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To review and analyze the currently available MRI motion phantoms. Publications were collected from the Toronto Metropolitan University Library, PubMed, and IEEE Xplore. Phantoms were categorized based on the motions they generated: linear/cartesian, cardiac-dilative, lung-dilative, rotational, deformation or rolling. Metrics were extracted from each publication to assess the motion mechanisms, construction methods, as well as phantom validation. A total of 60 publications were reviewed, identifying 48 unique motion phantoms. Translational movement was the most common movement (used in 38% of phantoms), followed by cardiac-dilative (27%) movement and rotational movement (23%). The average degrees of freedom for all phantoms were determined to be 1.42. Motion phantom publications lack quantification of their impact on signal-to-noise ratio through standardized testing. At present, there is a lack of phantoms that are designed for multi-role as many currently have few degrees of freedom., (© 2024. The Author(s), under exclusive licence to European Society for Magnetic Resonance in Medicine and Biology (ESMRMB).)

Introduction: Placenta accreta spectrum (PAS) is an obstetric disorder arising from the abnormal adherence of the placenta to the uterine wall, often leading to life-threatening complications including postpartum hemorrhage. Despite its significance, PAS remains frequently underdiagnosed before delivery. This study delves into the realm of machine learning to enhance the precision of PAS classification. We introduce two distinct models for PAS classification employing ultrasound texture features., Methods: The first model leverages machine learning techniques, harnessing texture features extracted from ultrasound scans. The second model adopts a linear classifier, utilizing integrated features derived from 'weighted z-scores'. A novel aspect of our approach is the amalgamation of classical machine learning and statistical-based methods for feature selection. This, coupled with a more transparent classification model based on quantitative image features, results in superior performance compared to conventional machine learning approaches., Results: Our linear classifier and machine learning models attain test accuracies of 87 % and 92 %, and 5-fold cross validation accuracies of 88.7 (4.4) and 83.0 (5.0), respectively., Conclusions: The proposed models illustrate the effectiveness of practical and robust tools for enhanced PAS detection, offering non-invasive and computationally-efficient diagnostic tools. As adjunct methods for prenatal diagnosis, these tools can assist clinicians by reducing the need for unnecessary interventions and enabling earlier planning of management strategies for delivery., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dafna Sussman reports financial support was provided by Natural Sciences and Engineering Research Council of Canada. Dafna Sussman reports financial support was provided by Government of Ontario., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: The prostatic urethral lift (PUL) has been used as a minimally invasive surgery for benign prostatic hyperplasia (BPH) since April 2022 in Japan. This study evaluated the initial outcomes and surgical techniques of PUL for BPH., Methods: In this prospective, single-center study, indications were based on the proper use guidelines for PUL in Japan. Preoperative patient status, postoperative progress at 1 and 3 months, and perioperative complications were evaluated. The surgical technique was changed twice, and the subgroup analysis and technique were evaluated., Results: Of the 50 patients who underwent surgeries performed by a single surgeon, the median age and prostate volume were 71 years and 42.0 mL, respectively. Furthermore, the median operative time and number of implants used were 20 min and 5, respectively. No postoperative fever or severe hematuria requiring reoperation occurred. All patients were discharged from the hospital the day following the PUL, as scheduled. Postoperative International Prostate Symptom Score, quality of life score, maximum flow rate, and postvoid residual volume at 1 and 3 months were significantly improved compared with the preoperative values. A significant improvement in maximum flow rate was observed in the subgroup analysis from 1 month postoperatively in the group with an anterior channel creation focus., Conclusions: PUL is effective and safe in cases with prostate volumes of <100 mL. Lifting the bladder neck is important for opening an anterior prostatic urethral channel and improving urinary function during the early postoperative period., (© 2024 The Author(s). International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Urological Association.)

Antibody effector functions including antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP) are mediated through the interaction of the antibody Fc region with Fcγ receptors present on immune cells. Several approaches have been used to modulate antibody Fc-Fcγ interactions with the goal of driving an effective antitumor immune response, including Fc point mutations and glycan modifications. However, robust antibody-Fcγ engagement and immune cell binding of Fc-enhanced antibodies in the periphery can lead to the unwanted induction of systemic cytokine release and other dose-limiting infusion-related reactions. Creating a balance between effective engagement of Fcγ receptors that can induce antitumor activity without incurring systemic immune activation is an ongoing challenge in the field of antibody and immuno-oncology therapeutics. Herein, we describe a method for the reversible chemical modulation of antibody-Fcγ interactions using simple poly(ethylene glycol) (PEG) linkers conjugated to antibody interchain disulfides with maleimide attachments. This method enables dosing of a therapeutic with muted Fcγ engagement that is restored in vivo in a time-dependent manner. The technology was applied to an effector function enhanced agonist CD40 antibody, SEA-CD40, and experiments demonstrate significant reductions in Fc-induced immune activation in vitro and in mice and nonhuman primates despite showing retained efficacy and improved pharmacokinetics compared to the parent antibody. We foresee that this simple, modular system can be rapidly applied to antibodies that suffer from systemic immune activation due to peripheral FcγR binding immediately upon infusion.

Background: Despite the established efficacy of multidisciplinary chronic pain care, barriers such as inflated referral wait times and uncoordinated care further hinder patient health care access., Aims: Here we describe the evolution of a single-entry model (SEM) for coordinating access to chronic pain care across seven hospitals in Toronto and explore the impact on patient care 6 years after implementation., Methods: In 2017, an innovative SEM was implemented for chronic pain referrals in Toronto and surrounding areas. Referrals are received centrally, triaged by a clinical team, and assigned an appointment according to the level of urgency and the most appropriate care setting/provider. To evaluate the impact of the SEM, a retrospective analysis was undertaken to determine referral patterns, patient characteristics, and referral wait times over the past 6 years., Results: Implementation of an SEM streamlined the number of steps in the referral process and led to a standardized referral form with common inclusion and exclusion criteria across sites. Over the 6-year period, referrals increased by 93% and the number of unique providers increased by 91%. Chronic pain service wait times were reduced from 299 (±158) days to 176 (±103) days. However, certain pain diagnoses such as chronic pelvic pain and fibromyalgia far exceed the average., Conclusions: The results indicate that the SEM helped reduce wait times for pain conditions and standardized the referral pathway. Continued data capture efforts can help identify gaps in care to enable further health care refinement and improvement., Competing Interests: Anuj Bhatia is a consultant for Bioventus and has funded research from Medtronic. Hance Clarke receives salary support from a Merit Award from the Department of Anesthesiology and Pain Medicine. Andrea Furlan is a member of the Drug Advisory Committee on the Workplace Safety and Insurance Board, is receiving a grant from the Canadian Institutes for Health research (CIHR) and the Canadian Generic Product Association, has received payments from Google Inc. as a member of the YouTube partner program, and holds a patent for the My Opioid Manager App. All other authors have no conflicts of interest to declare., (© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Phantoms with tissue-mimicking properties play a crucial role in the calibration of medical imaging modalities, including Magnetic Resonance Imaging (MRI). Among these phantoms, silicone-based ones are widely used due to their long-term stability in MR imaging. Most of these phantoms are manufactured using traditional pour-mold techniques which often result in the production of air bubbles that can damage the phantom. This research investigates the feasibility of utilizing extrusion techniques to fabricate silicone phantoms and explores the effects of extrusion parameters including plunger speed and nozzle diameter on void content, T1 and T2 relaxation times, and dielectric properties. A custom double-syringe silicone extrusion apparatus was developed to prepare the silicone samples. The void content, relaxometry, and dielectric properties of extruded samples were measured and compared with traditional poured samples. The results show that extrusion parameters can affect the void content of the silicone samples. The presence of voids in the samples resulted in lower T1 values, indicating an inverse relationship between void content and relaxometry. This study demonstrates the potential of extrusion techniques for manufacturing silicone phantoms with reduced air bubble formation and provides valuable insights into the relationship between extrusion parameters and phantom properties.

