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Abstract Introduction Melanoma, a deadly form of skin cancer, has witnessed a notable increase in incidence over the past decades. Despite advancements in treatment, it remains a significant cause of cancer mortality. Understanding demographic trends and variations in melanoma mortality is crucial for addressing disparities and implementing effective interventions. Methods Using the Centers for Disease Control Wide Ranging Online Data for Epidemiologic Research (CDC WONDER) database, we analyzed melanoma mortality data in the United States from 1999 to 2020. Data were stratified by demographic and regional variables, and age-adjusted mortality rates were calculated. Descriptive analysis was performed and Joinpoint regression analysis was employed to identify temporal trends. Results Between 1999 and 2020, there were 184,416 melanoma-related deaths in the United States Overall, the age-adjusted mortality rate declined from 2.7 to 2.0 per 100,000 people at a rate of -1.3% annually, with significant variations across demographic groups and regions. Men, non-Hispanic White individuals, and those aged > 65 experienced higher mortality rates. Non-Hispanic White individuals noted the steepest decrease in AAMR after 2013 at a rate of -6.1% annually. Disparities were seen by geographic density, with rural populations exhibiting higher mortality compared to their urban and suburban counterparts. Conclusion The study highlights a significant reduction in melanoma mortality in the U.S. since 2013, potentially attributed to advancements in diagnostic techniques such as dermoscopy and the introduction of immune checkpoint inhibitors. Disparities persist, particularly among rural populations. Targeted interventions focusing on increased screening and education are warranted to further mitigate melanoma mortality and address demographic disparities.

Abstract Targeting the estrogen receptor alpha (ERα) pathway is validated in the clinic as an effective means to treat ER+ breast cancers. Here we present the development of a VHL-targeting and orally bioavailable proteolysis-targeting chimera (PROTAC) degrader of ERα. In vitro studies with this PROTAC demonstrate excellent ERα degradation and ER antagonism in ER+ breast cancer cell lines. However, upon dosing the compound in vivo we observe an in vitro-in vivo disconnect. ERα degradation is lower in vivo than expected based on the in vitro data. Investigation into potential causes for the reduced maximal degradation reveals that metabolic instability of the PROTAC linker generates metabolites that compete for binding to ERα with the full PROTAC, limiting degradation. This observation highlights the requirement for metabolically stable PROTACs to ensure maximal efficacy and thus optimisation of the linker should be a key consideration when designing PROTACs.

OBJECTIVES Programmatic assessment approaches can be extended to the design of allied health professions training, to enhance the learning of trainees. The Australasian College of Physical Scientists and Engineers in Medicine worked with assessment specialists at the Australian Council for Educational Research and Amplexa Consulting, to revise their medical physics and radiopharmaceutical science training programs. One of the central aims of the revisions was to produce a training program that provides standardized training support to their registrars throughout the 3 years, better supporting their registrars to successfully complete the program in the time frame through providing timely and constructive feedback on the registrar's progression. METHODS We used the principles of programmatic assessment to revise the assessment methods and progression decisions in the three training programs. RESULTS We revised the 3-year training programs for diagnostic imaging medical physics, radiation oncology medical physics and radiopharmaceutical science in Australia and New Zealand, incorporating clear stages of training and associated progression points. CONCLUSIONS We discuss the advantages and difficulties that have arisen with this implementation. We found 5 key elements necessary for implementing programmatic assessment in these specialized contexts: embracing blurred boundaries between assessment of and for learning, adapting the approach to each specialized context, change management, engaging subject matter experts, and clear communication to registrars/trainees.

Abstract This paper presents a data processing pipeline designed to extract information from the hyperspectral signature of unknown space objects. The methodology proposed in this paper determines the material composition of space objects from single pixel images. Two techniques are used for material identification and classification: one based on machine learning and the other based on a least square match with a library of known spectra. From this information, a supervised machine learning algorithm is used to classify the object into one of several categories based on the detection of materials on the object. The behaviour of the material classification methods is investigated under non-ideal circumstances, to determine the effect of weathered materials, and the behaviour when the training library is missing a material that is present in the object being observed. Finally the paper will present some preliminary results on the identification and classification of space objects.

Abstract Background Despite substantial illness burden and healthcare utilization conferred by pain from vaso-occlusive episodes (VOE) in children with sickle cell disease (SCD), disease-modifying therapies to effectively treat SCD-VOE are lacking. The aim of the Sickle Cell Disease Treatment with Arginine Therapy (STArT) Trial is to provide definitive evidence regarding the efficacy of intravenous arginine as a treatment for acute SCD-VOE among children, adolescents, and young adults. Methods STArT is a double-blind, placebo-controlled, randomized, phase 3, multicenter trial of intravenous arginine therapy in 360 children, adolescents, and young adults who present with SCD-VOE. The STArT Trial is being conducted at 10 sites in the USA through the Pediatric Emergency Care Applied Research Network (PECARN). Enrollment began in 2021 and will continue for 5 years. Within 12 h of receiving their first dose of intravenous opioids, enrolled participants are randomized 1:1 to receive either (1) a one-time loading dose of L-arginine (200 mg/kg with a maximum of 20 g) administered intravenously followed by a standard dose of 100 mg/kg (maximum 10 g) three times a day or (2) a one-time placebo loading dose of normal saline followed by normal saline three times per day at equivalent volumes and duration as the study drug. Participants, research staff, and investigators are blinded to the participant’s randomization. All clinical care is provided in accordance with the institution-specific standard of care for SCD-VOE based on the 2014 National Heart, Lung, and Blood Institute guidelines. The primary outcome is time to SCD-VOE pain crisis resolution, defined as the time (in hours) from study drug delivery to the last dose of parenteral opioid delivery. Secondary outcomes include total parental opioid use and patient-reported outcomes. In addition, the trial will characterize alterations in the arginine metabolome and mitochondrial function in children with SCD-VOE. Discussion Building on the foundation of established relationships between emergency medicine providers and hematologists in a multicenter research network to ensure adequate participant accrual, the STArT Trial will provide definitive information about the efficacy of intravenous arginine for the treatment of SCD-VOE for children. Trial registration The STArT Trial was registered in ClinicalTrials.gov on April 9, 2021, and enrollment began on June 21, 2021 (NCT04839354).

