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Acute compartment syndrome (ACS) of the thigh following femoral fracture has been rarely reported in previous literature. This condition must be diagnosed quickly to prevent the affected limb becoming ischaemic. We document the management of ACS of the thigh in a healthy male patient who suffered a proximal femur fracture following a high-speed road traffic accident. Early identification of characteristic clinical signs allowed for a diagnosis of ACS to be made and then managed with an emergency fasciotomy. The patient is a bodybuilder with an exceptionally large muscle mass. This made ACS more difficult to identify and wound closure a complex process over a period of 13 days. We aimed to highlight the importance of maintaining a high index of suspicion for ACS following traumatic injuries, recognising that ACS in larger patients can be mistaken for an increased analgesia requirement and closing fasciotomies slowly using mass tension sutures.

Many head acceleration events (HAEs) observed in youth football emanate from a practice environment. This study aimed to evaluate HAEs in youth football practice drills using a mouthpiece-based sensor, differentiating between inertial and direct HAEs. Head acceleration data were collected from athletes participating on 2 youth football teams (ages 11–13 y) using an instrumented mouthpiece-based sensor during all practice sessions in a single season. Video was recorded and analyzed to verify and assign HAEs to specific practice drill characteristics, including drill intensity, drill classification, and drill type. HAEs were quantified in terms of HAEs per athlete per minute and peak linear and rotational acceleration and rotational velocity. Mixed-effects models were used to evaluate the differences in kinematics, and generalized linear models were used to assess differences in HAE frequency between drill categories. A total of 3237 HAEs were verified and evaluated from 29 football athletes enrolled in this study. Head kinematics varied significantly between drill categorizations. HAEs collected at higher intensities resulted in significantly greater kinematics than lower-intensity drills. The results of this study add to the growing body of evidence informing evidence-based strategies to reduce head impact exposure and concussion risk in youth football practices.

Occupational therapy is beneficial among adults with chronic pain; however, occupational therapy interventions addressing earlier phases of pain have not been clearly explicated. This systematic review characterized acute and subacute interventions billable by occupational therapy after hip or knee replacement to improve pain and function. Seven articles met inclusion criteria. Six articles had a low risk of bias. Three intervention types were found: task-oriented exercise, water-based, and modalities. Only task-oriented interventions improved both pain and function one-year after surgery. There are long-term benefits to early task-oriented exercise. Further research is needed to contextualize occupational therapy's role in early pain interventions.

Introduction Il existe des différences liées au sexe dans les taux d’obésité, les régimes alimentaires et les temps d’écoute de télévision des enfants. Les enfants continuent à être exposés aux publicités d’aliments malsains à la télévision au Canada. Notre objectif était d’étudier les différences entre les sexes dans l’exposition à la publicité alimentaire chez les enfants et les jeunes de 2 à 17 ans dans quatre marchés anglophones canadiens. Méthodologie Nous avons obtenu des données sur la publicité télé diffusée sur 24 heures auprès de la société Numerator pour janvier à décembre 2019, dans quatrevilles canadiennes (Vancouver, Calgary, Montréal et Toronto). L’exposition à la publicité alimentaire destinée aux enfants a été analysée dans les 10 stations de télévision les plus populaires chez les enfants puis a été comparée selon le sexe, globalement et en fonction de la catégorie d’aliments, de la station de télévision, du modèle de profilage des nutriments proposé par Santé Canada et des techniques de marketing. L’exposition a été estimée à l’aide de points d’exposition bruts et les différences entre les sexes ont été décrites en valeurs relatives et en valeurs absolues. Résultats Les garçons et les filles ont été exposés à un niveau élevé de publicité sur les aliments malsains et à une multitude de techniques de marketing dans les quatre villes. Des différences entre les sexes ont été relevées entre les villes et au sein de celles-ci. Par rapport aux filles, les garçons à Vancouver et à Montréal ont visionné respectivement 24,7 % et 24,0 % plus de publicités sur des aliments malsains par personne sur un an etont été exposés à 90,2 et 133,4 appels à l’action supplémentaires, à 93,3 et 97,8 évocations supplémentaires d’un avantage lié à la santé et à 88,4 et 81,0 produits supplémentaires attrayants pour les enfants. Conclusion La télévision est une source importante d’exposition des enfants à la publicité alimentaire, avec des différences claires entre les sexes. Les décideurs doivent tenir compte du sexe lorsqu’ils mettent en place des restrictions et des activités de surveillance en lien avec la publicité alimentaire.

