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Leime, Aine Ni. "Masculinities and Aging in Ireland." Innovation in Aging 4, Supplement_1 (December 1, 2020): 826. http://dx.doi.org/10.1093/geroni/igaa057.3017.
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Abstract There is a need for research to gain understanding of the social and cultural constructions of ageing masculinities that, as Gullette emphasises, operate together to construct a ‘culture of decline’. This presentation explores how cultural images of older men inform constructions of ageing and lived realities in Ireland. It draws on the Irish findings from a cross-national, inter-disciplinary project conducted in 2019 investigating older men’s perceptions of how they are represented in film and advertising. It applies innovative narrative and thematic analysis to data from four focus group discussions, interviews and reflective diaries, to explore participants’ (Irish men aged 65+) reactions to the portrayal of older men in TV and film. Stereotypes identified included older men as conservative, grumpy, sad, streetwise, trickster, or action hero. Thematic analysis identified themes including men’s identification with their jobs; their diminishing roles in the family; and old age as a matter of perception.
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Goss, Marcin, Iwona Wawer, and Katarzyna Paradowska. "Radioprotekcyjne właściwości ekstraktów z kory sosny." HERBALISM 8, no. 1 (May 17, 2023): 73–94. http://dx.doi.org/10.12775/herb.2022.005.
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Zbadano przeżywalność komórek nerek zielonej małpy (GMK) poddanych rosnącym dawkom promieniowania γ. Do hodowli komórek dodano kompleks 99mTcDMSA (technetu 99mTc z kwasem merkaptobursztynowym, DMSA). Rozmiary zmian post-radiacyjnych oszacowano na podstawie liczenia komórek. Dodanie ekstraktów z kory zwiększyło przeżywalność komórek, w porównaniu do grupy bez dodatku radioizotopu, a zwłaszcza potraktowanej technetem bez środków ochronnych. Badania ekstraktów z sosny zwyczajnej Pinus silvestris i Pinus maritina (Pyc-nogenol) metodą EPR pokazały, że oba są efektywne w zmiataniu rodnika DPPH. Sugerowany mechanizm radioprotekcyjny obejmuje działanie antyoksydacyjne i przeciwrodnikowe.
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Zarzecka, Krystyna, Agnieszka Ginter, and Iwona Mystkowska. "Wartość odżywcza i prozdrowotna zbóż bezglutenowych." HERBALISM 10, no. 1 (June 14, 2024): 138–48. http://dx.doi.org/10.12775/herb.2024.012.
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W pracy przedstawiono charakterystykę wybranych gatunków zbóż niezawierających białek glutenowych z podaniem zawartości składników odżywczych i związków bioaktywnych oraz produktów zbożowych stosowanych przez konsumenta. Omówiono białka glutenowe i znaczenie diety bezglutenowej. Podkreślono, że bezglutenowe produkty zbożowe zawierają mniej składników mineralnych, witamin z grupy B i błonnika i z tego powodu dieta bezglutenowa powinna być wzbogacana nie tylko o pseudozboża, ale też o inne produkty naturalnie bezglutenowe, takie jak: warzywa i owoce, oleje roślinne, nasiona roślin strączkowych, jaja, nieprzetworzone mięso i ryby, mleko i naturalne produkty mleczne. Bezpieczne produkty można kupić nie tylko w Polsce, ale i w całej Europie i są one oznaczone graficznie licencjonowanym znakiem Przekreślonego Kłosa.
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Fröhlich, Sebastian. "Johannes Treutler (1820–1892) – kontekst historyczno- -kulturowy oraz postać pustelnika z Mariańskiej Góry." HERBALISM 9, no. 1 (June 16, 2023): 178–82. http://dx.doi.org/10.12775/herb.2023.014.
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Ważnym elementem w życiu Johannesa Treutlera jest pustelnia – to tam zaczyna interesować się recepturami i wytwarzaniem preparatów zielarskich; prawdopodobnie dzięki strojowi pustelniczemu (a konkretnie – habitowi franciszkańskiemu)otrzymuje przepis na balsam jerozolimski. Jednak Treutler życie pustelnicze prowadzi w czasach, gdy nie ma ogólnych norm dotyczących jego stanu – choć pierwsi anachoreci pojawiają się około III w. [1], to prawna regulacja tej grupy na poziomie całego Kościoła pojawia się dopiero w Kodeksie prawa kanonicznego z 1983 r. Tak więc do drugiej połowy XX w. pustelnicy i pustelnice żyją i funkcjonują na zasadzie tradycji lub miejscowych regulacji wprowadzonych przez biskupów lub synody lokalne – te natomiast wdrażane nieumiejętnie doprowadzały do zanikania indywidualnych form życia konsekrowanego na danym terenie [2].
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Zych, Maria, Weronika Wojnar, Anna Bońka, and Ilona Kaczmarczyk-Sedlak. "Wpływ chryzyny na parametry histomorfometryczne kości owariektomizowanych szczurów." HERBALISM 3, no. 1 (October 18, 2021): 41–54. http://dx.doi.org/10.12775/herb.2017.003.
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Osteoporoza jest schorzeniem wynikającym między innymi z niedoboru estrogenów u kobiet w okresie menopauzalnym. Choroba ta charakteryzuje się zmniejszoną wytrzymałością kości na uszkodzenia mechaniczne. Osłabienie układu szkieletowego wynika z zaburzeń na poziomie mikroarchitektury tkanki kostnej. Aby zapobiec rozwojowi osteoporozy pomenopauzalnej, można stosować terapię hormonalną, która jednak niesie za sobą wiele działań niepożądanych. W związku z tym poszukuje się bezpiecznej alternatywy dla hormonalnej terapii zastępczej. W tym celu wykorzystywane są związki pochodzenia roślinnego, w tym substancje o charakterze flawonoidów, nazywane fitoestrogenami. Celem pracy było zbadanie, czy związek o strukturze flawonoidu – chryzyna – może wykazywać ochronne działanie na tkankę kostną na poziomie mikroarchitektury u szczurów z eksperymentalnie wywołaną osteoporozą. Badania prowadzono na samicach szczurów szczepu Wistar podzielonych na grupy: SHAM – pozornie operowane, OVX – owariektomizowane i OVX+CHR – owariektomizowane, którym podawano doustnie chryzynę w dawce 50 mg/kg przez 4 tygodnie. Po izolacji kości zanalizowano parametry makrometryczne oraz wykonano preparaty histologiczne i oznaczono szereg parametrów histomorfometrycznych. Uzyskane wyniki wskazują, że chryzyna podawana szczurom owariektomizowanym powoduje nieznaczną poprawę badanych parametrów.
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Baranowska, Alicja, Iwona Mystkowska, Krystyna Zarzecka, and Marek Gugała. "Cenne owoce maliny właściwej (Fructus Rubi idaei)." HERBALISM 3, no. 1 (October 18, 2021): 70–79. http://dx.doi.org/10.12775/herb.2017.005.
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Malina właściwa (Rubus idaeus L.) jest jedną z najstarszych roślin znanych ludzkości i od wieków wykorzystywana do celów spożywczych oraz leczniczych. O przydatności owoców maliny (Fructus Rubi idaei) i liści (Folium Rubi idaei) decyduje w dużej mierze ich skład chemiczny. Wartość biologiczna owoców maliny właściwej zależy od poziomu antyoksydantów, do których między innymi zalicza się kwas askorbinowy i antocyjany. Natomiast o smaku i aromacie owoców decyduje stopień ich dojrzałości, odmiana, zawartość cukrów prostych, kwasów organicznych oraz substancji lotnych. Owoce maliny są również bogatym źródłem witamin (głównie witaminy C, witamin z grupy B, PP, A, E oraz K), składników mineralnych: potasu (K), wapnia (Ca), magnezu (Mg), żelaza(Fe) oraz w mniejszych ilościach manganu (Mn), miedzi (Cu), cynku (Zn) (dlatego mają działanie odkwaszające, wzmacniają serce i regulują pracę układu nerwowego). Zawierają również spore ilości błonnika i pektyn. Wyniki ostatnich badań naukowych dowiodły,że zawarty w owocach malin kwas elagowy (pestki malin zawierają aż 87,5% kwasu elagowego) hamuje procesy nowotworowe oraz posiada właściwości przeciwwirusowe i przeciwzapalne. Najnowsze badania naukowe potwierdzają również pozytywny wpływketonu malinowego (C10H12O2) na leczenie otyłości.
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Henning, Peter. "T-DM1 als Innovation beim HER2-positiven Brustkrebs: Antikörper und Zytostatikum als duale Wirkkombination." Onkologische Welt 03, no. 04 (2012): 172. http://dx.doi.org/10.1055/s-0038-1630203.
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Das Antikörper-Wirkstoff-Konjugat Trastuzumab-Emtansin (T-DM1) steht für ein neues Wirkprinzip in der Therapie des HER2-positiven Mammakarzinoms. über Thioether Linker SMCC ist das Zytostatikum DM1, ein Spindelgift aus der Gruppe der Maytansinoide an den Antikörper Trastuzumab gebunden.
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Dykiel, Magdalena, Angelika Uram-Dudek, and Iwona Wajs. "Wpływ marynowania mięsa wieprzowego z wykorzystaniem fermentowanych niepasteryzowanych octów na jego właściwości reologiczne." HERBALISM 10, no. 1 (June 14, 2024): 40–53. http://dx.doi.org/10.12775/herb.2024.004.
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Konsumenci domagają się mięsa i produktów mięsnych z naturalnymi składnikami, które gwarantują wysoką jakość żywności, a im samym zapewnią zdrowie. Celem podjętych badań było określenie wpływu marynaty z wykorzystaniem niepasteryzowanych octów i octu spirytusowego na właściwości reologiczne mięsa wieprzowego. Surowcem do badań było mięso wieprzowe – karkówka. Karkówkę podzielono na pięć porcji, z czego jedna stanowiła próbę kontrolną (bez octu), a pozostałe cztery marynowano octem: I – spirytusowym (pH 2,83), niepasteryzowanym octem: II – jabłkowym (pH 3,24), III – gruszkowym (pH 3,72), IV – malinowym (pH 3,01).Próbki oceniono pod kątem właściwości reologicznych. Wyniki niniejszego badania pokazują, że stosowanie octu w marynowaniu karkówki wieprzowej wpływa nacechy reologiczne mięsa, przy czym wpływ ten zależy od rodzaju użytego octu. Wykazano, że marynowanie z wykorzystaniem fermentowanych niepasteryzowanych octów miało znaczący (p < 0,05) wpływ na adhezyjność, odbojność i żylastość, ale nie na ich twardość, sprężystość, żujność oraz gumowatość (p > 0,05), co pokazało porównanie z próbkami kontrolnymi. Proces marynowania mięsa wieprzowego octem malinowym wpłynął istotnie na zwiększenie takich cech mięsa jak twardość, gumowatość i adhezyjność, co pokazało porównanie z próbkami kontrolnymi. Marynowanie octem gruszkowym wpłynęło na zmniejszenie odbojności, zaś zabieg marynowania octem jabłkowym miał istotny wpływ na adhezyjność, odbojność i żylastość, co pokazało porównanie z próbkami kontrolnymi. Proces marynowania przy użyciu octu spirytusowego, jabłkowego, gruszkowego oraz malinowego wpłynął na zmniejszenie odbojności mięsa, co pokazało porównanie z próbkami z grupy kontrolnej. Konieczne jest stałe analizowanie i badanie tekstury żywności, gdyż jest to ważna cecha, która wpływa na to, czy dany produkt spożywczy jest akceptowany, czy odrzucany przez konsumenta.
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Stolarek, Karolina, Angelika Uram-Dudek, Iwona Wawer, and Katarzyna Paradowska. "Ocena jakości szafranu (Crocus sativus L.) z wykorzystaniem metod spektroskopowych." HERBALISM 8, no. 1 (May 17, 2023): 6–26. http://dx.doi.org/10.12775/herb.2022.001.