BackgroundVirtual reality (VR) use in brain injury rehabilitation is emerging. Recommendations for VR development in this field encourage end user engagement to determine the benefits and challenges of VR use; however, existing literature on this topic is limited. Data from social networking sites such as Twitter may further inform development and clinical practice related to the use of VR in brain injury rehabilitation. ObjectiveThis study collected and analyzed VR-related tweets to (1) explore the VR tweeting community to determine topics of conversation and network connections, (2) understand user opinions and experiences of VR, and (3) identify tweets related to VR use in health care and brain injury rehabilitation. MethodsPublicly available tweets containing the hashtags #virtualreality and #VR were collected up to twice weekly during a 6-week period from July 2020 to August 2020 using NCapture (QSR International). The included tweets were analyzed using mixed methods. All tweets were coded using inductive content analysis. Relevant tweets (ie, coded as “VR in health care” or “talking about VR”) were further analyzed using Dann’s content coding. The biographies of users who sent relevant tweets were examined descriptively. Tweet data networks were visualized using Gephi computational analysis. ResultsA total of 260,715 tweets were collected, and 70,051 (26.87%) were analyzed following eligibility screening. The sample comprised 33.68% (23,596/70,051) original tweets and 66.32% (46,455/70,051) retweets. Content analysis generated 10 main categories of original tweets related to VR (ie, advertising and promotion, VR content, talking about VR, VR news, general technology, VR industry, VR live streams, VR in health care, VR events, and VR community). Approximately 4.48% (1056/23,596) of original tweets were related to VR use in health care, whereas 0.19% (45/23,596) referred to VR in brain injury rehabilitation. In total, 14.86% (3506/23,596) of original tweets featured commentary on user opinions and experiences of VR applications, equipment, and software. The VR tweeting community comprised a large network of 26,001 unique Twitter users. Users that posted tweets related to “VR in health care” (2124/26,001, 8.17%) did not form an interconnected VR network, whereas many users “talking about VR” (3752/26,001, 14.43%) were connected within a central network. ConclusionsThis study provides valuable data on community-based experiences and opinions related to VR. Tweets showcased various VR applications, including in health care, and identified important user-based considerations that can be used to inform VR use in brain injury rehabilitation (eg, technical design, accessibility, and VR sickness). Limited discussions and small user networks related to VR in brain injury rehabilitation reflect the paucity of literature on this topic and the potential underuse of this technology. These findings emphasize that further research is required to understand the specific needs and perspectives of people with brain injuries and clinicians regarding VR use in rehabilitation.

Objective: Despite recognition that coronavirus disease 2019 (COVID-19) pandemic created an unprecedented impact on global mental health, information on the psychological health among trauma survivors during the COVID-19 pandemic is rare. We sought to examine psychological outcomes among individuals with preexisting traumatic experiences during COVID-19. Methods: We sampled 1 242 adults in the mid-Atlantic region of the United States under a state-issued Phase 1 stay-at-home mandate to examine associations between pre-pandemic trauma exposure as measured by the Brief Trauma Questionnaire (BTQ) and anxiety and depression, as measured by the Patient Reported Outcome Scale Anxiety and Depression (PROMIS-A and PROMIS-D). Results: Pre-pandemic trauma exposure among the sample was reported, with 281 (22.6%) participants identifying as experiencing one trauma, 209 (16.8%) reporting two, and 468 (37.7%) reporting three or more. As reported experiences of trauma increased, so did participant anxiety and depressive symptomatology. One-way Analysis of Variance indicated that reported trauma was significantly positively correlated with anxiety (P < 0.01) and depressive symptomatology (P < 0.01). Conclusion: Findings highlight the immense psychological toll of the COVID-19 pandemic, specifically with individuals who were previously exposed to trauma. Public health officials can encourage physicians, employers, and universities to screen patients, employees, and students to assess previous trauma, psychological functioning, and risk factors. Collaboration between physicians and mental health providers including psychiatrists, psychologists, counselors, and social workers to provide evidence informed rapid coordination of care can better meet the global mental health crisis that is arising as a result of this unprecedented global trauma.

Case: A 29-year-old male jumped from the 6th floor of a building, sustaining multiple injuries, including comminuted fracture-dislocations of the talus and calcaneus in both feet, tibial plateau, vertebral and pelvic fractures, with MESS scores of 9 bilaterally. A multi-disciplinary team of orthopedics and podiatry performed a 1-stage modified midfoot-hindfoot-ankle fusion to salvage both feet, at a level 2 trauma center. At 3-year follow up, the patient ambulated with assistance of crutches and regular shoes. Conclusion: This polytrauma patient underwent lower extremity salvage with a 1-stage modified bilateral midfoot-hindfoot-ankle fusion and was ambulating with regular shoes at 3-year follow-up.

Antibody-based assays are commonly used in clinical laboratories for analyzing plasma, serum and other samples for particular protein markers. Although such assays have been traditionally based on antibodies raised in mammals (e.g., mice, rabbits, goats), there are several advantages of using avian antibodies (IgY) raised in chickens, including production volumes, costs, and ethical/animal welfare considerations. A further disadvantage of using mammalian IgG in such assays is the potential for agglutination when exposed to rheumatoid factor (RF) in serum. However, when used in the free form the immune complexes formed with avian antibodies have been reported to have less ability than those formed with mammalian antibodies to cause the light scatter which are used for instrument measurement. In addition, when the amount of antigen exceeds the maximum precipitating point in relation to the amount of antibody, there is a rapid decline in the absorbance values of the immune complexes (antigen excess) when IgY is used. However, when avian antibodies are conjugated to a substrate and used in particle enhanced turbidimetric assays (PETIA), these problems are avoided. Here we investigated three clinical assays using chicken antibodies, one using free (unbound) IgY and two with IgY-based PETIA. The IgY PETIA demonstrated a strong scatter response, even at high antigen concentrations in contrast to the steep decline seen with free IgY antibodies. IgY PETIA reagents can provide test results with low coefficient of variation (

Abstract Background Despite having the highest prevalence of sickle cell disease (SCD) in the world, no country in Sub-Saharan Africa has a universal screening program for the disease. We sought to capture the diagnosis patterns of SCD (age at SCD diagnosis, method of SCD diagnosis, and age of first pain crisis) in Accra, Ghana. Methods We administered an in-person, voluntary survey to parents of offspring with SCD between 2009 and 2013 in Accra as a part of a larger study and conducted a secondary data analysis to determine diagnosis patterns. This was conducted at a single site: a large academic medical center in the region. Univariate analyses were performed on diagnosis patterns; bivariate analyses were conducted to determine whether patterns differed by participant’s age (children: those = 18 years old whose parents completed a survey about them), or their disease severity based on SCD genotype. Pearson’s chi-squared were calculated. Results Data was collected on 354 unique participants from parents. Few were diagnosed via SCD testing in the newborn period. Only 44% were diagnosed with SCD by age four; 46% had experienced a pain crisis by the same age. Most (66%) were diagnosed during pain crisis, either in acute (49%) or primary care (17%) settings. Children were diagnosed with SCD at an earlier age (74% by four years old); among the adults, parents reflected that 30% were diagnosed by four years old (p

