Lessons Learned Study Final Report for the Exploration Systems Mission Directorate

This report is the final product of a 90-day study performed for the Exploration Systems Mission Directorate. The study was to assemble lessons NASA has learned from previous programs that could help the Exploration Systems Mission Directorate pursue the Exploration vision. It focuses on those lessons that should have the greatest significance to the Directorate during the formulation of program and mission plans. The study team reviewed a large number of lessons learned reports and data bases, including the Columbia Accident Investigation Board and Rogers Commission reports on the Shuttle accidents, accident reports from robotic space flight systems, and a number of management reviews by the Defense Sciences Board, Government Accountability Office, and others. The consistency of the lessons, findings, and recommendations validate the adequacy of the data set. In addition to reviewing existing databases, a series of workshops was held at each of the NASA centers and headquarters that included senior managers from the current workforce as well as retirees. The full text of the workshop reports is included in Appendix A. A lessons learned website was opened up to permit current and retired NASA personnel and on-site contractors to input additional lessons as they arise. These new lessons, when of appropriate quality and relevance, will be brought to the attention of managers. The report consists of four parts: Part 1 provides a small set of lessons, called the Executive Lessons Learned, that represent critical lessons that the Exploration Systems Mission Directorate should act on immediately. This set of Executive Lessons and their supporting rationale have been reviewed at length and fully endorsed by a team of distinguished NASA alumni; Part 2 contains a larger set of lessons, called the Selected Lessons Learned, which have been chosen from the lessons database and center workshop reports on the basis of their specific significance and relevance to the near-term work of the Exploration Directorate. These lessons frequently support the Executive lessons but are more general in nature; Part 3 consists of the reports of the center workshops that were conducted as part of this activity. These reports are included in their entirety (approximately 200 pages) in Appendix G and have significance for specific managers; Part 4 consists of the remainder of the lessons that have been selected by this effort and assembled into a database for the use of the Explorations Directorate. The database is archived and hosted in the Lessons Learned Knowledge Network, which provides a flexible search capability using a wide variety of search terms. Finally, a spreadsheet lists databases searched and a bibliography identifies reports that have been reviewed as sources of lessons for this task. NASA has been presented with many learning opportunities. We have conducted numerous programs, some extremely successful and others total failures. Most have been documented with a formal lessons learned activity, but we have not always incorporated these learning opportunities into our normal modes of business. For example, the Robbins Report of 2001 clearly indicates that many project failures of the past two decades were the result of violating well documented best practices, often in direct violation of management instructions and directives. An overarching lesson emerges: that disciplined execution in accordance with proven best practices is the greatest single contributor to a successful program. The Lessons Learned task team offers a sincere hope that the lessons presented herein will be helpful to the Exploration Systems Directorate in charting and executing their course. The success of the Directorate and of NASA in general depends on our collective ability to move forward without having to relearn the lessons of those who have gone before

Exile Vol. XXI No. 1

FICTION Lonely Wire Hangers by Larry Weber 7-11 untitled by Peggy Gifford 15-16 Anything by Joe Bolster 20-21 Easter Story by Ellen Claffy 25-27 Melanie by Dawn Patnode 31-34 PHOTOGRAPHY by Nanny Trippe 4, 22, 24, 28 by Geoffery Yeomans 6, 11, 17, 28, 30, 35, 36, 40 POETRY untitled by Martin Cloran 5 Mirror, Mirror by Tigger Montague 12 Twenty-Two Year Decay by Tigger Montague 13 Rice Puddin\u27 by Mary Mueller 14 untitled by Sharon Singleton 18 untitled by Sharon Singleton 19 untitled by Kim McMullen 23 Audience by Dawn Patnode 29 Extinction by Vic Coccimiglio 37 The Only Way I Know Her by Vic Coccimiglio 38 Touch by Vic Coccimiglio 38 Family by Vic Coccimiglio 3

Six Action Steps to Address Global Disparities in Parkinson Disease: A World Health Organization Priority

