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Sample records for henry lynch heredity

  1. Distinct Gene Expression Signatures in Lynch Syndrome and Familial Colorectal Cancer Type X

    DEFF Research Database (Denmark)

    Valentin, Mev; Therkildsen, Christina; Veerla, Srinivas

    2013-01-01

    Heredity is estimated to cause at least 20% of colorectal cancer. The hereditary nonpolyposis colorectal cancer subset is divided into Lynch syndrome and familial colorectal cancer type X (FCCTX) based on presence of mismatch repair (MMR) gene defects.......Heredity is estimated to cause at least 20% of colorectal cancer. The hereditary nonpolyposis colorectal cancer subset is divided into Lynch syndrome and familial colorectal cancer type X (FCCTX) based on presence of mismatch repair (MMR) gene defects....

  2. Mike Lynch

    DEFF Research Database (Denmark)

    Irwin, Alan; Horst, Maja

    In ’Science as a vacation’, Michael Lynch argues that ’STS might aim for something other than the serious job of doing business’. In so doing, he makes a strong case for an STS that does not aim to be useful but instead does ‘its own job’. In our presentation, we will explore some of the challenges...... associated with this position and especially its relationship to STS traditions of policy relevance and engagement. What does it mean for STS to do its job? Or rather, what does it mean for us to do our jobs? Taking inspiration both from Lynch’s published work and the different ways he has performed his STS...

  3. Lynch syndrome: the patients' perspective

    NARCIS (Netherlands)

    Seppen, Jurgen; Bruzzone, Linda

    2013-01-01

    People with Lynch syndrome have a high lifetime risk for the development of colorectal, endometrial and several other types of cancer. Lynch syndrome is caused by germline mutations in genes encoding DNA mismatch repair proteins. In this review, issues that concern Lynch patients are highlighted

  4. Heredity before genetics: a history.

    Science.gov (United States)

    Cobb, Matthew

    2006-12-01

    Two hundred years ago, biologists did not recognize that there was such a thing as 'heredity'. By the 1830s, however, insights from medicine and agriculture had indicated that something is passed from generation to generation, creating the context for the brilliant advances of Mendel and Darwin. Recent work on the history and philosophy of science has shed light on how seventeenth-, eighteenth- and nineteenth-century thinkers sought to understand similarities between parents and offspring.

  5. Diagnosing Lynch Syndrome

    LENUS (Irish Health Repository)

    Gleeson, J

    2016-11-01

    Lynch Syndrome, also known as Hereditary Non-Polyposis Colorectal Cancer (HNPCC), is a hereditary condition that increases an individual’s risk of developing a constellation of cancers. These most commonly arise in the colon, but also involve other solid organs such as the endometrium and ovaries in women, the stomach, brain and the skin. Ireland’s small population offers an opportunity to identify all those with Lynch Syndrome (LS) in the country, which would represent a powerful preventive opportunity to meaningfully impact on the incidence of cancer in Ireland.

  6. Human development, heredity and evolution.

    Science.gov (United States)

    Nishinakamura, Ryuichi; Takasato, Minoru

    2017-06-15

    From March 27-29 2017, the RIKEN Center for Developmental Biology held a symposium entitled 'Towards Understanding Human Development, Heredity, and Evolution' in Kobe, Japan. Recent advances in technologies including stem cell culture, live imaging, single-cell approaches, next-generation sequencing and genome editing have led to an expansion in our knowledge of human development. Organized by Yoshiya Kawaguchi, Mitinori Saitou, Mototsugu Eiraku, Tomoya Kitajima, Fumio Matsuzaki, Takashi Tsuji and Edith Heard, the symposium covered a broad range of topics including human germline development, epigenetics, organogenesis and evolution. This Meeting Review provides a summary of this timely and exciting symposium, which has convinced us that we are moving into the era of science targeted on humans. © 2017. Published by The Company of Biologists Ltd.

  7. Lynch Syndrome: An Updated Review

    Directory of Open Access Journals (Sweden)

    Rishabh Sehgal

    2014-06-01

    Full Text Available Lynch syndrome is one of the most common cancer susceptibility syndromes. Individuals with Lynch syndrome have a 50%–70% lifetime risk of colorectal cancer, 40%–60% risk of endometrial cancer, and increased risks of several other malignancies. It is caused by germline mutations in the DNA mismatch repair genes MLH1, MSH2, MSH6 or PMS2. In a subset of patients, Lynch syndrome is caused by 3' end deletions of the EPCAM gene, which can lead to epigenetic silencing of the closely linked MSH2. Relying solely on age and family history based criteria inaccurately identifies eligibility for Lynch syndrome screening or testing in 25%–70% of cases. There has been a steady increase in Lynch syndrome tumor screening programs since 2000 and institutions are rapidly adopting a universal screening approach to identify the patients that would benefit from genetic counseling and germline testing. These include microsatellite instability testing and/or immunohistochemical testing to identify tumor mismatch repair deficiencies. However, universal screening is not standard across institutions. Furthermore, variation exists regarding the optimum method for tracking and disclosing results. In this review, we summarize traditional screening criteria for Lynch syndrome, and discuss universal screening methods. International guidelines are necessary to standardize Lynch syndrome high-risk clinics.

  8. Ovarian cancer linked to lynch syndrome typically presents as early-onset, non-serous epithelial tumors

    DEFF Research Database (Denmark)

    Ketabi, Zohreh; Bartuma, Katarina; Bernstein, Inge

    2011-01-01

    OBJECTIVE: Heredity is a major cause of ovarian cancer and during recent years the contribution from germline mismatch repair (MMR) gene mutations linked to Lynch syndrome has gradually been recognized. METHODS: We characterized clinical features, tumor morphology and mismatch repair defects in all...... ovarian cancers identified in Swedish and Danish Lynch syndrome families. RESULTS: In total, 63 epithelial ovarian cancers developed at mean 48 (range 30-79) years of age with 47% being early stage (FIGO stage I). Histologically, endometrioid (35%) and clear cell (17%) tumors were overrepresented....... The underlying MMR gene mutations in these families affected MSH2 in 49%, MSH6 in 33% and MLH1 in 17%. Immunohistochemical loss of the corresponding MMR protein was demonstrated in 33/36 (92%) tumors analyzed. CONCLUSION: The combined data from our cohorts demonstrate that ovarian cancer associated with Lynch...

  9. Predicting Lynching Atrocity: The Situational Norms of Lynchings in Georgia.

    Science.gov (United States)

    Ritchey, Andrew J; Ruback, R Barry

    2017-09-01

    From 1882 to 1926, lynch mobs in Georgia killed 514 victims in 410 separate events. Based on a new comprehensive dataset, this study examined characteristics of the mobs related to the level of the atrocity of the violence in the lynchings. Consistent with prior research, the size of the crowd was a stable predictor of level of atrocity. However, in contrast to two prior studies, results did not uniformly support the self-attention perspective. Instead, the findings were more consistent with the concept that situational norms were the important mechanism behind collective violence, particularly because the violence used in a lynching event reflected the violence used in nearby lynchings. These results suggest that, rather than losing all norms of behavior through a process of deindividuation, lynchers adopted norms they viewed as appropriate for the situation.

  10. Lynch Syndrome: A Pediatric Perspective

    National Research Council Canada - National Science Library

    Huang, Sherry C; Durno, Carol A; Erdman, Steven H

    .... The most common hereditary colon cancer susceptibility condition, Lynch syndrome (LS), previously known as hereditary nonpolyposis colorectal cancer, is an autosomal dominant condition caused by a germline mutation in 1 of 4 DNA mismatch repair (MMR...

  11. Family perspectives in lynch syndrome becoming a family at risk, patterns of communication and influence on relations

    Directory of Open Access Journals (Sweden)

    Bartuma Katarina

    2012-05-01

    Full Text Available Abstract Background A growing number of individuals are diagnosed with hereditary cancer. Though increased levels of anxiety and depression have been demonstrated around the time of genetic counselling, most individuals handle life at increased risk well. Data have, however, been collected on individual basis, which led us to focus on family perspectives of hereditary cancer. Methods Lynch syndrome represents a major type of hereditary colorectal and gynaecological cancer. We preformed open-ended interviews with 27 informants from 9 Lynch syndrome families. Inductive content analysis revealed three major themes: transition to a risk family, patterns of communication and influence on family relations and individual roles. Results Family members described how learning about Lynch syndrome shifted focus from daily issues to concerns about cancer. Changes in communication related to difficulties in talking to children about heredity and informing new family members and distant relatives about an increased risk of cancer. Influence on relations was exemplified by family members taking on different roles, e.g. females often being responsible for coordinating information about heredity and providing support. Families in which members had experienced cancer at young age typically informed children soon after learning about heredity and at young age, whereas families with experience of cancer at higher age postponed information and thereby also genetic counselling. Conclusions Three major family perspectives are described in Lynch syndrome families; becoming a risk family, patterns of communication and influence on family relations. Since these issues are central, our findings suggests that such family perspectives should be considered during genetic counselling in order to contribute to information spread, help family members cope with the increased risk, and motivate family members at risk to undergo surveillance.

  12. Family perspectives in lynch syndrome becoming a family at risk, patterns of communication and influence on relations.

    Science.gov (United States)

    Bartuma, Katarina; Nilbert, Mef; Carlsson, Christina

    2012-05-25

    A growing number of individuals are diagnosed with hereditary cancer. Though increased levels of anxiety and depression have been demonstrated around the time of genetic counselling, most individuals handle life at increased risk well. Data have, however, been collected on individual basis, which led us to focus on family perspectives of hereditary cancer. Lynch syndrome represents a major type of hereditary colorectal and gynaecological cancer. We preformed open-ended interviews with 27 informants from 9 Lynch syndrome families. Inductive content analysis revealed three major themes: transition to a risk family, patterns of communication and influence on family relations and individual roles. Family members described how learning about Lynch syndrome shifted focus from daily issues to concerns about cancer. Changes in communication related to difficulties in talking to children about heredity and informing new family members and distant relatives about an increased risk of cancer. Influence on relations was exemplified by family members taking on different roles, e.g. females often being responsible for coordinating information about heredity and providing support. Families in which members had experienced cancer at young age typically informed children soon after learning about heredity and at young age, whereas families with experience of cancer at higher age postponed information and thereby also genetic counselling. Three major family perspectives are described in Lynch syndrome families; becoming a risk family, patterns of communication and influence on family relations. Since these issues are central, our findings suggests that such family perspectives should be considered during genetic counselling in order to contribute to information spread, help family members cope with the increased risk, and motivate family members at risk to undergo surveillance.

  13. Exploring Podcasting in Heredity and Evolution Teaching

    Science.gov (United States)

    Almeida-Aguiar, Cristina; Carvalho, Ana Amélia

    2016-01-01

    Podcasts are digital files very popular in several and very distinct areas. In higher education, they have been explored in a multitude of ways mainly to support teaching and learning processes. The study here described focuses the integration of podcasts in Heredity and Evolution, a course from the Biology and Geology Degree Program at University…

  14. Lynch syndrome-associated neoplasms

    DEFF Research Database (Denmark)

    Shia, Jinru; Holck, Susanne; Depetris, Giovanni

    2013-01-01

    of such information. This article provides an overview of the development of histopathology and immunohistochemistry in Lynch syndrome-associated tumors, particularly in colorectal and endometrial cancers, and outlines the issues and current status of these specific pathologic aspects in not only the major tumors...

  15. Vanglateenistuse enesekaitsekoolitus / Henri Palm

    Index Scriptorium Estoniae

    Palm, Henri

    2014-01-01

    Vanglateenistus korraldab Tartus, Tallinnas ja Jõhvis enesekaitsekoolitusi gümnaasiumiõpilastele. Jakob Westholmi abiturient Henri Palm on osalenud treeningutel osalenud kolm aastat ning jagab kogemusi

  16. William Henry Perkin

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education. William Henry Perkin. Articles written in Resonance – Journal of Science Education. Volume 15 Issue 9 September 2010 pp 856-859 Classics. Dyeing Fabrics · William Henry Perkin · More Details Fulltext PDF ...

  17. Do Surrealismo em David Lynch

    Directory of Open Access Journals (Sweden)

    Mirian Tavares

    2009-01-01

    Full Text Available O surrealismo, como a arte do seu tempo, propõe uma nova estética, capaz de extrair o belo do absurdo e de instaurar o desvio para que daí surja, de fato, o real. Através da análise de algumas obras de David Lynch e dos livros Les champs magnétiques de Breton e Philippe Soupault e Poisson soluble, de Breton, irei mostrar a pertinência da designação surrealista para a obra do cineasta norte-americano. Lynch, como os surrealistas, constrói uma operação dialética entre o racional/irracional. Ao mesmo tempo em que opera no campo artístico em direção à irracionalidade absoluta, Lynch não nega a sua inserção na sociedade. Acredito que o realizador, como os surrealistas, tenha conseguido encontrar um equilíbrio entre as duas formas de se estar no mundo, racional/irracional, jogando com suas antíteses. O prazer do jogo surrealista consiste em ir até as profundezas do inconsciente e retornar com matéria suficiente para fazer uma obra de arte.Surrealism, as the art of its time, proposes a new aesthetics, one that is able to extract the beautiful from the absurd and to establish the swerve from the standard, from which, in fact, the real comes through. Through the analysis of some works by David Lynch, of Breton and Soupault's Les champs magnétiques, and of Breton's Poisson soluble, I will attempt to show the relevance of the surrealist designation for the work of the American filmmaker. Lynch, like the surrealists, builds a dialectic operation between the rational and the irrational. While operating in the artistic field towards absolute irrationality, Lynch does not deny its role in society. It is my belief that the director, as the surrealists, has managed to find a balance between the two ways of being in the world: rational and irrational; by playing with their antitheses. The pleasure of the surrealist game is to go to the depths of the unconscious and return with sufficient material to make a work of art out of it.

  18. Milestones of Lynch syndrome: 1895-2015.

    Science.gov (United States)

    Lynch, Henry T; Snyder, Carrie L; Shaw, Trudy G; Heinen, Christopher D; Hitchins, Megan P

    2015-03-01

    Lynch syndrome, which is now recognized as the most common hereditary colorectal cancer condition, is characterized by the predisposition to a spectrum of cancers, primarily colorectal cancer and endometrial cancer. We chronicle over a century of discoveries that revolutionized the diagnosis and clinical management of Lynch syndrome, beginning in 1895 with Warthin's observations of familial cancer clusters, through the clinical era led by Lynch and the genetic era heralded by the discovery of causative mutations in mismatch repair (MMR) genes, to ongoing challenges.

  19. Lynch syndrome-related small intestinal adenocarcinomas.

    Science.gov (United States)

    Jun, Sun-Young; Lee, Eui-Jin; Kim, Mi-Ju; Chun, Sung Min; Bae, Young Kyung; Hong, Soon Uk; Choi, Jene; Kim, Joon Mee; Jang, Kee-Taek; Kim, Jung Yeon; Kim, Gwang Il; Jung, Soo Jin; Yoon, Ghilsuk; Hong, Seung-Mo

    2017-03-28

    Lynch syndrome is an autosomal-dominant disorder caused by defective DNA mismatch repair (MMR) genes and is associated with increased risk of malignancies in multiple organs. Small-intestinal adenocarcinomas are common initial manifestations of Lynch syndrome. To define the incidence and characteristics of Lynch syndrome-related small-intestinal adenocarcinomas, meticulous familial and clinical histories were obtained from 195 patients with small-intestinal adenocarcinoma, and MMR protein immunohistochemistry, microsatellite instability, MLH1 methylation, and germline mutational analyses were performed. Lynch syndrome was confirmed in eight patients (4%), all of whom had synchronous/metachronous malignancies without noticeable familial histories. Small-intestinal adenocarcinomas were the first clinical manifestation in 37% (3/8) of Lynch syndrome patients, and second malignancies developed within 5 years in 63% (5/8). The patients with accompanying Lynch syndrome were younger (≤50 years; P=0.04) and more likely to have mucinous adenocarcinomas (P=0.003), and tended to survive longer (P=0.11) than those with sporadic cases. A meticulous patient history taking, MMR protein immunolabeling, and germline MMR gene mutational analysis are important for the diagnosis of Lynch syndrome-related small-intestinal adenocarcinomas. Identifying Lynch syndrome in patients with small-intestinal adenocarcinoma can be beneficial for the early detection and treatment of additional Lynch syndrome-related cancers, especially in patients who are young or have mucinous adenocarcinomas.

  20. Neuron-based heredity and human evolution.

    Science.gov (United States)

    Gash, Don M; Deane, Andrew S

    2015-01-01

    It is widely recognized that human evolution has been driven by two systems of heredity: one DNA-based and the other based on the transmission of behaviorally acquired information via nervous system functions. The genetic system is ancient, going back to the appearance of life on Earth. It is responsible for the evolutionary processes described by Darwin. By comparison, the nervous system is relatively newly minted and in its highest form, responsible for ideation and mind-to-mind transmission of information. Here the informational capabilities and functions of the two systems are compared. While employing quite different mechanisms for encoding, storing and transmission of information, both systems perform these generic hereditary functions. Three additional features of neuron-based heredity in humans are identified: the ability to transfer hereditary information to other members of their population, not just progeny; a selection process for the information being transferred; and a profoundly shorter time span for creation and dissemination of survival-enhancing information in a population. The mechanisms underlying neuron-based heredity involve hippocampal neurogenesis and memory and learning processes modifying and creating new neural assemblages changing brain structure and functions. A fundamental process in rewiring brain circuitry is through increased neural activity (use) strengthening and increasing the number of synaptic connections. Decreased activity in circuitry (disuse) leads to loss of synapses. Use and disuse modifying an organ to bring about new modes of living, habits and functions are processes in line with Neolamarckian concepts of evolution (Packard, 1901). Evidence is presented of bipartite evolutionary processes-Darwinian and Neolamarckian-driving human descent from a common ancestor shared with the great apes.

  1. Neuron-Based Heredity and Human Evolution

    Directory of Open Access Journals (Sweden)

    Don Marshall Gash

    2015-06-01

    Full Text Available Abstract:Abstract: It is widely recognized that human evolution has been driven by two systems of heredity: one DNA-based and the other based on the transmission of behaviorally acquired information via nervous system functions. The genetic system is ancient, going back to the appearance of life on Earth. It is responsible for the evolutionary processes described by Darwin. By comparison, the nervous system is relatively newly minted and in its highest form, responsible for ideation and mind-to-mind transmission of information. Here the informational capabilities and functions of the two systems are compared. While employing quite different mechanisms for encoding, storing and transmission of information, both systems perform these generic hereditary functions. Three additional features of neuron-based heredity in humans are identified: the ability to transfer hereditary information to other members of their population, not just progeny; a selection process for the information being transferred; and a profoundly shorter time span for creation and dissemination of survival-enhancing information in a population. The mechanisms underlying neuron-based heredity involve hippocampal neurogenesis and memory and learning processes modifying and creating new neural assemblages changing brain structure and functions. A fundamental process in rewiring brain circuitry is through increased neural activity (use strengthening and increasing the number of synaptic connections. Decreased activity in circuitry (disuse leads to loss of synapses. Use and disuse modifying an organ to bring about new modes of living, habits and functions are processes are in line with Neolamarckian concepts of evolution (Packard, 1901. Evidence is presented of bipartite evolutionary processes – Darwinian and Neolamarckian – driving human descent from a common ancestor shared with the great apes.

  2. Heredity in one-dimensional quadratic maps

    Science.gov (United States)

    Romera, M.; Pastor, G.; Alvarez, G.; Montoya, F.

    1998-12-01

    In an iterative process, as is the case of a one-dimensional quadratic map, heredity has never been mentioned. In this paper we show that the pattern of a superstable orbit of a one-dimensional quadratic map can be expressed as the sum of the gene of the chaotic band where the pattern is to be found, and the ancestral path that joins all its ancestors. The ancestral path holds all the needed genetic information to calculate the descendants of the pattern. The ancestral path and successive descendant generations of the pattern constitute the family tree of the pattern, which is important to study and understand the orbit's ordering.

  3. Darbishire expands his vision of heredity from Mendelian genetics to inherited memory.

    Science.gov (United States)

    Wood, Roger J

    2015-10-01

    The British biologist A.D. Darbishire (1879-1915) responded to the rediscovery in 1900 of Mendel's theory of heredity by testing it experimentally, first in Oxford, then in Manchester and London. He summarised his conclusions in a textbook 'Breeding and the Mendelian Discovery' (1911), in which he questioned whether Mendelism alone could explain all aspects of practical breeding experience. Already he had begun to think about an alternative theory to give greater emphasis to the widely held conviction among breeders regarding the inheritance of characteristics acquired during an individual's life. Redefining heredity in terms of a germ-plasm based biological memory, he used vocabulary drawn partly from sources outside conventional science, including the metaphysical/vitalistic writings of Samuel Butler and Henri Bergson. An evolving hereditary memory fitted well with the conception of breeding as a creative art aimed at greater economic efficiency. For evolution beyond human control he proposed a self-modifying process, claiming it to surpass in efficiency the chancy mechanism of natural selection proposed by Darwin. From his writings, including early chapters of an unfinished book entitled 'An Introduction to a Biology', we consider how he reached these concepts and how they relate to later advances in understanding the genome and the genetic programme. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. In conversation: Henry Mintzberg

    National Research Council Canada - National Science Library

    Stephen Bernhut

    2000-01-01

      An interview with Henry Mintzberg is presented. Mintzberg is one of the world's leading management thinkers, and the author of 11 books on management, including the forthcoming Managing publicly...

  5. Henry Ford Health Systems

    Science.gov (United States)

    Henry Ford Health Systems evolved from a hospital into a system delivering care to 2.5 million patients and includes the Cancer Epidemiology, Prevention and Control Program, which focuses on epidemiologic and public health aspects of cancer.

  6. Modernization and Lynching in the New South

    Directory of Open Access Journals (Sweden)

    Mattias Smångs

    2016-09-01

    Full Text Available This article evaluates an emerging body of historical scholarship that challenges prevailing views of the primacy of rural conditions in southern lynching by positing that it was symbiotically associated with the processes of modernization underway in the region in the decades around 1900. Statistical analyses of lynching data that differentiate among events according to communal participation, support, and ceremony in Georgia and Louisiana from 1882 to 1930 and local-level indices of modernization (urbanization, rural depopulation, industrialization, agricultural commercialization, and dissolution of traditional family roles yield results that both support and contradict such a modernization thesis of lynching. The findings imply that the consequences of the social transformation in the South coinciding with the lynching era were not uniform throughout the region with regard to racial conflict and violence and that broad arguments proposing an intrinsic connection between modernization and lynchings therefore are overstated.

  7. Meet EPA Environmental Scientist Kira Lynch

    Science.gov (United States)

    Environmental Scientist Kira Lynch is currently the Superfund and Technology Liaison in EPA’s Region 10, where she uses her expertise in characterizing environmental contamination to help evaluate and clean up hazardous waste sites.

  8. Role for Genetic Anticipation in Lynch Syndrome

    DEFF Research Database (Denmark)

    Nilbert, Mef; Timshel, Susanne; Bernstein, Inge

    2009-01-01

    PURPOSE: Anticipation (ie, an earlier age at onset in successive generations) is linked to repeat expansion in neurodegenerative syndromes, whereas its role in hereditary cancer is unclear. We assessed anticipation in Lynch syndrome (hereditary nonpolyposis colorectal cancer [HNPCC]), in which DN...... to initiate surveillance programs at young age. It should also stimulate research into the genetic mechanisms that determine age at onset and whether the genetic instability that characterizes Lynch syndrome can be linked to anticipation....

  9. Bragg, Prof. William Henry

    Indian Academy of Sciences (India)

    Elected: 1935 Honorary. Bragg, Prof. William Henry Nobel Laureate (Physics) - 1915. Date of birth: 2 July 1862. Date of death: 10 March 1972 ... Posted on 21 December 2017. ASTROPHYSICS: An Observational View of the Universe. Math Art and Design: MAD about Math, Math Education and Outreach. Math and Finance ...

  10. Clinicopathological comparison of colorectal and endometrial carcinomas in patients with Lynch-like syndrome versus patients with Lynch syndrome.

