Malignant Cerebral Edema following CT Myelogram Using Isovue-M 300 Intrathecal Nonionic Water-Soluble Contrast: A Case Report

Lumbar myelogram utilizing nonionic contrast is a commonly performed procedure to identify spinal pathology. Complication rates are low. Cerebral edema has been shown to occur following intrathecal injection of ionic contrast; however, no current literature has documented this complication relating to the ubiquitously used nonionic contrast medium. We report a case of a patient who developed malignant cerebral edema following a lumbar myelogram with Isovue-M 300 nonionic water-soluble intrathecal contrast. We believe this is the first reported case of cerebral edema resulting from the use of a nonionic contrast

The Effect of Simulation based Training on Medical Students’ Perceptions, Knowledge, and Skill at Baseline and 6 month Follow up

The principal goal of most simulation-based learning is enhanced clinical skill, with the desired outcome being skill retention and improved performance over time. While evide nce supports simulation based training at the clerkship, graduate, and post graduate level, the evidence supporting its long term benefit at the pre clerkship level is less well established. Using quantitative methods, this research assessed the effect of skill based clinical simulation training on all second year medical students’ enrolled in two simulation courses at the University of Michigan during the 2013 2014 academic year (n=39). Pre course, post course, and 6 month follow up questionnaires were adm inistered, and analysis of variance was used to assess change in students\u27 knowledge, self reported confidence, and competency. Students in Course 1 (n=12) completed a post course and 6 month follow up skills test, and results were compared to faculty cont rols. Differences between groups were assessed using t tests. Odds ratios were calculated.Knowledge improved from pre course to post course; the gain was retained at follow up only for students in Course 1. Students perceived the courses as improving know ledge, confidence, and skill, though scores were significantly lower at follow up. For the subset of students participating in the skills test, the time to complete central line and thoracentesis at follow up did not significantly differ from post course; however, an increase was observed for lumbar puncture. Compared to faculty, students took significantly more time to complete the central line procedure. Outcomes for needle redirects and correct sequencing were mixed, with most procedures showing no signi ficant difference between measurement periods. Assessing students’ skill and the maintenance of that skill over time using objective and empirically derived measures can be challenging. The evaluation strategy described herein could be adapted to many proc edures commonly practiced within primary care and other medical specialties. Brief exposure to clinical simulation early in medical training and prior to clerkships can have a positive and lasting effecton medical students’ knowledge, confidence, and skil l for selected procedures

Sleep to Reduce Incident Depression Effectively (STRIDE): study protocol for a randomized controlled trial comparing stepped-care cognitive-behavioral therapy for insomnia versus sleep education control to prevent major depression

BACKGROUND: Prevention of major depressive disorder (MDD) is a public health priority. Strategies targeting individuals at elevated risk for MDD may guide effective preventive care. Insomnia is a reliable precursor to depression, preceding half of all incident and relapse cases. Thus, insomnia may serve as a useful entry point for preventing MDD. Cognitive-behavioral therapy for insomnia (CBT-I) is recommended as the first-line treatment for insomnia, but widespread implementation is limited by a shortage of trained specialists. Innovative stepped-care approaches rooted in primary care can increase access to CBT-I and reduce rates of MDD. METHODS/DESIGN: We propose a large-scale stepped-care clinical trial in the primary care setting that utilizes a sequential, multiple assignment, randomized trial (SMART) design to determine the effectiveness of dCBT-I alone and in combination with clinician-led CBT-I for insomnia and the prevention of MDD incidence and relapse. Specifically, our care model uses digital CBT-I (dCBT-I) as a first-line intervention to increase care access and reduce the need for specialist resources. Our proposal also adds clinician-led CBT-I for patients who do not remit with first-line intervention and need a more personalized approach from specialty care. We will evaluate negative repetitive thinking as a potential treatment mechanism by which dCBT-I and CBT-I benefit insomnia and depression outcomes. DISCUSSION: This project will test a highly scalable model of sleep care in a large primary care system to determine the potential for wide dissemination and implementation to address the high volume of population need for safe and effective insomnia treatment and associated prevention of depression. TRIAL REGISTRATION: ClinicalTrials.gov NCT03322774. Registered on October 26, 2017

EC62-219 Nebraska Swine Production Report

This 1962 Nebraska Swine Production Report was developed by the Animal Husbandry Department of the University of Nebraska-Lincoln. Authors from the departments of Animal Husbandry, Agricultural Economics Veterinary Science, Agricultural Engineering contributed to this publication. It covers the following areas: breeding, feeding, economics, disease control, mechanization, housing and equipment

