2nd ESMO Consensus Conference on Lung Cancer: non-small-cell lung cancer first-line/second and further lines of treatment in advanced disease.

To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines of treatment in advanced disease, early-stage disease and locally advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on first line/second and further lines of treatment in advanced disease.

Evidence of systematic and proportional error in a widely used glucose oxidase analyser: Impact for clinical research?

Real time glycemia is a cornerstone for metabolic research, particularly when performing oral glucose tolerance tests (OGTT) or glucose clamps. From 1965 to 2009, the gold standard device for real time plasma glucose assessment was the Beckman glucose analyzer 2 (Beckman Instruments, Fullerton, CA), which technology couples glucose oxidase enzymatic assay with oxygen sensors. Since its discontinuation in 2009, today's researchers are left with few choices that utilize glucose oxidase technology. The first one is the YSI 2300 (Yellow Springs Instruments Corp., Yellow Springs, OH), known to be as accurate as the Beckman(1). The YSI has been used extensively for clinical research studies and is used to validate other glucose monitoring devices(2). The major drawback of the YSI is that it is relatively slow and requires high maintenance. The Analox GM9 (Analox instruments, London), more recent and faster, is increasingly used in clinical research(3) as well as in basic sciences(4) (e.g. 23 papers in Diabetes or 21 in Diabetologia). This article is protected by copyright. All rights reserved.

Successful migration of three tracers without identification of sentinel nodes during intraoperative lymphatic mapping for non-small cell lung cancer.

Prospective comparative evaluation of patent V blue, fluorescein and (99m)TC-nanocolloids for intraoperative sentinel lymph node (SLN) mapping during surgery for non-small cell lung cancer (NSCLC). Ten patients with peripherally localised clinical stage I NSCLC underwent thoracotomy and peritumoral subpleural injection of 2 ml of patent V blue dye, 1 ml of 10% fluorescein and 1ml of (99m)Tc-nanocolloids (0.4 mCi). The migration and spatial distribution pattern of the tracers was assessed by direct visualisation (patent V blue), visualisation of fluorescence signalling by a lamp of Wood (fluorescein) and radioactivity counting with a hand held gamma-probe ((99m)Tc-nanocolloids). Lymph nodes at interlobar (ATS 11), hilar (ATS 10) and mediastinal (right ATS 2,4,7; left ATS 5,6,7) levels were systematically assessed every 10 min up to 60 min after injection, followed by lobectomy and formal lymph node dissection. Successful migration from the peritumoral area to the mediastinum was observed for all three tracers up to 60 min after injection. The interlobar lympho-fatty tissue (station ATS 11) revealed an early and preferential accumulation of all three tracers for all tumours assessed and irrespective of the tumour localisation. However, no preferential accumulation in one or two distinct lymph nodes was observed up to 60 min after injection for all three tracers assessed. Intraoperative SLN mapping revealed successful migration of the tracers from the site of peritumoral injection to the mediastinum, but in a diffuse pattern without preferential accumulation in sentinel lymph nodes.

Determinants of science-based cooperation: evidence in a sample of small and micro firms

We study the determining factors of cience-based cooperation in the case of small and micro firms. In this research, we propose an analytical framework based on the resource-based view of the firm and we identify a set of organisational characteristics, which we classify as internal, external and structural factors. Each factor can be linked to at least one reason, from the firm¿s point of view, to cooperate with universities and public research centres. Each reason can, in turn, be used as an indicator of a firm¿s organisational needs or organisational capacities. In order to validate the theoretical model, we estimate a logistic regression that models the propensity to participate in science-based cooperation activities within a sample of 285 small and micro firms located in Barcelona. The results show the key role played by the absorptive capacity of new and small companies.

Individual-based modelling and simulation: towards a better understanding of growth dynamics from small inocula

Postprint (published version)

Treatment of brain metastases from non-small cell lung cancer with whole-brain radiotherapy (wbrt) in combination with gefitinib (gft) or temozolomide (tmz): a randomized multicenter phase ii trial of the swiss group of clinical cancer research (sakk #70/03)

