Randomised, multicentre, phase III, open-label study of alectinib vs crizotinib in treatment-naïve anaplastic lymphoma kinase (ALK)-positive advanced NSCLC (ALEX study).

Background: In ∼5% of advanced NSCLC tumours, ALK tyrosine kinase is constitutively activated after translocation of ALK. ALK+ NSCLC was shown to be highly sensitive to the first approved ALK inhibitor, crizotinib. However, all pts eventually relapse on crizotinib mainly due to secondary ALK mutations/amplification or CNS metastases. Alectinib is a highly selective, potent, oral next-generation ALK inhibitor. Clinical phase II alectinib data in 46 crizotinib-naïve pts with ALK+ NSCLC reported an objective response rate (ORR) of 93.5% and a 1-year progression-free rate of 83% (95% CI: 68-92) (Inoue et al. J Thorac Oncol 2013). CNS activity was seen: of 14 pts with baseline brain metastasis, 11 had prior CNS radiation, 9 of these experienced CNS and systemic PFS of >12 months; of the 3 pts without prior CNS radiation, 2 were >15 months progression free. Trial design: Randomised, multicentre, phase III, open-label study in pts with treatment-naïve ALK+ advanced, recurrent, or metastatic NSCLC. All pts must provide pretreatment tumour tissue to confirm ALK rearrangement (by IHC). Pts (∼286 from ∼180 centres, ∼30 countries worldwide) will be randomised to alectinib (600mg oral bid, with food) or crizotinib (250mg oral bid, with/without food) until disease progression (PD), unacceptable toxicity, withdrawal of consent, or death. Stratification factors are: ECOG PS (0/1 vs 2), race (Asian vs non-Asian), baseline CNS metastases (yes vs no). Primary endpoint: PFS by investigators (RECIST v1.1). Secondary endpoints: PFS by Independent Review Committee (IRC); ORR; duration of response; OS; safety; pharmacokinetics; quality of life. Additionally, time to CNS progression will be evaluated (MRI) for the first time in a prospective randomised NSCLC trial as a secondary endpoint. Pts with isolated asymptomatic CNS progression will be allowed to continue treatment beyond documented progression until systemic PD and/or symptomatic CNS progression, according to investigator opinion. Time to CNS progression will be retrospectively assessed by the IRC using two separate criteria, RECIST and RANO. Further details: ClinicalTrials.gov (NCT02075840). Disclosure: T.S.K. Mok: Advisory boards: AZ, Roche, Eli Lilly, Merck Serono, Eisai, BMS, AVEO, Pfizer, Taiho, Boehringer Ingelheim, Novartis, GSK Biologicals, Clovis Oncology, Amgen, Janssen, BioMarin; board of directors: IASLC; corporate sponsored research: AZ; M. Perol: Advisory boards: Roche; S.I. Ou: Consulting: Pfizer, Chugai, Genentech Speaker Bureau: Pfizer, Genentech, Boehringer Ingelheim; I. Bara: Employee: F. Hoffmann-La Roche Ltd; V. Henschel: Employee and stock: F. Hoffmann-La Roche Ltd.; D.R. Camidge: Honoraria: Roche/Genentech. All other authors have declared no conflicts of interest.

L'Ús del mètode verbotonal per a la correcció fonètica: estudi de cas d'un parlant de català com a L2 amb problemes de pronúncia de les laterals palatals

Aquest treball pretén ser l’estudi i la correcció fonètica d’un parlant de castellà com a primera llengua que té la llengua catalana coma segona llengua i presenta un problema a l’hora de pronunciar les laterals palatals. Per tant, és l’estudi d’un cas molt concret. Per a fer aquest estudi s’ha seguit el mètode verbotonal de correcció fonètica, ja que també es pretén comprovar la funcionalitat d’aquest mètode i els resultats possibles

