Throughout the last two decades, Bayesian statistical methods have proliferated throughout ecology and evolution. Numerous previous references established both philosophical and computational ...guidelines for implementing Bayesian methods. However, protocols for incorporating prior information, the defining characteristic of Bayesian philosophy, are nearly nonexistent in the ecological literature. Here, I hope to encourage the use of weakly informative priors in ecology and evolution by providing a ‘consumer's guide’ to weakly informative priors. The first section outlines three reasons why ecologists should abandon noninformative priors: 1) common flat priors are not always noninformative, 2) noninformative priors provide the same result as simpler frequentist methods, and 3) noninformative priors suffer from the same high type I and type M error rates as frequentist methods. The second section provides a guide for implementing informative priors, wherein I detail convenient ‘reference’ prior distributions for common statistical models (i.e. regression, ANOVA, hierarchical models). I then use simulations to visually demonstrate how informative priors influence posterior parameter estimates. With the guidelines provided here, I hope to encourage the use of weakly informative priors for Bayesian analyses in ecology. Ecologists can and should debate the appropriate form of prior information, but should consider weakly informative priors as the new ‘default’ prior for any Bayesian model.
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Abstract
Background
Infections caused by fungi can be important causes of morbidity and mortality in certain patient populations, including those who are highly immunocompromised or critically ill. ...Invasive mycoses can be caused by well-known species, as well as emerging pathogens, including those that are resistant to clinically available antifungals.
Content
This review highlights emerging fungal infections, including newly described species, such as Candida auris, and those that having undergone taxonomic classification and were previously known by other names, including Blastomyces and Emergomyces species, members of the Rasamsonia argillacea species complex, Sporothrix brasiliensis, and Trichophyton indotinae. Antifungal resistance also is highlighted in several of these emerging species, as well as in the well-known opportunistic pathogen Aspergillus fumigatus. Finally, the increased recognition and importance of fungal co-infections with respiratory pathogens, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is discussed.
Summary
Both clinicians and clinical microbiology laboratories should remain vigilant regarding emerging fungal infections. These may be difficult both to diagnose and treat due to the lack of experience of clinicians and laboratory personnel with these organisms and the infections they may cause. Many of these fungal infections have been associated with poor clinical outcomes, either due to inappropriate therapy or the development of antifungal resistance.
•VT-1161, VT-1129, and VT-1598 have greater specificity for fungal Cyp51 than mammalian CYP 450 enzymes.•CD101 and SCY-078 target 1,3-β-D-glucan and may offer advantages over available ...echinocandins.•VT-1598, CD101, and SCY-078 have in vitro activity against the emerging pathogen Candida auris.•AX001 targets glycosylphosphadidylinositol (GPI) biosynthesis and has potent, broad–spectrum antifungal activity.•F901318 targets fungal pyrimidine biosynthesis with potent activity against certain molds.
Clinically available antifungals for the treatment of invasive fungal infections primarily target either ergosterol in the fungal cell membrane or 1,3-β-D-glucan in the fungal cell wall. These classes include the polyene amphotericin B, the triazoles, and the echinocandins. Although newer antifungals and improved formulations of others have advanced our ability to treat patients with invasive mycoses, these drugs are often limited by toxicities, drug interactions, and the need for intravenous administration. Several investigational agents are currently under development. These include those that also target either ergosterol or 1,3-β-D-glucan, but have advantages over currently available drugs. Among these are the tetrazoles VT-1129, VT-1161, and VT-1598 that are more specific for fungal Cyp51 and less so for mammalian CYP 450 enzymes, the echinocandin CD101 that has an extended half-life, and the glucan synthase inhibitor SCY-078, which is being developed for oral administration. In addition, several agents with novel mechanisms of action are also under development. These include the inositol acyltransferase AX001, the dihydroorotate dehydrogenase inhibitor F901318, and VL-2397, which is similar in structure to the siderophore ferrichrome. In addition to possibly overcoming the limitations of currently available antifungals, these newer agents may be less susceptible to mechanisms of resistance that may render antifungals ineffective. Each of these investigational agents has the potential to improve patient outcomes in the treatment of invasive mycoses.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Ideology is a central construct in political psychology. Even so, the field's strong claims about an ideological public rarely engage evidence of enormous individual differences: a minority with real ...ideological coherence and weak to nonexistent political belief organization for everyone else. Here, I bridge disciplinary gaps by showing the limits of mass political ideology with several popular measures and components—self‐identification, core political values (egalitarian and traditionalism's resistance to change), and policy indices—in representative U.S. surveys across four decades (Ns ~ 13 k–37 k), plus panel data testing stability. Results show polar, coherent, stable, and potent ideological orientations only among the most knowledgeable 20–30% of citizens. That heterogeneity means full‐sample tests overstate ideology for most people but understate it for knowledgeable citizens. Whether through top‐down opinion leadership or bottom‐up ideological reasoning, organized political belief systems require political attention and understanding to form. Finally, I show that convenience samples make trouble for ideology generalizations. I conclude by proposing analytic best practices to help avoid overclaiming ideology in the public. Taken together, what first looks like strong and broad ideology is actually ideological innocence for most and meaningful ideology for a few.
