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There is an urgent clinical need to identify patients likely to benefit from immune checkpoint inhibitor ICI treatment. Approaches available in the clinic today, such as PD-L1 immunohistochemistry (IHC) and tumor mutation burden (TMB), are insufficient for this task, in part as differences in microenvironments expressed by individual tumors may lead to heterogeneous response patterns. Recent efforts exploring the utility of quantitative imaging (radiomic) biomarkers to predict response to ICIs have shown promise to provide a more accurate and scalable method. In contrast to previously published models, our work focuses on generalizable models for predicting individual lesion-level as well as patient-level response at 3-month follow-up per RECIST criteria, using a large multi-institutional “real-world” dataset. The models combine radiomics features with demographic, molecular, and laboratory values routinely available in patients’ electronic medical records. We analyzed radiomic characteristics of 6,295 primary and metastatic lesions from 1,206 metastatic NSCLC patients treated with anti-PD-1/anti-PD-L1 ICIs from 8 institutions across the US and Europe. Patients with unavailable PD-L1 IHC, imaging follow-up, or with oncogenic driver mutations were excluded from analysis, resulting in a total dataset of 766 subjects randomly assigned to training (N=514) and validation sets (N=252). Using gradient-boosted decision tree algorithms, we developed a multi-modal predictive model to identify patients responding to ICI therapy at 3-months and evaluated its performance against an imaging-only CT radiomics model and the clinical standard of care, biopsy-based PD-L1 IHC. The multi-modal model contains CT radiomic features capturing lesion heterogeneity and spicularity, patient demographics, PD-L1 TPS, and tumor burden volume in the lung, lymph nodes, and the liver. Under the two-tailed DeLong test, the multi-modal model demonstrated statistically significant benefit over the current standard of care (PD-L1 IHC) in predicting multi-lesion 3-month response: 0.81 (P=.005) area under the receiver operating characteristic curve (ROC-AUC) in first-line ICI monotherapy patients, 0.72 (P=.044) in all-lines ICI monotherapy, and 0.71 (P=.025) in all-lines ICI-chemotherapy combination. The imaging-only model demonstrated predictive performance comparable to PD-L1 IHC: 0.71 (P=.226), 0.61 (P=.905), 0.62 (P=.674) on the same cohorts respectively. A multi-modal CT radiomics-based approach demonstrated predictive accuracy benefit over the current clinical standard and may provide an opportunity for more personalized patient management, such as risk-based escalation/de-escalation of concurrent chemotherapy in NSCLC patients. We will evaluate this methodology in prospective studies. Citation Format: Ravi B. Parikh, Petr Jordan, Rita J. Ciaravino, Ryan A. Beasley, Arpan A. Patel, Dwight H. Owen, Arya Amini, Brendan D. Curti, Ray Page, Aurelie Swalduz, Jean-Paul Beregi, Jan Chrusciel, Eric Snyder, Pritam Mukherjee, Heather M. Selby, Soohee Lee, Roshanthi Weerasinghe, Shwetha Pindikuri, Jakob B. Weiss, Andrew L. Wentland, Anish Kirpalani, An Liu, Olivier Gevaert, George Simon, Hugo JWL Aerts. Multi-institutional validation of a radiomics-based artificial intelligence method for predicting response to PD-1/PD-L1 immune checkpoint inhibitor (ICI) therapy in stage IV NSCLC. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5618.

Aims The aim of this study was to determine the immediate post-fixation stability of a distal tibial fracture fixed with an intramedullary nail using a biomechanical model. This was used as a surrogate for immediate weight-bearing postoperatively. The goal was to help inform postoperative protocols. Methods A biomechanical model of distal metaphyseal tibial fractures was created using a fourth-generation composite bone model. Three fracture patterns were tested: spiral, oblique, and multifragmented. Each fracture extended to within 4 cm to 5 cm of the plafond. The models were nearly-anatomically reduced and stabilized with an intramedullary nail and three distal locking screws. Cyclic loading was performed to simulate normal gait. Loading was completed in compression at 3,000 N at 1 Hz for a total of 70,000 cycles. Displacement (shortening, coronal and sagittal angulation) was measured at regular intervals. Results The spiral and oblique fracture patterns withstood simulated weight-bearing with minimal displacement. The multifragmented model had early implant failure with breaking of the distal locking screws. The spiral fracture model shortened by a mean of 0.3 mm (SD 0.2), and developed a mean coronal angulation of 2.0° (SD 1.9°) and a mean sagittal angulation of 1.2° (SD 1.1°). On average, 88% of the shortening, 74% of the change in coronal alignment, and 75% of the change in sagittal alignment occurred in the first 2,500 cycles. No late acceleration of displacement was noted. The oblique fracture model shortened by a mean of 0.2 mm (SD 0.1) and developed a mean coronal angulation of 2.4° (SD 1.6°) and a mean sagittal angulation of 2.6° (SD 1.4°). On average, 44% of the shortening, 39% of the change in coronal alignment, and 79% of the change in sagittal alignment occurred in the first 2,500 cycles. No late acceleration of displacement was noted. Conclusion For spiral and oblique fracture patterns, simulated weight-bearing resulted in a clinically acceptable degree of displacement. Most displacement occurred early in the test period, and the rate of displacement decreased over time. Based on this model, we offer evidence that early weight-bearing appears safe for well reduced oblique and spiral fractures, but not in multifragmented patterns that have poor bone contact. Cite this article: Bone Joint J 2021;103-B(2):294–298.

Criminologists have long speculated that economic conditions play a role in driving crime trends. Emerging research finds that inflation rates are associated with crime rates both within the United States and cross-nationally. Inflation is hypothesized to increase crime by incentivizing illegal markets and organized criminal activity and by reducing the legitimacy of social institutions. Existing research on the association between inflation and homicide rates has been limited to single-country studies or multicountry studies consisting of developed countries only. Moreover, there has been limited attention to the potential complexity of this relationship, including whether it is nonlinear, as crime rates may only increase after a certain threshold of inflation is reached, and whether the criminogenic impact of inflation may be moderated by socioeconomic development, as developing countries are anticipated to be more adversely impacted by the criminogenic influence of inflation. Drawing on a sample of 65 economically diverse countries from 1965 to 2015, we find a positive direct relationship between inflation and homicide rates, although we do not find evidence that this association is nonlinear. Finally, contrary to expectation, we find that the inflation–homicide relationship is most impactful in countries with higher levels of development. We discuss these findings in the context of cross-national predictors of crime.