BACKGROUND: Patients with BM rarely survive .6 months and are commonly excluded from clinical trials. We aimed at improving outcome by exploring 2 combined modality regimens with at the time novel agents for which single-agent activity had been shown. METHODS: NSCLC patients with multiple BM were randomized to WBRT (10 × 3 Gy) and either GFT 250 mg p.o. daily or TMZ 75 mg/m2 p.o. daily ×21/28 days, starting on Day 1 of RT and to be continued until PD. Primary endpoint was overall survival, a Simon's optimal 2-stage design was based on assumptions for the 3-month survival rate. Cognitive functioning and quality of life were also evaluated. RESULTS: Fifty-nine patients (36 M, 23 F; 9 after prior chemo) were included. Median age was 61 years (range 46-82), WHO PS was 0 in 18 patients, 1 in 31 patients, and 2 in 10 patients. All but 1 patients had extracranial disease; 33 of 43 (TMZ) and 15 of 16 (GFT) had adenocarcinoma histology. GFT arm was closed early after stage 1 analysis when the prespecified 3-mo survival rate threshold (66%) was not reached, causes of death were not GFT related. Main causes of death were PD in the CNS 24%, systemic 41%, both 8%, and toxicity 10% [intestinal perforation (2 patients), pneumonia (2), pulmonary emboli (1), pneumonitis NOS (1), seizure (1)]. We summarize here other patients' characteristics for the 2 trial arms: TMZ (n ¼ 43)/GFT (n ¼ 16); median treatment duration: 1.6 /1.8 mo; Grade 3-4 toxicity: lymphopenia 5 patients (12%)/0; fatigue 8 patients (19%)/2 patients (13%). Survival data for TMZ/GFT arms: 3-month survival rate: 58.1% (95% CI 42.1-73)/62.5% (95% CI 35- 85); median OS: 4.9 months (95% CI 2.5-5.6)/6.3 months (95% CI 2.2- 14.6); median PFS: 1.8 months (95% CI 1.5-1.8)/1.8 (95% CI 1.1-3.9); median time to neurol. progr.: 8.0 months (95% CI 2.2-X)/4.8 (95% CI 3.9-10.5). In a model to predict survival time including the variables' age, PS, number of BM, global QL, total MMSE score, and subjective cognitive function, none of the variables accounted for a significant improvement in survival time. CONCLUSIONS: The combinations of WBRT with GFT or TMZ were feasible. However, in this unselected patient population, survival remains poor and a high rate of complication was observed. Four patients died as a result of high-dose corticosteroids. Preliminary evaluation of cognitive function andQL failed to show significant improvement. Indications and patient selection for palliative treatment should be revisited and careful monitoring and supportive care is required. Research and progress for this frequent clinical situation is urgently needed. Trial partly supported by AstraZeneca (Switzerland), Essex Chemie (Switzerland) and Swiss Federal Government.

Power supply noise and logic error probability

Voltage fluctuations caused by parasitic impedances in the power supply rails of modern ICs are a major concern in nowadays ICs. The voltage fluctuations are spread out to the diverse nodes of the internal sections causing two effects: a degradation of performances mainly impacting gate delays anda noisy contamination of the quiescent levels of the logic that drives the node. Both effects are presented together, in thispaper, showing than both are a cause of errors in modern and future digital circuits. The paper groups both error mechanismsand shows how the global error rate is related with the voltage deviation and the period of the clock of the digital system.

Error probability in synchronous digital circuits due to power supply noise

This paper presents a probabilistic approach to model the problem of power supply voltage fluctuations. Error probability calculations are shown for some 90-nm technology digital circuits.The analysis here considered gives the timing violation error probability as a new design quality factor in front of conventional techniques that assume the full perfection of the circuit. The evaluation of the error bound can be useful for new design paradigms where retry and self-recoveringtechniques are being applied to the design of high performance processors. The method here described allows to evaluate the performance of these techniques by means of calculating the expected error probability in terms of power supply distribution quality.

Motion estimation using higher-order statistics

The objective of this paper is to introduce a fourth-order cost function of the displaced frame difference (DFD) capable of estimatingmotion even for small regions or blocks. Using higher than second-orderstatistics is appropriate in case the image sequence is severely corruptedby additive Gaussian noise. Some results are presented and compared to those obtained from the mean kurtosis and the mean square error of the DFD.

Erään hienopaperikoneen paksuusprofiilin hallinta

Työn kirjallisuusosassa perehdytään paperikoneen online-mittarien toimintaan, poikkisuuntaisten profiilien säätämiseen ja kalanterointiin. Työn tavoitteena oli löytää syyt erään hienopaperikoneen heikkoon paksuusprofiiliin ja siitä aiheutuvaan suureen rullahylkymäärään. Syitä heikkoon paksuusprofiiliin on haettu kalanterin, päällystysasemien ja laatusäätöjärjestelmän toiminnoista. Työssä on tutkittu myös karheusprofiilin vaikutusta paksuusmittaukseen. Työssä löydettiin selvä yhteys paperin karheusprofiilin ja paperikoneen paksuusmittarin mittaaman paksuusprofiilin välille. Radan reuna-alueiden karheus suurentaa online-paksuusmittarin mittaustulosta. Karheusprofiili ei kuitenkaan vaikuta laboratoriomittareilla mitattuun paksuusprofiiliin. Paperikoneen onlinepaksuusmittarin mittausvirhe on kompensoitava, jotta paperin todellinen paksuusprofiili saadaan suoraksi. Työssä tehtyjen tutkimusten perusteella muodostettiin ajomalli, jolla ajettiin koeajojakso. Ajomallin päällimmäinen tarkoitus oli kompensoida paperikoneen online- paksuusmittarin mittausvirhe. Koeajo onnistui hyvin. Koeajojakson profiilivioista johtuva rullahylyn määräoli merkittävästi pienempi kuin referenssijakson profiilivioista johtuva rullahylyn määrä.

Metabolism of oral glucose in children born small for gestational age : evidence for an impaired whole body glucose oxidation

Résumé Les études épidémiologiques indiquent que la restriction intra-utérine confère un risque accru de développement de diabète de type 2 au cours de la vie. Certaines études ont documenté la présence d'une résistance à l'insuline chez les jeunes adultes ou les adolescents nés petits pour l'âge gestationnel. Comme la plupart des études ont impliqués des individus post-pubères et comme la puberté influence de manière marquée le métabolisme énergétique, nous avons évalué le devenir du glucose administré oralement dans un groupe incluant essentiellement des enfants pré-pubères ou en début de puberté avec restriction intra-utérine, et chez des enfants matchés pour l'âge et pour le poids. Tous les enfants ont eu une évaluation de leur composition corporelle par mesure des plis cutanés. Ils ont ensuite été étudiés dans des conditions standardisées et ont reçu 4 charges consécutives orales de glucose à raison de 180 mg/kg de poids corporel jusqu'à atteindre un état d'équilibre relatif. La dépense énergétique et l'oxydation des substrats ont été évaluées durant la quatrième heure par calorimétrie indirecte. Comparativement avec les enfants matchés pour l'âge et le poids, les enfants nés petits pour l'âge gestationnel avaient une plus petite stature. Leur dépense énergétique n'était pas significativement abaissée, mais leur oxydation du glucose était plus basse. Ces résultats indiquent que des altérations métaboliques sont présentes précocement chez les enfants nés petits pour l'âge gestationnel, et qu'elles sont possiblement reliées à des altérations de la composition corporelle. Abstract: Epidemiological studies indicate that intrauterine growth restriction confers an increased risk of developing type 2 diabetes mellitus in subsequent life. Several studies have further documented the presence of insulin resistance in young adults or adolescent children born small for gestational age. Since most studies addressed postpubertal individuals, and since puberty markedly affects energy metabolism, we evaluated the disposal of oral glucose in a group including mainly prepubertal and early pubertal children with intrauterine growth restriction and in healthy age- and weight-matched control children. All children had an evaluation of their body composition by skinfold thickness measurements. They were then studied in standardized conditions and received 4 consecutive hourly loads of 180 mg glucose/kg body weight to reach a near steady state. Energy expenditure and substrate oxidation were evaluated during the fourth hour by indirect calorimetry. Compared to both age- and weight-matched children, children born small for gestational age had lower stature. Their energy expenditure was not significantly decreased, but they had lower glucose oxidation rates. These results indicate that metabolic alterations are present early in children born small for gestational age, and are possibly related to alterations of body composition.

Optimisation of data analysis method for a fluidized bed combustion test rig

Nowadays the used fuel variety in power boilers is widening and new boiler constructions and running models have to be developed. This research and development is done in small pilot plants where more faster analyse about the boiler mass and heat balance is needed to be able to find and do the right decisions already during the test run. The barrier on determining boiler balance during test runs is the long process of chemical analyses of collected input and outputmatter samples. The present work is concentrating on finding a way to determinethe boiler balance without chemical analyses and optimise the test rig to get the best possible accuracy for heat and mass balance of the boiler. The purpose of this work was to create an automatic boiler balance calculation method for 4 MW CFB/BFB pilot boiler of Kvaerner Pulping Oy located in Messukylä in Tampere. The calculation was created in the data management computer of pilot plants automation system. The calculation is made in Microsoft Excel environment, which gives a good base and functions for handling large databases and calculations without any delicate programming. The automation system in pilot plant was reconstructed und updated by Metso Automation Oy during year 2001 and the new system MetsoDNA has good data management properties, which is necessary for big calculations as boiler balance calculation. Two possible methods for calculating boiler balance during test run were found. Either the fuel flow is determined, which is usedto calculate the boiler's mass balance, or the unburned carbon loss is estimated and the mass balance of the boiler is calculated on the basis of boiler's heat balance. Both of the methods have their own weaknesses, so they were constructed parallel in the calculation and the decision of the used method was left to user. User also needs to define the used fuels and some solid mass flowsthat aren't measured automatically by the automation system. With sensitivity analysis was found that the most essential values for accurate boiler balance determination are flue gas oxygen content, the boiler's measured heat output and lower heating value of the fuel. The theoretical part of this work concentrates in the error management of these measurements and analyses and on measurement accuracy and boiler balance calculation in theory. The empirical part of this work concentrates on the creation of the balance calculation for the boiler in issue and on describing the work environment.