Modifying a battlefield dressing to prevent maternal death

Every day around the globe, more than 830 women die from preventable causes related to pregnancy and childbirth. Ninety-nine percent of these deaths occur in developing countries, where resources are limited and childbirth occurs outside of the health care system. Postpartum hemorrhage is one of the primary causes of maternal death and the leading cause of death for new mothers in developing countries. A major challenge in treating postpartum hemorrhage is that it is not possible to use tourniquets and other forms of wound compression to stop the bleeding.

Above: The MSD trauma applicator. Below: Revised design of obstetrical applicator and sponge removal system. “Sponges in a bag” system for ease of vaginal removal.

Above: The MSD trauma applicator. Below: Revised design of obstetrical applicator and sponge removal system. “Sponges in a bag” system for ease of vaginal removal.

A technique used to manage non-compressible wounds in battlefields and trauma settings is now being adapted by a team led by Maria I. Rodriguez, M.D., M.P.H., to treat severe postpartum hemorrhage. The trauma dressing and applicator device, XStat™ Mini Sponge Dressing, applies highly compressed medical sponges—similar to the ‘instant’ sponges sold in grocery stores—that stop high-flow arterial bleeding in about 20 seconds. Rodriguez, assistant professor of obstetrics and gynecology in the OHSU School of Medicine, and a team including Jeffrey JensenM.D., M.P.H., Alison EdelmanM.D., M.P.H., and Kenton Gregory, M.D., reported in BMC Pregnancy and Childbirth an adaptation of the device that allows for obstetrical use of the dressing.

This device addresses a key gap in a major treatment for postpartum hemorrhage—uterine tamponade—by adapting it for use in low-resource settings. Tamponade, which physically stems bleeding, stabilizes hemorrhage while transporting a woman or preparing her for surgery. Current methods to deliver uterine tamponade include uterine balloons and packing the uterus with gauze. These methods can be helpful but are not ideal for low-resource settings—each requires specialized skill equipment.

Rodriguez’s adaptation of the XStat has a long, tapered applicator that can be deployed during vaginal examination by nonspecialists, and it administers three times the volume of the sponges contained in the trauma applicator. Unlike the trauma device, the design of the obstetrical applicator allows for the sponges to be removed without surgery. In initial testing, it demonstrated excellent uterine fill and higher average uterine pressure than gauze packing or the uterine balloon, suggesting it may be a more effective alternative. Animal testing also showed good uterine fill and no short-term signs of uterine trauma or infection. The next step for Rodriguez’s team is a Phase 1 clinical study.


In addition to Rodriguez, Jensen, Gregory, and Edelman, co-authors included Mary Bullard, Paul Longo, and Jerry Heidel.

This research was supported by Saving Lives at Birth partners: The United States Agency for International Development (USAID), the Government of Norway, the Bill & Melinda Gates Foundation, Grand Challenges Canada, and the U.K. Government (AID-OAA-F-14-00007).

OHSU researcher Horner-Johnson: Groundbreaking research on disability and pregnancy


Height adjustable exam tables, scales that accommodate wheelchair users, and tactile models of the birth canal are not common equipment in OB/GYN offices. These are examples of accommodations that can improve prenatal care and the experience of pregnancy for women with specific disabilities. Often missing, too, are the knowledge and skills necessary to provide information to women with intellectual disabilities or to adjust the volume on a sonogram for women with hearing impairments.

These are increasingly important considerations, given that women with disabilities are now as likely to become pregnant as women without disabilities. Among women giving birth, the proportion with disabilities more than doubled between 2000 and 2010, according to data from California. However, there continue to be major gaps in knowledge on maternal health and pregnancy outcomes for these women—particularly within disability subgroups. New findings make clear that more attention to this population is needed in order to develop better care practices that may impact maternal and perinatal outcomes.

In the July 2017 Disability and Health Journal, a team led by Willi Horner-Johnson, Ph.D., published two first-of-their-kind studies: an analysis of live birth, miscarriage, and abortion in a national sample of women with and without disabilities, and a time-trend analysis of births and cesarean deliveries for women with physical, sensory, or intellectual disabilities. These studies are part of a larger pregnancy and disability project led by Horner-Johnson, an associate professor in the collaborative OHSU-PSU School of Public Health and in OHSU’s Institute on Development and Disability.

