Sorafenib delivery nanoplatform based on superparamagnetic iron oxide nanoparticles magnetically targets hepatocellular carcinoma

Currently,sorafenib is the only systemic therapy capable of increasing overall survival of hepatocellular carcinoma patients.Unfortunately,its side effects,particularly its overall toxicity,limit the therapeutic response that can be achieved.Superparamagnetic iron oxide nanoparticles (SPIONs) are very attractive for drug delivery because they can be targeted to specific sites in the body through application of a magnetic field,thus improving intratumoral accumulation and reducing adverse effects.Here,nanoformulations based on polyethylene glycol modified phospholipid micelles,loaded with both SPIONs and sorafenib,were successfully prepared and thoroughly investigated by complementary techniques.This nanovector system provided effective drug delivery,had an average hydrodynamic diameter of about 125 nm,had good stability in aqueous medium,and allowed controlled drug loading.Magnetic analysis allowed accurate determination of the amount of SPIONs embedded in each micelle.An in vitro system was designed to test whether the SPION micelles can be efficiently held using a magnetic field under typical flow conditions found in the human liver.Human hepatocellular carcinoma (HepG2) cells were selected as an in vitro system to evaluate tumor cell targeting efficacy of the superparamagnetic micelles loaded with sorafenib.These experiments demonstrated that this delivery platform is able to enhance sorafenib's antitumor effectiveness by magnetic targeting.The magnetic nanovectors described here represent promising candidates for targeting specific hepatic tumor sites,where selective release of sorafenib can improve its efficacy and safety profile.     

Recommendation of RILEM Technical Committee 250-CSM: Test method for Textile Reinforced Mortar to substrate bond characterization

Textile Reinforced Mortar (TRM), also known as Fabric Reinforced Mortar or Fabric Reinforced Cementitious Matrix, composites are an emerging technology for the external repair and strengthening of existing structures. For most applications, the effectiveness of the TRM reinforcement relies on its bond performance. This recommendation identifies the best practice to characterize the bond behaviour of TRM. A shear bond test method is proposed to determine the peak axial stress (associated with the maximum load that can be transferred from the structural member to the externally bonded TRM reinforcement), the stress–slip relationship and the failure mode that controls the TRM-to-substrate load transfer capacity. Guidelines on specimen manufacturing, experimental setup, test execution, and determination of test results are provided.     

Comparison between TRH-stimulated TSH and basal TSH measurement by a commercial immunoradiometric assay in the management of thyroid disease