The purpose of this systematic review was to evaluate both the clinical and radiographic outcomes following supramalleolar osteotomy (SMO) in patients with ankle osteoarthritis, and to analyse the level of evidence (LOE) and quality of evidence (QOE) of the included studies.A systematic review of the MEDLINE, EMBASE, and Cochrane Library databases was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies reporting clinical data following SMO for the treatment of ankle osteoarthritis were included and assessed. The level and quality of evidence of the included studies were also evaluated.Twenty-four studies with 1160 patients (1182 ankles) were included. Overall, 78.8% patients presented with post-traumatic ankle osteoarthritis. The weighted mean AOFAS score improved from 52.6 ± 9.7 (range 33.8-78.4) preoperatively to 78.1 ± 5.7 postoperatively at weighted mean follow-up of 50.4 ± 18.6 months (range 24.5-99.0). The most frequently utilised radiographic parameter was the tibial anterior surface angle, which improved from a preoperative weighted mean of 86.3° ± 5.6° (range 76.0°-102.0°) to a postoperative weighted mean of 89.9° ± 3.7° (range 84.9°-99.6°). The complication rate was 5.1% with non-union as the most commonly reported complication (1.6%). Secondary procedures were carried out in 28.2% of patients, the most common of which was implant and hardware removal (17.6%). The failure rate was 6.8%. Two studies were LOE II, 3 studies were LOE III, and 19 studies were LOE IV. The mean Modified Coleman Methodology Score was 59.3 ± 6.6 and the mean MINORS criteria score of all the included studies was 9.5 ± 3.7.This systematic review demonstrates good clinical and radiological outcomes, together with a low failure rate at mid-term follow-up following supramalleolar osteotomy in patients with ankle osteoarthritis. However, a moderate reoperation rate (28.2%) was reported. A low failure rate (6.8%) was reported, which must be interpreted in light of the shortcomings of the design of the included studies and a relatively short follow-up period. In addition, there is a low level and quality of evidence in the current literature with inconsistent reporting of data which underscores the need for further higher quality research to be conducted. Our review highlights that SMO may be an effective and safe procedure in the setting of early-to-intermediate-stage ankle osteoarthritis.IV.

This study investigates the longitudinal relationship between international migration and homicide using a sample of 88 developed and developing countries from 1993 to 2015. Drawing on research dem...

OBJECTIVE Standardization of prescriptions after specific procedures (laparoscopic appendectomy, cholecystectomy, inguinal/umbilical hernia repair) significantly reduces opioid prescriptions for these targeted procedures. We sought to determine the impact of increased attention to responsible opioid prescribing in the absence of protocolization. DESIGN Prescription practices of Laparoscopic Sleeve Gastrectomies and Roux-en-y Gastric Bypasses at a tertiary medical center (October 1, 2016-September 30, 2018) were retrospectively reviewed. Patients were grouped into whether surgical intervention took place before or after institution of an unrelated opioid protocol in November 2017. Patients with chronic opioid use or extended hospital stay (>4 days) were excluded. Discharge prescriptions, oral morphine equivalents (OME), and need for repeat prescriptions were compared. SETTING This study was set at Madigan Army Medical Center in Tacoma, Washington. PARTICIPANTS All general surgery residents engaged in clinical duties at our institution during the dates of the study were included. RESULTS Study population included 187 patients, with 91 patients undergoing surgery prior to the protocol and 88 post-protocol. Preprotocol patients were provided an average of 413 OME (SD 103) and 5.5% required repeat opioid prescriptions within 3 months of surgery. The most common opioid prescription was 300 mL of oxycodone elixir (450 OME, 88%). Postprotocol, opioid prescriptions fell 61% to an average of 161 OME (SD 71, p < 0.001). Repeat opioid requirements remained statistically unchanged (8.0%, p = 0.562). The most common opioid prescription postprotocol included 20 oxycodone tablets (150 OME, 76%). CONCLUSIONS Opioid reduction efforts reap benefits beyond those procedures specifically targeted. Focus on responsible opioid prescribing through standardization, even when limited to certain procedures, may result in a hospital culture change with global opioid prescription reduction.

Background Eteplirsen, the first FDA-approved RNA-modifying therapy for DMD, is applicable to ∼13% of patients with DMD. Because multiple exonic deletions are amenable to exon 51 skipping, the isoforms resulting from the various exon 51-skipped transcripts may vary in stability, function, and phenotype. Objective/methods We conducted a detailed review of dystrophinopathy published literature and unpublished databases to compile phenotypic features of patients with exon 51 "skip-equivalent" deletions. Results Theoretically, 48 different in-frame transcripts may result from exon 51 skipping. We found sufficient clinical information on 135 patients carrying mutations that would result in production of 11 (23%) of these transcripts, suggesting the remainder have not been identified in vivo. The majority had mild phenotypes: BMD (n = 81) or isolated dilated cardiomyopathy (n = 3). Particularly interesting are the asymptomatic (n = 10) or isolated hyperCKemia (n = 20) patients with deletions of exons 45- 51, 48- 51, 49- 51 and 50- 51. Finally, 16 (12%) had more severe phenotypes described as intermediate (n = 2) or DMD (n = 14), and 6 reports had no definitive phenotype. Conclusions This review shows that the majority of exon 51 "skip-equivalent" deletions result in milder (BMD) phenotypes and supports that exon 51 skipping therapy could provide clinical benefit, although we acknowledge that other factors, such as age at treatment initiation or ongoing standard of care, may influence the degree of benefit.

Research suggests that individuals may benefit from participation in a partial hospital program (PHP) following discharge from inpatient psychiatric hospitalization. Indeed, PHPs are designed to facilitate further stabilization and skill-building before discharge to the community. As a result, our hospital-located in a large metropolitan area in the Northeastern United States-has long maintained a commitment to providing this critical level of care. However, during the COVID-19 pandemic, these in-person PHP services were discontinued in response to public health recommendations and to ensure the safety and well-being of patients and staff. To maintain this important point along the psychiatric care continuum, hospital leadership encouraged our PHP team to pursue an alternative approach to treatment delivery: video-based telepsychotherapy. This article describes the development of a virtual PHP that serves acute psychiatric patients stepping down from inpatient hospitalization. First, we provide an overview of the original in-person PHP and then discuss the process of its transition to a virtual format. Next, we describe in detail the components of our newly developed virtual PHP, highlighting adaptations necessitated by patients and staff being remote from our physical hospital. Finally, we present preliminary evidence of our virtual PHP's acceptability and feasibility, based on experiences with our 23 patients to date; discuss lessons learned from this program development effort; and recommend future directions for research and clinical practice. Information provided herein aims to guide the development of other virtual PHPs and telepsychotherapy programs that similarly strive to offer intensive treatment to an acute psychiatric population.

There are several noteworthy cognitive and identity-based theories of desistance. Yet, there is little understanding about the role of one’s expectations of future events, which are tied to one’s sense of self, as they ultimately inform actions regarding offending. In this study, we test the extent to which optimistic and fatalistic expectations are related to desistance. We rely on negative binomial regression analyses and group-based trajectory modeling of data drawn from the National Longitudinal Survey of Youth 1997 to determine the relationship between future event expectations and criminal engagement. We assess continued criminal involvement through self-reported arrests and offending variety. We find that future expectations regarding negative events (arrest, victimization, and drunkenness) are associated with future self-reported arrest while future positive expectations (parenthood, education, and employment) are unrelated to future offending behavior. Higher expectations of being arrested and getting drunk in the following year were associated with a greater likelihood of being classified as a persister relative to a nonoffender. We also find that Blacks are more likely to be classified as persisters. Yet, future expectations in late adolescence appear to be poor predictors of whether an individual will desist from offending over the long term. Our results suggest that future fatalistic expectations of a ‘feared self’ are generally associated with short-term offending. Future studies should explore the degree to which expectations and the development of a future self may vary by race and gender and alternative interpretations of the NLSY97 expectation questions.

The study of the cratering history of asteroid (16) Psyche is one of the investigations to be performed by the NASA Psyche mission. A dedicated Relative Ages Working Group will carry on these investigations using primarily imaging and topographic data, and complement the interpretation of these data with theoretical models (hydrocodes to simulate impacts) as well as laboratory experiments (impact experiments on relevant target materials). The Psyche Science Team will also rely on experience and lessons learned from prior space missions, such as NASA Dawn and ESA Rosetta.The main goals of the cratering investigations are to map craters and characterize their morphology across Psyche’s surface over a range of spatial resolutions. These data will then be used to constrain relative and absolute ages of Psyche’s terrains, and impact-related processes will inform other investigations, such as geological mapping, surface composition, and internal structure. Psyche’s cratering data will also be used to perform comparative analyses with similar data from other rocky asteroids. The present chapter provides a pre-launch view of the planned activities and methodologies of the Relative Ages Working Group.

Background The serum metabolome contains potential disease biomarkers, some of which are produced endogenously, derived from the diet, or formed by the gut microbiome. We aimed to characterize metabolomics profiles linked with Crohn Disease (CD), with active CD, and with remitting pre-flare CD. Methods Serum untargeted metabolomics was performed using liquid chromatography Mass Spectrometer (LC/MS). PERMANOVA on beta diversity was used to define factors affecting serum metabolome. Multivariate analyses in MaAsLin2 were applied to identify differentially abundant metabolites between CD and controls, between active CD and those in remission, and between those that subsequently flared and those that remained in remission within 24 months of follow-up. Results The cohort included 202 samples from 53 CD patients and 31 healthy controls (156 samples from CD and 46 from controls; Table 1). 545 metabolites were included in our predefined library and were subsequently analyzed. PERMANOVA on the serum metabolomic data indicated that fasting, age, gender, disease, and subject are significant factors contributing to metabolomics variations. Using multivariate analyses and controlling for fasting, age, gender, and subject, we identified 34 specific metabolites that were significantly higher in CD and 26 that were significantly higher in Controls (FDR Conclusion CD, CD activity, and a subsequent flare in CD patients with longitudinal data were associated with distinct serum metabolic signature after controlling for confounders like age, gender, and fasting. Additional validation is needed to test if these can be used as predictive biomarkers.

The major determinant of disease severity in patients with severe Duchenne muscular dystrophy (DMD) or milder Becker muscular dystrophy (BMD) is whether their dystrophin gene (DMD) mutation disrupts the mRNA reading frame or allows expression of a partially functional protein. However, even in the complete absence of dystrophin, variability in disease severity is observed, and candidate gene studies have implicated several genes as possible modifiers. Our previous genome-wide association study (GWAS) for age at loss of ambulation (LOA) in DMD provided confirmation for the role of genetic modifiers of TGF-β signaling in disease progression. Here we present the largest genome-wide search to date for loci influencing disease severity in DMD patients. Availability of subjects for such studies is still quite limited, leading to modest sample sizes, which present a challenge for GWAS design. We have therefore taken special steps to minimize heterogeneity within our dataset at the DMD locus itself, taking a novel and conservative approach to mutation classification to effectively exclude the possibility of residual dystrophin expression. We have also utilized statistical methods that are well adapted to smaller sample sizes, including the use of a novel linear regression-like residual for time to ambulatory loss and the application of evidential statistics for the GWAS approach. Based on the resulting sample size of N = 419 patients, we have identified multiple potential candidate genetic modifier loci. In a companion paper to this one, we use a systematic bioinformatic pipeline to implicate specific genes within these loci as potential DMD modifiers.

Although the major determinant of disease severity in patients with severe Duchenne muscular dystrophy (DMD) or milder Becker muscular dystrophy (BMD) is whether their dystrophin gene (DMD) mutation disrupts the mRNA reading frame or allows expression of a partially functional protein, other genes have been proposed or demonstrated to modify the severity of disease progression. In a companion paper to this one, we describe our novel approaches to genome-wide association study (GWAS) of loss of ambulation (LOA) in the largest genome-wide search to date for loci influencing disease severity in DMD patients. Candidate regulatory SNPs that modify disease progression were identified using an evidential statistical paradigm and here we present a uniform application of recent functional genomic datasets to explore the potential functional impact of the top six candidate regions with PPLD scores of ≥0.4. The results of this analysis of the largest DMD GWAS survey to date elucidate recurrent and potentially new pathways for intervention in the dystrophinopathies.