    Science.gov (United States)

    Mas-Moya, Jenny; Dudley, Beth; Brand, Randall E; Thull, Darcy; Bahary, Nathan; Nikiforova, Marina N; Pai, Reetesh K

    2015-11-01

    Screening for DNA mismatch repair (MMR) deficiency in colorectal and endometrial carcinomas identifies patients at risk for Lynch syndrome. Some patients with MMR-deficient tumors have no evidence of a germline mutation and have been described as having Lynch-like syndrome. We compared the clinicopathological features of colorectal and endometrial carcinomas in patients with Lynch-like syndrome and Lynch syndrome. Universal screening identified 356 (10.6%) of 3352 patients with colorectal carcinoma and 72 (33%) of 215 patients with endometrial carcinoma with deficient DNA MMR. Sixty-six patients underwent germline mutation analysis with 45 patients (68%) having evidence of a germline MMR gene mutation confirming Lynch syndrome and 21 patients (32%) having Lynch-like syndrome with no evidence of a germline mutation. Most patients with Lynch-like syndrome had carcinoma involving the right colon compared to patients with Lynch syndrome (93% versus 45%; P Lynch syndrome confirmed by germline mutation analysis. Synchronous or metachronous Lynch syndrome-associated carcinoma was more frequently identified in patients with Lynch syndrome compared to Lynch-like syndrome (38% versus 7%; P = .04). There were no significant differences in clinicopathological variables between patients with Lynch-like syndrome and Lynch syndrome with endometrial carcinoma. In summary, 32% of patients with MMR deficiency concerning Lynch syndrome will have Lynch-like syndrome. Our results demonstrate that patients with Lynch-like syndrome are more likely to have right-sided colorectal carcinoma, less likely to have synchronous or metachronous Lynch syndrome-associated carcinoma, and less likely to demonstrate isolated loss of MSH6 expression within their tumor. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. HENRY'S "HAND OF GOD"

    Directory of Open Access Journals (Sweden)

    Željko Kaluđerović

    2014-04-01

    Full Text Available In this paper the author discusses the views and statements of the French football player Thierry Henry he gave after his illegal play during the playoff match between France and the Republic of Ireland to claim one of the final spots in the World Cup 2010 in South Africa. First, by controlling the ball with his hand before passing it on for the goal Henry has shown disregard for the constitutive rules of football. Then, by stating that he is "not a referee" he demonstrated that for some players rules are not inherent to football and that they can be relativized, given that for them winning is the goal of the highest ontological status. Furthermore, he has rejected the rules of sportsmanship, thus expressing his opinion that the opponents are just obstacles which have to be removed in order to achieve your goals. Henry's action has disrupted major moral values, such as justice, honesty, responsibility and beneficence. The rules of fair play have totally been ignored both in Henry's action and in the Football Association of France's unwillingness to comment on whether a replay should take place. They have ignored one of the basic principles stated in the "Declaration of the International Fair Play Committee", according to which, fair play is much more than playing to the rules of the game; it's about the attitude of the sportsperson. It's about respecting your opponent and preserving his or her physical and psychological integrity. Finally, the author believes that the rules, moral values and fair play in football are required for this game to become actually possible to play

  12. HENRY'S "HAND OF GOD"

    Directory of Open Access Journals (Sweden)

    Željko Kaluđerović

    2014-04-01

    Full Text Available In this paper the author discusses the views and statements of the French football player Thierry Henry he gave after his illegal play during the playoff match between France and the Republic of Ireland to claim one of the final spots in the World Cup 2010 in South Africa. First, by controlling the ball with his hand before passing it on for the goal Henry has shown disregard for the constitutive rules of football. Then, by stating that he is "not a referee" he demonstrated that for some players rules are not inherent to football and that they can be relativized, given that for them winning is the goal of the highest ontological status. Furthermore, he has rejected the rules of sportsmanship, thus expressing his opinion that the opponents are just obstacles which have to be removed in order to achieve your goals. Henry's action has disrupted major moral values, such as justice, honesty, responsibility and beneficence. The rules of fair play have totally been ignored both in Henry's action and in the Football Association of France's unwillingness to comment on whether a replay should take place. They have ignored one of the basic principles stated in the "Declaration of the International Fair Play Committee", according to which, fair play is much more than playing to the rules of the game; it's about the attitude of the sportsperson. It's about respecting your opponent and preserving his or her physical and psychological integrity. Finally, the author believes that the rules, moral values and fair play in football are required for this game to become actually possible to play.

  13. Herencia en asma Heredity in asthma

    Directory of Open Access Journals (Sweden)

    Irma Rosa López Pérez

    2008-03-01

    Full Text Available El asma es una enfermedad compleja, asociada a una alta prevalencia de alergia. Ambas, el asma y la alergia, son causadas por complejas interacciones del genoma con el medioambiente. Constituye un desafío investigar las bases de la susceptibilidad genética en asma y atopia, puesto que son múltiples los factores genéticos y medioambientales los que interactúan para modular su heterogénea expresión clínica. La expresión de la enfermedad se hace aún más heterogénea si consideramos aspectos como la gravedad, la evolución natural o la respuesta al tratamiento. Nos propusimos referirnos a los aspectos relacionados con la herencia en el asma, dada la relevancia que tiene la interpretación de esta participación genética en la comprensión de la fisiopatología que subyace en la historia natural del asma, en su gravedad y en la respuesta al tratamiento. Este análisis nos permitirá asumir conductas terapéuticas eficaces desde la misma emergencia del asma.Asthma is a complex disease associated with a high prevalence of allergy. Both, asthma and allergy are caused by complex interactions of the genoma with the environment. It is a challenge to investigate the bases of genetic susceptibility in asthma and atopy, since there are multiple genetic and environmental factors that interact to modulate their heterogeneous clinic expression. The expression of the disease is even more heterogeneous if we consider aspects such as severity, natural evolution or the response to treatment. We proposed to refer to those aspects related to heredity in asthma, taking into account the importance of interpreting this genetic participation in the understanding of the physiopathology underlying in the natural history of asthma, in its severity and in the response to treatment. This analysis will allow us to follow efficient therapeutic conducts from the very emergence of asthma.

  14. Lynch syndrome: still not a familiar picture

    Directory of Open Access Journals (Sweden)

    Hes Frederik J

    2008-02-01

    Full Text Available Abstract Background Germ line mutations in mismatch repair genes underlie Lynch syndrome and predispose carriers for colorectal carcinoma and malignancies in many other organ systems. Case presentation A large Lynch syndrome family with 15 affected family members and involvement in 7 organs is reported. It illustrates a lack of awareness and knowledge about this hereditary tumor syndrome among doctors as well as patients. None of the described family members underwent presymptomatic screening on the basis of the family history. Conclusion Hereditary features, like young age at diagnosis, multiple tumors in multiple organs and a positive family history, should lead to timely referral of suspected cases for genetic counseling and diagnostics. For Lynch syndrome, these features can be found in the Amsterdam and Bethesda criteria. Subsequently, early identification of mutation carriers might have diminished, at least in part, the high and early morbidity and mortality observed in this family.

  15. The Lynch syndrome: a management dilemma.

    Science.gov (United States)

    Palumbo, Piergaspare; Amatucci, Chiara; Perotti, Bruno; Dezzi, Claudia; Girolami, Marco; Illuminati, Giulio; Angelici, Alberto M

    2013-05-01

    The case of a familial Lynch syndrome is reported. The criteria for early diagnosis, management and surveillance are briefly reviewed. A germline mutation of genes responsible for mismatch repair is at the basis of the Lynch syndrome. Carriers are predisposed to colorectal cancer and other tumors. Two members of the presently reported family developed colorectal cancer, whereas two others developed other neoplasms. The syndrome was confirmed in members of the same family with appropriate genetic workup. Clinical examination and endoscopy were consequently scheduled once-a-year. Given the high risk of neoplastic disease, such yearly controls can be proposed as the standard follow-up of this condition.

  16. Henry Gray, plagiarist.

    Science.gov (United States)

    Richardson, Ruth

    2016-03-01

    The first edition of Anatomy Descriptive and Surgical (1858) was greeted with accolades, but also provoked serious controversy concerning Henry Gray's failure to acknowledge the work of earlier anatomists. A review in the Medical Times (1859) accused Gray of intellectual theft. The journal took the unusual step of substantiating its indictment by publishing twenty parallel texts from Gray and from a pre-existing textbook, Quain's Anatomy. At the recent "Vesalius Continuum" conference in Zakynthos, Greece (2014) Professor Brion Benninger disputed the theft by announcing from the floor the results of a computer analysis of both texts, which he reported exonerated Gray by revealing no evidence of plagiarism. The analysis has not been forthcoming, however, despite requests. Here the historian of Gray's Anatomy supplements the argument set out in the Medical Times 150 years ago with data suggesting unwelcome personality traits in Henry Gray, and demonstrating the utility of others' work to his professional advancement. Fair dealing in the world of anatomy and indeed the genuineness of the lustre of medical fame are important matters, but whether quantitative evidence has anything to add to the discussion concerning Gray's probity can be assessed only if Benninger makes public his computer analysis. © 2015 Wiley Periodicals, Inc.

  17. Human heredity after 1945: moving populations centre stage.

    Science.gov (United States)

    Bangham, Jenny; de Chadarevian, Soraya

    2014-09-01

    The essays in this issue look at the contested history of human heredity after 1945 from a new analytical angle, that of populations and the ways in which they were constructed and studied. One consequence of this approach is that we do not limit our attention to the disciplinary study of genetics. After the Second World War, populations became a central topic for an array of fields, including demography, anthropology, epidemiology, and public health. Human heredity had a role in all of these: demographers carried out mental surveys in efforts to distinguish hereditary from environmental factors, doctors screened newborns and tested pregnant women for chromosome disorders; anthropologists collected blood from remote locations to gain insights into the evolutionary history of human populations; geneticists monitored people exposed to radiation. Through this work, populations were labelled as clinical, normal, primitive, pure, vulnerable or exotic. We ask: how were populations chosen, who qualified as members, and how was the study of human heredity shaped by technical, institutional and geopolitical conditions? By following the practical and conceptual work to define populations as objects of research, the essays trace the circulation of practices across different fields and contexts, bringing into view new actors, institutions, and geographies. By doing so the collection shows how human heredity research was linked to the broader politics of the postwar world, one profoundly conditioned by Cold War tensions, by nationalist concerns, by colonial and post-colonial struggles, by modernisation projects and by a new internationalism. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Twenty hanging Dolls and a Lynching:

    DEFF Research Database (Denmark)

    Risør, Helene

    2010-01-01

    The article sets lynching of presumed criminals in the city of El Alto, Bolivia, in relation to both everyday experiences of insecurity about crime and violence and the enactment of neighborliness as a grounded notion of citizenship. Focusing on the experience and management of insecurity and its...

  19. Genetic counseling and cascade genetic testing in Lynch syndrome.

    Science.gov (United States)

    Hampel, Heather

    2016-07-01

    Lynch syndrome is the most common cause of inherited colorectal and endometrial cancers. Individuals with Lynch syndrome have a 10-80 % lifetime risk for colorectal cancer and a 15-60 % lifetime risk for endometrial cancer. Both cancers are preventable through chemoprevention, intensive cancer surveillance, and risk-reducing surgery options. Efforts to identify as many individuals with Lynch syndrome as possible will prevent cancers and save lives. This includes the traditional cancer genetic counseling model whereby individuals with and without cancer are evaluated for a possible Lynch syndrome diagnosis based on their personal and family history of colon polyps and cancers. It also includes universal tumor screening for Lynch syndrome whereby all individuals with colorectal or endometrial cancer are screened for tumor features of Lynch syndrome at the time of diagnosis. Those with tumors suspicious for Lynch syndrome are referred for cancer genetic counseling regardless of their family history of cancer. This two approaches must be maximized to attain high patient reach. Finally, and perhaps most importantly, cascade testing among the at-risk relatives of those diagnosed with Lynch syndrome is critically important to maximize the diagnosis of individuals with Lynch syndrome. In fact, the cost-effectiveness of universal tumor screening for Lynch syndrome relies entirely on counseling and testing as many at-risk individuals as possible since young unaffected individuals stand to benefit the most from an early diagnosis of Lynch syndrome. This approach must be optimized to achieve high family reach. It will take a concerted effort from patients, clinicians and public health officials to improve current approaches to the diagnosis of Lynch syndrome and the prevention and treatment of Lynch syndrome-associated cancer but these lessons can be applied to other conditions as the ultimate example of personalized medicine.

  20. Lynch syndrome and Lynch syndrome mimics: The growing complex landscape of hereditary colon cancer.

    Science.gov (United States)

    Carethers, John M; Stoffel, Elena M

    2015-08-21

    Hereditary non-polyposis colorectal cancer (HNPCC) was previously synonymous with Lynch syndrome; however, identification of the role of germline mutations in the DNA mismatch repair (MMR) genes has made it possible to differentiate Lynch syndrome from other conditions associated with familial colorectal cancer (CRC). Broadly, HNPCC may be dichotomized into conditions that demonstrate defective DNA MMR and microsatellite instability (MSI) vs those conditions that demonstrate intact DNA MMR. Conditions characterized by MMR deficient CRCs include Lynch syndrome (germline MMR mutation), Lynch-like syndrome (biallelic somatic MMR mutations), constitutional MMR deficiency syndrome (biallelic germline MMR mutations), and sporadic MSI CRC (somatic biallelic methylation of MLH1). HNPCC conditions with intact DNA MMR associated with familial CRC include polymerase proofreading associated polyposis and familial colorectal cancer type X. Although next generation sequencing technologies have elucidated the genetic cause for some HNPCC conditions, others remain genetically undefined. Differentiating between Lynch syndrome and the other HNPCC disorders has profound implications for cancer risk assessment and surveillance of affected patients and their at-risk relatives. Clinical suspicion coupled with molecular tumor analysis and testing for germline mutations can help differentiate the clinical mimicry within HNPCC and facilitate diagnosis and management.

  1. Childhood cancers in families with and without Lynch syndrome.

    Science.gov (United States)

    Heath, John A; Reece, Jeanette C; Buchanan, Daniel D; Casey, Graham; Durno, Carol A; Gallinger, Steven; Haile, Robert W; Newcomb, Polly A; Potter, John D; Thibodeau, Stephen N; Le Marchand, Loïc; Lindor, Noralane M; Hopper, John L; Jenkins, Mark A; Win, Aung Ko

    2015-12-01

    Inheritance of a germline mutation in one of the DNA mismatch repair (MMR) genes or the EPCAM gene is associated with an increased risk of colorectal cancer, endometrial cancer, and other adult malignancies (Lynch syndrome). The risk of childhood cancers in Lynch syndrome families, however, is not well studied. Using data from the Colon Cancer Family Registry, we compared the proportion of childhood cancers (diagnosed before 18 years of age) in the first-, second-, and third-degree relatives of 781 probands with a pathogenic mutation in one of the MMR genes; MLH1 (n = 275), MSH2 (n = 342), MSH6 (n = 99), or PMS2 (n = 55) or in EPCAM (n = 10) (Lynch syndrome families), with that of 5073 probands with MMR-deficient colorectal cancer (non-Lynch syndrome families). There was no evidence of a difference in the proportion of relatives with a childhood cancer between Lynch syndrome families (41/17,230; 0.24%) and non-Lynch syndrome families (179/94,302; 0.19%; p = 0.19). Incidence rate of all childhood cancers was estimated to be 147 (95% CI 107-206) per million population per year in Lynch syndrome families and 115 (95% CI 99.1-134) per million population per year in non-Lynch syndrome families. There was no evidence for a significant increase in the risk of all childhood cancers, hematologic cancers, brain and central nervous system cancers, Lynch syndrome-associated cancers, or other cancers in Lynch syndrome families compared with non-Lynch syndrome families. Larger studies, however, are required to more accurately define the risk of specific individual childhood cancers in Lynch syndrome families.

  2. Lynch Syndrome: Female Genital Tract Cancer Diagnosis and Screening.

    Science.gov (United States)

    Mills, Anne M; Longacre, Teri A

    2016-06-01

    Lynch syndrome is responsible for approximately 5% of endometrial cancers and 1% of ovarian cancers. The molecular basis for Lynch syndrome is a heritable functional deficiency in the DNA mismatch repair system, typically due to a germline mutation. This review discusses the rationales and relative merits of current Lynch syndrome screening tests for endometrial and ovarian cancers and provides pathologists with an informed algorithmic approach to Lynch syndrome testing in gynecologic cancers. Pitfalls in test interpretation and strategies to resolve discordant test results are presented. The potential role for next-generation sequencing panels in future screening efforts is discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Merrill Lynch kavandab äridelegatsiooni visiiti Eestisse

    Index Scriptorium Estoniae

    2000-01-01

    Investeerimispanga Merrill Lynch eestvedamisel kavandatakse mais ärimeeste visiiti Eestisse, ütles Jüri Mõis, kes viibis New Yorgis toimunud Maailmapanga seminaril "Omavalitsused rahvusvahelistel kapitaliturgudel"

  4. Role for Genetic Anticipation in Lynch Syndrome

    DEFF Research Database (Denmark)

    Nilbert, Mef; Timshel, Susanne; Bernstein, Inge

    2009-01-01

    PURPOSE: Anticipation (ie, an earlier age at onset in successive generations) is linked to repeat expansion in neurodegenerative syndromes, whereas its role in hereditary cancer is unclear. We assessed anticipation in Lynch syndrome (hereditary nonpolyposis colorectal cancer [HNPCC]), in which DNA...... mismatch repair (MMR) defects cause early and accelerated tumor development with a broad tumor spectrum. PATIENTS AND METHODS: In the population-based Danish HNPCC registry, 407 MMR gene mutation carriers who had developed cancer associated with Lynch syndrome, were identified. These individuals formed 290...... parent-child pairs in which age at the first cancer diagnosis was assessed. A paired t-test and a specifically developed bivariate model were used to assess a possible role of anticipation. RESULTS: Both methods revealed anticipation with children developing cancer mean 9.8 years (P

  5. Synthetic genetic polymers capable of heredity and evolution

    DEFF Research Database (Denmark)

    Pinheiro, Vitor B; Taylor, Alexander I; Cozens, Christopher

    2012-01-01

    in and recovered from six alternative genetic polymers based on simple nucleic acid architectures not found in nature [xeno-nucleic acids (XNAs)]. We also select XNA aptamers, which bind their targets with high affinity and specificity, demonstrating that beyond heredity, specific XNAs have the capacity......Genetic information storage and processing rely on just two polymers, DNA and RNA, yet whether their role reflects evolutionary history or fundamental functional constraints is currently unknown. With the use of polymerase evolution and design, we show that genetic information can be stored...... for Darwinian evolution and folding into defined structures. Thus, heredity and evolution, two hallmarks of life, are not limited to DNA and RNA but are likely to be emergent properties of polymers capable of information storage....

  6. Francis Galton on twins, heredity and social class.

    Science.gov (United States)

    Burbridge, D

    2001-09-01

    In 1875 Francis Galton was the first to study twins as a test of the relative strenght of heredity and environment. This paper examines Galton's work on twins, using his surviving working papers. It shows that his enquiry was larger and more systematic than previously realized. Galton issued several hundred questionnaires to parents of twins, with the aim of establishing how far the similarities and differences between twins were affected by their life experiences. The paper also discusses Galton's study in relation to his understanding of the physiology of twinning and his theory of heredity. The modern concept of monozygotic twins had not yet been established, and the similarity between Galton's work and modern twin studies should not be overstated. While Galton's work was important as a pioneering study, in some respects his conclusions went beyond his evidence. The paper finally examines whether Galton's twin studies influenced his position on the links between social class, heredity and social mobility, and surveys the evidence for his views on these issues.

  7. Advances in the study of Lynch syndrome in China.

    Science.gov (United States)

    Lu, Jun-Yu; Sheng, Jian-Qiu

    2015-06-14

    Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer, is an autosomal dominant genetic condition that has a high risk of colon cancer as well as other cancers due to inherited mutations in mismatch repair (MMR) genes. During the last decades, there have been great advances in research on Chinese Lynch syndrome. This review mainly focuses on the genetic basis, clinicopathologic features, diagnosis, intervention, chemoprevention, and surveillance of Lynch syndrome in China. In addition to frequently altered MMR genes, such as MLH1, MSH2, MSH6, and MLH3, other MMR-associated genes, such as those encoding human exonuclease 1, transforming growth factor β receptor 2, and alanine aminopeptidase, metastasis-associated protein 2, adenomatosis polyposis coli down-regulated 1, and hepatic and glial cell adhesion molecule have also been implicated in Chinese Lynch syndrome. Most Chinese researchers focused on the clinicopathologic features of Lynch syndrome, and it is noticeable that the most frequent extracolonic tumor in northeast China is lung cancer, which is different from other areas in China. The Chinese diagnostic criteria for Lynch syndrome have been established to identify gene mutation or methylation. With regard to chemoprevention, celecoxib may be effective to prevent polyps relapse in Lynch syndrome carriers. Additionally, a colonoscopy-based surveillance strategy for the prevention and early detection of neoplasms in Lynch-syndrome carriers has been proposed.

  8. PMS2 Involvement in Patients Suspected of Lynch Syndrome

    NARCIS (Netherlands)

    Niessen, Renee C.; Kleibeuker, Jan H.; Westers, Helga; Jager, Paul O. J.; Rozeveld, Dennie; Bos, Krista K.; Boersma-van Ek, Wytske; Hollema, Harry; Sijmons, Rolf H.; Hofstra, Robert M. W.

    It is well-established that germline mutations in the mismatch repair genes MLH1, MSH2, and MSH6 cause Lynch syndrome. However, mutations in these three genes do not account for all Lynch syndrome (suspected) families. Recently, it was shown that germline mutations in another mismatch repair gene,

  9. Mutation spectrum in South American Lynch syndrome families

    DEFF Research Database (Denmark)

    Dominguez-Valentin, Mev; Nilbert, Mef; Wernhoff, Patrik

    2013-01-01

    Genetic counselling and testing for Lynch syndrome have recently been introduced in several South American countries, though yet not available in the public health care system.......Genetic counselling and testing for Lynch syndrome have recently been introduced in several South American countries, though yet not available in the public health care system....

  10. Features of ovarian cancer in Lynch syndrome (Review).

    Science.gov (United States)

    Nakamura, Kanako; Banno, Kouji; Yanokura, Megumi; Iida, Miho; Adachi, Masataka; Masuda, Kenta; Ueki, Arisa; Kobayashi, Yusuke; Nomura, Hiroyuki; Hirasawa, Akira; Tominaga, Eiichiro; Aoki, Daisuke

    2014-11-01

    Lynch syndrome is a hereditary ovarian cancer with a prevalence of 0.9-2.7%. Lynch syndrome accounts for 10-15% of hereditary ovarian cancers, while hereditary breast and ovarian cancer syndrome accounts for 65-75% of these cancers. The lifetime risk for ovarian cancer in families with Lynch syndrome is ~8%, which is lower than colorectal and endometrial cancers, and ovarian cancer is not listed in the Amsterdam Criteria II. More than half of sporadic ovarian cancers are diagnosed in stage III or IV, but ≥80% of ovarian cancers in Lynch syndrome are diagnosed in stage I or II. Ovarian cancers in Lynch syndrome mostly have non-serous histology and different properties from those of sporadic ovarian cancers. A screening method for ovarian cancers in Lynch syndrome has yet to be established and clinical studies of prophylactic administration of oral contraceptives are not available. However, molecular profiles at the genetic level indicate that ovarian cancer in Lynch syndrome has a more favorable prognosis than sporadic ovarian cancer. Inhibitors of the phosphatidylinositol 3-kinase/mammalian target of the rapamycin pathway and anti-epidermal growth factor antibodies may have efficacy for the disease. To the best of our knowledge, this is the first review focusing on ovarian cancer in Lynch syndrome.

  11. Recent discoveries in the molecular genetics of Lynch syndrome.

    Science.gov (United States)

    Boland, C Richard

    2016-07-01

    Lynch syndrome is the inherited predisposition to cancer caused by a germline mutation in a DNA mismatch repair gene. The consequent tumors have a characteristic microsatellite instability (MSI) phenotype. Genomic sequencing of Lynch syndrome-associated colorectal cancers (CRCs) has demonstrated that these tumors have a substantially greater number of mutations than non-MSI CRCs, and that the target mutations driving tumor behavior are also different from what occurs in sporadic tumors. There are multiple non-Lynch syndrome entities that can create clinical confusion with that disease, including the acquired methylation of MLH1, Lynch-like syndrome, and Familial CRC-Type X. Patients with Lynch syndrome-associated CRCs have a substantially better prognosis, and there is growing evidence that this is due to the generation of immunogenic frameshift peptides as a consequence of defective DNA mismatch repair, and an effective immune response to the tumor.

  12. Heredity As Ideology: Ideas of the Woman's Christian Temperance Union of The United States and Ontario on Heredity and Social Reform, 1880-1910.

    Science.gov (United States)

    Bedford, Riiko

    2015-01-01

    The Woman's Christian Temperance Union (WCTU) of the United States and Ontario created in the 1880s departments of work dedicated to the study and care of heredity. This article examines the history of these departments and explores how the two organizations made differing use of the concept of heredity to support their particular agendas and methods for social reform. By exploring how heredity functioned as a malleable resource for the WCTU, this comparative case study also serves as an example of the cultural lives of scientific concepts.

  13. Genetic anticipation in Swedish Lynch syndrome families

    DEFF Research Database (Denmark)

    von Salomé, Jenny; Boonstra, Philip S; Karimi, Masoud

    2017-01-01

    Among hereditary colorectal cancer predisposing syndromes, Lynch syndrome (LS) caused by mutations in DNA mismatch repair genes MLH1, MSH2, MSH6 or PMS2 is the most common. Patients with LS have an increased risk of early onset colon and endometrial cancer, but also other tumors that generally have...... an earlier onset compared to the general population. However, age at first primary cancer varies within families and genetic anticipation, i.e. decreasing age at onset in successive generations, has been suggested in LS. Anticipation is a well-known phenomenon in e.g neurodegenerative diseases and several...

  14. Henry Giroux and the Arts

    Science.gov (United States)

    Trend, David

    2012-01-01

    Henry A. Giroux is well known for pushing the definitions of education. From his early forays into what has been termed the "New Sociology of Education" in the early 1980s to his more recent discussions of "public pedagogy", Giroux has methodically challenged existing orthodoxies. This essay will focus on the interdisciplinary broadening of…

  15. O legado de Henry Kissinger

    Directory of Open Access Journals (Sweden)

    PAULO ROBERTO DE ALMEIDA

    2010-10-01

    Full Text Available O presente artigo busca analisar criticamente a importância e o legado do ex-secretário de Estado e ex-Conselheiro de Segurança Internacional dos EUA Henry Kissinger, figura emblemática e multifacetada.