Understanding the extent to which caregivers perceive active shooter lockdown drills in K-12 schools as physically and emotionally safe for their children is pertinent, yet little empirical evidence exists. Negative parental perceptions of drills can lead to decreased student participation and compliance and amplify public concerns associated with school safety. This article introduces the Lockdown Impact Scale for Caregivers (LIS-C), a novel instrument developed to assess caregiver perceptions of K-12 school lockdown drills. Utilizing a national sample of 999 caregivers, this study validates the LIS-C through exploratory and confirmatory factor analyses, revealing a three-dimensional construct that includes perceived impact, school safety, and expressed concern. The development and validation of the LIS-C provide school-based mental health professionals with a psychometrically sound tool to address caregiver concerns, paving the way for a more informed and intentional implementation of lockdown drills. This research underscores the pertinence of examining caregiver perceptions to foster a safer and more supportive school environment.

BackgroundBehavioral representations obtained from mobile sensing data can be helpful for the prediction of an oncoming psychotic relapse in patients with schizophrenia and the delivery of timely interventions to mitigate such relapse. ObjectiveIn this study, we aim to develop clustering models to obtain behavioral representations from continuous multimodal mobile sensing data for relapse prediction tasks. The identified clusters can represent different routine behavioral trends related to daily living of patients and atypical behavioral trends associated with impending relapse. MethodsWe used the mobile sensing data obtained from the CrossCheck project for our analysis. Continuous data from six different mobile sensing-based modalities (ambient light, sound, conversation, acceleration, etc) obtained from 63 patients with schizophrenia, each monitored for up to a year, were used for the clustering models and relapse prediction evaluation. Two clustering models, Gaussian mixture model (GMM) and partition around medoids (PAM), were used to obtain behavioral representations from the mobile sensing data. These models have different notions of similarity between behaviors as represented by the mobile sensing data, and thus, provide different behavioral characterizations. The features obtained from the clustering models were used to train and evaluate a personalized relapse prediction model using balanced random forest. The personalization was performed by identifying optimal features for a given patient based on a personalization subset consisting of other patients of similar age. ResultsThe clusters identified using the GMM and PAM models were found to represent different behavioral patterns (such as clusters representing sedentary days, active days but with low communication, etc). Although GMM-based models better characterized routine behaviors by discovering dense clusters with low cluster spread, some other identified clusters had a larger cluster spread, likely indicating heterogeneous behavioral characterizations. On the other hand, PAM model-based clusters had lower variability of cluster spread, indicating more homogeneous behavioral characterization in the obtained clusters. Significant changes near the relapse periods were observed in the obtained behavioral representation features from the clustering models. The clustering model-based features, together with other features characterizing the mobile sensing data, resulted in an F2 score of 0.23 for the relapse prediction task in a leave-one-patient-out evaluation setting. The obtained F2 score was significantly higher than that of a random classification baseline with an average F2 score of 0.042. ConclusionsMobile sensing can capture behavioral trends using different sensing modalities. Clustering of the daily mobile sensing data may help discover routine and atypical behavioral trends. In this study, we used GMM-based and PAM-based cluster models to obtain behavioral trends in patients with schizophrenia. The features derived from the cluster models were found to be predictive for detecting an oncoming psychotic relapse. Such relapse prediction models can be helpful in enabling timely interventions.

Abstract The fourteenth annual ASCAT conference was held 21–23 October 2019. The theme of the conference was ‘Sickle Cell and Thalassaemia disorders new treatment horizon; while ensuring patient safety and delivering excellence in routine patient care.’ Over the three-day conference, topics on current and novel models of care, advances in bone marrow transplant and gene therapy, as well as the psychosocial aspects of mind, body and health related quality of life were discussed. In addition, blood transfusion, apheresis, iron chelation therapy and acute haemolytic complications were presented. Quality standards in the diagnosis and treatment of sickle cell and thalassaemia were reviewed. Experts from Europe, the United Kingdom, the Middle East, the United States and Africa reported up-to-date scientific data, guides to comprehensive care, and current research into developing cures and advancing current therapy were described. In addition, oral and poster presentations on novel research from all over the world were shown during the conference.

Abstract Increased stability in one’s daily routine is associated with well-being in the general population and often a goal of behavioral interventions for people with serious mental illnesses like schizophrenia. Assessing behavioral stability has been limited in clinical research by the use of retrospective scales, which are susceptible to reporting biases and memory inaccuracies. Mobile passive sensors, which are less susceptible to these sources of error, have emerged as tools to assess behavioral patterns in a range of populations. The present study developed and examined a metric of behavioral stability from data generated by a passive sensing system carried by 61 individuals with schizophrenia for one year. This metric—the Stability Index—appeared orthogonal from existing measures drawn from passive sensors and matched the predictive performance of state-of-the-art features. Specifically, greater stability in social activity (e.g., calls and messages) were associated with lower symptoms, and greater stability in physical activity (e.g., being still) appeared associated with elevated symptoms. This study provides additional support for the predictive value of individualized over population-level data in psychiatric populations. The Stability Index offers also a promising tool for generating insights about the impact of behavioral stability in schizophrenia-spectrum disorders.

The structural properties of cobalt phosphides were investigated at high pressures and temperatures to better understand the behavior of metal-rich phosphides in Earth and planetary interiors. Using single-crystal X-ray diffraction synchrotron data and a laser-heated diamond anvil cell, we discovered a new high pressure–temperature (HP–HT) cobalt phosphide, Co12P7, dodecacobalt heptaphosphide, synthesized at 27 GPa and 1740 K, and at 48 GPa and 1790 K. Co12P7 adopts a structure initially proposed for Cr12P7 (space-group type P\overline{6}, Z =1), consisting of chains of edge-sharing CoP5 square pyramids and chains of corner-sharing CoP4 tetrahedra. This arrangement leaves space for trigonal–prismatic channels running parallel to the c axis. Coupled disordering of metal and phosphorus atoms has been observed in this structure for related M12P7 (M = Cr, V) compounds, but all Co and P sites are ordered in Co12P7. All atomic sites in this crystal structure are situated on special positions. Upon decompression to ambient conditions, peak broadening and loss of reflections at high angles was observed, suggesting phase instability.

