282,216 research outputs found
Revised guidelines for the clinical management of Lynch syndrome (HNPCC): recommendations by a group of European experts
Full text linkLynch syndrome (LS) is characterised by the development of colorectal cancer, endometrial cancer and various other cancers, and is caused by a mutation in one of the mismatch repair genes: MLH1, MSH2, MSH6 or PMS2. In 2007, a group of European experts (the Mallorca group) published guidelines for the clinical management of LS. Since then substantial new information has become available necessitating an update of the guidelines. In 2011 and 2012 workshops were organised in Palma de Mallorca. A total of 35 specialists from 13 countries participated in the meetings. The first step was to formulate important clinical questions. Then a systematic literature search was performed using the Pubmed database and manual searches of relevant articles. During the workshops the outcome of the literature search was discussed in detail. The guidelines described in this paper may be helpful for the appropriate management of families with LS. Prospective controlled studies should be undertaken to improve further the care of these families
Caracterització i identificació de les formes hereditàries de càncer colorectal
Full text link[cat] El càncer colorectal (CCR) és una de les neoplàsies més prevalents en els països occidentals, i un dels tumors en el que els factors genètics juguen un paper fonamental en el seu desenvolupament. Així, l'anomenat CCR hereditari, entès com aquelles formes degudes a l'alteració de gens d'alta penetrança, suposa entre el 3-5% de tots els casos. Tot i que suposen un percentatge baix de forma global, l'elevada prevalença del CCR, i les conseqüències catastròfiques de les síndromes hereditàries, converteixen el diagnòstic d'aquestes malalties en un objectiu fonamental a la pràctica clínica, justificant la creació d'unitats específiques. El diagnòstic d'una síndrome hereditària té conseqüències potencialment beneficioses, no només pel pacient, sinó també pels familiars, podent realitzar un diagnòstic presimptomàtic. Per tant, el primer pas consisteix en identificar als individus o pacients que potencialment poden tenir una malaltia hereditària, per tal de poder realitzar en ells els estudis moleculars necessaris pel diagnòstic. Les síndromes hereditàries associades al CCR es divideixen des d'un punt de vista fenotípic en síndromes polipòsiques, com la poliposi adenomatosa familiar, i en síndromes no polipòsiques, encapçalades per la síndrome de Lynch, algunes formes de CCR associat al gen MYH i l'anomenat CCR hereditari tipus X. Mentre que a la pràctica clínica el diagnòstic de les síndromes polipòsiques és senzill donada la seva expressivitat clínica, el diagnòstic de les formes no polipòsiques representa un repte constant pel clínic, donat que en moltes ocasions el fenotip pot ser indistingible del CCR esporàdic. La síndrome de Lynch constitueix la forma més freqüent de CCR hereditari. L'estratègia diagnostica es basa en els criteris revisats de Bethesda, que tenen com objectiu identificar aquells pacients amb una major probabilitat de ser portadors d'una mutació germinal als gens reparadors de l'ADN, en els que estaria indicat avaluar la presència d'alteració del sistema de reparació de l'ADN en el tumor mitjançant l'estudi d'inestabilitat de microsatèl.lits o tinció per immunohistoquímica de les proteïnes reparadores de l'ADN. Encara que aquests criteris han demostrat ser una estratègia efectiva, han estat àmpliament criticats degut a la seva complexitat, i la necessitat d'avaluar el tumor, que en ocasions no és possible. Recentment, han aparegut diferents models predictius de mutació germinal en els gens reparadors de l'ADN, basats en la història personal, familiar i molecular. Aquests models, entre els que es troba l'anomenat PREMM1,2, ofereixen una aproximació quantitativa de la probabilitat de ser portador de mutacions, de forma que en funció de la magnitud d'aquesta, l'actitud preventiva i l'estratègia molecular podria ser diferent. No obstant, l'avaluació d'aquests models en una sèrie de pacients amb CCR de base poblacional no s'ha realitzat fins el moment. Per altra banda, el CCR associat al gen MYH és