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We study higher-rank Radon transforms of the form [Formula omitted], where [Formula omitted] is a j-dimensional totally geodesic submanifold in the n-dimensional real constant curvature space and [Formula omitted] is a similar submanifold of dimension [Formula omitted]. The corresponding dual transforms are also considered. The transforms are explored in the Euclidean case (affine Grassmannian bundles), the elliptic case (compact Grassmannians), and the hyperbolic case (the hyperboloid model, the Beltrami-Klein model, and the projective model). The main objectives are sharp conditions for the existence and injectivity of the Radon transforms in Lebesgue spaces, transition from one model to another, support theorems, and inversion formulas. Conjectures and open problems are discussed., Author(s): B. Rubin [sup.1] Author Affiliations: (1) https://ror.org/05ect4e57, grid.64337.35, 0000 0001 0662 7451, Department of Mathematics, Louisiana State University, , 70803, Baton Rouge, Louisiana, USA Contents 1. Introduction2 2. The [...]

Laura Murphy,1– 3 Kori Leblanc,1,2,4 Souzi Badr,1,2 Emily Ching,1 Lynda Mao,1,2 Naomi Steenhof,1,2 Bassem Hamandi,1,2,4 Bonita Rubin,1,2 Ada Seto,1 Andrea D Furlan3,5,6 1Department of Pharmacy, University Health Network, Toronto, ON, Canada; 2Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada; 3KITE Research Institute, University Health Network, Toronto, ON, Canada; 4Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada; 5Department of Medicine, University of Toronto, Toronto, ON, Canada; 6Institute for Work & Health, Toronto, ON, CanadaCorrespondence: Laura Murphy, Department of Pharmacy, University Health Network, 550 University Ave, Toronto, ON, M5G 2A2, Canada, Tel +1 416-597-3422 x 3657, Fax +1 416-260-2658, Email laura.murphy@uhn.caBackground: Opioid utilization and management in an inpatient rehabilitation setting have not been widely described, despite the unique opportunities that exist in this setting to support opioid stewardship across transitions in care. We aimed to characterize opioid utilization and management by interprofessional teams across a large, inpatient rehabilitation setting after incorporation of opioid stewardship principles by pharmacists as part of their daily practice.Patients and methods: This was a retrospective chart review at Toronto Rehab, University Health Network, Toronto, Canada. Patients with admission orders for any opioid from November 2017 to February 2018 were included. Complex continuing care and palliative care patients were excluded. Descriptive statistics were primarily used to describe the data as well as univariate linear regression to compare associations with milligram morphine equivalent (MME) reduction.Results: A total of 448 patients were included. A reduction in total daily MME was seen in 49% (n=219) of the patients during their inpatient stay, with 73% (n=159) of these patients having a reduction of ≥ 50%. Sixty-nine percent (n=311) of the patients received an opioid prescription at discharge, with most scheduled (90%, n=98) with a supply of less than 30 days. Rehabilitation length of stay was correlated with a MME decrease during rehab (p< 0.01), suggesting that longer lengths of stay contributed to a greater reduction in MME. Patients with chronic opioid use prior to acute care admission (p=0.01), and those who started extended-release opioids during acute care (p=0.02) were significantly less likely to discontinue opioids during rehab stay.Conclusion: Opioid utilization and management in the setting of opioid stewardship across inpatient rehab and transitions of care were characterized. Opportunities exist for further quality improvement initiatives within inpatient rehabilitation and acute care settings to identify and support patients with complex pain management needs.Keywords: opioid, pain management, medication reconciliation, pharmacy practice, medication safety, discharge prescription

Pregnancy is accompanied by hormonal fluctuation, including increased cortisol and oxytocin (OT). Although the implications of these hormones during pregnancy are extensively studied, their normative variability is not well established. Therefore, we evaluated how serum cortisol and OT levels behave throughout pregnancy. This longitudinal study is part of a population-based cohort of pregnant women living in a city in Southern Brazil. Pregnant women up to 24 gestational weeks were evaluated at the time of identification (1st wave, N=983) and 60 days after the initial interview (2nd wave, N=840). At both times, blood samples were collected for hormonal dosage. We investigated the trajectory of these hormones throughout pregnancy using growth curve modeling. The best-fitting model was the exponential growth model, in which the variance explains approximately 79.1 % of the outcome. Thus, the cortisol level was, on average, at 44.2 μg/dl (95 %CI: 29.2;59.1, p<0.001) in the first gestational week, with an increase of approximately 2.0 % (95 %CI: 1.01;1.02, p<0.001) each week. OT showed no significant changes. While cortisol appears to follow a trajectory of exponential increase, possibly in response to the demands of fetal development, the variation in OT levels throughout pregnancy still remains constant subject to further investigation., Competing Interests: Declaration of Competing Interest Conflict of interest On behalf of all authors, the corresponding author states that no conflicts of interest exist., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Because there is no reliable method on admission to predict whether a patient will require neurosurgical intervention in the future, the general approach remains to treat each patient with mild traumatic brain injury (mTBI) and subdural hematoma (SDH) as if they will require such an intervention. Consequently, there is a growing population of patients with mTBI and SDH that is overtriaged despite having a low probability of needing neurosurgical intervention. This study aimed to train and validate a predictive rule-out tool for neurosurgical intervention in patients with mTBI and SDH., Methods: This was a retrospective cohort study of all trauma patients admitted to six level I trauma centers in three states. Patients were included if they met the following criteria: admitted between 2016 and 2020, ≥ 18 years of age, ICD-10 diagnosis of isolated SDH, initial head imaging available, initial Glasgow Coma Scale score of 13-15, and arrived within 48 hours of injury. Exclusion criteria included skull fracture, intracranial hemorrhage other than an SDH, and no neurosurgical consultation. Prediction variables included 34 demographic, clinical, and radiographic variables. The study outcome was neurosurgical intervention within 48 hours of hospital admission. Seventy-five percent of the data were used for training, and 25% for testing. Multivariable logistic regression with fivefold cross-validation was used on the training set to identify covariates with the highest specificity while holding sensitivity at 100%. Results were validated on the testing set., Results: In total, 1000 patients were in the training set and 333 in the testing set. The overall neurosurgical intervention rate was 8.8%. For the fivefold cross-validation process, three variables were selected that maximized specificity while holding sensitivity at 100%: maximum hematoma thickness, initial Glasgow Coma Scale score, and preinjury antithrombotic use (sensitivity 100%, specificity 56%, area under the receiver operating characteristic curve 0.94). With a cutoff probability of neurosurgical intervention set at 1.88%, the final model was validated to predict neurosurgical intervention with a sensitivity of 100% (95% CI 88.4%-100%) and specificity of 55.1% (95% CI 49.3%-60.8%)., Conclusions: In this study, the largest of its kind to date, the authors successfully developed and validated a new tool for ruling out the necessity of neurosurgical intervention in patients with mTBI and isolated SDH. By successfully identifying more than half of patients who are unlikely to require neurosurgery within the first 2 days of admission, this tool can be used to improve treatment efficiency and provide patients and clinicians with valuable prognostic information.

This study investigated the bioactivity of both aerial (GNAR) and underground (GNUG) parts of Gymnadenia nigra Rchb.f. (syn. Nigritella nigra (L.) Rchb. f.) (Orchidaceae). The obtained data proved interesting when the samples were tested in two adrenocortical cancer cell lines (SW13 and H295R). In particular, the GNAR 80% methanol extract distinctly inhibited their viability after 24 h at a concentration of 1 µg/µL by MTT assay and trypan blue dye exclusion method. Cell morphology evaluation by means Wright's staining also showed significant results, particularly in SW13 cells under the effect of both extracts. GNAR extract was able to scavenge the DPPH radical better than GNUG extract. It also was more active in albumin denaturation (a maximum % denaturation equal to 463.0 ± 8.3 vs 77.3 ± 13.3) and protease inhibition (a maximum % inhibition equal to 138.5 ± 7.0 vs 2.1 ± 2.0) tests. The results highlighted an important antitumor activity of G. nigra in vitro that deserves to be further studied.

Purpose: To determine the efficacy and safety of repetitive transorbital alternating current stimulation (rtACS) treatment by assessing vision-related quality of life and visual function outcome in subjects treated with rtACS versus sham-control., Study Design: Double masked, randomized, sham-controlled clinical trial (NCT03188042)., Subjects: Sixteen subjects with moderate-to-advanced glaucoma (visual field [VF] mean deviation [MD] ≤-6.00 decibels) randomized into sham (9 subjects) or rtACS intervention (7 subjects) groups., Methods: Subjects underwent 10 rtACS sessions over 2 weeks. All subjects had comprehensive ocular examination at baseline, 1-week, and 4-weeks posttreatment., Main Outcome Measures: Visual acuity (VA), contrast sensitivity (CS), VF MD, number of threshold sensitivity points that changed or were unchanged, and vision-related quality of life (VR-QoL) questionnaire scores., Results: The rtACS group showed a significantly greater improvement from baseline to 4 weeks posttreatment compared with sham in VR-QoL domains including near activities ( P < 0.01), dependency ( P  = 0.03), social functioning ( P  = 0.03), mental health ( P < 0.01) and in the overall composite score ( P  = 0.04). No significant changes were detected with VA, CS, and VF analyses for either group. No serious adverse events were noted in either study group., Conclusions: Repetitive transorbital alternating current stimulation therapy showed a significant beneficial effect on several domains of VR-QoL. Further studies will determine its utility in glaucoma., Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (© 2024 by the American Academy of Ophthalmology.)

Objective: The objective was to identify demographic, clinical, and radiographic risk factors for neurosurgical intervention within 48 hours of admission in patients with mild traumatic brain injury and isolated subdural hematoma., Methods: The authors conducted a multicenter retrospective cohort study of all trauma patients admitted to 6 level I/II trauma centers who met the following criteria: admitted between January 1, 2016, and December 31, 2020, age ≥ 18 years, ICD-10 diagnosis code for isolated subdural hematoma, available initial head imaging, initial Glasgow Coma Scale score of 13-15, and arrival at the hospital within 48 hours of injury. Patients were excluded for skull fracture, non-subdural hematoma, and absence of neurosurgical consultation. The study outcome was neurosurgical intervention within 48 hours of hospital admission. Multivariable logistic regression with backward selection examined 30 demographic, clinical, and radiographic risk factors for neurosurgery., Results: In total, 1333 patients were included, of whom 117 (8.8%) received a neurosurgical intervention. When only demographic and clinical variables were considered, sex, mechanism of injury, and hours from injury to initial head imaging were significant covariates (area under the receiver operating characteristic curve [AUROC] [95% CI] 0.70 [0.65-0.75]). When only radiographic risk factors were considered, only maximum hemorrhage thickness (in mm) and midline shift (in mm) were independent risk factors for the outcome (AUROC 0.95 [0.92-0.97]). When all demographic, clinical, and radiographic variables were considered together, advanced directive, Injury Severity Score, midline shift, and maximum hemorrhage thickness were identified as significant risk factors for neurosurgical intervention within 48 hours of hospital admission (AUROC 0.95 [0.94-0.97])., Conclusions: In the setting of mild traumatic brain injury with isolated subdural hematoma, radiographic risk factors were shown to be stronger than demographic and clinical variables in understanding future risk of neurosurgical intervention. These final radiographic risk factors should be considered in the creation of future prediction models and used to increase the efficiency of existing management guidelines.

Introduction: Patients with systemic lupus erythematosus (SLE) have variable treatment pathways, including antimalarials, glucocorticoids, immunosuppressants, and/or biologics. This study describes differences in clinical outcomes when initiating belimumab (BEL) before and after immunosuppressant use., Methods: This real-world, retrospective cohort study (GSK Study 217536) used de-identified administrative claims data from January 2015 to December 2022 in the Komodo Health Database. Adults with moderate/severe SLE initiating BEL (index date) were identified from January 2017 to May 2022, allowing a ≥ 24-month baseline period. Patients were stratified into those initiating BEL before immunosuppressant use (no immunosuppressant use within 24 months before index) and those initiating BEL after immunosuppressant use (one immunosuppressant used within 24 months before index). Oral glucocorticoid (OGC) use, SLE flares, new organ damage, and all-cause healthcare resource utilization (HCRU) were analyzed descriptively over a 24-month follow-up., Results: Baseline SLE severity was similar for patients initiating BEL before (n = 2295) versus after (n = 4114) immunosuppressant use (moderate, 83.1% vs 79.0%; severe, 16.8% vs 21.0%). Patients initiating BEL before versus after immunosuppressant use had lower SLE flare rates and OGC use. Post-index, patients initiating BEL before versus after immunosuppressant use discontinued their OGC sooner (moderate baseline SLE, 4.5 vs 8.9 months; severe baseline SLE, 6.2 vs 11.6 months). Patients initiating BEL before versus after immunosuppressant use had lower SLE flare rates per person-year at all time points (especially severe flare rates in patients with severe baseline SLE, 0.70 vs 1.48 through 24 months post-index). Median time to new organ damage occurrence was longer in patients initiating BEL before versus after immunosuppressant use (moderate baseline SLE, 32.1 vs 26.7 months; severe baseline SLE, 22.7 vs 21.6 months). All-cause HCRU was similar between cohorts., Conclusions: These results suggest that patients initiating BEL before versus after immunosuppressant use had more favorable outcomes., (© 2024. The Author(s).)