  16. Joseph Henry and the Telegraph

    Science.gov (United States)

    Hochfelder, David

    1997-04-01

    Morse's telegraph rested upon three scientific advances which occured between 1800 and 1830: the development of battery technology, the formulation of laws governing the behavior of electrical components in circuits, and the discovery of electromagnetic phenomena. Joseph Henry was crucial to the development of the early telegraph. His work on electromagnetism made it possible for the electric current to manifest itself as useful mechanical work. Henry developed electromagnets of sufficient lifting power, but which drew relatively small currents; these magnets were the heart of Morse's telegraph receiver. Morse also used electromagnets as relays, which allowed him to transmit signals over great distances. Morse often acknowledged his debt to Henry, and the two enjoyed a cordial working relationship until the mid-1840s. But during the bitter and protracted litigation over Morse's patent, Henry testified (unwillingly, he claimed) against the inventor. This began a lifelong quarrel between the two men, the specifics of which were tedious and petty. In general terms, however, their conflict arose over different notions regarding scientific discovery and technological innovation.

  17. [The Henry E. Huntington Library.

    Science.gov (United States)

    Abraham, Terry

    The biographical sketch of Henry E. Huntington includes a description of the establishment of the Huntington Library and the purpose and scope of its collection. Although this is a free and public library, its use is restricted to qualified scholars having legitimate research needs. Photographic techniques were developed at the Huntington Library…

  18. Evolving concepts of heredity and genetics in orthodontics.

    Science.gov (United States)

    Carlson, David S

    2015-12-01

    The field of genetics emerged from the study of heredity early in the 20th century. Since that time, genetics has progressed through a series of defined eras based on a number of major conceptual and technical advances. Orthodontics also progressed through a series of conceptual stages over the past 100 years based in part on the ongoing and often circular debate about the relative importance of heredity (nature) and the local environment (nurture) in the etiology and treatment of malocclusion and dentofacial deformities. During the past 20 years, significant advancements in understanding the genomic basis of craniofacial development and the gene variants associated with dentofacial deformities have resulted in a convergence of the principles and concepts in genetics and in orthodontics that will lead to significant advancement of orthodontic treatments. Fundamental concepts from genetics and applied translational research in orthodontics provide a foundation for a new emphasis on precision orthodontics, which will establish a modern genomic basis for major improvements in the treatment of malocclusion and dentofacial deformities as well as many other areas of concern to orthodontists through the assessment of gene variants on a patient-by-patient basis. Copyright © 2015 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  19. Glioblastomas, astrocytomas and oligodendrogliomas linked to Lynch syndrome

    DEFF Research Database (Denmark)

    Therkildsen, C; Ladelund, S; Rambech, E

    2015-01-01

    BACKGROUND AND PURPOSE: Brain tumors represent a rare and relatively uncharacterized tumor type in Lynch syndrome. METHODS: The national Danish Hereditary Nonpolyposis Colorectal Cancer Register was utilized to estimate the cumulative life-time risk for brain tumors in Lynch syndrome...... staining suggestive of the IDH1 R132H mutation. CONCLUSION: In Lynch syndrome brain tumors occurred in 14% of the families with significantly higher risks for individuals with MSH2 gene mutations and development of childhood brain tumors in individuals with constitutional MMR defects....

  20. Features of ovarian cancer in Lynch syndrome (Review)

    OpenAIRE

    NAKAMURA, KANAKO; Banno, Kouji; YANOKURA, MEGUMI; Iida, Miho; Adachi, Masataka; MASUDA, KENTA; UEKI, ARISA; Kobayashi, Yusuke; Nomura, Hiroyuki; Hirasawa, Akira; Tominaga, Eiichiro; Aoki, Daisuke

    2014-01-01

    Lynch syndrome is a hereditary ovarian cancer with a prevalence of 0.9–2.7%. Lynch syndrome accounts for 10–15% of hereditary ovarian cancers, while hereditary breast and ovarian cancer syndrome accounts for 65–75% of these cancers. The lifetime risk for ovarian cancer in families with Lynch syndrome is ~8%, which is lower than colorectal and endometrial cancers, and ovarian cancer is not listed in the Amsterdam Criteria II. More than half of sporadic ovarian cancers are diagnosed in stage II...

  1. Indsigter og udfordringer i danske Lynch-syndrom-familier

    DEFF Research Database (Denmark)

    Therkildsen, Christina; Timshel, Susanne; Nilbert, Mef

    2008-01-01

    identified 88 unique mutations in 164 Danish families delineated as Lynch syndrome families. Predictive genetic diagnostics enables the identification of high risk individuals, who are offered participation in surveillance programmes that effectively reduce morbidity and mortality in colorectal cancer....

  2. Pupazzi di neve. David Lynch fotografo e l’"Unheimliche"

    Directory of Open Access Journals (Sweden)

    Paolo Sebastiano Lanzi

    2013-02-01

    Full Text Available L’opera di David Lynch non si limita al cinema, come ha dimostrato l’esposizione del 2007 alla Fondation Cartier di Parigi, The Air is on Fire. Tuttavia gli studi teorici hanno trascurato ciò che gallerie e musei hanno evidenziato da tempo: il Lynch pittore, fotografo, musicista, artista poliedrico. L’articolo si focalizza su una serie fotografica, Snowmen, ed è tratto da una ricerca di Paolo Sebastiano Lanzi sulla figura di David Lynch fotografo. Alla luce del saggio di Freud sul Perturbante (Das Unheimliche, 1919 si interpretano gli Snowmen come immagini di morte. Si chiariscono alcuni aspetti della poetica dell’artista-regista, come l’inquietudine dell’Inland Empire o di certe idee care al Surrealismo. Lo studio della produzione fotografica di Lynch riempie un vuoto nell’analisi critica sul suo lavoro, che va necessariamente riconsiderato in una prospettiva più ampia.

  3. Epigenetic mechanisms in the pathogenesis of Lynch syndrome.

    Science.gov (United States)

    Peltomäki, P

    2014-05-01

    Inherited defects in the DNA mismatch repair (MMR) system, MLH1, MSH2, MSH6, and PMS2 genes, underlie Lynch syndrome, one of the most prevalent cancer syndromes in man. The syndrome offers a model for cancers arising through MMR defects and microsatellite instability, which applies to ~ 15% of all colorectal, endometrial, and other cancers. Lynch syndrome also illustrates the significance of the epigenetic component in cancer development. Inactivation of tumor suppressor genes by epigenetic mechanisms is an acquired property of many tumors developing in Lynch syndrome. Furthermore, constitutional epimutations of MMR genes may explain a proportion of mutation-negative families lacking MLH1 or MSH2 protein expression in tumor tissue. This review provides an update of the molecular basis of Lynch syndrome by focusing on the role of epigenetic mechanisms in the pathogenesis of the disease. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Quality colonoscopy and risk of interval cancer in Lynch syndrome

    NARCIS (Netherlands)

    Haanstra, J. F.; Vasen, H. F. A.; Sanduleanu, S.; van der Wouden, E. J.; Koornstra, J. J.; Kleibeuker, J. H.; Cappel, W. H. de Vos Tot Nederveen

    2013-01-01

    Despite colonoscopic surveillance, Lynch syndrome patients develop colorectal cancer (CRC). Identification of modifiable factors has the potential to improve outcome of surveillance. The aims of this study were to determine (1) characteristics of patients with CRC, (2) endoscopic and histological

  5. Upper urinary tract carcinoma in Lynch syndrome cases.

    Science.gov (United States)

    Crockett, David G; Wagner, David G; Holmäng, Sten; Johansson, Sonny L; Lynch, Henry T

    2011-05-01

    Patients with Lynch syndrome are much more likely to have generally rare upper urinary tract urothelial carcinoma but not bladder urothelial carcinoma. While the risk has been quantified, to our knowledge there is no description of how this population of patients with Lynch syndrome and upper urinary tract cancer differs from the general population with upper urinary tract cancer. We obtained retrospective data on a cohort of patients with Lynch syndrome from the Hereditary Cancer Center in Omaha, Nebraska and compared the data to those on a control general population from western Sweden. These data were supplemented by a new survey about exposure to known risk factors. Of the patients with Lynch syndrome 91% had mutations in MSH2 rather than in MSH1 and 79% showed upper tract urothelial carcinoma a mean of 15.85 years after prior Lynch syndrome-type cancer. Median age at diagnosis was 62 years vs 70 in the general population (p Lynch syndrome 51% had urothelial carcinoma in the ureter while it occurred in the renal pelvis in 65% of the general population (p = 0.0013). Similar numbers of high grade tumors were found in the Lynch syndrome and general populations (88% and 74%, respectively, p = 0.1108). Upper urinary tract tumors develop at a younger age and are more likely to be in the ureter with an almost equal gender ratio in patients with Lynch syndrome. It has high grade potential similar to that in the general population. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  6. Colorectal surveillance in Lynch syndrome families.

    Science.gov (United States)

    de Vos tot Nederveen Cappel, Wouter H; Järvinen, Heikki J; Lynch, Patrick M; Engel, Christoph; Mecklin, Jukka-Pekka; Vasen, Hans F A

    2013-06-01

    Lynch syndrome (LS) is an autosomal dominant disorder caused by a mutation in one of the mismatch repair genes. Mutation carriers have a life-time risk of developing colorectal cancer (CRC) of between 25 and 75 %. Since the importance of a centralized organization of surveillance was emphasized in the late 1980s, the number of registered LS families with a known mutation has increased enormously worldwide. Large-scale surveillance programs of these families have achieved a 62 % reduction in incidence of CRC and a 65-70 % decrease in mortality. Nevertheless, the risk of CRC is still substantial even when included in a program and the most optimal surveillance interval for gene carriers remains unknown. Hopefully, improvements in high quality colonoscopy and new endoscopic visualization techniques will further reduce CRC risk in those included in a surveillance program.

  7. 100 years lynch syndrome

    DEFF Research Database (Denmark)

    Bleiker, Eveline M A; Esplen, Mary Jane; Meiser, Bettina

    2013-01-01

    In the care of patients with Lynch Syndrome (LS), a range of psychosocial issues are encountered, which significantly affect patient outcomes. A brief historical background of 'psycho-onco-genetics' (the domain where psychology, oncology and genetics meet) in relation to LS is presented, followed...... by an overview of important psychosocial issues identified in the past 20 years. The identification of mismatch repair genes in 1993-1994 made possible genetic counseling and testing for patients who had cancer and for potentially high-risk relatives without cancer. At that time, concerns were raised about...... psychosocial impact (e.g. psychological adaptation, impact on risk perception and self-concept, and concerns about, and experiences of, genetic discrimination), psychological screening instruments, adherence to and decision-making about preventive strategies, family communication, lifestyle changes...

  8. MOUNT HENRY ROADLESS AREA, MONTANA.

    Science.gov (United States)

    Van Loenen, Richard E.; Conyac, Martin D.

    1984-01-01

    A mineral survey of the Mount Henry Roadless Area, Lincoln County, Montana, was conducted. A small area located along the southwest boundary was determined to have a probable mineral-resource potential for low-grade deposits of stratabound copper and silver. There is little possibility for locatable mineral, coal, oil, gas, and geothermal resources in the remainder of the area. There are no mines, prospects, or records of mineral production within the roadless area.

  9. The Henry's constant of monochloramine.

    Science.gov (United States)

    Garcia, Miguel A; Anderson, Michael A

    2018-02-01

    Monochloramine is a secondary disinfectant used in drinking water and is also formed in chlorinated wastewater. While known to hydrolyze over time and react with dissolved organic matter, its partitioning between the aqueous and gas phase has not been extensively studied. Preliminary experiments demonstrated that monochloramine concentrations in solutions open to the atmosphere or actively aerated decreased more rapidly than in sealed solutions, indicating significant losses to the atmosphere. For example, a monochloramine solution open to the atmosphere yielded a loss rate constant of 0.08 d-1, a value twice that for sealed samples without headspace (0.04 d-1) where loss occurs exclusively as a result of hydrolysis. A solution aerated at 10 mL s-1 had a loss rate constant nearly 10× greater than that for hydrolysis alone (0.35 d-1). To better understand partitioning of monochloramine to the gas phase and potential for volatilization, the dimensionless Henry's law constants of monochloramine (KH) were determined using an equilibrium headspace technique at five different temperatures (11, 16, 21, 27, and 32 °C). The resulting values ranged from 8 × 10-3 to 4 × 10-2, indicating a semi-volatile compound, and were found to be consistent with quantitative structure activity relationship predictions. At 20 °C, monochloramine exhibits a dimensionless Henry's constant of about 1.7 × 10-2 which is 35 times greater than ammonia but comparable to the Henry's constant of inorganic semi-volatile compounds such sulfur dioxide. The Henry's constant values for monochloramine suggests that volatilization could be a relevant loss process in open systems such as rivers receiving chlorinated wastewater effluent, swimming pools and cooling towers. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Further study on heredity of liquid aluminum modified by electric pulse

    Directory of Open Access Journals (Sweden)

    Qi Jingang

    2011-08-01

    Full Text Available The remarkable heredity of liquid aluminum modified by electric pulse (EP, EPM has been uncovered. For better understanding from all aspects on the hereditary properties, the present research deals with the heredity destruction and the secondary EPM procedure. It is shown that the secondary EPM is capable of preventing the heredity reduction of EP-modified liquid aluminum, and that the final refining effect has a close relationship with technique parameters of the secondary EPM. Furthermore, at a certain superheated temperature depending on the initial EPM technique parameters, the heredity relationship of EP-modified liquid aluminum can be cut off during remelting. High temperature X-ray diffraction combining with the DSC tests also indicates that the EP-induced structure changes have almost disappeared at an elevated remelting temperature.

  11. One to 2-year surveillance intervals reduce risk of colorectal cancer in families with Lynch syndrome

    NARCIS (Netherlands)

    Vasen, Hans F. A.; Abdirahman, Mohamed; Brohet, Richard; Langers, Alexandra M. J.; Kleibeuker, Jan H.; van Kouwen, Mariette; Koornstra, Jan Jacob; Boot, Henk; Cats, Annemieke; Dekker, Evelien; Sanduleanu, Silvia; Poley, Jan-Werner; Hardwick, James C. H.; de Vos tot Nederveen Cappel, Wouter H.; van der Meulen-de Jong, Andrea E.; Tan, T. Gie; Jacobs, Maarten A. J. M.; Mohamed, Faig Lall A.; de Boer, Sijbrand Y.; van de Meeberg, Paul C.; Verhulst, Marie-Louise; Salemans, Jan M.; van Bentem, Nico; Westerveld, B. Dik; Vecht, Juda; Nagengast, Fokko M.

    2010-01-01

    BACKGROUND & AIMS: Two percent to 4% of all cases of colorectal cancer (CRC) are associated with Lynch syndrome. Dominant clustering of CRC (non-Lynch syndrome) accounts for 1%-3% of the cases. Because carcinogenesis is accelerated in Lynch syndrome, an intensive colonoscopic surveillance program

  12. Recurrence and variability of germline EPCAM deletions in Lynch syndrome.

    Science.gov (United States)

    Kuiper, Roland P; Vissers, Lisenka E L M; Venkatachalam, Ramprasath; Bodmer, Danielle; Hoenselaar, Eveline; Goossens, Monique; Haufe, Aline; Kamping, Eveline; Niessen, Renée C; Hogervorst, Frans B L; Gille, Johan J P; Redeker, Bert; Tops, Carli M J; van Gijn, Marielle E; van den Ouweland, Ans M W; Rahner, Nils; Steinke, Verena; Kahl, Philip; Holinski-Feder, Elke; Morak, Monika; Kloor, Matthias; Stemmler, Susanne; Betz, Beate; Hutter, Pierre; Bunyan, David J; Syngal, Sapna; Culver, Julie O; Graham, Tracy; Chan, Tsun L; Nagtegaal, Iris D; van Krieken, J Han J M; Schackert, Hans K; Hoogerbrugge, Nicoline; van Kessel, Ad Geurts; Ligtenberg, Marjolijn J L

    2011-04-01

    Recently, we identified 3' end deletions in the EPCAM gene as a novel cause of Lynch syndrome. These truncating EPCAM deletions cause allele-specific epigenetic silencing of the neighboring DNA mismatch repair gene MSH2 in tissues expressing EPCAM. Here we screened a cohort of unexplained Lynch-like families for the presence of EPCAM deletions. We identified 27 novel independent MSH2-deficient families from multiple geographical origins with varying deletions all encompassing the 3' end of EPCAM, but leaving the MSH2 gene intact. Within The Netherlands and Germany, EPCAM deletions appeared to represent at least 2.8% and 1.1% of the confirmed Lynch syndrome families, respectively. MSH2 promoter methylation was observed in epithelial tissues of all deletion carriers tested, thus confirming silencing of MSH2 as the causative defect. In a total of 45 families, 19 different deletions were found, all including the last two exons and the transcription termination signal of EPCAM. All deletions appeared to originate from Alu-repeat mediated recombination events. In 17 cases regions of microhomology around the breakpoints were found, suggesting nonallelic homologous recombination as the most likely mechanism. We conclude that 3' end EPCAM deletions are a recurrent cause of Lynch syndrome, which should be implemented in routine Lynch syndrome diagnostics. © 2011 Wiley-Liss, Inc.

  13. The Don Henry Story. Teaching with Documents.

    Science.gov (United States)

    National Archives and Records Administration, Washington, DC.

    Don Henry was a student at the University of Kansas (Lawrence, Kansas) who experienced a profound political change during his years on campus. Henry became a leader in radical campus organizations, volunteered to fight in the Spanish Civil War with the Lincoln Brigade, and died on the battlefield in Aragon (Spain) in September 1937. An article in…

  14. Diagnosing lynch syndrome in absence of colorectal cancer.

    Science.gov (United States)

    Lynch, Henry T; Knezetic, Joseph; Lanspa, Stephen

    2012-11-01

    There are many ways in which a diagnosis of Lynch syndrome can be made, most prominent of which is family history, presence of cancer, high microsatellite instability, immunohistochemistry, and a mismatch repair germline mutation. There are at least four molecular pathways for colorectal cancer carcinogenesis: 1) adenoma-carcinoma sequence; 2) hereditary microsatellite instability; 3) serrated pathway; 4) epidermal growth factor receptor. The answer to diagnosing Lynch syndrome in the absence of colorectal cancer may be partially based upon the phenotypic characteristics of the colonic polyps should they be identified at colonoscopy, specifically their phenotypic characteristics of location, size, histology, number, and age of polyp onset.

  15. Mismatch repair genes in Lynch syndrome: a review

    OpenAIRE

    Silva,Felipe Cavalcanti Carneiro da; Valentin, Mev Dominguez; Ferreira, Fábio de Oliveira; Carraro, Dirce Maria; Rossi, Benedito Mauro

    2009-01-01

    Lynch syndrome represents 1-7% of all cases of colorectal cancer and is an autosomal-dominant inherited cancer predisposition syndrome caused by germline mutations in deoxyribonucleic acid (DNA) mismatch repair genes. Since the discovery of the major human genes with DNA mismatch repair function, mutations in five of them have been correlated with susceptibility to Lynch syndrome: mutS homolog 2 (MSH2); mutL homolog 1 (MLH1); mutS homolog 6 (MSH6); postmeiotic segregation increased 2 (PMS2); ...

  16. Women with double primary cancers of the colorectum and endometrium: do they have Lynch syndrome?

    Science.gov (United States)

    Song, Taejong; Kim, Min Kyu; Lee, Yoo-Young; Choi, Chel Hun; Kim, Tae-Joong; Lee, Jeong-Won; Bae, Duk-Soo; Kim, Byoung-Gie

    2016-04-01

    The aim of this study was to determine the clinical characteristics of women with double primary cancers of the colorectum and endometrium and assess the probability of Lynch syndrome. We identified 15 women with paraffin-embedded blocks available who were diagnosed, treated and followed for double primary colorectal and endometrial cancers at in a single institution between 1994 and 2014. If there was a family history that met the revised Amsterdam criteria for Lynch syndrome, the woman was considered to have 'clinically defined Lynch syndrome'. If immunohistochemical (IHC) loss of expression of mismatch repair genes (MLH1, MSH2, MSH6, or PMS2) or high microsatellite instability (MSI) was demonstrated in molecular testing, the case was considered 'suspected Lynch syndrome'. The incidence of clinically defined Lynch syndrome according to the revised Amsterdam criteria was 66% (8 of 15). All 8 of the women clinically diagnosed with Lynch syndrome had either abnormal IHC loss or MSI-high, indicating a suspected Lynch syndrome. Furthermore, 27% (4 of 15) experienced second primary colorectal cancer or other Lynch syndrome-related cancers. Overall, 66% (10 of 15) met the criteria for clinically defined Lynch syndrome or suspected Lynch syndrome. Based on our findings, a large percentage (66%) of women with double primary cancers of the colorectum and endometrium are likely to be diagnosed with Lynch syndrome. Copyright © 2015. Published by Elsevier Ireland Ltd.

  17. THE MELANCHOLY OF HENRY MORE

    Directory of Open Access Journals (Sweden)

    David Thorley

    2014-12-01

    Full Text Available This article treats Henry More’s philosophical approach to melancholy and his personal experience of the disease. Koen Vermeir argues that, in approaching the imagination philosophically, More was performing a 'balancing act' between addressing the subject as a medium between soul and body, and regarding it as a non-corporeal vehicle of reason and the spirit. 'In his life', Vermeir adds, 'More was also performing a balancing act': both an opponent of and subject to enthusiasm. In this article, I give closer scrutiny to that balancing act, charting the points of distinction and overlap between More’s philosophy of and encounters with melancholy. In the search for relief for his symptoms, I argue, More deployed two significant (and related techniques: practicing philosophy and engaging in epistolary correspondence.

  18. Henry's law constants of polyols

    Science.gov (United States)

    Compernolle, S.; Müller, J.-F.

    2014-12-01

    Henry's law constants (HLC) are derived for several polyols bearing between 2 and 6 hydroxyl groups, based on literature data for water activity, vapour pressure and/or solubility. While deriving HLC and depending on the case, also infinite dilution activity coefficients (IDACs), solid state vapour pressures or activity coefficient ratios are obtained as intermediate results. An error analysis on the intermediate quantities and the obtained HLC is included. For most compounds, these are the first values reported, while others compare favourably with literature data in most cases. Using these values and those from a previous work (Compernolle and Müller, 2014), an assessment is made on the partitioning of polyols, diacids and hydroxy acids to droplet and aqueous aerosol.

  19. Henry's law constants of polyols

    Directory of Open Access Journals (Sweden)

    S. Compernolle

    2014-12-01

    Full Text Available Henry's law constants (HLC are derived for several polyols bearing between 2 and 6 hydroxyl groups, based on literature data for water activity, vapour pressure and/or solubility. While deriving HLC and depending on the case, also infinite dilution activity coefficients (IDACs, solid state vapour pressures or activity coefficient ratios are obtained as intermediate results. An error analysis on the intermediate quantities and the obtained HLC is included. For most compounds, these are the first values reported, while others compare favourably with literature data in most cases. Using these values and those from a previous work (Compernolle and Müller, 2014, an assessment is made on the partitioning of polyols, diacids and hydroxy acids to droplet and aqueous aerosol.

  20. Small bowel endoscopy in familial adenomatous polyposis and Lynch syndrome

    NARCIS (Netherlands)

    Koornstra, Jan Jacob

    Patients with familial adenomatous polyposis (FAP) and patients with Lynch syndrome have an increased risk of developing small intestinal neoplasia. In both conditions, the lifetime risk to develop small bowel cancer is estimated to be around 5%. In FAP, this risk is associated with the degree of

  1. The identification of Lynch syndrome in Congolese colorectal cancer patients.

    Science.gov (United States)

    Poaty, Henriette; Aba Gandzion, Chandra; Soubeyran, Isabelle; Gassaye, Déby; Peko, Jean Félix; Nkoua Bon, Jean Bernard; Gombé Mbalawa, Charles

    2017-10-01

    We aimed to investigate the prevalence of Lynch syndrome as one of hereditary causes of colorectal cancer (CRC) among young Congolese individuals affected by the CRC, and to define methods for diagnosis in Congo Brazzaville. We conducted a transversal cohort study of 34 patients having a CRC with a family history for a period of eight years. They were selected among 89 CRCs of any type from the Bethesda guidelines criteria combined with pedigrees. Mismatch repair (MMR) genes alterations were researched by immunohistochemistry (IHC). We identified with the Bethesda criteria a total of 38.2% (34/89) patients having familial CRC with a confidence interval (CI) of 95%=[0.34-0.41]. Only 14.7% (5/34) 95% CI=[0.34-2.32] patients showed MMR immunodeficiency involving firstly MLH1 protein then MSH2 protein. These data account for 5.6% (5/89) 95% CI=[0.15-0.33] of patients affected by Lynch syndrome with an earlier median age of 35 years (range 20 to 47 years). The prevalence of Lynch syndrome found in Brazzaville is comparable to that is found in northern countries. The combined Bethesda guidelines, pedigree and IHC is an accessible and good alternative method for the positive diagnosis of Lynch syndrome in current practice in Congo. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  2. Fas Ligand Expression in Lynch Syndrome-Associated Colorectal Tumours

    NARCIS (Netherlands)

    Koornstra, Jan J.; de Jong, Steven; Boersma-van Eck, Wietske; Zwart, Nynke; Hollema, Harry; de Vries, Elisabeth G. E.; Kleibeuker, Jan H.

    Fas Ligand (FasL) expression by cancer cells may contribute to tumour immune escape via the Fas counterattack against tumour-infiltrating lymphocytes (TILs). Whether this plays a role in colorectal carcinogenesis in Lynch syndrome was examined studying FasL expression, tumour cell apoptosis and

  3. Role of new endoscopic techniques in Lynch syndrome

    NARCIS (Netherlands)

    Haanstra, Jasmijn F.; Kleibeuker, Jan H.; Koornstra, Jan J.

