Nonlinear integral equations for finite volume excited state energies of the O(3) and O(4) nonlinear sigma-models

We propose nonlinear integral equations for the finite volume one-particle energies in the O(3) and O(4) nonlinear sigma-models. The equations are written in terms of a finite number of components and are therefore easier to solve numerically than the infinite component excited state TBA equations proposed earlier. Results of numerical calculations based on the nonlinear integral equations and the excited state TBA equations agree within numerical precision.Comment: numerical results adde

AMPK Activators as Novel Drug Candidates for the Treatment of Inflammatory Bowel Diseases

Inflammatory bowel diseases (IBDs), mainly represented by ulcerative colitis and Crohn’s disease, are chronic and idiopathic diseases of the digestive tract. They incidence and prevalence is raising significantly in both developed and developing countries, thus representing a major challenge for the worldwide healthcare systems. The pharmacological armamentarium for the treatment of IBDs is far from being satisfactory, as the therapeutic success of the available drugs is still limited. Accordingly, the development of novel and effective compounds is highly requested. In this context, the serine/threonine heterotrimeric kinase AMPK (adenosine monophosphate-activated protein kinase) seems a sound target to strike. Known as the central hub of energy homeostasis in eukaryotic cells, AMPK contributes also to the modulation of immune/inflammatory cell functions. Actually, alterations in AMPK expression and/or activity play a key role in the pathophysiology of immune-mediated inflammatory diseases characterized by abnormal immune cell functions, like IBDs. Moreover, AMPK is able to improve intestinal health by enhancing para-cellular junctions, nutrient transporters, autophagy and apoptosis. Accordingly, AMPK activation represents a promising therapeutic strategy for the treatment of intestinal inflammatory disorders. Here we describe a novel heterocyclic derivative, developed as AMPK activator. Tested in C2C12 myoblast cell lines, our compound significantly increased AMPK activity, in a concentration-dependent manner, turning out to be more effective than the well-known activator acadesine (ACA). Moreover, assayed in a mouse model of acute DNBS-induced colitis, the novel heterocycle displayed a relevant anti-inflammatory efficacy, proving to ameliorate both systemic- and tissue-related inflammatory parameters like body and spleen weight, colon length, macroscopic damage, TNF and MDA levels. Also in this case, our compound turned out to be significantly more active that the known reference ACA, thus imposing itself as a novel and valuable drug candidate for the treatment of IBDs

Trabectedin for patients with advanced soft tissue sarcoma: A non-interventional, retrospective, multicenter study of the italian sarcoma group

The Italian Sarcoma Group performed this retrospective analysis of patients with advanced soft tissue sarcoma, pretreated with ≥1 anthracycline-based treatment, and treated with trabectedin every three weeks. Primary endpoint was to describe real-life use of trabectedin across Italy. Secondary endpoints included objective response rate (ORR) and safety. Overall, 512 patients from 20 Italian centers were evaluated. Leiomyosarcoma (37.7%)/liposarcoma (30.3%) were the most prevalent histological types (abbreviated as L-sarcoma). Patients received a median of four trabectedin cycles (range: 1–40), mostly as a second-line treatment (~60% of patients). The ORR was 13.7% superior (p < 0.0001) in patients with L-sarcoma compared with patients with non-L-sarcoma (16.6% vs. 9.0%). Median progression-free survival (PFS) was 5.1 months, whereas median overall survival (OS) was 21.6 months. Significantly better PFS and OS were observed in patients with L-sarcoma, those with objective responses and/or disease stabilization, treated in an early line and treated with reduced dose. Bone marrow toxicity (61.4%) and transaminase increases (21.9%) were the most common grade 3/4 adverse events. The results of this real-life study suggest that trabectedin is an active treatment, which is mostly given as a second-line treatment to patients with a good performance status and high-grade, metastatic L-sarcoma (clinical trial information: NCT02793050)

Steel-based applications in earthquake-prone areas

Steel-Earth project aims at distributing among technicians, engineers, design companies and standardization bodies the results of three past RFCS projects (Steel-Retro [3], Opus [2] and PrecaSteel [1]), providing useful tools for the design and for the retrofit of existing buildings. Technical documents and practical applications to case studies, regarding design of steel and composite steel/concrete buildings and innovative steel-based techniques for the retrofit of existing r.c. and masonry constructions, have been elaborated and collected into a volume distributed during the final workshop of the dissemination project. Pre-normative and background documents concerning the design of steel and composite structures and the rehabilitation of existing constructions have been prepared. A lot of attention has been paid to the analysis of the influence of overstrength factors on the seismic design of steel and composite structures. The prepared documents have been distributed to the attending people and to the members of WG 2 (CEN/TC 250/SC 8/WG 2 “Steel and Composite Structures”) during the final workshop of the project. Technical sheets, working examples and background documents have been translated into several languages (German, French, Italian, Romanian and Greek) and are free available on the website of the project (https://www.steelconstruct.com/site/), where information regarding Steel-Earth are also presented.11 Workshops in Italy, Greece, Germany, Belgium, Portugal, Spain and Romania and 5 conferences in Emilia-Romagna have been organized, as well as 2 practical courses for engineers and academic people in Pavia (Italy). Flash-drives with the technical documents and applications elaborated in Steel-Earth have been distributed to the attending people

International criteria for electrocardiographic interpretation in athletes: Consensus statement.

Sudden cardiac death (SCD) is the leading cause of mortality in athletes during sport. A variety of mostly hereditary, structural or electrical cardiac disorders are associated with SCD in young athletes, the majority of which can be identified or suggested by abnormalities on a resting 12-lead electrocardiogram (ECG). Whether used for diagnostic or screening purposes, physicians responsible for the cardiovascular care of athletes should be knowledgeable and competent in ECG interpretation in athletes. However, in most countries a shortage of physician expertise limits wider application of the ECG in the care of the athlete. A critical need exists for physician education in modern ECG interpretation that distinguishes normal physiological adaptations in athletes from distinctly abnormal findings suggestive of underlying pathology. Since the original 2010 European Society of Cardiology recommendations for ECG interpretation in athletes, ECG standards have evolved quickly, advanced by a growing body of scientific data and investigations that both examine proposed criteria sets and establish new evidence to guide refinements. On 26-27 February 2015, an international group of experts in sports cardiology, inherited cardiac disease, and sports medicine convened in Seattle, Washington (USA), to update contemporary standards for ECG interpretation in athletes. The objective of the meeting was to define and revise ECG interpretation standards based on new and emerging research and to develop a clear guide to the proper evaluation of ECG abnormalities in athletes. This statement represents an international consensus for ECG interpretation in athletes and provides expert opinion-based recommendations linking specific ECG abnormalities and the secondary evaluation for conditions associated with SCD

Thermodynamic Bethe Ansatz for planar AdS/CFT: a proposal

Moving from the mirror theory Bethe-Yang equations proposed by Arutyunov and Frolov, we derive the thermodynamic Bethe Ansatz equations which should control the spectrum of the planar $\text{AdS}_5/\text{CFT}_4$ correspondence. The associated set of universal functional relations (Y-system) satisfied by the exponentials of the TBA pseudoenergies is deduced, confirming the structure inferred by Gromov, Kazakov and Vieira.Comment: Main typos corrected, notations fixed, references adde

Diabetic Neuropathy and Axon Reflex-Mediated Neurogenic Vasodilatation in Type 1 Diabetes

Objective: Axon reflex-mediated neurogenic vasodilatation in response to cutaneous heating may reflect early, pre-clinical small fibre dysfunction. We aimed to evaluate the distribution of the vascular flare area measured by laser doppler imaging (‘‘LDI FLARE area’’) in type 1 diabetes and in healthy volunteers. Research and Methods: Concurrent with clinical and electrophysiological examination to classify diabetic sensorimotor polyneuropathy (DSP), LDIFLARE area (cm 2) was determined in 89 type 1 diabetes subjects matched to 64 healthy volunteers. We examined the association and diagnostic performance of LDI with clinical and subclinical measures of DSP and its severity. Results: Compared to the 64 healthy volunteers, the 56 diabetes controls without DSP had significantly lower LDIFLARE area (p = 0.006). The 33 diabetes cases with DSP had substantially lower LDIFLARE area as compared to controls without DSP (p = 0.002). There was considerable overlap in LDIFLARE area between all groups such that the ROC curve had an AUC of 0.72 and optimal sensitivity of 70 % for the detection of clinical DSP. Use of a subclinical definition for DSP, according to subclinical sural nerve impairment, was associated with improved AUC of 0.75 and sensitivity of 79%. In multivariate analysis higher HbA1c and body mass index had independent associations with smaller LDIFLARE area. Conclusions: Axon reflex-mediated neurogenic vasodilatation in response to cutaneous heating is a biomarker of earl

