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.

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.

The reliability, variability and minimal detectable change of multiplanar isometric trunk strength testing using a fixed digital dynamometer.

Trunk strength plays a vital role in athletic performance, rehabilitation and general health, however, current assessment methods are expensive, non-portable or unreliable. This study aimed to investigate the within- and between-session reliability, variability, standard error of measurement and minimal detectable change (MDC) of trunk strength in the sagittal (flexion and extension) and frontal planes (left and right lateral flexion) using a fixed digital dynamometer. Eighteen participants (ten men and eight women) attended two sessions separated by 7 days. Participants were fitted with a trunk harness which was secured to an immovable base via a digital dynamometer. Three maximal voluntary isometric contractions were completed across four positions (prone, supine, left-side recumbent and right-side recumbent, respectively) on a glute-hamstring raise machine. All positions demonstrated excellent reliability and low variability within session (ICC: 0.95-0.98; CV: 5-7%) and between sessions (ICC: 0.98-0.99; CV: 4-6%), across all positions. The between-session MDC ranged from 8% (prone) to 13% (right-side recumbent), translating to absolute values between 2.9 and 3.2 kg across all positions. Maximal isometric force testing using a fixed digital dynamometer provides reliable measurements of multiplanar trunk strength, providing a practical method for use in clinical practice.

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.

Measuring the spectral response of a division-of-focal-plane polarization imager using a grating monochromator.

Spectral characterizations are performed on imagers to obtain a relative spectral response (RSR) curve. This process often utilizes a grating monochromator with an output that changes polarization as a function of wavelength (our monochromator's degree of linear polarization was found to vary from less than 10% to more than 70%). When characterizing a polarization-sensitive imager, this introduces polarization artifacts into the RSR curve. We present a simple method to avoid these polarization artifacts for division-of-focal-plane polarization imagers by directly illuminating the camera with the monochromator output and calculating the S0 Stokes parameter at each super pixel, then we show consistent results from this method for two division-of-focal-plane polarization imagers. We also show that ignoring the monochromator polarization results in order-of-magnitude RSR errors. The recommended method uses an iris to limit the spatial extent of the monochromator output, which was found experimentally to increase the minimum signal-to-noise ratio by more than a factor of 2.

Cutaneous pleomorphic adenoma of the periocular region - a case series.

Mixed tumour of the skin is a rare entity also known as chondroid syringoma and pleomorphic adenoma. These usually present as slow-growing skin nodules with a smooth surface, clear boundaries, and no ulceration. Case series exist describing pleomorphic adenomas in the periocular region including the lids and orbit, separate to the more familiar lacrimal gland pleomorphic adenoma. These may arise from accessory or ectopic lacrimal gland tissue but in the eyelids are more likely to arise from sweat glands in the skin. Histopathological analysis of these lesions is important to identify complete excision, minimising recurrences and in identifying rare but potential malignant transformation. We describe the clinical features and outcomes in three cases of pleomorphic adenoma with two at the medial canthus (including one recurrence) and one in the brow region.

Optical transmittance of 3D printing materials.

The increasing prevalence of three-dimensional (3D) printing of optical housings and mounts necessitates a better understanding of the optical properties of printing materials. This paper describes a method for using multithickness samples of 3D printing materials to measure transmittance spectra at wavelengths from 400 to 2400 nm [visible to short-wave infrared (IR)]. In this method, 3D samples with material thicknesses of 1, 2, 3, and 4 mm were positioned in front of a uniform light source with a spectrometer probe on the opposing side to measure the light transmittance. Transmission depended primarily on the thickness and color of the sample, and multiple scattering prevented the use of a simple exponential model to relate transmittance, extinction, and thickness. A Solidworks file and a 3D printer file are included with the paper to enable measurements of additional materials with the same method.

Injury epidemiology in professional ballet: a five-season prospective study of 1596 medical attention injuries and 543 time-loss injuries.

