Cholesterol-modifying drugs in COVID-19

Infection with severe acute respiratory syndrom coronavirus 2 (SARS-CoV-2) is more likely to lead to poor outcomes in the elderly and those with cardiovascular disease, obesity or metabolic syndrome. Here, we consider mechanisms by which dyslipidaemia and the use of cholesterol-modifying drugs could influence the virus–host relationship. Cholesterol is essential for the assembly, replication and infectivity of enveloped virus particles; we highlight several cholesterol-modifying drugs with the potential to alter the SARS-CoV-2 life cycle that could be tested in in vitro and in vivo models. Although cholesterol is an essential component of immune cell membranes, excess levels can dysregulate protective immunity and promote exaggerated pulmonary and systemic inflammatory responses. Statins block the production of multiple sterols, oxysterols and isoprenoids, resulting in a pleiotropic range of context-dependent effects on virus infectivity, immunity and inflammation. We highlight antiviral, immunomodulatory and anti-inflammatory effects of cholesterol-modifying drugs that merit further consideration in the management of SARS-CoV-2 infection

Elastic Purcell Effect

© 2018 American Physical Society. In this work, we introduce an elastic analog of the Purcell effect and show theoretically that spherical nanoparticles can serve as tunable and robust antennas for modifying the emission from localized elastic sources. This effect can be qualitatively described by introducing elastic counterparts of the familiar electromagnetic parameters: local density of elastic states, elastic Purcell factor, and effective volume of elastic modes. To illustrate our framework, we consider the example of a submicron gold sphere as a generic elastic GHz antenna and find that shear and mixed modes of low orders in such systems offer considerable elastic Purcell factors. This formalism opens pathways towards extended control over dissipation of vibrations in various optomechanical systems and contributes to closing the gap between classical and quantum-mechanical treatments of phonons localized in elastic nanoresonators

A new technique for transumbilical insertion of central venous silicone catheters in newborn infants

Aim: A new technique allowing placement of umbilical silicone venous catheters (USVC) is described and compared with percutaneous silicone venous catheters (PSVC)

Have the roles of two functional polymorphisms in breast cancer, R72P in P53 and MDM2-309 in MDM2, become clearer?

Genetic differences between individuals have been predicted to account for disparate outcomes in patients diagnosed with cancer. The search for genetic determinants has been ongoing for a considerable amount of time and it is only now that insights have been gained into which polymorphisms are most likely to be important in determining not only disease likelihood but also outcome. The quest to be able to accurately predict patient outcomes in breast cancer may now be a step closer as increased sample size is leading to more robust statistical analysis and a better understanding of molecular mechanisms of disease are forthcoming

Pulsed Molecular Optomechanics in Plasmonic Nanocavities: From Nonlinear Vibrational Instabilities to Bond-Breaking

Small numbers of surface-bound molecules are shown to behave as would be expected for opto-mechanical oscillators placed inside plasmonic nano-cavities that support extreme confinement of optical fields. Pulsed Raman scattering reveals superlinear Stokes emission above a threshold, arising from the stimulated vibrational pumping of molecular bonds under pulsed excitation shorter than the phonon decay time, and agreeing with pulsed optomechanical quantum theory. Reaching the parametric instability (equivalent to a phonon laser or ‘phaser’ regime) is however hindered by motion of gold atoms and molecular reconfiguration at phonon occupations approaching unity. We show how this irreversible bond breaking can ultimately limit the exploitation of molecules as quantum mechanical oscillators, but accesses optically-driven chemistry

Browser-based Data Annotation, Active Learning, and Real-Time Distribution of Artificial Intelligence Models: From Tumor Tissue Microarrays to COVID-19 Radiology.

BACKGROUND: Artificial intelligence (AI) is fast becoming the tool of choice for scalable and reliable analysis of medical images. However, constraints in sharing medical data outside the institutional or geographical space, as well as difficulties in getting AI models and modeling platforms to work across different environments, have led to a "reproducibility crisis" in digital medicine. METHODS: This study details the implementation of a web platform that can be used to mitigate these challenges by orchestrating a digital pathology AI pipeline, from raw data to model inference, entirely on the local machine. We discuss how this federated platform provides governed access to data by consuming the Application Program Interfaces exposed by cloud storage services, allows the addition of user-defined annotations, facilitates active learning for training models iteratively, and provides model inference computed directly in the web browser at practically zero cost. The latter is of particular relevance to clinical workflows because the code, including the AI model, travels to the user's data, which stays private to the governance domain where it was acquired. RESULTS: We demonstrate that the web browser can be a means of democratizing AI and advancing data socialization in medical imaging backed by consumer-facing cloud infrastructure such as Box.com. As a case study, we test the accompanying platform end-to-end on a large dataset of digital breast cancer tissue microarray core images. We also showcase how it can be applied in contexts separate from digital pathology by applying it to a radiology dataset containing COVID-19 computed tomography images. CONCLUSIONS: The platform described in this report resolves the challenges to the findable, accessible, interoperable, reusable stewardship of data and AI models by integrating with cloud storage to maintain user-centric governance over the data. It also enables distributed, federated computation for AI inference over those data and proves the viability of client-side AI in medical imaging. AVAILABILITY: The open-source application is publicly available at , with a short video demonstration at

