Correlative relationship between body mass index and heart rate variability in psychiatric disorders.

OBJECTIVE: Indicators of heart rate variability (HRV) have been used to assess the autonomic activity. However, the influence of obesity on HRV in these patients remains to be determined. This study aimed to examine how obesity (measured with the body mass index [BMI]) affects HRV and determine whether the effect varies among different psychiatric disorders. We recruited 3159 consecutive patients, including 1744 with schizophrenia, 966 with mood disorders, and 449 with anxiety disorders. Patients were divided into four groups based on BMI: underweight (< 18.5), normal weight (18.5-23.9), overweight (24-27.9), and obese (≥ 28). The cardiovascular status was assessed using several time- and frequency-based HRV indicators, measured via electrocardiogram signals recorded for 5 min. The mean BMI of the participants was 23.6 ± 4.0. The patients in the overweight and obese groups were 29.4% and 13.6% of the total, respectively. The HRV indicators were higher in underweight and normal-weight patients than in the overweight and obese ones. After stratification based on the psychiatric diagnosis, the patients with mood disorders showed lower HRV than those with schizophrenia or anxiety disorder in the normal-weight group. In contrast, in the overweight and obese groups the patients with mood disorders showed higher HRV than those with the other disorders. The HRV variables were significantly associated with BMI, and higher BMI was associated with higher heart rates and lower HRV. These results indicate that weight gain in psychiatric disorders is associated with an imbalance in autonomic nerve activity. However, the relationship between autonomic activity, weight gain, and psychiatric disorders warrants further investigation.

A Dielectric MXene-Induced Self-Built Electric Field in Polymer Electrolyte Triggering Fast Lithium-Ion Transport and High-Voltage Cycling Stability.

Quasi-solid polymer electrolyte (QPE) lithium (Li)-metal battery holds significant promise in the application of high-energy-density batteries, yet it suffers from low ionic conductivity and poor oxidation stability. Herein, a novel self-built electric field (SBEF) strategy is proposed to enhance Li+ transportation and accelerate the degradation dynamics of carbon-fluorine bond cleavage in LiTFSI by optimizing the termination of MXene. Among them, the SBEF induced by dielectric Nb4C3F2 MXene effectively constructs highly conductive LiF-enriched SEI and CEI stable interfaces, moreover, enhances the electrochemical performance of the QPE. The related Li-ion transfer mechanism and dual-reinforced stable interface are thoroughly investigated using ab initio molecular dynamics, COMSOL, XPS depth profiling, and ToF-SIMS. This comprehensive approach results in a high conductivity of 1.34 mS cm-1, leading to a small polarization of approximately 25 mV for Li//Li symmetric cell after 6000 h. Furthermore, it enables a prolonged cycle life at a high voltage of up to 4.6 V. Overall, this work not only broadens the application of MXene for QPE but also inspires the great potential of the self-built electric field in QPE-based high-voltage batteries.

Parameter optimization method for light field 3D display.

A parameter optimization method for light field three-dimensional (3D) display is proposed to improve the performance of integral imaging (InI) and super multi-view (SMV) display. The parameters of light field display are divided into system parameters and display parameters. The multi-objective genetic algorithm is used to optimize the system parameters so that the display parameters can reach the target values. The influence of all display parameters on the imaging quality of light field 3D display are comprehensively considered. When the weight of the depth of field (DOF) and field of view (FOV) are set to the maximum, the DOF and FOV are respectively improved compared with the original display parameters. By setting the weight of resolution to the maximum, the image quality of InI and SMV is improved by 32% and 21%, respectively.

Impacts of COVID-19 on Appropriate Use of Screening Colonoscopy in a Large Integrated Healthcare Delivery System.