BackgroundPeople with serious mental illness (SMI) have significant unmet mental health needs. Development and testing of digital interventions that can alleviate the suffering of people with SMI is a public health priority. ObjectiveThe aim of this study is to conduct a fully remote randomized waitlist-controlled trial of CORE, a smartphone intervention that comprises daily exercises designed to promote reassessment of dysfunctional beliefs in multiple domains. MethodsIndividuals were recruited via the web using Google and Facebook advertisements. Enrolled participants were randomized into either active intervention or waitlist control groups. Participants completed the Beck Depression Inventory-Second Edition (BDI-II), Generalized Anxiety Disorder-7 (GAD-7), Hamilton Program for Schizophrenia Voices, Green Paranoid Thought Scale, Recovery Assessment Scale (RAS), Rosenberg Self-Esteem Scale (RSES), Friendship Scale, and Sheehan Disability Scale (SDS) at baseline (T1), 30-day (T2), and 60-day (T3) assessment points. Participants in the active group used CORE from T1 to T2, and participants in the waitlist group used CORE from T2 to T3. Both groups completed usability and accessibility measures after they concluded their intervention periods. ResultsOverall, 315 individuals from 45 states participated in this study. The sample comprised individuals with self-reported bipolar disorder (111/315, 35.2%), major depressive disorder (136/315, 43.2%), and schizophrenia or schizoaffective disorder (68/315, 21.6%) who displayed moderate to severe symptoms and disability levels at baseline. Participants rated CORE as highly usable and acceptable. Intent-to-treat analyses showed significant treatment×time interactions for the BDI-II (F1,313=13.38; P

OBJECTIVES:. To compare the performance of Sequential Organ Failure Assessment, systemic inflammatory response syndrome, Red Flag Sepsis, and National Institute of Clinical Excellence sepsis risk stratification tools in the identification of patients at greatest risk of mortality from sepsis in nonintensive care environments. DESIGN:. Secondary analysis of three annual 24-hour point-prevalence study periods. SETTING:. The general wards and emergency departments of 14 acute hospitals across Wales. Studies were conducted on the third Wednesday of October in 2017, 2018, and 2019. PATIENTS:. We screened all patients presenting to the emergency department and on the general wards. MEASUREMENTS AND MAIN RESULTS:. We recruited 1,271 patients, of which 724 (56.9%) had systemic inflammatory response syndrome greater than or equal to 2, 679 (53.4%) had Sequential Organ Failure Assessment greater than or equal to 2, and 977 (76.9%) had Red Flag Sepsis. When stratified according to National Institute of Clinical Excellence guidelines, 450 patients (35.4%) were in the “High risk” category in comparison with 665 (52.3%) in “Moderate to High risk” and 156 (12.3%) in “Low risk” category. In a planned sensitivity analysis, we found that none of the tools accurately predicted mortality at 90 days, and Sequential Organ Failure Assessment and National Institute of Clinical Excellence tools showed only moderate discriminatory power for mortality at 7 and 14 days. Furthermore, we could not find any significant correlation with any of the tools at any of the mortality time points. CONCLUSIONS:. Our data suggest that the sepsis risk stratification tools currently utilized in emergency departments and on the general wards do not predict mortality adequately. This is illustrated by the disparity in mortality risk of the populations captured by each instrument, as well as the weak concordance between them. We propose that future studies on the development of sepsis identification tools should focus on identifying predicator values of both the short- and long-term outcomes of sepsis.

BackgroundThe wide use of mobile health apps has created new possibilities in social anxiety education and treatment. However, the content and quality of social anxiety apps have been quite unclear, which makes it difficult for people to choose appropriate apps to use on smartphones and tablets. ObjectiveThis study aims to identify the psychoeducational social anxiety apps in the two most popular Australian app stores, report the descriptive and technical information provided in apps exclusively for social anxiety, evaluate app quality, and identify whether any apps would be appropriate for people with social anxiety or others who know someone with social anxiety. MethodsThis systematic stepwise app search was guided by the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) standards and entailed searching for, identifying, and selecting apps in the Australian Apple App and Google Play Stores; downloading, using, and reviewing the identified apps; reporting technical and descriptive information in the app stores, an online app warehouse, and individual apps; evaluating app quality; and deciding whether to recommend the use of the apps. ResultsIn the app stores, 1043 apps were identified that contained the keywords social anxiety, social phobia, or shyness in their names or descriptions. Of these, 1.15% (12/1043) were evaluated (3 iOS apps and 9 Android apps). At the time of evaluation, the apps were compatible with smartphones and tablet devices; 9 were free to download from the app stores, whereas 3 were priced between US $2.95 (Aus $3.99) and US $3.69 (Aus $5.00). Among the evaluated apps, 3 were intended for treatment purposes, 3 provided supportive resources, 1 was intended for self-assessment, and the remaining 5 were designed for multiple purposes. At the time of downloading, app store ratings were available for 5 apps. The overall app quality was acceptable according to the Mobile App Rating Scale (MARS). On the basis of the MARS app quality rating subscale (sections A-D), the apps functioned well in performance, ease of use, navigation, and gestural design. However, app quality was less favorable when rated using the MARS app subjective quality subscale (section E). ConclusionsThe psychoeducational social anxiety apps evaluated in our study may benefit people with social anxiety, health professionals, and other community members. However, given that none of the apps appeared to contain empirical information or were shown to clinically reduce social anxiety (or aid in managing social anxiety), we cannot recommend their use. App accessibility could be improved by developing apps that are free and available for a wider range of operating systems, both between and within countries and regions. Information communication and technology professionals should collaborate with academics, mental health clinicians, and end users (ie, co-design) to develop current, evidence-based apps.