Background: Pregnant people are particularly vulnerable to SARS-CoV-2 infection and to ensuing severe illness. Predicting adverse maternal and perinatal outcomes could aid clinicians in deciding on hospital admission and early initiation of treatment in affected individuals, streamlining the triaging processes., Methods: An international repository of 1501 SARS-CoV-2-positive cases in pregnancy was created, consisting of demographic variables, patient comorbidities, laboratory markers, respiratory parameters, and COVID-19-related symptoms. Data were filtered, preprocessed, and feature selection methods were used to obtain the optimal feature subset for training a variety of machine learning models to predict maternal or fetal/neonatal death or critical illness., Results: The Random Forest model demonstrated the best performance among the trained models, correctly identifying 83.3% of the high-risk patients and 92.5% of the low-risk patients, with an overall accuracy of 89.0%, an AUC of 0.90 (95% Confidence Interval 0.83 to 0.95), and a recall, precision, and F1 score of 0.85, 0.94, and 0.89, respectively. This was achieved using a feature subset of 25 features containing patient characteristics, symptoms, clinical signs, and laboratory markers. These included maternal BMI, gravidity, parity, existence of pre-existing conditions, nicotine exposure, anti-hypertensive medication administration, fetal malformations, antenatal corticosteroid administration, presence of dyspnea, sore throat, fever, fatigue, duration of symptom phase, existence of COVID-19-related pneumonia, need for maternal oxygen administration, disease-related inpatient treatment, and lab markers including sFLT-1/PlGF ratio, platelet count, and LDH., Conclusions: We present the first COVID-19 prognostication pipeline specifically for pregnant patients while utilizing a large SARS-CoV-2 in pregnancy data repository. Our model accurately identifies those at risk of severe illness or clinical deterioration, presenting a promising tool for advancing personalized medicine in pregnant patients with COVID-19., (© 2023. The Author(s).)

Amniotic Fluid Volume (AFV) is a crucial fetal biomarker when diagnosing specific fetal abnormalities. This study proposes a novel Convolutional Neural Network (CNN) model, AFNet, for segmenting amniotic fluid (AF) to facilitate clinical AFV evaluation. AFNet was trained and tested on a manually segmented and radiologist-validated AF dataset. AFNet outperforms ResUNet++ by using efficient feature mapping in the attention block and transposing convolutions in the decoder. Our experimental results show that AFNet achieved a mean Intersection over Union (mIoU) of 93.38% on our dataset, thereby outperforming other state-of-the-art models. While AFNet achieves performance scores similar to those of the UNet++ model, it does so while utilizing merely less than half the number of parameters. By creating a detailed AF dataset with an improved CNN architecture, we enable the quantification of AFV in clinical practice, which can aid in diagnosing AF disorders during gestation.

Background: With nearly one-third of patients with major depressive disorder being resistant to available antidepressants, there is a need to develop new treatments for this population. Stellate ganglion block (SGB) is a procedure used to block sympathetic input to the central autonomic system; it has been administered to treat several conditions, including pain. Recently, indications for SGB have extended and the potential benefits for psychiatric disorders are under investigation., Methods: The Local Injection For Treating Mood Disorders (LIFT-MOOD) study investigated the feasibility of a trial of 2 right-sided injections of bupivacaine 0.5% (7 mL) at the stellate ganglion in participants with treatment-resistant depression (TRD) using a randomized, placebo-controlled, pilot trial. Ten participants were randomized in a 1:1 allocation to receive active treatment or placebo (saline). Primary feasibility outcomes included recruitment rate, withdrawal, adherence, missing data, and adverse events. As a secondary, exploratory objective, we explored the efficacy of SGB in improving symptoms of depression by calculating the change in scores from baseline to follow-up on day 42 for each treatment group., Results: The recruitment rate was reasonable and sufficient, retention and adherence were high, missing data were low, and adverse events were mild and temporary. Both treatment groups demonstrated decreases in Montgomery-Åsberg Depression Rating Scale scores, compared to baseline, by the end of the study., Conclusion: This study supports the feasibility of a confirmatory trial of SGB in participants with TRD. Conclusions regarding efficacy cannot be made based on this preliminary study due to the small number of participants who completed active treatment. Larger-scale randomized controlled trials with long-term follow-ups and alternate sham procedures are needed to assess the efficacy and duration of symptom improvement with the use of SGB in TRD., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: KSL is supported in part by Merit Awards from the Department of Anesthesiology and Pain Medicine at the University of Toronto and is a co-principal investigator of a study funded by Shoppers Drug Mart. VB is supported by an Academic Scholar Award from the University of Toronto Department of Psychiatry and has received research support from the Canadian Institutes of Health Research, Brain & Behavior Foundation, Ontario Ministry of Health Innovation Funds, Royal College of Physicians and Surgeons of Canada, Department of National Defence (Government of Canada), New Frontiers in Research Fund, Associated Medical Services Inc. Healthcare, American Foundation for Suicide Prevention, Roche Canada, Novartis, and Eisai., (© The Author(s) 2023.)

Heterozygous, loss-of-function germline variants in ATM have been associated with an increased lifetime risk of breast, pancreas, prostate, stomach, ovarian, colorectal, and melanoma cancers. We conducted a retrospective review of thirty-one unrelated patients found to be heterozygous for a germline pathogenic variant in ATM and identified a significant proportion of patients in this cohort with cancers not currently associated with the ATM hereditary cancer syndrome, including carcinomas of the gallbladder, uterus, duodenum, kidney, and lung as well as a vascular sarcoma. A comprehensive review of the literature found 25 relevant studies where 171 individuals with a germline deleterious ATM variant have been diagnosed with the same or similar cancers. The combined data from these studies were then used to estimate the prevalence of germline ATM pathogenic variants in these cancers, which ranged between 0.45% and 2.2%. Analysis of tumor sequencing performed in large cohorts demonstrated that the frequency of deleterious somatic ATM alterations in these atypical cancers equaled or exceeded the alteration frequency in breast cancer and occurred at a significantly higher rate than in other DNA-damage response tumor suppressors, namely BRCA1 and CHEK2. Furthermore, multi-gene analysis of somatic alterations in these atypical cancers demonstrated significant co-occurrence of pathogenic alterations in ATM with BRCA1 and CHEK2 , while there was significant mutual exclusivity between pathogenic alterations in ATM and TP53. This indicates that germline ATM pathogenic variants may play a role in cancer initiation and progression in these atypical ATM malignancies, potentially influencing these cancers to be driven toward DNA-damage repair deficiency and away from loss of TP53 . As such, these findings provide evidence for broadening of the ATM -cancer susceptibility syndrome phenotype to improve the recognition of affected patients and provide more efficacious, germline-directed therapies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Borja, Silva-Smith, Huang, Parekh, Sussman and Tekin.)

Identifying fetal orientation is essential for determining the mode of delivery and for sequence planning in fetal magnetic resonance imaging (MRI). This manuscript describes a deep learning algorithm named Fet-Net, composed of convolutional neural networks (CNNs), which allows for the automatic detection of fetal orientation from a two-dimensional (2D) MRI slice. The architecture consists of four convolutional layers, which feed into a simple artificial neural network. Compared with eleven other prominent CNNs (different versions of ResNet, VGG, Xception, and Inception), Fet-Net has fewer architectural layers and parameters. From 144 3D MRI datasets indicative of vertex, breech, oblique and transverse fetal orientations, 6120 2D MRI slices were extracted to train, validate and test Fet-Net. Despite its simpler architecture, Fet-Net demonstrated an average accuracy and F1 score of 97.68% and a loss of 0.06828 on the 6120 2D MRI slices during a 5-fold cross-validation experiment. This architecture outperformed all eleven prominent architectures ( p < 0.05). An ablation study proved each component's statistical significance and contribution to Fet-Net's performance. Fet-Net demonstrated robustness in classification accuracy even when noise was introduced to the images, outperforming eight of the 11 prominent architectures. Fet-Net's ability to automatically detect fetal orientation can profoundly decrease the time required for fetal MRI acquisition.

Objectives: To examine the sociodemographic characteristics, activities, motivations, experiences, skills and challenges of patient partners working across multiple health system settings in Canada., Design: Online cross-sectional survey of self-identified patient partners., Setting: Patient partners in multiple jurisdictions and health system organisations., Participants: 603 patient partners who had drawn on their experiences with the health system as a patient, family member or informal caregiver to try to improve it in some way, through their involvement in the activities of a group, organisation or government., Results: Survey respondents predominantly identified as female (76.6%), white (84%) and university educated (70.2%) but were a heterogeneous group in the scope (activities and organisations), intensity (number of hours) and longevity (number of years) of their role. Primary motivations for becoming a patient partner were the desire to improve the health system based on either a negative (36.2%) or positive (23.3%) experience. Respondents reported feeling enthusiastic (83.6%), valued (76.9%) and needed (63.3%) always or most of the time; just under half felt they had always or often been adequately compensated in their role. Knowledge of the health system and the organisation they partner with are key skills needed. Two-thirds faced barriers in their role with over half identifying power imbalances. Less than half were able to see how their input was reflected in decisions or changes always or most of the time, and 40.3% had thought about quitting., Conclusions: This survey is the first of its kind to examine at a population level, the characteristics, experiences and dynamics of a large sample of self-identified patient partners. Patient partners in this sample are a sociodemographically homogenous group, yet heterogeneous in the scope, intensity and longevity of roles. Our findings provide key insights at a critical time, to inform the future of patient partnership in health systems., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Fetal MR imaging is subject to artifacts including motion, chemical shift, and radiofrequency artifacts. Currently, such artifacts are detected by the MRI operator, a process which is subjective, time consuming, and prone to errors. We propose a novel algorithm, RISE-Net, that can consistently, automatically, and objectively detect artifacts in 3D fetal MRI. It makes use of a CNN ensemble approach where the first CNN aims to identify and classify any artifacts in the image, and the second CNN uses regression to determine the severity of the detected artifacts. The main mechanism in RISE-Net is the stacked Residual, Inception, Squeeze and Excitation (RISE) blocks. This classification network achieved an accuracy of 90.34% and a F1 score of 90.39% and outperformed other state-of-the-art architectures, such as VGG-16, Inception, ResNet-50, ReNet-Inception, SE-ResNet, and SE-Inception. The severity regression network had an MSE of 0.083 across all classes. The presented algorithm facilitates rapid and accurate fetal MRI quality assurance that can be implemented into clinical use., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lim, Lo, Wagner, Ertl-Wagner and Sussman.)

Amniocentesis is the process of retrieving the nutrient-rich amniotic fluid (AF) that encompasses the growing fetus in order to diagnose fetal diseases and developmental disorders. Currently, it is only performed on pregnant persons at risk and is invasive with the potential for infection and in some cases, miscarriage. A non-invasive alternative is needed and could be developed using magnetic resonance spectroscopy (MRS). To develop such MRS sequences, ample testing and training are needed and could be most efficiently conducted on a phantom. We propose a protocol for creating such a synthetic AF phantom for MRS testing and optimization. The proposed AF is validated using nuclear magnetic resonance (NMR) proving it produces spectra comparable to those in the literature. The results from this study can aid in developing a non-invasive fetal diagnostic tool to replace amniocentesis., Competing Interests: The authors have declared no conflict of interest., (© 2022 The Authors. Analytical Science Advances published by Wiley‐VCH GmbH.)

Objective: To provide a systematic review of available brain MRI phantoms for comparison of structural and functional characteristics., Materials and Methods: Phantoms were identified from a literature search using two databases including Google Scholar and PubMed. Narrow inclusion criteria were followed for identification of only tissue-mimicking MRI phantoms excluding digital, computational, or numerical phantoms. Assessment criteria for the identified phantoms was based on three categories being anatomical accuracy, tissue-mimicking materials, and exhibiting relaxation times approximating in-vivo tissues. The available features and uses of each phantom were reported and discussed using the assessment criteria., Results: Ten phantoms were identified after screening; each proposed phantom was then summarized in a table (Table 2). Significant features and characteristics were shown in the comparisons of phantom type in each category, being anthropomorphic vs. traditional phantoms. Anthropomorphic phantoms had more anatomically accurate features than traditional phantoms. On the other hand, traditional phantoms commonly used effective tissue-mimicking materials and accurate electromagnetic properties., Discussion: The findings provide an overview of the different proposed tissue-mimicking MRI brain phantoms available. Various uses and features are highlighted by comparing criteria such as anatomical accuracy, tissue-mimicking material, and electromagnetic properties. Tissue-mimicking MRI phantoms are an extremely useful tool for researchers and clinicians. Future applications include personalized phantom technology and validation of MR imaging and segmentation methods., (© 2021. European Society for Magnetic Resonance in Medicine and Biology (ESMRMB).)

Rapid development in Magnetic Resonance Imaging (MRI) has played a key role in prenatal diagnosis over the last few years. Deep learning (DL) architectures can facilitate the process of anomaly detection and affected-organ classification, making diagnosis more accurate and observer-independent. We propose a novel DL image classification architecture, Fetal Organ Anomaly Classification Network (FOAC-Net), which uses squeeze-and-excitation (SE) and naïve inception (NI) modules to automatically identify anomalies in fetal organs. This architecture can identify normal fetal anatomy, as well as detect anomalies present in the (1) brain, (2) spinal cord, and (3) heart. In this retrospective study, we included fetal 3-dimensional (3D) SSFP sequences of 36 participants. We classified the images on a slice-by-slice basis. FOAC-Net achieved a classification accuracy of 85.06, 85.27, 89.29, and 82.20% when predicting brain anomalies, no anomalies (normal), spinal cord anomalies, and heart anomalies, respectively. In a comparison study, FOAC-Net outperformed other state-of-the-art classification architectures in terms of class-average F1 and accuracy. This work aims to develop a novel classification architecture identifying the affected organs in fetal MRI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lo, Lim, Wagner, Ertl-Wagner and Sussman.)

