"Making Safety Happen" Through Probabilistic Risk Assessment at NASA

NASA is using Probabilistic Risk Assessment (PRA) as one of the tools in its Safety & Mission Assurance (S&MA) tool belt to identify and quantify risks associated with human spaceflight. This paper discusses some of the challenges and benefits associated with developing and using PRA for NASA human space programs. Some programs have entered operation prior to developing a PRA, while some have implemented PRA from the start of the program. It has been observed that the earlier a design change is made in the concept or design phase, the less impact it has on cost and schedule. Not finding risks until the operation phase yields much costlier design changes and major delays, which can result in discussions of just accepting the risk. Risk contributors identified by PRA are not just associated with hardware failures. They include but are not limited to crew fatality due to medical causes, the environment the vehicle and crew are exposed to, the software being used, and the reliability of the crew performing required actions. Some programs have entered operation prior to developing a PRA, and while PRA can still provide a benefit for operations and future design trades, the benefit of implementing PRA from the start of the program provides the added benefit of informing design and reducing risk early in program development. Currently, NASAs International Space Station (ISS) program is in its 20th year of on-orbit operations around the Earth and has several new programs in the design phase preparing to enter the operation phase all of which have active (or living) PRAs. These programs incorporate PRA as part of their Risk-Informed, Decision-Making (RIDM) process. For new NASA human spaceflight programs discussion begins with mission concept, establishing requirements, forming the PRA team, and continues through the design cycles into the operational phase. Several examples of PRA related applications and observed lessons are included

Design considerations of the AO module for the Gemini South multiconjugate adaptive optics system

The adaptive optics system for the Gemini South telescope, currently in the design phase, consists of several major subsystem. The largest subsystem, called the AO module, contains most of the optics and electronics and is mounted on one of the Cassegrain instrument ports. The initial system will be a conventional laser guide star AO system, but the plan is to eventually expand it to a multi-conjugate system. The system is being designed to readily add the components necessary to upgrade to a multi-conjugate system. This paper describes the design challenges encountered and solutions that were derived for the AO module design. The complexity of the multi-conjugate version is illustrated, including optical, mechanical, electronic and controls issues

The Comparative Toxicogenomics Database (CTD).

The Mount Desert Island Biological Laboratory in Salsbury Cove, Maine, USA, is developing the Comparative Toxicogenomics Database (CTD), a community-supported genomic resource devoted to genes and proteins of human toxicologic significance. CTD will be the first publicly available database to a) provide annotated associations among genes, proteins, references, and toxic agents, with a focus on annotating data from aquatic and mammalian organisms; b) include nucleotide and protein sequences from diverse species; c) offer a range of analysis tools for customized comparative studies; and d) provide information to investigators on available molecular reagents. This combination of features will facilitate cross-species comparisons of toxicologically significant genes and proteins. These comparisons will promote understanding of molecular evolution, the significance of conserved sequences, the genetic basis of variable sensitivity to environmental agents, and the complex interactions between the environment and human health. CTD is currently under development, and the planned scope and functions of the database are described herein. The intent of this report is to invite community participation in the development of CTD to ensure that it will be a valuable resource for environmental health, molecular biology, and toxicology research

The Application of Geographic Information Systems (GIS) to Improving Health Systems in the Upper East Region of Ghana

Despite the increased use of Geographic Information System (GIS) for health research, the technology is least used in settings where evidence based decision-making is needed most: High mortality settings of Africa where resource constraints impede the provision of essential care. This paper reports on a case study of GIS application in the Upper East Region (UER), one of the poorest regions in Ghana. Methods: Ghana Health Service (GHS) workers were trained to use GPS handheld devices to gather waypoints (coordinates) of all health care facilities and amenities throughout the UER. The waypoints data were then exported to Excel spreadsheets and cleaned of all inconsistencies. The final data was imported into ArcMap 10.2.2 software for data manipulation, display, and analysis. Results: Preventive health issues portrayed by GIS visualization included a substandard access to potable water in one community and health facility deficiencies in the Binduri district. As examples of GIS morbidity surveillance, we map the temporal incidence of cholera in two districts, and evidence of a pattern in the seasonal outbreaks of cerebral spinal meningitis (CSM). Conclusion: Results attest to the feasibility of using GIS to clarify health issues in a severely health service deprived setting, enabling public health authorities to optimize system responses where mostly needed. GIS technology has enabled health officials in the region to visualize the geographic pattern of disease outbreaks in ways that permit the imposition of efficient containment strategies

Cyclic AMP stimulates sorting of the canalicular organic anion transporter (Mrp2/cMoat) to the apical domain in hepatocyte couplets

The canalicular membrane of rat hepatocytes contains an ATP-dependent multispecific organic anion transporter, also named multidrug resistance protein 2, that is responsible for the biliary secretion of several amphiphilic organic anions. This transport function is markedly diminished in mutant rats that lack the transport protein. To assess the role of vesicle traffic in the regulation of canalicular organic anion transport, we have examined the redistribution of the transporter to the canalicular membrane and the effect of cAMP on this process in isolated hepatocyte couplets, which retain secretory polarity. The partial disruption of cell-cell contact, due to the isolation procedure, leaves the couplet with both remnant apical membranes, as a source of apical proteins, and an intact apical domain and lumen, to which these proteins are targeted. The changes in distribution of the transporter were correlated to the apical excretion of a fluorescent substrate, glutathione-methyfluorescein. The data obtained in this study show that the transport protein, endocytosed from apical membrane remnants, first is redistributed along the basolateral plasma membrane. Then it is transcytosed to the remaining apical pole in a microtubule-dependent fashion, followed by the fusion of transporter-containing vesicles with the apical membrane. The cAMP analog dibutyrylcAMP stimulates all three steps, resulting in increased apically located transport protein, glutathione-methylfluorescein transport activity and apical membrane circumference. These findings indicate that the organic anion transport capacity of the apical membrane in hepatocyte couplets is regulated by cAMP-stimulated sorting of the multidrug resistance protein 2 to the apical membrane. The relevance of this phenomenon for the intact liver is discussed