Bostonia: The Boston University Alumni Magazine. Volume 9

Founded in 1900, Bostonia magazine is Boston University's main alumni publication, which covers alumni and student life, as well as university activities, events, and programs

Protein engineering to increase the potential of a therapeutic antibody Fab for long-acting delivery to the eye

To date, ocular antibody therapies for the treatment of retinal diseases rely on injection of the drug into the vitreous chamber of the eye. Given the burden for patients undergoing this procedure, less frequent dosing through the use of long-acting delivery (LAD) technologies is highly desirable. These technologies usually require a highly concentrated formulation and the antibody must be stable against extended exposure to physiological conditions. Here we have increased the potential of a therapeutic antibody antigen-binding fragment (Fab) for LAD by using protein engineering to enhance the chemical and physical stability of the molecule. Structure-guided amino acid substitutions in a negatively charged complementarity determining region (CDR-L1) of an anti-factor D (AFD) Fab resulted in increased chemical stability and solubility. A variant of AFD (AFD.v8), which combines light chain substitutions (VL-D28S:D30E:D31S) with a substitution (VH-D61E) to stabilize a heavy chain isomerization site, retained complement factor D binding and inhibition potency and has properties suitable for LAD. This variant was amenable to high protein concentration (>250 mg/mL), low ionic strength formulation suitable for intravitreal injection. AFD.v8 had acceptable pharmacokinetic (PK) properties upon intravitreal injection in rabbits, and improved stability under both formulation and physiological conditions. Simulations of expected human PK behavior indicated greater exposure with a 25-mg dose enabled by the increased solubility of AFD.v8

Quantifying methane emissions from the global scale down to point sources using satellite observations of atmospheric methane

[EN] We review the capability of current and scheduled satellite observations of atmospheric methane in the shortwave infrared (SWIR) to quantify methane emissions from the global scale down to point sources. We cover retrieval methods, precision and accuracy requirements, inverse and mass balance methods for inferring emissions, source detection thresholds, and observing system completeness. We classify satellite instruments as area flux mappers and point source imagers, with complementary attributes. Area flux mappers are high-precision (< 1 %) instruments with 0.1-10 km pixel size designed to quantify total methane emissions on regional to global scales. Point source imagers are fine-pixel (< 60 m) instruments designed to quantify individual point sources by imaging of the plumes. Current area flux mappers include GOSAT (2009-present), which provides a high-quality record for interpretation of long-term methane trends, and TROPOMI (2018-present), which provides global continuous daily mapping to quantify emissions on regional scales. These instruments already provide a powerful resource to quantify national methane emissions in support of the Paris Agreement. Current point source imagers include the GHGSat constellation and several hyperspectral and multispectral land imaging sensors (PRISMA, Sentinel-2, Landsat-8/9, WorldView-3), with detection thresholds in the 100-10 000 kg h(-1) range that enable monitoring of large point sources. Future area flux mappers, including MethaneSAT, GOSAT-GW, Sentinel-5, GeoCarb, and CO2M, will increase the capability to quantify emissions at high resolution, and the MERLIN lidar will improve observation of the Arctic. The averaging times required by area flux mappers to quantify regional emissions depend on pixel size, retrieval precision, observation density, fraction of successful retrievals, and return times in a way that varies with the spatial resolution desired. A similar interplay applies to point source imagers between detection threshold, spatial coverage, and return time, defining an observing system completeness. Expanding constellations of point source imagers including GHGSat and Carbon Mapper over the coming years will greatly improve observing system completeness for point sources through dense spatial coverage and frequent return times.This research has been supported by the Collaboratory to Advance Methane Science (CAMS) and the National Aeronautics and Space Administration, Earth Sciences Division (grant no. NNH20ZDA001N-CMS).Jacob, DJ.; Varon, DJ.; Cusworth, DH.; Dennision, PE.; Frankenberg, C.; Gautam, R.; Guanter-Palomar, LM.... (2022). Quantifying methane emissions from the global scale down to point sources using satellite observations of atmospheric methane. ATMOSPHERIC CHEMISTRY AND PHYSICS. 14:9617-9646. https://doi.org/10.5194/acp-22-9617-2022961796461