Background: We aimed to describe healthcare resource utilization (HCRU) and healthcare costs in patients with newly confirmed lupus nephritis (LN) in the United States over a 5-year follow-up period., Methods: This retrospective, longitudinal cohort study (GSK Study 214102) utilized administrative claims data to identify individuals with a newly confirmed diagnosis of LN between August 01, 2011, and July 31, 2018, based on LN-specific International Classification of Diseases diagnosis codes. Index was the date of first LN-related diagnosis code claim. HCRU, healthcare costs, and incidence of systemic lupus erythematosus (SLE) flares were reported annually among eligible patients with at least 5 years continuous enrollment post-index., Results: Of 2,159 patients with a newly confirmed diagnosis of LN meeting inclusion and exclusion criteria, 335 had at least 5 years continuous enrollment post-index. HCRU was greatest in the first year post-LN diagnosis across all categories (inpatient admission, emergency room [ER] visits, ambulatory visits, and pharmacy use), and trended lower, though remained substantial, in the 5-year follow-up period. Among patients with LN and HCRU, the mean (standard deviation [SD]) number of ER visits and inpatient admissions were 3.7 (4.6) and 1.8 (1.5), respectively, in Year 1, which generally remained stable in Years 2-5; the mean (SD) number of ambulatory visits and pharmacy fills were 35.8 (25.1) and 62.9 (43.8), respectively, in Year 1, and remained similar for Years 2-5. Most patients (≥ 91.6%) had ≥ 1 SLE flare in each of the 5 years of follow-up. The proportion of patients who experienced a severe SLE flare was higher in Year 1 (31.6%) than subsequent years (14.3-18.5%). Total costs (medical and pharmacy; mean [SD]) were higher in Year 1 ($44,205 [71,532]) than subsequent years ($29,444 [52,310]-$32,222 [58,216]), driven mainly by inpatient admissions (Year 1: $21,181 [58,886]; subsequent years: $7,406 [23,331]-$9,389 [29,283])., Conclusions: Patients with a newly confirmed diagnosis of LN have substantial HCRU and healthcare costs, particularly in the year post-diagnosis, largely driven by inpatient costs. This highlights the need for improved disease management to prevent renal damage, improve patient outcomes, and reduce costs among patients with renal involvement., (© 2024. The Author(s).)

Our 2022 published working definition of disease modification in systemic lupus erythematosus (SLE) was 'minimising disease activity with the fewest treatment-associated toxicities and slowing or preventing organ damage progression'. The objective of this review was to classify current SLE treatments according to the proposed non-renal disease modification criteria excluding toxicities. Based on a review of select clinical trial (n=32) and observational study (n=54) publications for 14 SLE medications across different therapeutic classes, and the authors' clinical experience, we evaluated disease modification potential as per the proposed framework at three time points. Specific criteria used to determine disease modification potential included a drug's capacity to reduce: (1) non-renal disease activity, (2) severe flares, (3) use of steroids/immunosuppressants and (4) organ damage accrual. Criteria 1-3 were assessed at 1 year and 2-5 years and, when positive, were considered evidence for disease modification potential; criterion 4 was used to confirm disease modification at >5 years. Each treatment received one of four mutually exclusive designations at each time point: (a) criterion met, (b) indications of criterion met despite insufficient evidence in the literature, (c) inconclusive and (d) no available supportive data. This review excludes an assessment of potential toxicities. Eight of the 14 SLE treatments met ≥1 disease modification criteria up to year 5. Hydroxychloroquine improved overall survival at >5 years, suggesting long-term disease modification, but no data on specific organ systems were reported. Belimumab was the only treatment to meet all criteria. Belimumab and hydroxychloroquine met disease modification definitions across three time points. Evidence for other SLE therapies was incomplete, particularly at >5 years. Future studies are warranted for other treatments to meet the disease modification criteria. We discuss challenges to classification and possible updates to our published criteria., Competing Interests: Competing interests: ADA has received consulting fees from AbbVie, Amgen, Aurinia, AstraZeneca, BMS and GSK; and has been an investigator for GSK, Janssen, Pfizer, UCB, Vielo, AstraZeneca and Eli Lilly. RAF has received research support from GSK and is an advisory board member for GSK. MD has received consulting fees from Aurinia, AstraZeneca, Biogen, Gilead, Pfizer and GSK. ASB has received consulting fees from Alexion, Principio, Calliditas, Aurinia, Catalyst, Travere, GSK, Visterra, Silence, Novo Nordisk, Otsuka, ChemoCentrx and Novartis. AS has received research grant support from GSK, Novartis and Pfizer; and has been an advisory board and speaker bureau member for GSK. M-HZ has been a consultant or advisory board member for GSK, AstraZeneca, Roche, Novartis, Bayer and BeiGene. INB is a National Institute for Health Research (NIHR) Senior Investigator and is funded by the NIHR Manchester Biomedical Research Centre (NIHR 203308). His institution has received research grants from GSK and Genzyme/Sanofi and consultancy fees from GSK, UCB, Eli Lilly, BMS, Merck Serono, Aurinia and IL-TOO. He has received speaker fees from GSK, AstraZeneca and UCB. RvV has received consulting fees from AbbVie, AstraZeneca, Biogen, Biotest, BMS, Galapagos, Gilead, Janssen, Pfizer, Sanofi, Servier, UCB and Vielabio; speaker honoraria from AbbVie, Galapagos, GSK, Janssen, Pfizer and UCB; and support for educational programmes and institutional grants from Pfizer and Roche. MBU has received research grant support from GSK and has been an advisory board and speaker bureau member for GSK, and an advisory board member for AstraZeneca, Eli Lilly and UCB. MD was an employee of GSK at the initial time of writing, and held a stock and shares in the company. MK, BR, AC and RAL are employees of GSK and hold stocks and shares in the company., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To investigate the real-world impact of intravenous belimumab treatment among patients with SLE using rheumatoid arthritis-derived disease activity measures and SLE-related laboratory values., Methods: This retrospective cohort study used US electronic medical record data from the United Rheumatology Normalised Integrated Community Evidence (UR-NICE) database. Adult patients with SLE who initiated intravenous belimumab between 1 January 2012 and 3 December 2019 (index), had 12 months of pre-index and 24 months of post-index clinical activity, and had ≥6 infusions of belimumab during the 24 months post-index were included. The primary outcome measure was time to first improvement of minimally important difference (MID) for Routine Assessment of Patient Index Data 3 (RAPID3), Patient Pain Index (PPI), swollen joint count, tender joint count (TJC), complement C3 and C4 and anti-double-stranded DNA antibodies during the on-treatment follow-up period of up to 24 months. The secondary outcome measure evaluated the trajectories of these outcome measures for up to 24 months of belimumab treatment., Results: Of 495 patients included, between 21.0% and 52.1% had ≥1 record for each of the disease activity measures or laboratory values in the pre-index and post-index periods and were included in analyses for that measure. The proportion of patients achieving MID for each measure increased rapidly within 3 months, with continued gradual improvement throughout the remaining on-treatment period, up to 24 months. After 6 months, 52.3% and 55.3% of patients had achieved MID in RAPID3 and PPI, respectively. Outcome measure trajectories indicated improved disease activity with belimumab treatment, particularly in RAPID3, TJC and laboratory values., Conclusions: In this real-world effectiveness study, belimumab therapy for SLE resulted in clinically meaningful improvements in rheumatoid arthritis-derived disease activity measures within 3 months of treatment, with patients who remained on belimumab therapy experiencing improvement even up to 24 months of observation., Competing Interests: Competing interests: KW, CFB and BR are employees of GSK and hold shares in the company. GG, FL, SDM, AU and MSD are employees of Analysis Group, a consulting company that received research funds from GSK to conduct this study. AC is chief innovation officer at Exagen and is EVP, Chief Medical Officer at United Rheumatology, which is the source of the data for this study., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Comparison of oral corticosteroid (OCS) use in patients with SLE in a US rheumatology network pre- and post-belimumab initiation., Methods: This retrospective cohort study (GSK Study 214140) used data from the Patient-Important Outcomes Data Repository (PIONEER)-Rheumatology database. Eligible adults with SLE initiated belimumab between 1 January 2012 and 30 June 2021, and had available data for >180 days pre- and >360 days post-belimumab initiation. The index was the date of belimumab initiation. Changes in OCS use were measured by: proportion of patients receiving OCS; mean total OCS dose/patient; mean total number of OCS days supplied/patient; mean daily OCS dose for days supplied/patient; the proportion of patients with OCS doses of ≤5 mg/day and ≤7.5 mg/day for days supplied. These changes were assessed between period (P)1 (6 months pre-index) and P2 (first 6 months post-index) and P3 (second 6 months post-index) in patients with OCS use in P1 who persisted with belimumab at each assessed period., Results: Overall, 608 patients received belimumab for 180 days (full analysis set (FAS)) and 492 for 360 days. Most patients were female (92.8%); 70.4% had moderate SLE. In P1, 56.3% of FAS patients and 54.5% of patients who persisted with belimumab for 360 days received OCS.Among patients receiving OCS in P1, significantly fewer patients received OCS in P2 (78.4%) and P3 (64.9%) vs P1 (100.0%). Significant reductions from P1 were observed in P2 and P3 in the mean total OCS dose/patient, the mean OCS daily dose for days supplied and the proportions of patients with OCS dose of ≤5 mg/day and ≤7.5 mg/day, and the mean total OCS days supplied/patient in P3 only., Conclusions: This analysis showed significant reductions in OCS dose and use in patients with SLE who persisted with belimumab, providing more real-world evidence for belimumab's steroid-sparing effect., Competing Interests: Competing interests: KW and BR are employees of GSK and hold stocks and shares in the company. SM is an employee of Trio Health Analytics, which has received research support from AbbVie, Actelion Pharmaceuticals, AstraZeneca, Gilead Sciences, GSK, Horizon Pharma, JNJ, Merck, Pharming Healthcare, Sanofi, Takeda, UCB Biosciences and ViiV Healthcare., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To determine if plasma concentrations of symmetric dimethylarginine (SDMA), N-acetyl-beta-d-glucosaminidase (NAG), GGT, ALT, AST, lactate, total calcium, and ionized calcium (iCa) and the calcium:phosphorus ratio are clinically relevant biomarkers to detect early stages of tubular lesions in snakes., Animals: 6 adult corn snakes (Pantherophis guttatus)., Methods: Corn snakes were administered 11 injections of gentamicin at 50 mg/kg, SC, q 24 h in an experimental model of induced tubular necrosis. Plasma biochemistry and blood gas analyses were performed at baseline and after the 3rd and 11th injections. Parameters were compared between time points using a paired Wilcoxon test. In 3 individuals, renal biopsies were collected at baseline before starting injections and at the 3rd and 11th injections, while renal tissue samples were procured after euthanasia in all individuals., Results: Renal proximal and distal tubular necrosis and hepatic steatosis were present in all individuals at necropsy. Compared to baseline, decreased blood concentrations of lactate, ionized calcium, and total calcium and a decreased calcium:phosphorus ratio were noted. A significant decrease of lactate and ionized calcium was observed after 3 days. Conversely, no changes in SDMA, NAG, ALT, AST, GGT, and sodium were detected., Clinical Relevance: Ionized calcium and lactate concentrations were the earliest parameters to decrease compared to baseline values in this experimental model. While SDMA is a sensitive indicator of renal disease in mammals, this biomarker did not increase in a model of induced acute tubular necrosis in corn snakes.

