS) since a large number of compounds need to be reproducibly tested against a biological target. Herein, we describe how we have automated two biophysical affinity screening methods that rely on a thermal shift in protein melting temperature upon small molecule binding: differential scanning fluorimetry (DSF) and the cellular thermal shift assay (CETSA).

Effect of PCC on Thrombin Generation among Patients on Factor Xa Inhibitors with Major Bleeding or Needing Urgent Surgery (GAUGE): Design and Rationale.

Background Direct factor Xa inhibitors (FXaIs) account for most oral anticoagulant use and FXaI-associated bleeding events are common. Clinicians have variable national and regional access to specific FXaI reversal agents such as andexanet alfa. Many centers have adopted the use of prothrombin complex concentrates (PCCs) as hemostatic therapy for FXaI-associated major bleeding events. PCC does not impact circulating FXaI levels and its mechanism of action to achieve hemostasis in FXaI-associated bleeding is uncertain. While PCC increases quantitative thrombin generation assay (TGA) parameters, it does not correct FXaI-altered thrombin generation kinetics, nor does it normalize thrombin generation. Clinical data supporting the use of PCC are based on cohort studies reporting clinical hemostatic efficacy, which is difficult to measure. The benefits of PCC for FXaI-associated bleeding beyond supportive care are uncertain. Objective GAUGE is a prospective observational study designed to measure the effects of four-factor PCC administration (Octaplex) on TGA parameters among patients with FXaI-associated bleeding or needing urgent surgery. Methods Laboratory outcomes will include the mean paired change in TGA parameters from pre- to post-PCC administration and the proportion of participants whose post-PCC TGA values fall within a defined reference range. Clinical outcomes will include hemostatic efficacy, thromboembolic complications, and all-cause death at 30 days post-PCC. Conclusion Development of a viable and universally accessible FXaI bleed management strategy is crucial. GAUGE will provide in vivo data on the effects of PCC among patients with FXaI-associated bleeding.

Normal and pathogenic variation of RFC1 repeat expansions: implications for clinical diagnosis.

Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is an autosomal recessive neurodegenerative disease, usually caused by biallelic AAGGG repeat expansions in RFC1. In this study, we leveraged whole genome sequencing data from nearly 10 000 individuals recruited within the Genomics England sequencing project to investigate the normal and pathogenic variation of the RFC1 repeat. We identified three novel repeat motifs, AGGGC (n = 6 from five families), AAGGC (n = 2 from one family) and AGAGG (n = 1), associated with CANVAS in the homozygous or compound heterozygous state with the common pathogenic AAGGG expansion. While AAAAG, AAAGGG and AAGAG expansions appear to be benign, we revealed a pathogenic role for large AAAGG repeat configuration expansions (n = 5). Long-read sequencing was used to characterize the entire repeat sequence, and six patients exhibited a pure AGGGC expansion, while the other patients presented complex motifs with AAGGG or AAAGG interruptions. All pathogenic motifs appeared to have arisen from a common haplotype and were predicted to form highly stable G quadruplexes, which have previously been demonstrated to affect gene transcription in other conditions. The assessment of these novel configurations is warranted in CANVAS patients with negative or inconclusive genetic testing. Particular attention should be paid to carriers of compound AAGGG/AAAGG expansions when the AAAGG motif is very large (>500 repeats) or the AAGGG motif is interrupted. Accurate sizing and full sequencing of the satellite repeat with long-read sequencing is recommended in clinically selected cases to enable accurate molecular diagnosis and counsel patients and their families.

Reliability of ankle mechanics during jump landings in turned-out and parallel foot positions in professional ballet dancers.

This study aimed to determine the within- and between-session reliability of ankle mechanics and vertical ground reaction forces (vGRF) during jump landings in turned-out and parallel foot positions in professional ballet dancers. Twenty-four professional ballet dancers (men = 13, women = 11) attended two data collection sessions where they completed five maximal countermovement jumps in each foot position. The ankle joint mechanics and vGRF of the right limb were recorded via a seven-camera motion capture system and one force platform. Within- and between-session intraclass correlation coefficients (ICC), coefficients of variation (CV), standard error of measurement, and minimal detectable change were calculated for three-dimensional ankle excursion, peak ankle angle, ankle joint velocity, moment, and power, as well as peak landing vGRF, time to peak landing vGRF, loading rate, and jump height. Across both foot positions, within- (ICC: 0.17-0.96; CV: 1.4-82.3%) and between-session (ICC: 0.02-0.98; CV:1.3-57.1%) reliability ranged from poor to excellent, with ankle excursion, peak ankle angle, and jump height demonstrating the greatest ICC values (ICC: 0.65-0.96; CV: 1.4-57%). Jump landings in a turned-out foot position demonstrated better within-session reliability compared to a parallel position, however, no difference in between-session reliability across the foot positions was observed. Most ankle mechanics provide adequate between-session, but not within-session, reliability during jump landings in professional ballet dancers.

Discovery and Optimization of the First ATP Competitive Type-III c-MET Inhibitor.

