Derivation and Validation of a Preoperative Prediction Rule for Delirium After Cardiac Surgery

Background— Delirium is a common outcome after cardiac surgery. Delirium prediction rules identify patients at risk for delirium who may benefit from targeted prevention strategies, early identification, and treatment of underlying causes. The purpose of the present prospective study was to develop a prediction rule for delirium in a cardiac surgery cohort and to validate it in an independent cohort. Methods and Results— Prospectively, cardiac surgery patients ≥60 years of age were enrolled in a derivation sample (n=122) and then a validation sample (n=109). Beginning on the second postoperative day, patients underwent a standardized daily delirium assessment, and delirium was diagnosed according to the confusion assessment method. Delirium occurred in 63 (52%) of the derivation cohort patients. Multivariable analysis identified 4 variables independently associated with delirium: prior stroke or transient ischemic attack, Mini Mental State Examination score, abnormal serum albumin, and the Geriatric Depression Scale. Points were assigned to each variable: Mini Mental State Examination ≤23 received 2 points, and Mini Mental State Examination score of 24 to 27 received 1 point; Geriatric Depression Scale >4, prior stroke/transient ischemic attack, and abnormal albumin received 1 point each. In the derivation sample, the cumulative incidence of delirium for point levels of 0, 1, 2, and ≥3 was 19%, 47%, 63%, and 86%, respectively (C statistic, 0.74). The corresponding incidence of delirium in the validation sample was 18%, 43%, 60%, and 87%, respectively (C statistic, 0.75). Conclusions— Delirium occurs frequently after cardiac surgery. Using 4 preoperative characteristics, clinicians can determine cardiac surgery patients’ risk for delirium. Patients at higher delirium risk could be candidates for close postoperative monitoring and interventions to prevent delirium

Susceptibility sets and the final outcome of collective Reed–Frost epidemics

This paper is concerned with exact results for the final outcome of stochastic SIR (susceptible → infective → recovered) epidemics among a closed, finite and homogeneously mixing population. The factorial moments of the number of initial susceptibles who ultimately avoid infection by such an epidemic are shown to be intimately related to the concept of a susceptibility set. This connection leads to simple, probabilistically illuminating proofs of exact results concerning the total size and severity of collective Reed–Frost epidemic processes, in terms of Gontcharoff polynomials, first obtained in a series of papers by Claude Lef`evre and Philippe Picard. The proofs extend easily to include general final state random variables defined on SIR epidemics, and also to multitype epidemics

Emerging Standards and the Hybrid Model for Organizing Scientific Events During and After The COVID-19 Pandemic.

Since the beginning of 2020, the COVID-19 pandemic has dramatically influenced almost every aspect of human life. Activities requiring human gatherings have either been postponed, cancelled, or held completely virtually. To supplement lack of in-person contact, people have increasingly turned to virtual settings on-line, advantages of which include increased inclusivity and accessibility and reduction of carbon footprint. However, emerging online technologies cannot fully replace, in-person scientific events. In-person meetings are not susceptible to poor internet connectivity problems, and they provide novel opportunities for socialization, creating new collaborations, and sharing ideas. To continue such activities, a hybrid model for scientific events could be a solution offering both in-person and virtual components. While participants can freely choose the mode of their participation, virtual meetings would most benefit those who cannot attend in-person due to the limitations. In-person portions of meetings should be organized with full consideration of prevention and safety strategies including risk assessment and mitigation, venue and environmental sanitation, participant protection and disease prevention, and promoting the hybrid model. This new way of interaction between scholars can be considered as a part of a resilience system which was neglected previously and should become a part of routine practice in scientific community