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Szafran (Croccus sativus L.) to wyjątkowa roślina, ceniona na całym świecie. Uznawana za jedną z najdroższych i najszlachetniejszych przypraw. Właściwości szafranu znali już starożytni, którzy nie tylko dodawali szafran do dań i napitków, barwili nim tkaniny, ale także stosowali go w celach prozdrowotnych. Roślina ta jest doskonałym środ-kiem wspomagającym trawienie, poprawiającym nastrój i apetyt. W wielu badaniach naukowych wykazano również jej właściwości antydepresyjne, przeciwdrgawkowe, przeciwnowotworowe, antybakteryjne oraz antyoksydacyjne. Ze względu na szerokie zastosowanie tego materiału roślinnego, różne pochodzenie czy czas przechowywania, ważna jest weryfikacja surowca pod względem składu oraz właściwości. Stąd też ważne jest poszukiwanie szybkich, nieniszczących metod analitycznych, pozwalających na kontrolę surowca. W artykule przedstawiono analizę jakościową głównych bioaktywnych związków szafranu: krocyny, pikrokrocyny oraz safranalu z wykorzy-staniem trzech technik spektroskopowych: spektroskopii UV-Vis, magnetycznego rezonansu jądrowego w stanie stałym (1H MAS i 13C CPMAS NMR) oraz paramagnetycznego rezonansu jądrowego (EPR). Materiał poddano również analizie właściwości antyoksydacyjnych szafranu z wykorzystaniem testu zmiatania wolnego rodnika DPPH. Test przeprowadzono na materiale świeżym i pookresie starzenia materiału –(promieniowanie UV). Na podstawie otrzymanych wyników stwierdzono, że do przeprowadzenia analizy jakościowej badanych próbek wskazane jest zastosowanie kilku metod analitycznych w celu uzyskania pełnego obrazu. Widma 1H MAS NMR zarejestrowane dla próbek w postaci proszku rozróżniają próbki na podstawie związków z mobilnymi łańcuchami alifatycznymi. Natomiast analiza widm 13C CPMAS NMR umożliwia odróżnienie próbek i identyfikacje głównych składników (pierścienie aromatyczne, cukry czy grupy karbonylowe). Wykorzystanie charakterystycznych pasm absorpcji dla głównych składników szafranu może stanowić podstawę do określenia jakości badanego materiału roślinnego. Przeprowadzona analiza z zastosowaniem rodnika DPPH wykazała, iż szafran posiada wysokie właściwości antyoksydacyjne, działanie promieni UV powoduje ich zmniejszenie średnio o 50%.
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Moritoki, Yoshinobu, Kentaro Mizuno, Taiki Kato, Takahiro Yasui, and Yutaro Hayashi. "Unusual Cause of Acute Scrotal Pain-Inflammatory Noncommunicating Hydrocele: A Pediatric Case Report." Case Reports in Medicine 2018 (2018): 1–4. http://dx.doi.org/10.1155/2018/2862514.
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The etiology of scrotal pain is clinically classified in terms of the necessity for emergency surgery. Lately, color Doppler ultrasonography has reduced unnecessary surgeries, but there are still some cases that require immediate exploration because of an uncertain diagnosis. Here, we describe the case of a 14-month-old boy, who could not deliver his complaint accurately, presenting with a grumpy mood and a red swollen scrotum. Emergency surgery revealed that the cause was intense inflammation of the hydrocele wall, which typically does not cause acute scrotum. We also reviewed rare etiologies of scrotal pain for general physicians to develop the differential diagnosis.
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Moran, Albert. "The International Face of Australian Television." Media International Australia 121, no. 1 (November 2006): 174–87. http://dx.doi.org/10.1177/1329878x0612100119.
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Australian television has always been part of an international cultural system. Programming, personnel, material resources, ideas and knowledge are among the elements that, historically, have moved between an audiovisual space, both here and elsewhere. Media executive Reg Grundy has been an important figure in this system. Over nearly 40 years, he built a television empire of considerable international significance. After sketching out this career, the article proceeds to outlines three moments in his company's development. The first occurred in the 1960s and early 1970s when it imported and remade many successful television game shows from the United States. A second occasion occurred in the mid-1970s when Reg Grundy Enterprises imported a small team from the United Kingdom who were highly experienced in the production of daily drama serials. The third moment happened in the very early 1990s, when Grundy World Wide began adapting drama serials that it had originally devised and produced in Australia to be remade elsewhere. These three occasions were important points where the national met the international. Collectively, they highlight not only the outwardlooking dimension of Australian television, but the need for home-based media historians to make such a perception central to their investigations of a pre ‘media globalisation’ past.
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Walter, Vincent P., Florin-Andrei Taran, Markus Wallwiener, Armin Bauer, Eva-Maria Grischke, Christina Barbara Walter, Markus Hahn, Sara Y. Brucker, and Andreas Daniel Hartkopf. "Verteilung des 21-Gen-Rezidiv-Scores bei Patientinnen mit primärem Mammakarzinom in Deutschland." Senologie - Zeitschrift für Mammadiagnostik und -therapie 18, no. 03 (September 2021): 285–93. http://dx.doi.org/10.1055/a-1578-9549.
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Zusammenfassung Einleitung Multigen-Assays werden zunehmend als Entscheidungshilfe für eine Chemotherapie beim Mammakarzinom verwendet. Wir stellen hier den 21-Gen-Recurrence-Score (RS) von Patientinnen mit Brustkrebs vor, die routinemäßig in Deutschland untersucht wurden. Patientinnen und Methoden 4695 Patientinnen mit hormonrezeptorpositivem und HER2-negativem Brustkrebs im Frühstadium (pT1–3, pN0–1, M0) wurden einer retrospektiven Analyse unterzogen. Bei diesen Patientinnen wurde in Deutschland zwischen November 2015 und Juli 2018 der Genexpressionstest Oncotype DX zur Ermittlung des Recurrence-Scores durchgeführt. Die Klassifikation der RS-Gruppen erfolgte gemäß der TAILORx Studie (RS: 0–10; 11–25; 26–100). Ergebnisse Von diesen Patientinnen wurden 21 % in die niedrige RS-Gruppe, 63 % in die mittlere RS-Gruppe, und 15 % in die hohe RS-Gruppe eingeteilt. 1772 (81 %) von 2175 Patientinnen im Alter von über 50 Jahren und ohne Lymphknotenbefall wurden entweder in die niedrige oder die mittlere RS-Gruppe eingeteilt. Der Prozentsatz an Patientinnen mit einem niedrigen oder mittleren RS betrug 90 % bei Patientinnen ohne Lymphknotenbefall (1284 von 1432 Patientinnen), 79 % bei Patientinnen mit einem hohen (≥ 20 %) Ki-67-Wert (1829 von 2310 Patientinnen), 86 % bzw. 70 % bei Patientinnen mit G2- bzw. G3-Tumoren (3244 von 3762 Patientinnen bzw. 368 von 522 Patientinnen), 88 % bei Patientinnen mit einem Tumordurchmesser von > 5 cm (140 von 159 Patientinnen) und 82 % bei Patientinnen ohne Lymphknotenbefall, aber mit einem hohen klinischen Risiko (1110 von 1352). Schlussfolgerung Die Verteilung des 21-Gens RS bei deutschen Patientinnen, die in der klinischen Routinepraxis getestet wurden, deutet darauf hin, dass gemäß den Ergebnissen der TAILORx-Studie die Chemotherapie bei den meisten dieser Patientinnen keinen Nutzen hat.
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Grasseni, Cristina. "Seeds of Trust. Italy's Gruppi di Acquisto Solidale (Solidarity Purchase Groups)." Journal of Political Ecology 21, no. 1 (December 1, 2014): 178. http://dx.doi.org/10.2458/v21i1.21131.
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This article presents a case study of the solidarity economy in Italy: the Italian G.A.S. – Gruppi di Acquisto Solidale, which I translate as Solidarity Purchase Groups. GAS are often conceptualized as "alternative food networks". Beyond this categorization, I highlight their novelty in relational, political, and ecological terms, with respect to their capacity to forge new partnerships between consumers and producers. Introducing an ethnographic study that I have developed in a recent monograph (Grasseni 2013), I dwell here in particular on how the solidarity economy is embedded in practice. I argue that gasistas' provisioning activism is something different to mere "ethical consumerism." Activists use the notion of "co-production" to describe their engagement as a concurrent rethinking of the social, economic, and ecological aspects of provisioning. Building also on a quantitative survey of the GAS movement in northern Italy, I pursue an ethnographic understanding of "co-production." I argue that producers and consumers in GAS networks "co-produce" both economic value and ecological knowledge, while re-embedding their provisioning practice in mutuality and relationality.Keywords: Solidarity economy, solidarity purchase groups, Gruppi di Acquisto Solidale, alternative food networks, provisioning, co-production, Gibson-Graham, Italy.
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Molinelli, Chiara, Virginia Delucchi, Eva Blondeaux, Luca Boni, Francesca Poggio, Grazia Arpino, Cecilia Nisticò, et al. "Dose-dense adjuvant chemotherapy in patients with HER2-low early breast cancer: An exploratory analysis of the GIM2 trial." Journal of Clinical Oncology 42, no. 16_suppl (June 1, 2024): 532. http://dx.doi.org/10.1200/jco.2024.42.16_suppl.532.
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532 Background: Dose-dense (DD) adjuvant chemotherapy represents the standard treatment for patients with node-positive early-stage HER2-negative breast cancer, but its role in HER2-low disease is unknown. In this exploratory analysis of the Gruppo Italiano Mammella 2 (GIM2) trial, we investigated efficacy of DD chemotherapy among patients affected by HER2-negative breast cancer according to HER2 immunohistochemistry (IHC) score (low vs. zero). Methods: Patients with node-positive early breast cancer were randomly assigned to receive either DD or standard schedule anthracycline- and taxane-based chemotherapy. HER2 status was assessed locally. Tumours with HER2 score 0 were classified as HER2-zero, while those with a HER2 score 1+ or 2+ without fluorescence in situ hybridization (FISH) amplification were defined as HER2-low. Some tumours were classified as HER2-negative with unknown IHC score. Survival outcomes were compared between patients with HER2-zero vs HER2-low tumours. Results: Among 2003 patients enrolled in the GIM2 trial, 1243 subjects were eligible for this analysis. Median age was 52 years (interquartile range [IQR] 44-59) and 604 patients (48.6%) were pre-menopausal. Hormone receptor status was positive in 87.9% of cancers. 475 tumours were classified as HER2-zero (38.2%), 446 (35.9%) were defined HER2-low and 322 (25.9%) were HER2-negative with unknown IHC score. No significant differences were found in terms of baseline characteristics between these three subgroups. At a median follow-up of 14.9 years (IQR 8.4-16.2), no significant interaction was observed between treatment effect and HER2 status in invasive disease-free survival (iDFS) (p for interaction=0.46) nor in overall survival (OS) (p for interaction=0.43). Comparing patients with HER2-zero breast cancer with those affected by HER2-low tumours, no significant differences in iDFS were observed (15yr iDFS were 61% vs. 54%, respectively, p=0.25), nor OS differences (15yr OS were 75% vs. 72%, respectively, p=0.19). When investigating DD schedule efficacy among patients with HER2-zero tumours, hazard ratio (HR) for iDFS was 0.64 (95% confidence interval [CI] 0.46-0.87) and HR for OS was 0.57 (95%CI 0.38-0.88). Similarly, within patients affected by HER2-low breast cancer, HR was 0.83 (95%CI 0.62-1.11) for iDFS and 0.83 (95%CI 0.57-1.22) for OS. These results were consistent with the findings of efficacy of DD chemotherapy in the overall population included in this analysis (HR for iDFS 0.73 [95%CI 0.61-0.89]; HR for OS 0.69 [95%CI 0.54-0.88]). Conclusions: In this exploratory analysis of a large phase III adjuvant trial, HER2 status (i.e. HER2-zero vs HER2low) did not show prognostic value. In patients with high-risk early breast cancer, the benefit of DD chemotherapy was observed irrespective of HER2 status. Clinical trial information: NCT00433420 .
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Isaacs, I. M. "The π-character theory of solvable groups." Journal of the Australian Mathematical Society. Series A. Pure Mathematics and Statistics 57, no. 1 (August 1994): 81–102. http://dx.doi.org/10.1017/s1446788700036077.
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AbstractThere is a deeper structure to the ordinary character theory of finite solvable groups than might at first be apparent. Mauch of this structure, which has no analog for general finite gruops, becomes visible onyl when the character of solvable groups are viewes from the persepective of a particular set π of prime numbers. This purely expository paper discusses the foundations of this πtheory and a few of its applications. Included are the definitions and essential properties of Gajendragadkar's π-special characters and their connections with the irreducible πpartial characters and their associated Fong characters. Included among the consequences of the theory discussed here are applications to questions about the field generated by the values of a character, about extensions of characters of subgroups and about M-groups.
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Fehm, Tanja N., Manfred Welslau, Volkmar Müller, Diana Lüftner, Florian Schütz, Peter A. Fasching, Wolfgang Janni, et al. "Update Mammakarzinom 2022 Teil 3 – Brustkrebs in frühen Krankheitsstadien." Senologie - Zeitschrift für Mammadiagnostik und -therapie 19, no. 04 (December 2022): 365–75. http://dx.doi.org/10.1055/a-1962-3985.
