The Cosmic Web from Perturbation Theory

Context: Analyzing the large-scale structure (LSS) with galaxy surveys demands accurate structure formation models. Such models should ideally be fast and have a clear theoretical framework to rapidly scan a variety of cosmological parameter spaces without requiring large training data sets. Aims: This study aims to extend Lagrangian perturbation theory (LPT), including viscosity and vorticity, to reproduce the cosmic evolution from dark matter N-body calculations at the field level. Methods: We extend LPT to an Eulerian framework, dubbed eALPT. An ultraviolet regularisation through the spherical collapse model provided by Augmented LPT, turns out to be crucial at low redshifts. This enables modelling the stress tensor, with this introducing vorticity. The model has two free parameters apart from the choice of cosmology, redshift snapshots, cosmic volume, and the number of particles-cells. Results: We find that the cross-correlation of the dark matter distribution as compared to N-body solvers increases at $k = 1\,h$ Mpc$^{-1}$ and $z = 0$ from $\sim$55\% with the Zel'dovich approximation ($\sim$70\% with ALPT), to $\sim$95\% with three timesteps eALPT, and power spectra within percentage accuracy up to $k \simeq 0.3\,h$ Mpc$^{-1}$.Comment: 6 pages, 3 figure

Understanding expertise in surgical gesture by means of Hidden Markov Models

Minimally invasive surgery (MIS) has became very widespread in the last ten years. Due to the difficulties encountered by the surgeons to learn and manage this technique, a huge importance has the improvement of training procedures, the improvement of surgical instrumentation and the robotic automation of surgical gesture. All these purposes require the analysis of surgical performance with the aim to understand it and to define what is expertise in surgical gesture. In this paper for the first time the Hidden Markov Models (HMMs) are used as a tool for the understanding of surgical performance and of the human factors that characterize it. In our experiments we used position data concerning the tools movements during exercises performed on a surgical simulator. Using Hidden Markov theory, we create a model of the expert surgeon performance able to evaluate surgical capability and to distinguish between expert and non-expert surgeons. By analyzing the trained model of the expert surgeon performance we show that it is possible to deduce information about features characterizing the surgical expertise

Activation of diacylglycerol kinase alpha is required for VEGF-induced angiogenic signaling in vitro.

Vascular endothelial growth factor-A (VEGF-A) promotes angiogenesis by stimulating migration, proliferation and organization of endothelium, through the activation of signaling pathways involving Src tyrosine kinase. As we had previously shown that Src-mediated activation of diacylglycerol kinase-alpha (Dgk-alpha) is required for hepatocytes growth factor-stimulated cell migration, we asked whether Dgk-alpha is involved in the transduction of angiogenic signaling. In PAE-KDR cells, an endothelial-derived cell line expressing VEGFR-2, VEGF-A165, stimulates the enzymatic activity of Dgk-alpha: activation is inhibited by R59949, an isoform-specific Dgk inhibitor, and is dependent on Src tyrosine kinase, with which Dgk-alpha forms a complex. Conversely in HUVEC, VEGF-A165-induced activation of Dgk is only partially sensitive to R59949, suggesting that also other isoforms may be activated, albeit still dependent on Src tyrosine kinase. Specific inhibition of Dgk-alpha, obtained in both cells by R59949 and in PAE-KDR by expression of Dgk-alpha dominant-negative mutant, impairs VEGF-A165-dependent chemotaxis, proliferation and in vitro angiogenesis. In addition, in HUVEC, specific downregulation of Dgk-alpha by siRNA impairs in vitro angiogenesis on matrigel, further suggesting the requirement for Dgk-alpha in angiogenic signaling in HUVEC. Thus, we propose that activation of Dgk-alpha generates a signal essential for both proliferative and migratory response to VEGF-A165, suggesting that it may constitute a novel pharmacological target for angiogenesis control.

Reopening schools during the COVID-19 pandemic: Overview and rapid systematic review of guidelines and recommendations on preventive measures and the management of cases

Given the limited evidence of school closure effectiveness in containing the pandemic and the consequences for young people, reopening schools with appropriate measures is essential. This overview aimed to describe the main measures planned for the 2020–2021 academic year within the WHO European Region. A rapid systematic review of scientific databases was also performed. The websites of the government, Ministry of Health, and Ministry of Education of European Region countries were searched through 1 October for official documents about the prevention and management of suspected cases/confirmed cases in primary and secondary schools. To find further suggestions, a rapid systematic review was conducted through 20 October searching Pubmed, Scopus, and Embase. There were 23 official documents. France, Luxembourg, Malta, Ireland, Italy, Portugal, the UK, Spain, and San Marino were considered. Performing the rapid review, 855 records were identified and 7 papers were finally selected. The recommendations mostly agreed. However, there was no consensus on the criteria for the return to school of students that tested positive, and the flexibility between attendance at school and remote education for high-risk children often varied. School closure was commonly considered as the very last resort for COVID-19 control. Studies are required to evaluate the impact of different recommendations during this autumn term