The study on live birth, miscarriage, and abortion among U.S. women with and without disabilities demonstrated that there is a good likelihood that women with disabilities will deliver successfully. Rates of live births and miscarriages (84 percent and 14 percent, respectively) for women with disabilities were similar to those for women without disabilities when adjusting for factors such as maternal age, marital status, and health status. There was no gap in rates of abortion.

The publication on time trends in births and cesarean deliveries builds on a previous paper on cesarean delivery among women with physical, sensory, or intellectual disabilities, published in the May–June 2017 Women’s Health Issues by Horner-Johnson’s team. That study found that women with disabilities were twice as likely as women without disabilities to deliver by cesarean—32 percent compared to 16 percent. Differences in cesarean delivery by disability subgroup were remarkable—58 percent of women with vision disabilities delivered their first child by cesarean, while women with hearing impairments had cesarean deliveries at roughly the same rate as women without disabilities. The new paper examines patterns of cesarean delivery across time, from 2000-2010. While differences between women with and without disabilities were apparent in every year of data analyzed, the size of the gap was significantly smaller in the most recent years than it had been in earlier years. Additionally, there was a steady increase in representation of women with disabilities among those giving birth in California during this time period.

These studies are some of the first to examine more than one type of disability. Horner-Johnson’s research underscores that understanding the heterogeneity across disability subgroups is important to addressing the distinct needs of women with particular types of disability—and to guiding clinical practice.


Horner-Johnson’s coauthors were Aaron B. Caughey, M.D., Ph.D., Sheetal Kulkarni-Rajasekhara, M.P.H., Blair Darney, Ph.D., M.P.H., and Mekhala Dissanayake, M.P.H., C.P.H. (Live birth, miscarriage, and abortion among U.S. women with and without disabilities);  Caughey, Fran Biel, M.P.H., M.S., and Darney (Time trends in births and cesarean deliveries among women with disabilities); and Caughey, Darney, Biel, and Brian Quigley (Primary cesarean delivery patterns among women with physical, sensory, or intellectual disabilities). 

Research reported in these publications was supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health under award #R21HD081309 (Horner-Johnson, PI). Support for Horner-Johnson’s time was provided by grant #K12HS022981 from the Agency for Healthcare Research and Quality (Guise, PI).

OHSU scientist Mandel elected to Society for Neuroscience leadership post


Gail Mandel, Ph.D., has been elected to the governing body of the Society for Neuroscience. Mandel, a senior scientist at the Vollum Institute and professor in the Department of Biochemistry and Molecular Biology in the School of Medicine, begins her four-year term on November 11, 2017.

Mandel’s lab focuses on understanding how neuronal cell identity is established and maintained. Her team discovered that this is achieved primarily through a repressor mechanism with the DNA-binding protein, REST, at its heart. The discovery provides a window into the molecular events governing nervous system formation.

Recently, she extended her studies to explore neuronal:glial interactions, uncovering a potential role for glia in inducing neuronal dysfunction in Rett Syndrome, one of the most common causes of mental retardation in young girls. The lab’s goal is to identify how the glial genes or proteins cause the underlying neuronal pathology.

Mandel joined the Vollum Institute in 2006 after holding faculty positions at Tufts-New England Medical Center and Stony Brook University—where she advanced to the rank of Distinguished Professor. She was a Howard Hughes Medical Institute Investigator from 1997 to 2016.

A recipient of the Jacob J. Javits Neuroscience Investigator Award, Mandel was elected to the National Academy of Sciences in 2008. She received the 2011 Discovery Award from the Medical Research Foundation of Oregon and a 2013-2018 NIH Transformative Research Award. She has also served as the senior editor of the Journal of Neuroscience.

The Society for Neuroscience, founded in 1969, now has nearly 38,000 members in more than 90 countries and over 130 chapters worldwide. It is the largest and most prestigious organization representing scientists and physicians devoted to understanding the brain and nervous system.