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ZusammenfassungIn dieser Übersichtsarbeit werden neueste Entwicklungen in der Prävention von Brustkrebs und Behandlung von Patientinnen mit frühen Krankheitsstadien mit Mammakarzinom zusammengefasst. Die Ermittlung von individuellen Erkrankungsrisiken nach molekularen Subtypen wurde in einer großen epidemiologischen Studie untersucht. Im Bereich der Behandlung gibt es neue Daten zur Langzeitnachbeobachtung der Aphinity-Studie ebenso wie neue Daten zur neoadjuvanten Therapie von HER2-positiven Patientinnen mit Atezolizumab. Biomarker wie Residual Cancer Burden wurden im Zusammenhang mit einer Pembrolizumab-Therapie untersucht. Eine Untersuchung des Genomic-Grade-Indexes bei älteren Patientinnen reiht sich ein in die Gruppe von Studien, die versucht, durch moderne Multigentests Patientinnen zu identifizieren, bei denen eine Chemotherapie vermieden werden kann, weil diese eine exzellente Prognose haben. Diese und weitere Aspekte der neuesten Entwicklungen bei der Diagnostik und Therapie des Mammakarzinoms werden in dieser Übersichtsarbeit beschrieben.
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Cinieri, S., L. Orlando, V. Lorusso, G. Filippelli, E. Maiello, L. Blasi, F. Verderame, S. Barni, S. Pisconti, and G. Colucci. "New biweekly combination of trastuzumab, docetaxel, and gemcitabine for HER2-positive metastatic breast cancer: First early results from a phase II multicentric trial on behalf of Gruppo Oncologico Italia Meridionale." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): 1096. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.1096.
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1096 Background: The clinical activity of the combination of chemotherapy plus trastuzumab in HER-2 overexpressing metastatic breast cancer has been well documentated. We report the first results in terms of efficacy and safety of a phase II trial on biweekly combination of trastuzumab plus docetaxel and gemcitabine as first line therapy in HER-2-positive metastatic breast cancer patients. Methods: Patients at first relapse or with synchronous metastasis, were treated with trastuzumab (4 mg/kg, loading dose 6 mg/kg) plus gemcitabine (1000 mg/m2) plus docetaxel (50 mg/m2) as biweekly schedule. Primary end-point was overall response rate (ORR), secondary end-point time to progression (TTP), clinical benefit rate (CBR; PR+ CR + prolonged SD for ≥ 24 weeks), and tolerability. Based on previous data, an ORR greater than 60% was considered to indicate clinical activity in this two stage design trial. Results: A total of 26 patients with histologically confirmed, measurable MBC, tumors scored as +3 positive for HER-2 by immuno-histochemistry or FISH +, no pretreated with chemotherapy or trastuzumab for metastatic disease have been enrolled, 22 actually evaluable for response and toxicity. Median age was 49 years (range 34–66), visceral metastases were present in most patients (73%). Median number of cycles was 8 (range 3–12). The ORR was 86% (95% CI, 80–91%), with two CR (9 %) and 17 PR (77%). 3 patients had SD, 1 prolonged (14%). The CBR was 91% (95% CI, 87%-94%). No progression of disease was observed. Median TTP was 7 months (range 5- 9+ months). The worst toxicity was WHO grade 2 neutropenia and grade 2 gastric pain. Conclusions: In this phase II study, the biweekly combination of trastuzumab, gemcitabine, and docetaxel in HER-2-positive breast cancer is very active. The toxicity observed was manageable and did not lead to treatment discontinuation. Thus, the patients accrual is ongoing to the preset target of 50 patients. No significant financial relationships to disclose.
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Jentzmik, Florian. "Standard Changing News in der Urologischen Onkologie 2020." Der Klinikarzt 49, no. 11 (November 2020): 462–66. http://dx.doi.org/10.1055/a-1296-7235.
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ZUSAMMENFASSUNGMit Einführung der Checkpoint-Inhibitoren hat sich die Therapielandschaft des metastasierten Urothelkarzinoms grundlegend verändert und verbessert. Ein völlig neuer Ansatz ist der Einsatz von Avelumab als Erhaltungstherapie bei Patienten mit lokal fortgeschrittenem oder metastasiertem Urothelkarzinom, die zumindest einen stabilen Krankheitsverlauf nach platinhaltiger Induktionstherapie hatten. In der JAVELIN bladder 100-Studie ereichte Avelumab + best supportive care (BSC) im Vergleich zur alleinigen BSC-Gruppe ein signifikant längeres Gesamtüberleben in den beiden primären Populationen aller randomisierten Patienten zum einen und Patienten mit PD-L1-positiven Tumoren zum anderen.In der HERO-Studie war die Androgendeprivation mit dem neuen GnRH-Antagonisten Relugolix bei Männern mit metastasiertem oder lokal fortgeschrittenem Prostatakarzinom der Behandlung mit dem GnRH-Agonisten Leuprorelin in allen primären und sekundären Endpunkten überlegen. Das einmal täglich oral applizierbare Relugolix erzielte höhere anhaltende Kastrationsraten und senkte die Testosteron-Spiegel und den PSA-Wert rascher als das 3-monatlich subkutan injizierte Leuprorelin. Außerdem zeigten sich weniger kardiovaskuläre Nebenwirkungen.In der PROfound-Studie war der PARP-Inhibitor Olaparib bei Männern mit mCRPC und BRCA1/2 oder ATM-Genmutation im Vergleich zur Standardtherapie (AR-gerichtete Therapie mit Abirateron oder Enzalutamid) mit einem längeren progressionsfreien Überleben und einem besseren Therapieansprechen assoziiert.
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Majchrowska, Justyna. "„Dziewczynki mogą wszystko” – o zwalczaniu stereotypu płci na przykładzie strategii marketingowej marki Lego." Media Biznes Kultura, no. 2 (13) (December 21, 2022): 121–32. http://dx.doi.org/10.4467/25442554.mbk.22.019.17105.
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Celem badania była próba zauważenia sposobów prowadzenia strategii marketingowej, w której łamie się stereotypy. Badanie pilotażowe, przeprowadzone za pomocą metody genologicznej analizy tekstu, ze szczególnym nastawieniem na aspekty strukturalny i językowy, pozwoliło zauważyć wielokanałowe komunikowanie nadawcy, Grupy Lego, z odbiorcami – konsumentami z całego świata, w tym z Polski. Poprzez prowadzoną strategię narracyjną firma zwraca uwagę na dotychczasowe, dość krzywdzące, zachowania społeczeństwa w stosunku do wychowywania dziewczynek (i analogicznie chłopców). Ten dualny, zapoczątkowany już w wieku niemowlęcym, podział, który jest powielany współcześnie, między innymi w ogólnodostępnych reklamach, jest jedną z przyczyn powstawania granicy między płciami. Respektowanie takiego wzorca przez społeczeństwo doprowadza obie grupy (kobiety i mężczyzn) do braków w umiejętnościach i kompetencjach, wprowadza rozgraniczenie i uprzedzenia, które – z czasem – mogą doprowadzić do krzywdzących zachowań jednej płci wobec drugiej lub wewnątrz każdej z nich. Wyniki przeprowadzonego badania wskazują na to, co kampania marki (tu Lego), a docelowo społeczeństwo, może osiągnąć poprzez promowanie określonych wartości, na przykład dzięki usunięciu stereotypów (stereotypów językowych), które tak mocno zakorzeniły się w języku i kulturze (nie tylko polskiej). Strategia określonej kampanii, dzięki korzystaniu z marketingu treści, pozwala również uzyskać pozytywny wizerunek marki (tu Lego) i zyskać nowych konsumentów. Łamanie stereotypów, wykorzystane w strategii marki, może stanowić zatem również perswazyjną technikę przyciągania uwagi klientów/potencjalnych nowych klientów. „Girls can do anything” – Remarks on Combating Gender Stereotype on Example of Lego Brand Marketing Strategy The aim of the study was to try to observe ways of conducting a marketing strategy in which stereotypes are broken. The pilot study carried out using the method of genological text analysis, with a particular focus on the structural and linguistic aspect, made it possible to notice the multi-channel communication of the addresser, the Lego Group, with recipients – consumers from all over the world, including Poland. Through its narrative strategy, the company draws attention to the existing, quite harmful, social attitudes to raising girls (and similarly boys). This Justyna Majchrowska 122 dual division, started already in infancy, which is being copied today, e.g. in publicly available advertisements, it is one of the reasons for the formation of the gender boundary. Respect for such a pattern by society leads both groups (women and men) to shortages in skills and competences, introduces demarcation and prejudices that – over time – can lead to harmful behavior of one sex towards the other or within each of them. The results of the study show what the brand campaign (here Lego), and ultimately the public, can achieve by promoting certain values, including by removing stereotypes (language stereotypes) so deeply rooted in language and culture (not only Polish). The strategy of a specific campaign, thanks to the use of content marketing, also allows for a positive brand image (here Lego) and attracting new consumers. Breaking stereotypes used in brand strategy can thus be a persuasive technique to attract the attention of customers/potential new customers.
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Pintarić, Mario, and Damir Tulić. "Prilog poznavanju kasnogotičke skulpture u Rijeci: prijedlog za Leonarda Thannera i nepoznata grupa Oplakivanje Krista." Ars Adriatica 8, no. 1 (December 28, 2018): 61–80. http://dx.doi.org/10.15291/ars.2755.
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The article discusses a late Gothic statue of Pietà in the permanent collection of the Maritime and Historical Museum of the Croatian Littoral in Rijeka. It is a wooden statue with poorly preserved traces of polychrome painting and gilding, discovered in 1920 in the attic of the parish church of Mary’s Assumption in Rijeka. Vanda Ekl dated it to the end of the third quarter of the 15th century without specifying its circle of origin or its history. Based on a stylistic analysis, as well as a series of typological and formal analogies, the Pietà of Rijeka can now be brought into connection with the woodcarver Leonardo Thannner from Bavarian Landshut, active in Friuli during the second half of the 15th century. A crucial comparative example can be found in Thanner’s polychromatic wooden group of The Lamentation of Christ from the church of Santa Maria della Fratta in San Daniele del Friuli (1488). Rijeka Lamentation, a hitherto unknown and here for the first time published statue, can be linked with a workshop or a circle of the Friulian sculptor Giovanni Martini and approximately dated to the first quarter of the 16th century.
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Silva, Rafael Costa da, and Antonio Carlos Sequeira Fernandes. "Review of Oliveirania santa catharinae (sic) Maury 1927 and associated ichnofossils (Itararé Group, Late Carboniferous of Paraná Basin, Brazil)." Terr Plural 15 (2021): e2117741. http://dx.doi.org/10.5212/terraplural.v.15.2117741.029.
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The sedimentary layers of Anitápolis, Santa Catarina, were the subject of relevant discussions about age and paleoenvironment in the first half of the 20th century. Today they are correlated to the ritmites from Itararé Group, but some of the fossils that are part of these studies were not subsequently revised. This is the case of Oliveirania santa catharinae (sic) Maury 1927, a species originally attributed to annelids, and the ichnofossils attributed to it by association. The Annelida fossils were considered here as pseudofossils of inorganic origin. The ichnofossils attributed to Oliveirania were redescribed as a new ichnospecies, Pterichnus mauryae isp. nov., possibly related to the activity of crustaceans. This is the first occurrence of Pterichnus in Brazil and the oldest in the world.
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Jalowiec, Katarzyna Aleksandra, Martin Andres, Behrouz Mansouri Taleghani, Anne Angelillo-Scherrer, Alicia Rovo, and Johanna A. Kremer Hovinga. "Acquired Hemophilia and Plasma Cell Neoplasms, a Rare Association." Blood 134, Supplement_1 (November 13, 2019): 4930. http://dx.doi.org/10.1182/blood-2019-128048.
