Use of Circumferentially Cracked Bar sample for CTOD fracture toughness determination in the upper shelf regime

In this work, the use of circumferentially cracked bar (CCB) sample to determine material fracture toughness in the upper shelf regime for carbon steels has been investigated. Since high fracture toughness materials are known to exhibit extensive crack tip blunting before ductile crack initiation, accurate specimen design is required to provide realistic fracture toughness measurement. Here, a CCB was designed to have similar loss of constraint as for SENT sample. Continuum damage mechanics was used to predict the occurrence of ductile crack initiation and propagation. Finite element analysis was performed to predict specimen response and to compare computed J-integral crack driving force with measured CTOD. Finally, experimental tests were performed on X65 carbon steel and the measured critical CTOD was compared with available fracture data obtained with SENT

Ruthenium(III) complexes entrapped in liposomes with enhanced cytotoxic and anti-metastatic properties

Metal-based anticancer drugs are pivotal in the fight against cancer pathologies. Since 1978 cis-platin was licensed for medical treatment of a wide number of tumor pathologies(1). However its chemiotherapic use is strongly limited by many and severe side effects and acquired tumor resistance. Since these limitations could be overcome by other metal complexes, in the last thirty years ruthenium compounds have been tested showing a remarkable antitumoral and antimetastatic activity associated with a lower toxicity. A hexacoordinate Ru(III) complex (NAMI-A) is currently undergoing advanced clinical evaluation (2). All data indicate that NAMI-A acts as a pro-drug, but the integrity of ruthenium complexes is essential to store the cytotoxic activity. In this scenario the condition of administration of ruthenium drugs are crucial to exploit their anticancer activity (3). In the last years innovative strategies have been produced to vehicle ruthenium ions in tumor cells like aggregates. This study aims to incorporate the ruthenium complexes in the inner aqueous compartment of liposomes and to test biological properties of two NAMI-A like pyridine derivatives. Specifically, we have investigated the pyridine derivatives of the sodium-compensated analogue of NAMI-A, Na[trans-RuCl4(pyridine)(DMSO)] (NAMI-Pyr) and Na[trans-RuCl4(Pytri)(DMSO)] (NAMI-Pytri). In thelatter complex the pyridine ligand is functionalized with a sugar moiety so as to increase biocompatibility and the ability to cross the cell membrane. The stability of the complexes was studied and compared in solution at different pH following UV-VIS spectra. Lipid formulations based on Egg PC were prepared adding Cholesterol, DSPE-PEG2000 joining molar ratio 57/38 /5% w/w respectively in MeOH/CHCl3 (50/50 v/v) mixture and hydrated with 0.9% w/w of NaCl. This composition was selected to reproduce analog supramolecular aggregates in clinical use to vehicle doxorubicin (Doxil). Ruthenium complexes were loaded into liposomes using the passive equilibration loading method. Full drug containing liposomes were structurally characterized by dynamic light scattering (DLS) measurements. Data indicate the formation of stable aggregates with size and shape in the right range for in vivo applications. The amount of encapsulated ruthenium complexes was quantified by means of ICP-AES. Stability and drug release properties of ruthenium containing liposomes were confirmed in buffer. The growth inhibitory effects of both liposomal and free complexes drug were tested on prostate cancer cells (PC3). Preliminary results show high cytotoxic effect of ruthenium complexes delivered by supramolecular aggregates with respect to free complexes drug

Hemostatic Agents in Hepatobiliary and Pancreas Surgery: A Review of the Literature and Critical Evaluation of a Novel Carrier-Bound Fibrin Sealant (TachoSil)

Background. Despite progress in surgical techniques applied during hepatobiliary and pancreas (HPB) surgery, bleeding and bile leak remain significant contributors to postoperative mortality and morbidity. Topical hemostatics have been developed and utilized across surgical specialties, but data regarding effectiveness remains inconsistent and sparse in HPB surgery. Methods. A comprehensive search for studies and reviews on hemostatics in HPB surgery was performed via an October 2011 query of Medline, EMBASE, and Cochrane Library. In-depth evaluation of a novel carrier-bound fibrin sealant (TachoSil) was also performed. Results. The literature review illustrates multiple attempts have been made at developing different topical hemostatics and sealants to aid in surgical procedures. In HPB surgery, efforts have been directed at decreasing bleeding, biliary leakage, and pancreatic fistula. Conflicting scientific evidence exists regarding the effectiveness of these agents. Critical evaluation of the literature demonstrates TachoSil is a valuable tool in achieving hemostasis, and possibly biliostasis and pancreatic fistula prevention. Conclusion. While progress has been made in topical hemostatics for HPB surgery, an ideal agent has not yet been identified. TachoSil is promising, but larger randomized, controlled clinical trials are required to more fully evaluate its efficacy in reducing bleeding, biliary leakage, and pancreatic fistulas in HPB surgery

Role of yttrium-90 selective internal radiation therapy in the treatment of liver-dominant metastatic colorectal cancer: An evidence-based expert consensus algorithm

Surgical resection of colorectal liver metastases is associated with greater survival compared with non-surgical treatment, and a meaningful possibility of cure. However, the majority of patients are not eligible for resection and may require other non-surgical interventions, such as liver-directed therapies, to be converted to surgical eligibility. Given the number of available therapies, a general framework is needed that outlines the specific roles of chemotherapy, surgery, and locoregional treatments [including selective internal radiation therapy (SIRT) with Y-90 microspheres]. Using a data-driven, modified Delphi process, an expert panel of surgical oncologists, transplant surgeons, and hepatopancreatobiliary (HPB) surgeons convened to create a comprehensive, evidence-based treatment algorithm that includes appropriate treatment options for patients stratified by their eligibility for surgical treatment. The group coined a novel, more inclusive phrase for targeted locoregional tumor treatment (a blanket term for resection, ablation, and other emerging locoregional treatments)

Strain Rate Effects on Fracture Behavior of Austempered Ductile Irons

In this work, the mechanical behavior of the austempered ductile iron (ADI) JS/1050-6 was investigated, with particular attention to the strain rate effects on the material ductility. Tensile tests at different strain rates (up to 103 s(-1)) and temperatures (ranging from 213 to 343 K) were performed. Samples with different geometries, smooth and round notched bars, were used to evaluate the effect of the stress triaxiality level on the strain at fracture. For each configuration, the evolution paths of stress and strain were extracted in the point where failure is expected performing numerical analyses at the continuum scale. Stress histories were used as input in a micromechanics analysis aimed to analyze the heterogeneous state of stress, determined by the presence of the graphite nuclei, under the different loading conditions obtained in the experiments. The main result is that, under dynamic conditions, the stress field redistribution, due to the adiabatic condition, postpones the failure occurrence, regardless temperature and strain rate effects on the matrix ductility

Mechanisms and therapeutic applications of electromagnetic therapy in Parkinson's disease

© 2015 Vadalà et al. Electromagnetic therapy is a non-invasive and safe approach for the management of several pathological conditions including neurodegenerative diseases. Parkinson's disease is a neurodegenerative pathology caused by abnormal degeneration of dopaminergic neurons in the ventral tegmental area and substantia nigra pars compacta in the midbrain resulting in damage to the basal ganglia. Electromagnetic therapy has been extensively used in the clinical setting in the form of transcranial magnetic stimulation, repetitive transcranial magnetic stimulation, high-frequency transcranial magnetic stimulation and pulsed electromagnetic field therapy which can also be used in the domestic setting. In this review, we discuss the mechanisms and therapeutic applications of electromagnetic therapy to alleviate motor and non-motor deficits that characterize Parkinson's disease