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Background The COVID-19 pandemic continues to demonstrate the risks and profound health impacts that result from infectious disease emergencies. Emergency preparedness has been defined as the knowledge, capacity and organizational systems that governments, response and recovery organizations, communities and individuals develop to anticipate, respond to, or recover from emergencies. This scoping review explored recent literature on priority areas and indicators for public health emergency preparedness (PHEP) with a focus on infectious disease emergencies. Methods Using scoping review methodology, a comprehensive search was conducted for indexed and grey literature with a focus on records published from 2017 to 2020 onward, respectively. Records were included if they: (a) described PHEP, (b) focused on an infectious emergency, and (c) were published in an Organization for Economic Co-operation and Development country. An evidence-based all-hazards Resilience Framework for PHEP consisting of 11 elements was used as a reference point to identify additional areas of preparedness that have emerged in recent publications. The findings were analyzed deductively and summarized thematically. Results The included publications largely aligned with the 11 elements of the all-hazards Resilience Framework for PHEP. In particular, the elements related to collaborative networks, community engagement, risk analysis and communication were frequently observed across the publications included in this review. Ten emergent themes were identified that expand on the Resilience Framework for PHEP specific to infectious diseases. Planning to mitigate inequities was a key finding of this review, it was the most frequently identified emergent theme. Additional emergent themes were: research and evidence-informed decision making, building vaccination capacity, building laboratory and diagnostic system capacity, building infection prevention and control capacity, financial investment in infrastructure, health system capacity, climate and environmental health, public health legislation and phases of preparedness. Conclusion The themes from this review contribute to the evolving understanding of critical public health emergency preparedness actions. The themes expand on the 11 elements outlined in the Resilience Framework for PHEP, specifically relevant to pandemics and infectious disease emergencies. Further research will be important to validate these findings, and expand understanding of how refinements to PHEP frameworks and indicators can support public health practice.

Evaluating one’s own performance on a task, typically known as ‘self-assessment’, is perceived as a fundamental skill, but people appear poorly calibrated to their abilities. Studies seem to show poorer calibration for low performers than for high performers, which could indicate worse metacognitive ability among low performers relative to others (the Dunning–Kruger effect). By developing a rational model of self-assessment, we show that such an effect could be produced by two psychological mechanisms, in either isolation or conjunction: influence of prior beliefs about ability or a relation between performance and skill at determining correctness on each problem. To disentangle these explanations, we conducted a large-scale replication of a seminal paper with approximately 4,000 participants in each of two studies. Comparing the predictions of two variants of our rational model provides support for low performers being less able to estimate whether they are correct in the domains of grammar and logical reasoning. Reinvestigating the well-known Dunning–Kruger effect, Jansen et al. apply rational models to the decisions and metacognitive judgments of participants in two large online studies, finding evidence that poor performance comes with inaccurate self-assessment.

Heat shock protein 70 (Hsp70) chaperones bind many different sequences and discriminate between incompletely folded and folded clients. Most research into the origins of this “selective promiscuity” has relied on short peptides as substrates to dissect the binding, but much less is known about how Hsp70s bind full-length client proteins. Here, we connect detailed structural analyses of complexes between the Escherichia coli Hsp70 (DnaK) substrate-binding domain (SBD) and peptides encompassing five potential binding sites in the precursor to E. coli alkaline phosphatase (proPhoA) with SBD binding to full-length unfolded proPhoA. Analysis of SBD complexes with proPhoA peptides by a combination of X-ray crystallography, methyl-transverse relaxation optimized spectroscopy (methyl-TROSY), and paramagnetic relaxation enhancement (PRE) NMR and chemical cross-linking experiments provided detailed descriptions of their binding modes. Importantly, many sequences populate multiple SBD binding modes, including both the canonical N to C orientation and a C to N orientation. The favored peptide binding mode optimizes substrate residue side-chain compatibility with the SBD binding pockets independent of backbone orientation. Relating these results to the binding of the SBD to full-length pro- PhoA, we observe that multiple chaperones may bind to the protein substrate, and the binding sites, well separated in the proPhoA sequence, behave independently. The hierarchy of chaperone binding to sites on the protein was generally consistent with the apparent binding affinities observed for the peptides corresponding to these sites. Functionally, these results reveal that Hsp70s “read” sequences without regard to the backbone direction and that both binding orientations must be considered in current predictive algorithms.

Empirical audit and review is an approach to assessing the evidentiary value of a research area. It involves identifying a topic and selecting a cross-section of studies for replication. We apply the method to research on the psychological consequences of scarcity. Starting with the papers citing a seminal publication in the field, we conducted replications of 20 studies that evaluate the role of scarcity priming in pain sensitivity, resource allocation, materialism, and many other domains. There was considerable variability in the replicability, with some strong successes and other undeniable failures. Empirical audit and review does not attempt to assign an overall replication rate for a heterogeneous field, but rather facilitates researchers seeking to incorporate strength of evidence as they refine theories and plan new investigations in the research area. This method allows for an integration of qualitative and quantitative approaches to review and enables the growth of a cumulative science.