OBJECTIVES: To describe the incidence rate, severity, burden and aetiology of medical attention and time-loss injuries across five consecutive seasons at a professional ballet company. METHODS: Medical attention injuries, time-loss injuries and dance exposure hours of 123 professional ballet dancers (women: n=66, age: 28.0±8.3 years; men: n=57, age: 27.9±8.5 years) were prospectively recorded between the 2015/2016 and 2019/2020 seasons. RESULTS: The incidence rate (per 1000 hours) of medical attention injury was 3.9 (95% CI 3.3 to 4.4) for women and 3.1 (95% CI 2.6 to 3.5) for men. The incidence rate (per 1000 hours) of time-loss injury was 1.2 (95% CI 1.0 to 1.5) for women and 1.1 (95% CI 0.9 to 1.3) for men. First Soloists and Principals experienced between 2.0-2.2 additional medical attention injuries per 1000 hours and 0.9-1.1 additional time-loss injuries per 1000 hours compared with Apprentices (p≤0.025). Further, intraseason differences were observed in medical attention, but not time-loss, injury incidence rates with the highest incidence rates in early (August and September) and late (June) season months. Thirty-five per cent of time-loss injuries resulted in over 28 days of modified dance training. A greater percentage of time-loss injuries were classified as overuse (women: 50%; men: 51%) compared with traumatic (women: 40%; men: 41%). CONCLUSION: This is the first study to report the incidence rate of medical attention and time-loss injuries in professional ballet dancers. Incidence rates differed across company ranks and months, which may inform targeted injury prevention strategies.

Jumping in Ballet: A Systematic Review of Kinetic and Kinematic Parameters.

AIMS: Understanding the biomechanics of jumping in ballet dancers provides an opportunity to optimize performance and mitigate injury risk. This systematic review aimed to summarize research investigating kinetics and kinematics of jumping in ballet dancers. METHODS: PubMed (MEDLINE), SPORTDiscus, and Web of Science were systematically searched for studies published before December 2020. Studies were required to investigate dancers specializing in ballet, assess kinetics or kinematics during take-off or landing, and be published in English. RESULTS: A total of 3,781 articles were identified, of which 29 met the inclusion criteria. Seven studies investigated take-off (kinetics: n = 6; kinematics: n = 4) and 23 studies investigated landing (kinetics: n = 19; kinematics: n = 12). Included articles were categorized into six themes: Activity Type (n = 10), Environment and Equipment (n = 10), Demographics (n = 8), Physical Characteristics (n = 3), Injury Status (n = 2), and Skill Acquisition and Motor Control (n = 1). Peak landing vertical ground reaction force (1.4-9.6 times body weight) was most commonly reported. Limited evidence suggests greater ankle involvement during the take-off of ballet jumps compared to countermovement jumps. There is also limited evidence indicating greater sagittal plane joint excursions upon landing in ballet dancers compared to non-dancers, primarily through a more extended lower extremity at initial contact. Only 4 articles investigated male ballet dancers, which is a notable gap in the literature. CONCLUSIONS: The findings of this review can be used by dance science and medicine practitioners to improve their understanding of jumping in ballet dancers.

D-Dimer Enhances Risk-Targeted Thromboprophylaxis in Ambulatory Patients with Cancer.

BACKGROUND: Thromboprophylaxis for ambulatory patients with cancer is effective, although uncertainties remain on who should be targeted. Using D-dimer values from individuals enrolled to the AVERT trial, we sought to identify and validate a more efficient venous thromboembolism (VTE) risk threshold for thromboprophylaxis. MATERIALS AND METHODS: The AVERT trial compared thromboprophylaxis with apixaban with placebo among patients with cancer with a Khorana Risk Score ≥2. The D-dimer measured at randomization was used to calculate an individualized 6-month VTE risk using the validated CATScore. A modified intention-to-treat analysis was used to assess efficacy (VTE) and safety (major and overall bleeding) in the (a) complete cohort and (b) ≥8% and < 8% 6-month VTE risk thresholds. RESULTS: Five hundred seventy-four patients were randomized in the AVERT trial; 466 (81%) with baseline D-dimer were included in the study. Two hundred thirty-seven subjects received apixaban; 229 received placebo. In the complete cohort, there were 13 (5.5%) VTE events in the apixaban arm compared with 26 (11.4%) events in the placebo arm (adjusted hazard ratio [aHR] 0.49 [0.25-0.95], p < .05). Number needed to treat (NNT) to prevent one VTE = 17. Eighty-two (35%) and 72 (31%) patients in the apixaban and placebo arms, respectively, had a 6-month VTE risk ≥8%. In this subgroup, 7 (8.4%) VTE events occurred with apixaban and 19 (26.3%) events with placebo (aHR 0.33 [0.14-0.81], p < .05), NNT = 6. Individuals with a VTE risk <8% derived no benefit from apixaban thromboprophylaxis (aHR 0.89 [0.30-2.65), p = .84). Increased rates of overall bleeding were observed with apixaban in both the complete (aHR 2.11 [1.09-4.09], p < .05) and ≥ 8% predicted risk cohorts (aHR 2.87 [0.91-9.13], p = .07). CONCLUSION: A 6-month VTE risk threshold of ≥8% increases the efficiency of risk-targeted thromboprophylaxis in ambulatory patients with cancer. IMPLICATIONS FOR PRACTICE: Ambulatory patients with cancer receiving chemotherapy have an increased risk of venous thromboembolism (VTE). A Khorana Risk Score (KRS) ≥2 is currently the suggested threshold for thromboprophylaxis. Using baseline D-dimer values from individuals enrolled to the AVERT trial, this retrospective validation study identifies a 6-month VTE risk of ≥8% as a more efficient threshold for thromboprophylaxis. At this threshold, the number needed to treat to prevent one VTE is 6, compared with 17 when using a KRS ≥2. Conversely, individuals with a predicted risk of <8% derive no clinical benefit from thromboprophylaxis. Future prospective studies should validate this threshold for outpatient thromboprophylaxis.

