The EXCEL Trial: The Interventionalists’ Perspective

Left main stem (LMS) disease is identified in up to 5% of diagnostic angiography cases, and is associated with significant morbidity and mortality due to the proportion of myocardium it subtends. In the past 10 years, there has been a significant change in the way we contemplate treating lesions in the LMS due to evolving experience and evidence in percutaneous coronary intervention (PCI) strategies and technologies. This has been reflected in recent changes in European and International guidance on managing patients with this lesion subset. Here, the authors provide an overview of the current literature regarding the management of LMS disease using PCI in light of new developments and emerging concepts in this field, specifically looking at the recent EXCEL trial

Large scale integration of renewable energy sources (RES) in the future Colombian energy system

The diversification of the energy matrix, including larger shares of Renewable Energy Sources (RES), is a significant part of the Colombian energy strategy towards a sustainable and more secure energy system. Historically, the country has relied on the intensive use of hydropower and fossil fuels as the main energy sources. Colombia has a huge renewables potential, and therefore the exploration of different pathways for their integration is required. The aim of this study was to build a model for a country with a hydro-dominated electric power system and analyse the impacts of integrated variable RES in long-term future scenarios. EnergyPLAN was the modelling tool employed for simulating the reference year and future alternatives. Initially, the reference model was validated, and successively five different scenarios were built. The results show that an increase in the shares of wind, solar and bioenergy could achieve an approximate reduction of 20% in both the CO2 emissions and the total fuel consumption of the country by 2030. Further, in the electricity sector the best-case scenario could allow an estimated 60% reduction in its emission intensity

The molecular details of a novel phosphorylation-dependent interaction between MRN and the SOSS complex

The repair of double-strand DNA breaks (DSBs) by homologous recombination is crucial in the maintenance of genome integrity. While the key role of the Mre11-Rad50-Nbs1 (MRN) complex in repair is well known, hSSB1 (SOSSB and OBFC2B), one of the main components of the sensor of single-stranded DNA (SOSS) protein complex, has also been shown to rapidly localize to DSB breaks and promote repair. We have previously demonstrated that hSSB1 binds directly to Nbs1, a component of the MRN complex, in a DNA damage-independent manner. However, recruitment of the MRN complex has also been demonstrated by an interaction between Integrator Complex Subunit 3 (INTS3; also known as SOSSA), another member of the SOSS complex, and Nbs1. In this study, we utilize a combined approach of in silico, biochemical, and functional experiments to uncover the molecular details of INTS3 binding to Nbs1. We demonstrate that the forkhead-associated domain of Nbs1 interacts with INTS3 via phosphorylation-dependent binding to INTS3 at Threonine 592, with contributions from Serine 590. Based on these data, we propose a model of MRN recruitment to a DSB via INTS3

Evaluation of contemporary treatment of high- and very high-risk patients for the prevention of cardiovascular events in Europe – Methodology and rationale for the multinational observational SANTORINI study

Publisher Copyright: © 2021 The AuthorsBackground and aims: Clinical practice before 2019 suggests a substantial proportion of high and very high CV risk patients taking lipid-lowering therapy (LLT) would not achieve the new LDL-C goals recommended in the 2019 ESC/EAS guidelines (<70 and < 55 mg/dL, respectively). To what extent practice has changed since the last ESC/EAS guideline update is uncertain, and quantification of remaining implementation gaps may inform health policy. Methods: The SANTORINI study is a multinational, multicentre, prospective, observational, non-interventional study documenting patient data at baseline (enrolment) and at 12-month follow-up. The study recruited 9606 patients ≥18 years of age with high and very high CV risk (as assigned by the investigators) requiring LLT, with no formal patient or comparator groups. The primary objective is to document, in the real-world setting, the effectiveness of current treatment modalities in managing plasma levels of LDL-C in high- and very high-risk patients requiring LLT. Key secondary effectiveness objectives include documenting the relationship between LLT and levels of other plasma lipids, high-sensitivity C-reactive protein (hsCRP) and overall predicted CV risk over one year. Health economics and patient-relevant parameters will also be assessed. Conclusions: The SANTORINI study, which commenced after the 2019 ESC/EAS guidelines were published, is ideally placed to provide important contemporary insights into the evolving management of LLT in Europe and highlight factors contributing to the low levels of LDL-C goal achievement among high and very high CV risk patients. It is hoped the findings will help enhance patient management and reduce the burden of ASCVD in Europe.Peer reviewe

Baryon Oscillations and Dark-Energy Constraints from Imaging Surveys

Baryonic oscillations in the galaxy power spectrum have been studied as a way of probing dark-energy models. While most studies have focused on spectroscopic surveys at high redshift, large multi-color imaging surveys have already been planned for the near future. In view of this, we study the prospects for measuring baryonic oscillations from angular statistics of galaxies binned using photometric redshifts. We use the galaxy bispectrum in addition to the power spectrum; this allows us to measure and marginalize over possibly complex galaxy bias mechanisms to get robust cosmological constraints. In our parameter estimation we allow for a weakly nonlinear biasing scheme that may evolve with redshift by two bias parameters in each of ten redshift bins. We find that a multi-color imaging survey that probes redshifts beyond one can give interesting constraints on dark-energy parameters. In addition, the shape of the primordial power spectrum can be measured to better accuracy than with the CMB alone. We explore the impact of survey depth, area, and calibration errors in the photometric redshifts on dark-energy constraints.Comment: 17 pages, 12 figure

LSST Science Book, Version 2.0

A survey that can cover the sky in optical bands over wide fields to faint magnitudes with a fast cadence will enable many of the exciting science opportunities of the next decade. The Large Synoptic Survey Telescope (LSST) will have an effective aperture of 6.7 meters and an imaging camera with field of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over 20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a total point-source depth of r~27.5. The LSST Science Book describes the basic parameters of the LSST hardware, software, and observing plans. The book discusses educational and outreach opportunities, then goes on to describe a broad range of science that LSST will revolutionize: mapping the inner and outer Solar System, stellar populations in the Milky Way and nearby galaxies, the structure of the Milky Way disk and halo and other objects in the Local Volume, transient and variable objects both at low and high redshift, and the properties of normal and active galaxies at low and high redshift. It then turns to far-field cosmological topics, exploring properties of supernovae to z~1, strong and weak lensing, the large-scale distribution of galaxies and baryon oscillations, and how these different probes may be combined to constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at http://www.lsst.org/lsst/sciboo

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie