Analyzing human errors in flight mission operations

A long-term program is in progress at JPL to reduce cost and risk of flight mission operations through a defect prevention/error management program. The main thrust of this program is to create an environment in which the performance of the total system, both the human operator and the computer system, is optimized. To this end, 1580 Incident Surprise Anomaly reports (ISA's) from 1977-1991 were analyzed from the Voyager and Magellan projects. A Pareto analysis revealed that 38 percent of the errors were classified as human errors. A preliminary cluster analysis based on the Magellan human errors (204 ISA's) is presented here. The resulting clusters described the underlying relationships among the ISA's. Initial models of human error in flight mission operations are presented. Next, the Voyager ISA's will be scored and included in the analysis. Eventually, these relationships will be used to derive a theoretically motivated and empirically validated model of human error in flight mission operations. Ultimately, this analysis will be used to make continuous process improvements continuous process improvements to end-user applications and training requirements. This Total Quality Management approach will enable the management and prevention of errors in the future

High-throughput screening with the Eimeria tenella CDC2-related kinase2/cyclin complex EtCRK2/EtCYC3a

The poultry disease coccidiosis, caused by infection with Eimeria spp. apicomplexan parasites, is responsible for enormous economic losses to the global poultry industry. The rapid increase of resistance to therapeutic agents, as well as the expense of vaccination with live attenuated vaccines, requires the development of new effective treatments for coccidiosis. Because of their key regulatory function in the eukaryotic cell cycle, cyclin-dependent kinases (CDKs) are prominent drug targets. The Eimeria tenella CDC2-related kinase 2 (EtCRK2) is a validated drug target that can be activated in vitro by the CDK activator XlRINGO (Xenopus laevis rapid inducer of G2/M progression in oocytes). Bioinformatics analyses revealed four putative E. tenella cyclins (EtCYCs) that are closely related to cyclins found in the human apicomplexan parasite Plasmodium falciparum. EtCYC3a was cloned, expressed in Escherichia coli and purified in a complex with EtCRK2. Using the non-radioactive time-resolved fluorescence energy transfer (TR-FRET) assay, we demonstrated the ability of EtCYC3a to activate EtCRK2 as shown previously for XlRINGO. The EtCRK2/EtCYC3a complex was used for a combined in vitro and in silico high-throughput screening approach, which resulted in three lead structures, a naphthoquinone, an 8-hydroxyquinoline and a 2-pyrimidinyl-aminopiperidine-propane-2-ol. This constitutes a promising starting point for the subsequent lead optimization phase and the development of novel anticoccidial drugs

Mission operations and command assurance: Instilling quality into flight operations

Mission Operations and Command Assurance (MO&CA) is a Total Quality Management (TQM) task on JPL projects to instill quality in flight mission operations. From a system engineering view, MO&CA facilitates communication and problem-solving among flight teams and provides continuous process improvement to reduce the probability of radiating incorrect commands to a spacecraft. The MO&CA task has evolved from participating as a member of the spacecraft team to an independent team reporting directly to flight project management and providing system level assurance. JPL flight projects have benefited significantly from MO&CA's effort to contain risk and prevent rather than rework errors. MO&CA's ability to provide direct transfer of knowledge allows new projects to benefit from previous and ongoing flight experience

Self-reported evaluation of competencies and attitudes by physicians-in-training before and after a single day legislative advocacy experience

BACKGROUND: Advocacy is increasingly being recognized as a core element of medical professionalism and efforts are underway to incorporate advocacy training into graduate and undergraduate medical school curricula. While limited data exist to quantify physician attitudes toward advocacy, even less has been done to assess the knowledge, skills, and attitudes of future physicians. The purpose of this study was to assess students’ experiences and attitudes toward legislative advocacy, cutting out using a convience sample. METHODS: A paper survey based on previously validated surveys was administered to a convenience sample of premedical and medical student participants attending a National Advocacy Day in Washington, DC, in March 2011, both before and after their advocacy experiences. Responses were anonymous and either categorical ( or ordinal, using a 5-point Likert scale. Data were analyzed statistically to evaluate demographics and compare changes in pre- and post-experience attitude and skills. RESULTS: Data from 108 pre-advocacy and 50 post-advocacy surveys were analyzed yielding a response rate of 46.3%. Following a single advocacy experience, subjects felt they were more likely to contact their legislators about healthcare issues (p = 0.03), to meet in person with their legislators (p < 0.01), and to advocate for populations' health needs (p = 0.04). Participants endorsed an increased perception of the role of a physician advocate extending beyond individual patients (p = 0.03). Participants disagreed with the statement that their formal curricula adequately covered legislative healthcare advocacy. Additionally, respondents indicated that they plan to engage in legislative advocacy activities in the future (p < 0.01). CONCLUSIONS: A one-time practical advocacy experience has a positive influence on students’ knowledge, skills and attitudes towards legislative advocacy. Practical experience is an important method of furthering medical education in advocacy and further research is necessary to assess its impact in a broader population

Mission operations and command assurance: Flight operations quality improvements

Mission Operations and Command Assurance (MO&CA) is a Total Quality Management (TQM) task on JPL projects to instill quality in flight mission operations. From a system engineering view, MO&CA facilitates communication and problem-solving among flight teams and provides continuous solving among flight teams and provides continuous process improvement to reduce risk in mission operations by addressing human factors. The MO&CA task has evolved from participating as a member of the spacecraft team, to an independent team reporting directly to flight project management and providing system level assurance. JPL flight projects have benefited significantly from MO&CA's effort to contain risk and prevent rather than rework errors. MO&CA's ability to provide direct transfer of knowledge allows new projects to benefit from previous and ongoing flight experience