BackgroundAlthough effective mental health treatments exist, the ability to match individuals to optimal treatments is poor, and timely assessment of response is difficult. One reason for these challenges is the lack of objective measurement of psychiatric symptoms. Sensors and active tasks recorded by smartphones provide a low-burden, low-cost, and scalable way to capture real-world data from patients that could augment clinical decision-making and move the field of mental health closer to measurement-based care. ObjectiveThis study tests the feasibility of a fully remote study on individuals with self-reported depression using an Android-based smartphone app to collect subjective and objective measures associated with depression severity. The goals of this pilot study are to develop an engaging user interface for high task adherence through user-centered design; test the quality of collected data from passive sensors; start building clinically relevant behavioral measures (features) from passive sensors and active inputs; and preliminarily explore connections between these features and depression severity. MethodsA total of 600 participants were asked to download the study app to join this fully remote, observational 12-week study. The app passively collected 20 sensor data streams (eg, ambient audio level, location, and inertial measurement units), and participants were asked to complete daily survey tasks, weekly voice diaries, and the clinically validated Patient Health Questionnaire (PHQ-9) self-survey. Pairwise correlations between derived behavioral features (eg, weekly minutes spent at home) and PHQ-9 were computed. Using these behavioral features, we also constructed an elastic net penalized multivariate logistic regression model predicting depressed versus nondepressed PHQ-9 scores (ie, dichotomized PHQ-9). ResultsA total of 415 individuals logged into the app. Over the course of the 12-week study, these participants completed 83.35% (4151/4980) of the PHQ-9s. Applying data sufficiency rules for minimally necessary daily and weekly data resulted in 3779 participant-weeks of data across 384 participants. Using a subset of 34 behavioral features, we found that 11 features showed a significant (P

BackgroundVirtual reality (VR) is increasingly being used for the assessment and treatment of impairments arising from acquired brain injuries (ABIs) due to perceived benefits over traditional methods. However, no tailored options exist for the design and implementation of VR for ABI rehabilitation and, more specifically, traumatic brain injury (TBI) rehabilitation. In addition, the evidence base lacks systematic reviews of immersive VR use for TBI rehabilitation. Recommendations for this population are important because of the many complex and diverse impairments that individuals can experience. ObjectiveThis study aims to conduct a two-part systematic review to identify and synthesize existing recommendations for designing and implementing therapeutic VR for ABI rehabilitation, including TBI, and to identify current evidence for using immersive VR for TBI assessment and treatment and to map the degree to which this literature includes recommendations for VR design and implementation. MethodsThis review was guided by PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). A comprehensive search of 11 databases and gray literature was conducted in August 2019 and repeated in June 2020. Studies were included if they met relevant search terms, were peer-reviewed, were written in English, and were published between 2009 and 2020. Studies were reviewed to determine the level of evidence and methodological quality. For the first part, qualitative data were synthesized and categorized via meta-synthesis. For the second part, findings were analyzed and synthesized descriptively owing to the heterogeneity of data extracted from the included studies. ResultsIn the first part, a total of 14 papers met the inclusion criteria. Recommendations for VR design and implementation were not specific to TBI but rather to stroke or ABI rehabilitation more broadly. The synthesis and analysis of data resulted in three key phases and nine categories of recommendations for designing and implementing VR for ABI rehabilitation. In the second part, 5 studies met the inclusion criteria. A total of 2 studies reported on VR for assessment and three for treatment. Studies were varied in terms of therapeutic targets, VR tasks, and outcome measures. VR was used to assess or treat impairments in cognition, balance, and anxiety, with positive outcomes. However, the levels of evidence, methodological quality, and inclusion of recommendations for VR design and implementation were poor. ConclusionsThere is limited research on the use of immersive VR for TBI rehabilitation. Few studies have been conducted, and there is limited inclusion of recommendations for therapeutic VR design and implementation. Future research in ABI rehabilitation should consider a stepwise approach to VR development, from early co-design studies with end users to larger controlled trials. A list of recommendations is offered to provide guidance and a more consistent model to advance clinical research in this area.

BackgroundGiven the high level of interest and increasing familiarity with virtual reality among adolescents, there is great potential to use virtual reality to address adolescents’ unique health care delivery needs while in hospital. While there have been reviews on the use of virtual reality for specific health conditions and procedures, none to date have reviewed the full scope of virtual reality hospital interventions for adolescents who are often combined with children as a homogenous group, despite the fact that adolescents experience virtual environments different from children. ObjectiveThe aim of this review was to systematically identify available evidence regarding the use of virtual reality interventions for adolescent patients in hospital settings to evaluate effectiveness, suitability, and safety and identify opportunities for future research. MethodsPubMed, PsycINFO, Medline, and Scopus databases were searched using keywords and phrases. Retrieved abstracts (n=1525) were double screened, yielding 276 articles for full-text screening. Of these, 8 articles met inclusion criteria. Data were extracted to a standardized coding sheet, and a narrative synthesis was performed due to the heterogeneity of the studies. ResultsFour RCTs and 4 single-case reports were identified for inclusion, all of which aimed to reduce pain or anxiety. The scenarios targeted were burn pain, venipuncture, chemotherapy, preoperative anxiety, and palliative care. Three out of 4 RCTs found significant reductions in pain or anxiety outcomes measures when using virtual reality compared to standard care or other distraction techniques; however, only 1 study combined self-reported experiences of pain or anxiety with any physiological measures. Single-case reports relied primarily upon qualitative feedback, with patients reporting reduced pain or anxiety and a preference for virtual reality to no virtual reality. ConclusionsVirtual reality can provide a safe and engaging way to reduce pain and anxiety in adolescents while in hospital, particularly when virtual reality software is highly immersive and specifically designed for therapeutic purposes. As VR becomes more accessible and affordable for use in hospitals, larger and more diverse studies that capitalize on adolescents’ interest in and aptitude for virtual reality, and on the full range of capabilities of this emerging technology, are needed to build on these promising results. Trial RegistrationPROSPERO International Prospective Register of Systematic Reviews CRD42020198760; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020198760