    Lynch syndrome, or hereditary nonpolyposis colorectal cancer (HNPCC), is the most common hereditary condition predisposing for colorectal cancer. International guidelines recommend surveillance of the colorectum by colonoscopy every 1-2 years starting at the age of 20-25 years. This has been shown

  4. Towards improved detection and management of Lynch Syndrome

    NARCIS (Netherlands)

    D. Ramsoekh (Dewkoemar)

    2009-01-01

    textabstractLynch syndrome is the most common hereditary colorectal cancer syndrome, responsible for 3-5% of all colorectal cancer (CRC) cases. In addition, tumors of the endometrium, ovaries, stomach, small bowel, biliary tract, urinary tract, skin and brain occur at higher frequencies compared to

  5. Colorectal choriocarcinoma in a patient with probable Lynch syndrome

    Directory of Open Access Journals (Sweden)

    Viktor Hendrik Koelzer

    2016-11-01

    Full Text Available Background: Personalized therapy of colorectal cancer (CRC is influenced by morphological, molecular and host-related factors. Here we report the comprehensive clinicopathological and molecular analysis of a pure extra-gestational colorectal choriocarcinoma in a patient with probable Lynch syndrome.Case presentation: A 61 year old female with history of gastric cancer at age 36 presented with a transmurally invasive tumor of the right hemicolon and liver metastasis. A right hemicolectomy was performed. Histopathological analysis showed a mixed trophoblastic and syncytiotrophoblastic differentiation, consistent with choriocarcinoma. Disease progression was rapid under oxaliplatin, capecitabine, irinotecan (XELOXIRI and bevacizumab. Molecular phenotyping identified loss of the mismatch-repair (MMR protein PMS2, microsatellite instability, a lack of MLH1 promoter methylation and lack of of BRAF mutation suggestive of Lynch-Syndrome. Targeted next generation sequencing revealed an Ataxia Telangiectasia Mutated (ATM p.P604S missense mutation. A bleomycin, etoposide and cisplatin (BEP treatment protocol targeting germ-cell neoplasia lead to disease remission and prolonged survival of 34 months.Conclusions: Comprehensive immunohistochemical and genetic testing is essential to identify uncommon cancers possibly related to Lynch syndrome. For rare tumors, personalized therapeutic approaches should take both molecular and morphological information into account.Key words: Colorectal cancer, choriocarcinoma, histopathology, prognostic factors, Lynch syndrome, microsatellite instability, ataxia telangiectasia mutated, molecular pathology, next generation sequencing, personalized medicine

  6. Pathological assessment of mismatch repair gene variants in Lynch syndrome

    DEFF Research Database (Denmark)

    Rasmussen, Lene Juel; Heinen, Christopher D; Royer-Pokora, Brigitte

    2012-01-01

    Lynch syndrome (LS) is caused by germline mutations in DNA mismatch repair (MMR) genes and is the most prevalent hereditary colorectal cancer syndrome. A significant proportion of variants identified in MMR and other common cancer susceptibility genes are missense or noncoding changes whose conse...

  7. Do lifestyle factors influence colorectal cancer risk in Lynch syndrome?

    NARCIS (Netherlands)

    van Duijnhoven, F.J.B.; Botma, A.; Winkels, R.; Nagengast, F.M.; Vasen, H.F.A.; Kampman, E.

    2013-01-01

    Lynch syndrome (LS) is one of the inherited colorectal cancer (CRC) syndromes and is due to germline mutations in one of the mismatch repair (MMR) genes. Within LS affected-families the expression of the syndrome varies, which suggests that other factors, such as lifestyle factors, have an influence

  8. Ovarian cancer in Lynch syndrome; a systematic review

    NARCIS (Netherlands)

    Heldering-Woolderink, J. M.; Blok, E. A.; Vasen, H. F. A.; Hollema, H.; Mourits, M. J.; De Bock, G. H.

    Objective: The aim was to systematically review the characteristics of ovarian cancer in women with Lynch syndrome (LS) and evaluate the role of surveillance in detection of ovarian cancer in LS. Methods: All studies between 1979 and 2015 of women with ovarian cancer and LS or at 50% risk of LS were

  9. Sense of coherence and self-concept in Lynch syndrome

    DEFF Research Database (Denmark)

    Petersen, Helle Vendel; Ladelund, Steen; Carlsson, Christina

    2013-01-01

    Most individuals who learn about hereditary cancer manage well, but identification of subgroups who find this knowledge burdening would allow psychosocial intervention. The objective of the study was to assess sense of coherence (SOC) in individuals with Lynch syndrome with comparison to a general...

  10. Revised guidelines for the clinical management of Lynch syndrome (HNPCC)

    DEFF Research Database (Denmark)

    Vasen, Hans F A; Blanco, Ignacio; Aktan-Collan, Katja

    2013-01-01

    Lynch 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...

  11. Pain evaluation during gynaecological surveillance in women with Lynch syndrome

    NARCIS (Netherlands)

    Helder-Woolderink, Jorien; de Bock, Geertruida; Hollema, Harry; van Oven, Magda; Mourits, Marian

    To evaluate perceived pain during repetitive annual endometrial sampling at gynaecologic surveillance in asymptomatic women with Lynch syndrome (LS) over time and in addition to symptomatic women without LS, undergoing single endometrial sampling. In this prospective study, 52 women with LS or first

  12. Genetic testing for Lynch syndrome: family communication and motivation

    NARCIS (Netherlands)

    C.H.M. Leenen (Celine); M.D. Heijer (Mariska den); C.A. van der Meer (Conny); E.J. Kuipers (Ernst); M.E. van Leerdam (Monique); A. Wagner (Anja)

    2016-01-01

    textabstractCurrent genetic counselling practice for Lynch syndrome (LS) relies on diagnosed index patients to inform their biological family about LS, referred to as the family-mediated approach. The objective of this study was to evaluate this approach and to identify factors influencing the

  13. Henrys Fork near Ashton, ID (YHEN)

    Data.gov (United States)

    Department of the Interior — Henrys Fork near Ashton, Idaho (YHEN) Sample Collection: Samples were collected near the USGS stream gage 13046000 (Latitude 44°04'11", Longitude 111°30'38" NAD83)....

  14. Genetic anticipation in Swedish Lynch syndrome families.

    Directory of Open Access Journals (Sweden)

    Jenny von Salomé

    2017-10-01

    Full Text Available Among hereditary colorectal cancer predisposing syndromes, Lynch syndrome (LS caused by mutations in DNA mismatch repair genes MLH1, MSH2, MSH6 or PMS2 is the most common. Patients with LS have an increased risk of early onset colon and endometrial cancer, but also other tumors that generally have an earlier onset compared to the general population. However, age at first primary cancer varies within families and genetic anticipation, i.e. decreasing age at onset in successive generations, has been suggested in LS. Anticipation is a well-known phenomenon in e.g neurodegenerative diseases and several reports have studied anticipation in heritable cancer. The purpose of this study is to determine whether anticipation can be shown in a nationwide cohort of Swedish LS families referred to the regional departments of clinical genetics in Lund, Stockholm, Linköping, Uppsala and Umeå between the years 1990-2013. We analyzed a homogenous group of mutation carriers, utilizing information from both affected and non-affected family members. In total, 239 families with a mismatch repair gene mutation (96 MLH1 families, 90 MSH2 families including one family with an EPCAM-MSH2 deletion, 39 MSH6 families, 12 PMS2 families, and 2 MLH1+PMS2 families comprising 1028 at-risk carriers were identified among the Swedish LS families, of which 1003 mutation carriers had available follow-up information and could be included in the study. Using a normal random effects model (NREM we estimate a 2.1 year decrease in age of diagnosis per generation. An alternative analysis using a mixed-effects Cox proportional hazards model (COX-R estimates a hazard ratio of exp(0.171, or about 1.19, for age of diagnosis between consecutive generations. LS-associated gene-specific anticipation effects are evident for MSH2 (2.6 years/generation for NREM and hazard ratio of 1.33 for COX-R and PMS2 (7.3 years/generation and hazard ratio of 1.86. The estimated anticipation effects for MLH1

  15. Colorectal Cancer Risk in Patients With Lynch Syndrome and Inflammatory Bowel Disease.

    Science.gov (United States)

    Derikx, Lauranne A A P; Smits, Lisa J T; van Vliet, Shannon; Dekker, Evelien; Aalfs, Cora M; van Kouwen, Mariëtte C A; Nagengast, Fokko M; Nagtegaal, Iris D; Hoogerbrugge, Nicoline; Hoentjen, Frank

    2017-03-01

    Lynch syndrome and inflammatory bowel diseases (IBD) are associated with an increased risk of colorectal cancer (CRC). However, it is not clear whether the risk of CRC is even higher for patients with a combination of Lynch syndrome and IBD. We investigated the risk for CRC in this subgroup by establishing a Lynch syndrome cohort from the Radboud University Medical Center (Nijmegen, The Netherlands) and the Academic Medical Center (Amsterdam, The Netherlands). Patients with heterozygous germline mutations in MLH1, MSH2 (and EPCAM deletion-mediated MSH2 methylation), MSH6, or PMS2 who were tested and/or treated from 1998 through 2014 were included. Patients who developed IBD were identified by linkage of this cohort to the Dutch nationwide Pathology Registry (PALGA). Subsequently, we compared the risk of CRC between Lynch syndrome patients with IBD and without IBD. Of 1046 patients with Lynch syndrome, 15 developed IBD (1.4%). Patients with Lynch syndrome and IBD were significantly younger (median age, 38.0 y) than patients with Lynch syndrome without IBD (median age, 52.0 y; P = .001). Nevertheless, a similar proportion of patients in each group developed CRC: 4 of the 15 patients (26.7%) with Lynch syndrome and IBD compared with 311 of the 1031 patients (30.2%) with Lynch syndrome without IBD. Patients with Lynch syndrome and IBD developed CRC at a younger age (median age, 36.0 y) than patients with Lynch syndrome without IBD (median age, 46.0 y; P = .045). However, the cumulative incidence of CRC was similar between groups (P = .121). All patients with Lynch syndrome and IBD who developed CRC had ulcerative colitis, producing a higher cumulative incidence of CRC for this IBD subgroup (P Lynch syndrome and IBD develop CRC risk at a younger age than patients without IBD; patients with ulcerative colitis are at especially high risk. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  16. Obituary: Henry Emil Kandrup, 1955-2003

    Science.gov (United States)

    Merritt, David; Gottesman, Stephen T.

    2004-12-01

    Henry Emil Kandrup died on 18 October 2003 at his home in Gainesville Florida. Henry was a theoretical astrophysicist specializing in the application of chaotic dynamics to stellar systems. At the time of his death, Henry was a Professor at the University of Florida where he had taught for 13 years. Henry was born in Manhasset, New York on July 24, 1955 and spent most of his childhood in Great Neck. His parents, Jytte and Fred, were immigrants from Denmark where his father had worked as a silver smith. Henry was a precocious child, skipping both third and fifth grades. With the help of Sidney Spivack, a professor of sociology at Columbia University, his parents enrolled Henry in the Brooks Preparatory School in Andover, Massachusetts. After graduating at age 16, Henry enrolled at Cornell, transferring to Princeton the following year. Henry's parents adored their only child and worked hard to provide him with intellectual opportunities. Henry became an accomplished musician (organ, piano, French horn) and linguist (English, Danish, German) and was a passionate devotee of opera and ballet. Henry received his PhD in 1980 from the University of Chicago, where his thesis advisor was James Ipser. He taught at Oakland University in Michigan and Syracuse University in New York before coming to the University of Florida in 1990. Henry was sui generis. He shunned conventionality in his personal appearance and in his public demeanor, and always chose forthrightness and candor over polite silence. But to those of us who knew Henry well, his bluntness was a reflection of his intellectual consistency. Henry always said exactly what he thought, both in his published work and his public presentations, and never compromised himself for the sake of appearances. Nothing that he said or wrote was less than fully thought out. Henry's PhD thesis was entitled "Stochastic Problems in Stellar Dynamics," and most of his subsequent research was in this field. Motion in stellar systems can be

  17. Later reproductive health after B-Lynch sutures: a follow-up study after 10 years' clinical use of the B-Lynch suture.

    Science.gov (United States)

    Fuglsang, Jens

    2014-04-01

    To evaluate the reproductive prognosis after having a B-Lynch suture placed previously. Follow-up study based on patients' records. University hospital setting (level three; 4,800 deliveries per year). All patients registered to have had a B-Lynch suture placed from 2002 to 2012. None. Future pregnancies. Forty-four B-Lynch procedures were identified in 43 women. Twenty-six were primiparas at the time of B-Lynch suture. Follow-up took place a median 45 months (range, 17-126 months) after B-Lynch suture placement; one woman was lost to follow-up. Overall, 16 of 42 women obtained a new pregnancy. Among primiparas, 44% either had an ongoing pregnancy or a delivery. Among women not having a succeeding pregnancy, one woman had a peripartum hysterectomy, one was advised against pregnancy, one developed Asherman's syndrome, and three women were known to attempt to obtain pregnancy. In deliveries after a previous B-Lynch suture, 3 of 13 women had estimated bleeding above 1,000 mL, and 2 of these had severe bleeding. A time trend was observed indicating that B-Lynch sutures are placed increasingly often. The reproductive prognosis after a B-Lynch suture has been placed seems to be relatively good. Nonetheless, complications that might influence future pregnancy may occur, and advice given should address this. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  18. Determining Parameters of Fractional-Exponential Heredity Kernels of Nonlinear Viscoelastic Materials

    Science.gov (United States)

    Golub, V. P.; Pavlyuk, Ya. V.; Fernati, P. V.

    2017-07-01

    The problem of determining the parameters of fractional-exponential heredity kernels of nonlinear viscoelastic materials is solved. The methods for determining the parameters that are used in the cubic theory of viscoelasticity and the nonlinear theories based on the conditions of similarity of primary creep curves and isochronous creep diagrams are analyzed. The parameters of fractional-exponential heredity kernels are determined and experimentally validated for the oriented polypropylene, FM3001 and FM10001 nylon fibers, microplastics, TC 8/3-250 glass-reinforced plastic, SWAM glass-reinforced plastic, and contact molding glass-reinforced plastic.

  19. Current hypotheses on how microsatellite instability leads to enhanced survival of Lynch Syndrome patients.

    Science.gov (United States)

    Drescher, Kristen M; Sharma, Poonam; Lynch, Henry T

    2010-01-01

    High levels of microsatellite instability (MSI-high) are a cardinal feature of colorectal tumors from patients with Lynch Syndrome. Other key characteristics of Lynch Syndrome are that these patients experience fewer metastases and have enhanced survival when compared to patients diagnosed with microsatellite stable (MSS) colorectal cancer. Many of the characteristics associated with Lynch Syndrome including enhanced survival are also observed in patients with sporadic MSI-high colorectal cancer. In this review we will present the current state of knowledge regarding the mechanisms that are utilized by the host to control colorectal cancer in Lynch Syndrome and why these same mechanisms fail in MSS colorectal cancers.

  20. Metachronous Uterine Endometrioid Adenocarcinoma and Peritoneal Mesothelioma in Lynch Syndrome: A Case Report.

    Science.gov (United States)

    Lu, Yuxin; Milchgrub, Sara; Khatri, Gaurav; Gopal, Purva

    2017-05-01

    Lynch syndrome is a hereditary disease with germline mutation in a DNA mismatch repair gene, most often presenting with colorectal and/or endometrial carcinomas; however, the spectrum of Lynch syndrome-associated tumors is expanding. In this article, we report a case of a primary peritoneal epithelioid mesothelioma that developed in a Lynch syndrome patient 10 months after diagnosis of uterine endometrioid adenocarcinoma. To our knowledge, this is the first reported case of a Lynch syndrome patient with metachronous uterine endometrioid adenocarcinoma and primary peritoneal mesothelioma.

  1. IDH1 mutated low grade astrocytoma occurring in MSH2 mutated Lynch syndrome family

    Directory of Open Access Journals (Sweden)

    Alaa Alkhotani

    2016-12-01

    Full Text Available Lynch syndrome (LS is an autosomal dominant tumour predisposition syndrome caused by a germline mutation in one of the DNA mismatch repair (MMR genes.Patients with these mutations have an increased risk of brain tumours, the vast majority of which are glioblastomas and medulloblastomas, and their occurrence has been termed Turcot Syndrome. The case presented herein of a member of a Lynch syndrome family with an MSH2 mutation expands the spectrum of brain tumours occurring in Lynch syndrome to include low grade astrocytomas, and is the first reported case of an IDH1 (R132H mutated brain tumour occurring in a Lynch syndrome family.

  2. Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability

    National Research Council Canada - National Science Library

    Umar, Asad; Boland, C Richard; Terdiman, Jonathan P; Syngal, Sapna; de la Chapelle, Albert; Rüschoff, Josef; Fishel, Richard; Lindor, Noralane M; Burgart, Lawrence J; Hamelin, Richard; Hamilton, Stanley R; Hiatt, Robert A; Jass, Jeremy; Lindblom, Annika; Lynch, Henry T; Peltomaki, Païvi; Ramsey, Scott D; Rodriguez-Bigas, Miguel A; Vasen, Hans F A; Hawk, Ernest T; Barrett, J Carl; Freedman, Andrew N; Srivastava, Sudhir

    2004-01-01

    Hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is a common autosomal dominant syndrome characterized by early age at onset, neoplastic lesions, and microsatellite instability (MSI...

  3. Current Hypotheses on How Microsatellite Instability Leads to Enhanced Survival of Lynch Syndrome Patients

    Directory of Open Access Journals (Sweden)

    Kristen M. Drescher

    2010-01-01

    Full Text Available High levels of microsatellite instability (MSI-high are a cardinal feature of colorectal tumors from patients with Lynch Syndrome. Other key characteristics of Lynch Syndrome are that these patients experience fewer metastases and have enhanced survival when compared to patients diagnosed with microsatellite stable (MSS colorectal cancer. Many of the characteristics associated with Lynch Syndrome including enhanced survival are also observed in patients with sporadic MSI-high colorectal cancer. In this review we will present the current state of knowledge regarding the mechanisms that are utilized by the host to control colorectal cancer in Lynch Syndrome and why these same mechanisms fail in MSS colorectal cancers.

  4. Ssk or Esw? -- the Bloor-Lynch Debate Revisited

    Science.gov (United States)

    Cheng, Kai-Yuan

    2014-03-01

    Philosophical discussions of rule-following in the later Wittgenstein (1953, 1967) are an important source of inspiration for the development of views on the social nature of scientific knowledge. Two major opposing views in this inquiry -- Bloor's sociology of scientific knowledge (SSK) (1983, 1991, 1992, 1997) and Lynch's (1992, 1993) ethnomethodological studies of work (ESW) -- represent two positions derived from two different readings of Wittgenstein's later writings on rule-following. The aim of this paper is two-fold. One is to re-examine the noted Bloor-Lynch debate by considering Kusch's (2004) recent discussion of this debate. Another is to show that a new semantic framework of rule-following ascriptions based on a cognitive approach to the study of generics can be provided such that SSK and ESW are compatible in it (Leslie, 2009; Cheng, 2011).

  5. Hollywood : industria de pesadillas, según David Lynch

    OpenAIRE

    Solís Samper, Arantxa

    2012-01-01

    Del análisis de la película de David Lynch Mulholland Drive se destila la crítica que el cineasta hace de la mayor industria mundial de cine: Hollywood. Se tiende a pensar comúnmente que es el lugar donde los sueños se hacen realidad, no sólo porque las fantasías se materializan en películas, sino porque los actores luchan durante años por ganarse un sitio. Pero Lynch no lo ve así, la película Mulholland Drive es un sueño en sí misma, que se torna pesadilla cuando la protagonista entra en con...

  6. Ectopic, retroperitoneal adrenocortical carcinoma in the setting of Lynch syndrome.

    Science.gov (United States)

    Wright, Jesse P; Montgomery, Kathleen W; Tierney, Joshua; Gilbert, Jill; Solórzano, Carmen C; Idrees, Kamran

    2017-09-22

    Adrenocortical carcinoma (ACC) is rare within the adult population. Ectopic ACC proves even rarer. This variant is formed by cortical fragments arrested during embryologic migration. ACC is also known to be associated with several genetic syndromes and has recently been linked to Lynch syndrome in 3% of cases. We present the case of a 68-year-old male with a confirmed diagnosis of Lynch syndrome secondary to a germline MSH2 mismatch-repair gene-mutation who presented with 2 months history of non-specific abdominal pain. After imaging work-up, the patient was found to have a right upper quadrant, retroperitoneal mass. Biochemical tests were without any evidence of a hormonally active process. Fine needle aspiration of the mass revealed a poorly differentiated carcinoma of unknown etiology. The lesion was resected and found to be consistent with ectopic ACC with an associated MSH2 mutation.

  7. Lynch Syndrome Caused by Germline PMS2 Mutations

    DEFF Research Database (Denmark)

    Ten Broeke, Sanne W; Brohet, Richard M; Tops, Carli M

    2015-01-01

    PURPOSE: The clinical consequences of PMS2 germline mutations are poorly understood compared with other Lynch-associated mismatch repair gene (MMR) mutations. The aim of this European cohort study was to define the cancer risk faced by PMS2 mutation carriers. METHODS: Data were collected from 98...... PMS2 families ascertained from family cancer clinics that included a total of 2,548 family members and 377 proven mutation carriers. To adjust for potential ascertainment bias, a modified segregation analysis model was used to calculate colorectal cancer (CRC) and endometrial cancer (EC) risks....... Standardized incidence ratios (SIRs) were calculated to estimate risks for other Lynch syndrome-associated cancers. RESULTS: The cumulative risk (CR) of CRC for male mutation carriers by age 70 years was 19%. The CR among female carriers was 11% for CRC and 12% for EC. The mean age of CRC development was 52...

  8. Correlation between Heredity Factor and Menarcheal Age among Adolescent Aged 9–15 Years Old

    Directory of Open Access Journals (Sweden)

    Nurul Khotimah

    2017-06-01

    Full Text Available Background: Menarche is a sign of maturity of the female reproductive function. It is influenced by many factors, such as heredity, general health status, nutrition, and socioeconomic status. The purpose of this study is to determine the correlation of heredity and menarcheal age. Methods:This study was a cross-sectional analytic study conducted from September–October 2014 in Bandung using a multi-stage sampling technique and it was  conducted in twelve elementary schools and junior high schools. A total of 123 subjects were included in this study. The instrument of this study was questionnaire containing menarcheal age of subject, older sister, biological mother, and maternal grandmother. The data were analyzed using Spearman correlation and linear regression test with the level of significance was determined at p<0.05. Results: Among 123 data, the majority of subjects had experienced menarche at the age of 11 (39% and 12 years (36.6% with an average of 11.46 years old. Based on the Spearman correlation and multiple linear regression tests, there was a correlation between heredity and menarcheal age. (P=0.00. Conclusions: There is a correlation between heredity and menarcheal age, with the highest correlation is between subject’s and older sister’s menarcheal age.   DOI: 10.15850/amj.v4n2.1081

  9. Renal albumin excretion: twin studies identify influences of heredity, environment, and adrenergic pathway polymorphism

    DEFF Research Database (Denmark)

    Rao, Fangwen; Wessel, Jennifer; Wen, Gen

    2007-01-01

    hydroxylase, chromogranin A, and sorting nexin 13. Dopamine D1 receptor polymorphism showed pleiotropic effects on both albumin and dopamine excretion. These studies establish new roles for heredity and environment in albumin excretion. Urinary excretions of albumin and catecholamines are highly heritable...

  10. The mutational spectrum of Lynch syndrome in cyprus.

    Directory of Open Access Journals (Sweden)

    Maria A Loizidou

    Full Text Available Lynch syndrome is the most common form of hereditary colorectal cancer and is caused by germline mutations in the mismatch repair (MMR genes MLH1, MSH2, MSH6 and PMS2. Mutation carriers have an increased lifetime risk of developing colorectal cancer as well as other extracolonic tumours. The aim of the current study was to evaluate the frequency and distribution of mutations in the MLH1, MSH2 and MSH6 genes within a cohort of Cypriot families that fulfilled the revised Bethesda guidelines. The study cohort included 77 patients who fulfilled at least one of the revised Bethesda guidelines. Mutational analysis revealed the presence of 4 pathogenic mutations, 3 in the MLH1 gene and 1 in the MSH2 gene, in 5 unrelated individuals. It is noted that out of the 4 pathogenic mutations detected, one is novel (c.1610delG in exon 14 of the MLH1 and has been detected for the first time in the Cypriot population. Overall, the pathogenic mutation detection rate in our patient cohort was 7%. This percentage is relatively low but could be explained by the fact that the sole criterion for genetic screening was compliance to the revised Bethesda guidelines. Larger numbers of Lynch syndrome families and screening of the two additional predisposition genes, PMS2 and EPCAM, are needed in order to decipher the full spectrum of mutations associated with Lynch syndrome predisposition in Cyprus.

  11. Henri-Jean Hugot (1916 -2014)

    OpenAIRE

    Amblard-Pison, Sylvie; Nantet, Bernard

    2015-01-01

    Henri-Jean Hugot nous a quittés le dimanche 8 juin 2014, dans sa 98e année. Né à Paris en 1916, il consacra sa vie à l’Afrique et plus spécialement au Sahara dont il devint l’un des spécialistes. Vie longue et riche, au parcours impossible à retracer en quelques lignes, dont nous tenons néanmoins à souligner ici quelques aspects. Figure 1 – Henri-Jean Hugot en 1973 (Akreijit, Dhar Tichitt) © B. Nantet À l’instar de Théodore Monod, Raymond Mauny et Jean Devisse, Henri Hugot faisait partie de ...

