Dacomitinib versus erlotinib in patients with EGFR-mutated advanced nonsmall-cell lung cancer (NSCLC): Pooled subset analyses from two randomized trials

Background: The irreversible epidermal growth factor receptor (EGFR) inhibitors have demonstrated efficacy in NSCLC patients with activating EGFR mutations, but it is unknown if they are superior to the reversible inhibitors. Dacomitinib is an oral, small-molecule irreversible inhibitor of all enzymatically active HER family tyrosine kinases. Methods: The ARCHER 1009 (NCT01360554) and A7471028 (NCT00769067) studies randomized patients with locally advanced/metastatic NSCLC following progression with one or two prior chemotherapy regimens to dacomitinib or erlotinib. EGFR mutation testing was performed centrally on archived tumor samples. We pooled patients with exon 19 deletion and L858R EGFR mutations from both studies to compare the efficacy of dacomitinib to erlotinib. Results: One hundred twenty-one patients with any EGFR mutation were enrolled; 101 had activating mutations in exon 19 or 21. For patients with exon19/21 mutations, the median progression-free survival was 14.6 months [95% confidence interval (CI) 9.0–18.2] with dacomitinib and 9.6 months (95% CI 7.4–12.7) with erlotinib [unstratified hazard ratio (HR) 0.717 (95% CI 0.458–1.124), two-sided log-rank, P = 0.146]. The median survival was 26.6 months (95% CI 21.6–41.5) with dacomitinib versus 23.2 months (95% CI 16.0–31.8) with erlotinib [unstratified HR 0.737 (95% CI 0.431–1.259), two-sided log-rank, P = 0.265]. Dacomitinib was associated with a higher incidence of diarrhea and mucositis in both studies compared with erlotinib. Conclusions: Dacomitinib is an active agent with comparable efficacy to erlotinib in the EGFR mutated patients. The subgroup with exon 19 deletion had favorable outcomes with dacomitinib. An ongoing phase III study will compare dacomitinib to gefitinib in first-line therapy of patients with NSCLC harboring common activating EGFR mutations (ARCHER 1050; NCT01774721). Clinical trials number: ARCHER 1009 (NCT01360554) and A7471028 (NCT00769067).

The determinants of fair value measurements of banks: International evidence

The purpose of this study is to investigate the accounting choice decisions of banks to employ Level 3 inputs in estimating the value of their financial assets and liabilities. Using a sample of 146 bank-year observations from 18 countries over 2009-2012, this study finds banks’ incentives to use Level 3 valuation inputs are associated with both firm-level and country-level determinants. At the firm-level, leverage, profitability (in term of net income), Tier 1 capital ratio, size and audit committee independence are associated with the percentage of Level 3 valuation inputs. At the country-level, economy development, legal region, legal enforcement and investor rights are also associated with the Level 3 classification choice. Lastly, ‘secrecy’, the proxy for culture dimensions and values, is found to be positively associated with the use of Level 3 valuation inputs. Altogether, these findings suggest that banks use the discretion available under Level 3 inputs opportunistically to avoid violating debt covenants limits, to increase earnings and manage their capital ratios. Results of this study also highlight that corporate governance quality at the firm-level (e.g. audit committee independence) and institutional features can constrain banks’ opportunistic behaviors in using the discretion available under Level 3 inputs. The results of this study have important implications for standard setters and contribute to the debate on the use of fair value accounting in an international context.

The determinants of fair value measurements of banks: International evidence

The purpose of this study is to investigate the accounting choice decisions of banks to employ Level 3 inputs in estimating the value of their financial assets and liabilities. Using a sample of 146 bank-year observations from 18 countries over 2009-2012, this study finds banks’ incentives to use Level 3 valuation inputs are associated with both firm-level and country-level determinants. At the firm-level, leverage, profitability (in term of net income), Tier 1 capital ratio, size and audit committee independence are associated with the percentage of Level 3 valuation inputs. At the country-level, economy development, legal region, legal enforcement and investor rights are also associated with the Level 3 classification choice. Lastly, ‘secrecy’, the proxy for culture dimensions and values, is found to be positively associated with the use of Level 3 valuation inputs. Altogether, these findings suggest that banks use the discretion available under Level 3 inputs opportunistically to avoid violating debt covenants limits, to increase earnings and manage their capital ratios. Results of this study also highlight that corporate governance quality at the firm-level (e.g. audit committee independence) and institutional features can constrain banks’ opportunistic behaviors in using the discretion available under Level 3 inputs. The results of this study have important implications for standard setters and contribute to the debate on the use of fair value accounting in an international context.

