Spatial agglomeration, global value chains, and productivity: micro-evidence from Italy and Spain

We investigate the relationship between spatial agglomeration and firms’ labor productivity in Italy and Spain, examining firm-level heterogeneity in Global Value Chain positioning. We analyze a sample of 4, 025 manufacturing firms during the period from 2010 to 2014 and employ a shift-share instrumental variable approach. We find that agglomeration has a positive effect on labor productivity for suppliers but not for final firms

Perturbations in fatty acid metabolism and collagen production infer pathogenicity of a novel MBTPS2 variant in Osteogenesis imperfecta

Osteogenesis imperfecta (OI) is a heritable and chronically debilitating skeletal dysplasia. Patients with OI typically present with reduced bone mass, tendency for recurrent fractures, short stature and bowing deformities of the long bones. Mutations causative of OI have been identified in over 20 genes involved in collagen folding, posttranslational modification and processing, and in bone mineralization and osteoblast development. In 2016, we described the first X-linked recessive form of OI caused by MBTPS2 missense variants in patients with moderate to severe phenotypes. MBTPS2 encodes site-2 protease, a Golgi transmembrane protein that activates membrane-tethered transcription factors. These transcription factors regulate genes involved in lipid metabolism, bone and cartilage development, and ER stress response. The interpretation of genetic variants in MBTPS2 is complicated by the gene’s pleiotropic properties; MBTPS2 variants can also cause the dermatological conditions Ichthyosis Follicularis, Atrichia and Photophobia (IFAP), Keratosis Follicularis Spinulosa Decalvans (KFSD) and Olmsted syndrome (OS) without skeletal abnormalities typical of OI. Using control and patient-derived fibroblasts, we previously identified gene expression signatures that distinguish MBTPS2-OI from MBTPS2-IFAP/KFSD and observed stronger suppression of genes involved in fatty acid metabolism in MBTPS2-OI than in MBTPS2-IFAP/KFSD; this was coupled with alterations in the relative abundance of fatty acids in MBTPS2-OI. Furthermore, we observed a reduction in collagen deposition in the extracellular matrix by MBTPS2-OI fibroblasts. Here, we extrapolate our observations in the molecular signature unique to MBTPS2-OI to infer the pathogenicity of a novel MBTPS2 c.516A>C (p.Glu172Asp) variant of unknown significance in a male proband. The pregnancy was terminated at gestational week 21 after ultrasound scans showed bowing of femurs and tibiae and shortening of long bones particularly of the lower extremity; these were further confirmed by autopsy. By performing transcriptional analyses, gas chromatography-tandem mass spectrometry-based quantification of fatty acids and immunocytochemistry on fibroblasts derived from the umbilical cord of the proband, we observed perturbations in fatty acid metabolism and collagen production similar to what we previously described in MBTPS2-OI. These findings support pathogenicity of the MBTPS2 variant p.Glu172Asp as OI-causative and highlights the value of extrapolating molecular signatures identified in multiomics studies to characterize novel genetic variants

A Novel Triangle-based Method for Scattered Data Interpolation

Abstract Local numerical methods for scattered data interpolation often require a smart subdivision of the domain in geometrical polyhedral structures. In particular triangulations in the plane (2D) and tetrahedrizations in the space (3D) are widely used to define interpolation models. In this paper we give a short survey on the main methods for the scattered data problem and we recall preliminaries on triangulations and their related properties. Finally, combining two well-known ideas we present a new triangle-based interpolation method and show its application to a case study. Mathematics Subject Classification: 41A05, 65D05, 68U0

Non-Equilibrium Processes in the Solar Corona, Transition Region, Flares, and Solar Wind \textit{(Invited Review)}

We review the presence and signatures of the non-equilibrium processes, both non-Maxwellian distributions and non-equilibrium ionization, in the solar transition region, corona, solar wind, and flares. Basic properties of the non-Maxwellian distributions are described together with their influence on the heat flux as well as on the rates of individual collisional processes and the resulting optically thin synthetic spectra. Constraints on the presence of high-energy electrons from observations are reviewed, including positive detection of non-Maxwellian distributions in the solar corona, transition region, flares, and wind. Occurrence of non-equilibrium ionization is reviewed as well, especially in connection to hydrodynamic and generalized collisional-radiative modelling. Predicted spectroscopic signatures of non-equilibrium ionization depending on the assumed plasma conditions are summarized. Finally, we discuss the future remote-sensing instrumentation that can be used for detection of these non-equilibrium phenomena in various spectral ranges.Comment: Solar Physics, accepte

On the Virtualization of CUDA Based GPU Remoting on ARM and X86 Machines in the GVirtuS Framework

The astonishing development of diverse and different hardware platforms is twofold: on one side, the challenge for the exascale performance for big data processing and management; on the other side, the mobile and embedded devices for data collection and human machine interaction. This drove to a highly hierarchical evolution of programming models. GVirtuS is the general virtualization system developed in 2009 and firstly introduced in 2010 enabling a completely transparent layer among GPUs and VMs. This paper shows the latest achievements and developments of GVirtuS, now supporting CUDA 6.5, memory management and scheduling. Thanks to the new and improved remoting capabilities, GVirtus now enables GPU sharing among physical and virtual machines based on x86 and ARM CPUs on local workstations, computing clusters and distributed cloud appliances

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe