Evidence for Community Face Masking to Limit the Spread of SARS-CoV-2: A Critical Review

The use of facemasks in community settings has become an accepted public policy response to decrease disease transmission during the COVID-19 pandemic. Yet evidence of facemask efficacy is based primarily on observational studies that are subject to confounding and on mechanistic studies that rely on surrogate endpoints (such as droplet dispersion) as proxies for disease transmission. The available clinical evidence of facemask efficacy is of low quality and the best available clinical evidence has mostly failed to show efficacy, with fourteen of sixteen identified randomized controlled trials comparing face masks to no mask controls failing to find statistically significant benefit in the intent-to-treat populations. Of sixteen quantitative meta- analyses, eight were equivocal or critical as to whether evidence supports a public recommendation of masks, and the remaining eight supported a public mask intervention on limited evidence primarily on the basis of the precautionary principle. Although weak evidence should not preclude precautionary actions in the face of unprecedented events such as the COVID-19 pandemic, ethical principles require that the strength of the evidence and best estimates of amount of benefit be truthfully communicated to the public

Repurposing tofacitinib as an anti-myeloma therapeutic to reverse growth-promoting effects of the bone marrow microenvironment.

The myeloma bone marrow microenvironment promotes proliferation of malignant plasma cells and resistance to therapy. Activation of JAK/STAT signaling is thought to be a central component of these microenvironment-induced phenotypes. In a prior drug repurposing screen, we identified tofacitinib, a pan-JAK inhibitor Food and Drug Administration (FDA) approved for rheumatoid arthritis, as an agent that may reverse the tumor-stimulating effects of bone marrow mesenchymal stromal cells. Herein, we validated in vitro, in stromal-responsive human myeloma cell lines, and in vivo, in orthotopic disseminated xenograft models of myeloma, that tofacitinib showed efficacy in myeloma models. Furthermore, tofacitinib strongly synergized with venetoclax in coculture with bone marrow stromal cells but not in monoculture. Surprisingly, we found that ruxolitinib, an FDA approved agent targeting JAK1 and JAK2, did not lead to the same anti-myeloma effects. Combination with a novel irreversible JAK3-selective inhibitor also did not enhance ruxolitinib effects. Transcriptome analysis and unbiased phosphoproteomics revealed that bone marrow stromal cells stimulate a JAK/STAT-mediated proliferative program in myeloma cells, and tofacitinib reversed the large majority of these pro-growth signals. Taken together, our results suggest that tofacitinib reverses the growth-promoting effects of the tumor microenvironment. As tofacitinib is already FDA approved, these results can be rapidly translated into potential clinical benefits for myeloma patients

Composition dependence of electronic structure and optical properties of Hf1-xSixOy gate dielectrics

Copyright © 2008 American Institute of Physics. This article is copyrighted as indicated in the article. Reuse of AIP content is subject to the terms at: http://scitation.aip.org/termsconditionsComposition-dependent electronic structure and optical properties of Hf1−xSixOy 0.1 x 0.6 gate dielectrics on Si at 450 °C grown by UV-photo-induced chemical vapor deposition UV-CVD have been investigated via x-ray photoemission spectroscopy and spectroscopy ellipsometry SE . By means of the chemical shifts in the Hf 4f, Si 2p, and O 1s spectra, the Hf–O–Si bondings in the as-deposited films have been confirmed. Analyses of composition-dependent band alignment of Hf1−xSixOy / Si gate stacks have shown that the valence band VB offset Ev demonstrates little change; however, the values of conduction band offset Ec increase with the increase in the silicon atomic composition, resulting from the increase in the separation between oxygen 2p orbital VB state and antibonding d states intermixed of Hf and Si. Analysis by SE, based on the Tauc–Lorentz model, has indicated that decreases in the optical dielectric constant and increase in band gap have been observed as a function of silicon contents. Changes in the complex dielectric functions and band gap Eg related to the silicon concentration in the films are discussed systematically. From the band offset and band gap viewpoint, these results suggest that Hf1−xSixOy films provide sufficient tunneling barriers for electrons and holes, making them promising candidates as alternative gate dielectrics.National Natural Science Foundation of China and Royal Society U.K