BACKGROUND: Indian Wild Orange (Citrus indica Tanaka) is an endangered and endemic species from northeast India for which effective ex situ conservation strategies, including embryo cryopreservation, are urgently needed. MATERIALS AND METHODS: Desiccation tolerance and cryopreservation ability for embryonic axes of Citrus indica was determined using three techniques (air desiccation-freezing, PVS2 vitrification-freezing and encapsulation-dehydration-freezing). Success was assessed as survival and recovery in vitro. RESULTS: Successful cryopreservation of embryonic axes was achieved using all three methods, with the highest survival achieved when using air desiccationfreezing (90%) followed by encapsulation-dehydration (85%) and PVS2 vitrification cryopreservation (80%). Regeneration levels were lower than survival levels for all three proceedures. Post-cryo regeneration success was: encapsulation-dehydration (64%) > air desiccation-freezing (55%) > PVS2 vitrification (52%). CONCLUSION: Although there was relatively high post-cryopreservation recovery growth obtained using all the three techniques, the air desiccation-freezing technique is preferred, as it is a simple, practical and reproducible technique for the long-term cryobanking of this important wild species.

Introduction Sex differences exist in children’s obesity rates, dietary patterns and television viewing. Television continues to be a source of unhealthy food advertising exposure to children in Canada. Our objective was to examine sex differences in food advertising exposure in children aged 2 to 17 years across four Canadian Englishlanguage markets. Methods We licensed 24-hour television advertising data from the company Numerator for January through December 2019, in four cities (Vancouver, Calgary, Montréal and Toronto) across Canada. Child food advertising exposure overall, by food category, television station, Health Canada’s proposed nutrient profiling model, and marketing techniques were examined on the 10 most popular television stations among children and compared by sex. Advertising exposure was estimated using gross rating points, and sex differences were described using relative and absolute differences. Results Both male and female children were exposed to an elevated level of unhealthy food advertising and a plethora of marketing techniques across all four cities. Differences between sexes were evident between and within cities. Compared to females, males in Vancouver and Montréal viewed respectively 24.7% and 24.0% more unhealthy food ads/person/year and were exposed to 90.2 and 133.4 more calls to action, 93.3 and 97.8 more health appeals, and 88.4 and 81.0 more products that appeal to children. Conclusion Television is a significant source of children’s exposure to food advertising, with clear sex differences. Policy makers need to consider sex when developing food advertising restrictions and monitoring efforts.

Mitochondrial function and metabolic homeostasis are integral to cardiovascular function and influence how vascular cells respond to stress. However, little is known regarding how mitochondrial redox control mechanisms and metabolic regulation interact in the developing lungs. Here we show that human Obg-like ATPase-1 (OLA1) couples redox signals to the metabolic response pathway by activating metabolic gene transcription in the nucleus. We observed that OLA1 phosphorylation at Ser232/Tyr236 triggers its translocation from the cytoplasm/mitochondria into the nucleus. Subsequent phosphorylation of OLA1 at Thr325 effectively changes its biochemical function from ATPase to GTPase, promoting the expression of genes involved in the mitochondrial bioenergetic function. This process is regulated by extracellular-regulated kinases (ERK1/2), which were restrained by protein phosphatases 1A (PP1A) when stress abated. Knockdowns of ERK1 or OLA1 mutated to a phosphoresistant T325A mutant blocked its nuclear translocation, compromised the expression of nuclear-encoded mitochondrial genes, and as a consequence, led to cellular energy depletion. Moreover, the lungs of OLA1 knockout mice have fewer numbers of mitochondria, lower cellular ATP levels, and higher lactate levels. The ensuing mitochondrial metabolic dysfunction resulted in abnormal behaviors of pulmonary vascular cells and significant vascular remodeling. Our findings demonstrate that OLA1 is an important component of the mitochondrial retrograde communication pathways that couple stress signals with metabolic genes in the nucleus. Thus, phosphorylation-dependent nuclear OLA1 localization that governs cellular energy metabolism is critical to cardiovascular function.

We characterized cryoablation as a mode of clinical intervention in adult woodchucks with hepatocellular carcinoma (HCC). Woodchucks (n = 4) were infected with woodchuck hepatitis virus at birth and developed LI-RADS-5 hypervascular HCC. At 21 mo of age, they underwent ultrasound (US), contrast-enhanced CT (CECT) imaging, and US-guided subtotal cryoablation (IcePearl 2.1 CX, Galil, BTG) of their largest tumor (Mean HCC volume of 49 ± 9 cm3). Cryoablation was performed using two 10-min freeze cycles, each followed by an 8-min thaw cycle. The first woodchuck developed significant hemorrhage after the procedure and was euthanized. In the other 3 woodchucks, the probe track was cauterized and all 3 completed the study. Fourteen days after ablation, CECT was performed, and woodchucks were euthanized. Explanted tumors were sectioned using subject-specific, 3D-printed cutting molds. Initial tumor volume, the size of the cryoablation ice ball, gross pathology and hematoxylin and eosin–stained tissue sections were evaluated. On US, the edges of the solid ice balls were echogenic with dense acoustic shadowing and average dimensions of 3.1 ± 0.5 × 2.1 ± 0.4 cm and cross-sectional area of 4.7 ± 1.0 cm 2. On day 14 after cryoablation, CECT of the 3 woodchucks showed devascularized hypo-attenuating cryolesions with dimensions of 2.8 ± 0.3 × 2.6 ± 0.4 × 2.93 ± 0.7 cm and a cross-sectional area of 5.8 ± 1.2 cm2. Histopathologic evaluation showed hemorrhagic necrosis with a central amorphous region of coagulative necrosis surrounded by a rim of karyorrhectic debris. A rim of approximately 2.5 mm of coagulative necrosis and fibrous connective tissue clearly demarcated the cryolesion from adjacent HCC. Partial cryoablation of tumors produced coagulative necrosis with well-defined ablation margins at 14 d. Cauterization appeared to prevent hemorrhage after cryoablation of hypervascular tumors. Our findings indicate that woodchucks with HCC may provide a predictive preclinical model for investigating ablative modalities and developing new combination therapies.

Background No definitive largescale data exist evaluating the role of pathologically defined regression changes within the primary tumour and lymph nodes (LN) of resected oesophagogastric (OG) adenocarcinoma following neoadjuvant chemotherapy and the impact on survival. Methods Data and samples from two large prospective randomised trials (UK MRC OE05 and ST03) were pooled. Stained slides were available for central pathology review from 1619 patients. Mandard tumour regression grade (TRG) and regression of tumour within LNs (LNR: scored as present/absent) were assessed and correlated with overall survival (OS) using a Cox regression model. An exploratory analysis to define subgroups with distinct prognoses was conducted using a classification and regression tree (CART) analysis. Results Neither trial demonstrated a relationship between TRG score and the presence or absence of LNR. In univariable analysis, lower TRG, lower ypN stage, lower ypT stage, presence of LNR, presence of well/moderate tumour differentiation, and absence of tumour at resection margin were all associated with better OS. However, the multivariable analysis demonstrated that only ypN, ypT, grade of differentiation and resection margin (R0) were independent indicators of prognosis. Exploratory CART analysis identified six subgroups with 3-year OS ranging from 83% to 22%; with ypN stage being the most important single prognostic variable. Conclusions Pathological LN stage within the resection specimen was the single most important determiner of survival. Our results suggest that the assessment of regression changes within the primary tumour or LNs may not be necessary to define the prognosis further.

The decision to intervene in endangered species management is often complicated. Migratory species exemplify this difficulty because they experience diverse threats at different times and places that can act cumulatively and synergistically on their populations. We use population viability analysis (PVA) to compare potential conservation interventions on the critically endangered, migratory Orange-bellied Parrot Neophema chrysogaster. This species suffers high juvenile mortality, but it is not clear why this is so. Given uncertainty about the best recovery strategy, we compare PVA scenarios that simulate various ways of utilizing captive-bred parrots to support the wild population in the context of unresolved threatening processes. Increasing the number of juveniles entering the population each year had the greatest benefit for population growth rate and size. Directly lowering juvenile mortality rates is difficult given uncertainty about the drivers of mortality in the wild. In lieu of this, releasing 100 juveniles from captivity to the wild population each autumn (either as a stand-alone action, or in combination with other interventions) was the most feasible and straightforward intervention of the options we tested. However, our PVAs also show that unless substantial and sustainable reductions can be made to juvenile mortality rates, Orange-bellied Parrots will remain dependent on intensive conservation management. This study highlights the utility of PVAs for answering practical questions about how to implement species conservation. PVAs provide a way to incorporate the best available information in a replicable modelling framework, and to identify impacts of parameter uncertainty on demographic trends.

With a range of programs focused on local plant and insect conservation, the Cincinnati Zoo & Botanical Garden works with partners and our communities to restore landscapes and thriving ecosystems for wildlife and people. We used organizational identity theory (OIT) to evaluate the current strategies and practices of five programs and determine opportunities for adaptation to better achieve our organizational conservation goals. Case studies ranged from habitat restoration of wetlands and gardens to community engagement to encourage individual gardeners and the reintroduction of endangered plants and insects. We present program characteristics and how collaborative partnerships facilitate opportunities for zoos to lead the conservation of local flora and fauna. The OIT framework reveals components critical to strategy implementation and best practices relevant to other zoos, aquariums, and botanical gardens when evaluating their collaborative conservation initiatives.

Although the previous World Radiocommunications Conference (WRC-19) attempted to resolve spectrum-sharing issues among the disparate new satellite constellations, issues have multiplied as these constellations are coming into use before all the rules have been created. The upcoming WRC, to be held at the end of 2023, will grapple with spectrum and situational sharing issues among constellations that are larger than ever before, and that are disrupting national regimes designed for licensing more traditional, one-at-a-time geostationary satellites. The agenda for WRC-27 will surely include multiple areas of study related to constellations, and the International Telecommunication Union (ITU) will need to work closely with the UN’s Office of Outer Space Affairs (UNOOSA) to resolve situational issues such as traffic management, debris, and the sustainability of the outer space environment. The emergence of operational constellations is disrupting legal regimes for states and industrial players, and future Agenda Items (AIs) should be added to WRC-27 or future Committee on the Peaceful Uses of Outer Space (COPUOS) sessions. constellations, LEO, ITU, spectrum, WRC