  12. Systematic immunohistochemical screening for Lynch syndrome in colorectal cancer: a single centre experience of 486 patients.

    Science.gov (United States)

    Zumstein, Valentin; Vinzens, Fabrizio; Zettl, Andreas; Heinimann, Karl; Koeberle, Dieter; von Flüe, Markus; Bolli, Martin

    2016-01-01

    Germline mutations in DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2 cause autosomal dominantly inherited Lynch syndrome. Lynch syndrome patients and their families benefit from life-saving intensive cancer surveillance. Approximately one in 30 colorectal cancers arises in the setting of Lynch syndrome. The aim of this study was to assess the detection rate of Lynch syndrome at our institution after introduction of systematic immunohistochemical screening for MMR deficiency in colorectal cancers from 2011 to 2015. Following the recommendations by the Evaluation of Genomic Applications in Practice and Prevention working group all colorectal cancers were immunohistochemically stained for the presence of MMR proteins MLH1, PMS2, MSH2 and MSH6, independent of clinical criteria. In the case of loss of MLH1, the somatic BRAF mutation V600E was assessed with molecular testing and/or immunohistochemistry. Clinical follow-up of potential Lynch syndrome carriers (patients with tumours showing loss of MLH1 expression with absence of BRAFV600E, loss of PMS2, MSH2 or MSH6) was evaluated. Of all patients (n = 486), loss of MMR protein expression was found in 73 (15.0%) tumours. Twenty-eight (6.0%) were classified as potential Lynch syndrome carriers. Of the genetically tested potential Lynch syndrome carriers (10 out of 28 patients), 40% were first diagnosed with Lynch syndrome. Implementation of systematic immunohistochemistry screening for Lynch syndrome showed that 6% of colorectal cancers were potentially Lynch-syndrome related. Tumour board protocols should systematically contain information on MMR status of all colorectal cancers and, in MMR deficient cases, include clear recommendations for genetic counselling for all potential Lynch syndrome patients.

  13. B-Lynch uterine compression sutures in the conservative surgical management of uterine atony.

    Science.gov (United States)

    Kaya, Baris; Tuten, Abdullah; Daglar, Korkut; Onkun, Murat; Sucu, Seyhun; Dogan, Askin; Unal, Orhan; Guralp, Onur

    2015-05-01

    To evaluate the success rate and possible complications of the B-Lynch uterine compression sutures in women who suffered from postpartum uterine atony unresponsive to medical treatment. A total of 36 women who were managed with the B-Lynch suture, with or without additional surgical procedures following uterine atony unresponsive to medical treatment, were evaluated retrospectively. Sixteen women were primarily managed with the B-Lynch compression sutures, and 11 women had the B-Lynch compression sutures following failure of achievement of hemostasis by ligation of uterine artery alone (n = 4), or uterine artery plus uterine branch of ovarian artery (n = 7). Eight women had bilateral internal iliac artery ligation (BIIAL) following failure of achievement of hemostasis by the B-Lynch compression sutures. Two women (5.5%) underwent post-cesarean hysterectomy. The overall success rate of B-Lynch was 75% (27/36), and the overall success rate of B-Lynch plus BIIAL was 94.4% (34/36). Three women were admitted to the intensive care unit. There was no death related to the hemorrhage in our series. No short-term complications such as uterine necrosis, hematometra, pyometra, or uterine erosion related to the uterine compression suture were observed. Overall success rate of the B-Lynch sutures and B-Lynch sutures plus BIIAL was 75 and 94.4%, respectively. The B-Lynch technique does not necessarily require specific suture material. Uterine devascularization or BIIAL did not increase the risk of the possible short-term complications such as uterine necrosis. In case of failure of the B-Lynch uterine compression sutures, BIIAL may be beneficial to save the uterus.

  14. Kolmanda maailma raudteekunn / Henry Posner ; interv. Krister Kivi

    Index Scriptorium Estoniae

    Posner, Henry

    2005-01-01

    Raudteeärimees Henry Posner III, kes kuulub ka Eesti Raudtee omanikeringi, oma äritegevusest, sealhulgas investeeringutest Eestisse. Suhtumisest raudteeturu avamisse. Lisa: Henry Posner mängib rongidega maailma hämarates nurkades

  15. Advancing Scholarship and Intellectual Productivity: An Interview with Clifford A. Lynch

    Science.gov (United States)

    Hawkins, Brian L.

    2006-01-01

    In this second part of a two-part interview with Clifford A. Lynch, Executive Director of the Coalition for Networked Information, Lynch talks to Hawkins about the most provocative and exciting projects that are being developed in the field of networked information worldwide. He also talks on how institutional repositories are being currently…

  16. Colorectal Cancer Risk in Patients With Lynch Syndrome and Inflammatory Bowel Disease

    NARCIS (Netherlands)

    Derikx, L.A.A.P.; Smits, L.J.T.; Lent-van Vliet, S. van; Dekker, E.; Aalfs, C.M.; Kouwen, M.C.A. van; Nagengast, F.M.; Nagtegaal, I.D.; Hoogerbrugge, N.; Hoentjen, F.

    2017-01-01

    Lynch syndrome and inflammatory bowel diseases (IBD) are associated with an increased risk of colorectal cancer (CRC). However, it is not clear whether the risk of CRC is even higher for patients with a combination of Lynch syndrome and IBD. We investigated the risk for CRC in this subgroup by

  17. Small-bowel cancer in Lynch syndrome : is it time for surveillance?

    NARCIS (Netherlands)

    Koornstra, Jan J.; Kleibeuker, Jan H.; Vasen, Hans F. A.

    Small-bowel cancer is part of the tumour spectrum of Lynch syndrome. Lynch syndrome, or hereditary non-polyposis colorectal cancer, is caused by germline mutations in one of the mismatch repair genes. Mutation carriers have an estimated lifetime risk for the development of small-bowel cancer of

  18. The B-Lynch technique for postpartum haemorrhage: an option for every gynaecologist.

    NARCIS (Netherlands)

    Holtsema, H.; Nijland, R.; Huisman, A.; Dony, J.M.J.; Berg, P.P. van den

    2004-01-01

    Postpartum haemorrhage may be a life threatening complication. Seven cases are described in which the B-Lynch surgical technique (a brace like suture over the uterus) was successful in obtaining haemostasis. In four cases, the B-Lynch technique was the first line of treatment. In three cases, the

  19. Risk of colorectal and endometrial cancers in EPCAM deletion-positive Lynch syndrome : a cohort study

    NARCIS (Netherlands)

    Kempers, Marlies J. E.; Kuiper, Roland P.; Ockeloen, Charlotte W.; Chappuis, Pierre O.; Hutter, Pierre; Rahner, Nils; Schackert, Hans K.; Steinke, Verena; Holinski-Feder, Elke; Morak, Monika; Kloor, Matthias; Buettner, Reinhard; Verwiel, Eugene T. P.; van Krieken, J. Han; Nagtegaal, Iris D.; Goossens, Monique; van der Post, Rachel S.; Niessen, Renee C.; Sijmons, Rolf H.; Kluijt, Irma; Hogervorst, Frans B. L.; Leter, Edward M.; Gille, Johan J. P.; Aalfs, Cora M.; Redeker, Egbert J. W.; Hes, Frederik J.; Tops, Carli M. J.; van Nesselrooij, Bernadette P. M.; van Gijn, Marielle E.; Garcia, Encarna B. Gomez; Eccles, Diana M.; Bunyan, David J.; Syngal, Sapna; Stoffel, Elena M.; Culver, Julie O.; Palomares, Melanie R.; Graham, Tracy; Velsher, Lea; Papp, Janos; Olah, Edith; Chan, Tsun L.; Leung, Suet Y.; van Kessel, Ad Geurts; Kiemeney, Lambertus A. L. M.; Hoogerbrugge, Nicoline; Ligtenberg, Marjolijn J. L.

    Background Lynch syndrome is caused by germline mutations in MSH2, MLH1, MSH6, and PMS2 mismatch-repair genes and leads to a high risk of colorectal and endometrial cancer. We previously showed that constitutional 3' end deletions of EPCAM can cause Lynch syndrome through epigenetic silencing of

  20. Transcendentalism and Henry Barnard's "School Architecture"

    Science.gov (United States)

    Rothfork, John

    1977-01-01

    Sketches the intellectual and sociological climate that led Henry Barnard to advocate Greek Revival architecture for school buildings, takes a look at why this style and its implicit values were popular in the era between 1820-1860, and examines a few of the plans in Barnard's "School Architecture" (1838-48). (Author/RK)

  1. Frequent mismatch-repair defects link prostate cancer to Lynch syndrome

    DEFF Research Database (Denmark)

    Dominguez-Valentin, Mev; Joost, Patrick; Therkildsen, Christina

    2016-01-01

    BACKGROUND: A possible role for prostate cancer in Lynch syndrome has been debated based on observations of mismatch-repair defective tumors and reports of an increased risk of prostate cancer in mutation carriers. Potential inclusion of prostate cancer in the Lynch syndrome tumor spectrum...... is relevant for family classification, risk estimates and surveillance recommendations in mutation carriers. METHODS: We used the population-based Danish HNPCC-register to identify all prostate cancers that developed in mutation carriers and in their first-degree relatives from 288 Lynch syndrome families...... at age 70 was 3.7 % (95 % CI: 2.3-4.9). CONCLUSION: We provide evidence to link prostate cancer to Lynch syndrome through demonstration of MMR defective tumors and an increased risk of the disease, which suggests that prostate cancer should be considered in the diagnostic work-up of Lynch syndrome....

  2. Universal Point of Care Testing for Lynch Syndrome in Patients with Upper Tract Urothelial Carcinoma.

    Science.gov (United States)

    Metcalfe, Michael J; Petros, Firas G; Rao, Priya; Mork, Maureen E; Xiao, Lianchun; Broaddus, Russell R; Matin, Surena F

    2018-01-01

    Patients with Lynch syndrome are at risk for upper tract urothelial carcinoma. We sought to identify the incidence and most reliable means of point of care screening for Lynch syndrome in patients with upper tract urothelial carcinoma. A total of 115 consecutive patients with upper tract urothelial carcinoma without a history of Lynch syndrome were universally screened during followup from January 2013 through July 2016. We evaluated patient and family history using AMS (Amsterdam criteria) I and II, and tumor immunohistochemistry for mismatch repair proteins and microsatellite instability. Patients who were positive for AMS I/II, microsatellite instability or immunohistochemistry were classified as potentially having Lynch syndrome and referred for clinical genetic analysis and counseling. Patients with known Lynch syndrome served as positive controls. Of the 115 patients 16 (13.9%) screened positive for potential Lynch syndrome. Of these patients 7.0% met AMS II criteria, 11.3% had loss of at least 1 mismatch repair protein and 6.0% had high microsatellite instability. All 16 patients were referred for germline testing, 9 completed genetic analysis and counseling, and 6 were confirmed to have Lynch syndrome. All 7 patients with upper tract urothelial carcinoma who had a known history of Lynch syndrome were positive for AMS II criteria and at least a single mismatch repair protein loss while 5 of 6 had high microsatellite instability. We identified 13.9% of upper tract urothelial carcinoma cases as potential Lynch syndrome and 5.2% as confirmed Lynch syndrome at the point of care. These findings have important implications for universal screening of upper tract urothelial carcinoma, representing one of the highest rates of undiagnosed genetic disease in a urological cancer. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  3. How-to-Do-It: Hands-on Activity for Mitosis, Meiosis and the Fundamentals of Heredity.

    Science.gov (United States)

    Taylor, Mark F.

    1988-01-01

    Described is an exercise which uses inexpensive and easy-to-make materials to demonstrate the basic fundamentals of heredity. Discusses two approaches using a hypothetical insert to demonstrate inheritance, mitosis, meiosis, and genotypic and phenotypic frequencies. (CW)

  4. The history of genetics in Mexico in the light of A Cultural History of Heredity.

    Science.gov (United States)

    Barahona, Ana

    2013-01-01

    In this paper I analyze the conditions for scientific research and the social relationships that allowed the establishment of genetics in Mexico, in the laboratory, the clinic and in agronomy. I give three examples to illustrate how the cultural history of heredity has enlightened this work: the introduction and institutionalization of Mendelism in Mexico, the hereditarian ideas of medical doctors in the late nineteenth century, and the introduction of medical genetics in Mexico.

  5. Surveillance for urinary tract cancer in Lynch syndrome

    DEFF Research Database (Denmark)

    Bernstein, Inge Thomsen; Myrhøj, Torben

    2013-01-01

    Hereditary non-polyposis colorectal cancer (HNPCC) is an inherited multiorgan cancer syndrome, which when caused by a germline mutation in the mismatch repair (MMR) genes is known as Lynch syndrome (LS). Mutation carriers are at risk for developing cancers primarily in the colon, rectum...... and endometrium, but also other extra-colonic cancers. Urinary tract cancers (UTC) have in many studies been reported increased in LS and it has been discussed among researchers and clinicians whether or not screening for urological tumours should be included in the surveillance programme and if so what screening...

  6. De hombres y monstruos: El hombre elefante, David Lynch, 1980

    OpenAIRE

    Ferrer, Anacleto

    2012-01-01

    Nacido en Leicester en 1862, Joseph Carey Merrick tuvo un desarrollo normal durante la primera parte de su infancia, hasta los 5 años, cuando aparecieron las primeras manifestaciones de su extraña enfermedad:El síndrome de Proteus. Esta emotiva película sobre su caso fue estrenada en 1980 por el cineasta británico David Lynch, un prolífico creador que viene cultivando con éxito distintas formas de expresión artística que alterna con sus rodajes. De este modo ha conseguido transmitir un u...

  7. Contaminant Monitoring Strategy for Henrys Lake, Idaho

    Energy Technology Data Exchange (ETDEWEB)

    John S. Irving; R. P. Breckenridge

    1992-12-01

    Henrys Lake, located in southeastern Idaho, is a large, shallow lake (6,600 acres, {approx} 17.1 feet maximum depth) located at 6,472 feet elevation in Fremont Co., Idaho at the headwaters of the Henrys Fork of the Snake River. The upper watershed is comprised of high mountains of the Targhee National Forest and the lakeshore is surrounded by extensive flats and wetlands, which are mostly privately owned. The lake has been dammed since 1922, and the upper 12 feet of the lake waters are allocated for downriver use. Henrys Lake is a naturally productive lake supporting a nationally recognized ''Blue Ribbon'' trout fishery. There is concern that increasing housing development and cattle grazing may accelerate eutrophication and result in winter and early spring fish kills. There has not been a recent thorough assessment of lake water quality. However, the Department of Environmental Quality (DEQ) is currently conducting a study of water quality on Henrys Lake and tributary streams. Septic systems and lawn runoff from housing developments on the north, west, and southwest shores could potentially contribute to the nutrient enrichment of the lake. Many houses are on steep hillsides where runoff from lawns, driveways, etc. drain into wetland flats along the lake or directly into the lake. In addition, seepage from septic systems (drainfields) drain directly into the wetlands enter groundwater areas that seep into the lake. Cattle grazing along the lake margin, riparian areas, and uplands is likely accelerating erosion and nutrient enrichment. Also, cattle grazing along riparian areas likely adds to nutrient enrichment of the lake through subsurface flow and direct runoff. Stream bank and lakeshore erosion may also accelerate eutrophication by increasing the sedimentation of the lake. Approximately nine streams feed the lake (see map), but flows are often severely reduced or completely eliminated due to irrigation diversion. In addition, subsurface

  8. ‘His father’s voice’: Phonographs and Heredity in the Fiction of Samuel Butler

    Directory of Open Access Journals (Sweden)

    Will Abberley

    2014-05-01

    Full Text Available The article explores the interaction between concepts of heredity and technologies of voice recording and reproduction in the late-Victorian imagination through the example of Samuel Butler. Butler’s writing on evolutionary topics frequently conceptualized heredity as a record of ancestral voices echoing through their descendants. His Lamarckian view of evolution caused him to present heredity as analogous to the phonograph, recording the experiences of individuals, storing them in the germ plasm and reproducing them in the offspring. Theorists of hereditary memory such as Ewald Hering described it as a form of vibration and inscription, emphasizing its parallels with phonography. At the same time, language and the physical voice seemed equally haunted for Butler, resonating with the thoughts, feelings, and urges of past generations. I pursue these themes through a close reading of his posthumously published novel The Way of All Flesh' (1903. Butler makes an interesting case study for this subject since his ideas about the inheritance of ancestral voices were inseparable from his complex personal relations with his family. His efforts to escape the influence of his parents were bound up with the notion of escaping the habitual ‘grooves’ in which they lived, thought, and spoke. Such escape sometimes seems impossible in Butler’s vision, with long-term heredity and immediate social convention rendering people echoes of their predecessors. However, the life experience of the individual offered possibilities for breaking with the voices of the past, etching new grooves of habit and redirecting old ones. Further, heredity in Butler’s vision was not a single, commanding voice but a cacophony of competing voices screaming to be heard. In this sense, what seemed like rebellion against the voice of one’s ancestor might turn out to be obedience towards another one. Butler conceived of intellectual influence in the same way, placing thinkers and

  9. Is there a role for prophylactic colectomy in Lynch syndrome patients with inflammatory bowel disease?

    Science.gov (United States)

    McNamara, Kate L; Aronson, Melyssa D; Cohen, Zane

    2016-01-01

    Lynch syndrome and chronic inflammatory bowel disease are two important risk factors for colorectal cancer. It is unclear whether Lynch syndrome patients with inflammatory bowel disease are at sufficiently increased risk for colorectal cancer to warrant prophylactic colectomy. This study aims to identify all cases of Lynch syndrome and concurrent inflammatory bowel disease in a large familial gastrointestinal cancer registry, define incidence of colorectal cancer, and characterize mismatch repair protein gene mutation status and inflammatory bowel disease-associated colorectal cancer risk factors. We retrospectively identified and collected clinical data for all cases with confirmed diagnoses of Lynch syndrome and inflammatory bowel disease in the Familial Gastrointestinal Cancer Registry at Mount Sinai Hospital in Toronto, Canada. Twelve cases of confirmed Lynch syndrome, and concurrent inflammatory bowel disease were identified. Four cases developed colorectal cancer. An additional five cases had colectomy; one was performed for severe colitis, and four were performed for low-grade dysplasia. None of these surgical specimens contained malignancy or high-grade dysplasia. The presentation of Lynch syndrome with inflammatory bowel disease is uncommon and not well described in the literature. This small but important series of twelve cases is the largest reported to date. In this series, patients with Lynch syndrome and concurrent inflammatory bowel disease do not appear to have sufficiently increased risk for colorectal cancer to recommend prophylactic surgery. Therefore, the decision to surgery should continue to be guided by surgical indications for each disease. Further evaluation of this important area will require multi-institutional input.

  10. Lynch syndrome in South America: past, present and future.

    Science.gov (United States)

    Vaccaro, Carlos A; Sarroca, Carlos; Rossi, Benedito; Lopez-Kostner, Francisco; Dominguez, Mev; Calo, Natalia Causada; Cutait, Raul; Valle, Adriana Della; Nuñez, Lina; Neffa, Florencia; Alvarez, Karin; Gonzalez, Maria Laura; Kalfayan, Pablo; Lynch, Henry T; Church, James

    2016-07-01

    After decades of unawareness about Lynch syndrome, the medical community in South America is increasingly interested and informed. The visits and support of mentors like H. T. Lynch had been crucial to this awakening. Several countries have at least one registry with skilled personnel in genetic counseling and research. However, this only represents a very restricted resource for the region. According to the GETH, there are 27 hereditary cancer care centers in South America (21 in Brazil, 3 in Argentina, 1 in Uruguay, 1 in Chile and 1 in Peru). These registries differ in fundamental aspects of function, capabilities and funding, but are able to conduct high quality clinical, research and educational activities due to the dedication and personal effort of their members, and organizational support. More support from the governments as well as the participation of the community would boost the initiatives of people leading these groups. Meantime, the collaboration among the South American registries and the involvement of registries and leaders from developed countries will allow to maximize the efficiency in caring for affected patients and their families. The aim of this article is to describe how the knowledge of LS began to be spread in South America, how the first registries were organized and to summarize the current state of progress. In addition, we will provide an update of the clinical and molecular findings in the region.

  11. History, genetics, and strategies for cancer prevention in Lynch syndrome.

    Science.gov (United States)

    Kastrinos, Fay; Stoffel, Elena M

    2014-05-01

    Colorectal cancer (CRC) is the most common gastrointestinal malignancy and the third cause of cancer death in men and women in the United States. The majority of CRC cases diagnosed annually are due to sporadic events, but up to 6% are attributed to known monogenic disorders that confer a markedly increased risk for the development of CRC and multiple extracolonic malignancies. Lynch syndrome is the most common inherited CRC syndrome and is associated with mutations in DNA mismatch repair genes, mainly MLH1 and MSH2 but also MSH6, PMS2, and EPCAM. Although the risk of CRC and endometrial cancer may approach near 75% and 50%, respectively, in gene mutation carriers, the identification of these individuals and at-risk family members through predictive genetic testing provides opportunities for cancer prevention including specialized cancer screening, intensified surveillance, and/or prophylactic surgeries. This article will provide a review of the major advances in risk assessment, molecular genetics, DNA mutational analyses, and cancer prevention and management made since Lynch syndrome was first described 100 years ago. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  12. Novel Implications in Molecular Diagnosis of Lynch Syndrome

    Directory of Open Access Journals (Sweden)

    Raffaella Liccardo

    2017-01-01

    Full Text Available About 10% of total colorectal cancers are associated with known Mendelian inheritance, as Familial Adenomatous Polyposis (FAP and Lynch syndrome (LS. In these cancer types the clinical manifestations of disease are due to mutations in high-risk alleles, with a penetrance at least of 70%. The LS is associated with germline mutations in the DNA mismatch repair (MMR genes. However, the mutation detection analysis of these genes does not always provide informative results for genetic counseling of LS patients. Very often, the molecular analysis reveals the presence of variants of unknown significance (VUSs whose interpretation is not easy and requires the combination of different analytical strategies to get a proper assessment of their pathogenicity. In some cases, these VUSs may make a more substantial overall contribution to cancer risk than the well-assessed severe Mendelian variants. Moreover, it could also be possible that the simultaneous presence of these genetic variants in several MMR genes that behave as low risk alleles might contribute in a cooperative manner to increase the risk of hereditary cancer. In this paper, through a review of the recent literature, we have speculated a novel inheritance model in the Lynch syndrome; this could pave the way toward new diagnostic perspectives.

  13. “Silencio”: hearing loss in David Lynch's Mulholland Drive

    Directory of Open Access Journals (Sweden)

    Allister Mactaggart

    2014-11-01

    Full Text Available In a filmmaking career replete with extraordinary images and sounds, David Lynch's Mulholland Drive (2001 stands out for attention as a striking and seemingly inexhaustible resource for analysis. In this article, this film is used to examine the specific ways in which Lynch uses pre-existing pop songs to wrap the spectator within the filmic soundscape. Nowhere is the complexity and uncanniness of pop music made more explicit than in Rebekah Del Rio's stunning performance of “Llorando (Crying” in the Club Silencio scene. The split between the singer's powerful performance and her subsequent collapse with the sound of the voice left hanging in the air marks a pivotal point in the film. This scene, coupled with other examples of feminine jouissance, is contrasted with the deadening roar of the master's voice, which solely demands obedience but is deaf to any reply. At the core of this article is an analysis of the status of the voice (and the gaze as examples of the Lacanian object a and its relationship to Marx's concept of surplus value. Mulholland Drive provides a powerful demonstration of how these concepts can be seen, heard, and felt in relation to film, and how sound can reverberate into the spaces and silences beyond the screen.

  14. Mismatch repair deficiency commonly precedes adenoma formation in Lynch Syndrome-Associated colorectal tumorigenesis.

    Science.gov (United States)

    Sekine, Shigeki; Mori, Taisuke; Ogawa, Reiko; Tanaka, Masahiro; Yoshida, Hiroshi; Taniguchi, Hirokazu; Nakajima, Takeshi; Sugano, Kokichi; Yoshida, Teruhiko; Kato, Mamoru; Furukawa, Eisaku; Ochiai, Atsushi; Hiraoka, Nobuyoshi

    2017-08-01

    Lynch syndrome is a cancer predisposition syndrome caused by germline mutations in mismatch repair (MMR) genes. MMR deficiency is a ubiquitous feature of Lynch syndrome-associated colorectal adenocarcinomas; however, it remains unclear when the MMR-deficient phenotype is acquired during tumorigenesis. To probe this issue, the present study examined genetic alterations and MMR statuses in Lynch syndrome-associated colorectal adenomas and adenocarcinomas, in comparison with sporadic adenomas. Among the Lynch syndrome-associated colorectal tumors, 68 of 86 adenomas (79%) and all adenocarcinomas were MMR-deficient, whereas all the sporadic adenomas were MMR-proficient, as determined by microsatellite instability testing and immunohistochemistry for MMR proteins. Sequencing analyses identified APC or CTNNB1 mutations in the majority of sporadic adenomas (58/84, 69%) and MMR-proficient Lynch syndrome-associated adenomas (13/18, 72%). However, MMR-deficient Lynch syndrome-associated adenomas had less APC or CTNNB1 mutations (25/68, 37%) and frequent frameshift RNF43 mutations involving mononucleotide repeats (45/68, 66%). Furthermore, frameshift mutations affecting repeat sequences constituted 14 of 26 APC mutations (54%) in MMR-deficient adenomas whereas these frameshift mutations were rare in MMR-proficient adenomas in patients with Lynch syndrome (1/12, 8%) and in sporadic adenomas (3/52, 6%). Lynch syndrome-associated adenocarcinomas exhibited mutation profiles similar to those of MMR-deficient adenomas. Considering that WNT pathway activation sufficiently drives colorectal adenoma formation, the distinct mutation profiles of WNT pathway genes in Lynch syndrome-associated adenomas suggest that MMR deficiency commonly precedes adenoma formation.