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BFBNIB, DOBA, FZAB, GIS, IJS, INZLJ, IZUM, KILJ, NLZOH, NMLJ, NUK, ODKLJ, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK, ZRSKP
The design and control of material interfaces is a foundational approach to realize technologically useful effects and engineer material properties. This is especially true for two-dimensional (2D) ...materials, where van der Waals stacking allows disparate materials to be freely stacked together to form highly customizable interfaces. This has underpinned a recent wave of discoveries based on excitons in stacked double layers of transition metal dichalcogenides (TMDs), the archetypal family of 2D semiconductors. In such double-layer structures, the elegant interplay of charge, spin and moiré superlattice structure with many-body effects gives rise to diverse excitonic phenomena and correlated physics. Here we review some of the recent discoveries that highlight the versatility of TMD double layers to explore quantum optics and many-body effects. We identify outstanding challenges in the field and present a roadmap for unlocking the full potential of excitonic physics in TMD double layers and beyond, such as incorporating newly discovered ferroelectric and magnetic materials to engineer symmetries and add a new level of control to these remarkable engineered materials.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
Abstract
The constant ratio of global warming to cumulative CO
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emissions underpins the use of cumulative emissions budgets as policy tools, and the need to reach net zero CO
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emissions to ...stabilize global mean temperature. Several studies have argued that this property arises because heat and carbon are mixed into the ocean by similar physical processes, and this argument was echoed in the latest Intergovernmental Panel on Climate Change report. Here we show that, contrary to this hypothesis, atmosphere-ocean fluxes of heat and carbon evolve very differently to each other in abrupt CO
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increase experiments in five earth system models, and that changes in the atmosphere, ocean and land carbon pools all contribute to making warming proportional to cumulative emissions. Our results strongly suggest that this proportionality is not amenable to a simple physical explanation, but rather arises because of the complex interplay of multiple physical and biogeochemical processes.
The incidence of invasive fungal infections caused by molds and endemic fungi is increasing. There is also concern regarding increased rates of reduced susceptibility or frank resistance among ...Aspergillus and Coccidioides species, while Scedosporium species, Lomentospora prolificans, and Fusarium species are inherently less susceptible or intrinsically resistant to clinically available antifungals. Olorofim (formerly F901318) is the first member of the orotomide class of antifungals to be evaluated clinically for the treatment of invasive mold infections. This agent inhibits dihydroorotate dehydrogenase, a key enzyme in the biosynthesis of pyrimidines. Olorofim has activity against many molds and thermally dimorphic fungi, including species that are resistant to azoles and amphotericin B, but lacks activity against yeasts and the Mucorales. It is currently being developed for both oral and intravenous administration. Although published clinical outcome data have been limited to case reports to date, the results against invasive and refractory infections are promising. This review describes the mechanism of action of olorofim, its in vitro spectrum of activity, and what is currently known about its pharmacokinetic profile and clinical efficacy.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting motor neurons and other neuronal cells, leading to severe disability and eventually death from ventilatory failure. It has ...a prevalence of 5 in 100,000, with an incidence of 1.7 per 100,000, reflecting short average survival. The pathogenesis is incompletely understood, but defects of RNA processing and protein clearance may be fundamental. Repeat expansions in the chromosome 9 open reading frame 72 gene (C9orf72) are the most common known genetic cause of ALS and are seen in approximately 40% of patients with a family history and approximately 10% of those without. No environmental risk factors are proved to be causative, but many have been proposed, including military service. The diagnosis of ALS rests on a history of painless progressive weakness coupled with examination findings of upper and lower motor dysfunction. No diagnostic test is yet available, but electromyography and genetic tests can support the diagnosis. Care for patients is best provided by a multidisciplinary team, and most interventions are directed at managing symptoms. Two medications with modest benefits have Food and Drug Administration approval for the treatment of ALS: riluzole, a glutamate receptor antagonist, and, new in 2017, edaravone, a free radical scavenger. Many other encouraging treatment strategies are being explored in clinical trials for ALS; herein we review stem cell and antisense oligonucleotide gene therapies.
Previous growth-rate studies covering 14 dinosaur taxa, as represented by 31 data sets, are critically examined and reanalyzed by using improved statistical techniques. The examination reveals that ...some previously reported results cannot be replicated by using the methods originally reported; results from new methods are in many cases different, in both the quantitative rates and the qualitative nature of the growth, from results in the prior literature. Asymptotic growth curves, which have been hypothesized to be ubiquitous, are shown to provide best fits for only four of the 14 taxa. Possible reasons for non-asymptotic growth patterns are discussed; they include systematic errors in the age-estimation process and, more likely, a bias toward younger ages among the specimens analyzed. Analysis of the data sets finds that only three taxa include specimens that could be considered skeletally mature (i.e., having attained 90% of maximum body size predicted by asymptotic curve fits), and eleven taxa are quite immature, with the largest specimen having attained less than 62% of predicted asymptotic size. The three taxa that include skeletally mature specimens are included in the four taxa that are best fit by asymptotic curves. The totality of results presented here suggests that previous estimates of both maximum dinosaur growth rates and maximum dinosaur sizes have little statistical support. Suggestions for future research are presented.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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