Historically, western societies have considered body image issues to predominantly affect young, White women. While in recent years men's body image issues have been increasingly highlighted by researchers and the media alike, many instruments currently used to identify clinically significant body image disturbances were developed and validated with samples solely of women and/or girls. One such measure, Killen et al.'s (1994) Weight Concerns Scale (WCS), was initially validated in a sample of adolescent girls. The WCS has yet to be validated in samples of men, despite being used in large national surveys of college men and women (e.g., the Healthy Minds Study; HMS) used to inform resources on college campuses. Accordingly, we used structural equation modeling to conduct invariance testing between college student cisgender men's (

Palm trees are propagated almost exclusively by seeds and each species germinates under a certain temperature range. In this sense, the two-way thermogradient plate may be used to determine temperature limits for germination and seed response to temperature. The objective was to define the alternating temperature regime promoting higher and faster seed germination of Carpentaria acuminata and Phoenix canariensis palms using a two-way thermogradient plate. This equipment allowed 64 combinations of alternating and constant temperatures, ranging from 6.97 to 36.42 ºC for C. acuminata, and 7.96 to 35.94 ºC for P. canariensis. Seeds were sown in Petri dishes (25 x 9 cm) containing 1% water agar. Linear regressions were estimated to determine cardinal temperatures. After 50 days, non-germinated seeds were transferred from the two-way thermogradient plate to a germination chamber at 30 °C. The temperature regime promoting highest seed germination percentage of C. acuminata was 30.45/33.00 °C (day/night), with minimum, optimum, and maximum temperatures of 9.13, 28.53, and 36.33 °C, respectively. For seed germination of P. canariensis, the most appropriate temperature regime was 29.77/17.93 °C (day/night), with minimum, optimum, and maximum temperatures of 9.53, 28.03, and 35.43 °C, respectively.

Uturuncu volcano in southern Bolivia last erupted around 250 ka but is exhibiting signs of recent activity, including over 50 yr of surface uplift, elevated seismic activity, and fumarolic activity. We studied the spatial and temporal scales of surface deformation from 1992 to 2021 to better understand subsurface activity. We tracked Uturuncu’s recent deformation using interferometric synthetic aperture radar (InSAR) data and the global navigation satellite system (GNSS) station UTUR, located near Uturuncu’s summit. We observed a spatially coherent signal of uplift from 2014 to 2021 from Sentinel-1 A/B satellites that indicates the Altiplano-Puna magma body, located 19–24 km below ground level, and previously noted as the source of the large region of deformation, is still active. The ground is now uplifting at a rate of ~3 mm/yr compared to prior rates of ~10 mm/yr. We corroborated this waning uplift with in situ data from station UTUR. We combined the Sentinel-1 data with TerraSAR-X interferograms to constrain an ~25 km2 region of subsidence located 11 km SSW of Uturuncu, with a source depth of 2.1 km below ground level to an active period of ~2.5 yr with ~5 mm/yr subsidence. We developed a conceptual model that relates these varying depths and time scales of activity in a transcrustal magmatic system. We associate the surface uplift with pressurization from ascending gases and brines from magmatic reservoirs in the midcrust. We infer the existence of brine lenses in the shallow hydrothermal system based on low subsurface resistivity correlated with surface subsidence.

This essay offers a summary of the impact of COVID-19 and efficacy of the responses in Latin America and the Caribbean, with a particular focus on Perú, México, and Cuba. Because so much has already been written on COVID-19, the goal of this article is to move beyond what has already been said, providing a briefing on what has been most unusual and counter-intuitive regarding the pandemic in the region. Focusing on Perú, México, and Cuba allows the spotlighting of several critical issues. Cuba, with a model public health care system and successful bio-tech sector, was largely spared the first wave of the pandemic, only to be severely affected by the Omicron variants. Perú and México have suffered during the pandemic the very worst excess mortality rates in the world. This essay explores these matters, explaining how a lethal confluence of negative forces came together with deadly consequences for the people of Latin America and the Caribbean.

Purpose: To describe the initial steps in the development of a family-completed, modified version of the Gross Motor Function Measure (GMFM-88) to report gross motor function of young people with cerebral palsy in their natural environments. Methods: Development of the Gross Motor Function – Family Report (GMF-FR) was based on expert opinion involving 13 experienced clinicians and researchers, in four steps: (1) item identification to target items that reflect functional gross motor performance; (2) item selection; (3) critical analysis of the items; and (4) item and scoring modification. Results: Several modifications to existing items and scoring were made, including wording changes to optimize ease of families’ understanding, the addition of photographs to illustrate all items, changes to the items to enable use of furniture instead of specialized equipment, and modifications to scoring criteria to ensure a focus on functional motor skills. Ultimately, 30 items were selected, and specific testing/scoring instructions were created for each item. Conclusions: GMF-FR is a new family-report tool, based on the GMFM-88. When validated, it can be used as a telehealth outcome measure to capture family-reported functional motor skill performance in home and community environments.