  15. Henri Fayol and Zero Tolerance Policies

    OpenAIRE

    Lee SCHIMMOELLER

    2012-01-01

    Zero tolerance policies have been increasingly popular in both education and business. Henri Fayol was the one of the earliest and influential thinkers in modern management theory. He defined management as a body of knowledge and defined his 14 administrative principles. It is an interesting exercise to apply Fayol’s teachings to the theory of zero tolerance and attempt to determine what Fayol would think of this new management technique.

  16. Henry P. McKean Jr. selecta

    CERN Document Server

    Moerbeke, Pierre; Moll, Victor

    2015-01-01

    This volume presents a selection of papers by Henry P. McKean, which illustrate the various areas in mathematics in which he has made seminal contributions. Topics covered include probability theory, integrable systems, geometry and financial mathematics. Each paper represents a contribution by Prof. McKean, either alone or together with other researchers, that has had a profound influence in the respective area.

  17. Henri Vetch and His French Bookstore Peking

    Directory of Open Access Journals (Sweden)

    Chiang Lei

    2013-12-01

    Full Text Available Based on enormous firsthand materials as journals, memoirs, newspapers, correspondences, archives, bibliographies and books etc., this article tries to clarify some important aspects concerning Henri Vetch and his French Bookstore Peking such as when Henri Vetch took over his father Francis Vetch’s La Librairie Francaise and established his own French Bookstore Peking, how its inner structure worked and what its major businesses covered. By doing so, the author tells the story of the French Bookstore Peking: how it had witnessed the vicissitudes of its time and its own, how it had contributed to the cultural exchange and communication between China and the West through its daily business activities such as book retails, consignments, purchases on demand, and publication of books on various aspects of China in English and other languages written by distinguished western sinologists and authors. In all, this article makes efforts to explore the publishing history of an individual-Henri Vetch from 1930 to 1953, whose publishing house, the French Bookstore Peking, served both for an academic club and a private library, and had played an active role in the cultural life of Beijing or even the whole China during that time. [Article content in Chinese

  18. Prevalence of Lynch syndrome and Lynch-like syndrome among patients with colorectal cancer in a Japanese hospital-based population.

    Science.gov (United States)

    Chika, Noriyasu; Eguchi, Hidetaka; Kumamoto, Kensuke; Suzuki, Okihide; Ishibashi, Keiichiro; Tachikawa, Tetsuhiko; Akagi, Kiwamu; Tamaru, Jun-Ichi; Okazaki, Yasushi; Ishida, Hideyuki

    2017-02-09

    We investigated the prevalence of Lynch syndrome and Lynch-like syndrome among Japanese colorectal cancer patients, as there have been no credible data from Japan. Immunohistochemical analyses for mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2) were carried out in surgically resected, formalin-fixed paraffin-embedded specimens obtained from 1,234 newly diagnosed colorectal cancer patients between March 2005 and April 2014. The presence/absence of the BRAF V600E mutation and hypermethylation of the MLH1 promoter was analyzed where necessary. Genetic testing was finally undertaken in patients suspected as having Lynch syndrome. By the universal screening approach with immunohistochemical analysis for mismatch repair proteins followed by analyses for the BRAF V600E mutation and MLH1 promoter methylation status, 11 (0.9%) of the 1,234 patients were identified as candidates for genetic testing. Out of the 11 patients, 9 (0.7%) were finally diagnosed as having Lynch syndrome; the responsible genes included MLH1 (n = 1), MSH2 (n = 4), EPCAM (n = 1) and MSH6 (n = 3). The remaining two patients (0.2%) were regarded as having Lynch-like syndrome, since biallelic somatic deletion of the relevant mismatch repair genes was detected in the absence of germline mismatch repair alterations. None of the cases was identified as having germline MLH1 epimutation. The prevalence of Lynch syndrome among all newly diagnosed cases of colorectal cancer in Japan is in the same range as that recently reported by studies in Western population. The prevalence of Lynch-like syndrome seems to be extremely low.

  19. Compilation of Henry's law constants, version 3.99

    Science.gov (United States)

    Sander, R.

    2014-11-01

    Many atmospheric chemicals occur in the gas phase as well as in liquid cloud droplets and aerosol particles. Therefore, it is necessary to understand the distribution between the phases. According to Henry's law, the equilibrium ratio between the abundances in the gas phase and in the aqueous phase is constant for a dilute solution. Henry's law constants of trace gases of potential importance in environmental chemistry have been collected and converted into a uniform format. The compilation contains 14775 values of Henry's law constants for 3214 species, collected from 639 references. It is also available on the internet at law.org">http://www.henrys-law.org.

  20. Lynch 002: A New Lunar Meteorite from the Nullarbor Desert, Western Australia

    Science.gov (United States)

    Smith, C. L.; Kearsley, A. T.; Bermingham, K. R.; Deacon, G. L.; Kurahashi, E.; Franchi, I. A.; Bevan, A. W. R.

    2012-09-01

    Lynch 002, found in September 2010, is a highly brecciated meteorite containing diverse lunar lithologies and mineral phases, reflecting a wide range of igneous activity and multiple phases of impact and regolith processing.

  1. Surveillance colonoscopy practice in Lynch syndrome in the Netherlands : A nationwide survey

    NARCIS (Netherlands)

    Koornstra, Jan J.; Vasen, Hans Fa

    2007-01-01

    Lynch syndrome, or hereditary nonpolyposis colorectal cancer (HNPCC), is the most common genetic disorder predisposing to colorectal cancer. As regular colonoscopic surveillance has been shown to reduce the incidence of colorectal cancer, this strategy is recommended worldwide. Recently, several

  2. Syndrome de Lynch: à propos d'un cas et revue de la litterature ...

    African Journals Online (AJOL)

    Syndrome de Lynch: à propos d'un cas et revue de la litterature. Laila Bouguenouch, Imane Samri, Khadija Belhassan, Hanane Sayel, Meriame Abbassi, Sanae Bennis, Dafr Allah Benajah, Adil Ibrahimi, Afaf Amarti, Karim Ouldim ...

  3. Distinct gene expression profiles in ovarian cancer linked to Lynch syndrome

    DEFF Research Database (Denmark)

    Jönsson, Jenny-Maria; Bartuma, Katarina; Dominguez-Valentin, Mev

    2014-01-01

    with the aim to identify key discriminators and central tumorigenic mechanisms in hereditary ovarian cancer. Global gene expression profiling using whole-genome c-DNA-mediated Annealing, Selection, extension, and Ligation was applied to 48 histopathologically matched Lynch syndrome-associated and sporadic...... ovarian cancers. Lynch syndrome-associated and sporadic ovarian cancers differed by 349 significantly deregulated genes, including PTPRH, BIRC3, SHH and TNFRSF6B. The genes involved were predominantly linked to cell growth, proliferation, and cell-to-cell signaling and interaction. When stratified......Ovarian cancer linked to Lynch syndrome represents a rare subset that typically presents at young age as early-stage tumors with an overrepresentation of endometrioid and clear cell histologies. We investigated the molecular profiles of Lynch syndrome-associated and sporadic ovarian cancer...

  4. Upper tract urothelial carcinomas: frequency of association with mismatch repair protein loss and lynch syndrome.

    Science.gov (United States)

    Harper, Holly L; McKenney, Jesse K; Heald, Brandie; Stephenson, Andrew; Campbell, Steven C; Plesec, Thomas; Magi-Galluzzi, Cristina

    2017-01-01

    Increased risk for upper tract urothelial carcinoma is described in patients with Lynch syndrome, caused by germline mutations in mismatch repair genes. We aimed to identify the frequency of mismatch repair protein loss in upper tract urothelial carcinoma and its potential for identifying an association with Lynch syndrome. We queried our database to identify upper tract urothelial carcinomas. Patients were cross-referenced for history of colorectal carcinoma or other common Lynch syndrome-associated neoplasms to enrich for potential Lynch syndrome cases. Tumor histopathologic characteristics were reviewed and each case was analyzed for loss of mismatch repair proteins, MLH1, MSH2, MSH6, and PMS2, by immunohistochemistry. Of 444 patients with upper tract urothelial carcinoma, a subset of 215 (encompassing 30 with upper tract urothelial carcinoma and another common Lynch syndrome-associated neoplasm) was analyzed for loss of mismatch repair protein expression. Of 30 patients with Lynch syndrome-associated neoplasms, six had documented Lynch syndrome, including two with Muir-Torre syndrome. Mismatch repair protein loss was identified in 7% of total upper tract urothelial carcinomas and 30% of patients with Lynch syndrome-associated neoplasms (including all patients with Lynch syndrome/Muir-Torre syndrome). Of patients without history of Lynch syndrome-associated neoplasms, 5 of 184 (2.7%) had loss of mismatch repair protein expression. Twelve cases with mismatch repair protein loss demonstrated loss of MSH2 and MSH6, and 2 had isolated loss of MSH6. MLH1 and PMS2 expression were consistently retained. Although increased intratumoral lymphocytes, inverted growth, pushing tumor-stromal interface, and lack of nuclear pleomorphism were more commonly seen in cases with mismatch repair protein loss, only intratumoral lymphocytes and presence of pushing borders were statistically significant. MLH1 and PMS2 testing appear to have little utility in upper tract urothelial

  5. Lynch Syndrome: Awareness among Medical Students at a United States Medical School

    OpenAIRE

    Frey, Melissa K; Biewald, Mollie A; Worley, Michael J.; Taylor, Jolyn S; Lin, Stephanie N; Holcomb, Kevin

    2012-01-01

    Introduction: Lynch syndrome was first described in the 1950s however until recently it was rarely included in medical school curricula. As a result, many practicing physicians have limited exposure, potentially contributing to significant under diagnosis. As identification of Lynch syndrome prior to malignancy allows for intensified screening, prophylactic surgery and improved patient outcomes, all physicians should be aware of the characteristics of affected families. We aim to determine th...

  6. Effect of technological heredity on the fatigue strength in the manufacture of gas turbine engine blades

    Science.gov (United States)

    Smirnov, G. V.; Pronichev, N. D.; Nekhoroshev, M. V.

    2017-02-01

    In the study, the task of researching of the finishing-strengthening machining stage of gas turbine engine compressor blades manufactured of titanium and nickel-chromium alloys in order to extend their service life was solved. The application of electrochemical pulse machining as a technological heredity barrier was substantiated since this method allows a considerable decrease of the residual stress and surface layer work hardening. To ensure the extended service life of blades, the conditions for the subsequent finishing-strengthening machining were identified.

  7. Clinicopathological Features and Management of Cancers in Lynch Syndrome

    Directory of Open Access Journals (Sweden)

    Markku Aarnio

    2012-01-01

    Full Text Available Lynch syndrome (LS is characterized by an autosomal dominant inheritance of the early onset of colorectal cancer (CRC and endometrial cancer, as well as increased risk for several other cancers including gastric, urinary tract, ovarian, small bowel, biliary tract, and brain tumors. The syndrome is due to a mutation in one of the four DNA mismatch repair (MMR genes MLH1, MSH2, MSH6, or PMS2. The majority of LS patients and families can now be identified, and the underlying mutation detected using genetic diagnostics. Regular surveillance for CRC and endometrial cancer has proved beneficial for mutation carriers. However, screening for other tumors is also recommended even though experiences in the screening of these tumors is limited. Prophylactic colectomy, prophylactic hysterectomy, and bilateral salpingo-oophorectomy may be reasonable options for selected patients with LS. This paper describes the features and management of LS.

  8. Henri Tamm : algul küsiti mult kogu aeg autogrammi / Henri Tamm ; interv. Ada Kallam

    Index Scriptorium Estoniae

    Tamm, Henri

    2005-01-01

    Draamaseriaali "Kodu keset linna" lapsnäitleja. Lisaks kolleegid Henrist : M. Veinmann "Tekst on tal esimesena peas", K. Maibaum "Võrdväärne partner suurtele". Artikkel pealkirjaga "Henri Tamm : nüüd saan veidi puhkust" : Linnaleht nr. 22, 3. juuni 2005, A2-A3

  9. Universal Versus Targeted Screening for Lynch Syndrome: Comparing Ascertainment and Costs Based on Clinical Experience.

    Science.gov (United States)

    Erten, Mujde Z; Fernandez, Luca P; Ng, Hank K; McKinnon, Wendy C; Heald, Brandie; Koliba, Christopher J; Greenblatt, Marc S

    2016-10-01

    Strategies to screen colorectal cancers (CRCs) for Lynch syndrome are evolving rapidly; the optimal strategy remains uncertain. We compared targeted versus universal screening of CRCs for Lynch syndrome. In 2010-2011, we employed targeted screening (age syndrome and estimated the 5-year costs of preventing CRC by colonoscopy screening, using a system dynamics model. Using targeted screening, 51/175 (29 %) cancers fit criteria and were tested by immunohistochemistry; 15/51 (29 %, or 8.6 % of all CRCs) showed suspicious loss of ≥1 mismatch repair protein. Germline mismatch repair gene mutations were found in 4/4 cases sequenced (11 suspected cases did not have germline testing). Using universal screening, 17/292 (5.8 %) screened cancers had abnormal immunohistochemistry suspicious for Lynch syndrome. Germline mismatch repair mutations were found in only 3/10 cases sequenced (7 suspected cases did not have germline testing). The mean cost to identify Lynch syndrome probands was ~$23,333/case for targeted screening and ~$175,916/case for universal screening at our institution. Estimated costs to identify and screen probands and relatives were: targeted, $9798/case and universal, $38,452/case. In real-world Lynch syndrome management, incomplete clinical follow-up was the major barrier to do genetic testing. Targeted screening costs 2- to 7.5-fold less than universal and rarely misses Lynch syndrome cases. Future changes in testing costs will likely change the optimal algorithm.

  10. Henry Fuseli’s Alternative Classicism

    Directory of Open Access Journals (Sweden)

    Martin Myrone

    2015-12-01

    Full Text Available The review considers Andrei Pop’s Antiquity, Theatre & The Painting of Henry Fuseli. This argues for the history painter and writer Fuseli as an exemplary ‘Neopagan’, a term coined by Pop to refer to the new sense of cultural pluralism and historical relativism which emerged in Europe after the discovery of the remains of Pompeii and Herculaneum in 1748. While this perspective offers a fresh view of the artist, relating him to the emergence of modernity, and illuminates some important aspects of his work, the reviewer also suggests that the monographic focus risks re-asserting a sense of Fuseli’s exceptionalism.

  11. HENRY C. WALLICH: A THIRD GENERATION BANKER

    Directory of Open Access Journals (Sweden)

    Saul Engelbourg

    2001-01-01

    Full Text Available Born in Germany and descendant of a wealthy banking family, Henry C. Wallich emigrated to the United States like others of Jewish ancestry who fled during the 1930s. A professor of money and banking at Yale for two decades, Wallich capped his career as a Governor of the Federal Reserve. During the stagflation of the late 1960s, Wallich, a dissenter, tirelessly advocated tighter monetary policy to stem inflation. Always a scholar, Wallich published extensively; he also served as the Fed’s public spokesman. Owing to his Harvard doctorate and his eminence as an economist, Wallich knew everyone worth knowing in the economics profession.

  12. La poetica del tradurre di Henri Meschonnic

    OpenAIRE

    Mattioli, Emilio

    2003-01-01

    La poetica del tradurre ha nell’opera di Henri Meschonnic una importanza capitale e, nello stesso tempo, rappresenta una delle posizioni più nuove e originali nell’ambito della teoria del tradurre. Poétique du traduire, Verdier, Lagrasse, 1999, è l’opera più vasta, con le sue 478 pagine, dedicata da Meschonnic a quest’argomento, ma non può assolutamente esser presa in considerazione isolatamente, è soltanto nel complesso dell’attività di questo pensatore che trova il suo sig...

  13. The medical life of Henry Norman Bethune

    Science.gov (United States)

    Deslauriers, Jean; Goulet, Denis

    2015-01-01

    BACKGROUND: Henry Norman Bethune is one of the most exciting and incredible surgeons that Canada has ever produced. Indeed, he is often characterized as one of the world’s best-known surgeons. He was an innovator and his scientific contributions have stood the test of time. In Canada, he will forever be remembered as a social activist committed to the welfare of the poor and to the reform of the health care system. In the People’s Republic of China, he is idolized and remains the only foreigner to ever become a national hero. OBJECTIVE: To detail the numerous and significant achievements of Henry Norman Bethune in the field of thoracic surgery and as a social activist and describe his heroic war-time actions on the battlefields of both Spain and China. METHOD: Information was gathered through the reading of the numerous publications written about the life and work of Bethune, interviews with knowledgeable people from Canadian and Chinese universities, analysis of Bethune’s own publications, and extensive experience of one of the authors in China. RESULTS: In the social sense, Henry Norman Bethune had a difficult personality, but he was deeply caring about the plight of his patients, especially the poor. As a thoracic surgeon, he could be ingenious, thoughtful and effective but he could also be abrasive, restless and temperamental. His scientific contributions were sound and, at the time, gained worldwide attention. As an activist, he led a crusade to reform the Canadian health care system, demanding free health care for all. His outstanding work during the Spanish Civil War, where he organized the first ever mobile blood transfusion unit, and during the Sino-Japanese war, where he was totally committed to the welfare of both soldiers and civilian population, were deliberate acts of resistance against Fascist onslaught and enthusiasm for the Communist cause. CONCLUSIONS: Henry Norman Bethune was unconventional and a revolutionary, but he was brilliant. He will

  14. Henry Clay et la South American Question.

    Directory of Open Access Journals (Sweden)

    Monica Henry

    2006-03-01

    Full Text Available In March 1818 the Speaker of the House of Representatives Henry Clay raised the question of recognition of the new Spanish‑American Republics in the House by presenting a resolution making an appropriation for a minister to Buenos Aires. This article argues that beyond the debate that took place in Congress about whether to recognize or not the new governments in Spanish America, what really divided the Representatives was opposing visions of future relations between North and South America in the post‑revolutionary period.

  15. How theories became knowledge: Morgan's chromosome theory of heredity in America and Britain.

    Science.gov (United States)

    Brush, Stephen G

    2002-01-01

    T. H. Morgan, A. H. Sturtevant, H. J. Muller and C. B. Bridges published their comprehensive treatise The Mechanism of Mendelian Heredity in 1915. By 1920 Morgan's "Chromosome Theory of Heredity" was generally accepted by geneticists in the United States, and by British geneticists by 1925. By 1930 it had been incorporated into most general biology, botany, and zoology textbooks as established knowledge. In this paper, I examine the reasons why it was accepted as part of a series of comparative studies of theory-acceptance in the sciences. In this context it is of interest to look at the persuasiveness of confirmed novel predictions, a factor often regarded by philosophers of science as the most important way to justify a theory. Here it turns out to play a role in the decision of some geneticists to accept the theory, but is generally less important than the CTH's ability to explain Mendelian inheritance, sex-linked inheritance, non-disjunction, and the connection between linkage groups and the number of chromosome pairs; in other words, to establish a firm connection between genetics and cytology. It is remarkable that geneticists were willing to accept the CTH as applicable to all organisms at a time when it had been confirmed only for Drosophila. The construction of maps showing the location on the chromosomes of genes for specific characters was especially convincing for non-geneticists.

  16. [Natural history and eighteenth-century ideas regarding generation and heredity: Buffon and Bonnet].

    Science.gov (United States)

    Castañeda, L A

    1995-01-01

    The intellectual course of natural history reveals three conceptual approaches. The first was the taxonomic point of view, where naturalists worked to name and classify the living beings created by God. The second approach was provided by the eighteenth century's philosophical doctrine of mechanism, which lent natural history its method of endeavoring to comprehend the workings of organisms, inasmuch as the world "ran". Calling into question the adequacy of prior message, the third approach argued that living things display characteristics quite distinct from those of non-living matter, making it necessary to understand processes rather than simply decompose phenomena to then analyze them. This inadequacy became apparent at the moment when ideas of generation and heredity ascribed a reproductive history to living things, a history where the act of one fellow creature being formed by another plays an important role in coming to understand the workings of life. The paper analyzes these conceptual approaches from the perspective of Buffon's and Bonnet's ideas on reproduction and heredity, which represented opposite schools of thought: epigenesis and preformation.

  17. Study on heredity value in communication skills, for improving individual performance in the workplace

    Directory of Open Access Journals (Sweden)

    Bratu Mihaela Laura

    2017-01-01

    Full Text Available Effective communication is the wish of every intelligent organization. In today’s society, modern communication means saved time, reduced costs, multiplied resources. Communication can be improved early in the development. Heredity of communication can be an excuse, a brake but also a mean of focus personal resources early in child development. To establish the link between communication and heredity was conducted a study at a nursery school in Sibiu. It have been questioned a number of 98 adults and 45 children, using questionnaires for the evaluation of social and communication skills, attention to detail and distributive, and tolerance to change, carried out by researchers from United Kingdom. Adults who have significant problems of communication, have children with communication problems. The results slightly above average obtained by some adults do not always correlate with slightly different results of the children. Another conclusion is that communication ability has a social and cultural coordinated. The correlations have been established between the responses of children and adults, but cannot identify precisely, slightly above average for the cases, which is the incidence of occurrence of communication problems.

  18. Heredity of small hard drusen in twins aged 20-46 years

    DEFF Research Database (Denmark)

    Munch, Inger Christine; Sander, Birgit; Kessel, Line

    2007-01-01

    PURPOSE: To examine the prevalence and heredity of small hard drusen in 220 healthy twins aged 20-46 years. METHODS: Grayscale digital fundus photography, four-field 50 degrees nonstereoscopic, in red-free illumination was performed in 58 pairs of monozygotic (MZ) twins and 52 pairs of dizygotic ...... of age-related macular degeneration later in life and to explore the relation to AMD genotypes......PURPOSE: To examine the prevalence and heredity of small hard drusen in 220 healthy twins aged 20-46 years. METHODS: Grayscale digital fundus photography, four-field 50 degrees nonstereoscopic, in red-free illumination was performed in 58 pairs of monozygotic (MZ) twins and 52 pairs of dizygotic...... of distribution: scattered drusen (66 subjects), macular drusen (18 subjects), and stippled, innumerable drusen (5 subjects). When analyzed as a continuous trait, the heritability of small hard drusen was 63% (95% confidence interval [CI], 43% to 77%). More than 20 drusen per eye were found in 26 subjects...

  19. RNA-mediated epigenetic heredity requires the cytosine methyltransferase Dnmt2.

    Directory of Open Access Journals (Sweden)

    Jafar Kiani

    2013-05-01

    Full Text Available RNA-mediated transmission of phenotypes is an important way to explain non-Mendelian heredity. We have previously shown that small non-coding RNAs can induce hereditary epigenetic variations in mice and act as the transgenerational signalling molecules. Two prominent examples for these paramutations include the epigenetic modulation of the Kit gene, resulting in altered fur coloration, and the modulation of the Sox9 gene, resulting in an overgrowth phenotype. We now report that expression of the Dnmt2 RNA methyltransferase is required for the establishment and hereditary maintenance of both paramutations. Our data show that the Kit paramutant phenotype was not transmitted to the progeny of Dnmt2(-/- mice and that the Sox9 paramutation was also not established in Dnmt2(-/- embryos. Similarly, RNA from Dnmt2-negative Kit heterozygotes did not induce the paramutant phenotype when microinjected into Dnmt2-deficient fertilized eggs and microinjection of the miR-124 microRNA failed to induce the characteristic giant phenotype. In agreement with an RNA-mediated mechanism of inheritance, no change was observed in the DNA methylation profiles of the Kit locus between the wild-type and paramutant mice. RNA bisulfite sequencing confirmed Dnmt2-dependent tRNA methylation in mouse sperm and also indicated Dnmt2-dependent cytosine methylation in Kit RNA in paramutant embryos. Together, these findings uncover a novel function of Dnmt2 in RNA-mediated epigenetic heredity.

  20. Heredity, development and evolution: the unmodern synthesis of E.S. Russell.

    Science.gov (United States)

    Esposito, Maurizio

    2013-09-01

    In 1930, while R.A. Fisher, J.B.S. Haldane, E.B. Ford and S.G. Wright were laying the foundations of what a decade later J.S. Huxley dubbed "Modern Synthesis", E.S. Russell published a groundbreaking work, The Interpretation of Development and Heredity. In this book Russell not only condemned Mendelian genetics and neo-Darwinism, but also proposed an alternative synthesis unifying heredity, development, and evolution. The book did not represent the work of a mind operating in isolation. Rather, it was a synthetic work connecting ideas and doctrines of many influential scientists working in Europe and the USA. Through the analysis of archival documents and rarely or never mentioned sources, this article provides an unconventional picture of Russell's theoretical biology. It will be shown that Russell was an international celebrity; he was at the centre of a large network of scholars who shared his ideas and insights. He was one of several biologists arguing for a different synthesis; a synthesis perhaps less visible, less institutionalised, and less 'modern', nevertheless with its influential advocates and international support. Finally, this study shows that Russell's synthesis was not rooted in the classic pantheon of towering figures in the history of biology, i.e. Darwin, Wallace, and Mendel, but was based on the teachings of Kant, Goethe, Cuvier, von Baer, and Müller.

  1. Dialogue of Differences: The Writing of Henry Holmes Smith.

    Science.gov (United States)

    Bossen, Howard

    In addition to surveying the writings of Henry Holmes Smith, this paper explains his importance as a theoretician and practitioner of photography. After a discussion of Smith's ideas on "reading photographs" and his concerns with the ethics of photography, particularly of photojournalism, the essays in the book, "Henry Holmes Smith:…

  2. Memory Drum Theory's C Movement: Revelations from Franklin Henry

    Science.gov (United States)

    Fischman, Mark G.; Christina, Robert W.; Anson, J. Greg

    2008-01-01

    Franklin Henry's "memory drum" theory of neuromotor reaction (Henry & Rogers, 1960) was one of the most influential studies of the response programming stage of information processing. The paper is the most-cited study ever published in the "Research Quarterly for Exercise and Sport." However, few people know there is a noteworthy error in the…

  3. Henry James – Modern Theoretician of Narration

    Directory of Open Access Journals (Sweden)

    Alexandra - Denisa IGNA

    2013-01-01

    Full Text Available Henry James, properly named world writer, was one of the first modern novelists, with an exigent writing conscience. The American writer subverted the prejudgement of the omniscient author in favour of the narration which is centred on the characters’ point of view, thus modernising the novel before V. Woolf, Huxley, Thomas Mann, or in our case Camil Petrescu and G. Călinescu. Some bio-bibliographical information familiarises the reader with the life and work of this writer. The larger part of the article is dedicated to a case study of the novel with the metaphorical title: The Figure in the Carpet, where Henry James tries to illustrate in an artistic manner his conception regarding the profundity and ineffability of the literary creation. The conclusion which the author reaches, alternating the familiar plan of the relationship between a married couple with the esthetical plan, is that the relationship between writer and his work represents an act of fully intimacy, just like a ceremony that takes place in the wedding night

  4. Thyroid cancer in a patient with Lynch syndrome - case report and literature review.

    Science.gov (United States)

    Fazekas-Lavu, Monika; Parker, Andrew; Spigelman, Allan D; Scott, Rodney J; Epstein, Richard J; Jensen, Michael; Samaras, Katherine

    2017-01-01

    Lynch syndrome describes a familial cancer syndrome comprising germline mutations in one of four DNA mismatch repair genes, MLH1, MSH2, MSH6, and PMS2 and is characterized by colorectal, endometrial, and other epithelial malignancies. Thyroid cancer is not usually considered to be part of the constellation of Lynch syndrome cancers nor have Lynch syndrome tumor gene mutations been reported in thyroid malignancies. This study reports a woman with Lynch syndrome (colonic cancer and a DNA mismatch repair mutation in the MSH2 gene) with a synchronous papillary thyroid cancer. Six years later, she developed metachronous breast cancer. Metastatic bone disease developed after 3 years, and the disease burden was due to both breast and thyroid diseases. Despite multiple interventions for both metastatic breast and thyroid diseases, the patient's metastatic burden progressed and she died of leptomeningeal metastatic disease. Two prior case reports suggested thyroid cancer may be an extraintestinal malignancy of the Lynch syndrome cancer group. Hence, this study examined the genetic relationship between the patient's known Lynch syndrome and her thyroid cancer. The thyroid cancer tissue showed normal expression of MSH2, suggesting that the tumor was not due to the oncogenic mutation of Lynch syndrome, and molecular analysis confirmed BRAF V600E mutation. Although in this case the thyroid cancer was sporadic, it raises the importance of considering cancer genetics in familial cancer syndromes when other cancers do not fit the criteria of the syndrome. Careful documentation of other malignancies in patients with thyroid cancer and their families would assist in better understanding of any potential association. Appropriate genetic testing will clarify whether a common pathogenic mechanism links seemingly unrelated cancers.

  5. The development of Francis Galton's ideas on the mechanism of heredity.

    Science.gov (United States)

    Bulmer, M

    1999-01-01

    Galton greeted Darwin's theory of pangenesis with enthusiasm, and tried to test the assumption that the heredity particles circulate in the blood by transfusion experiments on rabbits. The failure of these experiments led him to reject this assumption, and in the 1870s he developed an alternative theory of heredity, which incorporated those parts of Darwin's theory that did not involve the transportation of hereditary particles throughout the system. He supposed that the fertilized ovum contains a large number of hereditary elements, which he collectively called the "stirp," a few of which are patent, developing into particular cell types, while the rest remain latent; the latent elements can be transmitted to the next generation, while the patent elements, with rare exceptions, cannot since they have developed into cells. The problem with this theory is that it does not explain the similarity between parent and child unless there is a high correlation between latent and patent elements. Galton probably came to realize this problem during his subsequent statistical work on heredity, and he quietly dropped the idea that patent elements are not transmitted in Natural Inheritance (1889). Galton thought that brothers and sisters had identical stirps, and he attributed differences between them to variability in the choice of patent elements from the stirp, that is to say to developmental variability. He attributed the likeness of monozygotic twins to the similarity of their developmental environment. Galton's twin method was to track the life history changes of twins to see whether twins who were similar at birth diverged in dissimilar environments or whether twins who were dissimilar at birth converged in similar environments. It is quite different from the modern twin method of comparing the similarities between monozygotic and dizygotic twins, on the assumption that monozygotic twins are genetically identical whereas dizygotic twins are not. It has been argued that

  6. Obituary: Henry Albers (1925-2009)

    Science.gov (United States)

    Chromey, Fred

    2011-12-01

    Henry Albers, professor of astronomy at Vassar College for over thirty years, died March 29, 2009, in Fairhope, Alabama. For his work at Vassar, where he held the Maria Mitchell Chair, Albers received the first Maria Mitchell Women in Science Award for his inspiration of women astronomers. He said "In the final analysis it is the students who bring the joy into teaching." As a professional astronomer, Albers did observational work on Galactic structure in the southern Milky Way, and on the structure of the Magellanic Clouds. In retirement, Albers published Maria Mitchell - A Life in Journals and Letters, the firsthand account of America's first woman astronomer. Albers's research was on photographic near-infrared spectroscopy of red giant stars in the southern Milky Way, some proper motion studies, and on the structure of the Magellanic Clouds. A series of seven NSF grants supported his six trips to Chile to make spectroscopic observations, as well as his sabbatical collaborations at Minnesota, Leiden, and the Royal Observatory in Edinburgh. Henry Albers arrived at Vassar in 1958, to find an astronomy program that had been recently absorbed by the physics department, and that was suffering neglect after the retirement of Maud Makemson. For the next 31 years, with incredible energy -- he sometimes taught seven courses a year -- he built the astronomy program into one double in size (from one to two tenure lines), whose th century facilities have been replaced with a st century observatory. For a remarkable stretch of 20-some-years, Albers and physicist Bob Stearns, with considerable grace, alternated chairmanship of the joint department of physics and astronomy. Henry Albers was a devoted citizen of Vassar College and an enthusiastic participant in the process of faculty governance at that institution. He would have been the first to concede that his enthusiasm was sometimes excessive, and that his contributions at faculty meetings occasionally failed to move the

  7. Genetic Conditions: A Resource Book and Instructional Guide to Human Heredity and Birth Defects for Kindergarten Through Adult Education.

    Science.gov (United States)

    California State Dept. of Education, Sacramento.

    Designed for administrators, teachers, school nurses, and others involved in health education for kindergarten through adult education, the resource guide provides curriculum ideas for instruction in genetic conditions, heredity, and birth defects. Student learning objectives, content information, learning activities, and evaluation methods are…

  8. Learning about Heredity and Embryology. Superific Science Book II. A Good Apple Science Activity Book for Grades 5-8+.

    Science.gov (United States)

    Conway, Lorraine

    Designed to provide teachers with low cost laboratory exercises, project ideas, and classroom activities for individuals and groups, this document focuses on the concepts of heredity and embryology. The materials address the topics of: (1) cell division; (2) the identification of the human embryo; (3) chromosomes; (4) DNA; (5) differences in the…

  9. Lynch Syndrome: Awareness among Medical Students at a United States Medical School.

    Science.gov (United States)

    Frey, Melissa K; Biewald, Mollie A; Worley, Michael J; Taylor, Jolyn S; Lin, Stephanie N; Holcomb, Kevin

    2012-08-01

    INTRODUCTION: Lynch syndrome was first described in the 1950s however until recently it was rarely included in medical school curricula. As a result, many practicing physicians have limited exposure, potentially contributing to significant under diagnosis. As identification of Lynch syndrome prior to malignancy allows for intensified screening, prophylactic surgery and improved patient outcomes, all physicians should be aware of the characteristics of affected families. We aim to determine the overall level of awareness of Lynch syndrome among medical students at an American medical school. METHODS: A voluntary and anonymous questionnaire was delivered to students at an American medical school. The survey instrument assessed the respondent's perceived knowledge regarding the genetics and recommended screening for carriers of Lynch syndrome mutations. RESULTS: The questionnaire was distributed to the entire student body (405 students) with a response rate of 50%. Fifty-nine percent of students reported that they had learned about Lynch syndrome; 27% of first year students, 44% of second year students; 90% of third year students and 100% of fourth year students. Of the students familiar with Lynch syndrome, the reported knowledge of the underlying genetics was 46%, available genetic screening, 18%, criteria used to screen for the syndrome, 24%, recommendations for colon screening, 31% and recommendations for endometrial cancer screening, 17%. CONCLUSION: The majority of medical students surveyed had been exposed to Lynch syndrome and awareness increased over each year of education. Significantly more students were aware of recommendations for colon cancer screening than endometrial cancer screening (32% versus 17%, p = 0.01). Studies of the natural history of Lynch syndrome indicate that affected women are more likely to present with endometrial cancer than colon cancer and while there are no prospective data proving the efficacy of endometrial cancer screening in

  10. Fisher's contributions to genetics and heredity, with special emphasis on the Gregor Mendel controversy.

    Science.gov (United States)

    Piegorsch, W W

    1990-12-01

    R. A. Fisher is widely respected for his contributions to both statistics and genetics. For instance, his 1930 text on The Genetical Theory of Natural Selection remains a watershed contribution in that area. Fisher's subsequent research led him to study the work of (Johann) Gregor Mendel, the 19th century monk who first developed the basic principles of heredity with experiments on garden peas. In examining Mendel's original 1865 article, Fisher noted that the conformity between Mendel's reported and proposed (theoretical) ratios of segregating individuals was unusually good, "too good" perhaps. The resulting controversy as to whether Mendel "cooked" his data for presentation has continued to the current day. This review highlights Fisher's most salient points as regards Mendel's "too good" fit, within the context of Fisher's extensive contributions to the development of genetical and evolutionary theory.

  11. An improved sheep flock heredity algorithm for job shop scheduling and flow shop scheduling problems

    Directory of Open Access Journals (Sweden)

    Chandramouli Anandaraman

    2011-10-01

    Full Text Available Job Shop Scheduling Problem (JSSP and Flow Shop Scheduling Problem (FSSP are strong NP-complete combinatorial optimization problems among class of typical production scheduling problems. An improved Sheep Flock Heredity Algorithm (ISFHA is proposed in this paper to find a schedule of operations that can minimize makespan. In ISFHA, the pairwise mutation operation is replaced by a single point mutation process with a probabilistic property which guarantees the feasibility of the solutions in the local search domain. A Robust-Replace (R-R heuristic is introduced in place of chromosomal crossover to enhance the global search and to improve the convergence. The R-R heuristic is found to enhance the exploring potential of the algorithm and enrich the diversity of neighborhoods. Experimental results reveal the effectiveness of the proposed algorithm, whose optimization performance is markedly superior to that of genetic algorithms and is comparable to the best results reported in the literature.

  12. Consciousness, social heredity, and development: the evolutionary thought of James Mark Baldwin.

    Science.gov (United States)

    Wozniak, Robert H

    2009-01-01

    James Mark Baldwin is one of the most important and least known early American scientific psychologists. Drawing inspiration from Charles Darwin and other evolutionists of the period, Baldwin developed a biosocial theory of psychological development that influenced both Jean Piaget and Lev S. Vygotsky; and he proposed a mechanism relating learned adaptations in the individual to phylogenesis (frequently termed the "Baldwin effect") that is of considerable interest to those currently modeling processes of learning and evolution. After a brief introduction to Baldwin's career, this article describes the intellectual context within which his evolutionary thinking developed. Three of his most important contributions are then discussed: his theory of individual adaptation or learning, his concept of "social heredity," and his articulation of the "Baldwin effect." The article concludes with a brief evaluation of the contemporary importance of Baldwin's ideas. 2009 APA, all rights reserved

  13. Mechanisms of twinning: VII. Effect of diet and heredity on the human twinning rate.

    Science.gov (United States)

    Steinman, Gary

    2006-05-01

    To evaluate the possible biochemical effect of diet and heredity on the rates of monozygotic and dizygotic twinning. In that insulin-like growth factor (IGF) has been found to be elevated in cows selected for their demonstrated increased twinning rate, the effect of agents that influence the level of IGF in women was examined. This was correlated with their prior history of singleton versus twin birthing. In particular, the effect of diets consisting of or excluding animal products that have elevated IGF content (e.g., milk) was considered. Vegan women, who exclude dairy products from their diets, have a twinning rate which is one-fifth that of vegetarians and omnivores. The results reported here support the proposed IGF model of dizygotic twinning. Genotypes favoring elevated IGF and diets including dairy products, especially in areas where growth hormone is given to cattle, appear to enhance the chances of multiple pregnancies due to ovarian stimulation.

  14. Guy V. Henry: A Study in Military Leadership

    Science.gov (United States)

    1985-05-13

    retired.17 1 Although Henry remained in command of Fort Myer, his promotion severed his formal attachment to the 9th Cavalry. In his farewell message to...3 Henry’s welcome in Vermont was as warm as his farewell from St. Louis was cold. Many New Englanders recalled with great fondness the 139 Colonel’s...the.U.S. Military Acade y Annual Reunion, June 12, 190, -. pp. 76-79. 85 " Mourn Gen. Henry’s Death,’ New York Times, October 29, 1899; ’Guardsmen

  15. Lynch syndrome in the 21st century: clinical perspectives.

    Science.gov (United States)

    Tiwari, A K; Roy, H K; Lynch, H T

    2016-03-01

    Lynch syndrome (LS) is the most common of all inherited cancer syndromes, associated with substantially elevated risks for colonic and extracolonic malignancies, earlier onset and high rates of multiple primary cancers. At the genetic level, it is caused by a defective mismatch repair (MMR) system due to presence of germline defects in at least one of the MMR genes- MLH1, MSH2, MSH6, PMS2 or EPCAM. An impaired MMR function during replication introduces infidelity in DNA sequence and leads to ubiquitous mutations at simple repetitive sequences (microsatellites), causing microsatellite instability (MSI). Although previously, clinicopathological criteria such as Amsterdam I/II and Revised Bethesda Guidelines were commonly used to identify suspected LS mutation carriers, there has been a recent push towards universally testing, especially in case of colorectal cancers (CRCs), through immunohistochemistry for expression of MMR proteins or through molecular tests (polymerase chain reaction, PCR) for MSI, in order to identify LS mutation carriers and subject them to genetic testing to ascertain the specific gene implicated. In this review, we have discussed the latest diagnostic strategies and the current screening and treatment guidelines for colonic and extracolonic cancers in clinically affected and at-risk individuals for LS. © The Author 2015. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Using Social Media Data to Understand the Impact of Promotional Information on Laypeople's Discussions: A Case Study of Lynch Syndrome.

    Science.gov (United States)

    Bian, Jiang; Zhao, Yunpeng; Salloum, Ramzi G; Guo, Yi; Wang, Mo; Prosperi, Mattia; Zhang, Hansi; Du, Xinsong; Ramirez-Diaz, Laura J; He, Zhe; Sun, Yuan

    2017-12-13

    Social media is being used by various stakeholders among pharmaceutical companies, government agencies, health care organizations, professionals, and news media as a way of engaging audiences to raise disease awareness and ultimately to improve public health. Nevertheless, it is unclear what effects this health information has on laypeople. This study aimed to provide a detailed examination of how promotional health information related to Lynch syndrome impacts laypeople's discussions on a social media platform (Twitter) in terms of topic awareness and attitudes. We used topic modeling and sentiment analysis techniques on Lynch syndrome-related tweets to answer the following research questions (RQs): (1) what are the most discussed topics in Lynch syndrome-related tweets?; (2) how promotional Lynch syndrome-related information on Twitter affects laypeople's discussions?; and (3) what impact do the Lynch syndrome awareness activities in the Colon Cancer Awareness Month and Lynch Syndrome Awareness Day have on laypeople's discussions and their attitudes? In particular, we used a set of keywords to collect Lynch syndrome-related tweets from October 26, 2016 to August 11, 2017 (289 days) through the Twitter public search application programming interface (API). We experimented with two different classification methods to categorize tweets into the following three classes: (1) irrelevant, (2) promotional health information, and (3) laypeople's discussions. We applied a topic modeling method to discover the themes in these Lynch syndrome-related tweets and conducted sentiment analysis on each layperson's tweet to gauge the writer's attitude (ie, positive, negative, and neutral) toward Lynch syndrome. The topic modeling and sentiment analysis results were elaborated to answer the three RQs. Of all tweets (N=16,667), 87.38% (14,564/16,667) were related to Lynch syndrome. Of the Lynch syndrome-related tweets, 81.43% (11,860/14,564) were classified as promotional and 18

  17. Gain of chromosomal region 20q and loss of 18 discriminates between Lynch syndrome and familial colorectal cancer

    DEFF Research Database (Denmark)

    Therkildsen, Christina; Jönsson, Göran; Dominguez-Valentin, Mev

    2013-01-01

    Lynch syndrome and familial colorectal cancer type X, FCCTX, represent the two predominant colorectal cancer syndromes. Whereas Lynch syndrome is clinically and genetically well defined, the genetic cause of FCCTX is unknown and genomic differences between Lynch syndrome and FCCTX tumours...... are largely unknown. We applied array-based comparative genomic hybridisation to 23 colorectal cancers from FCCTX with comparison to 23 Lynch syndrome tumours and to 45 sporadic colorectal cancers. FCCTX tumours showed genomic complexity with frequent gains on chromosomes 20q, 19 and 17 and losses of 18, 8p...... and 15. Gain of genetic material in two separate regions encompassing, 20q12-13.12 and 20q13.2-13.32, was identified in 65% of the FCCTX tumours. Gain of material on chromosome 20q and loss on chromosome 18 significantly discriminated colorectal cancers associated with FCCTX from Lynch syndrome, which...

  18. Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance

    DEFF Research Database (Denmark)

    Møller, Pål; Seppälä, Toni; Bernstein, Inge

    2015-01-01

    OBJECTIVE: Estimates of cancer risk and the effects of surveillance in Lynch syndrome have been subject to bias, partly through reliance on retrospective studies. We sought to establish more robust estimates in patients undergoing prospective cancer surveillance. DESIGN: We undertook a multicentre...... study of patients carrying Lynch syndrome-associated mutations affecting MLH1, MSH2, MSH6 or PMS2. Standardised information on surveillance, cancers and outcomes were collated in an Oracle relational database and analysed by age, sex and mutated gene. RESULTS: 1942 mutation carriers without previous......%; and for ovarian cancer 11%, 15%, 0% and 0%. Ten-year crude survival was 87% after any cancer, 91% if the first cancer was colorectal, 98% if endometrial and 89% if ovarian. CONCLUSIONS: The four Lynch syndrome-associated genes had different penetrance and expression. Colorectal cancer occurred frequently despite...

  19. Cancer risks and immunohistochemical profiles linked to the Danish MLH1 Lynch syndrome founder mutation

    DEFF Research Database (Denmark)

    Therkildsen, Christina; Isinger-Ekstrand, Anna; Ladelund, Steen

    2012-01-01

    Founder mutations with a large impact in distinct populations have been described in Lynch syndrome. In Denmark, the MLH1 c.1667+2_1667_+8TAAATCAdelinsATTT mutation accounts for 25 % of the MLH1 mutant families. We used the national Danish hereditary nonpolyposis colorectal cancer register...... to estimate the cumulative lifetime risks for Lynch syndrome-associated cancer in 16 founder mutation families with comparison to 47 other MLH1 mutant families. The founder mutation conferred comparable risks for colorectal cancer (relative risks, RR, of 0.99 for males and 0.79 for females) and lower risks...... in 68 % with extensive inter-tumor variability despite the same underlying germline mutation. In conclusion, the Danish MLH1 founder mutation that accounts for a significant proportion of Lynch syndrome and is associated with a lower risk for extracolonic cancers....

  20. Neuroendocrine-type prostatic adenocarcinoma with microsatellite instability in a patient with lynch syndrome.

    Science.gov (United States)

    Wagner, David G; Gatalica, Zoran; Lynch, Henry T; Kohl, Shane; Johansson, Sonny L; Lele, Subodh M

    2010-12-01

    Lynch syndrome is an autosomal-dominant cancer syndrome that can be identified with microsatellite instability molecular tests or immunohistochemical stains on pathologic material from patients who meet the Amsterdam Criteria II. The development of prostatic carcinoma in situ or invasive small cell carcinoma (SCC) of the prostate has not been previously reported in a patient with this syndrome. In this report, an 87-year-old White man with the Lynch syndrome had a prostate biopsy that revealed a mixed high-grade conventional adenocarcinoma and SCC of the prostate with high-grade prostatic intraepithelial neoplasia of the small cell neuroendocrine-type (HGPIN-NE), all showing MSH2 microsatellite instability and loss of MSH2 expression, a finding not previously published. These findings suggest that HGPIN-NE is a precursor of invasive SCC and also that prostatic SCC can develop in a patient with the Lynch syndrome.

  1. Genetic screens to identify pathogenic gene variants in the common cancer predisposition Lynch syndrome

    DEFF Research Database (Denmark)

    Drost, Mark; Lützen, Anne; van Hees, Sandrine

    2013-01-01

    In many individuals suspected of the common cancer predisposition Lynch syndrome, variants of unclear significance (VUS), rather than an obviously pathogenic mutations, are identified in one of the DNA mismatch repair (MMR) genes. The uncertainty of whether such VUS inactivate MMR, and therefore...... function. When a residue identified as mutated in an individual suspected of Lynch syndrome is listed as critical in such a reverse diagnosis catalog, there is a high probability that the corresponding human VUS is pathogenic. To investigate the applicability of this approach, we have generated....... Nearly half of these critical residues match with VUS previously identified in individuals suspected of Lynch syndrome. This aids in the assignment of pathogenicity to these human VUS and validates the approach described here as a diagnostic tool. In a wider perspective, this work provides a model...

  2. Small cell carcinoma: arising in Lynch syndrome: a previously undocumented occurrence.

    Science.gov (United States)

    Oman, Sarah A; Ballinger, Lori; Cerilli, Lisa A

    2009-02-01

    Lynch syndrome is a genetic cancer predisposition syndrome caused by an inherited defect in 1 of 4 DNA mismatch repair genes (mutL homolog 1, mutS homolog 2, mutS homolog 6, and postmeiotic segregation 2). Despite the theoretically increased risk in all tissues, Lynch syndrome exhibits tissue specificity, with a particular tendency among affected individuals to develop colorectal and endometrial cancer at a young age. A number of other malignancies, including those derived from the ovary, stomach, small bowel, and urothelium, have also been linked to this syndrome. A growing body of evidence exists to support an association between mismatch repair mutations and a growing spectrum of hereditary nonpolyposis colon cancer-associated neoplasms. In this article, a previously undocumented mismatch repair-related malignancy in a patient with Lynch syndrome is reported.

  3. Mismatch repair gene mutation spectrum in the Swedish Lynch syndrome population

    DEFF Research Database (Denmark)

    Lagerstedt-Robinson, Kristina; Rohlin, Anna; Aravidis, Christos

    2016-01-01

    Lynch syndrome caused by constitutional mismatch‑repair defects is one of the most common hereditary cancer syndromes with a high risk for colorectal, endometrial, ovarian and urothelial cancer. Lynch syndrome is caused by mutations in the mismatch repair (MMR) genes i.e., MLH1, MSH2, MSH6 and PMS2....... After 20 years of genetic counseling and genetic testing for Lynch syndrome, we have compiled the mutation spectrum in Sweden with the aim to provide a population-based perspective on the contribution from the different MMR genes, the various types of mutations and the influence from founder mutations....... Mutation data were collected on a national basis from all laboratories involved in genetic testing. Mutation analyses were performed using mainly Sanger sequencing and multiplex ligation-dependent probe amplification. A total of 201 unique disease-predisposing MMR gene mutations were identified in 369...

  4. General practitioner attitudes towards prescribing aspirin to carriers of Lynch Syndrome: findings from a national survey.

    Science.gov (United States)

    Smith, Samuel G; Foy, Robbie; McGowan, Jennifer; Kobayashi, Lindsay C; Burn, John; Brown, Karen; Side, Lucy; Cuzick, Jack

    2017-10-01

    A dose non-inferiority study comparing 100 mg, 300 mg and 600 mg of aspirin for cancer prevention among Lynch Syndrome carriers is underway (Colorectal Adenoma/Carcinoma Prevention Programme trial 3, CaPP3). To guide implementation of the findings, we investigated general practitioner (GP) attitudes towards aspirin prescribing for Lynch Syndrome carriers. We surveyed 1007 UK GPs (9.6% response rate). Using a within-subjects design, GPs read a statement on harms and benefits of aspirin and indicated their willingness to prescribe aspirin at three doses (100 mg, 300 mg, 600 mg). Approximately two-thirds (70.8%) of GPs had heard of Lynch Syndrome or its associated names, and among those 46.7% were aware of the cancer preventive effects of aspirin among carriers. Two-thirds (68.1%) of GPs reported feeling comfortable discussing harms and benefits of aspirin with a Lynch Syndrome patient. Willingness to prescribe was 91.3% at 100 mg, and declined to 81.8% at 300 mg and 62.3% at 600 mg (p Lynch Syndrome patient in practice (OR 1.44, 95% CI 1.01-2.05, p = 0.045). GPs report limited awareness of Lynch Syndrome and the preventive effects of aspirin among carriers. To ensure the optimal dose identified in the CaPP3 trial is readily available to patients, prescribing guidance and strategies to educate GPs should be developed.