Two ex situ fungal technologies to treat contaminated soil

Wood-degrading fungi are able to degrade a large range of recalcitrant pollutants which resemble the lignin biopolymer. This ability is attributed to the production of lignin-modifying enzymes, which are extracellular and non-specific. Despite the potential of fungi in bioremediation, there is still an understanding gap in terms of the technology. In this thesis, the feasibility of two ex situ fungal bioremediation methods to treat contaminated soil was evaluated. Treatment of polycyclic aromatic hydrocarbons (PAHs)-contaminated marsh soil was studied in a stirred slurry-phase reactor. Due to the salt content in marsh soil, fungi were screened for their halotolerance, and the white-rot fungi Lentinus tigrinus, Irpex lacteus and Bjerkandera adusta were selected for further studies. These fungi degraded 40 - 60% of a PAH mixture (phenanthrene, fluoranthene, pyrene and chrysene) in a slurry-phase reactor (100 ml) during 30 days of incubation. Thereafter, B. adusta was selected to scale-up and optimize the process in a 5 L reactor. Maximum degradation of dibenzothiophene (93%), fluoranthene (82%), pyrene (81%) and chrysene (83%) was achieved with the free mycelium inoculum of the highest initial biomass (2.2 g/l). In autoclaved soil, MnP was the most important enzyme involved in PAH degradation. In non-sterile soil, endogenous soil microbes together with B. adusta also degraded the PAHs extensively, suggesting a synergic action between soil microbes and the fungus. A fungal solid-phase cultivation method to pretreat contaminated sawmill soil with high organic matter content was developed to enhance the effectiveness of the subsequent soil combustion. In a preliminary screening of 146 fungal strains, 28 out of 52 fungi, which extensively colonized non-sterile contaminated soil, were litter-decomposing fungi. The 18 strains further selected were characterized by their production of lignin-modifying and hydrolytic enzymes, of which MnP and endo-1,4-β-glucanase were the main enzymes during cultivation on Scots pine (Pinus sylvestris) bark. Of the six fungi selected for further tests, Gymnopilus luteofolius, Phanerochaete velutina, and Stropharia rugosoannulata were the most active soil organic matter degraders. The results showed that a six-month pretreatment of sawmill soil would result in a 3.5 - 9.5% loss of organic matter, depending on the fungus applied. The pretreatment process was scaled-up for a 0.56 m3 reactor, in which perforated plastic tubes filled with S. rugosoannulata growing on pine bark were introduced into the soil. The fungal pretreatment resulted in a soil mass loss of 30.5 kg, which represents 10% of the original soil mass (308 kg). Despite the fact that Scots pine bark contains several antimicrobial compounds, it was a suitable substrate for fungal growth and promoter of the production of oxidative enzymes, as well as an excellent and cheap natural carrier of fungal mycelium. This thesis successfully developed two novel fungal ex situ bioremediation technologies and introduce new insights for their further full-scale application. Ex situ slurry-phase fungal reactors might be applied in cases when the soil has a high water content or when the contaminant bioavailability is low; for example, in wastewater treatment plants to remove pharmaceutical residues. Fungal solid-phase bioremediation is a promising remediation technology to ex situ or in situ treat contaminated soil.