Background Centralising specialist cancer surgical services is an example of major system change. High-volume centres are recommended to improve specialist cancer surgery care and outcomes. Objective Our aim was to use a mixed-methods approach to evaluate the centralisation of specialist surgery for prostate, bladder, renal and oesophago-gastric cancers in two areas of England [i.e. London Cancer (London, UK), which covers north-central London, north-east London and west Essex, and Greater Manchester Cancer (Manchester, UK), which covers Greater Manchester]. Design Stakeholder preferences for centralising specialist cancer surgery were analysed using a discrete choice experiment, surveying cancer patients (n = 206), health-care professionals (n = 111) and the general public (n = 127). Quantitative analysis of impact on care, outcomes and cost-effectiveness used a controlled before-and-after design. Qualitative analysis of implementation and outcomes of change used a multisite case study design, analysing documents (n = 873), interviews (n = 212) and non-participant observations (n = 182). To understand how lessons apply in other contexts, we conducted an online workshop with stakeholders from a range of settings. A theory-based framework was used to synthesise these approaches. Results Stakeholder preferences – patients, health-care professionals and the public had similar preferences, prioritising reduced risk of complications and death, and better access to specialist teams. Travel time was considered least important. Quantitative analysis (impact of change) – only London Cancer’s centralisations happened soon enough for analysis. These changes were associated with fewer surgeons doing more operations and reduced length of stay [prostate –0.44 (95% confidence interval –0.55 to –0.34) days; bladder –0.563 (95% confidence interval –4.30 to –0.83) days; renal –1.20 (95% confidence interval –1.57 to –0.82) days]. The centralisation meant that renal patients had an increased probability of receiving non-invasive surgery (0.05, 95% confidence interval 0.02 to 0.08). We found no evidence of impact on mortality or re-admissions, possibly because risk was already low pre-centralisation. London Cancer’s prostate, oesophago-gastric and bladder centralisations had medium probabilities (79%, 62% and 49%, respectively) of being cost-effective, and centralising renal services was not cost-effective (12% probability), at the £30,000/quality-adjusted life-year threshold. Qualitative analysis, implementation and outcomes – London Cancer’s provider-led network overcame local resistance by distributing leadership throughout the system. Important facilitators included consistent clinical leadership and transparent governance processes. Greater Manchester Cancer’s change leaders learned from history to deliver the oesophago-gastric centralisation. Greater Manchester Cancer’s urology centralisations were not implemented because of local concerns about the service model and local clinician disengagement. London Cancer’s network continued to develop post implementation. Consistent clinical leadership helped to build shared priorities and collaboration. Information technology difficulties had implications for interorganisational communication and how reliably data follow the patient. London Cancer’s bidding processes and hierarchical service model meant that staff reported feelings of loss and a perceived ‘us and them’ culture. Workshop – our findings resonated with workshop attendees, highlighting issues about change leadership, stakeholder collaboration and implications for future change and evaluation. Limitations The discrete choice experiment used a convenience sample, limiting generalisability. Greater Manchester Cancer implementation delays meant that we could study the impact of only London Cancer changes. We could not analyse patient experience, quality of life or functional outcomes that were important to patients (e.g. continence). Future research Future research may focus on impact of change on care options offered, patient experience, functional outcomes and long-term sustainability. Studying other approaches to achieving high-volume services would be valuable. Study registration National Institute for Health and Care Research (NIHR) Clinical Research Network Portfolio reference 19761. Funding This project was funded by the NIHR Health and Social Care Delivery Research programme and will be published in full in Health and Social Care Delivery Research; Vol. 11, No. 2. See the NIHR Journals Library website for further project information.

PURPOSE: New therapies including oral anticancer agents (OAAs) have improved outcomes for patients with metastatic renal cell carcinoma (mRCC). However, little is known about the quality of end-of-life (EOL) care and systemic therapy use at EOL in patients receiving OAAs or with mRCC. METHODS: We retrospectively analyzed EOL care for decedents with mRCC in two parallel cohorts: (1) patients (RCC diagnosed 2004-2015) from the University of North Carolina's Cancer Information and Population Health Resource (CIPHR) and (2) patients (diagnosed 2007-2015) from SEER-Medicare. We assessed hospice use in the last 30 days of life and existing measures of poor-quality EOL care: systemic therapy, hospital admission, intensive care unit admission, and > 1 ED visit in the last 30 days of life; hospice initiation in the last 3 days of life; and in-hospital death. Associations between OAA use, patient and provider characteristics, and EOL care were examined using multivariable logistic regression. RESULTS: We identified 410 decedents in the CIPHR cohort (53.4% received OAA) and 1,508 in SEER-Medicare (43.5% received OAA). Prior OAA use was associated with increased systemic therapy in the last 30 days of life in both cohorts (CIPHR: 26.5% v 11.0%; P < .001; SEER-Medicare: 23.4% v 11.7%; P < .001), increased in-hospital death in CIPHR, and increased hospice in the last 30 days in SEER-Medicare. Older patients were less likely to receive systemic therapy or be admitted in the last 30 days or die in hospital. CONCLUSION: Patients with mRCC who received OAAs and younger patients experienced more aggressive EOL care, suggesting opportunities to optimize high-quality EOL care in these groups.