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Acquired hemophilia A (AHA) is a rare autoimmune disease caused by circulating autoantibodies inhibiting coagulation factor VIII (FVIII), leading to a clinically significant bleeding diathesis. While in half of AHA cases, no underlying cause is identified, in the other half an association with autoimmune diseases, cancer, the use of certain drugs, pregnancy or the post-partum period is found. We present a case with severe bleeding in which AHA was diagnosed and subsequently a smoldering myeloma was found as underlying disease (case 16, Table 1). We conducted a systematic review of the literature in PubMed looking for the association of AHA and plasma cell neoplasm (PCN) (key words used: hemophilia, inhibitor, factor VIII, myeloma, plasma cell disorder or neoplasms, smoldering myeloma, MGUS, monoclonal gammopathy, paraprotein) and identified 15 additional cases. Description of the cases, sequence of occurrence of both diseases, their treatment, evolution and outcome are here analyzed (Table 1). We found that patients having AHA and PCN were more often males (9/16, 56%), had a median age of 61.5 (range 43-87) years at AHA diagnosis. The most common pattern of bleeding was a soft tissue bleeding. In two cases, AHA was diagnosed after excessive post-operative bleeding, in one patient following a life threatening pericardial bleeding and a hemarthrosis. AHA with active bleeding was the presenting sign in 6 cases (38%) (Table 1, cases 4, 5, 6, 10, 13, 16), in search for an underlying diseases, a PCN was diagnosed subsequently. In the other 10 cases, AHA was diagnosed after PCN. In 3 of them, the occurrence of AHA was interpreted to be secondary to multiple myeloma treatment; the implicated drugs were interferon alpha in one and lenalidomide in two cases. Information about the type of monoclonal gammopathy was available in 11 cases; no particular type of paraprotein or clonal light-chain was discernable. Factor concentrates were used in 12 cases to treat relevant bleedings. Further treatment of AHA consisted of immunosuppression with steroids (N=4), steroids in combination with cyclophosphamide (N=5), or cyclophosphamide alone (N=1). Rituximab was used in 3 cases. Plasma exchange to remove FVIII antibodies was performed in 2 cases, and immunoadsorption was done in our patient. Different therapy regimens were used to treat the underlying PCN over the years (Table 1). At the time of reporting 13 patients were alive, while 2 of 3 patients who died, died of bleeding complications. Information on outcome of AHA and/or PCN was available for 9 of 13 survivors: 6 had normal coagulation tests, while FVIII activity was mildly reduced in two. PCN was in complete and partial remission in 7 and 2 cases, respectively (table 1). Management of AHA is based on four pillars: avoidance of procedures that may have induced bleedings, control of bleeding, inhibitor eradication and treatment of the underlying disease. Our case, together with those described in the literature, emphasizes the possibility of PCN as an underlying cause of AHA. Accordingly, diagnostics including protein-electrophoresis, immune-fixation and free light chains should be considered in patients with AHA. In our experience, early intervention with immunoadsorption can be lifesaving in cases with high FVIII inhibitor titers. The occurrence of excessive unexplained bleeding in PCN should raise the suspicion of secondary AHA and trigger the investigation of coagulations tests. Whether PCN treatment alone can control AHA in these cases remains open, 11/16 (69%) of the reported cases received treatment for both diseases. Disclosures Jalowiec: Amgen: Other: Travel grant; Pfizer: Other: Travel grant; Novartis: Other: Travel grant. Andres:AbbVie: Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees; Roche: Other: Travel support ; Gilead: Other: Travel support ; Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Other: Travel support ; Mundipharma: Other: Travel support ; AbbVie: Other: Travel support; Celgene: Other: Travel support . Kremer Hovinga:CSL-Behring: Honoraria, Other: Honoraria go to employer (Insel Gruppe AG, Department of Hematology); Ablynx/Sanofi: Consultancy, Honoraria, Other: Honoraria go to employer (Insel Gruppe AG, Department of Hematology); Roche: Honoraria, Other: Honoraria go to employer (Insel Gruppe AG, Department of Hematology); Shire: Consultancy, Other: Honoraria go to employer (Insel Gruppe AG, Department of Hematology), Research Funding; Siemens: Honoraria, Other: Honoraria go to employer (Insel Gruppe AG, Department of Hematology).
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Sulikan, Sulikan. "Pengaruh Peregangan – Pemanasan dan Pemanasan – Peregangan Terhadap Kecepatan Lari 54,86 Meter (60 Yard)." Paradigma: Jurnal Filsafat, Sains, Teknologi, dan Sosial Budaya 24, no. 2 (September 11, 2018): 1–8. http://dx.doi.org/10.33503/paradigma.v24i2.468.
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The purpose of the the research is to know the effectiveness of the influence of stretching-up and warming-up-stretching toward the velocity of 60 yard dash. Population used are the students ( male ) of IKIP Budi Utomo Malang S1 program especially the ffth semester. Here the writer takes 80 students as samples from 178 students ramdomly. The samples are divided into 4 gruops by matching them that each group consists of 20 students.The kind of research experiments is using the design of the study latin square. The experiments is done about 4 weeks, once a week. That uses four treatmen as follow : treatment A, B, C and D. Each group is treated differently a week, so in 4 weeks all group will have same 4 kind of treatment. Tehnik collecting data obtained from pre-test and post-test that carried on four times.The analysis of data obtained Anava and “ t “ test which use the value of signifcant 5 % and 1 %. From the analysis of data above here the result : There is different influence that is very signifcant among treatment A, B, C, D in increasing the velocity of the 60 yard dash. Conclusion the influence of stretching-warning-up is more effective in increasing the velocity of 60 yard dash than the warming-up – stretching.
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Conte, Benedetta, Alessandra Fabi, Francesca Poggio, Eva Blondeaux, Chiara Dellepiane, Alessia D’alonzo, Giuseppe Buono, et al. "T-DM1 EFFICACY AND ACTIVITY IN HER2-POSITIVE METASTATIC BREAST CANCER PATIENTS PROGRESSING AFTER FRONTLINE TAXANE PLUS PERTUZUMAB AND TRASTUZUMAB: AN ITALIAN MULTICENTER OBSERVATIONAL STUDY OF THE GRUPPO ITALIANO MAMMELLA (GIM) STUDY GROUP." Breast 48 (November 2019): S45. http://dx.doi.org/10.1016/s0960-9776(19)30674-5.
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Rossi, Maurizio, Alice Plutino, Andrea Siniscalco, and Alessandro Rizzi. "Teaching color and color science: the experience of an international master course." Electronic Imaging 2020, no. 15 (January 26, 2020): 165–1. http://dx.doi.org/10.2352/issn.2470-1173.2020.15.color-163.
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There are not many international courses that teach color science applied to non-technical fields. Here, we want to present the experience from a master course organized by Gruppo del Colore – Associazione Italiana Colore and Politecnico of Milano: the Master in Color Design & Technology. It has the aim of training students in the use of color mainly for design purposes, and color science and colorimetry have a big role in the program. The Master is organized in three main phases: Fundamentals, Project Works and Internship. The first part is a series of lectures and frontal lessons that gives to the students the theorical and technical bases to be used in project works practical applications of and internship. In fact, in the second and third parts students are asked to design and develop different applicative design projects. After the first part of Fundamentals training, students will be able to manage disciplines such as colorimetry, visual perception, physics, chemistry, optics and psychology, to build up their future professional career in different fields.
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Sterling, Mark J., David C. Lees, and Dave Grundy. "Xenotorodor stygioxanthus gen. nov., sp. nov. (Lepidoptera, Lecithoceridae, Torodorinae), described from an established population in Spain with discussion of taxonomic placement." Nota Lepidopterologica 46 (March 17, 2023): 103–23. http://dx.doi.org/10.3897/nl.46.101457.
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The family Lecithoceridae is not well represented in the Palaearctic region, with very few taxa in Europe. Here we describe a new genus and species of lecithocerid moth, Xenotorodor stygioxanthus Sterling, Lees & Grundy, gen. nov., sp. nov. The taxon represents a subfamily new to Europe. We consider placement of the genus within Crocanthinae or Torodorinae. We place it in Torodorinae, notwithstanding the reduced gnathos in the male genitalia. DNA barcodes suggest that the taxon belongs within a distal clade of this subfamily. They are over 9.2% pairwise divergent from any hitherto cleanly sequenced Lepidoptera taxon and over 10.1% from nearest taxonomically identified neighbours in Neighbor Joining and ML trees. Characteristics of the DNA barcode and morphology of this new taxon suggest that refinement of synapomorphies for the family and two subfamilies is needed. We have nearly 100 records for this new species since 2020, all from a small area of Southern Spain, close to the Straits of Gibraltar. The life history and early stages of the species are unknown.
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Fabi, Alessandra, Matteo Allegretti, Elena Giordani, Gianluigi Ferretti, Grazia Arpino, Alberto Zambelli, Claudia Omarini, et al. "Abstract OT1-22-01: Liquid biopsy and Ado-trastuzumab emtansine (T-DM1): drug-resistance traits in the blood of HER2-positive metastatic breast cancer patients." Cancer Research 83, no. 5_Supplement (March 1, 2023): OT1–22–01—OT1–22–01. http://dx.doi.org/10.1158/1538-7445.sabcs22-ot1-22-01.
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Abstract Background: A previous study on 22 metastatic breast cancer (mBC) patients (Allegretti et al. Mol Cancer 2021) has associated drug resistance to Ado-trastuzumab emtansine (T-DM1) with two sets of genomic events: a) reversal of HER2 amplification, b) ‘oncogenic replacement’ of HER2 by alternative cancer drivers. To expand on this, we designed GIM21 (Gruppo Italiano Mammella) study. Materials and Methods: GIM21 is a multicentre, prospective study; tumor and circulating total nucleic acids (tTNA and ctTNA) were obtained from primary and metastatic lesions (n=36 altogether), as well as plasma samples (n=501), the latter serially collected coincident with medical imaging re-evaluations. tCNAs/ctTNAs were sequenced by ultra-deep, largely overlapping 50-gene panels on Ion Torrent Gene Studio S5. Ortogonal dPCR validation was by dPCR (Quant Studio 3D). ctTNAs were correlated with clinical readouts and patient outcomes. Results: from September 2018 to January 2022, 50 HER2+ mBC patients receiving T-DM1 as second-line treatment. Median time to progression was 6.5 months (range 2.0-27.2). As previously shown, only a minority of patients (9/50 – 18%) retained residual HER2 amplification in blood at baseline, likely due to HER2 counterselection during previous therapy lines; all of them (9/9) underwent further neutralization during T-DM1 treatment, but an HER2-neutral blood status was reached in only 5 patients. In contrast, 2 HER2-neutral patients acquired HER2 amplification, suggesting either insufficient T-DM1 pressure or an unprecedented clonal escape mechanism. Overall, the circulating HER2 status did not correlate with progression free survival (PFS), further highlighting a loss of clinically relevant HER2 oncogenic dependence. At baseline, 24 circulating mutations were detected in 29/50 (58%) patients, 9 of which did not overlap with tissue mutations. Of note, carrying a given aberration in either blood or tissue resulted in outcome trends (p=0.16), but no clear association with therapeutic response. Rather, it was serial monitoring (appearance of any aberration in the blood) that predicted a dismal clinical outcome in 16/41 (39%) patients, with a median time to progression of 2.8 months (2.2-3.9). Unfortunately, liquid biopsy (LB) was confirmed to miss most patients developing brain (3/3 patients) or skin (2/3 patients) metastases. Most circulating alterations present at progression (40/60) were actionable (OncoKB level < 3B) in 34/41 (82.9%) patients, suggesting that LB may guide therapeutic strategies in post-T-DM1 settings. Conclusions: GIM21 trial showed that LB accurately predicts clinical outcome and reveals actionable drivers of T-DM1 escape. The final analysis are ongoing. Citation Format: Alessandra Fabi, Matteo Allegretti, Elena Giordani, Gianluigi Ferretti, Grazia Arpino, Alberto Zambelli, Claudia Omarini, Ida Paris, Andrea Botticelli, Emilio Bria, Antonella Palazzo, Stefania Gori, Francesco Cognetti, Patrizio Giacomini. Liquid biopsy and Ado-trastuzumab emtansine (T-DM1): drug-resistance traits in the blood of HER2-positive metastatic breast cancer patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-22-01.
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Möbus, Volker. "Adjuvant Dose-Dense Chemotherapy in Breast Cancer: Standard of Care in High-Risk Patients." Breast Care 11, no. 1 (2016): 8–12. http://dx.doi.org/10.1159/000444004.
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Meta-analyses persistently confirm the superiority of dose-dense chemotherapy in comparison with standard chemotherapy. In contrast, individual studies have shown conflicting results. These may be explained by different risk profiles of the treated patient populations. Some trials show a significant advantage in disease-free survival (DFS) and overall survival (OS) in the estrogen receptor (ER)-negative population only, whereas trials with high-risk populations like GIM-2 (Gruppo Italiano Mammella) and AGO-iddETC (Arbeitsgemeinschaft Gynäkologische Onkologie, intense dose-dense epirubicin, paclitaxel, and cyclophosphamide) show a significant superiority in DFS and OS for both, ER-negative and ER-positive patients even after 7 and 10 years, respectively, of follow-up. In contrast, the 10-year follow-up data of the E1199/Intergroup trial no longer showed any superiority of weekly paclitaxel for ER-positive/HER2-negative patients; superiority was observed in the triple-negative subgroup only. Although a direct head-to-head comparison is missing, iddETC or 4 cycles each of dose-dense epirubicin/cyclophosphamide followed by paclitaxel are the preferred adjuvant regimens for patients at risk. Patients with ≥ 4 positive lymph nodes should preferentially be treated with iddETC.