The Problem of Invasive Species in River Ecosystems

Invasive nonnative species are a major problem in river ecosystems, and have large ecological and economic costs. Few ecosystems can resist invasions. The species that tend to invade most readily are those that humans. Introduce the most, and the ecosystems they invade are those with the most human activity. Most invasions are irreversible, and control is expensive, so efforts should be focused on prevention of future invasions

Brook Trout Removal as a Conservation Tool to Restore Eagle Lake Rainbow Trout

Nonnative brook trout Salvelinus fontinalis are abundant in Pine Creek and its main tributary, Bogard Spring Creek, California. These creeks historically provided the most spawning and rearing habitat for endemic Eagle Lake rainbow trout Oncorhynchus mykiss aquilarum. Three-pass electrofishing removal was conducted in 2007–2009 over the entire 2.8-km length of Bogard Spring Creek to determine whether brook trout removal was a feasible restoration tool and to document the life history characteristics of brook trout in a California meadow stream. After the first 2 years of removal, brook trout density and biomass were severely reduced from 15,803 to 1,192 fish/ha and from 277 to 31 kg/ha, respectively. Average removal efficiency was 92–97%, and most of the remaining fish were removed in the third year. The lack of a decrease in age-0 brook trout abundance between 2007 and 2008 after the removal of more than 4,000 adults in 2007 suggests compensatory reproduction of mature fish that survived and higher survival of age-0 fish. However, recruitment was greatly reduced after 2 years of removal and is likely to be even more depressed after the third year of removal assuming that immigration of fish from outside the creek continues to be minimal. Brook trout condition, growth, and fecundity indicated a stunted population at the start of the study, but all three features increased significantly every year, demonstrating compensatory effects. Although highly labor intensive, the use of electrofishing to eradicate brook trout may be feasible in Bogard Spring Creek and similar small streams if removal and monitoring are continued annually and if other control measures (e.g., construction of barriers) are implemented. Our evidence shows that if brook trout control measures continue and if only Eagle Lake rainbow trout are allowed access to the creek, then a self-sustaining population ofEagle Lake rainbow trout can become reestablished

Homogenization Dynamics and Introduction Routes of Invasive Freshwater Fish in the Iberian Peninsula

Nonnative invasive species are one of the main global threats to biodiversity. The understanding of the traits characterizing successful invaders and invasion-prone ecosystems is increasing, but our predictive ability is still limited. Quantitative information on biotic homogenization and particularly its temporal dynamics is even scarcer. We used freshwater fish distribution data in the Iberian Peninsula in four periods (before human intervention, 1991, 1995, and 2001) to assess the temporal dynamics of biotic homogenization among river basins. The percentage of introduced species among fish faunas has increased in recent times (from 41.8% in 1991 to 52.5% in 2001), leading to a clear increase in the similarity of community composition among basins. The mean Jaccard's index increase (a measure of biotic homogenization) from the pristine situation to the present (17.1%) was similar to that for Californian fish but higher than for other studies. However, biotic homogenization was found to be a temporally dynamic process, with finer temporal grain analyses detecting transient stages of biotic differentiation. Introduced species assemblages were spatially structured along a latitudinal gradient in the Iberian Peninsula, with species related to sport fishing being characteristic of northern basins. Although the comparison of fish distributions in the Iberian Peninsula and France showed significant and generalized biotic homogenization, nonnative assemblages of northeastern Iberian basins were more similar to those of France than to those of the rest of the Iberian Peninsula, indicating a main introduction route. Species introduced to the Iberian Peninsula tended to be mainly piscivores or widely introduced species that previously had been introduced to France. Our results indicate that the simultaneous analysis of the spatial distribution of introduced assemblages (excluding native species that reflect other biogeographical patterns) and their specific traits can be an effective tool to detect introduction and invasion routes and to predict future invaders from donor regions

