975 resultados para Roth, Venla


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This book is the transcript of a witness seminar on the history of experimental economics, in which eleven high-profile experimental economists participated, including Nobel Laureates Vernon Smith, Reinhard Selten and Alvin Roth. The witness seminar was constructed along four different topics: skills, community, laboratory, and funding. The transcript is preceded by an introduction explaining the method of the witness seminar and its specific set-up and resuming its results. The participants' contribution and their lively discussion provide a wealth of insights into the emergence of experimental economics as a field of research.

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Aim: One standard option in the treatment of stage IIIA/N2 NSCLC is neoadjuvant chemotherapy followed by surgery. We investigated in a randomized trial whether the addition of neoadjuvant radiotherapy would improve the outcome. Here we present the final results of this study. Methods: Patients (pts.) with pathologically proven, resectable stage IIIA/N2 NSCLC, performance status 0-1, and adequate organ function were randomized 1:1 to chemoradiation (CRT) with 3 cycles of neoadjuvant chemotherapy (cisplatin 100 mg/m2 and docetaxel 85 mg/m2 d1, q3weeks) followed by accelerated concomitant boost radiotherapy (RT) with 44 Gy in 22 fractions in 3 weeks, or neoadjuvant chemotherapy alone (CT), with subsequent surgery for all pts. The primary endpoint was event-free survival (EFS). Results: 232 pts. were randomized in 23 centers, the median follow-up was 53 months. Two thirds were men, median age was 60 years (range 37-76). Histology was squamous cell in 33%, adenocarcinoma in 43%. Response rate to CRT was 61% vs. 44% with CT. 85% of all pts. underwent surgery, 30-day postoperative mortality was 1%. The rate of complete resection was 91% (CRT) vs. 81% (CT) and the pathological complete remission (pCR) rate was 16% vs. 12%. The median EFS was 13.1 months (95% CI 9.9 - 23.5) for the CRT group vs. 11.8 months (95% CI 8.4 - 15.2) in the CT arm (p 0.665). The median overall survival (OS) with CRT was 37.1 months (95% CI 22.6 -50), with CT 26.1 months ( 95% CI 26.1 - 52.1, p 0.938). The local failure rate was 23% in both arms. In the CT arm 12 pts. were given postoperative radiotherapy (PORT) for R1 resection, 6 pts. received PORT in violation of the protocol. Pts. with a pCR, mediastinal downstaging to ypN0/1 and complete resection had a better outcome. Toxicity of chemotherapy was substantial, especially febrile neutropenia was common, whereas RT was well tolerated. Conclusions: This is the first completed phase III trial to evaluate the role of induction chemoradiotherapy and surgery, in comparison to neoadjuvant CT alone followed by surgery. RT was active, it increased response, complete resection and pCR rates. However, this failed to translate into an improvement of local control, EFS or OS. Notably, surgery after induction treatment was safe, including pneumonectomy. The overall survival rates of our neoadjuvant regimen are very encouraging, especially for a multicenter setting. Disclosure: M. Pless: Advisory Board for Sanofi; R. Cathomas: Advisory Board Sanofi D.C. Betticher: Advisory Board Sanofi. All other authors have declared no conflicts of interest.

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Iron is essential for retinal function but contributes to oxidative stress-mediated degeneration. Iron retinal homeostasis is highly regulated and transferrin (Tf), a potent iron chelator, is endogenously secreted by retinal cells. In this study, therapeutic potential of a local Tf delivery was evaluated in animal models of retinal degeneration. After intravitreal injection, Tf spread rapidly within the retina and accumulated in photoreceptors and retinal pigment epithelium, before reaching the blood circulation. Tf injected in the vitreous prior and, to a lesser extent, after light-induced retinal degeneration, efficiently protected the retina histology and function. We found an association between Tf treatment and the modulation of iron homeostasis resulting in a decrease of iron content and oxidative stress marker. The immunomodulation function of Tf could be seen through a reduction in macrophage/microglial activation as well as modulated inflammation responses. In a mouse model of hemochromatosis, Tf had the capacity to clear abnormal iron accumulation from retinas. And in the slow P23H rat model of retinal degeneration, a sustained release of Tf in the vitreous via non-viral gene therapy efficently slowed-down the photoreceptors death and preserved their function. These results clearly demonstrate the synergistic neuroprotective roles of Tf against retinal degeneration and allow identify Tf as an innovative and not toxic therapy for retinal diseases associated with oxidative stress.

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PURPOSE: Prospective-retrospective assessment of theTOP1gene copy number andTOP1mRNA expression as predictive biomarkers for adjuvant irinotecan in stage II/III colon cancer. EXPERIMENTAL DESIGN: Formalin-fixed, paraffin-embedded tissue microarrays were obtained from an adjuvant colon cancer trial (PETACC3) where patients were randomized to 5-fluorouracil/folinic acid with or without additional irinotecan.TOP1copy number status was analyzed by fluorescencein situhybridization (FISH) using aTOP1/CEN20 dual-probe combination.TOP1mRNA data were available from previous analyses. RESULTS: TOP1FISH and follow-up data were obtained from 534 patients.TOP1gain was identified in 27% using a single-probe enumeration strategy (≥4TOP1signals per cell) and in 31% when defined by aTOP1/CEN20 ratio ≥ 1.5. The effect of additional irinotecan was not dependent onTOP1FISH status.TOP1mRNA data were available from 580 patients with stage III disease. Benefit of irinotecan was restricted to patients characterized byTOP1mRNA expression ≥ third quartile (RFS: HRadjusted, 0.59;P= 0.09; OS: HRadjusted, 0.44;P= 0.03). The treatment byTOP1mRNA interaction was not statistically significant, but in exploratory multivariable fractional polynomial interaction analysis, increasingTOP1mRNA values appeared to be associated with increasing benefit of irinotecan. CONCLUSIONS: In contrast to theTOP1copy number, a trend was demonstrated for a predictive property ofTOP1mRNA expression. On the basis ofTOP1mRNA, it might be possible to identify a subgroup of patients where an irinotecan doublet is a clinically relevant option in the adjuvant setting of colon cancer.Clin Cancer Res; 22(7); 1621-31. ©2015 AACR.

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Kirjallisuusarvostelu

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Molecules expressed at the surface cuticle (SC) of plant parasitic nematodes represent the primary plant-nematode interface, and together with secreted-excreted (S-E) products are probably the first signals perceived by the host. These molecules, which are released into plant tissue, probably play important roles in the host-parasite interactions. Characterisation of these antigens will help in the identification of nematode targets useful for novel control strategies, which interfere with the nematode infection of plants. Three monoclonal (MAbs) and three polyclonal (PAbs) antibodies produced to S-E products of Meloidogyne spp. and Heterodera avenae were used to examine their reactivity towards M. incognita and/or M. arenaria second stage juveniles and adult females. The three PAbs showed cross-reactivity with M. incognita and M. arenaria. Antibody Roth-PC 373 strongly recognised molecules present in the SC, amphids and intestine, antibody Roth-PC 389 recognised the nematode amphids and metacorpus, while antibody Roth-PC 419 bound to molecules present in the subventral glands. Reactivity of the MAbs was only tested against M. arenaria. Monoclonal antibody Roth-MAb T116C1.1 showed intense reactivity with molecules present in the amphidial and phasmidial glands. Monoclonal antibodies Roth-MAb T46.2 and T42D.2 labeled the nematode amphids and molecules present in the nematode oesophagus (metacorpus), respectively.

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Kirjallisuusarvostelu

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Lectio praecursoria University of Helsinki 5.2.2011.

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Kirjallisuusarvostelu

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Kirja-arvio

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OBJETIVOS: analisar a freqüência e os fatores associados à ocorrência da espinha bífida. MÉTODOS: os dados foram obtidos por meio de entrevista de 47 casos e 47 controles, nascidos nas cinco maternidades da cidade de Pelotas, durante o período de 1 de Janeiro de 1990 a 31 de Dezembro de 2003. É estudo com delineamento de caso-controle, de base populacional que abrangeu todos os nascimentos hospitalares. O controle foi o neonato normal que nasceu após cada caso com malformação. Todos os dados foram obtidos mediante questionário-modelo. A análise do planejamento de análise de dados incluiu o uso do teste t de Student, chi² e odds ratio. RESULTADOS: ocorreram aproximadamente 77.000 nascimentos nesse período. Desses, 1.043 (1,3%) apresentaram algum tipo de malformação congênita. Dentre essas, 47 de 162 anomalias do fechamento do tubo neural foram diagnosticadas como espinha bífida. Foram encontradas diferenças significativas quanto ao número de natimortos prévios, bem como proporção superior de casos de espinha bífida em recém-nascidos do sexo feminino. Neste estudo, muitos fatores como o uso de medicamentos; doenças agudas; afecções crônicas; número de gestações; idade, escolaridade e ocupação dos pais, entre outros, não mostraram associação com o nascimento de recém-nascido com espinha bífida. CONCLUSÕES: a espinha bífida deve ser considerada como importante fator de risco para a morbidade perinatal, e sua ocorrência está associada a um histórico gestacional de natimortos prévios.