Objective: The objective of this review was to identify quantitative biomechanical measurements of human tissues, the methods for obtaining these measurements, and the primary motivations for conducting biomechanical research., Introduction: Medical skills trainers are a safe and useful tool for clinicians to use when learning or practicing medical procedures. The haptic fidelity of these devices is often poor, which may be because the synthetic materials chosen for these devices do not have the same mechanical properties as human tissues. This review investigates a heterogeneous body of literature to identify which biomechanical properties are available for human tissues, the methods for obtaining these values, and the primary motivations behind conducting biomechanical tests., Inclusion Criteria: Studies containing quantitative measurements of the biomechanical properties of human tissues were included. Studies that primarily focused on dynamic and fluid mechanical properties were excluded. Additionally, studies only containing animal, in silico , or synthetic materials were excluded from this review., Methods: This scoping review followed the JBI methodology for scoping reviews and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). Sources of evidence were extracted from CINAHL (EBSCO), IEEE Xplore, MEDLINE (PubMed), Scopus, and engineering conference proceedings. The search was limited to the English language. Two independent reviewers screened titles and abstracts as well as full-text reviews. Any conflicts that arose during screening and full-text review were mediated by a third reviewer. Data extraction was conducted by 2 independent reviewers and discrepancies were mediated through discussion. The results are presented in tabular, figure, and narrative formats., Results: Data were extracted from a total of 186 full-text publications. All of the studies, except for 1, were experimental. Included studies came from 33 countries, with the majority coming from the United States. Ex vivo methods were the predominant approach for extracting human tissue samples, and the most commonly studied tissue type was musculoskeletal. In this study, nearly 200 unique biomechanical values were reported, and the most commonly reported value was Young's (elastic) modulus. The most common type of mechanical test performed was tensile testing, and the most common reason for testing human tissues was to characterize biomechanical properties. Although the number of published studies on biomechanical properties of human tissues has increased over the past 20 years, there are many gaps in the literature. Of the 186 included studies, only 7 used human tissues for the design or validation of medical skills training devices. Furthermore, in studies where biomechanical values for human tissues have been obtained, a lack of standardization in engineering assumptions, methodologies, and tissue preparation may implicate the usefulness of these values., Conclusions: This review is the first of its kind to give a broad overview of the biomechanics of human tissues in the published literature. With respect to high-fidelity haptics, there is a large gap in the published literature. Even in instances where biomechanical values are available, comparing or using these values is difficult. This is likely due to the lack of standardization in engineering assumptions, testing methodology, and reporting of the results. It is recommended that journals and experts in engineering fields conduct further research to investigate the feasibility of implementing reporting standards., Review Registration: Open Science Framework https://osf.io/fgb34., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 JBI.)

Amaranthus tuberculatus is the most common weed in soybean and corn in the USA and Canada. In Israel, it has been a minor riverbank weed. However, in recent years, growing densities of this plant have been observed in field crops, orchards, and roadsides. Between 2017 and 2022, we surveyed the distribution of A. tuberculatus and collected seeds for further study. We identified three main distribution zones in Israel: the Jezreel Valley, Hula Valley, and Coastal Plain. Most of the populations were found near water sources, fishponds, barns, dairies, or bird-feeding sites, suggesting the involvement of imported grain in introducing A. tuberculatus to Israel. Populations were screened for their responses to various post-emergence herbicides (i.e., ALS, EPSPS, PPO, HPPD, and PSII inhibitors). Several populations from the Jezreel Valley were found to be putatively resistant to ALS, EPSPS, and PPO inhibitors. The responses of those populations to trifloxysulfuron, glyphosate, and carfentrazone-ethyl were also studied. A single ALS-, EPSPS- and PPO-resistant plant was vegetatively propagated to create a clonal population, which was treated with foramsulfuron, glyphosate, and carfentrazone-ethyl. No resistance to PSII or HPPD inhibitors was observed, but resistance to herbicides that inhibit ALS, EPSPS, and PPO was observed. A clonal propagation assay revealed the existence of a population that was resistant to ALS, EPSPS, and PPO inhibitors. Since the local A. tuberculatus populations have not been exposed to herbicide selection pressure, these traits probably reached Israel through seed-mediated gene flow via imported grain.