Objective: To synthesize peer-reviewed evidence related to the use of artificial intelligence (AI) in surgical education DESIGN: We conducted and reported a scoping review according to the standards outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis with extension for Scoping Reviews guideline and the fourth edition of the Joanna Briggs Institute Reviewer's Manual. We systematically searched eight interdisciplinary databases including MEDLINE-Ovid, ERIC, EMBASE, CINAHL, Web of Science: Core Collection, Compendex, Scopus, and IEEE Xplore. Databases were searched from inception until the date of search on April 13, 2021., Setting/participants: We only examined original, peer-reviewed interventional studies that self-described as AI interventions, focused on medical education, and were relevant to surgical trainees (defined as medical or dental students, postgraduate residents, or surgical fellows) within the title and abstract (see Table 2). Animal, cadaveric, and in vivo studies were not eligible for inclusion., Results: After systematically searching eight databases and 4255 citations, our scoping review identified 49 studies relevant to artificial intelligence in surgical education. We found diverse interventions related to the evaluation of surgical competency, personalization of surgical education, and improvement of surgical education materials across surgical specialties. Many studies used existing surgical education materials, such as the Objective Structured Assessment of Technical Skills framework or the JHU-ISI Gesture and Skill Assessment Working Set database. Though most studies did not provide outcomes related to the implementation in medical schools (such as cost-effective analyses or trainee feedback), there are numerous promising interventions. In particular, many studies noted high accuracy in the objective characterization of surgical skill sets. These interventions could be further used to identify at-risk surgical trainees or evaluate teaching methods., Conclusions: There are promising applications for AI in surgical education, particularly for the assessment of surgical competencies, though further evidence is needed regarding implementation and applicability., Competing Interests: Conflicts of interest The authors report no conflicts of interest., (Copyright © 2021 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Stellate ganglion block (SGB) is a procedure involving the injection of a local anesthetic surrounding the stellate ganglion to inhibit sympathetic outflow. The objective of this review was to summarize existing evidence on the use of SGB in adults with psychiatric disorders. A systematic search identified 17 published studies and 4 registered clinical trials. Eighty-eight percent of published studies, including 2 randomized controlled trials (RCTs), used SGB for posttraumatic stress disorder (PTSD), although its use for schizophrenia spectrum disorders was also explored. Administration of 1 to 2 SGBs using right-sided laterality with 0.5% ropivacaine was most common. Preliminary evidence from clinical trials and case studies supports the feasibility of SGB for treating psychiatric disorders involving dysregulation of the sympathetic nervous system, although effectiveness evidence from RCTs is mixed. One RCT concluded that improvement in PTSD symptoms was significant, while the other concluded that it was nonsignificant. Improvements were noted within 5 minutes of SGB and lasted 1 month or longer. Registered clinical trials are exploring the use of SGB in new psychiatric disorders, including major depressive disorder and borderline personality disorder. More studies with larger sample sizes and alternate protocols are needed to further explore therapeutic potential of SGB for psychiatric disorders., Competing Interests: Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Kerzner, Liu, Sussman, and Demchenko do not have any disclosures. Wijeysundera is supported in part by Merit Awards from the Department of Anesthesiology and Pain Medicine at the University of Toronto (Toronto, Canada), a New Investigator Award from the Canadian Institutes of Health Research (Ottawa, Canada) and the Endowed Chair in Translational Anesthesiology Research at St. Michael’s Hospital (Toronto, Canada) and the University of Toronto (Toronto, Canada). The opinions, results, and conclusions reported in this article are those of the authors and are independent from the funding sources. Kennedy has received honoraria or research funds from Abbott, Alkermes, Allergan, Boehringer Ingelheim, Brain Canada, Canadian Institutes of Health Research, Janssen, Lundbeck, Lundbeck Institute, Ontario Brain Institute, Ontario Research Fund, Otsuka, Pfizer, Servier, Sunovion, Sun Pharmaceuticals, and holds stock in Field Trip Health. Ladha is supported in part by Merit Awards from the Department of Anesthesiology and Pain Medicine at the University of Toronto (Toronto, Canada), and is a Co-Principal Investigator of a study funded by Shoppers Drug Mart. Bhat is supported by an Academic Scholar Award from the University of Toronto Department of Psychiatry, and has received research support from CIHR, Brain & Behavior Foundation, Ministry of Health Innovation Funds, Royal College of Physicians and Surgeons of Canada, Department of Defense, Canada, and an investigator-initiated trial from Roche Canada., (© The Author(s) 2021.)

Context.—: The gastrointestinal (GI) tract is the most common site of extranodal non-Hodgkin lymphoma, accounting for 20% to 40% of all extranodal lymphomas. The majority of these are systemic processes secondarily involving the GI tract. Primary GI lymphomas are less common, accounting for approximately 10% to 15% of all non-Hodgkin lymphomas. Most non-Hodgkin lymphomas involving the GI tract are of B-cell lineage, of which diffuse large B-cell lymphoma is the most common subtype, irrespective of location., Objective.—: To review the lymphoproliferative neoplasms of B-cell and T-cell lineage involving the luminal GI tract according to the most prevalent subtypes at each anatomic site., Data Source.—: Systematic search of the PubMed database for updated literature on GI lymphoma epidemiology, subtypes, clinical, endoscopic, and genetic findings. Histologic images are derived from our collection of clinical cases., Conclusions.—: The GI tract is the most common site of extranodal lymphoproliferative neoplasms. Recognition of the most frequently encountered GI lymphomas is imperative for patient management and treatment.

Deep learning (DL) algorithms have become an increasingly popular choice for image classification and segmentation tasks; however, their range of applications can be limited. Their limitation stems from them requiring ample data to achieve high performance and adequate generalizability. In the case of clinical imaging data, images are not always available in large quantities. This issue can be alleviated by using data augmentation (DA) techniques. The choice of DA is important because poor selection can possibly hinder the performance of a DL algorithm. We propose a DA policy search algorithm that offers an extended set of transformations that accommodate the variations in biomedical imaging datasets. The algorithm makes use of the efficient and high-dimensional optimizer Bi-Population Covariance Matrix Adaptation Evolution Strategy (BIPOP-CMA-ES) and returns an optimal DA policy based on any input imaging dataset and a DL algorithm. Our proposed algorithm, Medical Augmentation (Med-Aug), can be implemented by other researchers in related medical DL applications to improve their model's performance. Furthermore, we present our found optimal DA policies for a variety of medical datasets and popular segmentation networks for other researchers to use in related tasks.

The incidence of colorectal cancer (CRC) and cancer-related mortality has increased in patients <55 years old. 1 Consensus on optimal intervals for post-CRC surveillance colonoscopy in young patients is lacking. The primary endpoint of this study was comparison of rates of metachronous advanced neoplasia (AN) in patients diagnosed with CRC at <50 and 50-75 years. The secondary aim was to evaluate risk factors of metachronous AN., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Segmentation of the fetus from 2-dimensional (2D) magnetic resonance imaging (MRI) can aid radiologists with clinical decision making for disease diagnosis. Machine learning can facilitate this process of automatic segmentation, making diagnosis more accurate and user independent. We propose a deep learning (DL) framework for 2D fetal MRI segmentation using a Cross Attention Squeeze Excitation Network (CASE-Net) for research and clinical applications. CASE-Net is an end-to-end segmentation architecture with relevant modules that are evidence based. The goal of CASE-Net is to emphasize localization of contextual information that is relevant in biomedical segmentation, by combining attention mechanisms with squeeze-and-excitation (SE) blocks. This is a retrospective study with 34 patients. Our experiments have shown that our proposed CASE-Net achieved the highest segmentation Dice score of 87.36%, outperforming other competitive segmentation architectures.