Purpose: This cross-sectional study determines the sensitivity of muscle architecture and fat measurements of the rectus femoris (RF) and vastus lateralis (VL) muscles from ultrasound images acquired with varying transducer tilt, using a novel transducer attachment, in healthy adults. Secondary objectives were to estimate intrarater and interrater reliability of image measurement and acquisition, respectively. Methods: Thirty healthy adults participated (15 women and 15 men; 25 [SD 2.5] y). Ultrasound image acquisition was conducted by two raters at different transducer tilts relative to the skin: estimated perpendicular, and five measured angles (80°, 85°, 90°, 95°, 100°) using the transducer attachment. Muscle thickness (MT), subcutaneous fat thickness (FT), pennation angle (PA), and fascicle length (FL) were measured. Sensitivity and reliability were assessed using intra-class correlation coefficients (ICCs) and standard error of measurements (SEMs). Results: MT and FT for RF and VL were not sensitive to transducer tilt. However, PA and FL were sensitive to transducer tilt. MT and FT for both muscles showed high ICCs and low SEMs for intrarater and interrater reliability. For PA of both muscles, standardizing transducer tilt improved interrater ICCs and lowered SEMs. Conclusion: MT and FT measurements of RF and VL acquired at 60° knee flexion are robust to varying transducer tilt angles. PA measurements benefit from standardizing transducer tilt.

BackgroundA panel of IgA-based serologic assays might aid in the diagnosis of chronic enteropathy (CE) in dogs, a syndrome encompassing conditions such as food-responsive enteropathy, immunosuppressant-responsive enteropathy, and inflammatory bowel disease (also referred to as chronic inflammatory enteropathy). However, it is unclear whether these biomarkers discriminate between CE and other types of primary intestinal disorders.ObjectivesTo evaluate a diagnostic panel that measures serum concentrations of IgA directed against OmpC (ACA), canine calprotectin (ACNA), and gliadin-derived peptides (AGA) in dogs with well-characterized intestinal diseases.AnimalsFifty-five dogs with primary intestinal disease.MethodsSerum ACA, ACNA, and AGA concentrations were measured in 30 dogs with CE and 25 dogs with other intestinal diseases (non-CE population), including histoplasmosis, parasitism, E. coli-associated granulomatous colitis, and lymphoma. Serum IgA concentrations were compared among populations, and sensitivities and specificities were calculated using laboratory-provided cut-points.ResultsTwenty-six of 30 (87%) CE dogs and 21 of 25 (84%) non-CE dogs had abnormal concentrations (intermediate or high) of at least 2 markers; these proportions were not significantly different (P=.99). A serum ACA concentration ≥15 EU/mL was 86.7% (95% confidence interval [CI], 69.3%-96.2%) sensitive and 24.0% (95% CI, 9.4%-45.1%) specific for CE diagnosis. High AGA concentrations were observed in 16 of 25 (64%) non-CE dogs.Conclusions and clinical importanceThe evaluated serologic markers were poorly specific for CE diagnosis, which raises concerns that their use in clinical practice might lead to misdiagnoses and delayed or even detrimental treatments in dogs with non-CE intestinal diseases.

Immune checkpoint inhibitors (ICIs) have fundamentally improved survival from advanced cutaneous melanoma. Significant efforts have been made to understand the ICI response to identify ways to further improve outcomes. One such approach has been to investigate gene expression associated with response to ICI, which has identified various immune-related mRNA signatures, including a 6-gene IFN-γ signature (IFN-γ

Soccer, one of the most popular sports in the world, has one of the highest rates of sports-related concussions. Additionally, soccer players are frequently exposed to nonconcussive impacts from intentionally heading the ball, a fundamental component of the sport. There have been many studies on head impact exposure in soccer, but few focus on soccer practices or practice activities. This study aimed to characterize the frequency and magnitude of head impacts in National Collegiate Athletic Association Division I female soccer practice activities using a custom-fit instrumented mouthpiece. Sixteen players were instrumented over the course of 54 practice sessions. Video analysis was performed to verify all mouthpiece-recorded events and classify practice activities. Category groupings of practice activities include technical training, team interaction, set pieces, position-specific, and other. Differences in head impact rates and peak resultant kinematics were observed across activity types and category groupings. Technical training had the highest impact rate compared to other category groupings. Impacts occurring during set piece activities had the highest mean kinematic values. Understanding drill exposure can help inform coaches on training plans aimed to reduce head impact exposure for their athletes.