BACKGROUND: Decreasing low-value colonoscopy is critical to optimizing access for high-need patients, particularly in resource-constrained environments such as those created by the COVID-19 pandemic. We hypothesized that rates of screening colonoscopy overuse would decline during COVID compared to pre-COVID due to enhanced procedural scrutiny and prioritization in the setting of constrained access. OBJECTIVE: To characterize impacts of COVID-19 on screening colonoscopy overuse DESIGN: Retrospective national cohort study using Veterans Health Administration administrative data PARTICIPANTS: Veterans undergoing screening colonoscopy in Q4 2019 (pre-COVID) and Q4 2020 (COVID) at 109 endoscopy facilities MAIN MEASURES: Rates of screening colonoscopy overuse KEY RESULTS: 18,376 screening colonoscopies were performed pre-COVID, 19% (3,641) of which met overuse criteria. While only 9,360 screening colonoscopies were performed in Q4 2020, 25% met overuse criteria. Overall change in median facility-level overuse during COVID compared to pre-COVID was 6% (95%CI 5%-7%), with significant variability across facilities (IQR: 2%-11%). Of colonoscopies meeting overuse criteria, the top reason for overuse in both periods was screening colonoscopy performed <9 years after previous screening procedure (55% pre-COVID, 49% during COVID). The largest shifts in overuse category were in screening procedures performed <9 years after prior screening colonoscopy (-6% decline COVID vs. pre-COVID) and screening procedures performed in patients below average-risk screening age (i.e., age <40 (5% increase COVID compared to pre-COVID), age 40-44 (4% increase COVID vs. pre-COVID)). Within facility performance was stable over time; 83/109 facilities changed their performance by <=1 quartile during COVID compared to pre-COVID. CONCLUSIONS: Despite pandemic-related resource constraints and enhanced procedural scrutiny and prioritization in the setting of COVID-related backlogs, screening colonoscopy overuse rates remained roughly stable during COVID compared to pre-COVID, with continued variability across facilities. These data highlight the need for systematic and concerted efforts to address overuse, even in the face of strong external motivating factors.

Pharmacokinetics of remimazolam after intravenous infusion in anaesthetised children.

BACKGROUND: The pharmacokinetic properties of the new benzodiazepine remimazolam have been studied only in adults. We investigated the pharmacokinetics of remimazolam after i.v. infusion in anaesthetised paediatric patients. METHODS: Twenty-four children (2-6 yr, ASA physical status 1-2, BMI 15-18 kg m-2) undergoing general anaesthesia with sevoflurane were enrolled. During surgery, remimazolam was administered as an i.v. infusion over 1 h at 5 mg kg-1 h-1 for 5 min, followed by 1.5 mg kg-1 h-1 for 55 min. Plasma concentrations of remimazolam and its metabolite CNS7054 were determined from arterial blood samples using ultra-high performance liquid chromatography-mass spectrometry. Pharmacokinetic modelling was performed by population analysis. RESULTS: Pharmacokinetics were best described by a three-compartment model for remimazolam and a two-compartment model for CNS7054 linked by a transit compartment. Remimazolam showed a high clearance of 15.9 (12.9, 18.2) ml kg-1 min-1 (median, Q25, Q75), a small central volume of distribution of 0.11 (0.08, 0.14) L kg-1 and a short terminal half-life of 67 (49, 85) min. The context-sensitive half-time after an infusion of 4 h was 17 (12, 21) min. The metabolite CNS7054 showed a low clearance of 0.89 (0.33, 1.40) ml kg-1 min-1, a small central volume of distribution of 0.011 (0.005, 0.016) L kg-1, and a long terminal half-life of 321 (230, 770) min. CONCLUSIONS: Remimazolam in children was characterised by a high clearance and short context-sensitive half-time. When normalised to weight, pharmacokinetic properties were similar to those reported for adults. CLINICAL TRIAL REGISTRATION: ChiCTR2200057629.

Myelocytomatosis-Protein Arginine N-Methyltransferase 5 Axis Defines the Tumorigenesis and Immune Response in Hepatocellular Carcinoma.

BACKGROUND AND AIMS: HCC is a leading cause of cancer-related deaths globally with poor outcome and limited therapeutic options. Although the myelocytomatosis (MYC) oncogene is frequently dysregulated in HCC, it is thought to be undruggable. Thus, the current study aimed to identify the critical downstream metabolic network of MYC and develop therapies for MYC-driven HCC. APPROACH AND RESULTS: Liver cancer was induced in mice with hepatocyte-specific disruption of Myc and control mice by administration of diethylnitrosamine. Liquid chromatography coupled with mass spectrometry-based metabolomic analyses revealed that urinary dimethylarginine, especially symmetric dimethylarginine (SDMA), was increased in the HCC mouse model in an MYC-dependent manner. Analyses of human samples demonstrated a similar induction of SDMA in the urines from patients with HCC. Mechanistically, Prmt5, encoding protein arginine N-methyltransferase 5, which catalyzes SDMA formation from arginine, was highly induced in HCC and identified as a direct MYC target gene. Moreover, GSK3326595, a PRMT5 inhibitor, suppressed the growth of liver tumors in human MYC-overexpressing transgenic mice that spontaneously develop HCC. Inhibition of PRMT5 exhibited antiproliferative activity through up-regulation of the tumor suppressor gene Cdkn1b/p27, encoding cyclin-dependent kinase inhibitor 1B. In addition, GSK3326595 induced lymphocyte infiltration and major histocompatibility complex class II expression, which might contribute to the enhanced antitumor immune response. Combination of GSK3326595 with anti-programed cell death protein 1 (PD-1) immune checkpoint therapy (ICT) improved therapeutic efficacy in HCC. CONCLUSIONS: This study reveals that PRMT5 is an epigenetic executer of MYC, leading to repression of the transcriptional regulation of downstream genes that promote hepatocellular carcinogenesis, highlights a mechanism-based therapeutic strategy for MYC-driven HCC by PRMT5 inhibition through synergistically suppressed proliferation and enhanced antitumor immunity, and finally provides an opportunity to mitigate the resistance of "immune-cold" tumor to ICT.