TAZ::CAMTA1 is a fusion protein found in over 90% of Epithelioid Hemangioendothelioma (EHE), a rare vascular sarcoma with an unpredictable disease course. To date, how TAZ::CAMTA1 initiates tumour formation remains unexplained. To study the oncogenic mechanism leading to EHE initiation, we developed a model system whereby TAZ::CAMTA1 expression is induced by doxycycline in primary endothelial cells. Using this model, we establish that upon TAZ::CAMTA1 expression endothelial cells rapidly enter a hypertranscription state, triggering considerable DNA damage. As a result, TC-expressing cells become trapped in S phase. Additionally, TAZ::CAMTA1-expressing endothelial cells have impaired homologous recombination, as shown by reduced BRCA1 and RAD51 foci formation. Consequently, the DNA damage remains unrepaired and TAZ::CAMTA1-expressing cells enter senescence. Knockout of Cdkn2a, the most common secondary mutation found in EHE, allows senescence bypass and uncontrolled growth. Together, this provides a mechanistic explanation for the clinical course of EHE and offers novel insight into therapeutic options., (© 2023. The Author(s).)

(1) Objective: Systemic lupus erythematosus (SLE) is a complex disease involving immune dysregulation, episodic flares, and poor quality of life (QOL). For a decentralized digital study of SLE patients, machine learning was used to assess patient-reported outcomes (PROs), QOL, and biometric data for predicting possible disease flares. (2) Methods: Participants were recruited from the LupusCorner online community. Adults self-reporting an SLE diagnosis were consented and given a mobile application to record patient profile (PP), PRO, and QOL metrics, and enlisted participants received smartwatches for digital biometric monitoring. The resulting data were profiled using feature selection and classification algorithms. (3) Results: 550 participants completed digital surveys, 144 (26%) agreed to wear smartwatches, and medical records (MRs) were obtained for 68. Mining of PP, PRO, QOL, and biometric data yielded a 26-feature model for classifying participants according to MR-identified disease flare risk. ROC curves significantly distinguished true from false positives (ten-fold cross-validation: p < 0.00023; five-fold: p < 0.00022). A 25-feature Bayesian model enabled time-variant prediction of participant-reported possible flares (P(true) > 0.85, p < 0.001; P(nonflare) > 0.83, p < 0.0001). (4) Conclusions: Regular profiling of patient well-being and biometric activity may support proactive screening for circumstances warranting clinical assessment.

Rhabdomyosarcoma accounts for roughly 1% of adult sarcomas, with pleomorphic rhabdomyosarcoma (PRMS) as the most common subtype. Survival outcomes remain poor for patients with PRMS, and little is known about the molecular drivers of this disease. To better characterize PRMS, we performed a broad array of genomic and immunostaining analyses on 25 patient samples. In terms of gene expression and methylation, PRMS clustered more closely with other complex karyotype sarcomas than with pediatric alveolar and embryonal rhabdomyosarcoma. Immune infiltrate levels in PRMS were among the highest observed in multiple sarcoma types and contrasted with low levels in other rhabdomyosarcoma subtypes. Lower immune infiltrate was associated with complete loss of both TP53 and RB1 . This comprehensive characterization of the genetic, epigenetic, and immune landscape of PRMS provides a roadmap for improved prognostications and therapeutic exploration., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

Background: Pulmonary hypertension (PH) is life-threatening, and often diagnosed late in its course. We aimed to evaluate if a deep learning approach using electrocardiogram (ECG) data alone can detect PH and clinically important subtypes. We asked: does an automated deep learning approach to ECG interpretation detect PH and its clinically important subtypes?, Methods and Results: Adults with right heart catheterization or an echocardiogram within 90 days of an ECG at the University of California, San Francisco (2012-2019) were retrospectively identified as PH or non-PH. A deep convolutional neural network was trained on patients' 12-lead ECG voltage data. Patients were divided into training, development, and test sets in a ratio of 7:1:2. Overall, 5016 PH and 19,454 patients without PH were used in the study. The mean age at the time of ECG was 62.29 ± 17.58 years and 49.88% were female. The mean interval between ECG and right heart catheterization or echocardiogram was 3.66 and 2.23 days for patients with PH and patients without PH, respectively. In the test dataset, the model achieved an area under the receiver operating characteristic curve, sensitivity, and specificity, respectively of 0.89, 0.79, and 0.84 to detect PH; 0.91, 0.83, and 0.84 to detect precapillary PH; 0.88, 0.81, and 0.81 to detect pulmonary arterial hypertension, and 0.80, 0.73, and 0.76 to detect group 3 PH. We additionally applied the trained model on ECGs from participants in the test dataset that were obtained from up to 2 years before diagnosis of PH; the area under the receiver operating characteristic curve was 0.79 or greater., Conclusions: A deep learning ECG algorithm can detect PH and PH subtypes around the time of diagnosis and can detect PH using ECGs that were done up to 2 years before right heart catheterization/echocardiogram diagnosis. This approach has the potential to decrease diagnostic delays in PH., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Transfusion-associated circulatory overload (TACO) is a severe adverse reaction (AR) contributing to the leading cause of mortality associated with transfusions. As strategies to mitigate TACO have been increasingly adopted, an update of prevalence rates and risk factors associated with TACO using the growing sources of electronic health record (EHR) data can help understand transfusion safety., Study Design and Methods: This retrospective study aimed to provide a timely and reproducible assessment of prevalence rates and risk factors associated with TACO. Novel natural language processing methods, now made publicly available on GitHub, were developed to extract ARs from 3178 transfusion reaction reports. Other patient-level data were extracted computationally from UCSF EHR between 2012 and 2022. The odds ratio estimates of risk factors were calculated using a multivariate logistic regression analysis with case-to-control matched on sex and age at a ratio of 1:5., Results: A total of 56,208 patients received transfusions (total 573,533 units) at UCSF during the study period and 102 patients developed TACO. The prevalence of TACO was estimated to be 0.2% per patient (102/total 56,208). Patients with a history of coagulopathy (OR, 1.36; 95% CI, 1.04-1.79) and transplant (OR, 1.99; 95% CI, 1.48-2.68) were associated with increased odds of TACO., Discussion: While TACO is a serious AR, events remained rare, even in populations enriched with high-risk patients. Novel computational methods can be used to find and continually surveil for transfusion ARs. Results suggest that patients with history or presence of coagulopathy and organ transplant should be carefully monitored to mitigate potential risks of TACO., (© 2023 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Introduction: This study aimed to describe the clinical burden, healthcare resource utilisation (HCRU) and healthcare costs for patients with systemic lupus erythematosus (SLE) in the 12-60 months preceding an end-stage kidney disease (ESKD) diagnosis in the USA., Methods: This retrospective observational study identified adult patients with SLE with newly diagnosed ESKD between 1 March 2012 and 31 December 2018 using administrative claims data. Clinical characteristics, mean all-cause HCRU (i.e. any HCRU visit and pharmacy fill) and total all-cause healthcare costs (comprising medical and pharmacy costs in 2019 US dollars) were assessed during the 12 months pre-ESKD diagnosis and yearly during the 5 years pre-ESKD diagnosis among patients with ≥ 5 years of continuous health plan enrolment., Results: Of the 1356 patients included, 51.2% had severe SLE, 71.2% had lupus nephritis (LN) and 20.6% underwent kidney biopsy during the 12 months pre-ESKD. The mean (standard deviation [SD]) number of HCRU visits during the 12 months pre-ESKD was 78.0 (64.1) per patient. The mean (SD) total healthcare costs per patient in the 12 months pre-ESKD diagnosis was $64,887 (106,822), driven by medical costs $51,764 (96,458). The proportions of patients with severe SLE, LN and those undergoing biopsy increased from year 5 to year 1 pre-ESKD diagnosis. The mean (SD) number of HCRU visits increased from year 5 (61.6 [54.0]) to year 1 (83.2 [62.1]) pre-ESKD. Mean (SD) total healthcare costs rose year on year from year 5 ($34,890 [74,346]) to year 1 ($73,236 [114,584]) pre-ESKD., Conclusion: There were substantial clinical burden and healthcare costs among patients with SLE in the 12 months pre-ESKD diagnosis. The clinical burden and healthcare costs generally increased with each year approaching ESKD diagnosis. Early interventions for patients with SLE could prevent the development of ESKD, mitigating the burden of the disease., (© 2023. The Author(s).)

