Everolimus-induced pneumonitis associates with favourable outcome in patients with metastatic renal cell carcinoma

Background: Mammalian target of rapamycin inhibitors may induce pneumonitis. We analysed the association of pneumonitis with outcomes in everolimus treated metastatic renal cell carcinoma (mRCC) patients. Patients and methods: Eighty-five mRCC patients received everolimus at Helsinki University Hospital (cohort A). Computed tomography (CT) verified pneumonitis was correlated with outcome using Kaplan-Meier, Cox regression and logistic regression. An independent cohort of 148 everolimus treated mRCC patients (cohort B) at Aarhus University Hospital was assessed for validation. Results: In cohort A, CT-verified pneumonitis (N = 29, 34.1%) was associated with improved overall survival (OS) (24.7 versus 8.5 months; P <0.001), progression-free survival (PFS) (5.5 versus 3.2 months; P = 0.002) and clinical benefit rate (CBR) 57.1% versus 24.1% (P = 0.003). In multivariate analyses pneumonitis was associated with improved OS (hazard ratio [HR], 0.22; 95% confidence interval [CI] 0.12-0.44; P <0.001), PFS (HR 0.37; 95% CI 0.21-0.66; P = 0.001) and CBR (odds ratio [OR] 4.11; 95% CI 1.42-11.95; P = 0.01). In cohort B, CT-verified pneumonitis (N = 29, 19.6%) was associated with improved OS (12.9 versus 6.0 months; P = 0.02), PFS (6.0 versus 2.8 months; P = 0.02) and CBR (79.3% versus 39.5%; P <0.001). In multivariate analyses pneumonitis was associated with improved OS (HR 0.58; 95% CI 0.36-0.94; P = 0.03), PFS (HR 0.61; 95% CI 0.39-0.95; P = 0.03) and CBR (OR 5.65; 95% CI 2.10-15.18; P = 0.001). In a combined multivariate analysis (N = 233), with pneumonitis as a time-dependent covariate, CT-verified pneumonitis was associated with longer OS (HR, 0.67; 95% CI 0.46-0.97; P = 0.03). Furthermore, in a landmark analysis, pneumonitis was associated with longer OS (17.4 versus 7.8 months; P = 0.01). Conclusions: Everolimus-induced pneumonitis is associated with improved outcome in patients with mRCC and may serve as a biomarker of everolimus efficacy. (C) 2017 Elsevier Ltd. All rights reserved.Peer reviewe