On-farm euthanasia of poultry, including turkeys, may not be possible for most people as birds gain weight; thus alternative mechanical methods have been developed. Our objective was to compare mechanical cervical dislocation with the Koechner Euthanizing Device (KED), captive bolt euthanasia with the Turkey Euthanasia Device (TED), head-only CO2 euthanasia (CO2), and electric euthanasia as potential humane methods for euthanizing individual, heavy turkeys. We assessed their impact on loss of brain stem reflexes, acute distress (corticosterone, CORT), kill success, torn skin, and blood loss. Turkeys (n = 174) were euthanized on 3 sampling days, while birds were restrained using a mobile bird euthanasia apparatus. Brain stem reflexes recorded were the cessation and return of induced nictitating membrane reflex (loss of consciousness and brain stem dysfunction), mouth gaping reflex (brain stem dysfunction), and musculoskeletal movements (spinal cord dysfunction). Overall, KED resulted in more frequent (at 4 min: KED 7 of 14; electric 0 of 13; TED 0 of 11; CO2 2 of 14 birds on day 1) and longer durations of the induced nictitating reflex compared to the other methods (means of day 2 and 3: KED 233; electric 15; TED 15; CO2 15 s). The mouth gaping reflex endured the longest after KED euthanasia (means of day 2 and 3: KED 197; electric 15; TED 51; CO2 15 s). Musculoskeletal movements endured longest after KED euthanasia (means of day 2 and 3: KED 235; electric 15; TED 219; CO2 15 s). Returning reflexes were more frequent after KED and TED compared to CO2 and electric euthanasia, where it was absent. CO2, electric, and TED euthanasia showed comparable kill success (success: CO2 42 out of 43; electric 44 of 45; TED 42 of 44), with KED resulting in most unsuccessful kills (unsuccessful: 8 out of 42). CORT responses were inconsistent. Torn skin and blood loss occurred more frequently after KED and TED compared to CO2 and electric applications. Therefore, we conclude that, based on a comparison of these 4 methods, the most discernibly humane was electric euthanasia, which consistently resulted in quick loss of consciousness within 15 s, no returning reflexes, and no torn skin or blood loss.

Abstract Background Proteins of the ubiquitously expressed core proteome are quantitatively correlated across multiple eukaryotic species. In addition, it was found that many protein paralogues exhibit expression anticorrelation, suggesting that the total level of protein with a given functionality must be kept constant. Methods We performed Spearman’s rank correlation analyses of gene expression levels for the RAS GTPase subfamily and their regulatory GEF and GAP proteins across tissues and across individuals for each tissue. A large set of published data for normal tissues from a wide range of species, human cancer tissues and human cell lines was analysed. Results We show that although the multidomain regulatory proteins of Ras GTPases exhibit considerable tissue and individual gene expression variability, their total amounts are balanced in normal tissues. In a given tissue, the sum of activating (GEFs) and deactivating (GAPs) domains of Ras GTPases can vary considerably, but each person has balanced GEF and GAP levels. This balance is impaired in cell lines and in cancer tissues for some individuals. Conclusions Our results are relevant for critical considerations of knock out experiments, where functionally related homologs may compensate for the down regulation of a protein.

Thermal and mechanical processes alter the microstructure of materials, which determines their mechanical properties. This makes reliable microstructural analysis important to the design and manufacture of components. However, the analysis of complex microstructures, such as Ti6Al4V, is difficult and typically requires expert materials scientists to manually identify and measure microstructural features. This process is often slow, labour intensive and suffers from poor repeatability. This paper overcomes these challenges by proposing a new set of automated techniques for 2D microstructural analysis. Digital image processing algorithms are developed to isolate individual microstructural features, such as grains and alpha lath colonies. A segmentation of the image is produced, where regions represent grains and colonies, from which morphological features such as; grain size, volume fraction of globular alpha grains and alpha colony size can be measured. The proposed measurement techniques are shown to obtain similar results to existing manual methods while drastically improving speed and repeatability. The benefits of the proposed approach when measuring complex microstructures are demonstrated by comparing it with existing analysis software. Using a few parameter changes, the proposed techniques are effective on a variety of microstructure types and both SEM and optical microscopy images. Keywords: Microstructure analysis, Segmentation, Watershed algorithm, Titanium alloy

Abstract Progression of demyelinating diseases is caused by an imbalance of two opposing processes: persistent destruction of myelin and myelin repair by differentiating oligodendrocyte progenitor cells (OPCs). Repair that cannot keep pace with destruction results in progressive loss of myelin. Viral infections have long been suspected to be involved in these processes but their specific role remains elusive. Here we describe a novel mechanism by which HHV-6A, a member of the human herpesvirus family, may contribute to inadequate myelin repair after injury.

The brain-electrode interface is arguably one of the most important areas of study in neuroscience today. A stronger foundation in this topic will allow us to probe the architecture of the brain in unprecedented functional detail and augment our ability to intervene in disease states. Over many years, significant progress has been made in this field, but some obstacles have remained elusive—notably preventing glial encapsulation and electrode degradation. In this review, we discuss the tissue response to electrode implantation on acute and chronic timescales, the electrical changes that occur in electrode systems over time, and strategies that are being investigated in order to minimize the tissue response to implantation and maximize functional electrode longevity. We also highlight the current and future clinical applications and relevance of electrode technology.

Glecaprevir (an NS3/4A protease inhibitor) and pibrentasvir (an NS5A inhibitor) are potent and pangenotypic hepatitis C virus (HCV) direct-acting antivirals. This report describes the baseline polymorphisms and treatment-emergent substitutions in NS3 or NS5A detected in samples from HCV genotype 1-infected patients receiving 3-day monotherapy of glecaprevir or pibrentasvir, respectively. None of the NS3 polymorphisms detected in the 47 baseline samples collected prior to glecaprevir monotherapy conferred reduced susceptibility to glecaprevir. The NS3 A156T substitution, which conferred resistance to glecaprevir but had low replication efficiency, emerged in one genotype 1a-infected patient among the 35 patients with available post-baseline sequence data. Baseline NS5A polymorphisms were detected in 12 of 40 patients prior to pibrentasvir monotherapy; most polymorphisms were single-position NS5A amino acid substitutions that did not confer resistance to pibrentasvir. Among the 19 patients with available post-baseline NS5A sequence data, 3 had treatment-emergent NS5A substitutions during pibrentasvir monotherapy. All treatment-emergent NS5A substitutions were linked multiple-position, almost exclusively double-position, substitutions that conferred resistance to pibrentasvir. Replicons engineered with these double-position substitutions had low replication efficiency. In conclusion, resistance-conferring substitutions emerged in a small number of genotype 1-infected patients during glecaprevir or pibrentasvir monotherapy; unlike other NS5A inhibitors, pibrentasvir did not select single-position NS5A substitutions during monotherapy.