Background: The incidence of hospitalizations for cardiovascular events has been associated with specific weather conditions and air pollution. A comprehensive model including the interactions between various environmental factors remains to be developed., Objectives: The purpose of this study was to develop a comprehensive model of the association between weather patterns and the incidence of cardiovascular events and use this model to forecast near-term spatiotemporal risk., Methods: We present a spatiotemporal analysis of the association between atmospheric data and the incidence rate of hospital admissions related to heart failure (922,132 episodes), myocardial infarction (521,988 episodes), and ischemic stroke (263,529 episodes) in ∼24 million people in Canada between 2007 and 2017. Our hierarchical Bayesian model captured the spatiotemporal distribution of hospitalizations and identified weather and air pollution-related factors that could partially explain fluctuations in incidence., Results: Models that included weather and air pollution variables outperformed models without those covariates for most event types. Our results suggest that environmental factors may interact in complex ways on human physiology. The impact of environmental factors was magnified with increasing age. The weather and air pollution variables included in our models were predictive of the future incidence of heart failure, myocardial infarction, and ischemic strokes., Conclusions: The increasing importance of environmental factors on cardiovascular events with increasing age raises the need for the development of educational materials for older patients to recognize environmental conditions where exacerbations are more likely. This model could be the basis of a forecasting system used for local, short-term clinical resource planning based on the anticipated incidence of events., Competing Interests: This study was funded by the Ted Rogers Centre for Heart Research, 10.13039/100009663University Health Network, Toronto, Ontario, Canada. The study funder had no involvement in study design, data analysis, or in the decision to publish the results of this study. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Background: Lupus nephritis (LN) is among the most severe organ manifestations of systemic lupus erythematosus (SLE), affecting between 31% and 48% of patients, usually within five years of SLE diagnosis. SLE without LN is associated with a high economic burden on the healthcare system, and although data are limited, several studies have shown that SLE with LN could increase this burden.  Aim: We aimed to compare the economic burden of LN versus SLE without LN among patients managed in routine clinical practices in the USA and describe the clinical course of these patients., Materials and Methods: This was a retrospective observational study of patients with commercial or Medicare Advantage health insurance. It included 2310 patients with LN and 2310 matched patients who had SLE without LN; each patient was followed for 12 months after diagnosis (the patient's index date). Outcome measures included healthcare resource utilization (HCRU), direct healthcare costs, and SLE clinical manifestations.  Results: In all healthcare settings, the mean (SD) use of all-cause healthcare resources was significantly higher in the LN versus SLE without LN cohort, including the mean number of ambulatory visits (53.9 (55.1) vs 33.0 (26.0)), emergency room visits (2.9 (7.9) vs 1.6 (3.3)), inpatient stays (0.9 (1.5) vs 0.3 (0.8)), and pharmacy fills (65.0 (48.3) vs 51.2 (42.6)) (all p<0.001). Total all-cause costs per patient in the LN cohort were also significantly higher compared with the SLE without LN cohort ($50,975 (86,281) vs $26,262 (52,720), p<0.001), including costs for inpatient stays and outpatient visits. Clinically, a significantly higher proportion of patients with LN experienced moderate or severe SLE flares compared with the SLE without LN cohort (p<0.001), which may explain the difference in HCRU and healthcare costs., Conclusion: All-cause HCRU and costs were higher for patients with LN than for matched patients with SLE without LN, highlighting the economic burden associated with LN., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2023, Bell et al.)

Introduction: This analysis aims to describe real-world clinical outcomes in US African American and Hispanic patients with systemic lupus erythematosus (SLE) receiving belimumab., Methods: In this post hoc analysis of OBSErve US (GSK Study 117,295) data, patients received intravenous belimumab (10 mg/kg) over 24 months. Outcomes assessed every 6 months after belimumab initiation (index) included: physician-assessed overall clinical response (worse, no improvement, < 20%, 20-49%, 50-79%, ≥ 80% improvement), physician-assessed disease severity (mild, moderate, severe), oral corticosteroid (OCS) use and healthcare resource utilization (HCRU)., Results: Of 501 patients enrolled, 123 and 88 were African American and Hispanic respectively; 69 (56.1%) and 43 (48.8%) were receiving belimumab at 24 months. Of those, 88.4%/95.3% (African American/Hispanic) were female; mean (standard deviation [SD]) age was 41.6 (12.5)/42.2 (10.5) years. Within 6 months post-index, 91.3%/90.7% of patients still receiving belimumab had a ≥ 20% physician-assessed clinical improvement. Among 24 months completers, proportions of patients with severe SLE fell from 34.8%/25.6% at index to 2.9%/4.7% at Month 6 and 2.9%/0% at Month 24. The proportion of patients receiving OCS and mean (SD) daily OCS dose also decreased, from 82.6%/81.4% and 19.7 (12.8)/18.8 (10.0) mg/day at index to 50.7%/34.9% and 3.1 (3.2)/1.6 (2.4) mg/day at Month 24. Fewer patients were hospitalized or required ancillary care services at 18-24 months post-index versus 6 months pre-index., Conclusion: Belimumab treatment for up to 2 years improved clinical outcomes, disease severity, mean OCS dose and HCRU in US African American and Hispanic patients with SLE, providing real-world evidence for enduring belimumab effectiveness in populations that are markedly impacted by SLE., (© 2023. The Author(s).)