Lidar remote sensing of the aquatic environment: invited.

This paper is a review of lidar remote sensing of the aquatic environment. The optical properties of seawater relevant to lidar remote sensing are described. The three main theoretical approaches to understanding the performance of lidar are considered (the time-dependent radiative transfer equation, Monte Carlo simulations, and the quasi-single-scattering assumption). Basic lidar instrument design considerations are presented, and examples of lidar studies from surface vessels, aircraft, and satellites are given.

Lidar measurements of the diffuse attenuation coefficient in Yellowstone Lake.

Airborne lidar study of lake ecosystems is still a relatively unexplored field. In this paper we present measurements of the diffuse attenuation coefficient of downwelling irradiance (Kd) obtained using a 532 nm airborne lidar in flights during 2004 and 2016 over Yellowstone Lake, Yellowstone National Park, Wyoming, USA. We compare the lidar measurements with MODIS Kd data, discuss the impact that local weather and river inflows/outflows may have had on the data, compare to previous models of the diffuse attenuation coefficient, and examine several published relationships converting Kd to Secchi disk depth.

Digital all-sky polarization imaging of the total solar eclipse on 21 August 2017 in Rexburg, Idaho, USA.

All-sky polarization images were measured from sunrise to sunset and during a cloud-free totality on 21 August 2017 in Rexburg, Idaho using two digital three-camera all-sky polarimeters and a time-sequential liquid-crystal-based all-sky polarimeter. Twenty-five polarimetric images were recorded during totality, revealing a highly dynamic evolution of the distribution of skylight polarization, with the degree of linear polarization becoming nearly zenith-symmetric by the end of totality. The surrounding environment was characterized with an infrared cloud imager that confirmed the complete absence of clouds during totality, an AERONET solar radiometer that measured aerosol properties, a portable weather station, and a hand-held spectrometer with satellite images that measured surface reflectance at and near the observation site. These observations confirm that previously observed totality patterns are general and not unique to those specific eclipses. The high temporal image resolution revealed a transition of a neutral point from the zenith in totality to the normal Babinet point just above the Sun after third contact, providing the first indication that the transition between totality and normal daytime polarization patterns occurs over of a time period of approximately 13 s.

Detection of polarization neutral points in observations of the combined corona and sky during the 21 August 2017 total solar eclipse.

We report the results of polarimetric observations of the total solar eclipse of 21 August 2017 from Rexburg, Idaho (USA). We use three synchronized DSLR cameras with polarization filters oriented at 0°, 60°, and 120° to provide high-dynamic-range RGB polarization images of the corona and surrounding sky. We measure tangential coronal polarization and vertical sky polarization, both as expected. These observations provide detailed detections of polarization neutral points above and below the eclipsed Sun where the coronal polarization is canceled by the sky polarization. We name these special polarization neutral points after Minnaert and Van de Hulst.

High mutational rates of large-scale duplication and deletion in Daphnia pulex.

Knowledge of the genome-wide rate and spectrum of mutations is necessary to understand the origin of disease and the genetic variation driving all evolutionary processes. Here, we provide a genome-wide analysis of the rate and spectrum of mutations obtained in two Daphnia pulex genotypes via separate mutation-accumulation (MA) experiments. Unlike most MA studies that utilize haploid, homozygous, or self-fertilizing lines, D. pulex can be propagated ameiotically while maintaining a naturally heterozygous, diploid genome, allowing the capture of the full spectrum of genomic changes that arise in a heterozygous state. While base-substitution mutation rates are similar to those in other multicellular eukaryotes (about 4 × 10(-9) per site per generation), we find that the rates of large-scale (>100 kb) de novo copy-number variants (CNVs) are significantly elevated relative to those seen in previous MA studies. The heterozygosity maintained in this experiment allowed for estimates of gene-conversion processes. While most of the conversion tract lengths we report are similar to those generated by meiotic processes, we also find larger tract lengths that are indicative of mitotic processes. Comparison of MA lines to natural isolates reveals that a majority of large-scale CNVs in natural populations are removed by purifying selection. The mutations observed here share similarities with disease-causing, complex, large-scale CNVs, thereby demonstrating that MA studies in D. pulex serve as a system for studying the processes leading to such alterations.