Administration of olaquindox impairs spermatogenesis and sperm quality by increasing oxidative stress and early apoptosis in mice.

Olaquindox (OLA), a potent antibacterial agent, has been widely used as a feed additive and growth promoter in animal husbandry. Our previous study has shown that OLA administration in female mice could markedly cause sub-fertility. Here we established the model in male mice to investigate the toxic effects of OLA on mammalian spermatozoa quality and fetal development. After continuous 45 days of OLA gavage, the dosage of 60 mg/kg/day (high dose) significantly affected body weight, organ weights and coefficients, and the morphology of the testis seminiferous tubule in male mice. Dosage of 60 mg/kg/day also reduced sperm count, motility, and viability. OLA at both low-dose (5 mg/kg/day) and high-dose induced peroxidation, early apoptosis, and abnormal mitochondrial membrane potential in sperm. Significantly, high-dose OLA impaired in vitro fertilized embryo development, indicated by the decreased percentages of 2-cell and blastocyst formation. Surprisingly, the natural fertility of males was unaffected after OLA gavage, which was indicated by the comparable litter size after mating. However, paternal gavage of OLA significantly decreased the survival rate of the offspring from the age of 4 weeks. In sum, our study showed that OLA gavage in male mice damages sperm quality and offspring survival, illustrating the use of OLA as a feed additive should be strictly restricted.

Modeling and Analysis of Acoustic Emission Generated by Fatigue Cracking.

The acoustic emission (AE) method is a popular and well-developed method for passive structural health monitoring of metallic and composite structures. The current study focuses on the analysis of one of its processes, sound source or signal propagation. This paper discusses the principle of plate wave signal sensing using piezoelectric transducers, and derives an analytical expression for the response of piezoelectric transducers under the action of stress waves, to obtain an overall mathematical model of the acoustic emission signal from generation to reception. The acoustic emission caused by fatigue crack extension is simulated by a finite element method, and the actual acoustic emission signal is simulated by a pencil lead break experiment. The results predicted by the mathematical model are compared with the experimental results and the simulation results, respectively, and show good agreement. In addition, the presence of obvious S0 mode Lamb waves is observed in the simulation results and experimental results, which further verifies the correctness of the analytical model prediction.

A novel CT-based radiomics in the distinction of severity of coronavirus disease 2019 (COVID-19) pneumonia.

BACKGROUND: Convenient and precise assessment of the severity in coronavirus disease 2019 (COVID-19) contributes to the timely patient treatment and prognosis improvement. We aimed to evaluate the ability of CT-based radiomics nomogram in discriminating the severity of patients with COVID-19 Pneumonia. METHODS: A total of 150 patients (training cohort n = 105; test cohort n = 45) with COVID-19 confirmed by reverse transcription polymerase chain reaction (RT-PCR) test were enrolled. Two feature selection methods, Max-Relevance and Min-Redundancy (mRMR) and least absolute shrinkage and selection operator (LASSO), were used to extract features from CT images and construct model. A total of 30 radiomic features were finally retained. Rad-score was calculated by summing the selected features weighted by their coefficients. The radiomics nomogram incorporating clinical-radiological features was eventually constructed by multivariate regression analysis. Nomogram, calibration, and decision-curve analysis were all assessed. RESULTS: In both cohorts, 40 patients with COVID-19 pneumonia were severe and 110 patients were non-severe. By combining the 30 radiomic features extracted from CT images, the radiomics signature showed high discrimination between severe and non-severe patients in the training set [Area Under the Curve (AUC), 0.857; 95% confidence interval (CI), 0.775-0.918] and the test set (AUC, 0.867; 95% CI, 0.732-949). The final combined model that integrated age, comorbidity, CT scores, number of lesions, ground glass opacity (GGO) with consolidation, and radiomics signature, improved the AUC to 0.952 in the training cohort and 0.98 in the test cohort. The nomogram based on the combined model similarly exhibited excellent discrimination performance in both training and test cohorts. CONCLUSIONS: The developed model based on a radiomics signature derived from CT images can be a reliable marker for discriminating the severity of COVID-19 pneumonia.