First- and second-language phonological representations in the mental lexicon

Performance-based studies on the psychological nature of linguistic competence can conceal significant differences in the brain processes that underlie native versus nonnative knowledge of language. Here we report results from the brain activity of very proficient early bilinguals making a lexical decision task that illustrates this point. Two groups of SpanishCatalan early bilinguals (Spanish-dominant and Catalan-dominant) were asked to decide whether a given form was a Catalan word or not. The nonwords were based on real words, with one vowel changed. In the experimental stimuli, the vowel change involved a Catalan-specific contrast that previous research had shown to be difficult for Spanish natives to perceive. In the control stimuli, the vowel switch involved contrasts common to Spanish and Catalan. The results indicated that the groups of bilinguals did not differ in their behavioral and event-related brain potential measurements for the control stimuli; both groups made very few errors and showed a larger N400 component for control nonwords than for control words. However, significant differences were observed for the experimental stimuli across groups: Specifically, Spanish-dominant bilinguals showed great difficulty in rejecting experimental nonwords. Indeed, these participants not only showed very high error rates for these stimuli, but also did not show an error-related negativity effect in their erroneous nonword decisions. However, both groups of bilinguals showed a larger correctrelated negativity when making correct decisions about the experimental nonwords. The results suggest that although some aspects of a second language system may show a remarkable lack of plasticity (like the acquisition of some foreign contrasts), first-language representations seem to be more dynamic in their capacity of adapting and incorporating new information. &

Short story

Digitoitu 14. 1. 2009

Reconeixement de veu mitjançant xarxes neuronals

La interacció home-màquina per mitjà de la veu cobreix moltes àrees d’investigació. Es destaquen entre altres, el reconeixement de la parla, la síntesis i identificació de discurs, la verificació i identificació de locutor i l’activació per veu (ordres) de sistemes robòtics. Reconèixer la parla és natural i simple per a les persones, però és un treball complex per a les màquines, pel qual existeixen diverses metodologies i tècniques, entre elles les Xarxes Neuronals. L’objectiu d’aquest treball és desenvolupar una eina en Matlab per al reconeixement i identificació de paraules pronunciades per un locutor, entre un conjunt de paraules possibles, i amb una bona fiabilitat dins d’uns marges preestablerts. El sistema és independent del locutor que pronuncia la paraula, és a dir, aquest locutor no haurà intervingut en el procés d’entrenament del sistema. S’ha dissenyat una interfície que permet l’adquisició del senyal de veu i el seu processament mitjançant xarxes neuronals i altres tècniques. Adaptant una part de control al sistema, es podria utilitzar per donar ordres a un robot com l’Alfa6Uvic o qualsevol altre dispositiu.

Segmental Durations of Speech

This dissertation considers the segmental durations of speech from the viewpoint of speech technology, especially speech synthesis. The idea is that better models of segmental durations lead to higher naturalness and better intelligibility. These features are the key factors for better usability and generality of synthesized speech technology. Even though the studies are based on a Finnish corpus the approaches apply to all other languages as well. This is possibly due to the fact that most of the studies included in this dissertation are about universal effects taking place on utterance boundaries. Also the methods invented and used here are suitable for any other study of another language. This study is based on two corpora of news reading speech and sentences read aloud. The other corpus is read aloud by a 39-year-old male, whilst the other consists of several speakers in various situations. The use of two corpora is twofold: it involves a comparison of the corpora and a broader view on the matters of interest. The dissertation begins with an overview to the phonemes and the quantity system in the Finnish language. Especially, we are covering the intrinsic durations of phonemes and phoneme categories, as well as the difference of duration between short and long phonemes. The phoneme categories are presented to facilitate the problem of variability of speech segments. In this dissertation we cover the boundary-adjacent effects on segmental durations. In initial positions of utterances we find that there seems to be initial shortening in Finnish, but the result depends on the level of detail and on the individual phoneme. On the phoneme level we find that the shortening or lengthening only affects the very first ones at the beginning of an utterance. However, on average, the effect seems to shorten the whole first word on the word level. We establish the effect of final lengthening in Finnish. The effect in Finnish has been an open question for a long time, whilst Finnish has been the last missing piece for it to be a universal phenomenon. Final lengthening is studied from various angles and it is also shown that it is not a mere effect of prominence or an effect of speech corpus with high inter- and intra-speaker variation. The effect of final lengthening seems to extend from the final to the penultimate word. On a phoneme level it reaches a much wider area than the initial effect. We also present a normalization method suitable for corpus studies on segmental durations. The method uses an utterance-level normalization approach to capture the pattern of segmental durations within each utterance. This prevents the impact of various problematic variations within the corpora. The normalization is used in a study on final lengthening to show that the results on the effect are not caused by variation in the material. The dissertation shows an implementation and prowess of speech synthesis on a mobile platform. We find that the rule-based method of speech synthesis is a real-time software solution, but the signal generation process slows down the system beyond real time. Future aspects of speech synthesis on limited platforms are discussed. The dissertation considers ethical issues on the development of speech technology. The main focus is on the development of speech synthesis with high naturalness, but the problems and solutions are applicable to any other speech technology approaches.

