An automated pattern recognition system for the quantification of inflammatory cells in hepatitis-C-infected liver biopsies

This paper presents an automated system for the quantification of inflammatory cells in hepatitis-C-infected liver biopsies. Initially, features are extracted from colour-corrected biopsy images at positions of interest identified by adaptive thresholding and clump decomposition. A sequential floating search method and principal component analysis are used to reduce dimensionality. Manually annotated training images allow supervised training. The performance of Gaussian parametric and mixture models is compared when used to classify regions as either inflammatory or healthy. The system is optimized using a response surface method that maximises the area under the receiver operating characteristic curve. This system is then tested on images previously ranked by a number of observers with varying levels of expertise. These results are compared to the automated system using Spearman rank correlation. Results show that this system can rank 15 test images, with varying degrees of inflammation, in strong agreement with five expert pathologists

Limitations in Predicting the Space Radiation Health Risk for Exploration Astronauts

Despite years of research, understanding of the space radiation environment and the risk it poses to long-duration astronauts remains limited. There is a disparity between research results and observed empirical effects seen in human astronaut crews, likely due to the numerous factors that limit terrestrial simulation of the complex space environment and extrapolation of human clinical consequences from varied animal models. Given the intended future of human spaceflight, with efforts now to rapidly expand capabilities for human missions to the moon and Mars, there is a pressing need to improve upon the understanding of the space radiation risk, predict likely clinical outcomes of interplanetary radiation exposure, and develop appropriate and effective mitigation strategies for future missions. To achieve this goal, the space radiation and aerospace community must recognize the historical limitations of radiation research and how such limitations could be addressed in future research endeavors. We have sought to highlight the numerous factors that limit understanding of the risk of space radiation for human crews and to identify ways in which these limitations could be addressed for improved understanding and appropriate risk posture regarding future human spaceflight.Comment: Accepted for publication by Nature Microgravity (2018

Aerospace Medicine and Biology: A continuing bibliography with indexes (supplement 141)

This special bibliography lists 267 reports, articles, and other documents introduced into the NASA scientific and technical information system in April 1975

Characterizing pre-transplant and post-transplant kidney rejection risk by B cell immune repertoire sequencing.

Studying immune repertoire in the context of organ transplant provides important information on how adaptive immunity may contribute and modulate graft rejection. Here we characterize the peripheral blood immune repertoire of individuals before and after kidney transplant using B cell receptor sequencing in a longitudinal clinical study. Individuals who develop rejection after transplantation have a more diverse immune repertoire before transplant, suggesting a predisposition for post-transplant rejection risk. Additionally, over 2 years of follow-up, patients who develop rejection demonstrate a specific set of expanded clones that persist after the rejection. While there is an overall reduction of peripheral B cell diversity, likely due to increased general immunosuppression exposure in this cohort, the detection of specific IGHV gene usage across all rejecting patients supports that a common pool of immunogenic antigens may drive post-transplant rejection. Our findings may have clinical implications for the prediction and clinical management of kidney transplant rejection

Integrated Research Plan to Assess the Combined Effects of Space Radiation, Altered Gravity, and Isolation and Confinement on Crew Health and Performance: Problem Statement