Suomalaisten opettajien asenteita ja valmiuksia ohjelmoinnin opetukseen

Tiivistelmä. Tässä pro gradu -tutkielmassa tarkastellaan suomalaisten perusopetuksen opettajien valmiuksia opettaa ohjelmointia sekä asenteita ohjelmoinnin opettamista kohtaan. Lähtökohtana tutkielmalle on uusi Perusopetuksen opetussuunnitelman perusteet ja sen mukanaan tuoma ohjelmoinnin opetuksen sisällyttäminen opetukseen. Pro gradun teoreettinen osa ja sen pohjalta laadittu mittaristo perustuu kahteen pääteoriaan. Tutkielmassa kerätty aineisto on avointa ja se on kaikkien käytettävissä Aalto-yliopiston kautta. Aineistonkeruun instrumentissa opettajien teknologia-asenteen taustalla ovat Davisin (1989) teknologian hyväksymismalli (Technology Acceptance Model, TAM) sekä Venkatesh et al. (2003) Yhdistetty teoria teknologian hyväksymisestä ja käytöstä (Unified Theory of Acceptance and Use of Technology, UTAUT). Tutkielmassa on tarkoituksena tarkastella suomalaisen perusopetuksen opettajan valmiuksia opettaa ohjelmointia sekä asenteita niin ohjelmoinnin asemasta perusopetuksessa, kuin ohjelmoinnin opetuksesta yleisesti. Työn tuloksien avulla pyritään kehittämään suomalaisten peruskoulun opettajien koulutusta ohjelmoinnin opetuksessa. Pro gradu tutkielman aineisto on kerätty yhteistyössä koodiaapinen.fi-sivuston ohjelmointikurssin kanssa. Tutkimuskysely järjestettiin kurssin osallistujille. Tutkielma perustuu 317 suomalaisen opettajan web-kyselylomakkeeseen. Tutkielman päätulokset: Noin yksi kymmenestä vastaajasta ilmoitti pystyvänsä opettamaan joitakin seuraavista kielistä: Scratch, Scratch Jr., Code.org, ja HTML/CSS. Muiden ohjelmointikielten ja -ympäristöjen osaajia oli merkittävästi vähemmän. Uskoa ohjelmoinnin opettamisen osaamiseen vastaajien keskuudessa kuitenkin on, sillä lähes puolet vastaajista ilmoitti pystyvänsä ratkaisemaan ohjelmoinnin opetuksen ongelmia, vaikka paikalla ei olisi ketään ohjeistamassa ja yli 70 % vastaajasta ilmoitti pystyvänsä ratkaisemaan ohjelmoinnin opetuksen ongelmia, jos käytettävissä on runsaasti (riittävästi) aikaa. Ohjelmoinnin opettaminen peruskoulussa nähdään tarpeellisena vastaajien keskuudessa. 74,1 % on osittain samaa mieltä tai täysin samaa mieltä väittämän ”Ohjelmoinnin opettamista tarvitaan peruskoulussa”. Suomalaisten opettajien suhtautuminen ohjelmoinnin opettamiseen on hieman neutraalia positiivisempi tai opettajat eivät tiedä miten he asennoituvat ohjelmointia kohtaan. Yleinen suhtautuminen ja ahdistuksen vähyys kertovat kuitenkin opettajien ottavan ohjelmoinnin opettamisen ennakkoluulotomasti käyttöönsä.Abstract. The main objective of this Master’s thesis is to explore Finnish primary school teachers’ readiness to teach programming and their attitudes towards teaching of programming. The new National Curriculum of Finland requires teachers to be able to teach programming commencing from autumn 2016. Koodiaapinen.fi has designed a massive open online course to educate Finnish teachers on teaching of programming to tackle this requirement. The research questionnaire was offered to the teachers who participated in the course. The results of this thesis are intended to be used on developing of the Finnish primary school teacher training on the area of teaching of programming. Research method of this thesis was web-based questionnaire (n=317). Instrument of the research is based on TAM (Technology Acceptance Model) (Davis, 1989.) and UTAUT (Unified Theory of Acceptance and Use of Technology) (Venkatesh et al., 2003.). Those models were translated and modified to match the research problem and the language of this thesis. One great contributor to the instrument was the questionnaire developed by the researchers of ”The programming studio: investigating teachers’ readiness for teaching programming in the Island of Ireland”. The questionnaire used in this thesis is partially similar to the one used in Ireland to allow direct comparison of the results between these studies. Main results of the thesis: About one in ten of the respondents declared to be able to teach some of the following programming languages: Scratch, Scratch Jr., Code.org and HTML/CSS. The respondents were significantly less familiar with other programming languages. However, almost half of the respondents indicated ability to solve problems of the teaching of programming even if there were no help available and over 70 % of the respondents declared they would solve those problems if they had enough time to work on the problem. Teaching of programming was seen necessary among the respondents as 74,1 % partially agreed or strongly agreed with the statement “the teaching of programming is needed in primary school”. The attitude towards teaching of programming is somewhat more positive than neutral among the respondents or the respondents were not yet able to state their attitudes. The general attitude and lack of anxiety among the respondents denotes that Finnish teachers are openmindedly welcoming programming into primary school’s curriculum

People Interpret Robotic Non-linguistic Utterances Categorically

We present results of an experiment probing whether adults exhibit categorical perception when affectively rating robot-like sounds (Non-linguistic Utterances). The experimental design followed the traditional methodology from the psychology domain for measuring categorical perception: stimulus continua for robot sounds were presented to subjects, who were asked to complete a discrimination and an identification task. In the former subjects were asked to rate whether stimulus pairs were affectively different, while in the latter they were asked to rate single stimuli affectively. The experiment confirms that Non-linguistic Utterances can convey affect and that they are drawn towards prototypical emotions, confirming that people show categorical perception at a level of inferred affective meaning when hearing robot-like sounds. We speculate on how these insights can be used to automatically design and generate affect-laden robot-like utterances