Introduction Studies consistently find that humans average approximately six hours of sleep per night in space, which is less than they sleep on Earth. It is unclear whether the sleep loss observed during spaceflight is related to modifiable factors, such as irregular scheduling and inadequate sleep environment or due to features of spaceflight that may alter physiology, such as microgravity. Recent missions have afforded crew better, more stable sleep schedules, and an improved sleep environment. Hence, the evaluation of sleep under these improved conditions should provide insight into the causes of sleep deficiency observed in space thus far. Methods Crewmembers (n = 19) wore actiwatches for two bouts of data collection lasting two weeks each before flight (at approximately L-270 and L-180), either continuously (n = 9) or for two weeks every two months while in space (n = 10), and for seven days postflight, immediately upon return to Earth. We compared sleep outcomes (sleep duration, wake after sleep onset [WASO], sleep efficiency, and sleep latency) between phases of flight using mixed effects models, with participant and intercept included as a random effect. Results Crewmembers averaged 7.3 +/- 0.4 hours of sleep per night in space. Though this was less than they achieved preflight (7.9 +/- 0.5) or postflight (7.8 +/- 0.8; F (2, 2866) = 86.26, p < .0001, ηp2 = .06), this duration of sleep meets the recommended amount for optimal human health and well-being. Sleep efficiency (%) also increased inflight (88.7 +/- 2.7) compared to preflight (84.7 +/- 5.5) and postflight (84.4 +/- 6.1; F (2, 2630) = 124.08, p < .0001, ηp2 = .09), while WASO (min) decreased inflight (29.6 +/- 8.2) compared to preflight (46.4 +/- 15.5) and postflight (48.7 +/- 16.0); F (2, 2629) = 285.90, p < .0001, ηp2 = .18). There were no changes across these variables over time inflight. Conclusion We conclude that humans are capable of achieving sufficient sleep in space. Going forward, it is imperative that crewmembers are provided with stable schedules, with moderate workload, and environments that are conducive to sleep. Support (if any) NASA Human Factors and Behavioral Health Element, NASA Human Research Program

What does the word \"math\" evoke? It is in many ways a fraught term eliciting negative reactions and unpleasant memories. In this dissertation, I explore the variety of ways we humans perceive this concept, starting with the internal (perceptions of ability), then the personal journey (perceptions of belonging), and finally the external (perceptions of conception). I employ a mixture of experiments and computational modeling in order to develop a more holistic understanding of how people perceive math and reinforce human studies with data collected from naturalistic settings - specifically, the internet, to explore word usage and how discussions of math seem to differ from mentions of other concepts.

mTORC1 regulates cell growth and catabolism in response to fluctuations in nutrients through phosphorylation of key substrates. The tumor suppressor FLCN is a RagC GTPase activating protein (GAP) that regulates mTORC1 phosphorylation of TFEB, controlling lysosome biogenesis and autophagy. Here, we determined the cryo-EM structure of the active FLCN complex (AFC) containing FLCN, FNIP2, the N-terminal tail of SLC38A9, the RagAGDP:RagCGDP.BeFx- GTPase dimer, and the Ragulator scaffold. Relative to the inactive lysosomal FLCN complex (LFC) structure, FLCN reorients by 90°, breaks its contacts with RagA, and makes new contacts with RagC that position its Arg164 finger for catalysis. Disruption of the AFC-specific interfaces of FLCN and FNIP2 with RagC eliminated GAP activity in vitro and led to nuclear retention of TFE3, with no effect on mTORC1 phosphorylation of S6K or 4E-BP1. The structure thus provides a roadmap to discover TFEB-selective mTORC1 antagonists. The cryo-EM structure of the active FLCN RagC GAP complex provides a structural basis for TFEB/TFE3 substrate-selective targeting of mTORC1.

mTORC1 regulates cell growth and catabolism in response to fluctuations in nutrients through phosphorylation of key substrates. The tumor suppressor FLCN is a RagC/D GTPase activating protein (GAP) that regulates mTORC1 phosphorylation of MiT-TFE family transcription factors, controlling lysosome biogenesis and autophagy. Here, we determined the cryo-EM structure of the active FLCN complex (AFC) containing FLCN, FNIP2, the N-terminal tail of SLC38A9, the RagAGDP:RagCGDP.BeFx- GTPase dimer, and the Ragulator scaffold. Relative to the inactive lysosomal FLCN complex (LFC) structure, FLCN reorients by 90o, breaks its contacts with RagA, and makes new contacts with RagC that position its Arg164 finger for catalysis. Disruption of the AFC-specific interfaces of FLCN and FNIP2 with RagC eliminated GAP activity in vitro and led to nuclear retention of the MiT-TFE family member TFE3, with no effect on mTORC1 phosphorylation of S6K or 4E-BP1. The structure thus provides a structural basis for the regulation of an mTORC1 substrate-specific pathway and a roadmap to discover MiT-TFE family selective mTORC1 antagonists. Competing Interest Statement J.H.H. is a co-founder and shareholder of Casma Therapeutics and receives research funding from Casma Therapeutics, Genentech, and Hoffmann-La Roche. R.Z. is a cofounder and shareholder of Frontier Medicines and receives research funding from Genentech. Footnotes * This version corresponds to the initial submission to the journal which has provisionally accepted the associated manuscript and complies with the journal's embargo policy.

On March 9, I danced with three of my best friends at a local bar, chasing tequila shots with pineapple juice because they had run out of limes. At 1 a.m., the bar's lights came on and we walked 20 minutes to another bar in the area, not wanting...