Abstracts for short works are not provided

Abstracts for short works are not provided

Abstracts for short works are not provided

Abstract Introduction Pediatric hematologists/oncologists frequently find that there is a lack of fundamental understanding of the genetic variability and clinical presentation of sickle cell disease. In addition, there are often barriers to care due to lack of smooth handoff from pediatrics to adult specialties. Moreover, there may be limited knowledge of quality-of-care pathways that reduce hospitalizations and improve quality. This case-based workshop illustrates the various complications of sickle cell anemia, with an emphasis on the presentation, workup, and treatment of these complications. It is ideal for third- or fourth-year medical students in both inpatient or outpatient pediatric rotations, as well as for residents and fellows who are primary caregivers for acutely ill patients. Methods Workshop materials include a PowerPoint presentation with a sickle cell overview, and eight cases. The session can be delivered in either 60 or 90 minutes, depending on number of cases selected, amount of time given to discussion, and level of learner. The ideal time frame is 90 minutes. If delivered in 60 minutes, we recommend presenting no more than five or six of the available cases. The workshop is designed to use active, rather than passive, learning styles. Therefore, the majority of activities involve participant discussion and interaction. Results Residents/fellows, hospitalists (medicine and pediatrics), and medical students found this workshop to be effective in all domains (e.g., content, presentation, clinical relevance). They reported that the workshop helped them gain a better understanding of the material and that having interactive discussions was particularly useful. Discussion This workshop has been requested annually as part of the fellows' crash course in pediatric hematology/oncology, as well as being part of the pediatric intern boot camp. Many of the clinical care guidelines presented in the workshop have been incorporated into our hospital guidelines in pediatrics as a means of improving the quality of care provided to patients with sickle cell disease.

A comparison of growth data (fish length) with latitude shows that southern juvenile mackerel attain a greater length than those originating from further north before growth ceases during their first winter. A similar significant relationship was found between the growth in the first year (derived from the otolith inner winter ring) and latitude for adult mackerel spawning between 44°N (Bay of Biscay) and 54°N (west of Ireland). These observations are consistent with spatial segregation of the spawning migration; the further north that the fish were hatched, the further north they will tend to spawn. No such relationship was found in mackerel spawning at more northerly latitudes, possibly as a consequence of increased spatial mixing in a more energetic regime with stronger currents. This study provides previously lacking support for spawning segregation behaviour among North East Atlantic mackerel--an important step towards understanding the migratory behaviour of mackerel and hence the spatiotemporal distribution dynamics around spawning time.

It has been suggested that observed spatial variation in mackerel fisheries, extending over several hundreds of kilometers, is reflective of climate-driven changes in mackerel migration patterns. Previous studies have been unable to clearly demonstrate this link. In this paper we demonstrate correlation between temperature and mackerel migration/distribution as proxied by mackerel catch data from both scientific bottom trawl surveys and commercial fisheries. We show that mackerel aggregate and migrate distances of up to 500 km along the continental shelf edge from mid-November to early March. The path of this migration coincides with the location of the relatively warm shelf edge current and, as a consequence of this affinity, mackerel are guided towards the main spawning area in the south. Using a simulated time series of temperature of the shelf edge current we show that variations in the timing of the migration are significantly correlated to temperature fluctuations within the current. The proposed proxies for mackerel distribution were found to be significantly correlated. However, the correlations were weak and only significant during periods without substantial legislative or technical developments. Substantial caution should therefore be exercised when using such data as proxies for mackerel distribution. Our results include a new temperature record for the shelf edge current obtained by embedding the available hydrographic observations within a statistical model needed to understand the migration through large parts of the life of adult mackerel and for the management of this major international fishery.

This article will focus on The Ascent of F6 (1936) and work back to Paid On Both Sides, as both plays explore the psychological malaise of the protagonist and the domineering influence of the mother to striking effect. These dramas find their central protagonists grappling with the malignant influence of mothers who compel the climactic acts of revenge through the neurotic anxiety they have engendered within their sons. The first act of vengeance examined is figurative and illusory as the mother of the Ransom brothers pits her neurotic sons against each other in an Oedipal battle for glory or favour in F6. The second, more formative, action to be examined is literal and physical, as the matriarchs of Paid's Nower and Shaw families demand that their remaining sons commit acts of murderous revenge for slain fathers and brothers. Both are undoubtedly responses to the psychic deprivation and distress caused by the mother characters and their divided affections for their sons. While much work remains to be conducted in gendered approaches to the study of these texts, this article will explore the significance of vengeance and matrilineal legacy in W.H. Auden's poetic drama and locate this theme within the context of his poetry from the late Twenties to the late Thirties. This study anticipates further discussion of the role of matriarchal figures and gender debates arising from post-war literature.

Background Bone changes are common in sickle cell disease, but the pathogenesis is not fully understood. Tartrate-resistant acid phosphatase (TRACP) type 5b is produced by bone-resorbing osteoclasts. In other forms of hemolytic anemia, increased iron stores are associated with osteoporosis. We hypothesized that transfusional iron overload would be associated with increased osteoclast activity in patients with sickle cell disease.Design and Methods We examined tartrate-resistant acid phosphatase 5b concentrations in patients with sickle cell disease and normal controls of similar age and sex distribution at steady state. Serum tartrate-resistant acid phosphatase 5b concentration was measured using an immunocapture enzyme assay and plasma concentrations of other cytokines were assayed using the Bio-Plex suspension array system. Tricuspid regurgitation velocity, an indirect measure of systolic pulmonary artery pressure, was determined by echocardiography.Results Tartrate-resistant acid phosphatase 5b concentrations were higher in 58 adults with sickle cell disease than in 22 controls (medians of 4.4 versus 2.4 U/L, respectively; P=0.0001). Among the patients with sickle cell disease, tartrate-resistant acid phosphatase 5b independently correlated with blood urea nitrogen (standardized beta=0.40, P=0.003), interleukin-8 (standardized beta=0.30, P=0.020), and chemokine C-C motif ligand 5 (standardized beta=−0.28, P=0.031) concentrations, but not with serum ferritin concentration. Frequent blood transfusions (>10 units in life time) were not associated with higher tartrate-resistant acid phosphatase 5b levels in multivariate analysis. There were strong correlations among tartrate-resistant acid phosphatase 5b, alkaline phosphatase and tricuspid regurgitation velocity (r>0.35, P

