Fit-for-purpose validation of a drug-tolerant immunogenicity assay for a human mAb drug in animal safety studies.

A modified biotin-drug extraction and acid dissociation (BEAD) immunogenicity assay was developed to detect anti-drug-antibodies (ADA) against the human anti-FXIIa monoclonal antibody (mAb) drug, Garadacimab (previously called CSL312). Multiple strategies were tested to optimize the signal-to-background (S/B) ratio, assay sensitivity and the drug tolerance. The modified BEAD assay was found to be highly drug tolerant (>500 μg/ml) with a sensitivity of 100 ng/ml, in line with current FDA regulatory guidelines.

Airway inflammation and dysbiosis in antibody deficiency despite the presence of IgG.

Background: Patients with antibody deficiency suffer chronic respiratory symptoms, recurrent exacerbations, and progressive airways disease despite systemic replacement of IgG. Little is known about the respiratory tract biology of these patients.

Objective: We sought to measure immunoglobulin levels, inflammatory cytokines, and mediators of tissue damage in serum and sputum from patients with antibody deficiency and healthy controls; to analyze the respiratory microbiome in the same cohorts.

Control of Pelvic Blood Flow Using a Novel Pneumatic Abdominal Binder.

Background Obstetrical hemorrhage continues to be the leading cause of maternal death; additional means of treatment are needed to reach women who are currently not being saved. We developed the "Ball and Binder", an inexpensive and innovative pneumatic abdominal-pelvic compression device made with a cloth binder and soccer ball. Objective To measure the change in distal aortic blood flow before and after placement of the device.

Obstetric hemorrhage in resource-limited locations: A quality improvement project after adoption of abdominopelvic compression devices.

Objective: To evaluate obstetric hemorrhage outcomes and present data specific to adoption of pneumatic circumferential abdominopelvic compression devices.

Methods: Two resource-limited locations added low-cost pneumatic compression devices to their standard protocols for obstetric hemorrhage between 2010 and 2019. Providers in rural Nepal and Papua New Guinea used devices that incorporated a bicycle tube or soccer ball ("Ball and Binder") to provide abdominopelvic pressure after all available routine treatments had failed.

Comparative Transcriptomic Analysis of Temozolomide Resistant Primary GBM Stem-Like Cells and Recurrent GBM Identifies Up-Regulation of the Carbonic Anhydrase Gene as Resistance Factor.

About 95% of patients with Glioblastoma (GBM) show tumor relapse, leaving them with limited therapeutic options as recurrent tumors are most often resistant to the first line chemotherapy standard Temozolomide (TMZ). To identify molecular pathways involved in TMZ resistance, primary GBM Stem-like Cells (GSCs) were isolated, characterized, and selected for TMZ resistance in vitro. Subsequently, RNA sequencing analysis was performed and revealed a total of 49 differentially expressed genes (|log2-fold change| > 0.

Interaction of Discoidin Domain Receptor 1 with a 14-3-3-Beclin-1-Akt1 Complex Modulates Glioblastoma Therapy Sensitivity.

Glioblastoma (GBM) is highly refractory to therapy and associated with poor clinical outcome. Here, we reveal a critical function of the promitotic and adhesion-mediating discoidin domain receptor 1 (DDR1) in modulating GBM therapy resistance. In GBM cultures and clinical samples, we show a DDR1 and GBM stem cell marker co-expression that correlates with patient outcome.

The Practitioner's Guide to Global Health: an interactive, online, open-access curriculum preparing medical learners for global health experiences.

Background: Short-term experiences in global health (STEGH) are increasingly common in medical education, as they can provide learners with opportunities for service, learning, and sharing perspectives. Academic institutions need high-quality preparatory curricula and mentorship to prepare learners for potential challenges in ethics, cultural sensitivity, and personal safety; however, availability and quality of these are variable.

Objective: The objective of this study is to create and evaluate an open-access, interactive massive open online course (MOOC) that prepares learners to safely and effectively participate in STEGH, permits flexible and asynchronous learning, is free of charge, and provides a certificate upon successful completion.