The quest for the solar g modes

Solar gravity modes (or g modes) -- oscillations of the solar interior for which buoyancy acts as the restoring force -- have the potential to provide unprecedented inference on the structure and dynamics of the solar core, inference that is not possible with the well observed acoustic modes (or p modes). The high amplitude of the g-mode eigenfunctions in the core and the evanesence of the modes in the convection zone make the modes particularly sensitive to the physical and dynamical conditions in the core. Owing to the existence of the convection zone, the g modes have very low amplitudes at photospheric levels, which makes the modes extremely hard to detect. In this paper, we review the current state of play regarding attempts to detect g modes. We review the theory of g modes, including theoretical estimation of the g-mode frequencies, amplitudes and damping rates. Then we go on to discuss the techniques that have been used to try to detect g modes. We review results in the literature, and finish by looking to the future, and the potential advances that can be made -- from both data and data-analysis perspectives -- to give unambiguous detections of individual g modes. The review ends by concluding that, at the time of writing, there is indeed a consensus amongst the authors that there is currently no undisputed detection of solar g modes.Comment: 71 pages, 18 figures, accepted by Astronomy and Astrophysics Revie

Transgenic Expression of Nonclassically Secreted FGF Suppresses Kidney Repair

FGF1 is a signal peptide-less nonclassically released growth factor that is involved in angiogenesis, tissue repair, inflammation, and carcinogenesis. The effects of nonclassical FGF export in vivo are not sufficiently studied. We produced transgenic mice expressing FGF1 in endothelial cells (EC), which allowed the detection of FGF1 export to the vasculature, and studied the efficiency of postischemic kidney repair in these animals. Although FGF1 transgenic mice had a normal phenotype with unperturbed kidney structure, they showed a severely inhibited kidney repair after unilateral ischemia/reperfusion. This was manifested by a strong decrease of postischemic kidney size and weight, whereas the undamaged contralateral kidney exhibited an enhanced compensatory size increase. In addition, the postischemic kidneys of transgenic mice were characterized by hyperplasia of interstitial cells, paucity of epithelial tubular structures, increase of the areas occupied by connective tissue, and neutrophil and macrophage infiltration. The continuous treatment of transgenic mice with the cell membrane stabilizer, taurine, inhibited nonclassical FGF1 export and significantly rescued postischemic kidney repair. It was also found that similar to EC, the transgenic expression of FGF1 in monocytes and macrophages suppresses kidney repair. We suggest that nonclassical export may be used as a target for the treatment of pathologies involving signal peptide-less FGFs

Adaptations to Climate-Mediated Selective Pressures in Humans

Humans inhabit a remarkably diverse range of environments, and adaptation through natural selection has likely played a central role in the capacity to survive and thrive in extreme climates. Unlike numerous studies that used only population genetic data to search for evidence of selection, here we scan the human genome for selection signals by identifying the SNPs with the strongest correlations between allele frequencies and climate across 61 worldwide populations. We find a striking enrichment of genic and nonsynonymous SNPs relative to non-genic SNPs among those that are strongly correlated with these climate variables. Among the most extreme signals, several overlap with those from GWAS, including SNPs associated with pigmentation and autoimmune diseases. Further, we find an enrichment of strong signals in gene sets related to UV radiation, infection and immunity, and cancer. Our results imply that adaptations to climate shaped the spatial distribution of variation in humans

The urgent need for integrated science to fight COVID-19 pandemic and beyond

The COVID-19 pandemic has become the leading societal concern. The pandemic has shown that the public health concern is not only a medical problem, but also afects society as a whole; so, it has also become the leading scientifc concern. We discuss in this treatise the importance of bringing the world’s scientists together to fnd efective solu‑ tions for controlling the pandemic. By applying novel research frameworks, interdisciplinary collaboration promises to manage the pandemic’s consequences and prevent recurrences of similar pandemics

Significance testing as perverse probabilistic reasoning

Truth claims in the medical literature rely heavily on statistical significance testing. Unfortunately, most physicians misunderstand the underlying probabilistic logic of significance tests and consequently often misinterpret their results. This near-universal misunderstanding is highlighted by means of a simple quiz which we administered to 246 physicians at two major academic hospitals, on which the proportion of incorrect responses exceeded 90%. A solid understanding of the fundamental concepts of probability theory is becoming essential to the rational interpretation of medical information. This essay provides a technically sound review of these concepts that is accessible to a medical audience. We also briefly review the debate in the cognitive sciences regarding physicians' aptitude for probabilistic inference

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field