On the regularity of curvature fields in stress-driven nonlocal elastic beams

AbstractElastostatic problems of Bernoulli–Euler nanobeams, involving internal kinematic constraints and discontinuous and/or concentrated force systems, are investigated by the stress-driven nonlocal elasticity model. The field of elastic curvature is output by the convolution integral with a special averaging kernel and a piecewise smooth source field of elastic curvature, pointwise generated by the bending interaction. The total curvature is got by adding nonelastic curvatures due to thermal and/or electromagnetic effects and similar ones. It is shown that fields of elastic curvature, associated with piecewise smooth source fields and bi-exponential kernel, are continuously differentiable in the whole domain. The nonlocal elastic stress-driven integral law is then equivalent to a constitutive differential problem equipped with boundary and interface constitutive conditions expressing continuity of elastic curvature and its derivative. Effectiveness of the interface conditions is evidenced by the solution of an exemplar assemblage of beams subjected to discontinuous and concentrated loadings and to thermal curvatures, nonlocally associated with discontinuous thermal gradients. Analytical solutions of structural problems and their nonlocal-to-local limits are evaluated and commented upon

Medieval Glassworks in the City of Ferrara (North Eastern Italy): The Case Study of Piazza Municipale

Compositional and structural characterization was carried out on transparent glass fragments found in a brick rubbish pit discovered in basal floor of the ducal palace of Ferrara, during the excavation of Piazza Municipale. This study aims to identify raw materials and glass-working techniques through X-Ray Fluorescence (XRF) quantitative chemical analyses and semi-quantitative Scanning Electron Microscopy (SEM) observations. The studied fragments were produced using siliceous-lime sands with natron as flux, and allowed us to better understand the production technologies in a historical period of great innovation for European glass art. The numerous findings of glass fragments discovered in brick underground cellars built for the specific purpose of household rubbish of wealthy complexes in Ferrara testify a consolidated system of separate discharge of solid waste into underground containers, which were closed and sealed once filled. The high volume of the finds indicates the absence of recycling of accumulated materials due to the well-being of the city. Compositional analysis confirmed the local production of glass shops in Ferrara during the late Middle Ages, characterized by differences with the glasses of the nearby city of Venice. Morphological analyses also defined the nature and relative abundance of the products, exploring the types and compositions of the Ferrara glass art

Identification of organic material in Los Buitres 1 rock art shelter, Badajoz, Spain

This research aimed to characterize the chemical and mineralogical nature of prehistoric painted figures from the Los Buitres 1 rock shelter and to identify organic material from the pigment samples. MicroRaman spectroscopy and ATR-FTIR analysis were made. Four pigment samples were selected: three red and one dark-red granules of pigment. Micro-Raman spectroscopy was applied to determine the mineralogical composition of selected samples while ATR-FTIR was applied in order to identify organic material present in each. Samples 1 and 2 are almost identical and registered montmorillonite being present. Analyses by ATRFTIR points to organic components in sample 3 while sample 4 was identified as burnt umber. A comparison with a nearby shelter with the same organic compounds in the same type of figure causes some alarms to sound due to the possibility that a real pigment recipe has been in use in the same region for the same time spectrum.El objetivo de esta investigación ha sido caracterizar la naturaleza química y mineralógica del pigmento empleado en los motivos esquemáticos prehistóricos de la cueva de Los Buitres 1 (Capilla, Badajoz), y tratar de identificar la presencia de materia orgánica en su composición. Para ello se han realizado análisis de espectroscopia Micro-Raman y ATR-FTIR sobre cuatro muestras de pigmento, tres de pigmento rojo y una más también roja, aunque de tonalidad más oscura. Se aplicó la espectroscopia Micro-Raman para determinar la composición mineralógica de las muestras seleccionadas, mientras que el ATR-FTIR se aplicó para determinar la presencia de materia orgánica presente en cada una de ellas. Destacar que las muestras 1 y 2 son casi idénticas y registraron la presencia de montmorillonite. Por su parte, los análisis por ATR-FTIR señalaron la presencia de componentes orgánicos en la muestra 3, mientras que la muestra 4 se caracterizó como ocre oscuro quemado. La comparación con los pigmentos empleados en el arte rupestre esquemático de un abrigo cercano, en donde han sido identificados los mismos componentes orgánicos en similares tipologías figurativas, invita a considerar la posibilidad de que nos encontremos con una suerte de “receta” para preparar el pigmento que debió estar en uso en este territorio durante un periodo cronológico concreto

