The battle over Syria's reconstruction

Reconstruction is becoming the new battleground in the Syrian conflict—its continuation by other means. It is instrumentalized by the regime as a way to reconsolidate its control over the country and by rival regional and international powers to shape the internal balance of power and establish spheres of influence in the country. The paper examines the Asad regime’s practices, including co-optation of militia leaders via reconstruction concessions and use of reconstruction to clear strategic areas of opposition-dominated urban settlements. The paper then surveys how the geopolitical struggle in Syria has produced an asymmetry as regards reconstruction: those powers that lost the geo-political contest on the ground seek to use geo-economic superiority to reverse the geo-political outcome. Then the impact of proxy wars and spheres of influence in the country on the security context for reconstruction is examined. Finally, the reconstruction initiatives of the various external parties are assessed, including Russia, Iran and Turkey as well as the spoiler role by which the US seeks to obstruct reconstruction that would spell victory in Syria for its Russian and Iranian rivals.PostprintPeer reviewe

Glomerulocystic kidney disease

Glomerulocystic disease is a rare renal cystic disease with a long descriptive history. Findings from recent studies have significantly advanced the pathophysiological understanding of the disease processes leading to this peculiar phenotype. Many genetic syndromes associated with glomerulocystic disease have had their respective proteins localized to primary cilia or centrosomes. Transcriptional control of renal developmental pathways is dysregulated in obstructive diseases that also lead to glomerulocystic disease, emphasizing the importance of transcriptional choreography between renal development and renal cystic disease

Enhanced diagnostic yield in Meckel-Gruber and Joubert syndrome through exome sequencing supplemented with split-read mapping

Background The widespread adoption of high-throughput sequencing technologies by genetic diagnostic laboratories has enabled significant expansion of their testing portfolios. Rare autosomal recessive conditions have been a particular focus of many new services. Here we report a cohort of 26 patients referred for genetic analysis of Joubert (JBTS) and Meckel-Gruber (MKS) syndromes, two clinically and genetically heterogeneous neurodevelopmental conditions that define a phenotypic spectrum, with MKS at the severe end. Methods Exome sequencing was performed for all cases, using Agilent SureSelect v5 reagents and Illumina paired-end sequencing. For two cases medium-coverage (9×) whole genome sequencing was subsequently undertaken. Results Using a standard analysis pipeline for the detection of single nucleotide and small insertion or deletion variants, molecular diagnoses were confirmed in 12 cases (4 %). Seeking to determine whether our cohort harboured pathogenic copy number variants (CNV), in JBTS- or MKS-associated genes, targeted comparative read-depth analysis was performed using FishingCNV. These analyses identified a putative intragenic AHI1 deletion that included three exons spanning at least 3.4 kb and an intergenic MPP4 to TMEM237 deletion that included exons spanning at least 21.5 kb. Whole genome sequencing enabled confirmation of the deletion-containing alleles and precise characterisation of the mutation breakpoints at nucleotide resolution. These data were validated following development of PCR-based assays that could be subsequently used for “cascade” screening and/or prenatal diagnosis. Conclusions Our investigations expand the AHI1 and TMEM237 mutation spectrum and highlight the importance of performing CNV screening of disease-associated genes. We demonstrate a robust increasingly cost-effective CNV detection workflow that is applicable to all MKS/JBTS referrals

Multiple-criteria optimization of residential buildings envelope toward nZEBs: simplified approach for Damascus post-war

Syria faces significant challenges in optimizing residential building energy consumption to subsequently reduce CO2 emissions due to its conventional construction methods and systems, exacerbated by the recent conflict. Post-war re-construction provides new opportunities for improvement in building standards through the 2009 BIC insulation code towards nearly Zero Energy Buildings (nZEBs). However, the decline in economy growth poses significant challenges. In this study, we formulate a simplified building envelope selection approach using multi-criterion optimization methodology based on simulated thermal loads using IESVE and cost-energy trade-off. IESVE was used to evaluate the thermal performances of five cases representing 5 different building envelope structures on existing buildings in Damascus, Syria. Four out of the five cases were BIC compliant, and their thermal performances and cost energy trade-offs were evaluated against that of a conventional building representing the construction-as-usual case. Payback on the investment in insulation improvement of the envelope structures were also calculated. The results overall shows that the envelope structures incorporating insulation layer reduced annual heating, cooling, and combined energy loads of those buildings. Comparatively, these improvements were slightly better under winter conditions than in summer. Based on payback period analysis, none of the improvements provided acceptable economical payback within five years, as energy consumption tariffs were extremely low and insulation material costs were extremely high. A Multi-Criteria Decision Making (MCDM) framework was developed and applied to the cases investigated. Based on the limitations of the BIC, no optimal solution was obtained. However, the framework provides a good basis for stakeholders to make sound decisions in transitioning buildings especially under post war context towards nZEBs

