Autism spectrum disorders (ASD) are common, complex and heterogeneous neurodevelopmental disorders. Cellular and molecular mechanisms responsible for ASD pathogenesis have been proposed based on ...genetic studies, brain pathology and imaging, but a major impediment to testing ASD hypotheses is the lack of human cell models. Here, we reprogrammed fibroblasts to generate induced pluripotent stem cells, neural progenitor cells (NPCs) and neurons from ASD individuals with early brain overgrowth and non-ASD controls with normal brain size. ASD-derived NPCs display increased cell proliferation because of dysregulation of a β-catenin/BRN2 transcriptional cascade. ASD-derived neurons display abnormal neurogenesis and reduced synaptogenesis leading to functional defects in neuronal networks. Interestingly, defects in neuronal networks could be rescued by insulin growth factor 1 (IGF-1), a drug that is currently in clinical trials for ASD. This work demonstrates that selection of ASD subjects based on endophenotypes unraveled biologically relevant pathway disruption and revealed a potential cellular mechanism for the therapeutic effect of IGF-1.
Background
Geant4 is a Monte Carlo code extensively used in medical physics for a wide range of applications, such as dosimetry, micro‐ and nanodosimetry, imaging, radiation protection, and nuclear ...medicine. Geant4 is continuously evolving, so it is crucial to have a system that benchmarks this Monte Carlo code for medical physics against reference data and to perform regression testing.
Aims
To respond to these needs, we developed G4‐Med, a benchmarking and regression testing system of Geant4 for medical physics.
Materials and Methods
G4‐Med currently includes 18 tests. They range from the benchmarking of fundamental physics quantities to the testing of Monte Carlo simulation setups typical of medical physics applications. Both electromagnetic and hadronic physics processes and models within the prebuilt Geant4 physics lists are tested. The tests included in G4‐Med are executed on the CERN computing infrastructure via the use of the geant‐val web application, developed at CERN for Geant4 testing. The physical observables can be compared to reference data for benchmarking and to results of previous Geant4 versions for regression testing purposes.
Results
This paper describes the tests included in G4‐Med and shows the results derived from the benchmarking of Geant4 10.5 against reference data.
Discussion
Our results indicate that the Geant4 electromagnetic physics constructor G4EmStandardPhysics_option4 gives a good agreement with the reference data for all the tests. The QGSP_BIC_HP physics list provided an overall adequate description of the physics involved in hadron therapy, including proton and carbon ion therapy. New tests should be included in the next stage of the project to extend the benchmarking to other physical quantities and application scenarios of interest for medical physics.
Conclusion
The results presented and discussed in this paper will aid users in tailoring physics lists to their particular application.
This article was updated on TK because of a previous error, which was discovered after the preliminary version of the article was posted online. In Table VII, the fracture rate in the study by Walch ...et al. that had read “4.6% (21 of 457)” now reads “0.9% (4 of 457).”
BACKGROUND:Acromial and scapular fractures after reverse total shoulder arthroplasty (rTSA) are rare and challenging complications, and little information is available in the literature to identify patients who are at risk. This study analyzes risk factors for, and compares the outcomes of patients with and without, acromial and scapular fractures after rTSA with a medialized glenoid/lateralized humeral implant.
METHODS:Four thousand one hundred and twenty-five shoulders in 3,995 patients were treated with primary rTSA with 1 design of reverse shoulder prosthesis by 23 orthopaedic surgeons. Sixty-one of the 4,125 shoulders had radiographically identified acromial and scapular fractures. Demographic characteristics, comorbidities, implant-related data, and clinical outcomes were compared between patients with and without fractures to identify risk factors. A multivariate logistic regression, 2-tailed unpaired t test, and chi-square test or Fisher exact test identified significant differences (p < 0.05).
RESULTS:After a minimum duration of follow-up of 2 years, the rate of acromial and scapular fractures was 1.77%, with the fractures occurring at a mean (and standard deviation) of 17.7 ± 21.1 months after surgery. Ten patients had a Levy Type-1 fracture, 32 had a Type-2 fracture, 18 had a Type-3 fracture, and 1 fracture could not be classified. Patients with acromial and scapular fractures were more likely to be female (84.0% versus 64.5% p = 0.004; odds ratio OR = 2.75 95% confidence interval (CI) = 1.45 to 5.78), to have rheumatoid arthritis (9.8% versus 3.3% p = 0.010; OR = 3.14 95% CI = 1.18 to 6.95), to have rotator cuff tear arthropathy (54.1% versus 37.8% p = 0.005; OR = 2.07 95% CI = 1.24 to 3.47), and to have more baseplate screws (4.1 versus 3.8 screws p = 0.017; OR = 1.53 95% CI = 1.08 to 2.17) than those without fractures. No other implant-related differences were observed in the multivariate analysis. Patients with fractures had significantly worse outcomes than patients without fractures, and the difference in mean improvement between these 2 cohorts exceeded the minimum clinically important difference for the majority of measures.
CONCLUSIONS:Acromial and scapular fractures after rTSA are uncommon, and patients with these fractures have significantly worse clinical outcomes. Risk factors, including female sex, rheumatoid arthritis, cuff tear arthropathy, and usage of more baseplate screws were identified on multivariate logistic regression analysis. Consideration of these findings and patient-specific risk factors may help the orthopaedic surgeon (1) to better inform patients about this rare complication preoperatively and (2) to be more vigilant for this complication when evaluating patients postoperatively.
LEVEL OF EVIDENCE:Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
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