una síndrome de recent descripció, en el que a diferència de la síndrome de Lynch, la informació de les manifestacions fenotípiques i el risc de CCR associat a la presència de mutacions és molt reduïda. Així, tot i que els pacients amb mutacions bial.lèliques solen presentar una forma de poliposi adenomatosa, fins en un 30% no presenten adenomes associats al CCR. A més, el risc de CCR associat a mutacions monoal.lèliques és controvertit. Basant-se en el projecte EPICOLON, un estudi multicèntric de base poblacional que va recollir tots els pacients amb CCR incidents a Espanya durant els anys 2000-2001, la present tesi doctoral aprofundeix en la caracterització i identificació de la síndrome de Lynch i el CCR associat al gen MYH, aportant informació rellevant i novedosa al respecte.[eng] Colorectal cancer (CRC) is the second most common cancer in most developed countries. AColorectal cancer (CRC) is the second most common cancer in most developed countries. Although it is assumed that up to 20-25% of cases develop as a result of inherited genetic factors, known genes predisposing to this malignancy account for less than 5%. Hereditary CRC is traditionally divided into polyposic syndromes, such as familial adenomatous polyposis, and non polyposic syndromes, such as Lynch syndrome. Early diagnosis of these hereditary forms is crucial since intensive cancer screening and prophylactic surgery have been shown to reduce the incidence and mortality of CRC. Moreover, appropriate presymptomatic testing can be offered to reduce mortality among at-risk family members, and relatives not at risk can avoid unnecessary intensive surveillance. However, heterogeneity of non polyposic syndromes complicates early recognition, which is critical and often difficult. In parallel with this difficulty, diagnostic criteria continue to evolve as understanding and characterization of these syndromes improve. Indeed, identification of Lynch syndrome can be done by molecular pre-screening using microsatellite instability analysis and/or immunostaining in combination or not with clinical criteria. Nevertheless, Lynch syndrome identification is moving toward more refined algorithms and multivariable models which combine personal and familial data in order to obtain a quantitative estimation of the risk. Following this direction, the PREMM1,2 model provides a new and easy-to-use model to predict mutations in the MLH1/MSH2 genes. Whereas the model accurately discriminates gene mutation carriers in the subset of individuals at moderate to high risk for Lynch syndrome, its usefulness in an unselected CRC population is unknown. Furthermore, efficacy of the PREMM1,2 model in combination with tumor MMR testing has not yet been assessed. On the other hand, whereas it has conclusively demonstrated that biallelic MYH mutations confer a significant risk for colorectal cancer (CRC), the influence of monoallelic mutations remains controversial. In this sense, characterization of MYH-associated CRC is critical to identify individuals who may benefit from preventive strategies.Using data from the EPICOLON study, a prospective, multicenter, population-based cohort of CRC patients in Spain, the present Doctoral Thesis study in depth the characterization and identification of non polyposic hereditary colorectal syndromes.lthough it is assumed that up to 20-25% of cases develop as a result of inherited genetic factors, known genes predisposing to this malignancy account for less than 5%. Hereditary CRC is traditionally divided into polyposic syndromes, such as familial adenomatous polyposis, and non polyposic syndromes, such as Lynch syndrome. Early diagnosis of these hereditary forms is crucial since intensive cancer screening and prophylactic surgery have been shown to reduce the incidence and mortality of CRC. Moreover, appropriate presymptomatic testing can be offered to reduce mortality among at-risk family members, and relatives not at risk can avoid unnecessary intensive surveillance. However, heterogeneity of non polyposic syndromes complicates early recognition, which is critical and often difficult. In parallel with this difficulty, diagnostic criteria continue to evolve as understanding and characterization of these syndromes