Fractoluminescence characterization of the energy dissipated during fast fracture of glass

Fractoluminescence experiments are performed on two kinds of silicate glasses. All the light spectra collected during dynamic fracture reveal a black body radiator behaviour, which is interpreted as a crack velocity-dependent temperature rise close to the crack tip. Crack velocities are estimated to be of the order of 1300 m.s$^{-1}$ and fracture process zones are shown to extend over a few nanometers.Comment: Accepted for publication in Europhysics Letters; 5 pages; 4 figure

Modeling the series of (n x 2) Si-rich reconstructions of beta-SiC(001): a prospective atomic wire?

We perform ab initio plane wave supercell density functional calculations on three candidate models of the (3 x 2) reconstruction of the beta-SiC(001) surface. We find that the two-adlayer asymmetric-dimer model (TAADM) is unambiguously favored for all reasonable values of Si chemical potential. We then use structures derived from the TAADM parent to model the silicon lines that are observed when the (3 x 2) reconstruction is annealed (the (n x 2) series of reconstructions), using a tight-binding method. We find that as we increase n, and so separate the lines, a structural transition occurs in which the top addimer of the line flattens. We also find that associated with the separation of the lines is a large decrease in the HOMO-LUMO gap, and that the HOMO state becomes quasi-one-dimensional. These properties are qualititatively and quantitatively different from the electronic properties of the original (3 x 2) reconstruction.Comment: 22 pages, including 6 EPS figure

Prioritising systemic cancer therapies applying ESMO's tools and other resources to assist in improving cancer care globally:the Kazakh experience

BACKGROUND: In Kazakhstan, cancer is the second leading cause of death with a major public health and economic burden. In the last decade, cancer care and cancer medicine costs have significantly increased. To improve the efficiency and efficacy of cancer care expenditure and planning, the Kazakhstan Ministry of Health requested assistance from the World Health Organization (WHO) and the European Society for Medical Oncology (ESMO) to review its systemic cancer treatment protocols and essential medicines list and identify high-impact, effective regimens. MATERIALS AND METHODS: ESMO developed a four-phase approach to review Kazakhstan cancer treatment protocols: (i) perform a systematic analysis of the country’s cancer medicines and treatment protocols; (ii) cross-reference the country’s cancer protocols with the WHO Model List of Essential Medicines, the ESMO-Magnitude of Clinical Benefit Scale and the European Medicines Agency’s medicine availability and indications database; (iii) extract treatment recommendations from the ESMO Clinical Practice Guidelines; (iv) expert review for all cancer medicines not on the WHO Model List of Essential Medicines and the country treatment protocols. RESULTS: This ESMO four-phase approach led to the update of the Kazakhstan national essential cancer medicines list and the list of cancer treatment protocols. This review has led to the withdrawal of several low-value or non-evidence-based medicines and a budget increase for cancer care to include all essential and highly effective medicines and treatment options. CONCLUSION: When applied effectively, this four-phase approach can improve access to medicines, efficiency of expenditure and sustainability of cancer systems. The WHO–ESMO collaboration illustrated how, by sharing best practices, tools and resources, we can address access to cancer medicines and positively impact patient care

Combined paclitaxel and gemcitabine as first-line treatment in metastatic non-small cell lung cancer: a multicentre phase II study

The efficacy and toxicity of combined paclitaxel and gemcitabine was evaluated in 54 chemotherapy-naive patients with metastatic non-small cell lung cancer (NSCLC). Gemcitabine i.v. 1000 mg/m2was administered on days 1 and 8 and paclitaxel 200 mg/m2as a continuous 3-hour infusion on day 1. Treatment was repeated every 21 days. Patients had a median age of 53 years. ECOG performance status was 0 or 1 in 48 patients. 41 patients (75.9%) had initial stage IV disease; histology was mainly adenocarcinoma (46.3%). 2 patients (4.3%) achieved a complete response and 15 (31.9%) achieved a partial response giving an overall response rate of 36.2% (95% CI: 22.4–49.9%); 19 patients (40.4%) had stable disease and 10 (21.3%) had progressive disease. The median survival time was 51 weeks (95% CI: 46.5–59.3), with a 1-year survival probability of 0.48 (95% CI: 0.34–0.63). Grade 3/4 neutropenia and febrile neutropenia occurred in 15.2% and 2.2% of courses, respectively. Grade 3/4 thrombocytopenia was rare (1.8% of courses). Peripheral neurotoxicity developed in 25 patients (47.2%), mostly grade 1/2. Arthalgia/myalgia was observed in 30 patients (56.6%), generally grade 1 or 2. Grade 3 abnormal levels of serum glutamate pyruvate transaminase (SGPT) and serum glutamate oxaloacetate transaminase (SGOT) occurred in 5 patients (9.4%) and 1 patient (1.9%), respectively. Combined paclitaxel and gemcitabine is an active and well-tolerated regimen for the treatment of advanced NSCLC, and warrants further investigation in comparative, randomized trials. © 2001 Cancer Research Campaign http://www.bjcancer.co

