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Experimental in vitro models that capture pathophysiological characteristics of human tumours are essential for basic and translational cancer biology. Here, we describe a fully synthetic hydrogel extracellular matrix designed to elicit key phenotypic traits of the pancreatic environment in culture. To enable the growth of normal and cancerous pancreatic organoids from genetically engineered murine models and human patients, essential adhesive cues were empirically defined and replicated in the hydrogel scaffold, revealing a functional role of laminin-integrin α 3 /α 6 signalling in establishment and survival of pancreatic organoids. Altered tissue stiffness-a hallmark of pancreatic cancer-was recapitulated in culture by adjusting the hydrogel properties to engage mechano-sensing pathways and alter organoid growth. Pancreatic stromal cells were readily incorporated into the hydrogels and replicated phenotypic traits characteristic of the tumour environment in vivo. This model therefore recapitulates a pathologically remodelled tumour microenvironment for studies of normal and pancreatic cancer cells in vitro., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Gait analysis in the pediatric and adult orthopedic patient populations can adjunct the diagnosis and treatment of a multitude of musculoskeletal conditions. Understanding of normal and abnormal gait biomechanics is an important aspect of orthopedic residency; yet, there is great variability in the time residency programs dedicate to gait analysis education. The purpose of this study was to investigate if formal gait analysis education during residency improves an orthopedic resident's understanding of normal and pathologic gait. Five residency programs consisting of 81 resident subjects were surveyed at the beginning of the 2016-2017 academic year. The residents were divided into those with formal gait analysis education (group A) and those without (group B). Each resident was sent an online survey with 11 questions from former orthopedic in-training exams (OITE) regarding gait pattern analysis. The average number of correct questions was compared between the two groups with Student's t-test. Fifty-three of the 81 surveys sent out were completed. There were 23 subjects in group A and 30 in group B. All five programs and all postgraduate years (PGYs) were represented (PGY1: 10, PGY2: 12, PGY3: 12, PGY4: 6, PGY5 12). The average score for all residents was 5.6 out of 11 correct (51%). The residents from group A averaged a significantly higher score (6.3) than group B (5.0) (P = 0.017). Understanding gait biomechanics is a critical skill for orthopedic surgeons, and residency training often lacks sufficient training in their curriculum. A good understanding of gait analysis allows orthopedic surgeons to analyze gait disturbances and develop patient-specific treatment plans in adult and pediatric populations. This study found improved knowledge of gait patterns amongst orthopedic residents with formal education. Even though the residents with formal education fared better than their counterparts, the overall percent correct was still low (51%). Evidence: Level 3: Prospective Cohort Study., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Medical malpractice is burdensome to the U.S. healthcare system. The following is an epidemiological analysis of the closed medical professional liability (MPL) claims in pediatric orthopedics using data maintained by the Physician Insurers Association of America., Methods: The Physician Insurers Association of America registry of MPL claims from 1985 to 2013 for all specialties included 286,021 closed claims in the United States. All closed MPL claims for orthopedic surgery in patients younger than 18 years were retrospectively reviewed (N = 2,671). The error categories, result of the claim, the most common procedures, severity of injury, and the most common presenting and resultant medical conditions were reported with the paid-to-close ratios, average indemnity payment, and average cost of litigation. The pediatric orthopedic population was compared with all orthopedics. The data were adjusted for inflation and trended for the 29-year period., Results: Of the 2671 pediatric orthopedic claims, 881 resulted in a payment and the average indemnity was U.S. $317,574 with adjustment for inflation - significantly higher than for all of orthopedics at U.S. $268,817 (P = 0.0013). The paid-to-close ratio was 33.0%, compared with 28.7% for all of orthopedics (P = 0.023)., Conclusions: Costs to defend individual medical malpractice claims and the average indemnity payment per claim have both increased over time, and pediatric (versus adult) orthopedic claims are more likely to result in payment and result in a higher payment. Knowledge of the details of liability claims should assist practicing general and pediatric orthopedic surgeons in improving patient safety and quality of care, reducing patient injury, and reducing the incidence of MPL claims., Competing Interests: The authors disclose no conflict of interest., (Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Osteoarticular infections (OAIs) are frequently encountered in children. Treatment may be guided by isolation of a pathogen; however, operative cultures are often negative. Metagenomic next-generation sequencing (mNGS) allows for broad and sensitive pathogen detection that is culture-independent. We sought to evaluate the diagnostic utility of mNGS in comparison to culture and usual care testing to detect pathogens in acute osteomyelitis and/or septic arthritis in children., Methods: This was a single-site study to evaluate the use of mNGS in comparison to culture to detect pathogens in acute pediatric osteomyelitis and/or septic arthritis. Subjects admitted to a tertiary children's hospital with suspected OAI were eligible for enrollment. We excluded subjects with bone or joint surgery within 30 days of admission or with chronic osteomyelitis. Operative samples were obtained at the surgeon's discretion per standard care (fluid or tissue) and based on imaging and operative findings. We compared mNGS to culture and usual care testing (culture and polymerase chain reaction [PCR]) from the same site., Results: We recruited 42 subjects over the enrollment period. mNGS of the operative samples identified a pathogen in 26 subjects compared to 19 subjects in whom culture identified a pathogen. In 4 subjects, mNGS identified a pathogen where combined usual care testing (culture and PCR) was negative. Positive predictive agreement and negative predictive agreement both were 93.0% for mNGS., Conclusions: In this single-site prospective study of pediatric OAI, we demonstrated the diagnostic utility of mNGS testing in comparison to culture and usual care (culture and PCR) from operative specimens., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

SWATH-mass spectrometry (MS) enables accurate and reproducible proteomic profiling in multiple model organisms including the mouse. Here, we present a comprehensive mouse reference spectral library (MouseRefSWATH) that permits quantification of up to 10,597 proteins (62.2% of the mouse proteome) by SWATH-MS. We exploit MouseRefSWATH to develop an analytical pipeline for species-specific deconvolution of proteomic alterations in human tumour xenografts (XenoSWATH). This method overcomes the challenge of high sequence similarity between mouse and human proteins, facilitating the study of host microenvironment-tumour interactions from 'bulk tumour' measurements. We apply the XenoSWATH pipeline to characterize an intraductal xenograft model of breast ductal carcinoma in situ and uncover complex regulation consistent with stromal reprogramming, where the modulation of cell migration pathways is not restricted to tumour cells but also operates in the mouse stroma upon progression to invasive disease. MouseRefSWATH and XenoSWATH open new opportunities for in-depth and reproducible proteomic assessment to address wide-ranging biological questions involving this important model organism., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

Visual and proprioceptive sensory inputs are naturally coded in different reference frames, i.e., eye-centered and body-centered, respectively. To use these signals in conjunction for motor planning or perception ultimately requires converting them into a common frame of reference using estimates of the relative orientation of the eyes, head, and body. Here, we examine whether extraretinal signals-specifically head roll-alter multisensory perception through noisy reference frame transformations. To do so, we examine the accuracy of visual localization relative to proprioceptive hand position for different head roll orientations. Subjects were required to judge whether a visual target was located closer or further and left or right (4-alternative forced-choice task) from their unseen hand. This was done for three different head roll rotations (-30, 0, and 30 deg). We show that eccentric head roll increased the variability in the subjects' ability to discriminate target location relative to the fingertip. We conclude that sensory perception is sensitive to body-geometry-dependent noise affecting the coordinate matching transformations of sensory data.