Laugh Like You Mean It:Authenticity Modulates Acoustic, Physiological and Perceptual Properties of Laughter

Several authors have recently presented evidence for perceptual and neural distinctions between genuine and acted expressions of emotion. Here, we describe how differences in authenticity affect the acoustic and perceptual properties of laughter. In an acoustic analysis, we contrasted spontaneous, authentic laughter with volitional, fake laughter, finding that spontaneous laughter was higher in pitch, longer in duration, and had different spectral characteristics from volitional laughter that was produced under full voluntary control. In a behavioral experiment, listeners perceived spontaneous and volitional laughter as distinct in arousal, valence, and authenticity. Multiple regression analyses further revealed that acoustic measures could significantly predict these affective and authenticity judgements, with the notable exception of authenticity ratings for spontaneous laughter. The combination of acoustic predictors differed according to the laughter type, where volitional laughter ratings were uniquely predicted by harmonics-to-noise ratio (HNR). To better understand the role of HNR in terms of the physiological effects on vocal tract configuration as a function of authenticity during laughter production, we ran an additional experiment in which phonetically trained listeners rated each laugh for breathiness, nasality, and mouth opening. Volitional laughter was found to be significantly more nasal than spontaneous laughter, and the item-wise physiological ratings also significantly predicted affective judgements obtained in the first experiment. Our findings suggest that as an alternative to traditional acoustic measures, ratings of phonatory and articulatory features can be useful descriptors of the acoustic qualities of nonverbal emotional vocalizations, and of their perceptual implications

Discrete Emotion Effects on Lexical Decision Response Times

Our knowledge about affective processes, especially concerning effects on cognitive demands like word processing, is increasing steadily. Several studies consistently document valence and arousal effects, and although there is some debate on possible interactions and different notions of valence, broad agreement on a two dimensional model of affective space has been achieved. Alternative models like the discrete emotion theory have received little interest in word recognition research so far. Using backward elimination and multiple regression analyses, we show that five discrete emotions (i.e., happiness, disgust, fear, anger and sadness) explain as much variance as two published dimensional models assuming continuous or categorical valence, with the variables happiness, disgust and fear significantly contributing to this account. Moreover, these effects even persist in an experiment with discrete emotion conditions when the stimuli are controlled for emotional valence and arousal levels. We interpret this result as evidence for discrete emotion effects in visual word recognition that cannot be explained by the two dimensional affective space account

The Contribution of Sound Intensity in Vocal Emotion Perception: Behavioral and Electrophysiological Evidence

Although its role is frequently stressed in acoustic profile for vocal emotion, sound intensity is frequently regarded as a control parameter in neurocognitive studies of vocal emotion, leaving its role and neural underpinnings unclear. To investigate these issues, we asked participants to rate the angry level of neutral and angry prosodies before and after sound intensity modification in Experiment 1, and recorded electroencephalogram (EEG) for mismatching emotional prosodies with and without sound intensity modification and for matching emotional prosodies while participants performed emotional feature or sound intensity congruity judgment in Experiment 2. It was found that sound intensity modification had significant effect on the rating of angry level for angry prosodies, but not for neutral ones. Moreover, mismatching emotional prosodies, relative to matching ones, induced enhanced N2/P3 complex and theta band synchronization irrespective of sound intensity modification and task demands. However, mismatching emotional prosodies with reduced sound intensity showed prolonged peak latency and decreased amplitude in N2/P3 complex and smaller theta band synchronization. These findings suggest that though it cannot categorically affect emotionality conveyed in emotional prosodies, sound intensity contributes to emotional significance quantitatively, implying that sound intensity should not simply be taken as a control parameter and its unique role needs to be specified in vocal emotion studies

Happiness Through Vacationing: Just a Temporary Boost or Long-Term Benefits?

