Targeted antiangiogenic agents in combination with cytotoxic chemotherapy in preclinical and clinical studies in sarcoma.

Sarcomas are a heterogeneous group of mesenchymal malignancies. In recent years, studies have demonstrated that inhibition of angiogenic pathways or disruption of established vasculature can attenuate the growth of sarcomas. However, when used as monotherapy in the clinical setting, these targeted antiangiogenic agents have only provided modest survival benefits in some sarcoma subtypes, and have not been efficacious in others. Preclinical and early clinical data suggest that the addition of conventional chemotherapy to antiangiogenic agents may lead to more effective therapies for patients with these tumors. In the current review, the authors summarize the available evidence and possible mechanisms supporting this approach

A continuous non-linear shadowing model of columnar growth

We propose the first continuous model with long range screening (shadowing) that described columnar growth in one space dimension, as observed in plasma sputter deposition. It is based on a new continuous partial derivative equation with non-linear diffusion and where the shadowing effects apply on all the different processes.Comment: Fast Track Communicatio

A Methodology to Engineer and Validate Dynamic Multi-level Multi-agent Based Simulations

This article proposes a methodology to model and simulate complex systems, based on IRM4MLS, a generic agent-based meta-model able to deal with multi-level systems. This methodology permits the engineering of dynamic multi-level agent-based models, to represent complex systems over several scales and domains of interest. Its goal is to simulate a phenomenon using dynamically the lightest representation to save computer resources without loss of information. This methodology is based on two mechanisms: (1) the activation or deactivation of agents representing different domain parts of the same phenomenon and (2) the aggregation or disaggregation of agents representing the same phenomenon at different scales.Comment: Presented at 3th International Workshop on Multi-Agent Based Simulation, Valencia, Spain, 5th June 201

Phase 1 study of sirolimus in combination with oral cyclophosphamide and topotecan in children and young adults with relapsed and refractory solid tumors.

PurposeTo determine the maximum tolerated dose (MTD), toxicities, and pharmacodynamics effects of sirolimus combined with oral metronomic topotecan and cyclophosphamide in a pediatric population.Materials and methodsPatients who were 1 to 30 years of age with relapsed/refractory solid tumors (including CNS) were eligible. Patients received daily oral sirolimus and cyclophosphamide (25-50 mg/m2/dose) on days 1-21 and oral topotecan (0.8 mg/m2/dose) on days 1-14 in 28-day cycles. Sirolimus steady-state plasma trough concentrations of 3-7.9 ng/mL and 8-12.0 ng/mL were evaluated, with dose escalation based on a 3+3 phase 1 design. Biomarkers of angiogenesis were also evaluated.ResultsTwenty-one patients were treated (median age 18 years; range 9-30). Dose-limiting toxicities included myelosuppression, ALT elevation, stomatitis, and hypertriglyceridemia. The MTD was sirolimus with trough goal of 8-12.0 ng/mL; cyclophosphamide 25 mg/m2/dose; and topotecan 0.8 mg/m2/dose. No objective responses were observed. Four patients had prolonged stable disease > 4 cycles (range 4-12). Correlative biomarker analyses demonstrated reductions in thrombospondin-1 (p=0.043) and soluble vascular endothelial growth factor receptor-2 plasma concentrations at 21 days compared to baseline.ConclusionsThe combination of oral sirolimus, topotecan, and cyclophosphamide was well tolerated and biomarker studies demonstrated modulation of angiogenic pathways with this regimen

A randomized controlled trial of a pharmacist-led intervention to enhance knowledge of Vietnamese patients with type 2 diabetes mellitus

OBJECTIVES: We aimed to assess whether a pharmacist-led intervention enhances knowledge, medication adherence and glycemic control in patients with type 2 diabetes mellitus (T2DM). METHODS: We conducted a single-blinded randomized controlled trial in Vietnam. Individuals with T2DM were recruited from a general hospital and randomly allocated to intervention and routine care. The intervention group received routine care plus counselling intervention by a pharmacist, including providing drug information and answering individual patients' queries relating to T2DM and medications, which had not been done in routine care. We assessed the outcomes: knowledge score as measured by the Diabetes Knowledge Questionnaire, self-reported adherence and fasting blood glucose (FBG) at the 1-month follow-up. KEY FINDINGS: A total of 165 patients (83 intervention, 82 control) completed the study; their mean age was 63.33 years, and 49.1% were males. The baseline characteristics of the patients were similar between the groups. At 1-month follow-up, the pharmacist's intervention resulted in an improvement in all three outcomes: knowledge score [B = 5.527; 95% confidence intervals (CI): 3.982 to 7.072; P < 0.001], adherence [odds ratio (OR) = 9.813; 95% CI: 2.456 to 39.205; P = 0.001] and attainment of target FBG (OR = 1.979; 95% CI: 1.029 to 3.806; P = 0.041). CONCLUSIONS: The pharmacist-led intervention enhanced disease knowledge, medication adherence and glycemic control in patients with T2DM. This study provides evidence of the benefits of pharmacist counselling in addition to routine care for T2DM outpatients in a Vietnam population

Nitrogen trapping ability of hydrogen-induced vacancy and the effect on the formation of AlN in aluminum

This paper presents the ternary interaction of N, H, and vacancy point defects and the nitrogen trapping ability of aluminum vacancies induced by hydrogen by means of DFT methods employed in VASP (Vienna Ab initio Simulation Package) and Abinit package

Axial-flexural coupled vibration and buckling of composite beams using sinusoidal shear deformation theory

A finite element model based on sinusoidal shear deformation theory is developed to study vibration and buckling analysis of composite beams with arbitrary lay-ups. This theory satisfies the zero traction boundary conditions on the top and bottom surfaces of beam without using shear correction factors. Besides, it has strong similarity with Euler–Bernoulli beam theory in some aspects such as governing equations, boundary conditions, and stress resultant expressions. By using Hamilton’s principle, governing equations of motion are derived. A displacement-based one-dimensional finite element model is developed to solve the problem. Numerical results for cross-ply and angle-ply composite beams are obtained as special cases and are compared with other solutions available in the literature. A variety of parametric studies are conducted to demonstrate the effect of fiber orientation and modulus ratio on the natural frequencies, critical buckling loads, and load-frequency curves as well as corresponding mode shapes of composite beams

Controlling a magnetic Feshbach resonance with laser light

The capability to tune the strength of the elastic interparticle interaction is crucial for many experiments with ultracold gases. Magnetic Feshbach resonances are a tool widely used for this purpose, but future experiments would benefit from additional flexibility such as spatial modulation of the interaction strength on short length scales. Optical Feshbach resonances offer this possibility in principle, but suffer from fast particle loss due to light-induced inelastic collisions. Here we show that light near-resonant with a molecular bound-to-bound transition can be used to shift the magnetic field at which a magnetic Feshbach resonance occurs. This makes it possible to tune the interaction strength with laser light and at the same time induce considerably less loss than an optical Feshbach resonance would do