improve. Indeed, identification of Lynch syndrome can be done by molecular pre-screening using microsatellite instability analysis and/or immunostaining in combination or not with clinical criteria. Nevertheless, Lynch syndrome identification is moving toward more refined algorithms and multivariable models which combine personal and familial data in order to obtain a quantitative estimation of the risk. Following this direction, the PREMM1,2 model provides a new and easy-to-use model to predict mutations in the MLH1/MSH2 genes. Whereas the model accurately discriminates gene mutation carriers in the subset of individuals at moderate to high risk for Lynch syndrome, its usefulness in an unselected CRC population is unknown. Furthermore, efficacy of the PREMM1,2 model in combination with tumor MMR testing has not yet been assessed. On the other hand, whereas it has conclusively demonstrated that biallelic MYH mutations confer a significant risk for colorectal cancer (CRC), the influence of monoallelic mutations remains controversial. In this sense, characterization of MYH-associated CRC is critical to identify individuals who may benefit from preventive strategies.Using data from the EPICOLON study, a prospective, multicenter, population-based cohort of CRC patients in Spain, the present Doctoral Thesis study in depth the characterization and identification of non polyposic hereditary colorectal syndromes
“Publicidad by” La voz que escuchan las marcas: el caso Lynch
No full textTreball Final de Grau en Publicitat i Relacions Públiques. Codi: PU0932. Curs acadèmic: 2017/2018Este trabajo final de grado estudia la influencia de la voz autoral cinematográfica
en la comunicación audiovisual publicitaria. La pregunta que anima nuestra
investigación es: ¿pueden las marcas seleccionar unos valores y no otros del
universo construido por la voz de autor que las trabaja?. Trataremos de
responder esto a propósito del trabajo de David Lynch, por su particularidad y su
personalidad de trabajo tan definida e influyente desde hace décadas en la
publicidad. Para ello, por un lado, vamos a investigar en qué momento los
cineastas comenzaron a fimar spots publicitarios, al mismo tiempo que
profundizamos en el perfil de Scorsese y Wes Anderson dentro del ámbito
publicitario. Por otro lado, abordamos el concepto de autoría desde su origen, a
su vez investigamos cómo y de qué modo es asumida la voz autoral en la
publicidad, ejemplificándolo con la cineasta Sofía Coppola. Estudiaremos en
profundidad la figura de David Lynch ya que es un director de cine que ha dirigido
muchos spots publicitarios. Advertimos la necesidad de explorar aquellas
influencias estéticas que han terminado construyendo el universo lynchiano: lo
siniestro, la simbología y el surrealismo. La artes también tienen gran presencia
en el imaginario y en la vida de Lynch, algo que se puede comparar con escenas
de sus películas. Mediante el análisis fílmico de tres spots dirigidos por el
cineasta, se da respuesta a la pregunta en torno a la que gira el trabajo,
rastreando las huellas de la enunciación y profundizando al mismo tiempo en
estudiar el posicionamiento, los valores y la imagen que tienen las tres marcas
anunciadas. Ver la coherencia en términos comunicativos de las mismas es
fundamental para justificar la vinculación establecida entre Lynch y la marca para
la que trabaja.This degree final work study the influence of cinematographic author voice in the
audiovisual advertising communication. The question that animates our research
is: Can brands select some values and not others from the universe built by the
author's voice that works them?. We will try to answer this with regard to the work
of David Lynch, for his particulariy and his personality of work so defined and
influyent since decades in the advertising. For it, on the one hand, we will
research in what moment the filmmakers started to film Adversiting spots, at the
same time that we deepen in the profile to Scorsese and Wes Anderson within
the advertising field. On the other hand, we tackle the concepto to authorship
since your origin, at the same time we research how and in what way the author
voice is assumed in advertising, exemplifying it with the filmmaker Sofía Coppola.