A modern scleractinian coral with a two-component calcite–aragonite skeleton

Until now, all of the ca. 1,800 known modern scleractinian coral species were thought to produce skeletons exclusively of aragonite. Asymbiotic Paraconotrochus antarcticus living in the Southern Ocean is the first example of an extant scleractinian that forms a two-component carbonate skeleton, with an inner structure made of high-Mg calcite and an outer structure composed of aragonite. This discovery adds support to the notion that the coral skeletal formation process is strongly biologically controlled. Mitophylogenomic analysis shows that P. antarcticus represents an ancient scleractinian clade, suggesting that skeletal mineralogy/polymorph of a taxon, once established, is a trait conserved throughout the evolution of that clade.One of the most conserved traits in the evolution of biomineralizing organisms is the taxon-specific selection of skeletal minerals. All modern scleractinian corals are thought to produce skeletons exclusively of the calcium-carbonate polymorph aragonite. Despite strong fluctuations in ocean chemistry (notably the Mg/Ca ratio), this feature is believed to be conserved throughout the coral fossil record, spanning more than 240 million years. Only one example, the Cretaceous scleractinian coral Coelosmilia (ca. 70 to 65 Ma), is thought to have produced a calcitic skeleton. Here, we report that the modern asymbiotic scleractinian coral Paraconotrochus antarcticus living in the Southern Ocean forms a two-component carbonate skeleton, with an inner structure made of high-Mg calcite and an outer structure composed of aragonite. P. antarcticus and Cretaceous Coelosmilia skeletons share a unique microstructure indicating a close phylogenetic relationship, consistent with the early divergence of P. antarcticus within the Vacatina (i.e., Robusta) clade, estimated to have occurred in the Mesozoic (ca. 116 Mya). Scleractinian corals thus join the group of marine organisms capable of forming bimineralic structures, which requires a highly controlled biomineralization mechanism; this capability dates back at least 100 My. Due to its relatively prolonged isolation, the Southern Ocean stands out as a repository for extant marine organisms with ancient traits.Mitogenome sequences data have been deposited in GenBank (MT409109). All other study data are included in the article text and supporting information

Consensus Guidelines for Advancing Coral Holobiont Genome and Specimen Voucher Deposition

Coral research is being ushered into the genomic era. To fully capitalize on the potential discoveries from this genomic revolution, the rapidly increasing number of high-quality genomes requires effective pairing with rigorous taxonomic characterizations of specimens and the contextualization of their ecological relevance. However, to date there is no formal framework that genomicists, taxonomists, and coral scientists can collectively use to systematically acquire and link these data. Spurred by the recently announced “Coral symbiosis sensitivity to environmental change hub” under the “Aquatic Symbiosis Genomics Project” - a collaboration between the Wellcome Sanger Institute and the Gordon and Betty Moore Foundation to generate gold-standard genome sequences for coral animal hosts and their associated Symbiodiniaceae microalgae (among the sequencing of many other symbiotic aquatic species) - we outline consensus guidelines to reconcile different types of data. The metaorganism nature of the coral holobiont provides a particular challenge in this context and is a key factor to consider for developing a framework to consolidate genomic, taxonomic, and ecological (meta)data. Ideally, genomic data should be accompanied by taxonomic references, i.e., skeletal vouchers as formal morphological references for corals and strain specimens in the case of microalgal and bacterial symbionts (cultured isolates). However, exhaustive taxonomic characterization of all coral holobiont member species is currently not feasible simply because we do not have a comprehensive understanding of all the organisms that constitute the coral holobiont. Nevertheless, guidelines on minimal, recommended, and ideal-case descriptions for the major coral holobiont constituents (coral animal, Symbiodiniaceae microalgae, and prokaryotes) will undoubtedly help in future referencing and will facilitate comparative studies. We hope that the guidelines outlined here, which we will adhere to as part of the Aquatic Symbiosis Genomics Project sub-hub focused on coral symbioses, will be useful to a broader community and their implementation will facilitate cross- and meta-data comparisons and analyses