Clinical trials administration reorganized to speed processes

Shortening clinical trials contract turnaround by 20 percent—that is the goal of the new Clinical Research Support Office (CRSO). Processes for study staff and investigators will be simplified over time, and the institutional support functions are being brought under a single umbrella.

contract turnaround-aThe new structure, launched on July 3, will streamline communications and functions across administrative units and offices, including clinical trials contracting, clinical research billing, and the clinical trials management system. The contracting triage function will continue to provide customer service for all the contracting offices at OHSU, including determining the appropriate contract office for execution.

Improved processes have already reduced the turnaround times for industry-sponsored clinical trials contracts. The average turnaround time in 2016 was 112 days. In the first quarter of 2017, it was 101 days. The goal for the next 12 months is a 90-day turnaround time.

A new director, currently being recruited, will be charged with ensuring the research community receives the support they need. This includes customer service, adherence to regulatory requirements, risk assessment and mitigation, and operational excellence. The director and office will report to the vice president for research operations with joint reporting to the associate vice president for clinical and translational research and will work closely with key programs and units within OCTRI.

Five innovative education projects awarded mini-grants

 Members of the School of Medicine community embrace “outside the box” thinking when it comes to advancing the education mission. In order to spur this inventiveness, five projects designed to generate and support innovation within the school’s educational programs have been awarded mini-grants.

Faculty members, trainees, and staff in the school submitted 18 project ideas in response to the call for proposals earlier this year. The funded projects were chosen for their originality, feasibility, impact, sustainability, and plans for dissemination. The review group included members of the Educators’ Collaborative with expertise in undergraduate medical education and graduate studies programs.

The titles and team members of the funded projects are:

  • Women’s Leadership Development Program: An innovative curriculum for dissemination
    Megan Furnari, M.D., instructor in pediatric neonatology; Elizabeth Lahti, M.D., assistant professor of medicine
  • Implementation of a Jeopardy Point Study in the OHSU Internal Medicine Residency Program
    Erin Bonura, M.D., assistant professor of medicine; Claire Zeigler, M.D., M.P.H.; resident Kellie Littlefield, D.O.; Kelsey Shaver, M.D.
  • Development of a Mobile App for Entrustable Professional Activities
    Mark Engelstad, D.D.S., M.D., associate professor oral and maxillofacial surgery and NLM bioinformatics; James Morrison, M.D., clinical informatics fellow; Ryan Palmer, Ed.D., assistant professor of family medicine.
  • Innovation Support Workshops
    Aditi Martin, Ph.D., OCTRI Pilot Awards program director; Jonathan Jubera, OCTRI Biomedical Innovation Program project manager; David Ellison, M.D., professor of medicine and OCTRI director; Brendan Rauw, M.B.A., vice president of Technology Transfer and Business Development; Sarah Biber, Ph.D., OTRADI.
  • Education Scholarship Writing Group
    Jackie Wirz, Ph.D., assistant dean of Graduate Studies Student Affairs and director of the Career and Professional Development Center at the School of Medicine; Amy Miller Juve Ed. D, M.Ed., director of education and assistant professor of anesthesiology and perioperative medicine; Sylvia Nelsen, Ph.D., assistant professor of cell development and cancer biology.

Originally posted by Jennifer Smith in Inside the SoM.


NeuroFutures 2017: Brain connectivity in health and disease, July 9–11

Join some of the brightest minds in research, engineering, industry and clinical domains at NeuroFutures 2017. This year’s conference will focus on neuronal circuits, with topics including novel imaging approaches, brain clearing and expansion techniques, human and non-human primate circuit function, genetically engineered probes for circuit function, circuits in degeneration, and circuits in psychiatric disorders.

NeuroFutures 2017

July 9-11, 2017


University of British Columbia
Vancouver, Canada

Gary Marcus, Ph.D., director, NYU Center for Language and Music, and professor of psychology, New York University, will present a public lecture, “What artificial intelligence can learn from the brain, and vice versa.” Keynote addresses will be given by Loren Looger, Ph.D., group leader, Janelia Research Campus, Howard Hughes Medical Institute, and Brian MacVicar, Ph.D., co-director, Djavad Mowafaghian Centre for Brain Health, University of British Columbia. Looger will present “Genetically engineered indicators of neuronal activity.” MacVicar will present “Imaging metabolism using fluorescence lifetime.”