Silicone rubber's silicone-oxygen backbones give unique material properties which are applicable in various biomedical devices. Due to the diversity of potential silicone rubber compositions, the material properties can vary widely. This paper characterizes the dielectric and mechanical properties of two different silicone rubbers, each with a different cure system, and in combination with silicone additives. A tactile mutator (Slacker™) and/or silicone thickener (Thi-vex™) were mixed with platinum-cured and condensation-cured silicone rubber in various concentrations. The dielectric constants, conductivities, and compressive and shear moduli were measured for each sample. Our study contributes novel information about the dielectric and mechanical properties of these two types of silicone rubber and how they change with the addition of two common silicone additives.

Background: Underserved ethnic minority populations experience significant disparities in HIV, hepatitis C virus (HCV), colorectal cancer (CRC), and cervical cancer incidence and mortality. Much of the excess burden of these diseases among underserved communities is due to lack of preventive care, including screening. Barriers to disease screening include low awareness, lack of access to care and health insurance, and cultural beliefs regarding disease prevention. Our current trial aims to examine community health worker (CHW)-delivered, home-based multi-modality screening for HIV, HCV, CRC, and cervical cancer simultaneously., Design: We are conducting a randomized pragmatic trial among 900 Haitian, Hispanic, and African-American participants from diverse underserved communities in South Florida. People between the ages of 50 and 65 who have not had appropriate HIV, HCV, CRC, and cervical cancer screening per United States Preventive Services Task Force (USPSTF) recommendations are eligible for the study. Participants are recruited by CHWs and complete a structured interview to assess multilevel determinants of disease risk. Participants are then randomized to receive HIV, HCV, CRC, and cervical cancer screening via navigation to care by a CHW (Group 1) or via CHW-delivered home-based screening (Group 2). The primary outcome is completion of screening for each of these diseases within 6 months post-enrollment., Discussion: Our trial is among the first to examine the effectiveness of a CHW-delivered, multimodality, home-based disease-screening approach. If found to be effective, this approach may represent a cost-effective strategy for disease screening within underserved and underscreened minority groups., Trial Registration: Clinical Trials.gov # NCT02970136, registered November 21, 2016.

Objective: To provide a review and quantitative analysis of the available fetal MR imaging phantoms., Materials and Methods: A literature search was conducted across Pubmed, Google Scholar, and Ryerson University Library databases to identify fetal MR imaging phantoms. Phantoms were graded on a semi-quantitative scale in regards to four evaluation categories: (1) anatomical accuracy in size and shape, (2) dielectric conductivity similar to the simulated tissue, (3) relaxation times similar to simulated tissue, and (4) physiological motion similar to fetal gross body, cardiovascular, and breathing motion. This was followed by statistical analysis to identify significant findings., Results: Seventeen fetal phantoms were identified and had an average overall percentage accuracy of 26%, with anatomical accuracy being satisfied the most (56%) and physiological motion the least (7%). Phantoms constructed using 3D printing were significantly more accurate than conventionally constructed phantoms., Discussion: Currently available fetal phantoms lack accuracy and motion simulation. 3D printing may lead to higher accuracy compared with traditional manufacturing. Future research needs to focus on properly simulating both fetal anatomy and physiological motion to produce a phantom that is appropriate for fetal MRI sequence development and optimization.

One possible predictive factor that affects both pro-environmental behavior and health behavior is health consciousness (a psychological state where an individual is aware of and involved in his/her health condition). We examined the relationship between health consciousness and two pro-environmental behaviors (recycling and green purchasing) within health professionals in a Japanese large hospital. Multivariate linear regression analysis revealed a significant association between health consciousness and recycling behavior, while there was no association between health consciousness and green purchasing behavior. We assume that health consciousness can certainly be a factor promoting pro-environmental behavior, but that it may have been insufficient to cause green purchasing, because of the organizational norm of recycling in the Japanese context. Given that there is previous evidence about the relationship between health consciousness and health behavior, health consciousness might be a predictive factor that encourages both health behavior and pro-environmental behavior simultaneously.

Objective: This study aims to noninvasively quantify blood flow in the uterine arteries (UTAs) and umbilical vein (UV) using phase-contrast magnetic resonance imaging (PC-MRI) and test whether these correlate with maternal fitness parameters., Method: Resting UTA and UV flows were measured in 23 healthy 30 ± 3-year-old women who engaged in moderate-intensity physical activity during pregnancy. Participant fitness was characterized in the second and third trimesters using the submaximal oxygen uptake (VO 2 ) test measuring heart rate (HR), VO 2 , ventilation (ventilatory equivalent [VE]/VO 2 ), and the Borg rating of perceived exertion (respiratory quotient [RQ]). Linear regression models were used to determine the associations between blood flow and maternal fitness measures., Results: Blood flows in the UTA (957 ± 241 mL/min) and UV (132 ± 38 mL/min/kg) were successfully measured in 20 (87%) participants. Neither was associated with any physical fitness parameters (HR, VO 2 , VE/VO 2 , and RQ) nor with any second-to-third trimester change in these parameters., Conclusion: PC-MRI can be used to noninvasively measure blood flow in the UTA and UV. Neither resting UTA nor UV flow is associated with maternal fitness parameters. This is the first MRI-based study to provide novel hemodynamic data suggesting decoupling between maternal moderate fitness level and the maternal-placental-fetal hemodynamic system in healthy, normal body mass index (BMI) pregnancies., (© 2019 John Wiley & Sons, Ltd.)

Purpose: To image multidimensional flow in fetuses using golden-angle radial phase contrast cardiovascular magnetic resonance (PC-CMR) with motion correction and retrospective gating., Methods: A novel PC-CMR method was developed using an ungated golden-angle radial acquisition with continuously incremented velocity encoding. Healthy subjects (n = 5, 27 ± 3 years, males) and pregnant females (n = 5, 34 ± 2 weeks gestation) were imaged at 3 T using the proposed sequence. Real-time reconstructions were first performed for retrospective motion correction and cardiac gating (using metric optimized gating, MOG). CINE reconstructions of multidimensional flow were then performed using the corrected and gated data., Results: In adults, flows obtained using the proposed method agreed strongly with those obtained using a conventionally gated Cartesian acquisition. Across the five adults, bias and limits of agreement were - 1.0 cm/s and [- 5.1, 3.2] cm/s for mean velocities and - 1.1 cm/s and [- 6.5, 4.3] cm/s for peak velocities. Temporal correlation between corresponding waveforms was also high (R~ 0.98). Calculated timing errors between MOG and pulse-gating RR intervals were low (~ 20 ms). First insights into multidimensional fetal blood flows were achieved. Inter-subject consistency in fetal descending aortic flows (n = 3) was strong with an average velocity of 27.1 ± 0.4 cm/s, peak systolic velocity of 70.0 ± 1.8 cm/s and an intra-class correlation coefficient of 0.95 between the velocity waveforms. In one fetal case, high flow waveform reproducibility was demonstrated in the ascending aorta (R = 0.97) and main pulmonary artery (R = 0.99)., Conclusion: Multidimensional PC-CMR of fetal flow was developed and validated, incorporating retrospective motion compensation and cardiac gating. Using this method, the first quantification and visualization of multidimensional fetal blood flow was achieved using CMR.