In current clinical practice, weight-bearing is typically restricted for up to 12 weeks after definitive fixation of lower extremity periarticular fractures. However, muscle atrophy resulting from restricting weight-bearing has a deleterious effect on bone healing and overall limb function. Antigravity treadmill therapy may improve recovery by allowing patients to safely load the limb during therapy, thereby reducing the negative consequences of prolonged non-weight-bearing while avoiding complications associated with premature return to full weight-bearing. This article describes a multicenter randomized controlled trial comparing outcomes after a 10-week antigravity treadmill therapy program versus standard of care in adult patients with periarticular fractures of the knee and distal tibia. The primary hypothesis is that, compared with patients receiving standard of care, patients receiving antigravity treadmill therapy will report better function 6 months after definitive treatment.

Background Optimizing nerve regeneration and re-innervation of target muscle/s is the key for improved functional recovery following peripheral nerve damage. We investigated whether administration of mesenchymal stem cell (MSC), Granulocyte-Colony Stimulating Factor (G-CSF) and/or Dihexa can improve recovery of limb function following peripheral nerve damage in rat sciatic nerve transection-repair model. Materials and methods There were 10 experimental groups (n = 6–8 rats/group). Bone marrow derived syngeneic MSCs (2 × 106; passage≤6), G-CSF (200–400 μg/kg b.wt.), Dihexa (2–4 mg/kg b.wt.) and/or Vehicle were administered to male Lewis rats locally via hydrogel at the site of nerve repair, systemically (i.v./i.p), and/or to gastrocnemius muscle. The limb sensory and motor functions were assessed at 1–2 week intervals post nerve repair until the study endpoint (16 weeks). Results The sensory function in all nerve boundaries (peroneal, tibial, sural) returned to nearly normal by 8 weeks (Grade 2.7 on a scale of Grade 0–3 [0 = No function; 3 = Normal function]) in all groups combined. The peroneal nerve function recovered quickly with return of function at one week (∼2.0) while sural nerve function recovered rather slowly at four weeks (∼1.0). Motor function at 8–16 weeks post-nerve repair as determined by walking foot print grades significantly (P, Highlights • G-CSF in combination with MSCs improved limb function recovery in sciatic nerve transection- repair model. • Dihexa in combination with MSC improved limb function recovery in sciatic nerve transection- repair model. • Foot flexion contractures were reduced with G-CSF & MSC or Dihexa & MSC administration into target muscle gastrocnemius. • MSC, G-CSF or Dihexa combination therapy is attractive, feasible & promising in peripheral nerve injury repair and have implications in limb transplantation. • The findings warrant further investigation to understand the cellular/molecular mechanisms.

Neurofibromatosis type 1 (NF1) is associated with behavioral alterations and cognitive impairments. There is a genetic interaction between NF1 and the receptor tyrosine kinase Alk. Short-term pharmacological Alk inhibition, with a compound FDA-approved for cancer starting 10 days prior to cognitive testing, was shown to improve cognitive performance of NF1 heterozygous (HET) mice. However, effects of long-term Alk inhibition on behavioral cognitive performance are not known. Therefore, in the study described below we determine the effects of prolonged pharmacological Alk inhibition for 24 weeks on behavioral and cognitive performance of NF1 HET mice. As these studies have the ultimate objective of developing a treatment for humans with neurofibromatosis and acceptable side effects in the context of cancer are not acceptable in the context of long-term treatment of patients with neurofibromatosis, we included additional behavioral tests of anxiety-like and depressive-like behaviors as well. Long-term effects of Alk inhibition had genotype-dependent effects, consistent with a specific interaction between Alk and NF1. Beneficial effects of long-term Alk inhibition in NF1 HET mice included rescue of impairments in object recognition in NF1 HET males and females, and improved cognitive performance of NF1 HET males and females in the water maze test. In contrast, long-term Alk inhibition had detrimental effects in WT mice not seen after short-term treatments. As longer treatments are translationally more relevant for NF1 patients, these data highlight the important to assess long-term effects of drugs, especially of repurposed drugs used originally as part of cancer therapy.

Components made of nickel-based alloys are typically used for high-temperature applications because of their high corrosion resistance and very good creep and fatigue strength, even at temperatures around 1000 °C. Corrosive damage can significantly reduce the mechanical properties and the expected remaining service life of components. In the present study, a new method was introduced to continuously determine the change in microstructure occurring as a result of exposure to high temperature and cyclic mechanical loading. For this purpose, the conventional low-cycle fatigue test procedure was modified and a non-destructive, electromagnetic testing technique was integrated into a servohydraulic test rig to monitor the microstructural changes. The measured values correlate with the magnetic material properties of the specimen, allowing the microstructural changes in the specimen’s subsurface zone to be analyzed upon high-temperature fatigue. Specifically, it was possible to show how different loading parameters affect the maximum chromium depletion as well as the depth of chromium depletion, which influences the magnetic properties of the nickel-based material. It was also observed that specimen failure is preceded by a certain degree of microstructural change in the subsurface zone. Thus, the integration of the testing technology into a test rig opens up new possibilities for improved prediction of fatigue failure via the continuous recording of the microstructural changes.

As habitat generalists, urban coyote (Canis latrans) populations often utilize an abundance of diverse food sources in cities. Within southern California, domestic cats (Felis catus) comprise a higher proportion of coyote diets than in other studied urban areas throughout the United States. However, it is unclear which ecological factors contribute to higher rates of cat depredation by coyotes in this region. While previous research suggests that coyote presence may have a negative effect on free-ranging domestic cat distributions, few studies have determined whether urban green spaces affect coyote or free-ranging domestic cat occurrence and activity within a predominantly urbanized landscape. We placed 20 remote wildlife cameras across a range of green spaces and residential sites in Culver City, California, an area of Los Angeles County experiencing pronounced coyote-domestic cat conflict. Using data collected across 6 months from 2019–2020, we assessed the influence of green space and prey species (i.e., cottontail rabbits (Sylvilagusspp.) and domestic cats) on coyote habitat use and activity. Coyotes exhibited a preference for sites with higher amounts of green space, while domestic cat habitat use was high throughout our study region. Although cottontail rabbit habitat use was also highly associated with urban green space, neither cottontails nor domestic cats appeared to temporally overlap significantly with coyotes. Unlike other cities where coyotes and domestic cats exhibit strong habitat partitioning across the landscape, domestic cats and coyotes spatially overlapped in green space fragments throughout Culver City. We suggest that this pattern of overlap may be responsible for the frequent cases of domestic cat depredation by coyotes in Culver City.