Ultrasound Defect Localization in Shell Structures with Lamb Waves Using Spare Sensor Array and Orthogonal Matching Pursuit Decomposition.

Lamb waves have multimodal and dispersion effects, which reduces their performance in damage localization with respect to resolution. To detect damage with fewest sensors and high resolution, a method, using only two piezoelectric transducers and based on orthogonal matching pursuit (OMP) decomposition, was proposed. First, an OMP-based decomposition and dispersion removal algorithm is introduced, which is capable of separating wave packets of different propagation paths and removing the dispersion part successively. Then, two simulation signals, with nonoverlapped and overlapped wave packets, are employed to verify the proposed method. Thereafter, with the proposed algorithm, the wave packets reflected from the defect and edge are all separated. Finally, a sparse sensor array with only two transducers succeeds in localizing the defect. The experimental results show that the OMP-based algorithm is beneficial for resolution improvement and transducer usage reduction.

An Integrated LC-MS/MS Strategy for Quantifying the Oxidative-Redox Metabolome in Multiple Biological Samples.

The cellular redox balance plays a significant role in cell fate decisions and in the regulation of responses to various kinds of stress. In this study, we defined a novel concept of the oxidative-redox metabolome, and established a method for the simultaneous quantification of 23 metabolites involved in the oxidative-redox metabolome, covering NAD+ pathway, FAD pathway, GSSG pathway, and ATP pathway by using the AB SCIEX 5500 QTRAP LC/MS/MS system. Corresponding oxidative-redox metabolomics analysis was performed in plasma of humans, hamsters and mice, and hamsters were demonstrated to display a stronger resemblance than mice to humans. The known reductant dithiothreitol (DTT) and oxidant hydrogen peroxide (H2O2) were selected to treat A549 and HeLa cells to validate the current method, showing that DTT moderately increased while H2O2 greatly decreased most analytes. Antibiotic treatment may disturb the oxidative-redox balance in vivo. By comparing the oxidative-redox metabolome in antibiotic-fed hamsters with that of control hamsters, we demonstrated a substantial metabolic disparity between the two, further verifying the applicability and reliability of our method.

Oral administration of olaquindox negatively affects oocytes quality and reproductive ability in female mice.

As an effective feed additive in the livestock industry, olaquindox (OLA) has been widely used in domestic animal production. However, it is unclear whether OLA has negative effects on mammalian oocyte quality and fetal development. In this study, toxic effects of OLA were tested by intragastric gavage ICR mice with water, low-dose OLA (5 mg/kg/day), or high-dose OLA (60 mg/kg/day) for continuous 45 days. Results showed that high-dose OLA gavage severely affected the offspring birth and growth. Significantly, high-dose OLA impaired oocyte maturation and early embryo development, indicated by the decreased percentage of germinal vesicle breakdown, first polar body extrusion and blastocyst formation. Meanwhile, oxidative stress levels were increased in oocytes or ovaries, indexed by the increased levels of ROS, MDA, H2O2, NO, and decreased levels of GSH, SOD, CAT, GSH-Px and GSH-Rd. Furthermore, aberrant mitochondria distribution, defective spindle assembly, abnormal H3K4me2/H3K9me3 levels, increased DNA double-strand breaks and early apoptosis rate, were observed after high-dose OLA gavage. Taken together, our results for the first time illustrated that high-dose OLA gavage led to sub-fertility of females, which means that restricted utilization of OLA as feed additive should be considered.

Biological Characteristics and Molecular Mechanism of Fludioxonil Resistance in Botrytis cinerea From Henan Province of China.