Treatment choices for acute myelogenous leukemia (AML) patients resistant to conventional chemotherapies are limited and novel therapeutic agents are needed. IL3 receptor alpha (IL3Rα, or CD123) is expressed on the majority of AML blasts, and there is evidence that its expression is increased on leukemic relative to normal hematopoietic stem cells, which makes it an attractive target for antibody-based therapy. Here, we report the generation and preclinical characterization of SGN-CD123A, an antibody-drug conjugate using the pyrrolobenzodiazepine dimer (PBD) linker and a humanized CD123 antibody with engineered cysteines for site-specific conjugation. Mechanistically, SGN-CD123A induces activation of DNA damage response pathways, cell-cycle changes, and apoptosis in AML cells. In vitro , SGN-CD123A-mediated potent cytotoxicity of 11/12 CD123 + AML cell lines and 20/23 primary samples from AML patients, including those with unfavorable cytogenetic profiles or FLT3 mutations. In vivo , SGN-CD123A treatment led to AML eradication in a disseminated disease model, remission in a subcutaneous xenograft model, and significant growth delay in a multidrug resistance xenograft model. Moreover, SGN-CD123A also resulted in durable complete remission of a patient-derived xenograft AML model. When combined with a FLT3 inhibitor quizartinib, SGN-CD123A enhanced the activity of quizartinib against two FLT3-mutated xenograft models. Overall, these data demonstrate that SGN-CD123A is a potent antileukemic agent, supporting an ongoing trial to evaluate its safety and efficacy in AML patients (NCT02848248). Mol Cancer Ther; 17(2); 554-64. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Antibody-drug conjugates (ADCs) are fulfilling the promise of targeted therapy with meaningful clinical success. An intense research effort is directed towards improving pharmacokinetic profiles, toxicity and chemical stability of ADCs. The majority of ADCs use amide and thioether chemistry to link potent cytotoxic agents to antibodies via endogenous lysine and cysteine residues. While maleimide-cysteine conjugation is used for many clinical stage ADC programs, maleimides have been shown to exhibit some degree of post-conjugation instability. Previous research with site-directed mutagenic incorporation of cysteine residues for conjugation revealed that the stability of the drug-antibody linkage depends on the site of conjugation. Here we report on a collection of engineered cysteine antibodies (S239C, E269C, K326C and A327C) that can be site-specifically conjugated to potent cytotoxic agents to produce homogenous 2-loaded ADCs. These ADCs confirm that site of conjugation impacts maleimide stability and present a novel mechanism of thioether stabilization, effectively unlinking stability from either local chemical environment or calculated solvent accessibility and expanding the current paradigm for ADC drug-linker stability. These ADCs show potent in vitro and in vivo activity while delivering half of the molar equivalent dose of drug per antibody when compared to an average 4-loaded ADC. In addition, our lead engineered site shields highly hydrophobic drugs, enabling conjugation, formulation and clinical use of otherwise intractable chemotypes., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Despite a rising incidence of inflammatory bowel disease (IBD) in Hispanics in the United States, there are no studies examining the relationship between immigrant generation and IBD onset among Hispanics., Aims: To determine whether age of IBD diagnosis, time from immigration to IBD diagnosis and IBD phenotype, differed across immigration periods in South Florida Cuban immigrants., Methods: This was a cohort of consecutively identified Cuban-born adults who developed IBD in the United States and were followed in gastroenterology (GI) clinic. We divided time cohorts of immigration by historical relevance: before 1980, 1980-1994 and 1995-to-present. We examined differences across time cohorts in diagnosis age, time from immigration to IBD diagnosis, and IBD phenotype (ie, IBD type, disease location)., Results: A total of 130 Cuban patients with IBD were included. Age of IBD diagnosis was older in Cubans arriving before 1980 than in those arriving between 1980-1994 or after 1995 (44.7 vs 33.79 and 33.71, respectively, P<.0001). Time between immigration and diagnosis was shorter in patients arriving to the US after 1980 (31.77 years, Standard deviation (SD) 12.83 (<1980) vs 17.13 years, SD 8.55 (1980-1994) and 8.30 years, SD 4.72 (1995-to-present). IBD phenotype, including type of IBD, disease location and surgeries, did not differ significantly across time cohorts., Conclusions: Our study describes changing patterns of IBD onset following immigration in Cubans, suggesting that environmental changes either in the United States, Cuba or both are resulting in faster IBD onset in younger immigrant generations. These studies can inform the search for environmental triggers that may result in IBD., (© 2017 John Wiley & Sons Ltd.)

Concussion induces transient, and oftentimes chronic, lingering impairment to mental functioning, which must be driven by some underlying neurobiological perturbation - however, the physical changes related to sequelae are difficult to detect. Previous imaging studies on concussion have focused on alterations to cortical anatomy, but few have examined the cerebrum, subcortex, and cerebellum. Here, we present an analysis of these structures in a single cohort (all males, 21 patients, 22 controls) using MRI and diagnosed with a single-concussive episode in the acute and sub-acute stages of injury. Structural images were segmented into 78 cortical brain regions and 81,924 vertices using the CIVET algorithm. Subcortical volumetric analyses of the cerebellum, thalamus, globus pallidus, caudate and putamen were conducted following segmentation. Participants with concussion were found to have reduced white and grey matter volume, total cortical volume, as well as cortical thinning, primarily in left frontal areas. No differences were observed in the cerebellum or subcortical structures. In conclusion, just a single concussive episode induces measurable changes in brain structure manifesting as diffuse and local patterns of altered neuromorphometry., (Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.)

Background: Adherence and persistence rates of anticholinergic (ACH) therapies have been well described. To date, few studies describe these metrics for mirabegron in patients with overactive bladder., Methods: This retrospective analysis of MarketScan ® database assessed adherence and persistence of patients receiving either mirabegron or ACH. Study eligibility required an index date (first prescription filled) between July 2012 and June 2013 with 12 months of continuous enrolment preindex date and 12 months of follow-up. Adherence was defined as a proportion of days covered of ≥ 80% among patients with at least 2 fills of index medication. Persistence measures included treatment failure described as either treatment discontinuation (medication supply gap ≥ 30 days) or switching to a different medication. A medication supply gap of ≥ 45 days was used as a sensitivity analysis., Results: The mean age of mirabegron users (n = 4037) was 67 years and 43% were ACH naïve while the mean age of ACH users was 62 years (n = 67,943). Over the 12-month follow-up period, 44% of patients treated with mirabegron and 31% of patients treated with ACH were adherent to their indexed medications. Treatment failure was 81% for mirabegron and 88% for ACH. Most mirabegron treatment failures were because of treatment discontinuation (67%) versus switching to ACH therapy (14%). The ACH discontinuation rate was 84% and treatment switching rate was 4%. The mean (standard deviation) time to treatment failure was 143 (130) days for mirabegron and 69 (69) days for ACH. Adherence and persistence patterns were similar in the sensitivity analysis using a ≥ 45-day supply gap threshold., Conclusions: This real-world study demonstrated low adherence and persistence to mirabegron similar to ACH therapies., (© 2017 Allergan. International Journal of Clinical Practice Published by John Wiley & Sons Ltd.)