Category: Ankle; Ankle Arthritis; Basic Sciences/Biologics; Sports; Trauma Introduction/Purpose: Osteochondral lesion of the talus (OLT) is a commonly occurring injury, typically treated with bone marrow stimulation (BMS) in the small to medium-sized lesions after a failed course of conservative treatment. The current evidence suggests that biologics can improve chondrocyte growth and differentiation. However, the lack of consensus to date on the efficacy of biologics + BMS for OLT has warranted further investigation. The purpose of this study is to clarify the effectiveness and safety of biologics as an augmentation in BMS by assessing complication rates, continuous functional outcome scores and return to play data compared to BMS alone for OLT. Methods: A systematic review and meta-analysis were performed. The PubMed and Embase databases were searched using specific search terms and eligibility criteria according to the PRISMA guidelines. The level of evidence was assessed using published criteria by The Journal of Bone & Joint Surgery and the quality of evidence using the Modified Coleman Methodology Score. Fixed- effects models were employed if heterogeneity was graded low (I2 =25%). Results: For BMS versus BMS + hyaluronic acid (HA), the fixed-effects model for American Orthopaedic Foot and Ankle Society score revealed a mean difference increase that is an improvement of 4.88 (95% CI, 2.33 to 7.44; I2 = 0%; p = 0.0002) points, in favor of BMS + HA. The fixed-effects model for 10mm Visual Analog Scale pain revealed a mean difference decrease that is an improvement of 1.21 (95% CI, 0.70 to 1.73; I2 = 0%; p < 0.00001) points, also in favor of BMS + HA. For BMS versus BMS + concentrated bone marrow aspirate (CBMA), the pooled complication rate was 17/64 (26.6%) versus 11/71 (15.5%), respectively, with a chi-squared test of p = 0.11. The pool revision rate was 15/64 (23.4%) versus 6/71 (8.5%), respectively, with a chi-squared test of p = 0.016. Conclusion: Adjuvant biologic use with BMS may provide superior outcomes, notably that of HA and CBMA, based on the current evidence. Future studies must aim to establish the clinical superiority of the various other biologics + BMS versus BMS alone. These studies must compare the various biologics against one another to determine, if any, the optimal biologic for OLT.

Category: Sports; Other Introduction/Purpose: Depending upon the site of injury, Achilles tendinopathy (AT) can be either Insertional (IAT) or Non- Insertional (nIAT). AT has long been managed by conservative measures such as eccentric exercises, but now extracorporeal shock wave therapy (ESWT) has emerged as a non-invasive treatment to stimulate self-repair. However, the native biology at the insertion of the Achilles tendon and mid-substance are intrinsically different, with the mid-substance (2 to 6 cm above the insertion) being significantly less perfused. Thus, we performed a systematic review of the literature on shockwave therapy to determine if there was a difference in efficacy for patients who have undergone ESWT for IAT and nIAT. Methods: In January 2022, the MEDLINE and EMBASE databases were systematically reviewed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We included randomized controlled trials, prospective and retrospective studies, published in English, with pre- and post-operative scores for at least either Visual Analogue Scale (VAS) or Victorian Institute of Sport Assessment - Achilles (VISA-A). We excluded basic science studies, systematic reviews and meta- analyses, retrospective studies, case reports, studies without pre-operative scores, studies that don't differentiate IAT and nIAT. The LoE and QoE of the included studies were evaluated using the Journal of Bone and Joint Surgery Criteria and the Modified Coleman Methodology Score, respectively. We calculated weighted mean values for age, body mass index (BMI), the number of ESWT sessions and their frequency, duration of symptoms prior to ESWT, follow-up time, as well as for each outcome score. Results: 16 studies were included in this review, six with Level I evidence, four with Level II, five with Level III, and one with Level IV. There were 505 cases of AT: 325 patients with IAT and 180 with nIAT. For the IAT cohort, the weighted mean (WM) duration of symptoms prior to treatment was 18.1 months, and WM follow-up was 8.1 months. For the nIAT cohort, the WM duration of symptoms prior to treatment was 15.0 months, and WM follow-up was 11.6 months. In terms of outcome scores, for VAS, the WM pre-operative scores were 6.89 for IAT and 7.76 for nIAT and the WM post-operative scores were 2.76 for IAT and 2.49 for nIAT. For VISA-A, the WM pre-operative scores were 49.3 for IAT and 42.8 for nIAT, and the WM post-operative scores were 75.4 for IAT and 75.7 for nIAT. Conclusion: As the mid-substance portion of the Achilles tendon has diminished blood supply compared to the insertional portion, we expected outcomes after ESWT to be inferior for the nIAT cohort. Interestingly, the VAS pain scores and VISA-A functional scores displayed similar positive results for both cohorts. We see that the virtually equivalent functional and pain outcomes mean that ESWT is stimulating cellular components of the tendon to promote healing regardless of injury location.

Category: Ankle Introduction/Purpose: Acute Achilles tendon rupture (AATR) is a common injury of an incidence rate of up to 31 per 100,000 per year. The current meta-analyses on the treatment of AATR have conflicted data that may, in part, be due to the differences in their methodologies. The aim of this study is to systematically review and present the current meta-analyses for the treatment of AATR. The outcomes of this study can provide clinicians with a clear overview of the current literature to help decide on the optimal treatment for patients. Methods: Two independent reviewers searched PubMed and Embase on March 17, 2020 based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Assessment of evidence was two-fold: level of evidence (LoE) and quality of evidence (QoE). LoE was evaluated using published criteria by The Journal of Bone and Joint Surgery and the QoE by the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) scale. Pooled complication rates were highlighted for significance in favor of 1 group or no significance. Statistical analysis was performed using a statistical software package (R version 3.5.1; R Foundation for Statistical Computing, Vienna, Austria). Descriptive statistics were calculated for each study and statistical parameters analyzed. Continuous variables were reported as mean +- standard deviation and categorical variables were reported as frequencies with percentages. P-values < 0.05 was considered statistically significant. Results: 21 meta-analyses were included in the study. Re-rupture rates ranged between 2.3% to 5.0% for open repair/MIS and 3.9% to 13% for conservative treatment (p < 0.05). Re-rupture rates were reported in 3 of 4 meta-analyses that ranged between 2.3% to 7.8% for conservative treatment earlier rehabilitation and 5.0% to 12.2% for conservative treatment later rehabilitation. Re-rupture rates were 2.5% for open repair earlier rehabilitation and 3.8% for open repair later rehabilitation. When comparing surgical techniques, re-rupture rates ranged between 1.4% to 3.1% for percutaneous repair/MIS and 2.2% to 2.7% for open repair. Infection rates ranged between 2.8% to 5.0% for open repair/MIS and 0% to 0.02% for conservative treatment. The majority of meta-analyses (3 of 5) significantly favored by effect size, open repair/MIS for total infection rates (p < 0.05). Conclusion: The results of this study demonstrate that operative repair reduced the rate of re-rupture when compared to conservative treatment. There is currently conflicting information on whether early functional rehabilitation reduces the difference between the two treatments. Operative treatment has been shown to have a higher rate of wound complications, although the rates of deep wound infections remains to be determined. Percutaneous repair resulted in similar re-rupture rates when compared to open surgery but for the rates of other complications including wound infections, this was diminished. Further meta- analyses which compare all cohorts are needed to ascertain best evidence.