Non-Linear vibration of an elastic string

Equations proposed in previous work on the non-linear motion of a string show a basic disagreement, which is here traced to an assumption about the longitudinal displacement u. It is shown that it is neither necessary nor justifiable to assume that u is zero; and also that the velocity of propagation of u disturbances in a string is different from that in an infinite medium, although this difference is usually negligible. After formulating the exact equations of motion for the string, a systematic procedure is described for obtaining approximations to these equations to any order, making only the assumption that the strain in the material of the string is small. The lowest order equations in this scheme are non-linear, and are used to describe the response of a string near resonance. Finally, it is shown that in the absence of damping, planar motion of a string is always unstable at sufficiently high amplitudes, the critical amplitude falling to zero at the natural frequency and its subharmonics. The effect of slight damping on this instability is also discussed.

Oxidation of acetaldehyde to acetic acid in a sparger reactor

The kinetics of oxidation of acetaldehyde to acetic acid was studied in a sparger reactor using manganese acetate as the catalyst. Data obtained in a stirred tank reactor are used for analyzing the sparger reactor data. The rate of chemical reaction is extremely fast and can be neglected for the rate equation of the sparger reactor. A kinetic model applicable at any temperature and concentration within the range of the variables studied is developed which predicts the performance of the sparger reactor satisfactorily.

Raman spectrum of crystalline aminosulphonic acid

The Raman spectrum of a single crystal of sulphamic acid has been recorded withλ 2537 excitation. Thirty-eight lines have been observed, of which twenty-nine have been recorded for the first time. Seven Raman lines with shifts in the region 50–155 cm.−1 have been assigned to the lattice oscillations, two at 177 and 240 cm.−1 have been attributed to the low-frequency hydrogen bond vibrations.. The splitting of the degenerate modes and the appearance of N-H....O bonded stretching vibrations are consistent with the structural data which expect the presence of the free molecule as a Zwitter ion with only slight distortion from C3v symmetry.

Raman spectra of ferro-electric crystals Part IV. Lithium hydrazinium sulphate (LiN2H5SO4)

The Raman spectrum of lithium hydrazinium sulphate has been recorded both in the single crystal form and in aqueous solutions. The crystal exhibits thirty-eight Raman lines having the frequency shifts 52, 70, 104, 146, 174, 220, 260, 302, 350, 454, 470, 610, 630, 715, 977, 1094, 1115, 1132, 1177, 1191, 1260, 1444, 1493, 1577, 1630, 1670, 2205, 2484, 2553, 2655, 2734, 2848, 2894, 2939, 3028, 3132, 3290 and 3330 cm.−1 The aqueous solution gave rise to six Raman lines at 452, 980, 1050–1200, 1260, 1425 and 1570 cm.−1 apart from a maximum at 180 cm.−1 in the ‘wing’ accompanying the Rayleigh line. The observed Raman lines have been assigned as arising from the vibrations of the SO4 ion, N2H5+ ion, Li-O4 group, hydrogen bond and the lattice. The influence of the hydrogen bond on the N-H stretching vibrations has been pointed out. The various features of the observed spectrum strongly support the hypothesis that the NH3 group in the crystal is rotating around the N-N axis at room temperature.

Kde je jádro pudla? Missä on villakoiran ydin? : Eläinten nimistä johdetut fraasit, idiomit ja muut sanonnat tšekin ja suomen kielessä