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Reusswig, Fritz. "Landwirtschaft und Klimaskepsis in populistischen Zeiten." GAIA - Ecological Perspectives for Science and Society 33, no. 1 (May 1, 2023): 132–35. http://dx.doi.org/10.14512/gaia.33.1.3.
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Welche Rolle spielen sozio-demografische und lokale Umweltfaktoren für die Klimawandelwahrnehmung? Der hier besprochene Artikel von Landwehr et al. stellt interdisziplinäre Befunde zu dieser Frage vor, die besonders mit Blick auf die Gruppe der Landwirt(inn)e(n) interessant sind. Die Befunde werfen aber auch Fragen zum Abstraktionsgrad der Klimawahrnehmung, der Rigidität sozialer Identität, der Rolle der Medien und der Zielgruppenstrategie auf. Im Kontext der jüngsten ,,Bauernproteste“ und populistischer Narrative folgert der Autor dieser Reaktion, dass in künftigen interdisziplinären Forschungsprojekten zur Klimawahrnehmung auch politische Variablen und die Relevanz populistischer Diskurse untersucht werden sollten.What role do socio-demographic and local environmental factors play in the perception of climate change? The article of Landwehr et al. to be discussed here presents interdisciplinary findings on this question, which are particularly interesting regarding the group of farmers. However, the findings also raise questions about the degree of abstraction of climate perception, the rigidity of social identity, the role of the media and the strategy of targeting. In the context of recent “farmer protests” and populist narratives, the author of this response concludes that future interdisciplinary research projects on climate perceptions should also analyse political variables and the relevance of populist discourses.
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Morales-Contreras, José Antonio, Jesús Arturo Ruiz-Quiñonez, Alberto Roblero-Hernández, Gibran Horemheb-Rubio, and Samuel Suarez Mendez. "A single BNT162b2 dose protects against SARS-CoV-2: A case report of a family cluster of COVID-19." Revista Biomédica 32, no. 3 (September 1, 2021): 172–76. http://dx.doi.org/10.32776/revbiomed.v32i3.912.
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Background. Coronavirus 2019 (COVID-19) disease is an infectious disease caused by the virus "Severe Acute Respiratory Syndrome Coronavirus 2" (SARS-CoV-2). This virus generated a pandemic in 2020 and has affected millions of people worldwide. Facing the need to prevent its contagion, the vaccine BNT162b2 was approved in December 2020 in Mexico and started administered in healthcare workers. Case presentation. We presented here, two healthcare workers vaccinated with one single dose of BNT162b2, who lives in a family nucleus with high transmission rate of SARS-CoV-2. These healthcare workers, identified in the manuscript as patient E and F, were asymptomatic and their real-time RT-PCR test for SARS-CoV-2 resulted negative, while the rest of the family (patients A-D) were SARS-CoV-2 positive. The antibody titers IgG anti-spike of patient F (after the second dose; 1080 Au/mL) turned out greater than patient E (before the second dose; 37.1 Au/mL). Discussion. To our knowledge this is the first case report of the protective effect of single BNT162b2 vaccine dose in the context of high transmission rates within a family nucleus. Despite changes induced by BNT162b2 in the antibody titers with single or double dose vaccination, a single dose of BNT162b2 showed to be sufficient for immunization of patients against COVID-19.
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Marchioli, Roberto, Guido Finazzi, Giorgina Specchia, Arianna Masciulli, Maria Rosaria Mennitto, and Tiziano Barbui. "The CYTO-PV: A Large-Scale Trial Testing the Intensity of CYTOreductive Therapy to Prevent Cardiovascular Events in Patients with Polycythemia Vera." Thrombosis 2011 (May 17, 2011): 1–9. http://dx.doi.org/10.1155/2011/794240.
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Polycythemia vera (PV) is a chronic myeloproliferative disorder whose major morbidity and mortality are thrombohaemorragic events. Current guidelines advise maintaining hematocrit (HCT) level below 45% in males and 42% in females. Such targets lean on pathophysiological reasoning, while evidence from ECLAP and PVSG-01, the two largest prospective studies in this disease, suggests no difference in the rate of thrombosis in patients maintained at different HCT values below 50%–52%. Cytoreductive therapy in PV (CYTO-PV) is a multicenter, randomized, and controlled trial assess the benefit/risk profile of cytoreductive therapy with phlebotomy or HU aimed at maintaining HCT < 45% versus maintaining HCT in the range 45%–50%. CYTO-PV is being conducted in the framework of the Gruppo Italiano Malattie Ematologiche nell'Adulto (GIMEMA) and is funded by the Italian Drug Agency (AIFA). It is an independent trial with broad recruitment criteria to mimic clinical practice. We describe here the study and its advancement status. Conclusions. Clinical research in rare disease can be carried out with limited funds, provided a research hypothesis is felt as clinically relevant by a scientific community willing to share knowledge on the outcome of clinical practice, thus producing scientific results useful to improve treatment and prognosis of patients.
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Frolov, Dmitrij. "Reflections on Osip Mandelstam’s Poem “Erected on a Wet Stone …” (1909)." Izvestiia Rossiiskoi akademii nauk. Seriia literatury i iazyka 82, no. 5 (2023): 15. http://dx.doi.org/10.31857/s160578800028323-1.
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The poem “Erected on a wet stone …” was sent in the Autumn of 1909 first to Max Voloshin and them to Vyacheslav Ivanov and is part of “poems in letters” which were only published in the second half of 20th century. The central theme of the poem is the juxtaposition of love and death. Cupid finds himself standing on a tombstone (“green moss and wet stone”) and being surprised by what he discovers tries to avenge on death through love (“illegal flame of the heart”). The poetics of the poem represents another step in the development of Mandelstam’s inherent technique of subtexts and contexts. The “mentioning keys&8j1; here are combinations of nouns with uncommon adjectives (“illegal flame&8j1;, “naive valleys&8j1;, etc.), as well as pairs of rhymes: “nagoi – nogoi” (naked – foot), “kamen – plamen” (stone – flame), “grubiy – gubi” (rough – lips). The subtexts of the poem might be read on two levels, so that the motifs of classical poetry shine through the symbolist associations, linking together the poetry of the Russian Golden and Silver Ages. The key image of Cupid for the poem (the only context in the author's poetry) has, apparently, a literary origin.
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Кутырёва-Чубаля [Kutyriowa-Czubala], Галина [Galina]. "Лексика песенных зачинов в белорусской свадьбе: семантика, структурные трансформации (на примере одной группы текстов)." Acta Baltico-Slavica 40 (December 28, 2016): 291–309. http://dx.doi.org/10.11649/abs.2016.012.
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Lexical Forms of Song’s Incipits in Belarusian Wedding Cycle: Semantics, Structural Transformations (an Example of One Type of Texts) In the context of the study on dynamic typology and dialectal features of Belarusian folk songs, the paradigm of texts relating to the episode when the Bride parts with her parents is considered here. Such texts have the same lexical and poetic basis; are characterized by common type of incipit in different variants. All of these texts depict an dramatic for the Bride moment of “intrusion” into her backyard “an alien” family – the Groom’s family. Different versions of this incipit have been noticed within the large territory of Belarus and on the frontier (Latvia, Poland). Structural transformations of this type of incipits are manifested by reduction or, quite the opposite, by adding (affixation) syllables in verses. It is conditioned by non-verbal semantics expressed through vocalic rhythmic – the superiority of recitation elements or motor and somatic dynamics. Expansion of an incipit verses by adding to the initial word its rhymed synonym is also a typical phenomena.Diachrony of a given paradigm texts is also revealed by comparing the texts related thematically to the wedding moment mentioned above. A large number of these texts are abridged versions (a middle and a final part) of full texts of paradigm in question. A song in the abbreviated version begins with the culminative part and omits the metaphorical and descriptive initial part (such transformations can be observed in the periphery districts of a radical area). Accordingly, in such a case a different stanza fulfills the incipit function. The method of dynamic typology is applied while analyzing various texts that belong strictly to the same syllabic and rhythmic paradigm. It is a promising approach to study on linguo-musical dialects and diachronic changes in folk song language. Leksyka incipitów białoruskich pieśni weselnych: semantyka, transformacje strukturalne (na przykładzie jednej grupy tekstów)W kontekście badań typologii dynamicznej oraz cech dialektalnych białoruskiej pieśni ludowej rozpatrujemy paradygmat tekstów dotyczących epizodu rozstawania się panny młodej z rodzicami. Są to teksty o tym samym podłożu leksykalno-poetyckim, które charakteryzuje wspólny typ incipitu w różnych jego wariantach. Wszystkie one symbolizują dramatyczny dla panny młodej moment „wtargnięcia” na jej podwórko „obcego” rodu – rodu narzeczonego. Metafora ta zawarta jest w formule incipitu. Warianty formuły zanotowano na znacznym obszarze Białorusi oraz na terenach przygranicznych (Łotwa, Polska). Transformacje strukturalne tego typu incipitów polegają na redukcji lub rozrastaniu (afiksacji) składu sylabowego wersolinii. Wszystko to jest uwarunkowane semantyką pozawerbalną, wyrażoną przez rytmikę wokaliczną – z przewagą albo elementów deklamacyjności, albo dynamiki motoryczno-somatycznej. Charakterystyczne jest również poszerzenie wersu incipitu za pomocą dodawania do początkowego wyrazu synonimu rymowanego.Diachronia tekstów danego paradygmatu ujawnia się także przy zestawieniu tekstów tematycznie związanych z tymże epizodem wesela. Spora liczba tych tekstów przedstawia wersję skróconą – środkowy i końcowy fragmenty – tekstu pierwotnego danej grupy. Pieśń w wersji skróconej rozpoczyna się od punktu kulminacyjnego, z pominięciem metaforyczno-narracyjnej części wstępnej. Odpowiednio rolę incipitu pełni tu inna strofa. Teksty w wersji skróconej lokalizują się na peryferiach areału. Metodę dynamicznej typologii pieśni stosujemy do opisu tekstów różnych gatunków, o różnej tematyce, jednak należących ściśle do tego samego paradygmatu sylabo-rytmicznego. Otwiera to nowe perspektywy w badaniach dialektów lingwo-muzycznych oraz zmian diachronicznych w języku pieśni ludowej.
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Trojanowska, Maria. "Wizerunek herbu miasta Lublina w źródłach archiwalnych z XV–XVIII wieku." Studia Archiwalne 4 (2017): 11–29. http://dx.doi.org/10.4467/17347513sa.17.002.14514.
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W artykule zostały zebrane i opisane źródła ikonograficzne do dziejów herbu miasta Lublina z XV–XVIII w. przechowywane w zasobie Archiwum Państwowego w Lublinie. Wizerunki tego herbu podzielono na trzy grupy w zależności od rodzaju źródła i miejsca występowania znaku. Należą do nich: wyobrażenia na pieczęciach miasta, superekslibrisy na oprawach ksiąg miejskich i zdobienia malarskie o tematyce heraldycznej występujące na kartach tych ksiąg. Najstarsze wizerunki herbu Lublina zachowały się na pieczęciach z początku XV w., które z uwagi na swój urzędowy charakter są też najcenniejszym źródłem heraldycznym. Przedstawiony na nich herb, zarówno w swojej budowie, jak i stylistyce rysunku, był akceptowanym przez władze miejskie znakiem miasta. Z kolei pierwsze barwne wyobrażenia herbu Lublina, ważne dla poznania barw heraldycznych, pochodzą dopiero z pierwszej połowy XVII w. The Image of Lublin’s Coat of Arms in Archival Sources of 15th–18th Centuries The article has collects and described iconographic fifteenth-eighteenth century sources to the history of the Lublin coat of arm, which are kept in the State Archive in Lublin. The images of the coat of arms have been divided into three groups depending on the sort of the source and the place of its occurrence. They include: images on the seals of the town, super-bookplates on the bindings of city registers, and heraldic painting decorations present on the pages of these volumes. The oldest images of the Lublin coat of arms were preserved on seals from the beginning of the fifteenth century which, considering their official character, are also the most precious heraldic source. The coat of arms presented on them, both in its structure and the style of the drawing was the mark of the city, accepted by its authorities. However, the first color images of Lublin’s coat of arms, important for recognizing heraldic colors, come from the first half of the eighteenth century.
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Dojwa-Turczyńska, Katarzyna. "Stosunek Polaków do migrantów. Refleksje socjologiczne w świetle wybranych badań empirycznych." Rocznik Europeistyczny 2 (September 27, 2016): 61–82. http://dx.doi.org/10.19195/2450-274x.2.5.
