Laser Repair of Superalloy Single Crystals with Varying Substrate Orientations

The casting and repair of single-crystal gas turbine blades require specific solidification conditions that prevent the formation of new grains, equiaxed or columnar, ahead of the epitaxial columnar dendrites. These conditions are best determined by microstructure modeling. Present day analytical models of the columnar-to-equiaxed transition (CET) relate the microstructure to local solidification conditions (temperature gradient and interface velocity) without taking into account the effects of (1) a preferred growth direction of the columnar dendrites and (2) a growth competition between columnar grains of different orientations. In this article, the infiuence of these effects on the grain structure of nickel-base superalloy single crystals, which have been resolidified after laser treatment or directionally cast, is determined by experiment and by analytical and numerical modeling. It is shown that two effects arise for the case of a nonzero angle between the local heat flux direction and the preferred dendrite growth axis: (1) the regime of equiaxed growth is extended and (2) a loss of the crystal orientation of the substrate often occurs by growth competition of columnar grains leading to an "oriented-to-misoriented transition” (OMT). The results are essential for the definition of the single-crystal processing window and are important for the service life extension of expensive components in land-based or aircraft gas turbine

Worldwide variations in EGFR somatic mutations: a challenge for personalized medicine

Two studies recently reported around 10% of EGFR activating mutations in triple negative breast cancers from Asian patients. However, we did not find any EGFR activating mutation in a series of 229 breast tumor samples from European patients. Like in lung cancer, the EGFR mutation profiles seem to be related to the ethnical origin of patients. This is an important point that should be considered when developing anti-EGFR therapies

Severe cutaneous toxicity following treatment with radiotherapy and cetuximab: a case report

While the addition of cetuximab to radiotherapy improves clinical outcomes in locoregionally advanced head and neck squamous cell cancers, there are a small number of reports of severe radiation dermatitis occurring with this therapeutic combination. We present the case of a 69 year old male who developed severe radiation dermatitis following treatment with cetuximab and radiotherapy for a locoregionally advanced head and neck squamous cell cancer

Tumour biology, metastatic sites and taxanes sensitivity as determinants of eribulin mesylate efficacy in breast cancer: results from the ERIBEX retrospective, international, multicenter study.

BACKGROUND: Our retrospective, international study aimed at evaluating the activity and safety of eribulin mesylate (EM) in pretreated metastatic breast cancer (MBC) in a routine clinical setting. METHODS: Patients treated with EM for a locally advanced or MBC between March 2011 and January 2014 were included in the study. Clinical and biological assessment of toxicity was performed at each visit. Tumour response was assessed every 3 cycles of treatment. A database was created to collect clinical, pathological and treatment data. RESULTS: Two hundred and fifty-eight patients were included in the study. Median age was 59 years old. Tumours were Hormone Receptor (HR)-positive (73.3 %) HER2-positive (10.2 %), and triple negative (TN, 22.5 %). 86.4 % of the patients presented with visceral metastases, mainly in the liver (67.4 %). Median previous metastatic chemotherapies number was 4 [1-9]. Previous treatments included anthracyclines and/or taxanes (100 %) and capecitabine (90.7 %). Median number of EM cycles was 5 [1-19]. The relative dose intensity was 0.917. At the time of analysis (median follow-up of 13.9 months), 42.3 % of the patients were still alive. The objective response rate was 25.2 % (95 %CI: 20-31) with a 36.1 % clinical benefit rate (CBR). Median time to progression (TTP) and overall survival were 3.97 (95 %CI: 3.25-4.3) and 11.2 (95 %CI: 9.3-12.1) months, respectively. One- and 2-year survival rates were 45.5 and 8.5 %, respectively. In multivariate analysis, HER2 positivity (HR = 0.29), the presence of lung metastases (HR = 2.49) and primary taxanes resistance (HR = 2.36) were the only three independent CBR predictive factors, while HR positivity (HR = 0.67), the presence of lung metastases (HR = 1.52) and primary taxanes resistance (HR = 1.50) were the only three TTP independent prognostic factors. Treatment was globally well tolerated. Most common grade 3-4 toxicities were neutropenia (20.9 %), peripheral neuropathy (3.9 %), anaemia (1.6 %), liver dysfunction (0.8 %) and thrombocytopenia (0.4 %). Thirteen patients (5 %) developed febrile neutropenia. CONCLUSION: EM is an effective new option in heavily pretreated MBC, with a favourable efficacy/safety ratio in a clinical practice setting. Our results comfort the use of this new molecule and pledge for the evaluation of EM-trastuzumab combination in this setting. Tumour biology, primary taxanes sensitivity and metastatic sites could represent useful predictive and prognostic factors