The relativity of evaluative sentences: disagreeing over disagreement

Evaluative sentences (moral judgments, expressions of taste, epistemic modals) are relative to the speaker's standards. Lately, a phenomenon has challenged the traditional explanation of this relativity: whenever two speakers disagree over them they contradict each other without being at fault. Hence, it is thought that the correction of the assertions involved must be relative to an unprivileged standard not necessarily the speaker's. I will claim instead that so far, neither this nor any other proposal has provided an explanation of the phenomenon. I will point out several problems presented by them and I will hint to how this phenomenon could be explained by making minor adjustments to our semantic theory.

Nollapersoonalause suomessa ja virossa. Tutkimus kirjoitetun kielen aineistosta

The present study focuses on the zero person constructions both in Finnish and Estonian. In the zero person construction, there is no overt subject and the verb is in the 3rd person singular form: Fin. Tammikuussa voi hiihtää Etelä-Suomessakin. Est. Jaanuaris saab suusatada ka Lõuna-Soomes ‘In January one can ski even in South-Finland’. The meaning of the zero construction is usually considered generic and open. However, the zero may be interpreted as indexically open so that the reference can be construed from the context. This study demonstrates how the zero may be interpreted as referring to the speaker, the addressee, or anybody. The zero person construction in Finnish has been contrasted to the generic pronoun constructions in Indo-European languages. For example, the zero person is translated in English as you or one; in Swedish and German as man. The grammar and semantics of the Finnish zero person construction have been studied earlier to some extent. However, the differences and similarities between Finnish and Estonian, two closely related languages, have not been thoroughly studied before. The present doctoral thesis sheds light on the zero person construction, its use, functions, and interpretation both in Finnish and Estonian. The approach taken is contrastive. The data comes from magazine articles published in Finnish and translated into Estonian. The data consists of Finnish sentences with the zero person and their Estonian translations. In addition, the data includes literary fiction, and non-translated Estonian corpora texts as well. Estonian and Finnish are closely related and in principle the personal system of the two languages is almost identical, nevertheless, there are interesting differences. The present study shows that the zero person construction is not as common in Estonian as it is in Finnish. In my data, a typical sentence with the zero person in both languages is a generic statement which tells us what can or cannot be done. When making generic statements the two languages are relatively similar, especially when the zero person is used together with a modal verb. The modal verbs (eg. Fin. voida ‘can’, saada ‘may’, täytyä ‘must’; Est. võima ‘may’, saama ‘can’, tulema ’must’) are the most common verbs in both Finnish and Estonian zero person constructions. Significant differences appear when a non-modal verb is used. Overall, non-modal verbs are used less frequently in both languages. Verbs with relatively low agentivity or intentionality, such as perception verb nähdä in Finnish and nägema in Estonian, are used in the zero person clauses in both languages to certain extent. Verbs with more agentive and intentional properties are not used in the Estonian zero person clauses; in Finnish their use is restricted to specific context. The if–then-frame provides a suitable context for the zero person in Finnish, and the Finnish zero person may occur together with any kind of verb in conditional if-clause. Estonian if-clauses are not suitable contexts for zero person. There is usually a da-infinitive, a generic 2nd person singular or a passive form instead of the zero person in Estonian counterparts for Finnish if-clauses with zero person. The aim of this study was to analyze motivations for choosing the zero person in certain contexts. In Estonian, the use of the zero person constructions is more limited than in Finnish, and some of the constraints are grammatical. On the other hand, some of the constraints are motivated by the differences in actual language use. Contrasting the two languages reveals interesting differences and similarities between these two languages and shows how these languages may use similar means differently.