Adalimumab dose tapering in patients with rheumatoid arthritis who are in long-standing clinical remission: results of the phase IV PREDICTRA study

Objective: To investigate the association between baseline disease activity and the occurrence of flares after adalimumab tapering or withdrawal in patients with rheumatoid arthritis (RA) in sustained remission. Methods: The PREDICTRA phase IV, randomised, double-blind (DB) study (ImPact of Residual Inflammation Detected via Imaging TEchniques, Drug Levels, and Patient Characteristics on the Outcome of Dose TaperIng of Adalimumab in Clinical Remission Rheumatoid ArThritis (RA) Patients) enrolled patients with RA receiving adalimumab 40 mg every other week who were in sustained remission ≥6 months. After a 4-week, open-label lead-in (OL-LI) period, patients were randomised 5:1 to DB adalimumab taper (every 3 weeks) or withdrawal (placebo) for 36 weeks. The primary endpoint was the association between DB baseline hand and wrist MRI-detected inflammation with flare occurrence. Results: Of 146 patients treated during the OL-LI period, 122 were randomised to taper (n=102) or withdrawal (n=20) arms. Patients had a mean 12.9 years of active disease and had received adalimumab for a mean of 5.4 years (mean 2.2 years in sustained remission). Overall, 37 (36%) and 9 (45%) patients experienced a flare in the taper and withdrawal arms, respectively (time to flare, 18.0 and 13.3 weeks). None of the DB baseline disease characteristics or adalimumab concentration was associated with flare occurrence after adalimumab tapering. Approximately half of the patients who flared regained clinical remission after 16 weeks of open-label rescue adalimumab. The safety profile was consistent with previous studies. Conclusions: Approximately one-third of patients who tapered adalimumab versus half who withdrew adalimumab experienced a flare within 36 weeks. Time to flare was numerically longer in the taper versus withdrawal arm. Baseline MRI inflammation was not associated with flare occurrence. Trial registration number: NCT02198651, EudraCT 2014-001114-26

A cnidarian homologue of an insect gustatory receptor functions in developmental body patterning.

Insect gustatory and odorant receptors (GRs and ORs) form a superfamily of novel transmembrane proteins, which are expressed in chemosensory neurons that detect environmental stimuli. Here we identify homologues of GRs (Gustatory receptor-like (Grl) genes) in genomes across Protostomia, Deuterostomia and non-Bilateria. Surprisingly, two Grls in the cnidarian Nematostella vectensis, NvecGrl1 and NvecGrl2, are expressed early in development, in the blastula and gastrula, but not at later stages when a putative chemosensory organ forms. NvecGrl1 transcripts are detected around the aboral pole, considered the equivalent to the head-forming region of Bilateria. Morpholino-mediated knockdown of NvecGrl1 causes developmental patterning defects of this region, leading to animals lacking the apical sensory organ. A deuterostome Grl from the sea urchin Strongylocentrotus purpuratus displays similar patterns of developmental expression. These results reveal an early evolutionary origin of the insect chemosensory receptor family and raise the possibility that their ancestral role was in embryonic development

Human west nile virus lineage 2 infection: Epidemiological, clinical, and virological findings

West Nile virus (WNV) lineage 2 is expanding and causing large outbreaks in Europe. In this study, we analyzed the epidemiological, clinical, and virological features of WNV lineage 2 infection during the large outbreak that occurred in northern Italy in 2018. The study population included 86 patients with neuroinvasive disease (WNND), 307 with fever (WNF), and 34 blood donors. Phylogenetic analysis of WNV full genome sequences from patients' samples showed that the virus belonged to the widespread central/southern European clade of WNV lineage 2 and was circulating in the area at least since 2014. The incidence of WNND and WNF progressively increased with age and was higher in males than in females. Among WNND patients, the case fatality rate was 22%. About 70% of blood donors reported symptoms during follow-up. Within the first week after symptom onset, WNV RNA was detectable in the blood or urine of 80% of patients, while 20% and 40% of WNND and WNF patients, respectively, were WNV IgM-seronegative. In CSF samples of WNND patients, WNV RNA was typically detectable when WNV IgM antibodies were absent. Blunted or no WNV IgM response and high WNV IgG levels were observed in seven patients with previous flavivirus immunity