Risk Management and Adaptation for Extremes and Abrupt Changes in Climate and Oceans: Current Knowledge Gaps

Perspectives for risk management and adaptation have received ample attention in the recent IPCC Special Report on Changes in the Oceans and Cryosphere (SROCC). However, several knowledge gaps on the impacts of abrupt changes, cascading effects and compound extreme climatic events have been identified, and need further research. We focus on specific climate change risks identified in the SROCC report, namely: changes in tropical and extratropical cyclones; marine heatwaves; extreme ENSO events; and abrupt changes in the Atlantic Meridional Overturning Circulation. Several of the socioeconomic impacts from these events are not yet well-understood, and the literature is also sparse on specific recommendations for integrated risk management and adaptation options to reduce such risks. Also, past research has mostly focussed on concepts that have seen little application to real-world cases. We discuss relevant research needs and priorities for improved social-ecological impact assessment related to these major physical changes in the climate and oceans. For example, harmonised approaches are needed to better understand impacts from compound events, and cascading impacts across systems. Such information is essential to inform options for adaptation, governance and decision-making. Finally, we highlight research needs for developing transformative adaptation options and their governance

Brain metastases at the time of presentation of non-small cell lung cancer: a multi-centric AERIO analysis of prognostic factors

A multi-centre retrospective study involving 4 French university institutions has been conducted in order to identify routine pre-therapeutic prognostic factors of survival in patients with previously untreated non-small cell lung cancer and brain metastases at the time of presentation. A total of 231 patients were recorded regarding their clinical, radiological and biological characteristics at presentation. The accrual period was January 1991 to December 1998. Prognosis was analysed using both univariate and multivariate (Cox model) statistics. The median survival of the whole population was 28 weeks. Univariate analysis (log-rank), showed that patients affected by one of the following characteristics proved to have a shorter survival in comparison with the opposite status of each variable: male gender, age over 63 years, poor performance status, neurological symptoms, serum neuron-specific enolase (NSE) level higher than 12.5 ng ml−1, high serum alkaline phosphatase level, high serum LDH level and serum sodium level below 132 mmol l−1. In the Cox's model, the following variables were independent determinants of a poor outcome: male gender: hazard ratio (95% confidence interval): 2.29 (1.26–4.16), poor performance status: 1.73 (1.15–2.62), age: 1.02 (1.003–1.043), a high serum NSE level: 1.72 (1.11–2.68), neurological symptoms: 1.63 (1.05–2.54), and a low serum sodium level: 2.99 (1.17–7.62). Apart from 4 prognostic factors shared in common with other stage IV NSCLC patients, whatever the metastatic site (namely sex, age, gender, performance status and serum sodium level) this study discloses 2 determinants specifically resulting from brain metastasis: i.e. the presence of neurological symptoms and a high serum NSE level. The latter factor could be in relationship with the extent of normal brain tissue damage caused by the tumour as has been demonstrated after strokes. Additionally, the observation of a high NSE level as a prognostic determinant in NSCLC might reflect tumour heterogeneity and understimated neuroendocrine differentiation. © 2001 Cancer Research Campaignhttp://www.bjcancer.co

Severe skin reaction secondary to concomitant radiotherapy plus cetuximab

The therapeutic use of monoclonal antibodies against the epidermal growth factor receptor (EGFR) is specifically associated with dermatologic reactions of variable severity. Recent evidence suggests superiority of the EGFR inhibitor (EGFRI) cetuximab plus radiotherapy compared to radiotherapy alone in patients with squamous cell carcinoma of the head and neck. Although not documented in a study population, several reports indicate a possible overlap between radiation dermatitis and the EGFRI-induced skin rash. We here present a case of severe skin reaction secondary to the addition of cetuximab to radiotherapy