Does vacationing add to our happiness in the long run? This question was addressed in a study of 3,650 Dutch citizens who reported their leisure travel every 3 months during 2 years and rated their happiness at the end of each year. Participants who had been on vacation appeared to be marginally happier, in terms of hedonic level of affect, than those who had not. This difference in Affect balance between vacationers and non-vacationers is probably due to a very minor causal effect of vacationing on hedonic level of affect. Possibly, vacationing is positively reminisced and these memories allow for the prevalence of more positive affect in people's lives. Happiness did not predict vacationing. The effect of holiday trips on vacationers' happiness is mostly short-lived; among vacationers, happiness was unrelated to the number of trips and days spent on vacation. A separate analysis of vacationers, who value vacationing most, yielded the same results. Implications for future research are discussed

The Vascular Impairment of Cognition Classification Consensus Study

Introduction: Numerous diagnostic criteria have tried to tackle the variability in clinical manifestations and problematic diagnosis of vascular cognitive impairment (VCI) but none have been universally accepted. These criteria have not been readily comparable, impacting on clinical diagnosis rates and in turn prevalence estimates, research, and treatment. / Methods: The Vascular Impairment of Cognition Classification Consensus Study (VICCCS) involved participants (81% academic researchers) from 27 countries in an online Delphi consensus study. Participants reviewed previously proposed concepts to develop new guidelines. / Results: VICCCS had a mean of 122 (98–153) respondents across the study and a 67% threshold to represent consensus. VICCCS redefined VCI including classification of mild and major forms of VCI and subtypes. It proposes new standardized VCI-associated terminology and future research priorities to address gaps in current knowledge. / Discussion: VICCCS proposes a consensus-based updated conceptualization of VCI intended to facilitate standardization in research

Interactive visual music

How can Visual Music be composed and presented in such an engaging way that it will turn spectators into participants? How to connect a youthful, twenty-first century audience who are keen to update their Instagram story with Visual Music? Visual Music is an art form, which is “an equal and meaningful synthesis of the visible and audible” (Lund & Lund 2009 149) and “is typically non-narrative and non-representational” (Evans 2005 11). Visual Music is often presented as cinema. Cinema audiences are generally considered to be passive spectators, whose “reactions are pre-programmed by the director, crew, cast and writer” (Mackintosh 2003 2). This paper highlights the nexus between, to use McCall’s (2004) terms ‘the cinematic, the sculptural and the pictorial’, with a focus on creating interactive Visual Music installations

Plasma Apolipoprotein Levels Are Associated with Cognitive Status and Decline in a Community Cohort of Older Individuals

<div><h3>Objectives</h3><p>Apolipoproteins have recently been implicated in the etiology of Alzheimer’s disease (AD). In particular, Apolipoprotein J (ApoJ or clusterin) has been proposed as a biomarker of the disease at the pre-dementia stage. We examined a group of apolipoproteins, including ApoA1, ApoA2, ApoB, ApoC3, ApoE, ApoH and ApoJ, in the plasma of a longitudinal community based cohort.</p> <h3>Methods</h3><p>664 subjects (257 with Mild Cognitive Impairment [MCI] and 407 with normal cognition), mean age 78 years, from the Sydney Memory and Aging Study (MAS) were followed up over two years. Plasma apolipoprotein levels at baseline (Wave 1) were measured using a multiplex bead fluorescence immunoassay technique.</p> <h3>Results</h3><p>At Wave 1, MCI subjects had lower levels of ApoA1, ApoA2 and ApoH, and higher levels of ApoE and ApoJ, and a higher ApoB/ApoA1 ratio. Carriers of the apolipoprotein E ε4 allele had significantly lower levels of plasma ApoE, ApoC3 and ApoH and a significantly higher level of ApoB. Global cognitive scores were correlated positively with ApoH and negatively with ApoJ levels. ApoJ and ApoE levels were correlated negatively with grey matter volume and positively with cerebrospinal fluid (CSF) volume on MRI. Lower ApoA1, ApoA2 and ApoH levels, and higher ApoB/ApoA1 ratio, increased the risk of cognitive decline over two years in cognitively normal individuals. ApoA1 was the most significant predictor of decline. These associations remained after statistically controlling for lipid profile. Higher ApoJ levels predicted white matter atrophy over two years.</p> <h3>Conclusions</h3><p>Elderly individuals with MCI have abnormal apolipoprotein levels, which are related to cognitive function and volumetric MRI measures cross-sectionally and are predictive of cognitive impairment in cognitively normal subjects. ApoA1, ApoH and ApoJ are potential plasma biomarkers of cognitive decline in non-demented elderly individuals.</p> </div