Ecological and Carbon Footprints of Cities

Population and urbanisation are main contributors of carbon emissions, energy demand, resource consumption, waste generation and climate change. Tackling climate change is the emerging challenge of cities as through the process of obtaining their natural resource needs, they influence their ecological and carbon footprints. Ecological and carbon footprints have become critical indicators for navigating the progress towards reducing Greenhouse Gas (GHG) emissions and climate change. Thus, it is vital that the ecological and carbon footprints data capture the city supply chains comprehensively. In this article, we look at carbon and ecological footprints of cities at different levels and show how city input-output databases fulfill several necessities that allows comparisons of cities and help inform viable decision-making. We also consider input-output data of ecological and carbon footprints required to examine progress of cities towards reducing GHG emissions across whole supply chains to inform evidence-based policy making towards sustainability and climate change policies

Obesity, Sarcopenia, and Outcomes in Non-Small Cell Lung Cancer Patients Treated With Immune Checkpoint Inhibitors and Tyrosine Kinase Inhibitors

© Copyright © 2020 Khaddour, Gomez-Perez, Jain, Patel and Boumber. Body composition refers to the proportional content of body fat mass and lean body mass that can lead to a continuum of different phenotypes ranging from cachectic/sarcopenic state to obesity. The heterogenetic phenotypes of body composition can contribute to formation of some cancer types and can sometimes lead to disparate outcomes. Both of these extremes of the spectrum exist in patients with non-small cell lung carcinoma (NSCLC). The discovery of new pathways that drive tumorigenesis contributing to cancer progression and resistance have expanded our understanding of cancer biology leading to development of new targeted therapies including tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI) that have changed the landscape of NSCLC treatment. However, in the new era of precision medicine, the impact of body composition phenotypes on treatment outcomes and survival is now being elucidated. In this review, we will discuss the emerging evidence of a link between body composition and outcomes in patients with NSCLC treated with TKI and ICI. We will also discuss suggested mechanisms by which body composition can impact tumor behavior and anti-tumor immunological response

Targeting the epidermal growth factor receptor in egfr-mutated lung cancer: Current and emerging therapies

Epidermal growth factor receptor-targeting tyrosine kinase inhibitors (EGFR TKIs) are the standard of care for patients with EGFR-mutated metastatic lung cancer. While EGFR TKIs have initially high response rates, inherent and acquired resistance constitute a major challenge to the longitudinal treatment. Ongoing work is aimed at understanding the molecular basis of these resistance mechanisms, with exciting new studies evaluating novel agents and combination therapies to improve control of tumors with all forms of EGFR mutation. In this review, we first provide a discussion of EGFR-mutated lung cancer and the efficacy of available EGFR TKIs in the clinical setting against both common and rare EGFR mutations. Second, we discuss common resistance mechanisms that lead to therapy failure during treatment with EGFR TKIs. Third, we review novel approaches aimed at improving outcomes and overcoming resistance to EGFR TKIs. Finally, we highlight recent breakthroughs in the use of EGFR TKIs in non-metastatic EGFR-mutated lung cancer

Dynamic analysis of thick plates reinforced with agglomerated GNPs

In this work, the quasi-3D hyperbolic shear deformation theory (quasi-3D HSDT) is utilized to examine the dynamics of thick rectangular plates reinforced with rectangular nanofillers known as graphene nanoplatelets (GNPs). Agglomeration of the GNPs is incorporated and the mechanical characteristics like shear, elastic, and bulk moduli, Poisson's ratio, and density are analysed according to the mixture along with the Eshelby-Mori-Tanaka approach. Hamilton's principle is hired to derive the solving equations, the Navier approach is hired to present an analytical solution in the spatial domain, and the Newmark method is hired to provide an approximate solution in the time domain. The relevance of the dynamic response and the natural frequencies of the plate on several parameters are explored such as dispersion pattern and the GNPs percentage and agglomeration parameters. It is discovered that for a specific GNPs percentage, growth in the amount of agglomerated GNPs leads to lower natural frequencies and higher dynamic deflection. Meanwhile, for a specific mass fraction of the agglomerated GNPs, growth in the volume of clusters brings about higher natural frequencies and lower dynamic deflection