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Hitsauksen tuottavuuteen vaikuttavat hitsausmäärä, käytetyt prosessit ja laatu. Työn teoriaosuudessa tutustutaan hitsauksen tuottavuuteen sekä suunnittelullisesta että valmistuksellisesta näkökulmasta. Hitsauksen laadulliset asiat, kuten laatustandardit ja vaatimukset käydään läpi keskittyen standardin SFS-EN ISO 3834 kattaviin laatuvaatimuksiin. Rikkomaton ja rikkova aineenkoetus ja yleisimmät hitsausvirheet esitetään yleisellä tasolla. Hitsausprosesseista esitetään MIG/MAG- ja MAG-täytelankahitsauksen sekä pulssihitsauksen perusteet. Tässä diplomityössä tutkitaan pulssihitsauksen soveltuvuutta sähkögeneraattorin staattoripaketin eripariliitoksen hitsaukseen ja kykyä parantaa sekä tuottavuutta että laatua. Tutkimus perustuu koehitsauksiin ja niiden perusteella tehtyihin johtopäätöksiin. Lisäksi pohditaan sisätuulettimien hitsauksen kehittämistä ja annetaan kehitysehdotus valmistusprosessista. Koehitsauksien perusteella pulssihitsaus on hyvä prosessiparannus staattoripakettien hitsaukseen. Kohdistettu valokaari ja alhaisempi lämmöntuonti verrattuna perinteiseen MAG-hitsaukseen sekä hitsauksen yksinkertaisuus tuovat etuja eripariliitoksen hitsauksen laatuun. Kustannuslaskelmien myötä hitsausprosessin muutoksen odotetaan tuovan kustannussäästöjä. Hitsauslaadun parantuessa ja jälkityöstön määrän vähentyessä hitsausprosessin muutos on kannattava.

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Tämän tutkimuksen tavoitteena oli tutkia kahdeksan vuoden iässä arvioitujen perhetekijöiden, psyykkisten oireiden ja kiusaamiskäyttäytymisen yhteyttä äidiksi tulemiseen alle 20-vuotiaana, isäksi tulemiseen alle 22-vuotiaana ja raskaudenkeskeytyksen tekemiseen alle 29-vuotiaana. Tutkimus perustui suomalaiseen LAPSET-kohorttiin, joka on yleisväestöotos (n=5813) vuonna 1981 syntyneistä henkilöistä. Vuonna 1989 tutkittavat sekä heidän vanhempansa ja opettajansa vastasivat psyykkistä oireilua ja kiusaamista koskeviin kyselyihin. Vanhemmat antoivat tietoa myös perhetekijöistä ja opettajat koulumenestyksestä. Tiedot tyttöjen (n=2694, 94 % osallistuneista tytöistä) synnytyksistä ja raskaudenkeskeytyksistä kerättiin hoitoilmoitusrekisteristä ja raskaudenkeskeyttämisrekisteristä. Poikien (n=2721, 92 % osallistuneista pojista) osalta nuorena isäksi tuleminen selvitettiin väestötietojärjestelmästä. Nuorten äitien tyttäret tulivat vanhempien äitien tyttäriä todennäköisemmin nuorena äidiksi ja nuorten isien pojat nuorena isäksi. Matalasti koulutettujen äitien pojilla oli kohonnut todennäköisyys nuorena isäksi tulemiseen ja tyttärillä raskaudenkeskeytykseen. Muu kuin kahden biologisen vanhemman muodostama perherakenne oli yhteydessä nuorena äidiksi tulemiseen ja raskaudenkeskeytykseen. Lapsuuden käytösongelmat olivat yhteydessä nuorena vanhemmaksi tulemiseen sekä raskaudenkeskeytykseen. Ylivilkkaus oli yhteydessä nuorena äidiksi tulemiseen. Tytöistä ne, jotka olivat kiusaajia tai kiusaaja-kiusattuja, tulivat todennäköisimmin nuorena äidiksi ja pojista kiusaaja-kiusatut nuorena isäksi. Kiusaaminen ei ollut yhteydessä raskaudenkeskeytyksen tekemiseen. Tutkimustuloksia voidaan hyödyntää terveydenhuollossa kohdattaessa nuoria vanhempia ja muita nuoria. Lisäksi niillä voi olla merkitystä esimerkiksi suunniteltaessa toimenpiteitä, joiden tavoitteena on nuorten epätoivottujen raskauksien ehkäiseminen.