Background: Randomized trials are the gold-standard for clinical evidence generation, but they can sometimes be limited by infeasibility and unclear generalizability to real-world practice. External control arm (ECA) studies may help address this evidence gaps by constructing retrospective cohorts that closely emulate prospective ones. Experience in constructing these outside the context of rare diseases or cancer is limited. We piloted an approach for developing an ECA in Crohn's disease using electronic health records (EHR) data., Methods: We queried EHR databases and manually screened records at the University of California, San Francisco to identify patients meeting the eligibility criteria of TRIDENT, a recently completed interventional trial involving an ustekinumab reference arm. We defined timepoints to balance missing data and bias. We compared imputation models by their impacts on cohort membership and outcomes. We assessed the accuracy of algorithmic data curation against manual review. Lastly, we assessed disease activity following treatment with ustekinumab., Results: Screening identified 183 patients. 30% of the cohort had missing baseline data. Nonetheless, cohort membership and outcomes were robust to the method of imputation. Algorithms for ascertaining non-symptom-based elements of disease activity using structured data were accurate against manual review. The cohort consisted of 56 patients, exceeding planned enrollment in TRIDENT. 34% of the cohort was in steroid-free remission at week 24., Conclusion: We piloted an approach for creating an ECA in Crohn's disease from EHR data by using a combination of informatics and manual methods. However, our study reveals significant missing data when standard-of-care clinical data are repurposed. More work will be needed to improve the alignment of trial design with typical patterns of clinical practice, and thereby enable a future of more robust ECAs in chronic diseases like Crohn's disease., Competing Interests: NS, NE, CC, SR, DA, MC, NSK, CO, NT, and BDM are employees of Janssen Pharmaceuticals, a for-profit entity that owns all rights to the drug ustekinumab. UM is a consultant for Janssen Pharmaceuticals. AJB is a co-founder and consultant to Personalis and NuMedii; consultant to Mango Tree Corporation, and in the recent past, Samsung, 10x Genomics, Helix, Pathway Genomics, and Verinata (Illumina); has served on paid advisory panels or boards for Geisinger Health, Regenstrief Institute, Gerson Lehman Group, AlphaSights, Covance, Novartis, Genentech, and Merck, and Roche; is a shareholder in Personalis and NuMedii; is a minor shareholder in Apple, Meta (Facebook), Alphabet (Google), Microsoft, Amazon, Snap, 10x Genomics, Illumina, Regeneron, Sanofi, Pfizer, Royalty Pharma, Moderna, Sutro, Doximity, BioNtech, Invitae, Pacific Biosciences, Editas Medicine, Nuna Health, Assay Depot, and Vet24seven, and several other non-health related companies and mutual funds; and has received honoraria and travel reimbursement for invited talks from Johnson and Johnson, Roche, Genentech, Pfizer, Merck, Lilly, Takeda, Varian, Mars, Siemens, Optum, Abbott, Celgene, AstraZeneca, AbbVie, Westat, and many academic institutions, medical or disease specific foundations and associations, and health systems. Atul Butte receives royalty payments through Stanford University, for several patents and other disclosures licensed to NuMedii and Personalis. Atul Butte’s research has been funded by NIH, Peraton (as the prime on an NIH contract), Genentech, Johnson and Johnson, FDA, Robert Wood Johnson Foundation, Leon Lowenstein Foundation, Intervalien Foundation, Priscilla Chan and Mark Zuckerberg, the Barbara and Gerson Bakar Foundation, and in the recent past, the March of Dimes, Juvenile Diabetes Research Foundation, California Governor’s Office of Planning and Research, California Institute for Regenerative Medicine, L’Oreal, and Progenity. These commercial affiliations does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Rudrapatna et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: We evaluated the use of rheumatoid arthritis (RA) disease measures in patients with systemic lupus erythematosus (SLE) in a US community-based rheumatology physician network over 5 years., Methods: This retrospective, observational cohort study (GSK Study 213818) of patients with SLE utilized electronic medical records (01 January 2010-31 December 2019) from the United Rheumatology Normalized Integrated Community Evidence database. The index was the date of first SLE diagnosis recorded in the database; the observation period was 5 years post-index. RA disease measures evaluated were: Pain Index, Multi-Dimensional Health Assessment Questionnaire (MD-HAQ), Patient Global Assessment (PtGA), Physician Global Assessment (PGA), Swollen Joint Count (SJC), Tender Joint Count (TJC), Routine Assessment of Patient Index Data 3 (RAPID3), Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), and Disease Activity Score 28 (DAS-28). The number of patients with measures utilized, the score on each measure, and proportion of patients per disease activity category were assessed., Results: Overall, 5990 patients with SLE were included. The most frequently used measures were Pain Index, SJC, TJC, MD-HAQ, PtGA, RAPID3, and PGA (cumulative use over Years 1-5: 23.9-71.3%). For all measures, frequency of use was lowest in Year 1, followed by a general increase from Year 1 to Year 5. Scores remained relatively stable for most measures, and the proportion of patients in remission or with low/moderate disease activity per RAPID3 increased., Conclusion: RA disease measure utilization in SLE was generally infrequent but increased over time. Pain Index and MD-HAQ were the most commonly applied cumulatively across 5 years of follow-up. The rationale for the increased use of these measures in SLE over time requires further exploration. In the absence of a clinically applicable SLE-specific measure, the use of RA measures, for example in conjunction with SLE measures, may provide an alternative approach for measuring disease activity, representing an opportunity to improve patient outcomes., (© 2022. The Author(s).)

Tenosynovial giant cell tumour (TGCT) is a rare, locally aggressive, mesenchymal tumor arising from the joints, bursa and tendon sheaths. TGCT comprises a nodular- and a diffuse-type, with the former exhibiting mostly indolent course and the latter a locally aggressive behavior. Although usually not life-threatening, TGCT may cause chronic pain and adversely impact function and quality of life (QoL). CSFR1 inhibitors are effective with benefit on symptoms and QoL but are not available in most countries. The degree of uncertainty in selecting the most appropriate therapy and the lack of guidelines on the clinical management of TGCT make the adoption of new treatments inconsistent across the world, with suboptimal outcomes for patients. A global consensus meeting was organized in June 2022, involving experts from several disciplines and patient representatives from SPAGN to define the best evidence-based practice for the optimal approach to TGCT and generate the recommendations presented herein., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Field education is the signature pedagogy of social work education, but there is no standardized mechanism to ensure field instructors are trained in the same clinical modalities as social work students or are well-trained in the provision of clinical supervision. Feasibility was assessed of providing field instructors (n = 9) with a continuing education (CE) program to train them in a specialized evidence-based practice, motivational interviewing (MI) in a recovery context, and strategies for supervision. Participants of the CE program gained confidence (p < .05) and knowledge in the spirit (p < .01) and skills (p < .001) of MI; while participants described initial reactions of disdain when role-plays were introduced in the training, they ultimately identified role-plays and facilitator modeling as key features in producing their own practice change and mimicked the use of parallel process - using MI as a way to teach MI - in their provision of supervision. Findings suggest that offering a CE program to train field instructors in a specialized evidence-based practice embedded in course work and strategies for supervision is feasible and may result in enhanced supervision in field education., Competing Interests: Conflict of InterestThe authors declare that they have no conflict of interest., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