SWOG 1815: A phase III randomized trial of gemcitabine, cisplatin, and nab-paclitaxel versus gemcitabine and cisplatin in newly diagnosed, advanced biliary tract cancers

Background: Biliary tract cancers (BTCs) are a heterogeneous group of malignancies with a dismal prognosis. Gemcitabine-based regimens are the standard of care in advanced disease, but median overall survival (OS) is roughly 12 months. The addition of albumin-bound paclitaxel to gemcitabine and cisplatin (GAP) demonstrated promising efficacy in a 60 patient, single-arm phase II study (Shroff et al, JAMA Oncol 2019), with observed median OS of 19.2 months. Methods: SWOG 1815 is a randomized, open-label, phase III trial comparing GAP to gemcitabine/cisplatin (GC). The study included newly diagnosed advanced BTC patients (pts), randomized 2:1 to GAP vs. GC. GAP included gemcitabine at 800 mg/m2, cisplatin at 25 mg/m2 and albumin-bound paclitaxel at 100 mg/m2 on days 1 and 8 of a 21-day cycle. GC included standard dosing of gemcitabine at 1000 mg/m2 and cisplatin at 25 mg/m2 on days 1 and 8 of a 21-day cycle. Pts were treated until progression. The primary endpoint was overall survival (OS) with a target hazard ratio of 0.7 with 90% power and a 1-sided alpha of 0.025; randomization was stratified by disease site (intrahepatic cholangiocarcinoma [CCA] vs gallbladder adenocarcinoma [GBC] vs extrahepatic CCA), disease stage (locally advanced vs metastatic), and Zubrod PS 0 vs 1. Results: Of 441 eligible pts randomized, 55% were female. 67% of patients had intrahepatic CCA, 16% had GBC and 17% had extrahepatic CCA. Most pts had metastases (73%). Median OS with GAP vs. GC was 14 vs. 12.7 mo respectively (HR 0.93, 95% CI 0.74-1.19, p=0.58), ORR (confirmed and unconfirmed) 34% vs25% (p=0.11) and median PFS 8.2 vs 6.4 mo (HR 0.92, 95% CI 0.72-1.16, p=0.47), respectively. Grade 3 and 4 treatment related adverse events (TRAEs) in ≥10% of pts for GAP and GC were anemia, neutropenia, and thrombocytopenia. GAP had more ≥ grade 3 hematologic AEs compared to the GC arm (60% vs. 45%, p=0.003). Discontinuation due to toxicity was at 24% vs 19% (p=0.26) with GAP vs GC. In exploratory subset analyses, GAP vs GC improved OS in pts with locally advanced disease (medians 19.2 vs 13.7 mo; HR 0.67, 95% CI 0.42- 1.06, p=0.09) and in GBC pts (medians 17.0 vs 9.3 mo; HR 0.74, 95% CI 0.41-1.35, p=0.33). ORR for GAP vs GC in GBC was 50% vs 24% (p=0.09) and for locally advanced disease 28 vs 21% p=0.74. Conclusions: SWOG 1815 did not result in a statistically significant improvement in median OS with GAP vs. GC. The GAP regimen had higher rates of TRAEs without a statistically significant difference in discontinuation rates. Pts with locally advanced disease and GBC may benefit from the use of GAP. Further analyses are ongoing to understand potential benefit of GAP in subsets of BTC pts. Funding: NIH/National Cancer Institute grants CA180888, CA180819, CA180820, CA180821, and CA180868; and in part by Celgene Corporation, Summit, NJ (subsidiary of Bristol Myer Squibb)

Meeting Report of the Third Annual Tri-Service Microbiome Consortium Symposium

The Tri-Service Microbiome Consortium (TSMC) was founded to enhance collaboration, coordination, and communication of microbiome research among U.S. Department of Defense (DoD) organizations and to facilitate resource, material and information sharing among consortium members. The 2019 annual symposium was held 22–24 October 2019 at Wright-Patterson Air Force Base in Dayton, OH. Presentations and discussions centered on microbiome-related topics within five broad thematic areas: 1) human microbiomes; 2) transitioning products into Warfighter solutions; 3) environmental microbiomes; 4) engineering microbiomes; and 5) microbiome simulation and characterization. Collectively, the symposium provided an update on the scope of current DoD microbiome research efforts, highlighted innovative research being done in academia and industry that can be leveraged by the DoD, and fostered collaborative opportunities. This report summarizes the presentations and outcomes of the 3rd annual TSMC symposium