Category: Sports; Other Introduction/Purpose: Extracorporeal Shock Wave Therapy (ESWT) is one of the major advances in orthopedics over the last 20 years as a method for orthopedic surgeons to conservatively treat tendon pathologies such as Achilles tendinopathy (AT). Unfortunately, previous studies involve only a small number of cases, relatively short duration of symptoms, and simple measures of pain. The purpose of this study is to evaluate the impact of age, body mass index (BMI), and location of AT (Insertional (IAT) or Non-Insertional (nIAT)) on clinical outcomes and return to sport (RTS) time after ESWT. Methods: This is a retrospective cohort study that included existing clinical data from 40 patients from a single academic institution. Patients greater than 18 years of age who underwent ESWT for Achilles tendinopathy in the office setting between 8/1/2019 to 8/30/2021 were included. Clinical outcomes of patients were evaluated through the self-reported Visual Analogue Scale (VAS) and Victorian Institute of Sport Assessment-Achilles (VISA-A) scores for assessing pain and functional outcomes of Achilles Tendinopathy. Descriptive statistics were used to provide an overview of the patient characteristics, including sex, age, laterality of injury, BMI, duration of symptoms, RTS time, and follow-up. For these data, mean and standard deviation were calculated, and paired samples T-tests and Welch's T-tests were performed on clinical outcome scores. Results: This study included 48 patients (62 heels), with an average age of 50.8+-14.2 years, BMI of 27.3+-5.3, follow-up of 6.41+- 6.9 months, and RTP time of 5.39+-5.3 weeks. Patients with a BMI 25.0, and post-operative VAS scores displayed this trend without significance (p=0.07). Patients 50 years old, and post-operative VAS scores displayed this trend without significance (p=0.1). Pre- and post-operative VISA-A scores, and post- operative VAS scores, were not significantly different between IAT and nIAT cohorts, except for pre-operative VAS scores where nIAT was higher (p=0.03). Additionally, we found significant improvements in pre-operative to post-operative scores for VAS scores for IAT and nIAT cohorts (pConclusion: Increased BMI and age are determinant factors that significantly adversely affect functional scores (VISA-A) in patients with AT treated with ESWT, but no significant differences were found for these risk factors in terms of pain improvement (VAS). Additionally, we found that the nIAT cohort had significantly higher pre-operative pain than IAT, and no significant improvement in VISA-A scores (though there was a trend of functional improvement). This aligns with the fact that the mid- substance of the Achilles tendon is a watershed area with relatively low vascularity compared to the insertional portion, where lower perfusion weakens the healing benefits of ESWT.

Category: Sports; Other Introduction/Purpose: Although rare, Tibialis Anterior Tendon (TAT) tears or ruptures can have a detrimental effect on patients' quality of life. There is no current consensus as to the most appropriate surgical treatment for TAT rupture, in part because of the paucity of data surrounding this condition. Therefore, this study attempts to address this deficiency by performing a systematic review of the literature of the different surgical interventions for TAT rupture, analyzing the level of evidence (LoE) and quality of evidence (QoE) of the included studies, and recommending an algorithm approach to the surgical treatment of TAT injury. Methods: In September 2021, the MEDLINE and EMBASE databases were systematically reviewed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The following search terms were used: (anterior) AND (tibialis OR tibial) AND (tendon) AND (tear OR rupture) NOT (acl OR cruciate OR meniscal OR patellar). ??Full-length peer-reviewed studies in English with a sample size of 5 participants that reported functional outcome scores were included. We excluded systematic reviews, meta-analyses, review articles, and case series/reports with less than five participants. The LoE and QoE of the included studies were evaluated using the Journal of Bone and Joint Surgery Criteria and the Modified Coleman Methodology Score, respectively. In some cases, tabulated data from studies were analyzed to obtain relevant statistics for our analysis, including deriving descriptive statistics such as mean and standard deviation values, as well calculating p-values with two- sample t-tests assuming either equal or unequal variance. Results: Twelve studies with 171 patients were included in this review, 11 with Level IV evidence and one with Level II evidence. Additionally, there were 17 different types of repair techniques used, where direct repair (including end-to-end repair and bone fixation) was performed on 33.5% of tendons, tendon transfers were performed on 20.8% of tendons, and grafts were performed on 45.7% of tendons. For the mean postoperative AOFAS Ankle-Hindfoot (AOFAS-AH) scores, both the direct repair and autograft cohorts had significantly higher mean scores than the allograft cohort (p=0.008 and p=0.002 respectively). The autograft cohort was also found to have significantly higher post-operative means AOFAS-AH than the tendon transfer cohort (p=0.047). We also found statistically significant improvements in dorsiflexion strength after surgical intervention in early intervention (Conclusion: Surgical management of TAT ruptures produces good clinical outcomes in the intermediate follow-up. As there is no current consensus on the most appropriate surgical treatment, we have designed a treatment algorithm based upon the current literature citing statistical evidence determined in this systematic review.