High Harvest Yield, High Expansion, and Phenotype Stability of CD146 Mesenchymal Stromal Cells from Whole Primitive Human Umbilical Cord Tissue

Human umbilical cord blood is an excellent primitive source of noncontroversial stem cells for treatment of hematologic disorders; meanwhile, new stem cell candidates in the umbilical cord (UC) tissue could provide therapeutic cells for nonhematologic disorders. We show novel in situ characterization to identify and localize a panel of some markers expressed by mesenchymal stromal cells (MSCs; CD44, CD105, CD73, CD90) and CD146 in the UC. We describe enzymatic isolation and purification methods of different UC cell populations that do not require manual separation of the vessels and stroma of the coiled, helical-like UC tissue. Unique quantitation of in situ cell frequency and stromal cell counts upon harvest illustrate the potential to obtain high numerical yields with these methods. UC stromal cells can differentiate to the osteogenic and chondrogenic lineages and, under specific culturing conditions, they exhibit high expandability with unique long-term stability of their phenotype. The remarkable stability of the phenotype represents a novel finding for human MSCs, from any source, and supports the use of these cells as highly accessible stromal cells for both basic studies and potentially therapeutic applications such as allogeneic clinical use for musculoskeletal disorders

Recessive RYR1 mutations cause unusual congenital myopathy with prominent nuclear internalization and large areas of myofibrillar disorganization.

International audienceAIMS: To report the clinical, pathological and genetic findings in a group of patients with a previously not described phenotype of congenital myopathy due to recessive mutations in the gene encoding the type 1 muscle ryanodine receptor channel (RYR1). METHODS: Seven unrelated patients shared a predominant axial and proximal weakness of varying severity, with onset during the neonatal period, associated with bilateral ptosis and ophthalmoparesis, and unusual muscle biopsy features at light and electron microscopic levels. RESULTS: Muscle biopsy histochemistry revealed a peculiar morphological pattern characterized by numerous internalized myonuclei in up to 51% of fibres and large areas of myofibrillar disorganization with undefined borders. Ultrastructurally, such areas frequently occupied the whole myofibre cross section and extended to a moderate number of sarcomeres in length. Molecular genetic investigations identified recessive mutations in the ryanodine receptor (RYR1) gene in six compound heterozygous patients and one homozygous patient. Nine mutations are novel and four have already been reported either as pathogenic recessive mutations or as changes affecting a residue associated with dominant malignant hyperthermia susceptibility. Only two mutations were located in the C-terminal transmembrane domain whereas the others were distributed throughout the cytoplasmic region of RyR1. CONCLUSION: Our data enlarge the spectrum of RYR1 mutations and highlight their clinical and morphological heterogeneity. A congenital myopathy featuring ptosis and external ophthalmoplegia, concomitant with the novel histopathological phenotype showing fibres with large, poorly delimited areas of myofibrillar disorganization and internal nuclei, is highly suggestive of an RYR1-related congenital myopathy

Healthcare Reform and the Next Generation: United States Medical Student Attitudes toward the Patient Protection and Affordable Care Act

CONTEXT: Over one year after passage of the Patient Protection and Affordable Care Act (PPACA), legislators, healthcare experts, physicians, and the general public continue to debate the implications of the law and its repeal. The PPACA will have a significant impact on future physicians, yet medical student perspectives on the legislation have not been well documented. OBJECTIVE: To evaluate medical students' understanding of and attitudes toward healthcare reform and the PPACA including issues of quality, access and cost. DESIGN, SETTING, AND PARTICIPANTS: An anonymous electronic survey was sent to medical students at 10 medical schools (total of 6982 students) between October-December 2010, with 1232 students responding and a response rate of 18%. MAIN OUTCOME MEASURES: Medical students' views and attitudes regarding the PPACA and related topics, measured with Likert scale and open response items. RESULTS: Of medical students surveyed, 94.8% agreed that the existing United States healthcare system needs to be reformed, 31.4% believed the PPACA will improve healthcare quality, while 20.9% disagreed and almost half (47.7%) were unsure if quality will be improved. Two thirds (67.6%) believed that the PPACA will increase access, 6.5% disagreed and the remaining 25.9% were unsure. With regard to containing healthcare costs, 45.4% of participants indicated that they are unsure if the provisions of the PPACA will do so. Overall, 80.1% of respondents indicated that they support the PPACA, and 78.3% also indicated that they did not feel that reform efforts had gone far enough. A majority of respondents (58.8%) opposed repeal of the PPACA, while 15.0% supported repeal, and 26.1% were undecided. CONCLUSION: The overwhelming majority of medical students recognized healthcare reform is needed and expressed support for the PPACA but echoed concerns about whether it will address issues of quality or cost containment

A population of proinflammatory T cells coexpresses αβ and γδ T cell receptors in mice and humans

T cells are classically recognized as distinct subsets that express αβ or γδ TCRs. We identify a novel population of T cells that coexpress αβ and γδ TCRs in mice and humans. These hybrid αβ-γδ T cells arose in the murine fetal thymus by day 16 of ontogeny, underwent αβ TCR–mediated positive selection into CD4+ or CD8+ thymocytes, and constituted up to 10% of TCRδ+ cells in lymphoid organs. They expressed high levels of IL-1R1 and IL-23R and secreted IFN-γ, IL-17, and GM-CSF in response to canonically restricted peptide antigens or stimulation with IL-1β and IL-23. Hybrid αβ-γδ T cells were transcriptomically distinct from conventional γδ T cells and displayed a hyperinflammatory phenotype enriched for chemokine receptors and homing molecules that facilitate migration to sites of inflammation. These proinflammatory T cells promoted bacterial clearance after infection with Staphylococcus aureus and, by licensing encephalitogenic Th17 cells, played a key role in the development of autoimmune disease in the central nervous system