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Kryzys migracyjny roku 2015 można rozpatrywać z różnych perspektyw. Jedną z nich jest płaszczyzna społeczna, która w niniejszym artykule odnosi się do stosunku mieszkańców danego państwa do kwestii uchodźców. Tym społeczeństwem są Polacy. Generalnie stosunek Polaków do innych wedle badań porównawczych w latach 2002–2012 był korzystny. Wśród Europejczyków Polacy sytuowali się na stosunkowo wysokich pozycjach tolerancji dla tych, którzy w Polsce będą szukać schronienia bądź też zdecydują się tu żyć. Badania sondażowe pokazywały także relatywnie bardziej przychylne dla innych postawy Polaków względem społeczeństw Grupy Wyszehradzkiej. Badania ilościowe realizowane w 2015 r. pokazują, że w stosunku do innych społeczeństw Polacy nadal reprezentują postawy stosunkowo przychylne migrantom. Niemniej jeśli analizuje się w tym zakresie zmiany postaw w stosunku do poprzedniego badania, widoczne staje się coraz większe zamknięcie Polaków na obcych i niechęć do ich przyjmowania.The attitude of Polish citizens toward migrants. Socjological reflections in the light of chosen empirical research.The 2015 migration crisis can be viewed from various perspectives. One of them is the social level, which in this paper refers to the attitude of a country’s inhabitants to the issue of refugees. Here, Poles comprise such a society. Generally, Poles’ attitude to others, according to comparative studies in the period 2002–2012, was positive. Among Europeans, Poles occupied relatively high positions in terms of tolerance towards those that would seek refuge or decide to live in their country. Sample surveys also showed relatively more sympathetic attitudes of Poles to others compared to other societies within the Visegrad Group. Quantitative studies conducted in 2015 show that compared to other societies, Poles still present relatively sympathetic attitudes to incomers. However, if we analyse changes of attitudes compared to the previous survey, we can see that Poles are increasing closed to foreigners and unwilling to accept them.
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Zalewska, Anna. "FATAL IMMORTALITY. THE BLACKSMITH MOTIF IN POLISH FOLKTALES." Folklore: structure, typology, semiotics 5, no. 1 (2022): 54–68. http://dx.doi.org/10.28995/2658-5294-2022-5-1-54-68.
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Numerous texts of Slavic folklore, including the folk fairy tale, reflect ideas concerning the demonic properties of non-agricultural professions. These include, in particular, the hero of this analysis, namely the blacksmith. The primary research objective involves illustrating the specificity of the fairy tale image of a blacksmith. The peculiarities of his behaviour, forms of interaction with other characters, the attributes of the craft he mastered, the functions he performs, as well as his posthumous status will be taken into account. The fairy tale image of the blacksmith largely corresponds to his reception in traditional culture, in which he was classified as “stranger among his own” due to his specialized knowledge and skills. Therefore, the protagonist of these considerations practises magic, parleys with impure forces, abuses alcohol, and also excessively strives for material goods. Moreover, he shows a disrespectful attitude towards death, preventing it from fulfilling its duty. Because death is seen as a guarantee of harmony and balance, the blacksmith’s behaviour should be considered particularly dangerous, disruptive to the divine order of the world. A fairy tale blacksmith is characterized by the features of a mythological trickster who uses deception to defeat his opponent or gain access to certain goods. As a fraudster and devilish collaborator gaining earthly wealth through the aid of forces from the beyond, the craftsman fits into the rural image of a condemned sinner, which affects his posthumous status. Variants of the T 330A “Kowal i diabli (Śmierć na gruszy)” («Кузнец и черти (Смерть на груше)»; ATU 330 “The Smith and the Devil”) fairy tale plot were used as the source for the analysis
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Luckscheiter, Christian. ",,eine Brücke, ein Band zwischen den Völkern“. : Hermann Wendels Vortrag ,,Der Rhein. Deutschlands oder Europas Strom?“ von 1927 und seine (,jüngst-elsässischen‘) Kontexte." Zeitschrift für Germanistik 33, no. 3 (January 1, 2023): 524–42. http://dx.doi.org/10.3726/92174_524.
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Abstract Inmitten der nationalistischen ,,Kämpfe um den Rhein“ der 1920er Jahre bezeichnete Hermann Wendel 1927 den Fluss als eine Brücke zwischen den Ländern, durch die das Übernationale an seinen Ufern Wirklichkeit geworden sei. Die ,Formulierungschance‘ Wendels findet sich in einem spezifischen Kontext, der in die Zeit vor 1914 zurückführt: Wendel war Mitglied der 1901 in Straßburg gegründeten Gruppe ,,Das jüngste Elsaß“. Die Diskussionen der Nachkriegsjahre um das deutsch-französische Verhältnis wurden hier bereits zwei Jahrzehnte früher im Zusammenhang mit der sogenannten elsässischen Frage geführt. Um Frankreich und Deutschland einander anzunähern, propagierten die Gruppenmitglieder in ihren Texten ein übernationales Denken, für das sie das Rhein-Brücken-Motiv wiederholt einsetzten.In the midst of the nationalist ,,struggles around the Rhine“ of the 1920s, Hermann Wendel in 1927 described the river as a bridge between the countries through which the supranational had become a reality on its banks. Wendel’s ,formulation chance‘ is found in a specific context that leads back to the time before 1914: Wendel was a member of the group ,,Das jüngste Elsaß“ founded in Straßburg in 1901. Here, the discussions of the post-war years about the Franco-German relations had already been held two decades earlier in connection with the so-called Alsatian question. In order to bring France and Germany closer together, the group members propagated supranational thinking in their texts, for which they repeatedly used the motif of the Rhine as a bridge.
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Alderton, Zoe. "“Nothing Tastes as Good as Skinny Feels”." International Journal for the Study of New Religions 12, no. 2 (June 13, 2024): 157–84. http://dx.doi.org/10.1558/ijsnr.27320.
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There has always been something compelling about extreme bodies. Kate Moss exemplifies “the waif,” a body type both frightening and appealing. She is one of the most common celebrities discussed on pro-anorexia (or, pro-ana) websites. To explore the connection between Moss’s body and pro-ana participation, this article examines the potential for an extraordinary body to solidify the aims of an extremist group and to draw in new members. Her unusually slender form affirms this pro-starvation cluster by physically representing the emotional distress that lies at its core. There is no conclusive evidence that Moss suffers from an eating disorder, and she has been open about discouraging people from starving themselves to look like her. Nevertheless, she has been framed as a unique icon in the pro-ana sphere, despite her personal intent, due to the extreme nature of her body. She helps members to express mental illness and severe emotional distress via an emaciated frame and grungy-but-cool aesthetic. She therefore gives people a way to explore sickness and femininity concurrently, which is especially relevant for young women with eating disorders. The pro-ana community has adopted her as a cult icon for these reasons. Here, I analyse this process using Rodney Stark and William Sims Bainbridge’s sociological scholarship on the social role of religion broadly and “cult formation” more specifically. This raises important questions about consent in cult formation and the role required of a leader.
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Adirosi, Elisa, Federico Porcù, Mario Montopoli, Luca Baldini, Alessandro Bracci, Vincenzo Capozzi, Clizia Annella, et al. "Database of the Italian disdrometer network." Earth System Science Data 15, no. 6 (June 9, 2023): 2417–29. http://dx.doi.org/10.5194/essd-15-2417-2023.
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Abstract. In 2021, a group of seven Italian institutions decided to bring together their know-how, experience, and instruments for measuring the drop size distribution (DSD) of atmospheric precipitation, giving birth to the Italian Group of Disdrometry (in Italian named Gruppo Italiano Disdrometria, GID, https://www.gid-net.it/, last access: 16 May 2023). GID has made freely available a database of 1 min records of DSD collected by the disdrometer network along the Italian peninsula. At the time of writing, the disdrometer network was composed of eight laser disdrometers belonging to six different Italian institutions (including research centres, universities, and environmental regional agencies). This work aims to document the technical aspects of the Italian DSD database consisting of 1 min sampling data from 2012 to 2021 in a uniform standard format defined within GID. Although not all the disdrometers have the same data record length, the DSD data collection effort is the first of its kind in Italy, and from here onwards, it opens up new opportunities in the surface characterization of microphysical properties of precipitation in the perspective of climate records and beyond. The Version 01 GID database can be downloaded at https://doi.org/10.5281/zenodo.6875801 (Adirosi et al., 2022), while Version 02 can be downloaded at https://doi.org/10.5281/zenodo.7708563 (Adirosi et al., 2023). The difference among the two versions is the diameter–fall velocity relation used for the DSD computation.
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Аврамова [Avramova], Цветанка [TSvetanka]. "Словообразувателни модели на жителските имена (nomina habitatorum) в съвременния български и чешки език." Studia z Filologii Polskiej i Słowiańskiej 51 (December 31, 2016): 45–57. http://dx.doi.org/10.11649/sfps.2016.004.
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Word-formation models of inhabitant nouns (nomina habitatorum) in contemporary Bulgarian and CzechThe article analyses the word-formation models (WFM) of the nomina habitatorum in Bulgarian and Czech. The term WFM is very similar to, but not conterminous with, the concept of word-formation type (WFT) as defined by Miloš Dokulil. WFT is understood here as superordinate in relation to WFM. WFT is defined by the same set of properties as WFM but differs from the latter according to the character of the formant; while in FM the character is physical (formal, based on sound), in WFT the character of the formant is functional and structural. The formant assigns the derivative to affixation, paradigmatic or composition word-formation pattern. As lexemes naming a person in accordance with a particular place, the nomina habitatorum constitute a subcategory within the word-formation category of nouns of belonging (nomina pertinentia). The word-formation meaning of nomina habitatorum can be represented by the paraphrase “X belongs to Y,” where X is a person and Y – a place in a broad sense. Modele słowotwórcze rzeczowników oznaczających nazwy mieszkańców (nomina habitatorum) we współczesnym języku bułgarskim i czeskimArtykuł analizuje modele słowotwórcze rzeczowników z klasy nomina habitatorum we współczesnym języku bułgarskim i czeskim. Zakres pojęciowy terminu „model słowotwórczy” jest zbliżony do zakresu pojęcia „typ słowotwórczy” zaproponowanego przez Miloša Dokulila, nie jest jednak z nim tożsamy. Typ słowotwórczy (TS) rozumiany jest tutaj jako pojęcie podrzędne wobec modelu słowotwórczego (MS). TS jest określany przez ten sam zestaw właściwości co MS, różni się jednak od niego charakterystyką formantu. Podczas gdy w MS formant charakteryzuje się wedle cech fizycznych (formalnych, opartych na brzmieniu), w TS charakterystyka formantu oparta jest na kryteriach funkcjonalnych i strukturalnych. Na podstawie formantu derywat zaliczony zostaje do określonego wzorca słowotwórczego: afiksalnego, paradygmatycznego lub kompozycyjnego. Jako leksemy nadające danej osobie określenie związane z konkretnym miejscem nomina habitatorum stanowią podkategorię słowotwórczej kategorii nazw przynależności (nomina pertinentia). Znaczenie słowotwórcze rzeczowników z grupy nomina habitatorum można wyrazić parafrazą „X należy do Y”, gdzie X to osoba, a Y – szeroko pojęte miejsce.
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Perachino, Marta, Eva Blondeaux, Michelino De Laurentiis, Grazia Arpino, Fabio Puglisi, Alessandra Fabi, Stefania Gori, et al. "Impact of young age at diagnosis on survival outcomes in patients with early breast cancer according to tumor subtype: Pooled analysis of 5 randomized clinical trials from the Mammella InterGruppo (MIG) and Gruppo Italiano Mammella (GIM)." Journal of Clinical Oncology 42, no. 16_suppl (June 1, 2024): 523. http://dx.doi.org/10.1200/jco.2024.42.16_suppl.523.
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523 Background: The incidence of breast cancer (BC) among young patients is increasing. Historically, young age itself has been recognised as a poor prognostic factor for BC. However, there is limited evidence regarding the impact of age at diagnosis and on survival outcomesaccording to tumor subtype. Methods: We collected individual patient (pt)-level data from newly diagnosed stage I to III BC pts participating in 5 randomized clinical trials conducted by Mammella InterGruppo (MIG) and Gruppo Italiano Mammella (GIM) study groups. Patients were categorized into the following age groups based on their age at BC diagnosis: ≤40, 41-50, 51-60, 61-70, >70 years (yr). Multivariable Cox proportional hazards models were used to assess the relationship between age and breast cancer–free interval (BCFI) and breast cancer specific survival (BCSS). Results: 8,338 pts with stage I to III BC were included in the study: 778 (9%) aged ≤40 years, 1629 (20%) 41-50 years, 2,595 (31%) 51-60 years, 2,435 (29%) 61-70 years, and 901 (11%) >70 years. Compared to older, young pts were more likely to have ductal tumors as histology, larger than 2 cm, with nodal involvement, G3 and triple negative or HER2 positive subtypes (p<0.001). With a median follow-up of 9.0 years (IQR 5.5-14.4), 2,161 BCFI and 927 BCSS events were observed in the overall population. Pts ≤40 years at diagnosis had greater risk of reporting BC event (adjusted hazard ratio (adjHR) for BCFI 1.27, 95% CI 0.93-1.74) compared to pts aged 51-60 years (reference group), while pts 41-50 years had a lower risk (adjHR 0.74, 95%CI 0.55-0.99). Pts aged ≤40 years presented some evidence of a lower risk of BCSS events (adjHR 0.80, 95%CI 0.50-1.26) compared to pts aged 51-60 years, while pts aged 41-50 years had the lowest risk (adjHR 0.50, 95%CI 0.32-0.78). There was evidence of interaction between age and tumor subtype, nodal status both for BCFI and BCSS. A significant increase in risk of BC events was observed among pts ≤40 years with hormone-receptor positive/HER2 negative tumors (HR 1.70 for BCFI) and among ≤40 years with node negative tumors (HR for BCFI 2.43). Conclusions: The prognostic significance of young age at diagnosis may vary depending on tumor subtypes and nodal status, indicating poorer outcomes for young pts with hormone-receptor positive/HER2 negative and node negative tumors.
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Blondeaux, Eva, Arlindo R. Ferreira, Francesca Poggio, Fabio Puglisi, Claudia Bighin, Federico Sottotetti, Filippo Montemurro, et al. "Clinical outcomes of patients with breast cancer relapsing after (neo)adjuvant trastuzumab and receiving trastuzumab rechallenge or lapatinib-based therapy: a multicentre retrospective cohort study." ESMO Open 5, no. 4 (August 2020): e000719. http://dx.doi.org/10.1136/esmoopen-2020-000719.
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BackgroundIn the prepertuzumab era, we evaluated the clinical outcomes of patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer who underwent first-line trastuzumab-based or lapatinib-based therapy according to prior exposure to (neo)adjuvant trastuzumab.Materials and methodsIn this multicentre retrospective cohort study conducted in 14 Italian centres of the Gruppo Italiano Mammella, consecutive patients undergoing first-line trastuzumab or lapatinib-based therapy were included. Analyses were performed according to the type of first-line therapy for metastatic disease (trastuzumab or lapatinib). Dichotomous clinical outcomes were analysed using logistic regression and time-to-event outcomes using Cox proportional hazard models controlling for relevant demographic, clinicopathological and therapy characteristics.ResultsOut of 450 patients included in the study, 416 (92%) received trastuzumab and 34 (7.5%) lapatinib. As compared with the trastuzumab cohort, more patients in the lapatinib cohort had a trastuzumab-free interval <1 month (37% vs 13.9%; p=0.017) and brain metastasis as first site of relapse (38.2% vs 9.4%; p<0.001). Among the 128 patients who relapsed after prior (neo)adjuvant trastuzumab, 101 (78.9%) received first-line trastuzumab and 27 (21.1%) first-line lapatinib. The following outcomes were observed with first-line lapatinib or trastuzumab, respectively: overall response rate 45.5% vs 61.3% (p=0.184), clinical benefit rate 68.2% vs 72.5% (p=0.691), median progression-free survival (PFS) 11.4 vs 12.0 months (p=0.814) and median overall survival (OS) 34.7 vs 48.2 months (p=0.722). In patients with brain metastasis as first site of relapse, median PFS was 12.2 vs 9.9 months (p=0.093) and median OS 33.7 vs 28.5 months (p=0.280), respectively.ConclusionsIn patients with HER2-positive breast cancer relapsing after prior (neo)adjuvant trastuzumab, first-line treatment with trastuzumab or lapatinib was not associated with a significant difference in the clinical outcomes. A non-significant trend favouring the use of lapatinib was observed in patients with brain metastasis as the first site of relapse.
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Ferroni, Roberta. "AFFECTIVE AND INCLUSIVE LANGUAGE LEARNING THROUGH WHATSAPP: A CASE STUDY ON TRAINEE TEACHERS AND ITALIAN L2 LEARNERS IN A MULTILINGUAL AND MULTICULTURAL BACKGROUND." Trabalhos em Linguística Aplicada 62, no. 1 (January 2023): 104–20. http://dx.doi.org/10.1590/010318138672210v6212023.
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ABSTRACT The aim of the present study is twofold: 1 to investigate the strategies used by a group of trainee teachers during the implementation via WhatsApp of pre-task activities inspired by the autobiographical approach; 2. to analyse whether and how learners show emotional engagement through online messages, referred here as the ability to express their own personal sphere in the host country’s language. The case study consists of the observation of 900 WhatsApp messages sent over a period of 39 days, aimed at carrying out 9 pre-task activities to enhance the intra-personal emotional sphere. The data were collected during an Italian L2 course designed for students of A2 level according to Common European Framework of Reference for languages (CEFR) with a multilingual and multicultural background and taught by trainee teachers. The quantitative-qualitative survey, carried out on the basis of studies analysing digital communication and supported by the autobiographical approach, shows that pre-tasks offered the community of practice the opportunity to go beyond the teaching activity and to build an affiliate network with emotionally engaging communicative spaces, enriched by iconographic material and stylistically and linguistically refined life stories. From a professional perspective, the study shows the path taken by trainee teachers to acquire skills and competences – stylistic, pragmatic, linguistic, interactional and emotional – necessary to foster forms of affective and inclusive language learning through multimodal resources.
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Bruno, B., M. Rotta, F. Patriarca, D. Mattei, B. Allione, F. Carnevale-Schianca, A. Rambaldi, et al. "A Prospective Phase II Study on Tandem Autografting-Nonmyeloablative Allografting for Newly Diagnosed Myeloma: Final Results of the Gruppo Italiano Trapianto Midollo Osseo." Blood 110, no. 11 (November 16, 2007): 3026. http://dx.doi.org/10.1182/blood.v110.11.3026.3026.
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Abstract The development of nonmyeloablative conditionings has recently reduced the transplant-related mortality (TRM) and extended the eligible age for transplantation up to 65–70 years. From January 2000 to June 2005, 106 newly diagnosed patients younger than 65 years were enrolled in a prospective phase II study at 15 Italian Centers. Fifty-eight were also previously described in a comparison of autografting with allografting based on a genetic randomisation (Bruno et al. N Engl J Med 2007). Here we report on a larger GITMO experience with a longer follow-up. Induction chemotherapy consisted of VAD-based regimens, followed by a cytoreductive autograft with melphalan 200 mg/m2, and by a non-myeloablative 2 Gy TBI-based allograft from an HLA-identical sibling. Graft-vs-host disease (GVHD) prophylaxis included cyclosporin and mycophenolate mofetil. Primary endpoints were overall (OS) and event-free (EFS) survivals. Secondary endpoint was TRM. One-hundred-two (96%) patients, median age 54 (30–65), completed the tandem program whereas 4 withdrew their consent. After a median follow-up of 54 (21–94) months, OS was not reached and median EFS was 35 (31–56) months post-transplant. Incidences of acute grade II-IV GHVD and extensive chronic GVHD were 40% and 50% respectively. Fourteen (13%) patients died from TRM, 14 (13%) from disease progression, 2 from lung cancer (2%) and 1 from lymphoma (1%). Overall response, defined as complete (CR) and partial remission, was 91% (93/102), with 53 patients achieving CR. Overall 39/102 patients relapsed, however only 8/53 of those who reached CR post-transplant. By multivariate-analysis disease response prior to allografting was significantly associated with longer OS (HR 0.27, CI 0.09–0.80, p<0.018) and longer EFS (HR 0.23, CI 0.11–0.49, p<0.001). Interestingly, chronic GVHD was not correlated with either the achievement of post-transplant CR (HR 0.87, CI 0.45–1.65, p<0.66) or its duration (HR 0.79, CI 0.45–1.40, p<0.42). Presence of del(13) was evaluated only in a subset of 39 patients: 13 carried del(13) and 26 did not. OS was not reached in the patients without del(13) and was 52 months in patients with del(13) (p=0.32), however EFS was not reached in the patients without del(13) whereas was 27 months for patients with del(13) (p=0.04). Given the encouraging results, the design of prospective studies that incorporate new drugs to cytoreduce the disease pre-transplant and enhance graft-vs.-myeloma are warranted to lower relapse rates and improve clinical outcomes.
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Bengala, C., C. Zamagni, P. Pedrazzoli, P. Matteucci, A. Ballestrero, G. Da Prada, M. Martino, et al. "Cardiac tolerability of trastuzumab in metastatic breast cancer (MBC) patients previously treated with high-dose chemotherapy (HDC) with autologous hemopoietic support: Retrospective analysis from Gruppo Italiano Trapianto Midollo Osseo (GITMO) Solid Tumor Working Party." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 10558. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.10558.
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10558 Background: HER-2 overexpression is associated to a poor prognosis in high-risk and MBC patients treated with HDC. HER-2 status is also a predictive factor of response to trastuzumab: when trastuzumab is administered in combination with or sequentially to chemotherapy, a significant DFS and/or survival improvement has been observed in HER2+ early and MBC. Unfortunately, in both settings, trastuzumab was associated with an increased risk of cardiac dysfunctions (CD). Patients and Methods: In order to evaluate the cardiac safety of trastuzumab after HDC, we have reviewed the clinical charts of HER2-overexpressing MBC patients treated with HDC and trastuzumab at 11 centres of the GITMO group. Age, baseline LVEF, radiation therapy on cardiac area, exposure to anthracycline, single or multiple transplant, high-dose agents, trastuzumab treatment duration were recorded as potential risk factors. Cardiac dysfunction (CD) was defined as: 1) decline of LVEF ≥ 10% to below 50%, 2) decline of LVEF between 5 and 9% to below 50% with symptomatic (NYHA class III-IV) congestive heart failure (CHF), 3) any symptomatic CHF event. Results: Fifty-three patients treated between 1999 and 2005 have been included in the analysis. Median age was 47 years (range 29–66). Median interval between HDC and trastuzumab was 6 months. Median LVEF at baseline was 60.5%; at the end of trastuzumab (data available for 28 patients only) it was 55% (p = 0.01). Five out of the 28 (17.9%) pts experienced CD. Two out of 53 (3.8%) pts developed a symptomatic (NYHA class III) CHF. Age ≥ 50 years was the only factor significantly associated with CD. However age ≥ 50 years and multiple transplant procedure were associated with a significant decline of LVEF (p: 0.02). Conclusion: The incidence of CD is not superior to that reported with trastuzumab after standard chemotherapy. However pts with age ≥ 50 years or receiving multiple course of HDC, should be considered at risk for CD. No significant financial relationships to disclose.
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Orlando, Laura, Francesco Giotta, Margherita Cinefra, Daniele Rizzi, Salvatore Pisconti, Salvatore Del Prete, Mariangela Ciccarese, et al. "When less is better: Safety and efficacy of combination of trastuzumab and continuous low oral dose chemotherapy (HEX) as first-line therapy for HER2-positive advanced breast cancer (ABC)—First early results from a phase II trial on behalf of Gruppo Oncologico Italia Meridionale (GOIM)." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 618. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.618.
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618 Background: Clinical activity of the combination of chemotherapy plus trastuzumab in HER2+ ABC has been well documented. We report the first results in terms of activity and safety of the combination of trastuzumab plus metronomic capecitabine and cyclophosphamide as first line therapy in HER-2 positive ABC. Methods: Patients (pts) at first relapse or with synchronous metastasis, were treated with trastuzumab (4 mg/kg, loading dose 6 mg/kg) plus oral capecitabine (1500mg/daily) and cyclophosphamide (50 mg/daily). Primary end-point was overall response rate (ORR), secondary end-points time to progression (TTP), clinical benefit rate (CBR; PR+ CR + prolonged SD for ≥ 24 weeks) and tolerability. The optimal two-stage design was applied. Results: A total of 31 pts with measurable ABC, tumors scored as +3 positive for HER-2 or FISH +, no pretreated with chemotherapy or trastuzumab for advanced disease have been enrolled, 28 actually valuable for response and toxicity. Median age was 59 years (range 42-87), visceral metastases were present in most patients (61%). Median number of cycles was 12 (range 1-37+). The ORR was 61 % (95% CI, 41-78%), with 1 CR (3.6 %) and 16 PR (57.1%). 9 patients had prolonged SD (32%). The CBR was 82.1% (95% CI , 63%-94%). Five progressions were observed (18%). Median TTP was 7 months (range 2- 19 + months). Ten pts received more than 20 courses. Worst toxicities were grade 2 hand-foot syndrome in 4 pts, grade 2 anemia in 4 pts, grade 2 nausea in 2 pts and diarrhea grade 3 in 1 pt. Cardiac toxicity grade 2 in 1 pts. Alopecia was not reported. Conclusions: Combination of trastuzumab and low dose metronomic oral chemotherapy in HER-2 + breast cancer has shown clinical activity. The tolerability was excellent and allowed the prolonged delivery of the combination. Thus, the patients accrual is ongoing to the pre-set target of 66 patients. Clinical trial information: 2009-017083-16.