Category: Ankle; Hindfoot; Lesser Toes; Midfoot/Forefoot Introduction/Purpose: Ankle limitation to dorsiflexion in an extended knee is observed during the second rocker of gait in patients with positive Silfverskiold test confirming an isolated gastrocnemius contracture (IGC). Tendons and muscles share intrinsic contractility and relaxation properties which can be modified during physiotherapy in comparison to the fascia which lacks it. The present study describes a case series of patients with positive Silfverskiold associated with various foot pathologies who underwent a selective fasciotomy of the postero-medial superficial portion of the crural fascia. The purpose of this study is to describe the surgical technique and clinical outcomes of this procedure. We hypothesize that this procedure can reach satisfactory clinical outcomes with the advantage of being a less invasive procedure. Methods: 26 patients treated with partial postero-medial superficial release (PMSR) of the crural fascia from January to October 2021 for IGC with associated chronic foot pain were included. Inclusion criteria considered patients with diagnosis of foot pain with IGC and positive Silfverskiold test. A transverse incision was made 2 cm distal to the flexion crease starting at the intermuscular line of the gastrocnemius muscle, 4 cm medially (Figure 1). Subcutaneous dissection was performed identifying the neurovascular bundle. A horizontal incision was performed to the superficial posterior fascia of the medial gastrocnemius head. The medial gastrocnemius muscle was not sectioned. Patients completed the FADI score previous to surgery and at final follow- up. Data was analyzed using SPSS 20. Paired samples T-tests were performed to identify significance of the difference in pain and function preoperatively and postoperatively with statistical significance set at pResults: 18 patients underwent partial PMSR of the crural fascia while 8 patients had additional procedures. Mean age of the included patients was 40.6 +/-18.5 years. Specifically, this included 4 feet with a diagnosis of metatarsalgia, 3 feet with metatarsalgia and plantar fasciitis, 6 feet with metatarsalgia, plantar fasciitis and cavus foot, 5 feet with plantar fasciitis, 3 feet with plantar fasciitis and insertional achilles tendinopathy, 4 patients with non-insertional achilles tendinopathy and 1 foot with flexor hallucis longus tendinopathy.The average ankle dorsiflexion increased significantly (pConclusion: Partial postero-medial superficial release (PMSR) of the crural fascia was found to be an effective outpatient procedure when used to relieve foot pain in those patients with an isolated gastrocnemius contracture. Patients who have failed conservative treatment can expect notable improvement with satisfactory FADI scores after the procedure. Future prospective studies should involve a larger number of patients with no additional procedures to be compared with gastrocnemius muscle release procedure for isolated gastrocnemius contracture with associated foot pain.

Category: Sports; Other Introduction/Purpose: The Achilles tendon is the most commonly ruptured tendon in the lower limb, and when left untreated for at least 4 weeks, these are classified as chronic or 'neglected' Achilles tendon ruptures (CATR). There is discordance on the optimal surgical treatment to treat CATR. Given the prevalence of this injury, there is a need to determine the best treatment modality. In this study, we performed a systematic review of the literature to compare the different treatment options for CATR, analyze the level of evidence (LOE) and quality of evidence (QOE) of the included studies, and recommend a literature-based algorithmic approach to the treatment of CATR. Methods: In July 2019, MEDLINE, EMBASE, and Cochrane Library databases were systematically reviewed by 2 independent reviewers based on the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines. Full-length peer-reviewed studies in English with a sample size of 10 participants that reported functional outcome scores with a minimum follow-up of 24 months were included. We excluded systematic reviews, meta-analyses, review articles, cadaveric and animal studies, and case reports. The LOE and QOE of the included studies were evaluated using the Journal of Bone and Joint Surgery Criteria and the Modified Coleman Methodology Score, respectively. Patient demographic data, surgical procedure type, subjective outcomes, postoperative strength, range of motion, postoperative imaging, return to sports and work data, complications, failures, and reoperations were evaluated. Continuous variables were reported as weighted mean and estimated standard deviation, whereas categorical variables were reported as frequencies with percentages. Results: Thirty-one studies with 653 CATRs were included. Three studies were LOE III and 28 studies were LOE IV. A large variety of repair techniques were described and analyzed, and semitendinosus tendon grafting was the most frequently utilized technique (6 of 31 studies). The most commonly reported clinical outcome was the American Orthopaedic Foot and Ankle Society (AOFAS) score (58.6%). Most studies reported good postoperative subjective outcomes, strength outcomes, and return to sports data at mid-term follow-up. In total, 14.6% of patients experienced postoperative complications, where the most common was surgical wound complications (10.8%). Conclusion: Surgical management of CATR produces good clinical outcomes at mid-term follow-up, but a high complication rate (14.6%) was noted. This systematic review found that no evidence-based treatment guidelines exist for CATR. Future studies of higher QOE and LOE which focus on specific risk factors are warranted to determine in which case one particular technique would be suitable for CATR repair. Our proposed treatment algorithm (Figure 1) may assist in shared decision-making for this complex problem.

Category: Ankle; Hindfoot; Sports; Trauma Introduction/Purpose: While surgery is often indicated in the treatment of chronic ankle instability (CAI), there lacks consensus on which procedure is preferable in light of the multiple different procedures available. In this systematic review, we evaluate the recent literature on the anatomical reconstruction of the lateral ligaments in the treatment of CAI in an effort to identify differences in clinical and radiological outcomes between allograft and autograft reconstruction techniques. Methods: A systematic search of PubMed, EMBASE, and Cochrane Library databases was performed in October 2019 resulting in 13 studies ranging from the years 1991 to 2017. The studies included were carefully evaluated with regards to the level of evidence (LOE) and quality of evidence (QOE), clinical and radiological outcomes, complications, revision rates and return to sport. Results: Thirteen studies including a total of 296 ankles were included; Within the autograft group, the weighted mean AOFAS improved from 66.9 to 95.9 at a weighted mean follow-up of 29.6 months, KPSSAF scores improved from 48 to 92.2 at a weighted mean follow-up of 37 months, VAS scores improved from 6.8 to 0.2 at a weighted mean follow up of 33.5 months, and the complication rate was 7.7% at a follow up of 31.2 months. Within the allograft group the AOFAS improved from 53.7 to 89.3 at a follow-up of 35.5 months, KPSSAF scores improved from 42.8 to 90.4 at a follow up of 34 months, VAS scores improved from 7.3 to 1.9 at a follow up of 38 months, and the complication rate was 7% at a follow up of 34.9 months. Conclusion: The current systematic review demonstrated that anatomical reconstruction of CAI resulted in favorable clinical and radiological outcomes, low complication and revision rates and excellent return to sport rates in the short-term follow-up. Comparison of autograft and allograft reconstruction techniques for chronic lateral ankle instability showed minor differences both clinically and radiologically but none which would suggest superiority of one technique over another.