In order to assess the current diagnostic role of the TRH test following the introduction of more sensitive "second generation" TSH assays, we studied a series of 259 outpatients, 237 women and 22 men, mean age 44.7 years (range 12-82), 91 of whom (35%) with untreated simple goiter, 133 (51%) with simple nodular goiter on steady state I-thyroxine treatment, 18 (7%) with overt or subclinical hyperthyroidism and 17 (7%) with overt or subclinical hypothyroidism, compared to a control group of 26 euthyroid healthy subjects. Serum TSH was measured by a commercial immunoradiometric assay (clinical sensitivity 0.1 microU/ml). TSH response to TRH was evaluated 30 minutes after giving 200 micrograms TRH i.v. bolus, the results being analyzed both as absolute increase (delta-TSH=stimulated TSH minus basal TSH) and as relative increase (R-TSH stimulated TSH/basal TSH). Using cut-off values of 0.3-3.2 microU/ml, basal TSH measurement was able to detect hypothyroidism (specificity = 100%) and to exclude hyperthyroidism (sensivity = 96.9%), but failed to accurately prove hyperthyroidism (specificity = 93.4%) and, above all, to exclude hypothyroidism (sensitivity = 35.3%) in our ambulatory patients. The delta-TSH values showed a basal TSH dependent linear increase (r = + 0.87, p < 0.001) both including only patients (n = 139) with basal TSH level in the euthyroidism range and including all patients (n = 223) having TSH responsive to TRH. All the patients with detectable basal TSH level displayed detectable TSH response to TRH, as did 19 (= 23.5%) of 81 patients with undetectable (< 0.1 microU/ml) basal value. In particular: a) for subnormal but detectable basal TSH ranging between 0.1 and 0.2 microU/ml, TSH was always hyporesponsive (delta-TSH < or = 2.5 microU/ml), while between 0.2 and 0.3 microU/ml TSH was hyporesponsive in 72.2% and normoresponsive (delta-TSH > 2.5 and < or = 11.9 microU/ml) in the remaining 27.8%; b) for basal TSH values within the normal range (0.3-3.2 microU/ml). TSH was hyporesponsive in 13.7%, normoresponsive in 74.8% and hyperresponsive in 11.5%; c) for high basal TSH values TSH was always hyperresponsive. The analysis of R TSH showed relatively constant values in the range of euthyroidism and hypothyroidism (m +/- SD: 7.4 +/- 2.3 and 7.7 +/- 3.1, respectively), and a marked differentiation of hyperthyroid patients whose R-TSH values were significantly lower (4.2 +/- 3.4) but had a wide individual variability. Linear regression analysis of basal or stimulated TSH and circulating thyroid hormones showed a close negative relationship, being highly significant between delta-TSH and T4 (r = 0.57, p < 0.001) and delta-TSH and FT4 (r = 0.46, p < 0.001). In conclusion, after the introduction of current second generation TSH immunoradiometric assay, the diagnostic role of the TRH test is greatly limited but not to be excluded: it can provide additional information to that obtained with simple basal TSH measurement in the diagnosis of subclinical hypothyroidism and in the precise evaluation of the degree of TSH suppression in patients with a subnormal basal TSH, either for endogenous thyrotoxicosis or I.-thyroxine treatment.     

Segmentation of the carotid intima-media region in B-mode ultrasound images

This paper proposes a new approach for the segmentation of both near-end and far-end intima-media regions of the common carotid artery in ultrasound images. The method requires minimal user interaction and is able to segment the near-end wall in arteries with large, hypoechogenic and irregular plaques, issues usually not considered previously due to the increased segmentation difficulty.     

Preserving correctness during business process model configuration

A configurable process model captures a family of related process models in a single artifact. Such models are intended to be configured to fit the requirements of specific organizations or projects, leading to individualized process models that are subsequently used for domain analysis or solution design. This article proposes a formal foundation for individualizing configurable process models incrementally, while preserving correctness, both with respect to syntax and behavioral semantics. Specifically, assuming the configurable process model is behaviorally sound, the individualized process models are guaranteed to be sound. The theory is first developed in the context of Petri nets and then extended to a process modeling notation widely used in practice, namely Event-driven Process Chains.     

APROMORE: An advanced process model repository

Business process models are becoming available in large numbers due to their widespread use in many industrial applications such as enterprise and quality engineering projects. On the one hand, this raises a challenge as to their proper management: how can it be ensured that the proper process model is always available to the interested stakeholder? On the other hand, the richness of a large set of process models also offers opportunities, for example with respect to the re-use of existing model parts for new models. This paper describes the functionality and architecture of an advanced process model repository, named APROMORE. This tool brings together a rich set of features for the analysis, management and usage of large sets of process models, drawing from state-of-the art research in the field of process modeling. A prototype of the platform is presented in this paper, demonstrating its feasibility, as well as an outlook on the further development of APROMORE.     

Configurable multi-perspective business process models

A configurable process model provides a consolidated view of a family of business processes. It promotes the reuse of proven practices by providing analysts with a generic modeling artifact from which to derive individual process models. Unfortunately, the scope of existing notations for configurable process modeling is restricted, thus hindering their applicability. Specifically, these notations focus on capturing tasks and control-flow dependencies, neglecting equally important ingredients of business processes such as data and resources. This research fills this gap by proposing a configurable process modeling notation incorporating features for capturing resources, data and physical objects involved in the performance of tasks. The proposal has been implemented in a toolset that assists analysts during the configuration phase and guarantees the correctness of the resulting process models. The approach has been validated by means of a case study from the film industry.