Spectral radii of sparse random matrices

We establish bounds on the spectral radii for a large class of sparse random matrices, which includes the adjacency matrices of inhomogeneous Erd\H{o}s-R\'enyi graphs. Our error bounds are sharp for a large class of sparse random matrices. In particular, for the Erd\H{o}s-R\'enyi graph $G(n,d/n)$, our results imply that the smallest and second-largest eigenvalues of the adjacency matrix converge to the edges of the support of the asymptotic eigenvalue distribution provided that $d \gg \log n$. Together with the companion paper [3], where we analyse the extreme eigenvalues in the complementary regime $d \ll \log n$, this establishes a crossover in the behaviour of the extreme eigenvalues around $d \sim \log n$. Our results also apply to non-Hermitian sparse random matrices, corresponding to adjacency matrices of directed graphs. The proof combines (i) a new inequality between the spectral radius of a matrix and the spectral radius of its nonbacktracking version together with (ii) a new application of the method of moments for nonbacktracking matrices

Slow transit constipation: clinical and aetiological studies.

PhDConstipation is the second most commonly self-reported gastrointestinal symptom. On the basis of anorectal physiological investigations and colonic transit studies, a subgroup of patients with several intractable symptoms, but without organic disease will be found to have slow transit constipation (STC). STC is a condition of gut dysmotility which predominantly affects young women, and may result in surgical intervention with variable, often unsatisfactory results. The aetiology remains elusive. New aetiological hypotheses for STC were examined following full clinical and pathophysiological characterisation of a large cohort of 130 patients referred to our institution over the last 10 years. Aspects of nerve and muscle dysfunction were studied. A new scoring system demonstrated some ability of multiple symptoms to discriminate STC from other forms of constipation. Detailed clinical and gastrointestinal physiological studies confirmed the heterogeneity of STC patients. Some significant physiological differences were detectable between clinically defined sub-groups of patients and refuted previous assumptions based on smaller numbers. Detailed neurophysiological studies, including quantitative peripheral sensory and autonomic testing, provided evidence of a small fibre neuropathy in a proportion of patients with STC. Mutational screening of some early-onset cases for a possible congenital pathogenetic mechanism, based on the observation that some STC patients had relatives with Hirschsprung's disease demonstrated that mutation of 2 important genes now implicated in this disorder were not a frequent cause of STC. Serum immunoprecipitation assays showed that anti-neuronal ion channel autoantibodies may have an as yet unrecognised role in the development of STC in a small proportion of acquired cases. An inclusion body myopathy was identifiable in colonic tissue of patients with STC, and this appeared to arise secondary to denervation. Further knowledge of the single or multiple pathogenetic mechanisms leading to this clinical condition may allow more rational or directed therapies aimed at the correction of the disease process or processes themselves

Cell shape characteristics of human skeletal muscle cells as a predictor of myogenic competency: A new paradigm towards precision cell therapy

Skeletal muscle-derived cells (SMDC) hold tremendous potential for replenishing dysfunctional muscle lost due to disease or trauma. Current therapeutic usage of SMDC relies on harvesting autologous cells from muscle biopsies that are subsequently expanded in vitro before re-implantation into the patient. Heterogeneity can arise from multiple factors including quality of the starting biopsy, age and comorbidity affecting the processed SMDC. Quality attributes intended for clinical use often focus on minimum levels of myogenic cell marker expression. Such approaches do not evaluate the likelihood of SMDC to differentiate and form myofibres when implanted in vivo, which ultimately determines the likelihood of muscle regeneration. Predicting the therapeutic potency of SMDC in vitro prior to implantation is key to developing successful therapeutics in regenerative medicine and reducing implementation costs. Here, we report on the development of a novel SMDC profiling tool to examine populations of cells in vitro derived from different donors. We developed an image-based pipeline to quantify morphological features and extracted cell shape descriptors. We investigated whether these could predict heterogeneity in the formation of myotubes and correlate with the myogenic fusion index. Several of the early cell shape characteristics were found to negatively correlate with the fusion index. These included total area occupied by cells, area shape, bounding box area, compactness, equivalent diameter, minimum ferret diameter, minor axis length and perimeter of SMDC at 24 h after initiating culture. The information extracted with our approach indicates live cell imaging can detect a range of cell phenotypes based on cell-shape alone and preserving cell integrity could be used to predict propensity to form myotubes in vitro and functional tissue in vivo

Association Between Empathy and Burnout Among Emergency Medicine Physicians

Background: The association between physician self-reported empathy and burnout has been studied in the past with diverse findings. We aimed to determine the association between empathy and burnout among United States emergency medicine (EM) physicians using a novel combination of tools for validation. Methods: This was a prospective single-center observational study. Data were collected from EM physicians. From December 1, 2018 to January 31, 2019, we used the Jefferson scale of empathy (JSE) to assess physician empathy and the Copenhagen burnout inventory (CBI) to assess burnout. We divided EM physicians into different groups (residents in each year of training, junior/senior attendings). Empathy, burnout scores and their association were analyzed and compared among these groups. Results: A total of 33 attending physicians and 35 EM residents participated in this study. Median self-reported empathy scores were 113 (interquartile range (IQR): 105 - 117) in post-graduate year (PGY)-1, 112 (90 - 115) in PGY-2, 106 (93 - 118) in PGY-3 EM residents, 112 (105 - 116) in junior and 114 (101 - 125) in senior attending physicians. Overall burnout scores were 43 (33 - 50) in PGY-1, 51 (29 - 56) in PGY-2, 43 (42 - 53) in PGY-3 EM residents, 33 (24 - 47) in junior attending and 25 (22 - 53) in senior attending physicians separately. The Spearman correlation (ρ) was -0.11 and β-weight was -0.23 between empathy and patient-related burnout scores. Conclusion: Self-reported empathy declines over the course of EM residency training and improves after graduation. Overall high burnout occurs among EM residents and improves after graduation. Our analysis showed a weak negative correlation between self-reported empathy and patient-related burnout among EM physicians