NeuroFutures 2017 is sponsored by the University of British Columbia, OHSU, Leica Microsystems, the Allen Institute for Brain Science, the University of Washington, and the University of British Columbia. Following the conference, there will be a brain clearing and expansion workshop on July 12.

Registration and agenda information is available at the NeuroFutures website.

Sex matters: OHSU researchers shine light on mechanisms of ischemic stroke

Regulatory T cells are increased in the spleens of female mice.

Regulatory T cells are increased in the spleens of female mice.

Sex—like age, weight, and underlying health conditions—is a biological variable that is often a critical factor when it comes to health. However, sex has been largely absent in research and this has led to an incomplete understanding of sex-based differences in disease processes and treatment therapies that are appropriate for men and women.

Ischemic stroke is one of the diseases for which a lack of preclinical data on male and female subjects presents a critical gap in information for clinical researchers who are testing therapies in women and men.

A new study led by Halina Offner, Dr. Med., shines some light on the ways immune systems in female and male mice respond differently to ischemic stroke. The study was published in Cellular Immunology. Offner, OHSU professor of neurology, and immunologist at the Veterans Affairs Medical Center, and her team see this as an important step in developing effective treatments. In this case, successful therapies will be sex-specific.

Investigators examined the integration of the spleen—a major component of the immune system—in the regulation of immune responses in the brain and throughout the body. The severity of the stroke was measured using digital imaging, and levels of immune-related cells were measured and analyzed with a Cellometer cell counter and flow cytometry analysis.

The study demonstrated two important differences in immune regulation in male and female mice. Female mice had higher levels of regulatory B cells, which help suppress responses, but had lower levels of anti-inflammatory macrophages, another immune cell. These results make clear mechanisms that account for less severe strokes in females and also explain why immune modulating therapies, like splenectomy, protect male animals but not female animals.

This research, supported by a 2012–2016 NIH grant, underscores the importance of testing therapies for stroke in both males and females. Beginning in January, 2016, the NIH began ensuring that researchers account for sex as a biological variable in studies with vertebrate animals and humans. Closing the gaps in preclinical knowledge will provide scientific data to help improve treatments and recovery of women and men.


In addition to Offner and first author Hilary Seifert, Ph.D., (log-in required) co-authors include Gil Benedek, Jian Liang, Ha Nguyen, Gail Kent, Arthur Vandenbark, and Julie Saugstad. This work was supported by NIH/National Institute of Neurological Disorders and Stroke 1RO1 NS075887 (H.O.) and 1RO1 NS076013 (H.O., J.S.) and the American Heart Association 17GRNT33220001 (H.O). 

OHSU researchers: New discovery on obesity-high blood pressure relationship

Obesity contributes to high blood pressure, but why and how this happens remains unclear. One of the major causes of high blood pressure—or hypertension—is the inappropriate activation of the fight-or-flight sympathetic nervous system response, and most obesity researchers have focused on factors that increase sympathetic activity. Virginia Brooks, Ph.D., however, has been investigating mechanisms that inhibit this activity.

Model illustrating proposed neurocircuitry by which NPY neurons inhibit sympathetic nerve activity.

Model illustrating proposed neurocircuitry by which NPY neurons inhibit sympathetic nerve activity.

A team led by Brooks, professor of physiology and pharmacology at OHSU, identified a neuromodulator, neuropeptide Y (NPY), that inhibits sympathetic activity in a specific area of the hypothalamus, the paraventricular nucleus. They found that withdrawal of that inhibition is required for an increase in sympathetic activity to occur in certain conditions, like obesity. However, the sources of NPY inhibition to the paraventricular nucleus were unknown.

To investigate the blood pressure effects of NPY neurons, the team used designer receptors exclusively activated by designer drugs (DREADDs) to selectively activate or inhibit these particular neurons in another hypothalamic nucleus, the arcuate, in mice. They demonstrated that the same population of neurons that increases feeding also suppresses blood pressure. Brooks and senior research associate Zhigang Shi, Ph.D., have published their findings that both verify that NPY inhibits sympathetic activity and also identify a new hypothalamic site and neuronal pathway by which NPY suppresses that activity. The paper was published in the Journal of Clinical Investigation.

DREADDs, along with three concurrent technical accomplishments by Shi, made the experiments possible. He may have been the first person to successfully secure an electrode around the sympathetic nerve of a mouse, place a cannulae in blood vessels so the team could measure blood pressure and deliver infusions, and conduct nanoinjections using micropipettes with tips that were about 20 micrometers—the size of a couple of neurons. With these, he was able to inject treatments into the paraventricular nucleus, an area of the brain smaller than a ballpoint pen, while simultaneously measuring sympathetic nerve activity.

Neuropeptide Y antagonists are primary targets in the development of drugs for obesity and anxiety disorders, often without consideration of the effects on blood pressure. In addition to helping develop better drugs to treat high blood pressure in obese patients, research conducted in Brooks’ lab might help to understand the potential cardiovascular side effects of anti-obesity treatments.

Along with Brooks and Shi, Christopher Madden, Ph.D., coauthored the paper. This research was funded in part by NIH grants HL088552 and HL128181 (VLB), AHA15POST23040042 postdoctoral fellowship (ZS), ADA 1-13-BS-120 (CJM), and NINDS P30 NS061800 (PI, S. Aicher).

New bioinformatics services for all OHSU investigators available

Fee-for-service bioinformatics support, focused on next-generation sequencing, became available to all OHSU investigators on July 1, 2017.

cellsThis interim bioinformatics service will provide additional capacity and will complement the existing Oregon National Primate Research Center bioinformatics service core, which is primarily dedicated to ONPRC investigators, as well as the bioinformatics services provided for Knight Cardiovascular Institute Epigenetics Consortium members.

Investigators will have two new tiers of bioinformatics service available to them: (1) flat-fee based QA/QC and alignment, and (2) hourly rate analytical support. In addition, the Oregon Clinical and Translational Research Institute (OCTRI) Translational Bioinformatics Program will provide consultations regarding experimental design, data management and dissemination free of charge for FY18.

In order to assess the growing needs of OHSU investigators, the OCTRI Translational Bioinformatics Program will provide a unified point of contact and will connect investigators with available faculty collaborators from across campus for other bioinformatics needs (imaging, proteomics, immunophenotyping, natural language processing, etc.). Available collaborators are found in the Division of Bioinformatics and Computational Biomedicine in the Department of Medical Informatics and Clinical Epidemiology, Department of Biomedical Engineering, the OCTRI Biostatistics and Design Program (BDP), the OCTRI Research Data Warehouse, the OHSU-PSU School of Public Health Biostatistics, the Knight Cancer Institute Biostatistics Shared Resource, and other OHSU units.

The data collected by OCTRI Translational Bioinformatics Program and the MPSSR on support requests and utilization of these services will be critical to guide the university in the expansion of existing cores as well as the development of new ones. In particular, these data will help us restart a new bioinformatics core for OHSU if the demand shows its necessity.

This fee-for-service bioinformatics support has been made possible by a partnership between the Office of the Senior Vice President for Research, the University Shared Resources (USR) program, the OCTRI Translational Bioinformatics Program, the Integrated Genomics Laboratory’s Massively Parallel Sequencing Shared Resource (MPSSR) and the Advanced Computing Center (ACC).

For a free consultation or to request analytical support, please submit a service request. MPSSR users will also be able to request services when they initiate projects via the MPSSR’s online form at the OHSU iLab portal.




Upcoming class: Introduction to Research Administration, July 13

Research Administration Training & Education (RATE) connects the research community with workplace learning and offers classes for research administrators and others who support research at OHSU.

RDA 101 provides a big-picture overview of research administration. Meet Research Development and Administration unit leaders, tour valuable web resources, and meet face-to-face with your contacts in OPAM, IRB, TTBD, and others.

RDA 101: Introduction to Research Administration
Thursday, July 13
9:30 to 11:30 a.m.
Center for Health & Healing, CHH 3070, room 4

The class is designed for research administrators who are new to OHSU, as well as those who have been at OHSU for a while.

Use your network login to enroll through Compass. Questions? Contact Margaret Gardner.

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