Pro gradu -työssä tarkastelen tšekin ja suomen kielessä esiintyviä eläinten nimityksistä johdettuja fraseologisia ilmauksia ja sanontoja. Eläinfraseologia muodostaa kielessä keskeisen osan, jolle ovat tyypillisiä voimakas tunnelataus, rajoittunut, sovinnainen käyttö ja puhekielenomaisuus. Tarkastelen eläinilmauksia morfologisesti ja semanttis-leksikaalisesti, mutta muitakin piirteitä esiintyy. Vertailen kumpaakin kieltä ja selvitän kielten fraasien, idiomien ja muiden sanontojen yhtäläisyyksiä ja eroja. Sanonnat (ynnä johdokset ja sanaparit) jaan neljään eri ryhmään seuraavasti: 1. kummassakin kielessä olevat samanlaiset ilmaukset, 2. kummassakin kielessä olevat osittain samanlaiset ilmaukset, 3. tsekkiläiset ilmaukset ja 4. suomalaiset ilmaukset. Työni materiaali on peräisin tsekkiläisistä, suomalaisista ja muunkielisistä sanakirjoista (lähinnä fraseologisista). Selvittelen erityisesti keskeisimpien kotieläinten nimistä (koira, kissa, hevonen, lehmä, lammas, sika, kana), joidenkin muiden eläinten nimistä (karhu, susi, karppi, käärme) ja joidenkin ulkomaisten eläinten nimistä (leijona, elefantti, apina) johdettuja fraseologisia ilmauksia. Materiaali käsittää yhteensä 145 eri eläintä, 163 eläimen nimitystä ja 585 eläinilmausta. Aineistoni pohjalta voi todeta, että tšekin ja suomen kielessä on yllättävän paljon samantyyppisiä eläinilmauksia, vaikka kielet poikkeavat huomattavasti toisistaan. Korpuksessani olevista ilmauksista on täysin symmetrisiä 119/20,3 %, osittain samanlaisia (epäsymmetrisiä) 127/21,7 %, pelkästään tsekkiläisiä 161/27,5 % ja pelkästään suomalaisia 146/25,0 %. Sanaparit ja sananlaskut, joita käsittelin erillisenä ryhmänä (32 kpl) muodostivat aineistosta 5,5 % (niistäkin löytyi yhtäläisyyksiä). Yleisimmin esiintyvät eläimet ovat koira ja kissa. Koira on kuitenkin tšekin fraseologiassa yleisempi eläin kuin suomessa, jossa taas kissa on yleisimmin esiintyvä eläimen nimi. Yleisiä ovat myös mm. hevonen, sika, lintu, kala ja kana. Karitsa, hanhi ja vuohi esiintyvät paljon useammin tšekin fraseologiassa, suomessa esiintyy taas usein sika silloin, kun tšekissä on porsas. Joillakin eläinten nimillä on selvästi negatiivisempi tunnelataus (susi, käärme) kuin toisilla (koira, kissa). Toisin kuin suomessa, kissa on tšekissä valheellinen, vuohi herkuttelee, pöllö ja apina edustavat viisautta ja oppivaisuutta ja kovakuoriainen hellyttää. Yhteisiä eläinten nimityksiä kummassakin kielessä on aineistossani 106/163 (65,03 %). Tšekin fraseologiassa on lähes kaksi kertaa enemmän (37/163 = 22,7 %) sellaisia eläinten nimiä, joita ei esiinny suomen fraseologiassa verrattuna pelkästään suomen fraseologiassa esiintyviin eläinten nimiin (20/163 = 12,27 %). Pelkästään tšekissä esiintyviä eläimiä ovat mm. lumikko, majava, murmeli, mäyrä, näätä ja riikinkukko; pelkästään suomen fraseologiassa esiintyvät puolestaan mm. kiiski, muikku, peippo, poro, sopuli ja telkkä. Vertauskuvat ovat kummassakin kielessä erittäin tyypillisiä. Eläinten nimet viittaavat useimmiten ihmisen kielteisiin luonteenpiirteisiin tai ominaisuuksiin (mazaný jako liška ja viekas kuin kettu). Aineistoni pohjalta vaikuttaa siltä, että tšekissä on enemmän vaihtoehtoisia ja eri eläinten lajeista muodostettuja ilmauksia (mm. lintu- ja kalalajeista). Kummassakin kielessä on myös huudahduslauseita (Ty jsi ale liška pod itá! ja Senkin vanha kettu!), kansainvälisiä ilmauksia (jádro pudla ja villakoiran ydin) ja ns. petollisia ystäviä toisiaan erehdyttävästi muistuttavia, mutta eri asiaa merkitseviä sanontoja (tsekin kočičí život kissanelämä tarkoittaa ´sitkeähenkisyyttä´ − ei suomen kissanpäiviä). Kansallisista erityispiirteistä ovat esimerkkeinä mm. tšekin ilmaus mít se jako husa o Martině "voida kuin hanhi Martinpäivänä" (suomeksi ´voida kurjasti´; viittaus Martinpäivän hanhensyömisperinteeseen) tai suomen ilmaukset kuin hyttysen liraus Itämereen ja sopulilauma.