Effect of grain orientation and magnesium doping on β-tricalcium phosphate resorption behavior

The efficiency of calcium phosphate (CaP) bone substitutes can be improved by tuning their resorption rate. The influence of both crystal orientation and ion doping on resorption is here investigated for beta-tricalcium phosphate (β-TCP). Non-doped and Mg-doped (1 and 6 mol%) sintered β-TCP samples were immersed in acidic solution (pH 4.4) to mimic the environmental conditions found underneath active osteoclasts. The surfaces of β-TCP samples were observed after acid-etching and compared to surfaces after osteoclastic resorption assays. β-TCP grains exhibited similar patterns with characteristic intra-crystalline pillars after acid-etching and after cell-mediated resorption. Electron BackScatter Diffraction analyses, coupled with Scanning Electron Microscopy, Inductively Coupled Plasma–Mass Spectrometry and X-Ray Diffraction, demonstrated the influence of both grain orientation and doping on the process and kinetics of resorption. Grains with c-axis nearly perpendicular to the surface were preferentially etched in non-doped β-TCP samples, whereas all grains with simple axis (a, b or c) nearly normal to the surface were etched in 6 mol% Mg-doped samples. In addition, both the dissolution rate and the percentage of etched surface were lower in Mg-doped specimens. Finally, the alignment direction of the intra-crystalline pillars was correlated with the preferential direction for dissolution. Statement of significance: The present work focuses on the resorption behavior of calcium phosphate bioceramics. A simple and cost-effective alternative to osteoclast culture was implemented to identify which material features drive resorption. For the first time, it was demonstrated that crystal orientation, measured by Electron Backscatter Diffraction, is the discriminating factor between grains, which resorbed first, and grains, which resorbed slower. It also elucidated how resorption kinetics can be tuned by doping β-tricalcium phosphate with ions of interest. Doping with magnesium impacted lattice parameters. Therefore, the crystal orientations, which preferentially resorbed, changed, explaining the solubility decrease. These important findings pave the way for the design of optimized bone graft substitutes with tailored resorption kinetics

ESMO recommendations on the standard methods to detect NTRK fusions in daily practice and clinical research

Abstract Background NTRK1, NTRK2 and NTRK3 fusions are present in a plethora of malignancies across different histologies. These fusions represent the most frequent mechanism of oncogenic activation of these receptor tyrosine kinases, and biomarkers for the use of TRK small molecule inhibitors. Given the varying frequency of NTRK1/2/3 fusions, crucial to the administration of NTRK inhibitors is the development of optimal approaches for the detection of human cancers harbouring activating NTRK1/2/3 fusion genes. Materials and methods Experts from several Institutions were recruited by the European Society for Medical Oncology (ESMO) Translational Research and Precision Medicine Working Group (TR and PM WG) to review the available methods for the detection of NTRK gene fusions, their potential applications, and strategies for the implementation of a rational approach for the detection of NTRK1/2/3 fusion genes in human malignancies. A consensus on the most reasonable strategy to adopt when screening for NTRK fusions in oncologic patients was sought, and further reviewed and approved by the ESMO TR and PM WG and the ESMO leadership. Results The main techniques employed for NTRK fusion gene detection include immunohistochemistry, fluorescence in situ hybridization (FISH), RT-PCR, and both RNA-based and DNA-based next generation sequencing (NGS). Each technique has advantages and limitations, and the choice of assays for screening and final diagnosis should also take into account the resources and clinical context. Conclusion In tumours where NTRK fusions are highly recurrent, FISH, RT-PCR or RNA-based sequencing panels can be used as confirmatory techniques, whereas in the scenario of testing an unselected population where NTRK1/2/3 fusions are uncommon, either front-line sequencing (preferentially RNA-sequencing) or screening by immunohistochemistry followed by sequencing of positive cases should be pursued