Singular kernels, multiscale decomposition of microstructure, and dislocation models

We consider a model for dislocations in crystals introduced by Koslowski, Cuiti\~no and Ortiz, which includes elastic interactions via a singular kernel behaving as the $H^{1/2}$ norm of the slip. We obtain a sharp-interface limit of the model within the framework of $\Gamma$-convergence. From an analytical point of view, our functional is a vector-valued generalization of the one studied by Alberti, Bouchitt\'e and Seppecher to which their rearrangement argument no longer applies. Instead we show that the microstructure must be approximately one-dimensional on most length scales and exploit this property to derive a sharp lower bound

Tightness for a stochastic Allen--Cahn equation

We study an Allen-Cahn equation perturbed by a multiplicative stochastic noise which is white in time and correlated in space. Formally this equation approximates a stochastically forced mean curvature flow. We derive uniform energy bounds and prove tightness of of solutions in the sharp interface limit, and show convergence to phase-indicator functions.Comment: 27 pages, final Version to appear in "Stochastic Partial Differential Equations: Analysis and Computations". In Version 4, Proposition 6.3 is new. It replaces and simplifies the old propositions 6.4-6.

Therapeutic sequences in patients with grade 1−2 neuroendocrine tumors (NET): an observational multicenter study from the ELIOS group

Purpose: Many different treatments are suggested by guidelines to treat grade 1−2 (G1−G2) neuroendocrine tumors (NET). However, a precise therapeutic algorithm has not yet been established. This study aims at identifying and comparing the main therapeutic sequences in G1−G2 NET. Methods: A retrospective observational Italian multicenter study was designed to collect data on therapeutic sequences in NET. Median progression-free survival (PFS) was compared between therapeutic sequences, as well as the number and grade of side effects and the rate of dose reduction/treatment discontinuation. Results: Among 1182 patients with neuroendocrine neoplasia included in the ELIOS database, 131 G1–G2 gastroenteropancreatic, lung and unknown primary NET, unresectable or persistent/relapsing after surgery, treated with ≥2 systemic treatments, were included. Four main therapeutic sequences were identified in 99 patients: (A) somatostatin analogs (SSA) standard dose to SSA high dose (n = 36), (B) SSA to everolimus (n = 31), (C) SSA to chemotherapy (n = 17), (D) SSA to peptide receptor radionuclide therapy (PRRT) (n = 15). Median PFS of the second-line treatment was not reached in sequence A, 33 months in sequence B, 20 months in sequence C, 30 months in sequence D (p = 0.16). Both total number and severity of side effects were significantly higher in sequences B and C than A and D (p = 0.04), as well as the rate of dose reduction/discontinuation (p = 0.03). Conclusions: SSA followed by SSA high dose, everolimus, chemotherapy or PRRT represent the main therapeutic sequences in G1−G2 NET. Median PFS was not significantly different between sequences. However, the sequences with SSA high dose or PRRT seem to be better tolerated than sequences with everolimus or chemotherapy

Prognostic significance of DNA ploidy, S-phase fraction, and tissue levels of aspartic, cysteine, and serine proteases in operable gastric carcinoma

A consecutive series of 63 untreated patients undergoing surgical resection for stage I-IV gastric adenocarcinomas (GCs) has been prospectively studied. Our purpose was to analyze the predictive relevance of DNA ploidy, S-phase fraction (SPF), and tissue levels of lysosomal proteinases cathepsin D (CD), cathepsin B (CB), cathepsin L (CL), and urokinase-type plasminogen activator (uPA) and that of the intracellular cysteine proteinase inhibitor stefin A on clinical outcome. All of the patients taking part in this study were followed up for a median of 73 months. DNA aneuploidy was present in 71% of the cases (45/63), whereas 9% of these (4/45) showed multiclonality. Both DNA ploidy and SPF were associated with tumor-node-metastasis (TNM) stage and node status, whereas only DNA ploidy was related to depth of invasion. CB, CL, uPA, but not CD, levels were significantly higher in GC as compared to paired normal mucosa, whereas stefin A levels were lower in tumor tissues. CB levels were significantly associated with TNM stage, nodal status, histological grade, and DNA ploidy. At univariate analysis, only node involvement, advanced TNM stage, DNA aneuploidy, and high SPF proved to be significantly related to quicker relapse and to shorter overall survival, whereas depth of invasion was related only to survival. With multivariate analysis, only high SPF (>15.2%) was related to risk of relapse (RR = 8.50), whereas high SPF and DNA aneuploidy were independently related to risk of death (RR = 1.88 and 2.09, respectively). Our preliminary prospective study has identified SPF and DNA ploidy as important biological indicators for predicting the outcome of patients with GC