Background Vaccine development targeting the novel immunogenic Per ARNT Sim Domain containing 1 (PASD1) cancer testis antigen represents an attractive therapeutic approach for the significant number of patients with diffuse large B-cell lymphoma who are refractory to conventional treatment. Since CD4-positive T helper cells have crucial roles in promoting and maintaining immune responses to tumor antigens, the presence of a CD4-positive T-helper immune response to the PASD1 antigen in patients with diffuse large B-cell lymphoma was investigated in the current study.Design and Methods Thirty-one patients with diffuse large B-cell lymphoma (25 with de novo, five with transformed and one with T-cell-rich B-cell lymphoma) were studied. Five immunogenic PASD1 peptides predicted to bind to several major histocompatibiliy complex, class II DR beta 1 alleles were identified using web-based algorithms. Peripheral blood mononuclear cells from patients were used to investigate the immunogenicity of these DR beta 1-restricted peptides in vitro using both gamma-interferon release enzyme-linked immunospot and cytolytic assays.Results Two of the five PASD1 peptides, PASD1(6) and PASD1(7), were shown to be immunogenic in 14 out of 32 patients studied in a gamma-interferon release assay. CD4-positive T-helper cell lines from two patients raised against PASD1 peptides were able to lyse cell lines derived from hematologic malignancies expressing endogenous PASD1 protein.Conclusions This is the first report of a CD4-positive T-helper response to the PASD1 protein in patients with lymphoma. The immunogenic peptides described here represent valuable additional candidates for inclusion in a vaccine to treat patients with PASD1-positive diffuse large B-cell lymphoma whose disease is refractory to conventional therapies.

Abstract This resource represents how using multimedia artifacts in education is an engaging way to involve patients and health professionals in discussions of chronic disease, specifically sickle cell anemia and its potential impact on patients. These artifacts can be ideal for helping others understand perspectives on illness shared between and among patients as they seek role models and information on self-management of their condition. The goals of this case presentation are for learners to understand the multiple sides of patient care and how previous experiences influence patients' perceptions and behavior with their care. The use of multimedia, in this case, photographs and videos, can stimulate health care providers to consider the influence illness has on the everyday lives of their patients. Students have found these clips to be useful in stimulating their thinking about the patient's perspective. They also helped them understand the many faces of pain experiences. Finally, patients and adolescents in particular with sickle cell find the images powerful, allowing them a path forward as they enter adulthood, demonstrate role models and provide suggestions/insights on how to deal with sickle cell, chronic disease, and health professionals.

BACKGROUND:Pulmonary hypertension and left ventricular diastolic dysfunction are complications of sickle cell disease. Pulmonary hypertension is associated with hemolysis and hypoxia, but other unidentified factors are likely involved in pathogenesis as well. DESIGN AND METHODS:Plasma concentrations of three angiogenic markers (fibroblast growth factor, platelet derived growth factor-BB [PDGF-BB], vascular endothelial growth factor [VEGF]) and seven inflammatory markers implicated in pulmonary hypertension in other settings were determined by Bio-Plex suspension array in 237 children and adolescents with sickle cell disease at steady state and 43 controls. Tricuspid regurgitation velocity (which reflects systolic pulmonary artery pressure), mitral valve E/Edti ratio (which reflects left ventricular diastolic dysfunction), and a hemolytic component derived from four markers of hemolysis and hemoglobin oxygen saturation were also determined. RESULTS:Plasma concentrations of interleukin-8, interleukin-10 and VEGF were elevated in the patients with sickle cell disease compared to controls (P

Background Elevation of echocardiography-determined tricuspid regurgitant jet velocity predicts high systolic pulmonary artery pressure and early mortality in adults with sickle cell disease. The definition, prevalence and clinical correlates of elevated jet velocity have not been established in pediatric patients. The present study tested the hypotheses that elevated jet velocity affects 10% of pediatric patients, is associated with both hemolysis and hypoxia, and has clinical correlates with acute chest syndrome, stroke, transfusion requirement and abnormal 6-minute walk test results.Design and Methods A prospective multicenter study of 310 patients aged 3–20 years old with sickle cell disease under basal conditions and 54 matched controls was conducted. A hemolytic index was generated by principal component analysis of the levels of lactate dehydrogenase, aspartate aminotransferase and bilirubin and reticulocyte count.Results Elevated jet velocity (defined as ≥2.60 m/sec based on the mean±2 SD in controls) occurred in 32 patients (11.0%) including one child of 3 years old. After adjustment for hemoglobin concentration, systolic blood pressure and left ventricular diastolic function, a 2 SD increase in the hemolytic index was associated with a 4.5-fold increase in the odds of elevated jet velocity (p=0.009) and oxygen saturation ≤98% with a 3.2-fold increase (p=0.028). Two or more episodes of acute chest syndrome had occurred in 28% of children with elevated jet velocity compared to in 13% of other children (p=0.012), more than ten units of blood had been transfused in 39% versus 18% (p=0.017) and stroke had occurred in 19% versus 11% (p=0.2). The distance walked in 6-minute walk tests did not differ significantly, but oxygen saturation declined during the tests in 68% of children with elevated jet velocity compared to in 32% of other children (p=0.0002).Conclusions According to a pediatric-specific definition the prevalence of elevated jet velocity in this population of young patients with sickle cell disease was 11%. The study provides evidence for independent associations of elevated jet velocity with hemolysis and oxygen desaturation. Further investigations should address whether elevated jet velocity may indicate future complications and whether early intervention is beneficial.

Abstract Introduction Medical student clerkships are designed to provide students with an opportunity to develop a critical, problem-oriented approach to patient care. Given the time constraints of traditional medical student clerkships, it is not feasible during a short clinical rotation to expose students to all of the pathologic entities within a particular discipline. This is especially true at multiple, often distant clinical sites with varied patient populations. Methods To address this in Pediatrics, we created a series of web-supported case seminars to review a variety of common problems. The teaching cases for the core Pediatric Clerkship are based on the Council on Medical Student Education in Pediatrics Curriculum. Each case is organized to include case objectives, suggested references, a case presentation, and guiding questions. Students prepare for teaching sessions by reviewing the case's objectives, patient presentation, and guiding questions on-line. Seminar sessions use these cases for the review of the clinical approach to patients, organization of data, generation of a differential diagnosis, and management for a variety of pediatric conditions. Sessions are entirely small-group, interactive, and case-based. The curriculum is web-supported and uses multimedia resources to ensure that the cases are standardized and can be delivered efficiently across multiple and distant clinical sites. Results Their quality and presentation have been assessed using anonymous, written evaluations by each student. Responses to this method of teaching have been extremely positive. Students have reported that the teaching is of high caliber and that the topics are high yield. They were also impressed by both the format and the level of interactivity of the sessions. Discussion The cases have now been used as the primary teaching tool in the Pediatric Clerkship for four years. They are continually being refined to incorporate contemporary medical topics and further address LCME mandates.