The gray mold caused by Botrytis cinerea has a significant impact on tomato production throughout the world. Although the synthetic fungicide fludioxonil can effectively control B. cinerea, there have been several reports of resistance to this fungicide. This study indicated that all of the fludioxonil-resistant strains tested, including one field-resistant isolate and four laboratory strains, had reduced fitness relative to sensitive isolates. In addition to having reduced growth, sporulation, and pathogenicity, the resistant strains were more sensitive to osmotic stress and had significantly (P < 0.05) higher peroxidase activity. BOs1, a kinase in the high-osmolarity glycerol stress response signal transduction pathway, is believed to harbor mutations related to fludioxonil resistance. Sequence analysis of their BOs1 sequences indicated that the fludioxonil-resistant field isolate, XXtom1806, had four point mutations resulting in four amino acid changes (I365S, S531G, T565N, and T1267A) and three amino acids (I365S, S531G, and T565N) in the histidine kinases, adenylyl cyclases, methyl-accepting chemotaxis receptors, and phosphatases domain, which associated with fludioxonil binding. Similarly, two of the laboratory strains, XXtom-Lab1 and XXtom-Lab4, had three (Q846S, I1126S, and G415D) and two (P1051S and V1241M) point mutations, respectively. A third strain, XXtom-lab3, had a 52-bp insertion that included a stop codon at amino acid 256. Interestingly, the BOs1 sequence of the fourth laboratory strain, XXtom-lab5, was identical to those of the sensitive isolates, indicating that an alternative resistance mechanism exists. The study also found evidence of positive cross-resistance between fludioxonil and the dicarboximide fungicides procymidone and iprodione, but no cross-resistance was detected with any other fungicides tested, including boscalid, carbendazim, tebuconazole, and fluazinam.

A Subtle Network Mediating Axon Guidance: Intrinsic Dynamic Structure of Growth Cone, Attractive and Repulsive Molecular Cues, and the Intermediate Role of Signaling Pathways.

A fundamental feature of both early nervous system development and axon regeneration is the guidance of axonal projections to their targets in order to assemble neural circuits that control behavior. In the navigation process where the nerves grow toward their targets, the growth cones, which locate at the tips of axons, sense the environment surrounding them, including varies of attractive or repulsive molecular cues, then make directional decisions to adjust their navigation journey. The turning ability of a growth cone largely depends on its highly dynamic skeleton, where actin filaments and microtubules play a very important role in its motility. In this review, we summarize some possible mechanisms underlying growth cone motility, relevant molecular cues, and signaling pathways in axon guidance of previous studies and discuss some questions regarding directions for further studies.

Evaluation of a needle disinfectant technique to reduce infection-related hospitalisation after transrectal prostate biopsy.

OBJECTIVES: To determine whether a needle disinfectant step during transrectal ultrasonography (TRUS)-guided prostate biopsy is associated with lower rates of infection-related hospitalisation. PATIENTS AND METHODS: We conducted a retrospective analysis of all TRUS-guided prostate biopsies taken across the Michigan Urological Surgery Improvement Collaborative (MUSIC) from January 2012 to March 2015. Natural variation in technique allowed us to evaluate for differences in infection-related hospitalisations based on whether or not a needle disinfectant technique was used. The disinfectant technique was an intra-procedural step to cleanse the biopsy needle with antibacterial solution after each core was sampled (i.e., 10% formalin or 70% isopropyl alcohol). After grouping biopsies according to whether or not the procedure included a needle disinfectant step, we compared the rate of infection-related hospitalisations within 30 days of biopsy. Generalised estimating equation models were fit to adjust for potential confounders. RESULTS: During the evaluated period, 17 954 TRUS-guided prostate biopsies were taken with 5 321 (29.6%) including a disinfectant step. The observed rate of infection-related hospitalisation was lower when a disinfectant technique was used during biopsy (0.60% vs 0.90%; P = 0.04). After accounting for differences between groups the adjusted hospitalisation rate in the disinfectant group was 0.85% vs 1.12% in the no disinfectant group (adjusted odds ratio 0.76, 95% confidence interval 0.50-1.15; P = 0.19). CONCLUSIONS: In this observational analysis, hospitalisations for infectious complications were less common when the TRUS-guided prostate biopsy included a needle disinfection step. However, after adjusting for potential confounders the effect of needle disinfection was not statistically significant. Prospective evaluation is warranted to determine if this step provides a scalable and effective method to minimise infectious complications.

A Statewide Intervention Improves Appropriate Imaging in Localized Prostate Cancer.