Olmesartan-induced enteropathy mimics celiac disease clinically and pathologically. As in celiac disease, the pathologic findings are villous atrophy and increased intraepithelial lymphocytes. Clinical presentation of olmesartan-induced enteropathy includes diarrhea, weight loss, and nausea. In contrast to celiac disease, tissue transglutaminase is not elevated and there is no response to a gluten-free diet. Including this entity in the differential diagnosis of sprue-like enteropathy is critical for its early diagnosis since replacing olmesartan with an alternative antihypertensive drug can simplify the diagnostic workup and provide both clinical and histologic improvement.

Purpose: These are the final results of the prospective, multicenter, long-term (3.5-year) study of the efficacy/safety of onabotulinumtoxinA for overactive bladder syndrome., Materials and Methods: Patients who completed either of 2, 24-week phase 3 trials could enter a 3-year extension and continue treatment with onabotulinumtoxinA 100 U as needed to control overactive bladder symptoms. Data were analyzed by the treatment(s) received (up to 6) and in discrete subgroups that received 1, 2, 3, 4, 5 or 6 treatments (to evaluate the consistency of the response after repeat treatments in the same patient groups). Assessments included the change from baseline in the number of urinary incontinence episodes per day and the proportion of patients who reported improvement/great improvement in urinary symptoms on the TBS (Treatment Benefit Scale) at week 12 as co-primary end points. Other end points were the change from baseline in I-QOL (Incontinence Quality of Life), the number of urgency and micturition episodes per day; duration of effect; the number of adverse events; and the initiation of intermittent catheterization., Results: Consistent mean reductions in urinary incontinence were observed following continued onabotulinumtoxinA treatment, ranging from -3.1 to -3.8 in the overall population and -2.9 to -4.5 in the discrete subgroups. Durable improvements were seen in overactive bladder symptoms and quality of life. A high proportion of patients rated their condition as improved/greatly improved. The median duration of effect was 7.6 months. The most common adverse event was urinary tract infection. The rate of de novo catheterization after the first treatment was 4.0% and it ranged from 0.6% to 1.7% after subsequent treatments., Conclusions: Long-term onabotulinumtoxinA treatment consistently decreased overactive bladder symptoms and improved quality of life with no new safety signals., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

The auristatin class of microtubule destabilizers are highly potent cytotoxic agents against several cancer cell types when delivered as antibody drug conjugates. Here we describe the high resolution structures of tubulin in complex with both monomethyl auristatin E and F and unambiguously define the trans-configuration of both ligands at the Val-Dil amide bond in their tubulin bound state. Moreover, we illustrate how peptidic vinca-site agents carrying terminal carboxylate residues may exploit an observed extended hydrogen bond network with the M-loop Arg278 to greatly improve the affinity of the corresponding analogs and to maintain the M-loop in an incompatible conformation for productive lateral tubulin-tubulin contacts in microtubules. Our results highlight a potential, previously undescribed molecular mechanism by which peptidic vinca-site agents maintain unparalleled potency as microtubule-destabilizing agents.

[This corrects the article DOI: 10.1002/brb3.457.].

Background: Posttraumatic stress disorder (PTSD), an anxiety disorder that can develop after exposure to psychological trauma, impacts up to 20 % of soldiers returning from combat-related deployment. Advanced neuroimaging holds diagnostic and prognostic potential for furthering our understanding of its etiology. Previous imaging studies on combat-related PTSD have focused on selected structures, such as the hippocampi and cortex, but none conducted a comprehensive examination of both the cerebrum and cerebellum. The present study provides a complete analysis of cortical, subcortical, and cerebellar anatomy in a single cohort. Forty-seven magnetic resonance images (MRIs) were collected from 24 soldiers with PTSD and 23 Control soldiers. Each image was segmented into 78 cortical brain regions and 81,924 vertices using the corticometric iterative vertex based estimation of thickness algorithm, allowing for both a region-based and a vertex-based cortical analysis, respectively. Subcortical volumetric analyses of the hippocampi, cerebellum, thalamus, globus pallidus, caudate, putamen, and many sub-regions were conducted following their segmentation using Multiple Automatically Generated Templates Brain algorithm., Results: Participants with PTSD were found to have reduced cortical thickness, primarily in the frontal and temporal lobes, with no preference for laterality. The region-based analyses further revealed localized thinning as well as thickening in several sub-regions. These results were accompanied by decreased volumes of the caudate and right hippocampus, as computed relative to total cerebral volume. Enlargement in several cerebellar lobules (relative to total cerebellar volume) was also observed in the PTSD group., Conclusions: These data highlight the distributed structural differences between soldiers with and without PTSD, and emphasize the diagnostic potential of high-resolution MRI.

Introduction: This study is the first to characterize normal development and sex differences across neuroanatomical structures in cortical, subcortical, and cerebellar brain regions in a single large cohort., Methods: One hundred and ninety-two magnetic resonance images were examined from 96 typically developing females and 96 age-matched typically developing males from 4 to 18 years of age. Image segmentation of the cortex was conducted with CIVET, while that of the cerebellum, hippocampi, thalamus, and basal ganglia were conducted using the MAGeT algorithm., Results: Cortical thickness analysis revealed that most cortical regions decrease linearly, while surface area increases linearly with age. Volume relative to total cerebrum followed a quadratic trend with age, with only the left supramarginal gyrus showing sexual dimorphism. Hippocampal relative volume increased linearly, while the thalamus, caudate, and putamen decreased linearly, and the cerebellum did not change with age. The relative volumes of several subcortical subregions followed inverted U-shaped trends that peaked at ~12 years of age. Many subcortical structures were found to be larger in females than in males, independently of age, while others showed a sex-by-age interaction., Conclusion: This study provides a comprehensive assessment of cortical, subcortical, and cerebellar growth patterns during normal development, and draws attention to the role of sex on neuroanatomical maturation throughout childhood and adolescence.

Fetal movements, which include body and breathing movement, are important indicators of fetal well-being and nervous system development. These have been shown to be affected by intrauterine conditions. While maternal physical activity does induce a change in intrauterine conditions and physiology, its impact on fetal movements is still unclear. This paper will provide a brief review of the literature and outline the current knowledge with regards to the effects of maternal exercise on fetal body and breathing movements., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective: To evaluate the impact of onabotulinumtoxinA on individual domains of the quality of life questionnaires in a pooled analysis of two phase 3 trials in overactive bladder patients with urinary incontinence who were inadequately managed by ≥1 anticholinergic., Methods: Patients received intradetrusor injections of onabotulinumtoxinA 100U (n = 557) or placebo (n = 548). The proportions of patients with a positive response (condition "greatly improved" or "improved") on the Treatment Benefit Scale, and changes in Incontinence Quality of Life scores and King's Health Questionnaire domain scores were analyzed in the overall population and subgroups with clean intermittent catheterization use and urinary tract infection status during the first 12 weeks of treatment. Responses to individual King's Health Questionnaire items were also assessed., Results: Significantly greater proportions of onabotulinumtoxinA-treated patients achieved positive Treatment Benefit Scale response versus placebo (61.8% vs. 28.0%; P < 0.001). OnabotulinumtoxinA showed significantly greater improvements versus placebo in Incontinence Quality of Life total (22.5 vs. 6.6), Incontinence Quality of Life subscale scores and all domains of the King's Health Questionnaire. Notably, a similar trend was observed regardless of clean intermittent catheterization/urinary tract infection status. Additionally, onabotulinumtoxinA resulted in significantly greater improvements than the placebo in practical aspects of patients daily lives, including pad use, need to change undergarments, sleep, relationship with partner and work life/daily activities., Conclusion: In overactive bladder patients with urinary incontinence, onabotulinu-mtoxinA 100U demonstrated significant improvements across the individual domains of the quality of life questionnaires, regardless of clean intermittent catheterization or urinary tract infection status, and provided a positive impact on practical aspects of patients' daily lives., (© 2015 The Authors. International Journal of Urology published by Wiley Publishing Asia Pty Ltd on behalf of the Japanese Urological Association.)

