Changes in performance and bio-mathematical model performance predictions during 45 days of sleep restriction in a simulated space mission

Lunar habitation and exploration of space beyond low-Earth orbit will require small crews to live in isolation and confinement while maintaining a high level of performance with limited support from mission control. Astronauts only achieve approximately 6 h of sleep per night, but few studies have linked sleep deficiency in space to performance impairment. We studied crewmembers over 45 days during a simulated space mission that included 5 h of sleep opportunity on weekdays and 8 h of sleep on weekends to characterize changes in performance on the psychomotor vigilance task (PVT) and subjective fatigue ratings. We further evaluated how well bio-mathematical models designed to predict performance changes due to sleep loss compared to objective performance. We studied 20 individuals during five missions and found that objective performance, but not subjective fatigue, declined from the beginning to the end of the mission. We found that bio-mathematical models were able to predict average changes across the mission but were less sensitive at predicting individual-level performance. Our findings suggest that sleep should be prioritized in lunar crews to minimize the potential for performance errors. Bio-mathematical models may be useful for aiding crews in schedule design but not for individual-level fitness-for-duty decisions

Perspectives on fatigue in short-haul flight operations from US pilots: A focus group study

There are few studies investigating the impact of fatigue in short-haul flight operations conducted under United States (US) 14 Code of Federal Regulations Part 117 flight and duty limitations and rest requirements. In order to understand the fatigue factors unique to short-haul operations, we conducted a series of focus groups across four major commercial passenger airlines in the US. Ninety short-haul pilots were recruited through emails distributed by airline safety teams and labor representatives. Fourteen focus groups were conducted via an online conferencing platform in which participants were asked to identify short-haul schedules and operations that they felt: a) elevated fatigue, b) were not fatiguing, and c) were important to study. Data were collected anonymously and coded using conventional qualitative content analysis, with axial coding and summative analysis used to identify main themes and over-arching categories. The six fatigue factor categories identified were: circadian disruption, high workload, inadequate rest opportunity, schedule changes, regulation implementation and policy issues, and long sits. It appears that additional mitigation strategies may be needed to manage fatigue in short-haul operations beyond the current regulations. Future field studies of short-haul operations in the US should investigate the prevalence and impact of these factors

Changes in performance and bio-mathematical model performance predictions during 45 days of sleep restriction in a simulated space mission

Lunar habitation and exploration of space beyond low-Earth orbit will require small crews to live in isolation and confinement while maintaining a high level of performance with limited support from mission control. Astronauts only achieve approximately 6 h of sleep per night, but few studies have linked sleep deficiency in space to performance impairment. We studied crewmembers over 45 days during a simulated space mission that included 5 h of sleep opportunity on weekdays and 8 h of sleep on weekends to characterize changes in performance on the psychomotor vigilance task (PVT) and subjective fatigue ratings. We further evaluated how well bio-mathematical models designed to predict performance changes due to sleep loss compared to objective performance. We studied 20 individuals during five missions and found that objective performance, but not subjective fatigue, declined from the beginning to the end of the mission. We found that bio-mathematical models were able to predict average changes across the mission but were less sensitive at predicting individual-level performance. Our findings suggest that sleep should be prioritized in lunar crews to minimize the potential for performance errors. Bio-mathematical models may be useful for aiding crews in schedule design but not for individual-level fitness-for-duty decisions

Chemical genetics of Plasmodium falciparum.

Malaria caused by Plasmodium falciparum is a disease that is responsible for 880,000 deaths per year worldwide. Vaccine development has proved difficult and resistance has emerged for most antimalarial drugs. To discover new antimalarial chemotypes, we have used a phenotypic forward chemical genetic approach to assay 309,474 chemicals. Here we disclose structures and biological activity of the entire library-many of which showed potent in vitro activity against drug-resistant P. falciparum strains-and detailed profiling of 172 representative candidates. A reverse chemical genetic study identified 19 new inhibitors of 4 validated drug targets and 15 novel binders among 61 malarial proteins. Phylochemogenetic profiling in several organisms revealed similarities between Toxoplasma gondii and mammalian cell lines and dissimilarities between P. falciparum and related protozoans. One exemplar compound displayed efficacy in a murine model. Our findings provide the scientific community with new starting points for malaria drug discovery

Chemical genetics of Plasmodium falciparum

Malaria caused by Plasmodium falciparum is a disease that is responsible for 880,000 deaths per year worldwide. Vaccine development has proved difficult and resistance has emerged for most antimalarial drugs. To discover new antimalarial chemotypes, we have used a phenotypic forward chemical genetic approach to assay 309,474 chemicals. Here we disclose structures and biological activity of the entire library-many of which showed potent in vitro activity against drug-resistant P. falciparum strains-and detailed profiling of 172 representative candidates. A reverse chemical genetic study identified 19 new inhibitors of 4 validated drug targets and 15 novel binders among 61 malarial proteins. Phylochemogenetic profiling in several organisms revealed similarities between Toxoplasma gondii and mammalian cell lines and dissimilarities between P. falciparum and related protozoans. One exemplar compound displayed efficacy in a murine model. Our findings provide the scientific community with new starting points for malaria drug discovery.Full Tex