Convergence correction in colloid scattering

The error introduced in depolarisation measurements due to the convergence of the incident beam has been investigated theoretically as well as experimentally for the case of colloid scattering, where the particles are not small compared to the wavelength of light. Assuming the scattering particles to be anisotropic rods, it is shown that, when the incident unpolarised light is condensed by means of a lens with a circular aperture, the observed depolarisation ratio ϱ u is given by ϱ u = ϱ u0 + 5/3 θ2 where ϱ u0 is the true depolarisation for incident parallel light, and θ the semi-angle of convergence. Appropriate formulae are derived when the incident beam is polarised vertically and horizontally. Experiments performed on six typical colloids support the theoretical conclusions. Other immediate consequences of the theory are also discussed.

Micellar size and shape in solutions of calcium stearate in cetane from optical depolarization data

Observations at a series of temperatures of the changes in viscosities and depolarization factors of 1% and 18% solutions of calcium stearate in cetane to which varying amounts of water have been added can be interpreted in terms of the existence of anisometric micelles. In general, changes in the size of the micelles inferred from values of ρh agree with those deduced from the viscosity data. The correlation between anisometry of micelles from rheological and optical observations is much poorer in the case of ρν, presumably because of the difficulty in differentiating the contribution of anisometry and anisotropy to ρν.

Separation Of Beta-Apocarotenals And Related Compounds By Reversed-Phase Paper And Thin-Layer Chromatography

Tlie sclxuntion and clraractcrization of vitamins Al and An nnd related compoundsby reversed-pllasc paper cliromatogrnpl~y as well as ly thin-lqxr chromategraphy have hen rcportccl carlicrl * $. Thin-lnycr chromatography has also been used for the separatinn and charncterizatio11 of carotenoids from natural sourccs3~ ‘1. I-Iowcver, 130tr.rc,1~1~ofib scrvccl that carotenoid misturcs cannot be separated on a sin& aclsorhnt with ;1 sin& solvent. The scparntion and clctermi1wtion of carotenoid alclclydes from plants, microorganisms and animnl tissues have lxxn carriecl out by nicans of thin-layer clirf.~li~ato~apI~~U. Apocarotcnals awl apocarotcnoic acid have been detected in ornnges by the same technique’*

The Organisation of Policy Meets the Commercialisation of Sex - Global Linkages, Policies, Technologies

During recent years the commercialisation of sex has increased and intensified both locally and globally. This thesis explores the commercialisation of bodies, sex and sexualities, particularly the sex trade, and the impact of rapidly evolving information and communication technologies on this globalising trade. The main focus of this work is on the policies, discourses and policy developments in the area especially in the Finnish context. The study is based on multidisciplinary theoretical sources through which the framework of multiple linkages relevant to the commercialisation of sex is conceptualised. The sex trade functions through a web of intersecting linkages of a substantive, economic, organisational, temporal, spatial, cultural, technological, as well as of legislative and policy nature. This framework of linkages forms the basis for the analysis of the main empirical data, namely qualitative interviews with thirty key managers and professionals, who are responsible for the preparation and implementation of policies on commercial sex. In addition, the thesis addresses the policies and policy practices on the sex trade through the analysis of national and international policy instruments. In addition to analysing the processes of the commercialisation of sex and its effects, the study also discusses their further implications for organisational policy-making, research, and society more generally. The thesis thus seeks to contribute to practice, research and theory on gender, management and organisations.

Pricing Index Options with Stochastic Volatility

The objective of this paper is to investigate the pricing accuracy under stochastic volatility where the volatility follows a square root process. The theoretical prices are compared with market price data (the German DAX index options market) by using two different techniques of parameter estimation, the method of moments and implicit estimation by inversion. Standard Black & Scholes pricing is used as a benchmark. The results indicate that the stochastic volatility model with parameters estimated by inversion using the available prices on the preceding day, is the most accurate pricing method of the three in this study and can be considered satisfactory. However, as the same model with parameters estimated using a rolling window (the method of moments) proved to be inferior to the benchmark, the importance of stable and correct estimation of the parameters is evident.