In 2011, the Society for Vascular Surgery (SVS) prepared a set of clinical research priorities through a survey of its membership. These priorities were developed with the goal of enhancing clinical research to improve care for vascular patients. In the subsequent decade, several of these priorities served as the focus of clinical trials and significant research efforts. It was understood from the outset that this list of priorities represented a starting point with the intention that they be reevaluated at suitable intervals. In 2021, the SVS Research Council set out to update the research priorities by surveying the SVS membership and engaged a panel of subject matter experts. This process resulted in an updated set of vascular research priorities that more clearly align with current areas of emphasis. Our priorities remain focused on basic areas including aortic disease, carotid disease, lower extremity arterial disease, venous disease, dialysis access, and medical management of vascular disease, along with the topic of health care disparities. The 10 updated priorities reported herein reflect our increasing awareness of the need to understand vascular disease pathogenesis and prevention in the context of a diverse patient population. Importantly, patient-centered outcomes and personalized vascular care are at the core of these updated priorities. Similar to the aims of the original 2011 clinical research priorities, our hope is that this updated list will help to drive large-scale investigations that will improve how we care for our vascular patients., (Copyright © 2022 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Type 2N is a rare von Willebrand disease (VWD) variant involving an impairment in the factor VIII (FVIII) carrier function of von Willebrand factor (VWF). It has a phenotype that mimics hemophilia A, and FVIII binding to VWF (VWF:FVIIIB) is tested to differentiate between the two disorders. Type 2N VWF defects may also be associated with quantitative VWF mutations (type 2N/type 1), further complicating the identification of cases. We report on a new quantitative VWF mutation (c.2547-1G > T) revealed by a p.R854Q type 2N mutation acting as homozygous despite being carried as a heterozygous defect. The proband had near-normal VWF levels (initially ruling out a defective VWF synthesis) and slightly reduced FVIII levels, while a VWF:FVIIIB test showed significantly reduced binding. Routine tests on type 2N homozygotes or heterozygotes combined with quantitative VWF defects in our cohort showed reduced FVIII levels in both groups, but it was only in the former that the FVIII/VWF antigen (VWF:Ag) ratio was always significantly reduced. The two tests are therefore not enough to identify all forms of type 2N VWD. While relatives of type 2N homozygotes usually have normal FVIII levels and FVIII/VWF:Ag ratios, relatives of type 2N/type 1 may have high FVIII/VWF:Ag ratios, but their VWF:FVIIIB and/or VWF:FVIIIB/VWF:Ag ratios are always low. Measuring FVIII and VWF levels may therefore suggest type 2N VWD in patients carrying type 2N mutations alone, but not in type 2N combined with quantitative VWF defects. The VWF:FVIIIB test should consequently be included when exploring VWF function, whatever VWD patient's phenotype., Competing Interests: None declared., (Thieme. All rights reserved.)

The COVID-19 pandemic has strained healthcare resources the world over, requiring healthcare providers to make resource allocation decisions under extraordinary pressures. A year later, our understanding of COVID-19 has advanced, but our process for making ethical decisions surrounding resource allocation has not. During the first wave of the pandemic, our institution uniformly ramped-down clinical activity to accommodate the anticipated demands of COVID-19, resulting in resource waste and inefficiency. In preparation for the second wave, we sought to make such ramp down decisions more prudently and ethically. We report the development of a tool that can be used to make fair and ethical decisions in times of resource scarcity. We formed an interprofessional team to develop and use this tool to ensure that a diverse range of stakeholder perspectives were represented in this development process. This team, called the clinical activity recovery team, established institutional objectives that were combined with well-established procedural values, substantive ethical principles and decision-making criteria by using a variation on the well-known accountability for reasonableness ethical framework. The result of this is a stepwise, semiquantitative, ethical decision tool that can be applied to resource allocation challenges in order to reach fair and ethically defensible decisions. This ethical decision tool can be applied in various contexts and may prove useful at both the institutional and the departmental level; indeed this is how it is applied at our centre. As the second wave of COVID-19 strains healthcare resources, this tool can help clinical leaders to make fair decisions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

The field of ultraviolet (UV)-laser applications is currently experiencing rapid growth in the semiconductor processing, laser micromachining and biomedical markets. Key enablers for these technologies are optical coatings used to manipulate and guide laser beams in a targeted manner. As laser power, laser fluence and pulse frequencies increase, the demands on the physical properties of the coating materials become more stringent. Ion beam sputtering is a technique that allows producing optical coatings with the low losses required in these applications. In this study, we investigate the influence of ion beam sputtering (IBS) parameters on the optical properties of HfO 2 and SiO 2 single layers as well as the impact of annealing duration at 475 °C for anti-reflective (AR) and highly reflective (HR) optical coatings at 355 nm. For HfO 2 sputtered from a metal target the O 2 flow during the coating process is a key parameter to reduce absorption. SiO 2 single layers exhibit improved transmission in the UV-range as the ion beam energy for the sputtering process is reduced. Furthermore, a complex behavior for film stress, absorption, surface roughness and coating structure was unraveled as a function of annealing duration for AR- and HR-coatings at 355 nm. The reflectance of the HR-mirror after optimized annealing exceeded 99.94% at 355 nm and a high laser induced damage threshold (LIDT) of 6.9 J/cm 2 was measured after 2 hours of annealing. For the AR-coating a LIDT-value of 15.7 J/cm 2 was observed after 12 hours of annealing.

BACKGROUND Gastric carcinoma (GC) remains one of the most common and deadly neoplasms in the world. Liposarcoma (LPS) is the most common sarcoma of adults. However, synchronous or metachronous occurrence of GC with LPS seems to be very rare. Tumor staging and differential diagnosis with these cases are extremely difficult. CASE REPORT The patient was a man in his 70s, who reported anorexia and weight loss of 4 kg over 2 months. Gastroscopy demonstrated a large tumor of Borrmann type 3, of which histology was moderately to poorly differentiated adenocarcinoma. The clinical stage was initially defined as IVb due to a 11×6 cm retroperitoneal (RP) tumor. Despite chemotherapy for GC, the RP tumor rapidly enlarged. Endoscopic ultrasound-guided fine-needle aspiration biopsy showed that it was an undifferentiated sarcoma. He died of hepatorenal failure secondary to severe jaundice. The autopsy revealed a synchronous occurrence of GC and RP sarcoma. GC had no areas admixed with sarcoma. Histology of RP sarcoma showed that it mainly consisted of undifferentiated sarcoma and focally of well-differentiated LPS characterized by well-differentiated adipocytes admixed with scattered atypical stromal cells. The tumor cells in both areas were positive for MDM2 and CDK4 by immunohistochemistry. The diagnosis of the RP sarcoma was revised to dedifferentiated LPS. CONCLUSIONS There were no previous case reports of synchronous occurrence of GC with LPS in the English and Japanese literature. GC and LPS pose challenging problems in their diagnoses, staging, and treatments when they occur synchronously or metachronously.