ARRAW: Anti-resonant reflecting acoustic waveguides

© 2020 The Author(s). Published by IOP Publishing Ltd on behalf of the Institute of Physics and Deutsche Physikalische Gesellschaft. Development of acoustic and optoacoustic on-chip technologies calls for new solutions to guiding, storing and interfacing acoustic and optical waves in integrated silicon-on-insulator systems. One of the biggest challenges in this field is to suppress the radiative dissipation of the propagating acoustic waves, while co-localizing the optical and acoustic fields in the same region of an integrated waveguide. Here we address this problem by introducing anti-resonant reflecting acoustic waveguides (ARRAWs) - mechanical analogues of the anti-resonant reflecting optical waveguides. We discuss the principles of anti-resonant guidance and establish guidelines for designing efficient ARRAWs. Finally, we demonstrate examples of the simplest silicon/silica ARRAW platforms that can simultaneously serve as near-IR optical waveguides, and support strong backward Brillouin scattering

Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

INTRODUCTION: More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associations of all known BC susceptibility alleles with risk of BC subtypes in BRCA1 and BRCA2 carriers. METHODS: We used data from 15,252 BRCA1 and 8,211 BRCA2 carriers to analyze the associations between approximately 200,000 genetic variants on the iCOGS array and risk of BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and triple-negative- (TN) status; morphologic subtypes; histological grade; and nodal involvement. RESULTS: The estimated BC hazard ratios (HRs) for the 74 known BC alleles in BRCA1 carriers exhibited moderate correlations with the corresponding odds ratios from the general population. However, their associations with ER-positive BC in BRCA1 carriers were more consistent with the ER-positive associations in the general population (intraclass correlation (ICC) = 0.61, 95% confidence interval (CI): 0.45 to 0.74), and the same was true when considering ER-negative associations in both groups (ICC = 0.59, 95% CI: 0.42 to 0.72). Similarly, there was strong correlation between the ER-positive associations for BRCA1 and BRCA2 carriers (ICC = 0.67, 95% CI: 0.52 to 0.78), whereas ER-positive associations in any one of the groups were generally inconsistent with ER-negative associations in any of the others. After stratifying by ER status in mutation carriers, additional significant associations were observed. Several previously unreported variants exhibited associations at P <10(-6) in the analyses by PR status, HER2 status, TN phenotype, morphologic subtypes, histological grade and nodal involvement. CONCLUSIONS: Differences in associations of common BC susceptibility alleles between BRCA1 and BRCA2 carriers and the general population are explained to a large extent by differences in the prevalence of ER-positive and ER-negative tumors. Estimates of the risks associated with these variants based on population-based studies are likely to be applicable to mutation carriers after taking ER status into account, which has implications for risk prediction.published_or_final_versio

A new estimation of the recent tropospheric molecular hydrogen budget using atmospheric observations and variational inversion

This paper presents an analysis of the recent tropospheric molecular hydrogen (H2) budget with a particular focus on soil uptake and European surface emissions. A variational inversion scheme is combined with observations from the RAMCES and EUROHYDROS atmospheric networks, which include continuous measurements performed between mid-2006 and mid-2009. Net H2 surface flux, then deposition velocity and surface emissions and finally, deposition velocity, biomass burning, anthropogenic and N2 fixation-related emissions were simultaneously inverted in several scenarios. These scenarios have focused on the sensibility of the soil uptake value to different spatio-temporal distributions. The range of variations of these diverse inversion sets generate an estimate of the uncertainty for each term of the H2 budget. The net H2 flux per region (High Northern Hemisphere, Tropics and High Southern Hemisphere) varies between −8 and +8 Tg yr−1. The best inversion in terms of fit to the observations combines updated prior surface emissions and a soil deposition velocity map that is based on bottom-up and top-down estimations. Our estimate of global H2 soil uptake is −59±9 Tg yr−1. Forty per cent of this uptake is located in the High Northern Hemisphere and 55% is located in the Tropics. In terms of surface emissions, seasonality is mainly driven by biomass burning emissions. The inferred European anthropogenic emissions are consistent with independent H2 emissions estimated using a H2/CO mass ratio of 0.034 and CO emissions within the range of their respective uncertainties. Additional constraints, such as isotopic measurements would be needed to infer a more robust partition of H2 sources and sinks

Single-molecule optomechanics in "picocavities"

Trapping light with noble metal nanostructures overcomes the diffraction limit and can confine light to volumes typically on the order of 30 cubic nanometers. We found that individual atomic features inside the gap of a plasmonic nanoassembly can localize light to volumes well below 1 cubic nanometer ("picocavities"), enabling optical experiments on the atomic scale. These atomic features are dynamically formed and disassembled by laser irradiation. Although unstable at room temperature, picocavities can be stabilized at cryogenic temperatures, allowing single atomic cavities to be probed for many minutes. Unlike traditional optomechanical resonators, such extreme optical confinement yields a factor of 10$^{6}$ enhancement of optomechanical coupling between the picocavity field and vibrations of individual molecular bonds. This work sets the basis for developing nanoscale nonlinear quantum optics on the single-molecule level.Supported by Project FIS2013-41184-P from MINECO (Ministerio de Economía y Competitividad) and IT756-13 from the Basque government consolidated groups (M.K.S., Y.Z., A. Demetriadou, R.E., and J.A.); the Winton Programme for the Physics of Sustainability (F.B.); the Dr. Manmohan Singh scholarship from St. John’s College (R.C.); the UK National Physical Laboratory (C.C.); the Fellows Gipuzkoa Program of the Gipuzkoako Foru Aldundia via FEDER funds of the European Union “Una manera de hacer Europa” (R.E.); UK Engineering and Physical Sciences Research Council grants EP/G060649/1 and EP/L027151/1; and European Research Council grant LINASS 320503