The PPARγ2 Pro12Ala variant is protective against progression of nephropathy in people with type 2 diabetes

Cross-sectional studies suggest the association between diabetic nephropathy and the PPARγ2 Pro12Ala polymorphism of the peroxisome proliferator-activated receptor γ2 (PPARγ2). Prospective data are limited to microalbuminuria and no information on renal function is available to date. The present study evaluates the association between the Pro12Ala polymorphism of PPARγ2 and the progression of albuminuria and decay in glomerular filtration rate (GFR) in type 2 diabetes

Complete Versus Incomplete Surgical Resection in Intramedullary Astrocytoma: Systematic Review with Individual Patient Data Meta-Analysis

Study Design: Systematic review Background: Considering the infiltrative nature of intramedullary astrocytoma, the goal of surgery is to have a better patient related outcome. Objective: To compare the overall survival (OS) and neurologic outcomes of complete vs incomplete surgical resection for patients with intramedullary astrocytoma. Methods: A comprehensive search of MEDLINE, CENTRAL and EMBASE was conducted by two independent reviewers. Individual patient data (IPD) analysis and multivariate Cox Proportional Hazard Model was developed to measure the effect of surgical strategies on OS, post-operative neurological improvement (PNI), and neurological improvement in the last follow up (FNI). Results: We included 1079 patients from 35 studies. Individual patient data of 228 patients (13 articles) was incorporated into the integrative IPD analysis. Kaplan-Meier survival analysis showed complete resection (CR) significantly improved OS in comparison with the incomplete resection (IR) (log-rank test, P =.004). In the multivariate IPD analysis, three prognostic factors had significant effect on the OS: (1) Extent of Resection, (2) pathology grade, and (3) adjuvant therapy. We observed an upward trend in the popularity of chemotherapy, but CR, IR, and radiotherapy had relatively stable trends during three decades. Conclusion: Our study shows that CR can improve OS when compared to IR. Patients with spinal cord astrocytoma undergoing CR had similar PNI and FNI compared to IR. Therefore, CR should be the primary goal of surgery, but intraoperative decisions on the extent of resection should be relied on to prevent neurologic adverse events. Due to significant effect of adjuvant therapy on OS, PNI and FNI, it could be considered as the routine treatment strategy for spinal cord astrocytoma

Prognostic factors in gemcitabine-cisplatin polychemotherapy regimens in pancreatic cancer: XPD-Lys751Gln polymorphism strikes back

: The use of platinated agents in combination chemotherapy regimens for advanced pancreatic cancer is controversial owing to the lack of an outstanding impact on the outcome and a substantial increase in hematologic and extra-hematologic toxicities. Pharmacogenetic studies to identify patients who could benefit most from such therapies are urgently needed. The Xeroderma-Pigmentosum group-D polymorphism at codon-751 (XPD-Lys751Gln) emerged as the most significant independent predictor for death- and progression-risk in our previous study on functional polymorphisms in 122 advanced pancreatic cancer patients treated with cisplatin-docetaxel-capecitabine-gemcitabine and cisplatin-epirubicin-capecitabine-gemcitabine (or EC-GemCap). To confirm the prognostic role of this variable, we further evaluated the correlation of XPD-Lys751Gln with outcome in another 125 patients treated with the same regimens, and 90 treated with gemcitabine monotherapy. Genotyping was successfully carried out in the vast majority of DNA samples. Genotype frequencies followed Hardy-Weinberg equilibrium, and XPD-Lys751Gln was associated with differential progression-free and overall-survival. Multivariate analysis confirmed its prognostic significance in platinum-based regimens. In particular, XPD-Gln751Gln was significantly associated with risk of death (hazard ratio, HR = 1.7, 95% confidence interval [CI], 1.1-2.6, p = 0.011) and risk of progression (HR = 1.7, 95% CI, 1.1-2.5, p = 0.013). No correlation was observed in gemcitabine monotherapy-treated patients. The analysis of DNA damage using extra-long-PCR in lymphocytes supported the association of XPD-Gln751Gln with greater resistance to cisplatin-induced damage. The increasing evidence of XPD-Lys751Gln impact on the outcome of gemcitabine-cisplatin-based polychemotherapy leads to plan prospective studies to validate the role of this polymorphism as a new tool for optimization of the currently available treatments in pancreatic cancer

