Relevant academic literature, applicable federal regulations for the protection of human subjects on emergency research involving artificial/substitute blood products (including PolyHeme)

Federal oversight of research involving human subjects is found in two regulatory regimes within the Department of Health and Human Services (DHHS), Food and Drug Administration (FDA). 21 CFR 50, 56 - the Office of Human Research Protections (OHRP), and 45 CFR 46. Generally, any research that is testing a drug, device, or other product that will be submitted for FDA approval must follow their regulations (21 CFR 50/56), while research that is supported by federal funds (e.g., an NIH grant) must also comply at a minimum with 45 CFR 46 Subpart A (the federal policy for the protection of human subjects, also known as the Common Rule), and with Subparts B,C,D as appropriate. While most of the FDA and OHRP regulations are similar (or substantially overlap), there are a number of areas in which they differ. Further, all institutions supported by federal funds must negotiate a Federalwide Assurance with OHRP that provides for all research within an institution to be subject to the Common Rule, regardless of whether the research is federally funded.Indiana University Center for Bioethic

Recent advances in our understanding of the structure and function of more unusual cation channels.

As their name implies, cation channels allow the regulated flow of cations such as sodium, potassium, calcium, and magnesium across cellular and intracellular membranes. Cation channels have long been known for their fundamental roles in controlling membrane potential and excitability in neurons and muscle. In this review, we provide an update on the recent advances in our understanding of the structure-function relationship and the physiological and pathophysiological role of cation channels. The most exciting developments in the last two years, in our opinion, have been the insights that cryoelectron microscopy has provided into the inner life and the gating of not only voltage-gated channels but also mechanosensitive and calcium- or sodium-activated channels. The mechanosensitive Piezo channels especially have delighted the field not only with a fascinating new type of structure but with important roles in blood pressure regulation and lung function

Effect of Lesser Tuberosity Osteotomy Size and Repair Construct During Total Shoulder Arthroplasty

Background. Lesser tuberosity osteotomy has been shown to decrease post-operative subscapularis dysfunction. The purpose of this study was to determine the effect of osteotomy thickness and suture configuration on repair integrity. Methods. One side of twelve matched-pair cadaveric shoulders was randomly assigned either a thick osteotomy (100% lesser tuberosity height) or a thin (50% height) osteotomy. Both sides of the matched-pairs were given the same repair, either 1) compression-sutures or 2) compression-sutures plus one tension-suture. This created four groups of six paired specimens. CT imaging measured tuberosity dimensions pre- and post-osteotomy to validate fragment height and area. The repairs were loaded cyclically and then loaded to failure. A video system measured fragment displacement. Percent area of osteotomy contact was calculated from the CT and displacement data. Results. The average initial displacement was less in the thin osteotomy groups (p=0.011). Adding a tension-suture negated this difference. A significant number of thin compared to thick repair sites remained intact during load to failure (p=0.001). No difference occurred due to maximal load between the repair groups (p=0.40) and construct stiffness was greater when a tension-suture was used (p=0.032). Percent area of osteotomy contact revealed no differences between the osteotomy (p=0.431) and repair (p=0.25) groups. Conclusion. The study showed that thin osteotomies displaced less than thick osteotomies. Adding a tension band improved construct stability and eliminated some failure modes. The ideal repair was a thin wafer with both tension and compression sutures. This construct had smaller total displacement, a reasonable osteotomy percent contact area, and acceptable maximum load

A retrospective segmentation analysis of placental volume by magnetic resonance imaging from first trimester to term gestation

Background Abnormalities of the placenta affect 5–7% of pregnancies. Because disturbances in fetal growth are often preceded by dysfunction of the placenta or attenuation of its normal expansion, placental health warrants careful surveillance. There are limited normative data available for placental volume by MRI. Objective To determine normative ranges of placental volume by MRI throughout gestation. Materials and methods In this cross-sectional retrospective analysis, we reviewed MRI examinations of pregnant females obtained between 2002 and 2017 at a single institution. We performed semi-automated segmentation of the placenta in images obtained in patients with no radiologic evidence of maternal or fetal pathology, using the Philips Intellispace Tumor Tracking Tool. Results Placental segmentation was performed in 112 women and had a high degree of interrater reliability (single-measure intraclass correlation coefficient =0.978 with 95% confidence interval [CI] 0.956, 0.989; P<0.001). Normative data on placental volume by MRI increased nonlinearly from 6 weeks to 39 weeks of gestation, with wider variability of placental volume at higher gestational age (GA). We fit placental volumetric data to a polynomial curve of third order described as placental volume = –0.02*GA3 + 1.6*GA2 – 13.3*GA + 8.3. Placental volume showed positive correlation with estimated fetal weight (P=0.03) and birth weight (P=0.05). Conclusion This study provides normative placental volume by MRI from early first trimester to term gestation. Deviations in placental volume from normal might prove to be an imaging biomarker of adverse fetal health and neonatal outcome, and further studies are needed to more fully understand this metric. Assessment of placental volume should be considered in all routine fetal MRI examinations

Neutron-irradiation Effects on the V-I Characteristics of YBa2Cu3O7-δ Twinned Crystals:Linking Transport Results in a Variety of Copper Oxide Superconductors

We have investigated the depinning process of magnetic flux vortices in twinned crystals of YBa2Cu3O7-δ in intermediate applied magnetic fields parallel to the crystallographic c axis through precise resistivity measurements before and after fast-neutron irradiation. Of particular interest for each field is the power-law dependence of the electric field on current density, E∝Jn, at a well defined temperature which separates a nonlinear region below from a more linear, dissipative region above. We find that n shows a striking dependence on the estimated value of the Larkin-Ovchinnikov length. The relation is not only manifest before and after irradiation but also for a variety of samples, including films, crystals, and at least two copper oxides other than YBa2Cu3O7-δ

Focus: New Info from Slow Muons

No abstract available

Injury induced neuroplasticity and cell specific targeting of the lumbar enlargement for gene therapy.

This dissertation is an examination of spinal cord injury induced neuroplasticity and tests whether noninvasive gene therapy can successfully target neurons in the lumbar spinal cord. It begins with an overview of neural control of locomotion and a brief summary of therapeutics that are used and/or in development for treating spinal anatomically characterize s subset of neurons in the spinal cord, long ascending propriospinal neurons, that are involved in interlimb coordination. Characterization of these neurons allows for subsequent evaluation of their potential involvement in injury induced neuroplasticity. This dissertation is divided into five chapters, covering spinal cord injury and therapeutics. Chapter One gives background on locomotor control, propriospinal neurons, spinal cord injury, and therapeutics. Chapter Two develops and characterizes viral tracing methods for spinal cord anatomy. Chapter Three then uses these methods to characterize long ascending propriospinal neurons and evaluate their involvement in injury induced plasticity. Chapter Four then focuses on the development of noninvasive delivery of gene transfer to the lumbar enlargement. This involves optimizing focused ultrasound and intravenous microbubble delivery to focally and transiently permeabilize the blood spinal cord barrier of the lumbar spinal cord. This optimization then allows for successful gene transfer in neurons in the lumbar spinal cord following intravenous delivery of viral vector. Lasty, Chapter Five discusses the implications for all of these findings and how these findings have contributed to our understanding spinal cord anatomy and injury, and how the proof-of-concept in Chapter 4 provides a promising new avenue for spinal cord injury therapeutics

Herding Molecules

No abstract available