Is professional recognition in plastic surgery related to activity in research

OBJECTIVE: To evaluate the relation of medical research, with the participation of prominent plastic surgeon in Congress.METHODS: We reviewed the scientific programs of the last 3 Brazilian Congress of Surgery, were selected 21 Brazilian plástic surgeons invited to serve as panelists or speakers in roundtable sessions in the last 3 congresses (Group 1). We randomly selected and paired by other members (associates) of the Brazilian Society of Plastic Surgery, with no participation in congress as speaker (Group 2). We conducted a search for articles published in journals indexed in Medline, Lilacs and SciELO for all doctors selected during the entire academic career and the last 5 years from March 2007 until March 2012. We assessed the research activity through the simple counting of the number of publications in indexed journals for each professional. The number of publications groups was compared.RESULTS: articles produced throughout career: Group 1- 639 articles (average of 30.42 items each). Group 2- 79 articles (mean 3.95 articles each). Difference between medias: p <0.001.CONCLUSION: The results demonstrate that the Brazilian Society of Plastic Surgery seeking professionals with a greater number of publications and journals of higher impact. This approach encourages new members to pursue a higher qualification, and give security to congressmen, they can rely on the existence of a technical criterion in the choice of speakers.

Power Consumption Measurement and Scenario Based Energy Model in Wearable Computing Applications

The power is still today an issue in wearable computing applications. The aim of the present paper is to raise awareness of the power consumption of wearable computing devices in specific scenarios to be able in the future to design energy efficient wireless sensors for context recognition in wearable computing applications. The approach is based on a hardware study. The objective of this paper is to analyze and compare the total power consumption of three representative wearable computing devices in realistic scenarios such as Display, Speaker, Camera and microphone, Transfer by Wi-Fi, Monitoring outdoor physical activity and Pedometer. A scenario based energy model is also developed. The Samsung Galaxy Nexus I9250 smartphone, the Vuzix M100 Smart Glasses and the SimValley Smartwatch AW-420.RX are the three devices representative of their form factors. The power consumption is measured using PowerTutor, an android energy profiler application with logging option and using unknown parameters so it is adjusted with the USB meter. The result shows that the screen size is the main parameter influencing the power consumption. The power consumption for an identical scenario varies depending on the wearable devices meaning that others components, parameters or processes might impact on the power consumption and further study is needed to explain these variations. This paper also shows that different inputs (touchscreen is more efficient than buttons controls) and outputs (speaker sensor is more efficient than display sensor) impact the energy consumption in different way. This paper gives recommendations to reduce the energy consumption in healthcare wearable computing application using the energy model.

Discerning Cultural Depictions and Mistakes in Kafe Piter, a Russian Language Textbook for Finnish Students