Category: Sports; Ankle; Hindfoot; Other Introduction/Purpose: Osteochondral lesions of the talus (OLT) are common injuries that are often found in patients with chronic disabling pain after ankle sprains. While OLT is becoming increasingly prevalent in the younger active population, there is disagreement and a lack of strong evidence about the impact of age on outcomes. The purpose of this study is to perform an Age- Based multivariate analysis to evaluate the clinical outcomes of Autologous Osteochondral Transplantation (AOT) for the treatment of OLT. The goals of this study are to examine trends in patient characteristics and clinical outcomes that occur with age as a statistical variable when performing AOT for the treatment of OLT. Methods: All study protocols were approved by the Institutional Review Board at the senior author's institution. A retrospective cohort study using chart review for AOT procedures on approximately 80 patients from 2006 to 2019 performed by a single surgeon. Clinical outcomes of patients were evaluated via FAOS scores for Symptoms, Pain, Activities of Daily Living, Sports and Quality of Life. A multivariable linear regression was used to assess the independent factors predictive of the first post-operative FAOS after AOT. The independent variables included in the model were pre-operative FAOS, age, defect size, whether the lesion was a shoulder lesion, cystic lesion, or a result of a traumatic injury, and whether the patient had a prior microfracture surgery. A p-value Results: 78 patients were included in the analysis with an average age of 35.5 +- 13.6. The average follow-up was 54.4 months +- 18.9 months, average pre-operative FAOS was 54.3 +- 19.4 and the average post-operative FAOS was 83.4 +- 13.6. The average defect size was 109.3 mm2 (std. dev. = 62.4 mm). 56 patients had a shoulder lesion, 24 had a prior microfracture surgery, 42 had a cystic lesion, and 27 had a prior traumatic injury. The multivariable linear regression showed that the pre-operative FAOS was associated with a higher post-operative FAOS (est., 95% CL: 0.16, 0.012 - 0.307; p=0.034). Defect size (est., 95% CL: -0.05, -0.097 - -0.003; p=0.0358), having a shoulder lesion (est., 95% CL: -9.068, -15.448 - -2.688; p=0.006), or having a prior microfracture surgery (est., 95% CL: -7.07, -13.118 - -1.021; p=0.0226) were associated with a lower post-operative FAOS. Conclusion: The main finding of this study is patient age was not an independent risk factor for inferior clinical outcomes after AOT for OLT. Additionally, having a cystic lesion, or having a lesion because of a traumatic injury were not significantly associated with post-operative FAOS. Having a shoulder lesion had the largest marginal effect on post-operative FAOS. These findings provide important information for providers when counseling and selecting patients for AOT procedure for treatment of OLT.

To achieve conservation objectives for threatened and endangered species, managers must choose among potential recovery actions based on their efficacy. Yet, a lack of standardization in defining how conservation actions support recovery objectives can impede action efficacy and inhibit the efficient allocation of resources across species and projects. It is especially difficult to evaluate the effectiveness of actions in U.S. Endangered Species Act (ESA) recovery plans due to variation in how actions are described across different plans. To address this issue, we examined our ability to apply the internationally supported Conservation Measures Partnership (CMP) taxonomy to categorize existing ESA recovery plan action descriptions. Using ESA listed species in Arizona as a case study, we tested the feasibility of assigning CMP taxonomy categories to actions detailed in current recovery plans, and then used our assigned categories to assess the distribution of action categories. Pairs of researchers categorized and then compared levels of agreement between categories of recovery actions for 840 actions across 31 active recovery plans. Paired categorizations diverged for many of these actions, though confidence in action description assignments among pairs was highest in categorizing Research and Monitoring actions, which represented, on average, 53% (SD 0.9%) of actions with researcher agreement, and, on average, 42% (SD 0.08%) of classification among individual researchers. These results suggests that categorizable action descriptions most often correspond with Research and Monitoring objectives, and that other categories of actions required to delist species may be underrepresented in ESA recovery plans. We provide recommendations to support the application of the CMP taxonomy to current and future ESA recovery action descriptions using existing processes within the U.S. Fish and Wildlife Service. Our recommendations provide a roadmap for standardizing the description of recovery actions to improve decision‐support for ESA‐listed species.

Exon skipping therapies for Duchenne muscular dystrophy that restore an open reading frame can be induced by the use of non-coding U7 small nuclear RNA (U7snRNA) modified by an antisense exon-targeting sequence delivered by an adeno-associated virus (AAV) vector. We have developed an AAV vector (AAV9.U7-ACCA) containing four U7snRNAs targeting the splice donor and acceptor sites of dystrophin exon 2, resulting in highly efficient exclusion of DMD exon 2. We assessed the specificity of splice variation induced by AAV9.U7-ACCA delivery in the Dmd exon 2 duplication (Dup2) mouse model via an unbiased RNA-seq approach. Treatment-related effects on pre-mRNA splicing were quantified using local splicing variation (LSV) analysis. Filtering the transcriptome for differences in treatment-related splicing resulted in only 16 candidate off-target LSVs. Only a single candidate off-target LSV was found in both tissues and occurred at a known variable cassette exon. In contrast, four LSVs represented significant on-target correction of Dmd exon 2 splicing and transcriptome analysis showed correction of known dystrophin-deficient gene dysregulation. We conclude that the absence of off-target splicing induced by treatment with the U7-ACCA vector supports the continued clinical development of this approach.

Exon skipping therapies for Duchenne muscular dystrophy that restore an open reading frame can be induced by the use of noncoding U7 small nuclear RNA (U7snRNA) modified by an antisense exon-targeting sequence delivered by an adeno-associated virus (AAV) vector. We have developed an AAV vector (AAV9.U7-ACCA) containing four U7snRNAs targeting the splice donor and acceptor sites of dystrophin exon 2, resulting in highly efficient exclusion of

The closure of Philadelphia's Hahnemann University Hospital (HUH) in summer 2019 brought an abrupt end to its status as a sponsor of graduate medical education (GME). The Accreditation Council for Graduate Medical Education (ACGME) provided assistance to ensure that more than 550 residents and fellows in HUH's 35 ACGME-accredited programs were able to transfer to new programs in which they could continue their education. As the ACGME joined other organizations in responding to HUH's closure, it was apparent that the voices of residents and fellows should be emphasized in regulatory processes and policies that address substantial disruptions to GME and affect their education, their daily lives, and their professional futures.