Objectives: Here we present the final results from an extension study assessing long-term onabotulinumtoxinA treatment (3.5 years) in patients with idiopathic overactive bladder., Methods: Patients who completed either of 2 Phase III trials were eligible to enter a 3-year extension study in which they received multiple onabotulinumtoxinA (100 U) treatments. Data were analyzed for the overall population of patients who received 100 U in any treatment cycle (n=829) and within discrete subgroups of patients who received exactly 1 (n=105), 2 (n=118), 3 (n=117), 4 (n=83), 5 (n=46), or 6 (n=33) treatments of the 100 U dose throughout the study (n=502)., Results: Of the 829 patients enrolled, 51.7 % completed the study. Discontinuations due to AEs/lack of efficacy were low (5.1/5.7 %); other reasons were not treatment-related. Mean reductions from baseline in urinary incontinence (UI) episodes/day (week 12; co-primary endpoint) were consistent among discrete subgroups who received 1 (-3.1), 2 (-2.9, -3.2), 3 (-4.1 to -4.5), 4 (-3.4 to -3.8), 5 (-3.0 to -3.6), or 6 (-3.1 to -4.1) treatments. A consistently high proportion of patients reported improvement/great improvement on the Treatment Benefit Scale (week 12; co-primary endpoint) in the discrete subgroups across all treatments (70.0-93.5 %). Median time to request retreatment was ≤6 months for 34.2 %, >6-≤12 months for 37.2 %, and >12 months for 28.5 % of patients. Most common AE was UTI, with no changes in safety profile over time., Conclusion: Long-term onabotulinumtoxinA treatment resulted in consistent reductions in UI and high proportions of patients reporting improvement after each treatment, with no new safety findings., (Copyright © 2015. Published by Elsevier Masson SAS.)

Purpose: The primary objective of this study was to assess anesthesia residents' opinions and perceptions on wellness/burnout, fatigue, education, and patient safety after the initiation of a reduced call model (16-hour call)., Methods: A prospective cohort study was conducted at three time points during the 2013-2014 academic year. A web-based questionnaire consisting of 23 questions was electronically distributed to all anesthesia residents from postgraduate years (PGY) 1 to 5 who were part of the active call roster (n=84) at McMaster University in Hamilton, Ontario. Descriptive summaries were calculated, counts and percentages were used for categorical variables, and answers to open text questions were reviewed for themes., Results: A response rate of 67% was obtained for this study. A majority of anesthesia residents (65%) approved of 16-hour call, felt that their overall quality of life as a senior resident (PGY3 or greater) or junior resident (PGY2 and below) had improved (73% and 55%, respectively), and reported overall feeling less fatigued. Most respondents indicated that the quality of education remained unchanged (47%), or had improved (31%). And most felt better prepared for the royal college exam (52%). Most felt patient safety had improved or was unchanged (both 48%)., Conclusion: The study demonstrates that 16-hour call improved resident wellness, reduced burnout and fostered an environment where residents are less fatigued and more satisfied with their educational experience promoting an environment of patient safety. Overall, the anesthesia residency group demonstrated that not only is 16-hour call preferred but beneficial.

Autism Spectrum Disorder (ASD) is a clinically diagnosed, heterogeneous, neurodevelopmental condition, whose underlying causes have yet to be fully determined. A variety of studies have investigated either cortical, subcortical, or cerebellar anatomy in ASD, but none have conducted a complete examination of all neuroanatomical parameters on a single, large cohort. The current study provides a comprehensive examination of brain development of children with ASD between the ages of 4 and 18 years who are carefully matched for age and sex with typically developing controls at a ratio of one-to-two. Two hundred and ten magnetic resonance images were examined from 138 Control (116 males and 22 females) and 72 participants with ASD (61 males and 11 females). Cortical segmentation into 78 brain-regions and 81,924 vertices was conducted with CIVET which facilitated a region-of-interest- (ROI-) and vertex-based analysis, respectively. Volumes for the cerebellum, hippocampus, striatum, pallidum, and thalamus and many associated subregions were derived using the MAGeT Brain algorithm. The study reveals cortical, subcortical and cerebellar differences between ASD and Control group participants. Diagnosis, diagnosis-by-age, and diagnosis-by-sex interaction effects were found to significantly impact total brain volume but not total surface area or mean cortical thickness of the ASD participants. Localized (vertex-based) analysis of cortical thickness revealed no significant group differences, even when age, age-range, and sex were used as covariates. Nonetheless, the region-based cortical thickness analysis did reveal regional changes in the left orbitofrontal cortex and left posterior cingulate gyrus, both of which showed reduced age-related cortical thinning in ASD. Our finding of region-based differences without significant vertex-based results likely indicates non-focal effects spanning the entirety of these regions. The hippocampi, thalamus, and globus pallidus, were smaller in volume relative to total cerebrum in the ASD participants. Various sub-structures showed an interaction of diagnosis-by-age, diagnosis-by-sex, and diagnosis-by-age-range, in the case where age was divided into childhood (age < 12) and adolescence (12 < age < 18). This is the most comprehensive imaging-based neuro-anatomical pediatric and adolescent ASD study to date. These data highlight the neurodevelopmental differences between typically developing children and those with ASD, and support aspects of the hypothesis of abnormal neuro-developmental trajectory of the brain in ASD.

Introduction: The ketogenic diet (KD) has seen an increase in popularity for clinical and non-clinical purposes, leading to rise in concern about the diet's impact on following generations. The KD is known to have a neurological effect, suggesting that exposure to it during prenatal brain development may alter neuro-anatomy. Studies have also indicated that the KD has an anti-depressant effect on the consumer. However, it is unclear whether any neuro-anatomical and/or behavioral changes would occur in the offspring and persist into adulthood., Methods: To fill this knowledge gap we assessed the brain morphology and behavior of 8-week-old young-adult CD-1 mice, who were exposed to the KD in utero, and were fed only a standard-diet (SD) in postnatal life. Standardized neuro-behavior tests included the Open-Field, Forced-Swim, and Exercise Wheel tests, and were followed by post-mortem Magnetic Resonance Imaging (MRI) to assess brain anatomy., Results: The adult KD offspring exhibit reduced susceptibility to anxiety and depression, and elevated physical activity level when compared with controls exposed to the SD both in utero and postnatally. Many neuro-anatomical differences exist between the KD offspring and controls, including, for example, a cerebellar volumetric enlargement by 4.8%, a hypothalamic reduction by 1.39%, and a corpus callosum reduction by 4.77%, as computed relative to total brain volume., Conclusions: These results suggest that prenatal exposure to the KD programs the offspring neuro-anatomy and influences their behavior in adulthood.