All-sky polarization imaging of cloud thermodynamic phase.

Knowing the cloud thermodynamic phase (if a cloud is composed of ice crystals or liquid droplets) is crucial for many cloud remote sensing measurements. Further, this knowledge can help in simulating and interpreting cloud radiation measurements to better understand the role of clouds in climate, weather, and optical propagation. Knobelspiesse et al. [Atmos. Meas. Tech.8, 1537 (2015)10.5194/amt-8-1537-2015] showed that, for simulated zenith observations, the algebraic sign of the S1 Stokes parameter (related to the difference between perpendicular and parallel linear polarization in the scattering plane) can be used to detect cloud thermodynamic phase when observed with a ground-based passive polarimeter. In this paper, we describe the use of our all-sky imaging polarimeter to experimentally test this proposed method of detecting cloud thermodynamic phase in the entire sky dome. The zenith cloud phase was validated with a dual-polarization lidar instrument.

Dynamics of Cadmium Acclimation in Daphnia pulex: Linking Fitness Costs, Cross-Tolerance, and Hyper-Induction of Metallothionein.

Acclimation increases tolerance to stress in individuals but is assumed to contribute fitness costs when the stressor is absent, though data supporting this widely held claim are sparse. Therefore, using clonal (i.e., genetically identical) cultures of Daphnia pulex, we isolated the contributions of acclimation to the regulation of the metal response gene, metallothionein 1 (MT1), and defined the reproductive benefits and costs of cadmium (Cd)-acclimation. Daphnia pulex were exposed for 50 parthenogenetic generations to environmentally realistic levels (1 µg Cd/L), and tolerance to Cd and other metals assessed during this period via standard toxicity tests. These tests revealed (1) increased tolerance to Cd compared to genetically identical nonacclimated cultures, (2) fitness costs in Cd-acclimated Daphnia when Cd was removed, and (3) cross-tolerance of Cd-acclimated Daphnia to zinc and silver, but not arsenic, thereby defining a functional role for metallothionein. Indeed, Cd-acclimated clones had significantly higher expression of MT1 mRNA than nonacclimated clones, when Cd exposed. Both the enhanced induction of MT1 and tolerant phenotype were rapidly lost when Cd was removed (1-2 generations), which is further evidence of acclimation costs. These findings provide evidence for the widely held view that acclimation is costly and are important for investigating evolutionary principles of genetic assimilation and the survival mechanisms of natural populations that face changing environments.

Genome-Wide Stress Responses to Copper and Arsenic in a Field Population of Daphnia.

Over the past decade, significant advances have been made to unravel molecular mechanisms of stress response in different ecotoxicological model species. Within this study, we focus on population level transcriptomic responses of a natural population of Daphnia magna Straus, (1820), to heavy metals. We aim to characterize the population level transcriptomic responses, which include standing genetic variation, and improve our understanding on how populations respond to environmental stress at a molecular level. We studied population level responses to two heavy metals, copper and arsenic, and their binary mixture across time. Transcriptomic patterns identified significantly regulated gene families and genes at the population level including cuticle proteins and resilins. Furthermore, some of these differentially regulated gene families, such as cuticle proteins, were also significantly enriched for genetic variations including SNPs and MNPs. In general, genetic variation was observed in specific gene families, many of which are known to be involved in stress response. Overall, our results indicate that molecular stress responses can be identified within natural populations and that linking molecular mechanisms with genetic variation at the population level could contribute significantly to adverse outcome frameworks.

Reflective all-sky thermal infrared cloud imager.

A reflective all-sky imaging system has been built using a long-wave infrared microbolometer camera and a reflective metal sphere. This compact system was developed for measuring spatial and temporal patterns of clouds and their optical depth in support of applications including Earth-space optical communications. The camera is mounted to the side of the reflective sphere to leave the zenith sky unobstructed. The resulting geometric distortion is removed through an angular map derived from a combination of checkerboard-target imaging, geometric ray tracing, and sun-location-based alignment. A tape of high-emissivity material on the side of the reflector acts as a reference that is used to estimate and remove thermal emission from the metal sphere. Once a bias that is under continuing study was removed, sky radiance measurements from the all-sky imager in the 8-14 µm wavelength range agreed to within 0.91 W/(m2 sr) of measurements from a previously calibrated, lens-based infrared cloud imager over its 110° field of view.