FACE:Feasible and Actionable Counterfactual Explanations

Work in Counterfactual Explanations tends to focus on the principle of "the closest possible world" that identifies small changes leading to the desired outcome. In this paper we argue that while this approach might initially seem intuitively appealing it exhibits shortcomings not addressed in the current literature. First, a counterfactual example generated by the state-of-the-art systems is not necessarily representative of the underlying data distribution, and may therefore prescribe unachievable goals(e.g., an unsuccessful life insurance applicant with severe disability may be advised to do more sports). Secondly, the counterfactuals may not be based on a "feasible path" between the current state of the subject and the suggested one, making actionable recourse infeasible (e.g., low-skilled unsuccessful mortgage applicants may be told to double their salary, which may be hard without first increasing their skill level). These two shortcomings may render counterfactual explanations impractical and sometimes outright offensive. To address these two major flaws, first of all, we propose a new line of Counterfactual Explanations research aimed at providing actionable and feasible paths to transform a selected instance into one that meets a certain goal. Secondly, we propose FACE: an algorithmically sound way of uncovering these "feasible paths" based on the shortest path distances defined via density-weighted metrics. Our approach generates counterfactuals that are coherent with the underlying data distribution and supported by the "feasible paths" of change, which are achievable and can be tailored to the problem at hand.Comment: Presented at AAAI/ACM Conference on AI, Ethics, and Society 202

Identification of furfural resistant strains of Saccharomyces cerevisiae and Saccharomyces paradoxus from a collection of environmental and industrial isolates

Background Fermentation of bioethanol using lignocellulosic biomass as a raw material provides a sustainable alternative to current biofuel production methods by utilising waste food streams as raw material. Before lignocellulose can be fermented it requires physical, chemical and enzymatic treatment in order to release monosaccharides, a process that causes the chemical transformation of glucose and xylose into the cyclic aldehydes furfural and hydroxyfurfural. These furan compounds are potent inhibitors of Saccharomyces fermentation, and consequently furfural tolerant strains of Saccharomyces are required for lignocellulosic fermentation. Results This study investigated yeast tolerance to furfural and hydroxyfurfural using a collection of 71 environmental and industrial isolates of the baker’s yeast Saccharomyces cerevisiae and its closest relative Saccharomyces paradoxus. The Saccharomyces strains were initially screened for growth on media containing 100 mM glucose and 1.5 mg ml-1 furfural. Five strains were identified that showed a significant tolerance to growth in the presence of furfural and these were then screened for growth and ethanol production in the presence of increasing amounts (0.1-4 mg ml-1) of furfural. Conclusions Of the five furfural tolerant strains S. cerevisiae NCYC 3451 displayed the greatest furfural resistance, and was able to grow in the presence of up to 3.0 mg ml-1 furfural. Furthermore, ethanol production in this strain did not appear to be inhibited by furfural, with the highest ethanol yield observed at 3.0 mg ml-1 furfural. Although furfural resistance was not found to be a trait specific to any one particular lineage or population, three of the strains were isolated from environments where they might be continually exposed to low levels of furfural through the on-going natural degradation of lignocelluloses, and would therefore develop elevated levels of resistance to these furan compounds. Thus these strains represent good candidates for future studies of genetic variation relevant to understanding and manipulating furfural resistance and in the development of tolerant ethanologenic yeast strains for use in bioethanol production from lignocellulose processing

The detailed chemical composition of the terrestrial planet host Kepler-10

Chemical abundance studies of the Sun and solar twins have demonstrated that the solar composition of refractory elements is depleted when compared to volatile elements, which could be due to the formation of terrestrial planets. In order to further examine this scenario, we conducted a line-by-line differential chemical abundance analysis of the terrestrial planet host Kepler-10 and 14 of its stellar twins. Stellar parameters and elemental abundances of Kepler-10 and its stellar twins were obtained with very high precision using a strictly differential analysis of high quality Canada–France–Hawaii Telescope, Hobby–Eberly Telescope and Magellan spectra. When compared to the majority of thick disc twins, Kepler-10 shows a depletion in the refractory elements relative to the volatile elements, which could be due to the formation of terrestrial planets in the Kepler-10 system. The average abundance pattern corresponds to ∼13 Earth masses, while the two known planets in Kepler-10 system have a combined ∼20 Earth masses. For two of the eight thick disc twins, however, no depletion patterns are found. Although our results demonstrate that several factors [e.g. planet signature, stellar age, stellar birth location and Galactic chemical evolution (GCE)] could lead to or affect abundance trends with condensation temperature, we find that the trends give further support for the planetary signature hypothesis