This thesis presents the results of an analysis of the content in the series of Russian textbooks Kafe Piter, which is widely used in Finnish educational institutions for adult learners at the time that the research is conducted. The purpose of this study is to determine and describe how a textbook may purvey an image of a foreign country (in this case, Russia). Mixed-methods research with a focus on the qualitative content analysis of Kafe Piter is performed. The guidelines for textbook evaluation of cultural content proposed by Byram (1993) are used in this study as the basis for creating a qualitative analysis checklist, which is adopted according to the needs of the current research. The selection of the categories in the checklist is based on major themes where direct statements about Russia, Russian people and culture appear in the textbook. The cultural content and the way in which it is presented in Kafe Piter are also compared to the intercultural competence objectives of the Common European Framework of Reference for Languages. Because the textbook was not written by a native Russian speaker, it was also important to investigate the types of mistakes found in the books. A simple quantitative analysis in the form of descriptive statistics was done, which consisted of counting the mistakes and inaccuracies in Kafe Piter. The mistakes were categorized into several different groups: factual or cultural, lexicosemantic, grammatical, spelling and punctuation mistakes. Based on the results, the cultural content of Kafe Piter provides a rich variety of cultural information that allows for a good understanding of the Russian language and Russian culture. A sufficient number of cross-cultural elements also appear in the textbook, including cultural images and information describing and comparing Russian and Finnish ways of life. Based on the cultural topics covered in Kafe Piter, we conclude that the textbook is in line with the intercultural competence objectives set out in the Common European Framework of Reference for Languages. The results of the study also make it clear that a thorough proofreading of Kafe Piter is needed in order to correct mistakes - more than 130 cultural and linguistic mistakes and inaccuracies appear in the textbook.

Case: Kitaravahvistimen AB-luokan tehovahvistimen päivittäminen D-luokkaan

D-luokan vahvistimien etu perinteisiin A- tai AB-luokan vahvistimiin nähden on niitten korkea hyötysuhde ja pieni koko. Lisäksi ne ovat edullisia ja niihin voidaan asentaa pienemmät jäähdytyslevyt kuin perinteisiin vahvistimiin korkean hyötysuhteen ansiosta. Tässä tutkimuksessa asennetaan Peavey Solo –kitaravahvistimen pääteasteena toimivan AB-luokan päätevahvistimen tilalle tehokkaampi ja uudempaa vahvistinluokkaa edustava D-luokan vahvistin. Tutkimuksessa selvitetään, miten D-luokan vahvistimella toteutettu kytkentä toimii verrattuna alkuperäiseen kytkentään tutkimalla kitaravahvistimelle tyypillisiä sähköisiä ominaisuuksia. Työ toteutetaan mittauksin. Koska työssä olevissa kytkennöissä on jännitteisiä osia, on siinä perehdyttävä sähköturvallisuuteen. D-luokan vahvistin asettaa tietyt sähkötekniset kestävyysvaatimukset kytkennän teholähteelle ja kaiutinelementille, jolloin työssä paneudutaan myös niiden valintaan. D-luokan vahvistimeen päivitetyn kytkennän tuottamat äänenpainetasot olivat valtaosassa mittauksia suuremmat kuin alkuperäisellä kytkennällä. Äänenpainetasojen mittaustilanteissa myös kuormalle syötetyt tehot olivat suuremmat päivitetyllä kytkennällä verrattuna alkuperäiseen. Suurin päivitetyn kytkennän kuorman teho 72,72 W saavutettiin, kun kaiutinelementin yli oli 24,12 V:n jännitteen tehollisarvo ja kuorman teho oli noin 36 kertaa suurempi kuin alkuperäisellä kytkennällä. D-luokan vahvistimen mitatut harmonisen särön arvot ovat huomattavasti pienempiä kuin alkuperäisellä vahvistimella. Muokkaamattoman vahvistimen mitatusta sähköisestä taajuusvasteeesta nähdään, että alkuperäinen vahvistin korostaa tiettyjä taajuuksia, kun D-luokan vahvistimen taajuusvaste on sen sijaan likimain tasainen. Akustinen taajuusvaste ei ole niin tasainen D-luokan vahvistimeen päivitetyllä kytkennällä kuin alkuperäisellä kytkennällä ja sillä on myös kapeampi taajuusalue. Jos päivitetyn kytkennän sointia haluttaisiin parantaa, pitäisi tutkia lisää akustiseen taajuusvasteeseen vaikuttavia asioita.