A polymorphism in the promoter is associated with EZH2 expression but not with outcome in advanced pancreatic cancer patients

Aim: EZH2 expression is a prognostic marker in radically resected pancreatic ductal adenocarcinoma (PDAC) patients. Here we investigated its role in locally advanced/metastatic patients, as well as candidate polymorphisms. Materials & methods: EZH2 expression and polymorphisms were evaluated by quantitative reverse transcription PCR in 32 laser microdissected tumors, while polymorphisms were also studied in blood samples from two additional cohorts treated with gemcitabine monotherapy (n = 93) or polychemotherapeutic regimens (n = 247). Results: EZH2 expression correlated with survival and with the rs6958683 polymorphism in the first cohort of patients, but this polymorphism was not associated with survival in our larger cohorts. Conclusion: EZH2 is a prognostic factor for locally advanced/metastatic PDACs, while candidate polymorphisms cannot predict clinical outcome. Other factors involved in EZH2 regulation, such as miR-101, should be investigated in accessible samples in order to improve the clinical management of advanced PDAC

Impact of a mediterranean dietary pattern and its components on cardiovascular risk factors, glucose control, and body weight in people with type 2 diabetes: A real-life study

This study evaluates the relation of a Mediterranean dietary pattern and its individual components with the cardiovascular risk factors profile, plasma glucose and body mass index (BMI) in people with type 2 diabetes. We studied 2568 participants at 57 diabetes clinics. Diet was assessed with the EPIC (European Prospective Investigation into Cancer and Nutrition) questionnaire, adherence to the Mediterranean diet was evaluated with the relative Mediterranean diet score (rMED). A high compared to a low score was associated with a better quality of diet and a greater adherence to the nutritional recommendations for diabetes. However, even in the group achieving a high score, only a small proportion of participants met the recommendations for fiber and saturated fat (respectively 17% and 30%). Nonetheless, a high score was associated with lower values of plasma lipids, blood pressure, glycated hemoglobin, and BMI. The relationship of the single food items components of the rMED score with the achievement of treatment targets for plasma lipids, blood pressure, glucose, and BMI were also explored. The study findings support the Mediterranean dietary model as a suitable model for type 2 diabetes and the concept that the beneficial health effects of the Mediterranean diet lie primarily in its synergy among various nutrients and foods rather than on any individual component

The botanical drug PBI-05204, a supercritical CO2 extract of Nerium oleander, sensitizes alveolar and embryonal rhabdomyosarcoma to radiotherapy in vitro and in vivo

: Treatment of rhabdomyosarcoma (RMS), the most common a soft tissue sarcoma in childhood, provides intensive multimodal therapy, with radiotherapy (RT) playing a critical role for local tumor control. However, since RMS efficiently activates mechanisms of resistance to therapies, despite improvements, the prognosis remains still largely unsatisfactory, mainly in RMS expressing chimeric oncoproteins PAX3/PAX7-FOXO1, and fusion-positive (FP)-RMS. Cardiac glycosides (CGs), plant-derived steroid-like compounds with a selective inhibitory activity of the Na+/K+-ATPase pump (NKA), have shown antitumor and radio-sensitizing properties. Herein, the therapeutic properties of PBI-05204, an extract from Nerium oleander containing the CG oleandrin already studied in phase I and II clinical trials for cancer patients, were investigated, in vitro and in vivo, against FN- and FP-RMS cancer models. PBI-05204 induced growth arrest in a concentration dependent manner, with FP-RMS being more sensitive than FN-RMS, by differently regulating cell cycle regulators and commonly upregulating cell cycle inhibitors p21Waf1/Cip1 and p27Cip1/Kip1. Furthermore, PBI-05204 concomitantly induced cell death on both RMS types and senescence in FN-RMS. Notably, PBI-05204 counteracted in vitro migration and invasion abilities and suppressed the formation of spheroids enriched in CD133+ cancer stem cells (CSCs). PBI-05204 sensitized both cell types to RT by improving the ability of RT to induce G2 growth arrest and counteracting the RT-induced activation of both Non-Homologous End-Joining and homologous recombination DSBs repair pathways. Finally, the antitumor and radio-sensitizing proprieties of PBI-05204 were confirmed in vivo. Notably, both in vitro and in vivo evidence confirmed the higher sensitivity to PBI-05204 of FP-RMS. Thus, PBI-05204 represents a valid radio-sensitizing agent for the treatment of RMS, including the intrinsically radio-resistant FP-RMS