We have successfully identified a variety of methodological assessment tools for different types of study design. However, further efforts in the development of critical appraisal tools are warranted since there is currently a lack of such tools for other fields, e.g. genetic studies, and some existing tools (nested case-control studies and case reports, for example) are in need of updating to be in line with current research practice and rigor. In addition, it is very important that all critical appraisal tools remain subjective and performance bias is effectively avoided.

In this paper we describe the OpenGeoSys (OGS) project, which is a scientific open source initiative for numerical simulation of thermo-hydro-mechanical-chemical (THMC) processes in porous media. The basic concept is to provide a flexible numerical framework (using primarily the Finite Element Method (FEM)) for solving multi-field problems in porous and fractured media for applications in geoscience and hydrology. To this purpose OGS is based on an object-oriented FEM concept including a broad spectrum of interfaces for pre-and post-processing. The OGS idea has been in development since the mid eighties. We provide a short historical note about the continuous process of concept and software development having evolved through Fortran, C, and C++ implementations. The idea behind OGS is to provide an open platform to the community, outfitted with professional software engineering tools such as platform-independent compiling and automated benchmarking. A comprehensive benchmarking book has been prepared for publication. Benchmarking has been proven to be a valuable tool for cooperation between different developer teams, e.g. for code comparison and validation purposes (DEVOVALEX and CO2 BENCH projects). On one hand, object-orientation (OO) provides a suitable framework for distributed code development; however the parallelization of OO codes still lacks efficiency. High-performance-computin (HPC) efficiency of OO codes is subject to future research.

Immune checkpoint inhibitors of programmed cell death 1 (PD-1) and its ligand (PD-L1) have led to a paradigm shift in cancer treatment. Understanding the clinical efficacy and safety profile of these drugs is necessary for treatment strategy in clinical practice.OBJECTIVE To assess the differences between anti-PD-1 and anti-PD-L1 regarding efficacy and safety shown in randomized clinical trials across various tumor types.

Abstract. In 2013, China's government published the Air Pollution Prevention and Control Action Plan (APPCAP) with a specific target for Beijing, which aims to reduce annual mean PM2.5 concentrations in Beijing to 60 µg m−3 in 2017. During 2013–2017, the air quality in Beijing was significantly improved following the implementation of various emission control measures locally and regionally, with the annual mean PM2.5 concentration decreasing from 89.5 µg m−3 in 2013 to 58 µg m−3 in 2017. As meteorological conditions were more favourable to the reduction of air pollution in 2017 than in 2013 and 2016, the real effectiveness of emission control measures on the improvement of air quality in Beijing has frequently been questioned. In this work, by combining a detailed bottom-up emission inventory over Beijing, the MEIC regional emission inventory and the WRF-CMAQ (Weather Research and Forecasting Model and Community Multiscale Air Quality) model, we attribute the improvement in Beijing's PM2.5 air quality in 2017 (compared to 2013 and 2016) to the following factors: changes in meteorological conditions, reduction of emissions from surrounding regions, and seven specific categories of local emission control measures in Beijing. We collect and summarize data related to 32 detailed control measures implemented during 2013–2017, quantify the emission reductions associated with each measure using the bottom-up local emission inventory in 2013, aggregate the measures into seven categories, and conduct a series of CMAQ simulations to quantify the contribution of different factors to the PM2.5 changes. We found that, although changes in meteorological conditions partly explain the improved PM2.5 air quality in Beijing in 2017 compared to 2013 (3.8 µg m−3, 12.1 % of total), the rapid decrease in PM2.5 concentrations in Beijing during 2013–2017 was dominated by local (20.6 µg m−3, 65.4 %) and regional (7.1 µg m−3, 22.5 %) emission reductions. The seven categories of emission control measures, i.e. coal-fired boiler control, clean fuels in the residential sector, optimize industrial structure, fugitive dust control, vehicle emission control, improved end-of-pipe control, and integrated treatment of VOCs, reduced the PM2.5 concentrations in Beijing by 5.9, 5.3, 3.2, 2.3, 1.9, 1.8, and 0.2 µg m−3, respectively, during 2013–2017. We also found that changes in meteorological conditions could explain roughly 30 % of total reduction in PM2.5 concentration during 2016–2017 with more prominent contribution in winter months (November and December). If the meteorological conditions in 2017 had remained the same as those in 2016, the annual mean PM2.5 concentrations would have increased from 58 to 63 µg m−3, exceeding the target established in the APPCAP. Despite the remarkable impacts from meteorological condition changes, local and regional emission reductions still played major roles in the PM2.5 decrease in Beijing during 2016–2017, and clean fuels in the residential sector, coal-fired boiler control, and optimize industrial structure were the three most effective local measures (contributing reductions of 2.1, 1.9, and 1.5 µg m−3, respectively). Our study confirms the effectiveness of clean air actions in Beijing and its surrounding regions and reveals that a new generation of control measures and strengthened regional joint emission control measures should be implemented for continued air quality improvement in Beijing because the major emitting sources have changed since the implementation of the clean air actions.

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