BackgroundInnovations in imaging and molecular characterisation together with novel treatment options have improved outcomes in advanced prostate cancer. However, we still lack high-level evidence in many areas relevant to making management decisions in daily clinical practise. The 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) addressed some questions in these areas to supplement guidelines that mostly are based on level 1 evidence.ObjectiveTo present the voting results of the APCCC 2022.Design, setting, and participantsThe experts voted on controversial questions where high-level evidence is mostly lacking: locally advanced prostate cancer; biochemical recurrence after local treatment; metastatic hormone-sensitive, non-metastatic, and metastatic castration-resistant prostate cancer; oligometastatic prostate cancer; and managing side effects of hormonal therapy. A panel of 105 international prostate cancer experts voted on the consensus questions.Outcome measurements and statistical analysisThe panel voted on 198 pre-defined questions, which were developed by 117 voting and non-voting panel members prior to the conference following a modified Delphi process. A total of 116 questions on metastatic and/or castration-resistant prostate cancer are discussed in this manuscript. In 2022, the voting was done by a web-based survey because of COVID-19 restrictions.Results and limitationsThe voting reflects the expert opinion of these panellists and did not incorporate a standard literature review or formal meta-analysis. The answer options for the consensus questions received varying degrees of support from panellists, as reflected in this article and the detailed voting results are reported in the supplementary material. We report here on topics in metastatic, hormone-sensitive prostate cancer (mHSPC), non-metastatic, castration-resistant prostate cancer (nmCRPC), metastatic castration-resistant prostate cancer (mCRPC), and oligometastatic and oligoprogressive prostate cancer.ConclusionsThese voting results in four specific areas from a panel of experts in advanced prostate cancer can help clinicians and patients navigate controversial areas of management for which high-level evidence is scant or conflicting and can help research funders and policy makers identify information gaps and consider what areas to explore further. However, diagnostic and treatment decisions always have to be individualised based on patient characteristics, including the extent and location of disease, prior treatment(s), co-morbidities, patient preferences, and treatment recommendations and should also incorporate current and emerging clinical evidence and logistic and economic factors. Enrolment in clinical trials is strongly encouraged. Importantly, APCCC 2022 once again identified important gaps where there is non-consensus and that merit evaluation in specifically designed trials.

The Deeper, Wider, Faster (DWF) program coordinates observations with telescopes across the electromagnetic spectrum, searching for transients on time-scales of milliseconds to days. The tenth DWF observing run was carried out in near real-time during September 2021, and consisted of six consecutive days of observations of the NGC 6744 galaxy group and a field containing the repeating fast radio burst FRB 190711 with the Australian Square Kilometre Array Pathfinder, the Dark Energy Camera, the Hard X-ray Modulation Telescope, and the Parkes 64-m ‘Murriyang’ radio telescope. In this work, we present the results of an image-domain search for transient, variable, and circularly polarized sources carried out with ASKAP, using data from the observing run along with test observations prior to the run and follow-up observations carried out during and after the run. We identified eight variable radio sources, consisting of one pulsar, six stellar systems (five of which exhibit circularly polarized emission), and one previously uncatalogued source. Of particular interest is the detection of pulses from the ultra-cool dwarf SCR J1845–6357 with a period of 14.2 ± 0.3 h in good agreement with the known optical rotation period, making this the slowest rotating radio-loud ultra-cool dwarf discovered.

Optimal stomatal theory predicts that stomata operate to maximise photosynthesis (Anet) and minimise transpirational water loss to achieve optimal intrinsic water-use efficiency (iWUE). We tested whether this theory can predict stomatal responses to elevated atmospheric CO2 (eCO2), and whether it can capture differences in responsiveness among woody plant functional types (PFTs). We conducted a meta-analysis of tree studies of the effect of eCO2 on iWUE and its components Anet and stomatal conductance (gs). We compared three PFTs, using the unified stomatal optimisation (USO) model to account for confounding effects of leaf–air vapour pressure difference (D). We expected smaller gs, but greater Anet, responses to eCO2 in gymnosperms compared with angiosperm PFTs. We found that iWUE increased in proportion to increasing eCO2 in all PFTs, and that increases in Anet had stronger effects than reductions in gs. The USO model correctly captured stomatal behaviour with eCO2 across most datasets. The chief difference among PFTs was a lower stomatal slope parameter (g1) for the gymnosperm, compared with angiosperm, species. Land surface models can use the USO model to describe stomatal behaviour under changing atmospheric CO2 conditions. AG gratefully acknowledges a studentship provided by the John Horseman Trust and the University of Birmingham. The BIFoR FACE facility is supported by the JABBS Foundation, the University of Birmingham and the John Horseman Trust. ARMK acknowledges support from the UK Natural Environment Research Council through grant NE/S015833/1. MJ and BEM acknowledge funding from the Australian Research Council (DE210101654, FL190100003).

Targeted therapies have transformed clinical management of advanced biliary tract cancer (BTC). Cell-free DNA (cfDNA) analysis is an attractive approach for cancer genomic profiling that overcomes many limitations of traditional tissue-based analysis. We examined cfDNA as a tool to inform clinical management of patients with advanced BTC and generate novel insights into BTC tumor biology.We analyzed next-generation sequencing data of 2068 cfDNA samples from 1671 patients with advanced BTC generated with Guardant360. We carried out clinical annotation on a multi-institutional subset (n = 225) to assess intra-patient cfDNA-tumor concordance and the association of cfDNA variant allele fraction (VAF) with clinical outcomes.Genetic alterations were detected in cfDNA in 84% of patients, with targetable alterations detected in 44% of patients. Fibroblast growth factor receptor 2 (FGFR2) fusions, isocitrate dehydrogenase 1 (IDH1) mutations, and BRAF V600E were clonal in the majority of cases, affirming these targetable alterations as early driver events in BTC. Concordance between cfDNA and tissue for mutation detection was high for IDH1 mutations (87%) and BRAF V600E (100%), and low for FGFR2 fusions (18%). cfDNA analysis uncovered novel putative mechanisms of resistance to targeted therapies, including mutation of the cysteine residue (FGFR2 C492F) to which covalent FGFR inhibitors bind. High pre-treatment cfDNA VAF was associated with poor prognosis and shorter response to chemotherapy and targeted therapy. Finally, we report the frequency of promising targets in advanced BTC currently under investigation in other advanced solid tumors, including KRAS G12C (1.0%), KRAS G12D (5.1%), PIK3CA mutations (6.8%), and ERBB2 amplifications (4.9%).These findings from the largest and most comprehensive study to date of cfDNA from patients with advanced BTC highlight the utility of cfDNA analysis in current management of this disease. Characterization of oncogenic drivers and mechanisms of therapeutic resistance in this study will inform drug development efforts to reduce mortality for patients with BTC.

Stage III Wilms' tumour (WT) represents a heterogeneous group which includes different criteria, but all stage III patients are treated according to the same study regiment. The aim of the study was to retrospectively analyse outcomes in patients with stage III due to positive resection margins (RM) only, sub-grouped in RM with viable (RM-v) and nonviable (RM-nv) tumour. Patients were treated pre- and postoperatively according to the SIOP-WT-2001 protocol in the UK-CCLG and GPOH WT trials and studies (2001-2020). There were 197 patients, including 134 with localised, abdominal stage III and 63 with overall stage IV, but abdominal stage III. Stage III due to RM-v had 126 patients, and due to RM-nv 71 patients. The overall 5-year local-relapse-free survival (RFS), event-free (EFS) and overall survival (OS) estimates for all patients with abdominal stage III RM were 95.7% (±SE1.5%), 85.1 (±SE2.6%) and 90.3% (±SE2.2%), respectively. Patients with stage III RM-nv had significantly better RFS and EFS than patients with RM-v (P = .027 and P = .003, respectively). A multivariate analysis showed that RM-v remained a significant factor for EFS when adjusted for age, presence of metastasis at diagnosis, histological risk group and overall stage in Cox regression analysis (P = .006). Patients with stage III due to RM-nv only exhibited no local recurrence and have a significantly better RFS and EFS than patients with RM-v. The results suggest that exclusion of RM-nv as a stage III criterion in the UMBRELLA staging system and consequent treatment reduction is warranted.

Despite the importance of secondary dormancy for plant life cycle timing and survival, there is insufficient knowledge about the (epigenetic) regulation of this trait at the molecular level. Our aim was to determine the role of (epi)genetic processes in the regulation of secondary seed dormancy using natural genotypes of the widely distributedCapsella bursa-pastoris. Seeds of nine ecotypes were exposed to control conditions or histone deacetylase inhibitors [trichostatin A (TSA), valproic acid] during imbibition to study the effects of hyper-acetylation on secondary seed dormancy induction and germination. Valproic acid increased secondary dormancy and both compounds caused a delay of t50 for germination (radicle emergence) but not of t50 for testa rupture, demonstrating that they reduced speed of germination. Transcriptome analysis of one accession exposed to valproic acidversuswater showed mixed regulation of ABA, negative regulation of GAs, BRs and auxins, as well as up-regulation ofSNLgenes, which might explain the observed delay in germination and increase in secondary dormancy. In addition, two accessions differing in secondary dormancy depth (deepvsnon-deep) were studied using RNA-seq to reveal the potential regulatory processes underlying this trait. Phytohormone synthesis or signalling was generally up-regulated for ABA (e.g.NCED6,NCED2,ABCG40,ABI3) and down-regulated for GAs (GA20ox1,GA20ox2,bHLH93), ethylene (ACO1,ERF4-LIKE, ERF105,ERF109-LIKE), BRs (BIA1,CYP708A2-LIKE, probableWRKY46,BAK1,BEN1,BES1,BRI1) and auxin (GH3.3,GH3.6,ABCB19,TGG4,AUX1,PIN6,WAT1). Epigenetic candidates for variation in secondary dormancy depth includeSNLgenes, histone deacetylases and associated genes (HDA14,HDA6-LIKE,HDA-LIKE,ING2,JMJ30), as well as sequences linked to histone acetyltransferases (bZIP11,ARID1A-LIKE), or to gene silencing through histone methylation (SUVH7,SUVH9,CLF). Together, these results show that phytohormones and epigenetic regulation play an important role in controlling differences in secondary dormancy depth between accessions.