We will study in depth the figure of David Lynch since he is a film director who
has directed many advertising spots. We warn to need to explore those aesthetic
influences that have ended up building the Lynchian universe: the sinister, the
symbolism and the surrealism. The arts also have a great presence in the
imaginary and in the life of Lynch, something that can be compared with scenes
from his films. Through the filmic analysis of three spots directed by the
filmmaker, the question is answered around which the work revolves, tracing the
traces of the enunciation and deepening at the same time in studying the
positioning, values and image they have the three announced brands. Seeing the
coherence in communicative terms of the same is fundamental to justify the link
established between Lynch and the brand for which he works
Càncer colorectal hereditari: Aplicacions diagnòstiques de l'estudi de la dosi dels gens APC, MLH1 i MSH2
Full text link[cat] Les síndromes de càncer colorectal (CCR) hereditari representen entre un 3% i un 5% de tots els casos de CCR i inclouen tots aquells individus amb un elevat grau d'agregació familiar. La més freqüent és la síndrome de Lynch, causada per la presència de mutacions en els gens reparadors del DNA, majoritàriament MLH1 i MSH2. La poliposi adenomatosa familiar (FAP) és la segona en incidència, es caracteritza per l'aparició de pòlips precursors a la neoplàsia colorectal i la seva causa principal és la presència de mutacions en el gen supressor tumoral APC. En els últims anys s'ha descobert que els grans reordenaments d'aquests gens són responsables de la malaltia en una part de les famílies que pateixen aquestes síndromes. A més, estudis d'expressió d'aquests gens en línia germinal han demostrat l'existència de desequilibris al·lèlics tant en famílies portadores de mutacions com en famílies on no es detecten mutacions en el DNA. L'objectiu d'aquesta tesi és l'estudi de la dosi en la dels gens MLH1, MSH2 i APC, implicats en la síndrome de Lynch i la FAP. D'aquesta forma, hem analitzat la dosi tant a nivell de DNA (grans reordenaments) com a nivell d'RNA (expressió específica d'al·lel), sempre treballant amb línia germinal de pacients. Els resultats aquí recollits permeten millorar l'estratègia de diagnòstic molecular de les famílies amb síndrome de Lynch i FAP que són ateses al nostre centre, al mateix temps que la comprensió del procés tumorogènic.[eng] Hereditary colorectal cancer (CRC) syndromes represent about 3% to 5% of all cases of CRC and include all those individuals with high familiar aggregation. The most frequent syndrome is Lynch syndrome, caused by the presence of mutations in the mismatch repair (MMR) genes, mostly MLH1 and MSH2. Familiar adenomatous polyposis (FAP) is the second in incidence, is characterized by precursor polyps and its mainly caused by mutations in the tumoral suppressor gene APC. Recently, it has been discovered that gross rearrangements of these genes are responsible of these two syndromes. Also, expression analyses of these genes in the germline have demonstrated the existence of allelic imbalances in both families carrying pathogenic mutations and families without detected mutations. Our aim was to study de dose of MLH1, MSH2 and APC genes in the germline of Lynch syndrome and polyposis families, respectively. To that end, we analyzed the dose at DNA level (gross rearrangements) and at RNA level (allele-specific expression) of these patients. The results summarized in this thesis permit improving the molecular diagnostic strategy in Lynch syndrome and FAP families, and also improve the knowledge of the tumorogenic process
Louvre aulos basic scales – Classical setting (Lynch 2022)
No full textAs discussed in a forthcoming publication, this figure represents the Phrygian/Hypophrygian scales produced by the Louvre Aulos.
This setting is consistent with the Classical and Hellenistic evidence discussed in Lynch 2022a–b, and especially with Athenaeus' Paean (DAGM 20).
Lynch, T. A.C., 2022b ‘Unlocking the Riddles of Classical Greek Melodies II: the Revolution of the New Music in the Ashmolean Papyri (DAGM 5–6) and Athenaeus’ Paean (DAGM 20)’, Greek and Roman Musical Studies 10.2, 416-467. High-res file on Academia.edu
Lynch, T. A.C., 2022a ‘Unlocking the Riddles of Classical Greek Melodies I: Dorian Keys to the Harmonic Revolution of the New Music and the Hellenistic Musical Documents’, Greek and Roman Musical Studies 10.2, 383-415. High-res file on Academia.ed
Louvre aulos basic scales — Imperial setting (Lynch 2022)
No full textAs discussed in a forthcoming publication, this figure represents the Iastian/Hypoiastian scales produced by the Louvre Aulos in its Imperial setting.
This setting is consistent with the tunings recorded in the Imperial musical documents, discussed in Lynch forthcoming 1, and with Ptolemy's harmogai, transcribed and discussed in Lynch forthcoming.