Recent clinical reports have highlighted the need for wild-type (WT) and mutant dual inhibitors of c-MET kinase for the treatment of cancer. We report herein a novel chemical series of ATP competitive type-III inhibitors of WT and D1228V mutant c-MET. Using a combination of structure-based drug design and computational analyses, ligand 2 was optimized to a highly selective chemical series with nanomolar activities in biochemical and cellular settings. Representatives of the series demonstrate excellent pharmacokinetic profiles in rat in vivo studies with promising free-brain exposures, paving the way for the design of brain permeable drugs for the treatment of c-MET driven cancers.

The development and validation of an open-source accelerometery algorithm for measuring jump height and frequency in ballet.

The aim was to determine the validity of an open-source algorithm for measuring jump height and frequency in ballet using a wearable accelerometer. Nine professional ballet dancers completed a routine ballet class whilst wearing an accelerometer positioned at the waist. Two investigators independently conducted time-motion analysis to identify time-points at which jumps occurred. Accelerometer data were cross-referenced with time-motion data to determine classification accuracy. To determine the validity of the measurement of jump height, five participants completed nine jetés, nine sautés and three double tour en l'air from a force plate. The jump height predicted by the accelerometer algorithm was compared to the force plate jump height to determine agreement. Across 1440 jumps observed in time-motion analysis, 1371 true positives, 34 false positives and 69 false negatives were identified by the algorithm, resulting in a sensitivity of 0.98, a precision of 0.95 and a miss rate of 0.05. For all jump types, mean absolute error was 2.6 cm and the repeated measures correlation coefficient was 0.97. Bias was 1.2 cm and 95% limits of agreement were -4.9 to 7.2 cm. The algorithm may be used to manage jump load, implement periodization strategies, or plan return-to-jump pathways for rehabilitating athletes.

Rehearsal and Performance Volume in Professional Ballet: A Five-Season Cohort Study.

INTRODUCTION: Few studies have published data concerning the longitudinal rehearsal and performance demands experienced by professional ballet dancers. We aimed to describe the rehearsal and performance volumes undertaken across five professional ballet seasons and identify factors associated with inter-dancer and inter-production variation in dance hours. METHODS: Scheduling data were collected from 123 dancers over five seasons at The Royal Ballet. Linear mixed effects models were used to evaluate differences in: 1. weekly dance hours and seasonal performance counts across sexes, company ranks, and months; and 2. factors associated with the variation in rehearsal hours required to stage different productions. RESULTS: On average across the five seasons, a peak in performance volume was observed in December, whereas rehearsal hours peaked in October and November and between January and April. Differences in weekly dance hours were observed between company ranks (p < 0.001, range in means: 19.1 to 27.5 hours per week). Seasonal performance counts varied across company ranks (p < 0.001), ranging from 28 (95% CI: 22, 35) in principals to 113 (95% CI: 108, 118) in the rank of artist. Rehearsal durations were considerably greater in preparation for newly created ballets compared with existing ballets (77.8 vs. 37.5 hours). Rehearsal durations were also greater in preparation for longer ballets, with each additional minute of running time associated with a 0.43 hour increase in rehearsal duration (p < 0.001). Full-length ballets, however, were consistently the most time-efficient to stage due to their long performance runs compared with shorter ballets (16.2 vs. 7.4 performances). CONCLUSIONS: Training principles such as progressive overload and periodization should be implemented in professional ballet companies to manage the high and variable rehearsal and performance loads.

Effect modification of age and hypertension on cancer and prevalence of self-reported stroke - A cross-sectional study.

The objective of this study was to examine the effect modification of age on the relationship between cancer and prevalence of self-reported stroke. We used cross-sectional data from the 2015-2016 iteration of the Canadian Community Health Survey. A multivariable logistic regression model was used to assess the association between cancer and self-reported stroke. Covariates were assessed for effect modification using the maximum likelihood estimation method. We analyzed 86,809 subjects; the prevalence of self-reported stroke was 1.11%. The odds ratio for the association between cancer and self-reported stroke was 1.26 (95% CI 0.98-1.61) after adjusting for age, sex, dyslipidemia, hypertension, diabetes, heart disease, education, and household income. Age and hypertension were found to be effect modifiers, and the association between cancer and self-reported stroke was stronger in younger adults and in those without hypertension. These results suggest that cancer-associated strokes may have unique underlying mechanisms compared to conventional strokes.

Assessment of Chemical Toxicity in Adult Drosophila Melanogaster.

Human industries generate hundreds of thousands of chemicals, many of which have not been adequately studied for environmental safety or effects on human health. This deficit of chemical safety information is exacerbated by current testing methods in mammals that are expensive, labor-intensive, and time-consuming. Recently, scientists and regulators have been working to develop new approach methodologies (NAMs) for chemical safety testing that are cheaper, more rapid, and reduce animal suffering. One of the key NAMs to emerge is the use of invertebrate organisms as replacements for mammalian models to elucidate conserved chemical modes of action across distantly related species, including humans. To advance these efforts, here, we describe a method that uses the fruit fly, Drosophila melanogaster, to assess chemical safety. The protocol describes a simple, rapid, and inexpensive procedure to measure the viability and feeding behavior of exposed adult flies. In addition, the protocol can be easily adapted to generate samples for genomic and metabolomic approaches. Overall, the protocol represents an important step forward in establishing Drosophila as a standard model for use in precision toxicology.