Importance: The Global Burden of Disease study conducted between 1990 and 2016, based on a global study of 195 countries and territories, identified Parkinson disease (PD) as the fastest growing neurological disorder when measured using death and disability. Most people affected by PD live in low- and middle-income countries (LMICs) and experience large inequalities in access to neurological care and essential medicines. This Special Communication describes 6 actions steps that are urgently needed to address global disparities in PD. Observations: The adoption by the 73rd World Health Assembly (WHA) of resolution 73.10 to develop an intersectoral global action plan on epilepsy and other neurological disorders in consultation with member states was the stimulus to coordinate efforts and leverage momentum to advance the agenda of neurological conditions, such as PD. In April 2021, the Brain Health Unit at the World Health Organization convened a multidisciplinary, sex-balanced, international consultation workshop, which identified 6 workable avenues for action within the domains of disease burden; advocacy and awareness; prevention and risk reduction; diagnosis, treatment, and care; caregiver support; and research. Conclusions and Relevance: The dramatic increase of PD cases in many world regions and the potential costs of PD-associated treatment will need to be addressed to prevent possible health service strain. Across the board, governments, multilateral agencies, donors, public health organizations, and health care professionals constitute potential stakeholders who are urged to make this a priority

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Disruption of Lateral Efferent Pathways: Functional Changes in Auditory Evoked Responses

The functional consequences of selectively lesioning the lateral olivocochlear efferent system in guinea pigs were studied. The lateral superior olive (LSO) contains the cell bodies of lateral olivocochlear neurons. Melittin, a cytotoxic chemical, was injected into the brain stem using stereotaxic coordinates and near-field evoked potentials to target the LSO. Brain stem histology revealed discrete damage to the LSO following the injections. Functional consequences of this damage were reflected in depressed amplitude of the compound action potential of the eighth nerve (CAP) following the lesion. Threshold sensitivity and N1 latencies were relatively unchanged. Onset adaptation of the cubic distortion product otoacoustic emission (DPOAE) was evident, suggesting a reasonably intact medial efferent system. The present results provide the first report of functional changes induced by isolated manipulation of the lateral efferent pathway. They also confirm the suggestion that changes in single-unit auditory nerve activity after cutting the olivocochlear bundle are probably a consequence of disrupting the more lateral of the two olivocochlear efferent pathways.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41379/1/10162_2002_Article_3018.pd

Species differences in size discrimination in the paracellular pathway reflected by oral bioavailability of poly(ethylene glycol) and D-peptides

Animal models are frequently used to aid prediction of intestinal absorption in humans. However, there is little comparative quantitative information on species differences in paracellular permeation, which is an important route for oral absorption of small to medium-sized hydrophilic drug molecules. This study addresses this issue by comparing the molecular mass (MM) dependency in oral bioavailability between rat and dog of poly(ethylene glycol) (PEG), a polydispersed model mixture commonly used to characterize paracellular absorption, and of a series of eight D-peptides (based on D-phenylalanine). Fasted rats and dogs received PEG (400/900) and the D-peptides (MM 236-406 Da), orally and intravenously, with total 24-48 h urine collection to estimate oral bioavailability. After HPLC separation, the individual PEG oligomers and D-peptides were determined using radiometric detection, for radiolabeled material, and LC-MS, for unlabeled (PEG) material. All compounds were predominantly excreted unchanged following intravenous administration. After oral administration, the predominant peak in the radiochromatogram was unchanged material, indicating stability of the compounds in the gastrointestinal tract. A clear molecular mass dependency in oral bioavailability was seen with both series, but with absorption much greater in dog than rat. Thus, for PEG in rat, bioavailability decreased sharply from 79 to around 2% with increasing MM between 282 and 591 Da, and then tapered to around 1. 5% up to 1295 Da. Whereas in dog, bioavailability remained around 100% for oligomers up to 600 Da and then decreased quite sharply with increasing MM, tending to plateau around 13% beyond 900 Da. Likewise, for the d-peptides in rat, bioavailability decreased from 30 to 1% with increasing MM between 236 and 406 Da, whereas in dog it was 100%, declining to 16% over the same molecular range. This species difference appears to be due to a larger pore size and greater frequency of pores in the paracellular pathway of dog compared to rat. Furthermore, on the basis of comparison with literature data for PEG and selected drugs, rat would appear to be a better predictor than dog of absorption of hydrophilic compounds in human