Lynch, T. A. C. (2023a). Unlocking the Riddles of Imperial Greek Melodies I: the 'Lydian' metamorphosis of the Classical harmonic system. (Zenodo preprint: https://doi.org/10.5281/zenodo.6927929)
Lynch, T. A. C. (forthcoming). Unlocking the Riddles of Imperial Greek Melodies II: Ptolemy's harmogaí, the Louvre aulos and the Imperial Musical documents
Letter from the Taoiseach Mr. Jack Lynch to Mr. I. Fabron, Manager of the Russell Hotel
Full text linkA letter of appreciation from the then Taoiseach of Ireland, Mr. Jack Lynch and his wife to I. Fabron, Manager of the Russell Hotel, complimenting the staff on the occasion of a lunch in the Russell Hotel for Richard Nixon, President of the United States of America
Comparative Lynch Law: Lynch Trials and Vigilantism
No full textVol. 35:3Jim Whitman does serious comparative law, writing about new and
profound questions. I cannot begin to match that, but offer this small
contribution on the relationship between lynch trials and vigilantism on the
American frontier.
Any area on the frontier that is to say, Western areas not yet included
in a Territory or State lacked a legal system and, in particular, the
infrastructure for trying and punishing criminals. The frontier had no
government, laws, courts, jails, or sheriffs; but there were crimes in even
the smallest communities, as John Philip Ried showed in his books about
criminal law on the overland trail. When a member of a wagon train killed
one of his fellows, Reid found, the wagons stopped and their owners held
an Anglo-American style jury trial, asking members of other wagon trains
to serve as jurors
Portrait of a filmmaker painting in his studio: Connections between painting and cinema in David Lynch: The Art Life (2016)
Full text linkDavid Lynch: The Art life (2016) és un documental que suposa un interessantíssim apropament a una figura tan fascinant com polifacètica: David Lynch. El film indaga en les primeres dècades de vida de qui, començant pel seu periple artístic com a pintor, desembocaria en el sèptim art amb una suggeridora i pertorbadora obra. En aquest treball estudiem les relacions entre cine i pintura que es teixeixen al documental, tot atenent a com l’obra pictòrica del Lynch pre- i post- cinematogràfic condiciona el discurs del director mateix i dels autors del documental. Per tot allò, analitzem la pel·lícula, així com les diferents entrevistes concedides pels directors i diverses publicacions de David Lynch que expliquen el sentit del seu art.David Lynch: The Art Life (2016) is a documentary film that involves an interesting approach to a fascinating and multifaceted figure: David Lynch. This film explores the first decades of life of a filmmaker with a suggestive and disturbing work, wich began his artistic career as a painter. In this paper we study the relations between cinema and painting that are shown in the documentary, taking into account the way in which the pictorial work of pre and post cinematographic Lynch is conditioned by the discourse of the filmmaker and the authors of the documentary. To do this, we analyze the film, as well as the different interviews given by the directors, and various publications by David Lynch explaining the meaning of his art.David Lynch: The Art life (2016) es un documental que supone un interesantísimo acercamiento a una figura tan fascinante como polifacética: David Lynch. Este film indaga en las primeras décadas de vida de quien, empezando su periplo artístico como pintor, desembocaría en el séptimo arte con una obra sugerente y perturbadora. En este trabajo se estudian las relaciones entre cine y pintura que se tejen en el documental, atendiendo al modo en que la obra pictórica del Lynch pre y post cinematográfico va condicionando el discurso del propio director y de los autores del documental. Para ello, analizamos la película, así como las diferentes entrevistas concedidas por los directores, y diversas publicaciones de David Lynch que explican el sentido de su arte
Современная концепция патогенеза синдромов Lynch I И II
No full textУ більшості випадків діагноз може бути встановлено ретроспективно на підставі анамнестичних даних, характерного ураження організму та підтверджено результатами генетичної діагностики. Лікування оперативне симптоматичне — резекція пухлини кишечнику і, при встановленому синдромальному діагнозі, — профілактична білатеральна сальпінгооваріоектомія, гістероектомія зметою запобігти можливості розвитку раку ендометрія і яєчників.Analysis of home and foreign literature data about the basic etiopathogenetic mechanisms of the Lynch I and II syndromes origin and development was carried out in the article. The author has supposed that the Lynch syndromes rate highly exceed the official data. Basic directions of the screening measures in revealing the given pathology in population has been also shown.В статье проведен анализ данных отечественной и зарубежной литературы касательно основных этиопатогенетических механизмов возникновения и развития синдромов Lynch I и II типа. Автором высказано предположение, что частота встречаемости синдромов Lynch намного превышает официальные цифры. Показаны основные направления проведения скрининговых мероприятий по выявлению данной патологии в популяции
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