A Rationale for Targeting Extracellular Regulated Kinases ERK1 and ERK2 in Glioblastoma.

Glioblastoma (GBM) is the most common malignant primary brain tumor. It still carries a grim prognosis and new therapies are needed. This review summarizes the current status of mechanistic insights into the function of extracellular regulated kinase (ERK) and its potential as a therapeutic target for patients with GBM.

More than just a hobby: building an academic career in global emergency medicine.

Background: As the specialty of emergency medicine (EM) continues to spread around the world, a growing number of academic emergency physicians have become involved in global EM development, research, and teaching. While academic departments have always found this work laudable, they have only recently begun to accept global EM as a rigorous academic pursuit in its own right.

Objective: This article describes how emergency physicians can translate their global health work into "academic currency" within both the clinician-educator and clinician-researcher tracks.

An inexpensive device to treat postpartum hemorrhage: a preliminary proof of concept study of health provider opinion and training in Nepal.

Background: Obstetric hemorrhage remains the leading cause of maternal mortality in resource limited areas. An inexpensive pneumatic anti-shock garment was devised of bicycle tubes and tailored cloth which can be prepared from local materials in resource-limited settings. The main purposes of this study were: 1) to determine acceptability of the device by nurses and midwives and obtain suggestions for making the device more suitable for use in their particular work environments, 2) to determine whether a three hour training course provided adequate instruction in the use of this device for the application of circumferential abdominal pelvic pressure, and 3) determine production capability and cost in a resource-limited country.

Global health and emergency care: a resuscitation research agenda--part 2.

At the 2013 Academic Emergency Medicine global health consensus conference, a breakout session to develop a research agenda for resuscitation was held. Two articles are the result of that discussion. This second article addresses data collection, management, and analysis and regionalization of postresuscitation care, resuscitation programs, and research examples around the world and proposes a strategy to strengthen resuscitation research globally.

Ethics in acute care research: a global perspective and research agenda.

The 2013 Academic Emergency Medicine consensus conference focused on global health and emergency care research. One conference breakout session discussed research ethics and developed a research agenda concerning global acute care research ethics. This article represents the proceedings from that session, particularly focusing on ethical issues related to protecting human subjects while conducting acute care research.

Research priorities for data collection and management within global acute and emergency care systems.

Barriers to global emergency care development include a critical lack of data in several areas, including limited documentation of the acute disease burden, lack of agreement on essential components of acute care systems, and a lack of consensus on key analytic elements, such as diagnostic classification schemes and regionally appropriate metrics for impact evaluation. These data gaps obscure the profound health effects of lack of emergency care access in low- and middle-income countries (LMICs). As part of the Academic Emergency Medicine consensus conference "Global Health and Emergency Care: A Research Agenda," a breakout group sought to develop a priority research agenda for data collection and management within global emergency care systems.

Executive summary: global health and emergency care-what do we need to know to address the burden of illness and injury?

Emergency physicians are uniquely poised to address challenges in health services, health care systems development and management, and emerging global disease burdens (both communicable and noncommunicable). This special issue of Academic Emergency Medicine reports the results of the 2013 consensus conference, which included eight focus areas that are intended to advance emergency care research. Advancing our understanding of cardiac and injury resuscitation, ethics of research, health systems development, and the education of our future leaders in global health will ultimately affect the populations of all nations across the globe.

Making recording and analysis of chief complaint a priority for global emergency care research in low-income countries.

The chief complaint is a patient's self-reported primary reason for presenting for medical care. The clinical utility and analytical importance of recording chief complaints have been widely accepted in highly developed emergency care systems, but this practice is far from universal in global emergency care, especially in limited-resource areas. It is precisely in these settings, however, that the use of chief complaints may have particular benefit.

Education research: priority designs and common misperceptions.

In this commentary, common misperceptions about education research, and specifically for emergency medicine education research, are addressed. Recommendations for designing and publishing high-quality projects are also provided.