PURPOSE: We implemented a statewide intervention to improve imaging utilization for the staging of patients with newly diagnosed prostate cancer. MATERIALS AND METHODS: MUSIC (Michigan Urological Surgery Improvement Collaborative) is a quality improvement collaborative comprising 42 diverse practices representing approximately 85% of the urologists in Michigan. MUSIC has developed imaging appropriateness criteria (prostate specific antigen greater than 20 ng/ml, Gleason score 7 or higher and clinical stage T3 or higher) which minimize unnecessary imaging with bone scan and computerized tomography. After baseline rates of radiographic staging were established in 2012 and 2013, we used multidimensional interventions to deploy these criteria in 2014. Imaging utilization was then remeasured in 2015 to evaluate for changes in practice patterns. RESULTS: A total of 10,554 newly diagnosed patients with prostate cancer were entered into the MUSIC registry from January 1, 2012 through December 31, 2013 and January 1, 2015 through December 31, 2015. Of these patients 7,442 (79%) and 7,312 (78%) met our criteria to avoid bone scan and computerized tomography imaging, respectively. The use of bone scan imaging when not indicated decreased from 11.0% at baseline to 6.5% after interventions (p <0.0001). The use of computerized tomography when not indicated decreased from 14.7% at baseline to 7.7% after interventions (p <0.0001). Variability among practices decreased substantially after the interventions as well. The use of recommended imaging remained stable during these periods. CONCLUSIONS: An intervention aimed at appropriate use of imaging was associated with decreased use of bone scans and computerized tomography among men at low risk for metastases.

Appropriateness Criteria for Active Surveillance of Prostate Cancer.

PURPOSE: The adoption of active surveillance varies widely across urological communities, which suggests a need for more consistency in the counseling of patients. To address this need we used the RAND/UCLA Appropriateness Method to develop appropriateness criteria and counseling statements for active surveillance. MATERIALS AND METHODS: Panelists were recruited from MUSIC urology practices. Combinations of parameters thought to influence decision making were used to create and score 160 theoretical clinical scenarios for appropriateness of active surveillance. Recent rates of active surveillance among real patients across the state were assessed using the MUSIC registry. RESULTS: Low volume Gleason 6 was deemed highly appropriate for active surveillance whereas high volume Gleason 6 and low volume Gleason 3+4 were deemed appropriate to uncertain. No scenario was deemed inappropriate or highly inappropriate. Prostate specific antigen density, race and life expectancy impacted scores for intermediate and high volume Gleason 6 and low volume Gleason 3+4. The greatest degree of score dispersion (disagreement) occurred in scenarios with long life expectancy, high volume Gleason 6 and low volume Gleason 3+4. Recent rates of active surveillance use among real patients ranged from 0% to 100% at the provider level for low or intermediate biopsy volume Gleason 6, demonstrating a clear opportunity for quality improvement. CONCLUSIONS: By virtue of this work urologists have the opportunity to present specific recommendations from the panel to their individual patients. Community-wide efforts aimed at increasing rates of active surveillance and reducing practice and physician level variation in the choice of active surveillance vs treatment are warranted.

Notable Outcomes and Trackable Events after Surgery: Evaluating an Uncomplicated Recovery after Radical Prostatectomy.

PURPOSE: A priority of MUSIC (Michigan Urological Surgery Improvement Collaborative) is to improve patient outcomes after radical prostatectomy. As part of these efforts we developed a novel system that uses unambiguous events to define an uncomplicated 30-day postoperative recovery and compares these outcomes across diverse urology practices. MATERIALS AND METHODS: MUSIC used a consensus approach to develop an uncomplicated recovery pathway comprising a set of precise perioperative events that are reliably measured and collectively reflect resource utilization, technical complications and coordination of care. Events that occurred outside the uncomplicated recovery pathway were considered deviations, including rectal injury, high blood loss, extended length of stay, prolonged drain or catheter placement, catheter replacement, hospital readmission or mortality. For men undergoing radical prostatectomy trained abstractors prospectively recorded clinical and perioperative data in an electronic registry. When a deviation from the NOTES (Notable Outcomes and Trackable Events after Surgery) pathway occurred, precipitating events were described by abstractors and we analyzed the events. RESULTS: From April 2014 through July 2015 a total of 2,245 radical prostatectomies were performed by 100 surgeons in a total of 37 diverse participating MUSIC practices. In the 29 practices in which 10 or more radical prostatectomies were performed during the interval analyzed the risk adjusted deviation rate ranged from 0.0% to 46.1% (p <0.0001). Anastomotic and gastrointestinal events were contributing factors in 50.2% of deviated cases. CONCLUSIONS: The novel NOTES system provides comparative data on unambiguous and actionable short-term outcomes after radical prostatectomy. The observed variation in outcomes across practices suggests opportunities for quality improvement initiatives. Decreasing anastomotic and gastrointestinal events represents a high impact opportunity for initial quality improvement efforts.