DigiArt: towards a virtualization of Cultural Heritage

DigiArt is a Europe-wide project aimed at providing a new, cost efficient solution to the capture, processing and display of cultural artefacts. The project will change the ways in which the public interact with cultural objects and spaces in a dramatic way. This project is unique in its collaborative approach: cultural heritage professionals working directly with electrical, mechanical, optical and software engineers to develop a solution to current issues faced by the museum sector. The innovations created by the engineers are driven by the demand of the cultural heritage sector. The diversity of the objects and spaces of the three test museums are challenging the engineers to provide a tool useful for a broad variety of indoor and outdoor museums in the future. This goes from using Unmanned Aerial Vehicle (UAVs or drones) to fly and record large sites, to using scanners to record fine jewellery. As a case study, we present here the use-case of Scladina Cave. At the end of the project, the Scladina Cave Archaeological Centre will offer two different visitor experiences. The first uses virtual reality, which will be available anytime, anywhere, to anyone with an internet connected device. The second will use augmented reality technologies within the cave site. The augmented reality visit of the cave will enhance the tour of Scladina by offering visits that would not be possible where it not for the augmented reality, where 3D objects and animations will contribute to offer a new 3D-immersive experience

Case Report: Unmasking Hypercalcemia in Patients With Neuroendocrine Neoplasms. Experience From Six Italian Referral Centers.

Background: Hypercalcemia is a common paraneoplastic syndrome which can occur in up to 10% of patients with advanced neoplasms. Paraneoplastic parathyroid hormone-related protein (PTHrP) represents the most frequent cause of this syndrome. In neuroendocrine neoplasms (NENs) paraneoplastic hypercalcemia is rare. Case series: The present series includes all patients with NENs and paraneoplastic hypercalcemia from four Italian centres: (I) A 40-year-old man was hospitalized for repeated episodes of falls, hyposthenia and drowsiness. Severe hypercalcemia was found. Metastatic pancreatic G2 NEN and PTHrP-related hypercalcemia were diagnosed. The patient started therapy with somatostatin analogs (SSA) and Denosumab. After disease progression peptide receptor radionuclide therapy (PRRT) was started with an objective response associated with PTHrP reduction and normocalcemia. (II) A 45-year-old man was referred for pancreatic G2 NEN. SSA and subsequently everolimus were administered for metastases occurrence. Hypercalcemia occurred and PRRT and Denosumab were started for disease progression with the onset of bone metastases. Despite disease stability after four cycles of PRRT the patient's performance status worsened until death. (III) A 49-year-old woman was hospitalized for psychic slowdown, confusional state, sensory dullness. A severe hypercalcemia, associated with a pancreatic G1 NEN was diagnosed and treated with haemodialysis, bisphosphonates injections and continuous infusion of calcitonin. 1,25-dihydroxyvitamin D was high, PTHrP was undetectable. After surgery serum calcium levels and 1,25-dihydroxyvitamin D were normalized. (IV) A 69-year-old man was hospitalized after the onset of shortness of breath and dyspnea, asthenia and weight loss. Computed Tomography (CT) and 68Ga DOTATOC Positron Emission Tomography (PET)-CT revealed a left pulmonary nodule. Hypercalcemia and markedly elevated PTHrP levels were detected. The histological examination revealed an atypical carcinoid. After surgery, calcium levels were normalized, PTHrP was significantly reduced with an improvement of general conditions. Conclusion: In our series, paraneoplastic PTHrP-related hypercalcemia occurred in pancreatic NEN and in one bronchial carcinoid representing the third case in the literature. Our case associated with 1,25-dihydroxyvitamin D secretion represents the fourth case in the literature. PTHrP secretion should be considered in NENs' patients with hypercalcemia. Acute treatment should be focused on lowering calcium levels, and long-term control can be achieved by tumor cytoreduction inhibiting PTHrP release

Preliminary reports on the 2016-2017 excavation of the Neolithic ossuary and terrace

This article reports on the first three systematic excavation seasons at the Neolithic ossuary of Grotte de La Faucille, Belgium. The site was dated on human bone to 4266 ± 40 14C BP (3011-2702 cal BC; 2 sigma), corresponding to the transition from the late to the final Neolithic. The area excavated to date is clearly reworked and the individuals are distributed across the site. Further excavation will focus on the inferior levels at the entrance and inside the cave. This report presents the preliminary analysis of the anthropological and archaeological evidence recorded to date. Five archaeological artefacts were discovered made on bone, tooth and flint. The site has produced skeletal and dental remains of at least 12 humans (MNI 6 juveniles and 6 adults) as well as a number of bone and lithic artefacts. The skeletal remains are fragmentary and some elements, such as the cranium, are highly underrepresented given the number of individuals. The potential to find the remainder of at least 12 individuals is promising and continued excavation may result in one of the largest recent excavation of a multiple Neolithic burial site of the 21st century. The results presented here and ongoing analysis have the potential to significantly expand our understanding of the mortuary behaviours, or variation in behaviours, of the Belgian Neolithic and contribute further to the lively debate on the spread of the Neolithic

Neurodevelopmental Disorders and Suicide: A Narrative Review

Specific risk factors for self-harm and suicide in children and adolescents with neurodevelopmental disorders (NDD) may differ from those in the general population within this age range. In the present review paper, we conducted a narrative analysis of the literature, aiming to establish a connection between suicide and affective disorders in children and adolescents with NDD. Emotion dysregulation (ED) as an individual factor and adverse childhood experiences (ACE) as environmental factors are discussed as risk factors for suicidality in all individuals with NDD. We propose a theoretical model in which ED and ACE can directly lead to self-harm or suicide, directly or indirectly by interacting with depressive spectrum disorders. Additionally, we suggest that specific risk factors are more frequently associated with each of the neurodevelopmental disorders listed in the DSM-V. This review underlines the key points useful to improve the knowledge of the trajectory leading to suicide risk in NDDs with the purpose to facilitate the early identification of the suicide risk

Venom Diversity and Evolution in the Most Divergent Cone Snail Genus Profundiconus

Profundiconus is the most divergent cone snail genus and its unique phylogenetic position, sister to the rest of the family Conidae, makes it a key taxon for examining venom evolution and diversity. Venom gland and foot transcriptomes of Profundiconus cf. vaubani and Profundiconus neocaledonicus were de novo assembled, annotated, and analyzed for differential expression. One hundred and thirty-seven venom components were identified from P. cf. vaubani and 82 from P. neocaledonicus, with only four shared by both species. The majority of the transcript diversity was composed of putative peptides, including conotoxins, profunditoxins, turripeptides, insulin, and prohormone-4. However, there were also a significant percentage of other putative venom components such as chymotrypsin and L-rhamnose-binding lectin. The large majority of conotoxins appeared to be from new gene superfamilies, three of which are highly different from previously reported venom peptide toxins. Their low conotoxin diversity and the type of insulin found suggested that these species, for which no ecological information are available, have a worm or molluscan diet associated with a narrow dietary breadth. Our results indicate that Profundiconus venom is highly distinct from that of other cone snails, and therefore important for examining venom evolution in the Conidae family

New Prognostic Frontiers for Lung Neuroendocrine Tumors

Background: Well-differentiated neuroendocrine tumors of the lung (Lung NET) are classified as typical (TC) and atypical (AC) carcinoids, on the basis of mitotic count and presence of necrosis. However, the identification of prognostic factors, other than TNM stage and histopathological diagnosis of AC versus TC, are still lacking. Methods: We assessed the association of clinical and pathological data with survival in a multicenter retrospective series of 200 surgically resected lung NET from 8 Italian & 1 Spanish Institutions. Patients data were collected and analysed by SPSS program. Results: The study population presented a median age of 60 years (13-86), 40.0% presented a male gender, 31.5% were smokers, 31.0% AC, 40.5% left-sided tumors, 36.5% with a peripheral location. I&II TNM stages at diagnosis were present in 84.5% of cases, with 25% nodal positive status. Mitotic count 2/10 HPF in 31%, necrosis in 17.5%, Ki67 >20% in 8 patients (4%). The population had a median OS of 49 months (0.6-323), and a median PFS of 36.0 months (0.5-323). At Cox univariate regression model, male gender (p1⁄40.0001, p1⁄40.001), left side (p1⁄40.001, p1⁄40.015), nodal positive status (p1⁄40.0001, p1⁄40.0001), advanced TNM stage (p<0.0001, p<0.0001), mitotic count 2/10 HPF (p1⁄40.001,p1⁄40.031), Ki67 >20% (p1⁄40.017, p1⁄40.001), presence of necrosis (p1⁄40.001, p1⁄40.04), and AC histotype (p1⁄40.0001, p1⁄40.006), correlated with shorter PFS and OS, respectively. Tumoral peripheral location (p1⁄40.038) correlated with shorter OS. At Cox multivariate regression analysis, gender (male vs female) (p1⁄40.0057), tumor side (left vs right) (p1⁄40.0118), advanced stage (p1⁄40.0206), a Ki67 >20% and/or a mitotic count >10/10 HPF (p1⁄40.0109), and the presence of necrosis (p1⁄40.0010) were confirmed as independent prognostic factors in terms of PFS. Gender (male vs female) (p1⁄40.0127), tumor side (left vs right) (p1⁄40.0669) and advanced stage (p1⁄40.0208) were independent negative prognostic factors for OS. Conclusions: This study confirm the prognostic relevance of TNM stage and of the diagnosis of AC, to stratify NET patients. Additionally, our analysis suggests a potential prognostic value for new clinical and pathological features, as male gender, left-sided primary tumor and high proliferation inde