Future crewed exploration missions to Mars could last up to three years and will expose astronauts to unprecedented environmental challenges. Challenges to the nervous system during these missions will include factors of: space radiation that can damage sensitive neurons in the central nervous system (CNS); isolation and confinement can affect cognition and behavior; and altered gravity that will change the astronauts perception of their environment and their spatial orientation, and will affect their coordination, balance, and locomotion. In the past, effects of spaceflight stressors have been characterized individually. However, long-term, simultaneous exposure to multiple stressors will produce a range of interrelated behavioral and biological effects that have the potential to adversely affect operationally relevant crew performance. These complex environmental challenges might interact synergistically and increase the overall risk to the health and performance of the astronaut. Therefore, NASAs Human Research Program (HRP) has directed an integrated approach to characterize and mitigate the risk to the CNS from simultaneous exposure to these multiple spaceflight factors. The proposed research strategy focuses on systematically evaluating the relationships among three existing research risks associated with spaceflight: Risk of Acute (In-flight) and Late Central Nervous System Effects from Radiation (CNS), Risk of Adverse Cognitive or Behavioral Conditions and Psychiatric Disorders (BMed), and Risk of Impaired Control of Spacecraft/Associated Systems and Decreased Mobility Due to Vestibular/Sensorimotor Alterations Associated with Spaceflight (SM). NASAs HRP approach is intended to identify the magnitude and types of interactions as they affect behavior, especially as it relates to operationally relevant performance (e.g., performance that depends on reaction time, procedural memory, etc.). In order to appropriately characterize this risk of multiple spaceflight environmental stressors, there is a recognition of the need to leverage research approaches using appropriate animal models and behavioral constructs. Very little has been documented on the combined effects of altered gravity, space radiation, and other psychological and cognitive stressors on the CNS. Preliminary evidence from rodents suggest that a combination of a minimum of exposures to even two of three stressors of: simulated space radiation, simulated microgravity, and simulated isolation and confinement, have produced different and more pronounced biological and performance effects than exposure to these same stressors individually. Structural and functional changes to the CNS of rodents exposed to transdisciplinary combined stressors indicate that important processes related to information processing are likely altered including impairment of exploratory and risk taking behaviors, as well as executive function including learning, memory, and cognitive flexibility all of which may be linked to changes in related operational relevant performance. The fully integrated research plan outlines approaches to evaluate how combined, potentially synergistic, impacts of simultaneous exposures to spaceflight hazards will affect an astronauts CNS and their operationally relevant performance during future exploration missions, including missions to the Moon and Mars. The ultimate goals are to derive risk estimates for the combined, potentially synergistic, effects of the three major spaceflight hazards that will establish acceptable maximum decrement or change in a physiological or behavioral parameters during or after spaceflight, the acceptable limit of exposure to a spaceflight factor, and to evaluate strategies to mitigate any associated decrements in operationally relevant performance

Numerical Study of a Left Ventricular Assist Device (LVAD) With Different Blade Heights and Tip Clearances

One treatment modality for heart failure is to employ a mechanical heart assist device to increase blood flow to peripheral organs. There are various kinds of axial and centrifugal type mechanical pumps available for implantation depending on patient condition. Axial pumps are smaller in size comparatively, although centrifugal pumps have the advantages of lower rotational speed as well as better maintaining any native blood flow pulsatility. This work presents the results of the numerical study of the centrifugal blood pump configured as a Left Ventricular Assist Device (LVAD). The pump design utilized standard industrial centrifugal pump design principles but applied to smaller sized blood pumps. Flow characteristics are modelled using 3-dimensional steady state models operating at design speed of 2000 rpm using Newtonian blood properties for the fluid. Two design parameters of the pump are studied, the impeller blade height and tip clearance resulting in nine model variants. Analysis includes the hydrodynamic performance of the pump and the flow characteristics in the pump. A haemolysis prediction model quantifying red blood cell stress from exposure time and shear stress was used for quantitative predictions of haemolysis within the blood pump. Blood damage estimation was calculated along each path-line and averaged to a single value. By using a ranked selection method, the model with the 15 mm blade height and 800 µm tip clearance was selected as the preferred configuration with Haemolysis Index of 0.01 mmHg, efficiency of 58% at 104 mmHg outlet pressure

Aerospace Medicine and Biology: A continuing bibliography with indexes (supplement 314)

This bibliography lists 139 reports, articles, and other documents introduced into the NASA scientific and technical information system in August, 1988

Numerical Model to Predict Hemolysis and Transport in a Membrane-Based Microfluidic Device

Microfluidics has become an increasingly popular tool in the design and development of medical devices and artificial organs. Two promising applications of microfluidics are dialyzers and oxygenators. As a step toward portable dialysis treatment, continuous microfluidic dialysis may resolve many clinical issues with current dialysis treatments. Additionally, commercially available oxygenators exceed the blood volume of neonatal patients; low-volume microfluidic devices may safely deliver oxygen to these patients. Two critical parameters in the development of these devices is mechanical hemolysis and membrane diffusion, which are intricately connected to the geometry, flow rate, properties of the membrane, and each other. A computational model is developed to elucidate the connection between these phenomena to guide the design and optimization of these devices. In vitro experiments are conducted to validate the model. Importantly, a subset of hemolysis models agrees with experimental data, which is consistent with the literature. Additionally, the effect of microfluidic mixing elements that perturb flow near the membrane interface are studied in silico and in vitro. These data reveal that herringbone mixing elements increase hemolysis by 10% and flux across the membrane interface by 38% in silico and a statistically significant difference between smooth and herringbone devices is observed for a subset of devices tested. Furthermore, 10 of 18 computational models of hemolysis are shown to be statistically similar to experimental data. The agreement of these results suggest that finite element analysis may be able to quantitively model important factors in the design of microfluidic oxygenators and dialyzers