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De Muro, Marianna, Ambra Di Veroli, Marco Montanaro, Roberto Latagliata, Cristina Santoro, Massimo Breccia, Michele Cedrone, et al. "Latium (Italy) Epidemiology of Philadelphia Chromosome-Negative Myeloproliferative Neoplasms (MPNs) from 2011 to 2015: A Prospective Analysis from Gruppo Laziale of Ph Negative MPN." Blood 128, no. 22 (December 2, 2016): 5473. http://dx.doi.org/10.1182/blood.v128.22.5473.5473.
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Abstract Background: MPNs including Polycythemia Vera (PV), Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF), are clonal hematopoietic diseases in which the discovery of molecular driver mutations (JAK2, CALR, MPL) has deeply modified diagnostic approach in recent years. To date available data on epidemiology of MPNs and perspective analysis are rare. Our aim is to study the incidence of MPN Ph negative in a specific region of Italy named Latium and its variability across five years. Moreover we prospectively report the general features of our population. Method: We present here the prospective epidemiologic analysis of 1116 adult patients affected by MPNs (PV=289, ET=550, PMF=209) diagnosed according to 2008 WHO criteria, from January 2011 to December 2015 in 15 hematological Centers (5 academic and 10 community-based Hospitals) in Latium. A total of 289 PV, 550 ET and 209PMF were identified. The overall incidence rate of 289PV was 1.0/105 in 2011 and 2012, 1.1/105 in 2013, 0.9/105 in 2014 and 2015. The overall incidence rate of 550ET was 2.0/105 in 2011, 2.4/105 in 2012, 2.2/105 in 2013, 1.8/105 in 2014 and 1,2/105 in 2015 and the overall incidence rate of 209PMF was 0.7/105 in 2011 and 2012, 1.0/105 in 2013, 0.7/105 in 2014 and 0.5/105 in 2015. We have observed also 63 cases of MPNu (36M/32F) and the incidence rate was 0.3/105 in 2011 and 2012, 0.14/105 in 2013, 0.24/105 in 2014 and 0.22/105 in 2015. Baseline features of PV, ET and PMF patients are summarized in table 1. We have also analyzed the presence of comorbidities including obesity, arhythmia and neoplasia observed at the diagnosis in 1.6, 6.2 and 4% of all population, respectively; thirty-five percent of 1116 pts presented other comorbidities such as diabetes, inflammatory bowel disease, renal and liver failure. As thrombotic risk factors we considered diabetes, dislipidemia, smoke, essential hypertension and thrombophilia observed in 11,8, 16,2, 13,2, 51,7 and 3% of total pts, respectively. Conclusions: We confirm in our prospective observational protocol the overall incidence of MPN Ph negative, previously reported in the literature and the major incidence of male gender in PV and PMF, female in of ET. The annual incidence from 2011-2015 in Latium is remained substantially the same during the observation period. The decreasing trend observed in 2015 is probably due to the different update of some Centers that was done in October 2015 not including patients diagnosed in the last two months. Disclosures Latagliata: Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Honoraria; Celgene: Honoraria; Janssen: Consultancy, Honoraria; Shire: Honoraria. Breccia:Pfizer: Honoraria; Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Honoraria; Celgene: Honoraria; Ariad: Honoraria. Cimino:Celgene: Honoraria; Bristol-Mayer: Honoraria.
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Soldato, Davide, Eva Blondeaux, Marco Bruzzone, Silvia Mura, Michelino De Laurentiis, Anna Turletti, Sabino De Placido, et al. "Dissecting the prognostic role of baseline body mass index (BMI) in early breast cancer (BC): Individual patient-level analysis from five mammella interGruppo (MIG) and gruppo italiano mammella (GIM) randomized clinical trials (RCTs)." Journal of Clinical Oncology 41, no. 16_suppl (June 1, 2023): 12067. http://dx.doi.org/10.1200/jco.2023.41.16_suppl.12067.
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12067 Background: Nearly half of patients (pts) are overweight or obese at BC diagnosis (dx). Higher BMI at dx has been associated with cardiometabolic comorbidities, higher risk of severe treatment-related sequelae, and worse quality of life. Previous studies showed inferior survival outcomes among patients with early BC and high BMI, although not consistently. The aim of this study was to explore the prognostic role of BMI at dx using data from five RCTs of adjuvant therapy for early stage BC with long-term follow-up. Methods: Pts with known BMI at dx, randomized in the MIG-1, MIG-5, GIM-2, GIM-3 and GIM-6 phase III RCTs were included. BMI was categorized as lean ( < 25 kg/m2), overweight (25-30 kg/m2) or obese (≥ 30 kg/m2). Outcomes included disease-free survival (DFS), breast cancer free-interval (BCFI) and overall survival (OS). Survival estimates were compared using the Kaplan-Meier method and log-rank test. Multivariable Cox proportional hazard models stratified by trial and relevant prognostic factors assessed associations between BMI and outcomes. Results: Among 7334 pts in the overall population, mean age was 56.4 years (SD 11.2), 67.8% had node-positive disease, 76.9% received chemotherapy and 83.0% endocrine therapy. Most pts were overweight (33.1%) or obese (21.0%) and 45.9% were lean. Higher BMI was associated with older age, larger tumor size, higher nodal status, and HR+/HER2- subtype. At a median follow-up of 10.0 years (IQR 6.1-15.1) there were 2165 DFS, 1674 BCFI and 1354 OS events. Pts with higher BMI had worse DFS and OS (log-rank p = 0.007 and p < .0001, respectively), but similar BCFI (p = 0.48). BMI at dx was an independent risk factor for worse OS, but not for DFS and BCFI (Table). Results in the HR+/HER2- population (n = 4093) were consistent: pts with higher BMI had worse DFS, BCFI, and OS (log-rank p = 0.001, p < .006, and p < .0001, respectively) and BMI at dx was an independent risk factor only for worse OS (aHR [95%CI] 1.06 [0.84-1.32] and 1.31 [1.02-1.67] for overweight and obese vs lean pts, respectively). Conclusions: In this large study of pts with early BC treated in RCTs with long-term follow-up, higher BMI at dx was an independent risk factor for overall mortality but not for BC-specific outcomes. Weight loss interventions may mitigate the detrimental effect of excess body weight on outcomes of BC survivors, including by reducing the burden and risks of associated cardiometabolic comorbidities. [Table: see text]
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Mitry, Emmanuel, Anthony L. A. Fields, Harry Bleiberg, Roberto Labianca, Guillaume Portier, Dongsheng Tu, Donato Nitti, et al. "Adjuvant Chemotherapy After Potentially Curative Resection of Metastases From Colorectal Cancer: A Pooled Analysis of Two Randomized Trials." Journal of Clinical Oncology 26, no. 30 (October 20, 2008): 4906–11. http://dx.doi.org/10.1200/jco.2008.17.3781.
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Purpose Adjuvant systemic chemotherapy administered after surgical resection of colorectal cancer metastases may reduce the risk of recurrence and improve survival, but its benefit has never been demonstrated. Two phase III trials (Fédération Francophone de Cancérologie Digestive [FFCD] Trial 9002 and the European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada Clinical Trials Group/Gruppo Italiano di Valutazione Interventi in Oncologia [ENG] trial) used a similar design and showed a trend favoring adjuvant chemotherapy, but both had to close prematurely because of slow accrual, thus lacking the statistical power to demonstrate the predefined difference in survival. We report here a pooled analysis based on individual data from these two trials. Patients and Methods After complete resection of colorectal liver or lung metastases, patients were randomly assigned to chemotherapy (CT arm; fluorouracil [FU] 400 mg/m2 administered intravenously [IV] once daily plus dl-leucovorin 200 mg/m2 [FFCD] × 5 days or FU 370 mg/m2 plus l-leucovorin 100 mg/m2 IV × 5 days [ENG] for six cycles at 28-day intervals) or to surgery alone (S arm). Results A total of 278 patients (CT, n = 138; S, n = 140) were included in the pooled analysis. Median progression-free survival was 27.9 months in the CT arm as compared with 18.8 months in the S arm (hazard ratio = 1.32; 95% CI, 1.00 to 1.76; P = .058). Median overall survival was 62.2 months in the CT arm compared with 47.3 months in the S arm (hazard ratio = 1.32; 95% CI, 0.95 to 1.82; P = .095). Adjuvant chemotherapy was independently associated with both progression-free survival and overall survival in multivariable analysis. Conclusion This pooled analysis shows a marginal statistical significance in favor of adjuvant chemotherapy with an FU bolus–based regimen after complete resection of colorectal cancer metastases.
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Olivieri, Attilio, Michele Cimminiello, Paolo Corradini, Pasquale Iacopino, Amedea Donelli, Nicola Mordini, Carmine Selleri, et al. "Imatinib as Salvage Therapy for Patients with Refractory cGVHD: the Interim Analysis of the Prospective GITMO* Multicenter Study*Gruppo Italiano Trapianto Di Midollo Osseo." Blood 114, no. 22 (November 20, 2009): 3558. http://dx.doi.org/10.1182/blood.v114.22.3558.3558.
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Abstract Abstract 3558 Poster Board III-495 We recently reported in a pilot study, including 19 adult and pediatric patients affected by refractory cGvHD with fibrotic features, that the administration of Imatinib at low dose was well tolerated and effective, achieving an overall response rate (ORR) of 79% at 6 months; the response has been evaluated according to the modified Curiel Criteria. We report here the preliminary results of an Italian GITMO Multicenter study, aimed to confirm these promising data. Main objective of this study was to assess the response rate, evaluated according to the stringent criteria suggested by the NIH Consensus Conference for cGVHD and to confirm the safety of low dose Imatinib in this setting. Secondary objectives were both clinical and biological: 1-to evaluate the clinical outcome (OS at 1 and 2 years) and quality of life; 2-to test a reliable technique for screening these patients for the presence of stimulating anti-PDGFR antibodies before and after the end of Imatinib treatment. The study was planned as phase 2 trial (optimal two stages Simon design), and enrolled 24 patients with cGVHD, refractory to two or more lines of therapy, including steroids. Nine Italian Centres enrolled 24 adults patients, starting from February 2008 to August 2009; 18 patients are now evaluable for toxicity and for the response at 3 and 6 months; 13 were male and 5 female; the median age was 47 years (range 31-62). The median duration of cGVH was 36 (range 3-148) months and all patients received 2 or more lines of therapy; the main cGVH target was represented by lung in 9 patients (5 patients had severe abnormalities of the functional tests with compromised Lung Functional Score), skin in 8 patients and bowel in 8 patients. Most patients had multi-organ involvement. The treatment with Imatinib was planned for a minimum of 6 months, starting at the initial dose of 100 mg/day, then increasing the dose to 200 mg/day until 3rd month; if no response and in absence of severe toxicity, patients were allowed to receive 400 mg/day until 6th month. The response has been defined as CR or PR, and was evaluated after 3 and 6 months of therapy; the kind of response (CR or PR) was defined according to the Curiel criteria, integrated by the criteria suggested by the NIH Consensus Conference for cGVHD. Results the treatment was well tolerated (all patients were able to complete the treatment for at least 6 months) and we did not observe toxic deaths; the toxicity was mild (no grade 3-4 toxicities have been reported) and 3 Severe Adverse Events have been reported (3 cases of pneumonia), probably related to the immunesuppression due to cGVHD instead to the Imatinib treatment. The ORR at 3 months was 72% and 56% at 6 months (9 PR and 1CR); 3 patients were able to stop or significantly decrease steroids. With a median follow-up of 6 months 15 out of the 18 evaluable patients are alive while 3 died of progressive cGVHD. The preliminary results of this multicenter study confirm that low-dose Imatinib is safe and effective in patients affected by refractory cGVHD; the slightly lower response rate observed at 6 months, compared to the previous study probably reflects the different population enrolled: older patients in the present study (the median age was 47, compared to 27 in the previous study; absence of pediatric patients who showed the best responses), most of them with lung involvement (9) and 5 with severe impairment of Lung Functional Score. These data encourage the use of Thyrosin Kinase Inhibitors in patients with refractory cGVHD and the evaluation of these drugs in phase 3 trials; furthermore the extensive evaluation of biological activity of these drugs could be able to select those patients who could benefit of this approach. This study was supported by the Italian medicines Agency (AIFA) within the independent drug research program contract no. FARM7ZWZ7Y. Disclosures: Off Label Use: yes we report the results obtained with Imatinib off-label in patients with refractory cGVHD.