  5. Hereditary non-polyposis colorectal cancer/Lynch syndrome in three dimensions.

    Science.gov (United States)

    Kravochuck, Sara E; Church, James M

    2017-12-01

    Hereditary non-polyposis colorectal cancer (HNPCC) is defined by family history, and Lynch syndrome (LS) is defined genetically. However, universal tumour testing is now increasingly used to screen for patients with defective mismatch repair. This mixing of the results of family history, tumour testing and germline testing produces multiple permutations and combinations that can foster confusion. We wanted to clarify hereditary colorectal cancer using the three dimensions of classification: family history, tumour testing and germline testing. Family history (Amsterdam I or II criteria versus not Amsterdam criteria) was used to define patients and families with HNPCC. Tumour testing and germline testing were then performed to sub-classify patients and families. The permutations of these classifications are applied to our registry. There were 234 HNPCC families: 129 had LS of which 55 were three-dimensional Lynch (family history, tumour testing and germline testing), 66 were two-dimensional Lynch and eight were one-dimensional Lynch. A total of 10 families had tumour Lynch (tumours with microsatellite instability or loss of expression of a mismatch repair protein but an Amsterdam-negative family and negative germline testing), five were Lynch like (Amsterdam-positive family, tumours with microsatellite instability or loss of expression of a mismatch repair protein on immunohistochemistry but negative germline testing), 26 were familial colorectal cancer type X and 95 were HNPCC. Hereditary colorectal cancer can be confusing. Sorting families in three dimensions can clarify the confusion and may direct further testing and, ultimately, surveillance. © 2016 Royal Australasian College of Surgeons.

  6. Screening for Lynch syndrome (hereditary nonpolyposis colorectal cancer) among endometrial cancer patients.

    Science.gov (United States)

    Hampel, Heather; Frankel, Wendy; Panescu, Jenny; Lockman, Janet; Sotamaa, Kaisa; Fix, Daniel; Comeras, Ilene; La Jeunesse, Jennifer; Nakagawa, Hidewaki; Westman, Judith A; Prior, Thomas W; Clendenning, Mark; Penzone, Pamela; Lombardi, Janet; Dunn, Patti; Cohn, David E; Copeland, Larry; Eaton, Lynne; Fowler, Jeffrey; Lewandowski, George; Vaccarello, Luis; Bell, Jeffrey; Reid, Gary; de la Chapelle, Albert

    2006-08-01

    Endometrial cancer is the most common cancer in women with Lynch syndrome. The identification of individuals with Lynch syndrome is desirable because they can benefit from increased cancer surveillance. The purpose of this study was to determine the feasibility and desirability of molecular screening for Lynch syndrome in all endometrial cancer patients. Unselected endometrial cancer patients (N = 543) were studied. All tumors underwent microsatellite instability (MSI) testing. Patients with MSI-positive tumors underwent testing for germ line mutations in MLH1, MSH2, MSH6, and PMS2. Of 543 tumors studied, 118 (21.7%) were MSI positive (98 of 118 MSI high and 20 of 118 MSI low). All 118 patients with MSI-positive tumors had mutation testing, and nine of them had deleterious germ line mutations (one MLH1, three MSH2, and five MSH6). In addition, one case with an MSI-negative tumor had abnormal MSH6 immunohistochemical staining and was subsequently found to have a mutation in MSH6. Immunohistochemical staining was consistent with the mutation result in all seven truncating mutation-positive cases but was not consistent in two of the three missense mutation cases. We conclude that in central Ohio, at least 1.8% (95% confidence interval, 0.9-3.5%) of newly diagnosed endometrial cancer patients had Lynch syndrome. Seven of the 10 Lynch syndrome patients did not meet any published criteria for hereditary nonpolyposis colorectal cancer, and six of them were diagnosed at age >50. Studying all endometrial cancer patients for Lynch syndrome using a combination of MSI and immunohistochemistry for molecular prescreening followed by gene sequencing and deletion analysis is feasible and may be desirable.

  7. James McHenry, MD: physician, patriot, politician and poet.

    Science.gov (United States)

    Spiegel, Allen D; Kavaler, Florence

    2003-08-01

    James McHenry emigrated from Ireland to the American colonies in 1771. He studied medicine with Dr. Benjamin Rush in Philadelphia and immediately volunteered as an Army surgeon when the Revolutionary War began. After serving in the medical department in Massachusetts, New York and at Valley Forge in Pennsylvania, he became an aide to General George Washington and subsequently an aide to the Marquis de Lafayette. President Washington appointed McHenry Secretary of War and he continued in that post under president John Adams. While Secretary, he revised military regulations, established a professional standing Army, pacified the Indians, enlarged the naval forces, organized the armed forces under civilian authority and initiated plans for a military academy. Baltimore's Fort Whetstone was renamed Fort McHenry in his honor. During the War of 1812, Fort McHenry gained fame as the birthplace of the national anthem of the United States.

  8. INOVATION AND ANTREPRENEURIAL CREATIVITY BUSINESS DURING HENRY FORD

    National Research Council Canada - National Science Library

    GHICAJANU MIHAELA

    2015-01-01

    .... I chose as a case study the the Ford brand products, because it is considered that Henry Ford is one of the greatest innovators and entrepreneurs of all time and I decided to present and to analyze these things...

  9. (TIQ) Thiazole and Oxazoline Ligands for Asymmetric Henry Reactions

    African Journals Online (AJOL)

    NICO

    TIQ) backbone were synthesized. Their application in the catalytic asymmetric Henry reaction was investigated with comparison to a corresponding TIQ oxazoline ligand. The Cu(II)-oxazoline complex was more reactive and furnished moderate ...

  10. NOAA Ship Henry B. Bigelow Underway Meteorological Data, Quality Controlled

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA Ship Henry B. Bigelow Underway Meteorological Data (delayed ~10 days for quality control) are from the Shipboard Automated Meteorological and Oceanographic...

  11. Major contribution from recurrent alterations and MSH6 mutations in the Danish Lynch syndrome population

    DEFF Research Database (Denmark)

    Nilbert, Mef; Wikman, Friedrik P; Hansen, Thomas V O

    2009-01-01

    An increasing number of mismatch-repair (MMR) gene mutations have been identified in hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome. This study presents the population-based Danish MMR gene mutation profile, which contains 138 different MMR gene alterations. Among these, 88......+2_1667_+8TAAATCAdelinsATTT was identified in 14/58 (24%) MLH1 mutant families. The Danish Lynch syndrome population thus demonstrates that MSH6 mutations and recurrent/founder mutations have a larger contribution than previously recognized, which implies that the MSH6 gene should be included in routine diagnostics...

  12. Identification of a Variety of Mutations in Cancer Predisposition Genes in Patients With Suspected Lynch Syndrome.

    Science.gov (United States)

    Yurgelun, Matthew B; Allen, Brian; Kaldate, Rajesh R; Bowles, Karla R; Judkins, Thaddeus; Kaushik, Praveen; Roa, Benjamin B; Wenstrup, Richard J; Hartman, Anne-Renee; Syngal, Sapna

    2015-09-01

    Multigene panels are commercially available tools for hereditary cancer risk assessment that allow for next-generation sequencing of numerous genes in parallel. However, it is not clear if these panels offer advantages over traditional genetic testing. We investigated the number of cancer predisposition gene mutations identified by parallel sequencing in individuals with suspected Lynch syndrome. We performed germline analysis with a 25-gene, next-generation sequencing panel using DNA from 1260 individuals who underwent clinical genetic testing for Lynch syndrome from 2012 through 2013. All patients had a history of Lynch syndrome-associated cancer and/or polyps. We classified all identified germline alterations for pathogenicity and calculated the frequencies of pathogenic mutations and variants of uncertain clinical significance (VUS). We also analyzed data on patients' personal and family history of cancer, including fulfillment of clinical guidelines for genetic testing. Of the 1260 patients, 1112 met National Comprehensive Cancer Network (NCCN) criteria for Lynch syndrome testing (88%; 95% confidence interval [CI], 86%-90%). Multigene panel testing identified 114 probands with Lynch syndrome mutations (9.0%; 95% CI, 7.6%-10.8%) and 71 with mutations in other cancer predisposition genes (5.6%; 95% CI, 4.4%-7.1%). Fifteen individuals had mutations in BRCA1 or BRCA2; 93% of these met the NCCN criteria for Lynch syndrome testing and 33% met NCCN criteria for BRCA1 and BRCA2 analysis (P = .0017). An additional 9 individuals carried mutations in other genes linked to high lifetime risks of cancer (5 had mutations in APC, 3 had bi-allelic mutations in MUTYH, and 1 had a mutation in STK11); all of these patients met NCCN criteria for Lynch syndrome testing. A total of 479 individuals had 1 or more VUS (38%; 95% CI, 35%-41%). In individuals with suspected Lynch syndrome, multigene panel testing identified high-penetrance mutations in cancer predisposition genes, many

  13. Ovarian cancer in Lynch syndrome; a systematic review.

    Science.gov (United States)

    Helder-Woolderink, J M; Blok, E A; Vasen, H F A; Hollema, H; Mourits, M J; De Bock, G H

    2016-03-01

    The aim was to systematically review the characteristics of ovarian cancer in women with Lynch syndrome (LS) and evaluate the role of surveillance in detection of ovarian cancer in LS. All studies between 1979 and 2015 of women with ovarian cancer and LS or at 50% risk of LS were evaluated. Two reviewers independently evaluated eligible studies and extracted data on age at diagnosis, histological type, FIGO stage, and way of detection according to pre-specified criteria. The studies were assessed for quality using the Newcastle-Ottawa quality assessment scales. The quality score of the 49 identified studies was at least 6 out of 8 and provide clinical information on 747 LS women with ovarian cancer. The mean age at diagnosis was 45.3 (range 19-82) years. Most frequent mutations were MSH2 (47%) and MLH1 (38%). Histopathological data were available for 445 women. The most frequently reported histological type was mixed type (mucinous/endometrioid/clear cell carcinomas) (n = 136; 31%). Most tumours (281, 65%) were diagnosed at an early stage (FIGO I/II). Six studies evaluating the effect of surveillance of ovarian cancer, reported that seven of 22 (32%) ovarian cancers were found during surveillance, 6/7 (86%) were detected at an early stage. This systematic review describes that ovarian cancer in women with LS has a wide age-range of onset, is often diagnosed at an early stage with frequently endometrioid/clear cell histology. Data about the role of surveillance in detection of ovarian cancer in women with LS are scarce however detection at an early stage seems possible. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Lynch syndrome: genetics, natural history, genetic counseling, and prevention.

    Science.gov (United States)

    Lynch, H T; Lynch, J

    2000-11-01

    Lynch syndrome is the most common hereditary form of colorectal cancer (CRC). Its natural history has been investigated extensively, so that highly targeted surveillance and management strategies, melded to its natural history, have proven effective in cancer control. Most important is the early age of onset of cancer (approximately 44 years), involving CRC and the several extracolonic cancers that are integral to the syndrome. With respect to CRC, approximately 70% of cases occur proximal to the splenic flexure. Synchronous and metachronous CRCs are extremely common. Full colonoscopy should be initiated when the patient is between the ages of 20 and 25, and because of the accelerated carcinogenesis of CRC, it should be performed every 1 to 2 years. The presence of initial CRC requires subtotal colectomy, given the mentioned increased frequency of metachronous cancer. Options available for germ-line mutation carriers, in addition to cancer screening, include prophylactic colectomy as well as prophylactic total abdominal hysterectomy and bilateral salpingo-oophorectomy. The discovery of mismatch repair germ-line mutations (most commonly MSH2 or MLH1) has added significantly to the recognition of this disease as well as to the search for high-risk individuals throughout families who, with genetic counseling, may become candidates for germ-line mutation testing. Clearly, hereditary nonpolyposis colorectal cancer provides an excellent opportunity for learning about the etio-pathogenesis of cancer at the molecular and clinical levels and how this knowledge might ultimately be exploited for cancer control. A search for chemoprevention agents, such as cyclo-oxygenase 2 inhibitors, as well as for putative environmental effects and how they may interact with the genetic component in CRC etiology should abet this entire cancer control process.

  15. L'Abbe Henri Breuil: Archaeologist

    Directory of Open Access Journals (Sweden)

    Lawrence Guy Straus

    1992-05-01

    Full Text Available In his otherwise excellent book, A History of Archaeological Thought, Trigger (1989: 156 makes only one passing reference in a half-sentence to the central figure in the development of Paleolithic prehistory in the first half of the 20th century -- and manages to get his name wrong, confusing Henri Breuil with his long-time, close colleague, Hugo Obenrnaie . Thirty years after his death, Breuil's role in the history of Old World prehistory required more serious consideration. He was a seminal figure not only in rock art studies, but also in the archaeology of at least France, Spain, England, Portugal, South Africa, and China. Before I had read Trigger's work or Sackett's (1991 critique of my supposed misinterpretation of Breuil's theoretical stance (e.g., Straus 1986, 1987, I had presented a review of Breuil's contributions in the 1991 Annual Snead-Wertheim Lecture in Anthropology and History at the University of New Mexico (Straus n.d.. The following is a brief summary of some of my conclusions.

  16. Henry Darcy in his own words

    Science.gov (United States)

    Bobeck, Patricia

    2006-09-01

    A recently published English translation of the Les Fontaines publiques de la ville de Dijon1 provides access to Henry Darcy's own words on the importance of water for public sanitation and on questions engineers face in building water supply systems. Written near the end of Darcy's life, the book is a compendium of the water knowledge he had gained over decades and his opinions on these topics reveal his personality. In the 1840s, Darcy built a water supply system to provide water to 120 street fountains for domestic purposes, street washing and firefighting. Surrounded by poverty, Darcy insisted on free water for the poor and on sharing the spring water with towns located along the aqueduct that brought it to Dijon. In the preface to the book, Darcy introduces his experiment on water flow through sand with the modest words “to my knowledge, no one has experimentally demonstrated the laws of water flow through sand.” This article provides a sampling of the book's insights into the personality of this remarkable man.

  17. Henry Head and the Theatre of Reverie

    Directory of Open Access Journals (Sweden)

    Tiffany Watt-Smith

    2011-04-01

    Full Text Available In 1903, the neurologist Henry Head (1861-1940 embarked on a painful self-experiment, in which he severed the radial nerve of his left arm, and then charted the gradual and faltering return of sensitivity to the limb over the next four and a half years. To directly experience his own sensations, Head entered into a trance-like state of distraction or reverie he called a ‘negative attitude of attention’. This article explores Head’s peculiar technique for looking within, and argues that while introspection was an established strategy in psychological laboratories, Head’s reverie also resonated with techniques associated with actors and theatrical audiences during this period. Viewing psychological self-experimentation through the lens of theatre, this article makes visible aspects of Head’s embodied, affective laboratory encounters, often obscured in accounts of his experiment. At the same time, it proposes that the broader historical and cultural significance of Head’s experiment lies in his attempt to observe himself by producing states of inattention and reverie at will, mental ‘attitudes’ that were themselves the subject of a rapidly evolving debate in scientific and aesthetic circles at the turn of the twentieth century.

  18. James Henry Greathead and the London Underground

    Directory of Open Access Journals (Sweden)

    Laurence Wright

    2017-01-01

    Full Text Available This article investigates the origins and early history of the device known as the ‘Greathead Shield’, an important innovation in Victorian engineering crucial to constructing the London Underground. The aim is to explore the basis on which, many years later, a South African engineer, James Henry Greathead, was accorded prominent public acknowledgment, in the form of a statue, for ‘inventing’ the Shield. From a cultural studies perspective, how is the meaning of ‘invention’ to be understood, given that several other brilliant engineers were involved? The question is adjudicated using the notion of cultural ‘extelligence’, seen in relation to several contemporary and historical accounts, including Greathead’s own record of his achievements in the proceedings of the Institution of Civil Engineers and presented in The City and South London Railway (1896, edited by James Forrest. The paper was first delivered at the conference on ‘Novelty and Innovation in the Nineteenth Century’ held at the North-West University in May 2016.

  19. CTNNB1-mutant colorectal carcinomas with immediate invasive growth: a model of interval cancers in Lynch syndrome.

    Science.gov (United States)

    Ahadova, Aysel; von Knebel Doeberitz, Magnus; Bläker, Hendrik; Kloor, Matthias

    2016-10-01

    The implementation of regular colonoscopy programs has significantly decreased the mortality associated with colorectal cancer (CRC) in Lynch syndrome patients. However, interval CRCs in Lynch syndrome that remain undetected by colonoscopy still represent a substantial problem in the management of the syndrome. One possible reason of interval cancers could be a non-polypous pathway of cancer development. To examine the possibility of a non-polypous pathway of CRC development in Lynch syndrome, we analyzed the histological appearance of 46 Lynch syndrome-associated CRCs and compared them to 34 sporadic microsatellite unstable cancers. We observed that 25 (62.5 %) out of 40 assessable Lynch syndrome-associated carcinomas lacked evidence of polypous growth, compared to 17 (50 %) out of 34 sporadic MSI-H cancers. We detected CTNNB1 mutations in 8 (17.4 %) out of 46 Lynch syndrome-associated cancers compared to 0 out of 34 sporadic MSI-H cancers (p = 0.01). The majority of CTNNB1-mutant cancers presented with a histological appearance suggesting immediate invasive growth. Our results suggest that a distinct subgroup of CRCs in Lynch syndrome may in fact emerge from a non-polypous precursor, thus potentially explaining the phenomenon of interval cancers. Such a non-polypous precursor may be the recently described mismatch repair-deficient crypt focus, which remains invisible for the examiner during colonoscopy. This calls for considering the implementation of active, primary preventive measures in the management of Lynch syndrome. Future studies on pathogenic pathways and precursor lesions in Lynch syndrome are strongly encouraged, and the clinical efficacy of new prevention approaches should be evaluated in prospective clinical trials.

  20. Gene variants of unknown clinical significance in Lynch syndrome. An introduction for clinicians

    NARCIS (Netherlands)

    Sijmons, Rolf H.; Greenblatt, Marc S.; Genuardi, Maurizio

    Clinicians referring patients for genetic testing for Lynch syndrome will sooner or later receive results for DNA Mismatch Repair (MMR) genes reporting DNA changes that are unclear from a clinical point of view. These changes are referred to as variants of unknown, or unclear, clinical significance

  1. The Failure of Lehman Brothers and Merril Lynch: A Lesson for the ...

    African Journals Online (AJOL)

    DR Nneka

    and private banking. According to Andabai (2008) the bank was a primary dealer in the United State America treasury securities market. Ahimie (2008) stated that, while Merrill Lynch was founded in 1914. It had a capital base of $32 billion and total assets of $1.6 trillion. Olugun (2008) observed that, the bank reputed to be ...

  2. Lynch, Urry and city marketing: Taking advantage of the city as a built and graphic image

    NARCIS (Netherlands)

    Hospers, G-J.

    2009-01-01

    City marketing is usually addressed from the perspective of marketing theory. This article follows an alternative approach by exploring city marketing from the viewpoint of urban planning and the sociology of tourism. In his classic ‘The Image of the City’ (1960), planner Kevin Lynch found that

  3. Inflammatory potential of the diet and colorectal tumor risk in persons with Lynch syndrome

    NARCIS (Netherlands)

    Brouwer, Jesca G. M.; Makama, Maureen; van Woudenbergh, Geertruida J.; Vasen, Hans F. A.; Nagengast, Fokko M.; Kleibeuker, Jan H.; Kampman, Ellen; van Duijnhoven, Franzel J. B.

    2017-01-01

    Background: Persons with Lynch syndrome (LS) have high lifetime risk of developing colorectal tumors (CRTs) because of a germline mutation in one of their mismatch repair (MMR) genes. An important process in the development of CRTs is inflammation, which has been shown to be modulated by diet.

  4. No evidence of genetic anticipation in a large family with Lynch syndrome.

    Science.gov (United States)

    Stupart, D; Goldberg, P; Algar, U; Vorster, A; Ramesar, R

    2014-03-01

    Lynch syndrome is the commonest inherited cause of colorectal cancer (CRC). Genetic anticipation occurs when the age of onset of a disorder decreases in successive generations. It is controversial whether this occurs in Lynch syndrome. Previous studies have included heterogenous groups of subjects from multiple families, including subjects with a clinical diagnosis (based on family history) as well as those with proven germline mismatch repair gene mutations. The purpose of this study was to determine whether genetic anticipation occurs in mismatch repair gene carriers from a single Lynch syndrome family. This study includes members of a single family known to carry an MLH1 gene mutation who are proven germline mutation carriers or obligate carriers (based on their offspring's mutation status). Evidence of genetic anticipation (determined by age of onset of first CRC) was sought in two ways: Firstly, subjects were grouped as parent-child pairs and individuals were compared with their own offspring; secondly they were grouped by generation within the family tree. The Kaplan-Meier technique was used to adjust for variable follow up times. The family tree consisted of 714 subjects. Ninety-two subjects over five generations were included in the study. There was no evidence of genetic anticipation over the generations. (P = 0.37). Similarly, in the 75 parent-child pairs identified, age of onset of CRC was similar for parents and children (P = 0.51). We could not identify any evidence of genetic anticipation in mutation carriers from a single family with Lynch syndrome.

  5. The Kids Are (Mostly) Alright: Second-Generation Assimilation--Comments on Haller, Portes and Lynch

    Science.gov (United States)

    Alba, Richard; Kasinitz, Philip; Waters, Mary C.

    2011-01-01

    This paper presents the authors' comments on "Dreams Fulfilled, Dreams Shattered: Determinants of Segmented Assimilation in the Second Generation" by William Haller, Alejandro Portes and Scott M. Lynch. The overall well-being and integration of second-generation immigrant youth constitute an important topic for researchers and policy makers, one…

  6. Functional characterization of MLH1 missaense variants identified in lynch syndrome patients

    DEFF Research Database (Denmark)

    Andersen, Sofie Dabros; Liberti, Sascha Emilie; Lützen, Anne

    2012-01-01

    Germline mutations in the human DNA mismatch repair (MMR) genes MSH2 and MLH1 are associated with the inherited cancer disorder Lynch syndrome (LS), also known as hereditary nonpolyposis colorectal cancer or HNPCC. A proportion of MSH2 and MLH1 mutations found in suspected LS patients give rise t...

  7. Increasing awareness and knowledge of lifestyle recommendations for cancer prevention in Lynch syndrome carriers

    NARCIS (Netherlands)

    Vrieling, A.; Visser, A.; Hoedjes, Meeke; Hurks, H.M.H.; Gómez García, E.; Hoogerbrugge, N.; Kampman, E.

    2018-01-01

    Lynch syndrome (LS) mutation carriers may reduce their cancer risk by adhering to lifestyle recommendations for cancer prevention. This study tested the effect of providing LS mutation carriers with World Cancer Research Fund-the Netherlands (WCRF-NL) health promotion materials on awareness and

  8. Guidelines for the clinical management of Lynch syndrome (hereditary non-polyposis cancer).

    NARCIS (Netherlands)

    Vasen, H.F.; Moslein, G.; Alonso, A.; Bernstein, I.; Bertario, L.; Blanco, I.; Burn, J.; Capella, G.; Engel, C.; Frayling, I.; Friedl, W.; Hes, F.J.; Hodgson, S.; Mecklin, J.P.; Moller, P.; Nagengast, F.M.; Parc, Y.; Renkonen-Sinisalo, L.; Sampson, J.R.; Stormorken, A.; Wijnen, J.

    2007-01-01

    Lynch syndrome (hereditary non-polyposis colorectal cancer) 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. The discovery of these genes, 15 years ago,

  9. Dietary Patterns and Colorectal Adenomas in Lynch Syndrome The GEOLynch Cohort Study

    NARCIS (Netherlands)

    Botma, Akke; Vasen, Hans F. A.; van Duijnhoven, Franzel J. B.; Kleibeuker, Jan H.; Nagengast, Fokko M.; Kampman, Ellen

    2013-01-01

    BACKGROUND: Patients with Lynch syndrome (LS) have a high risk of developing colorectal cancer due to mutations in mismatch repair genes. Because dietary factors, alone and in combination, influence sporadic colorectal carcinogenesis, the association of dietary patterns with colorectal adenomas in

  10. The Failure of Lehman Brothers and Merril Lynch: A Lesson for the ...

    African Journals Online (AJOL)

    Therefore, the study examined the collapse of Lehman Brothers and Merril Lynch also as a rethink lesson for the Nigerian Banks. However, the study revealed that the two banks were absolutely limiting to the size and age in determining the future of their banks instead of depending on the effectiveness and efficient ...

  11. Determinants of adherence to recommendations for cancer prevention among Lynch Syndrome mutation carriers: A qualitative exploration

    NARCIS (Netherlands)

    Visser, A.; Vrieling, A.; Murugesu, L.; Hoogerbrugge, N.; Kampman, E.; Hoedjes, M.

    2017-01-01

    BACKGROUND: Lynch Syndrome (LS) mutation carriers are at high risk for various cancer types, particularly colorectal cancer. Adherence to lifestyle and body weight recommendations for cancer prevention may lower this risk. To promote adherence to these recommendations, knowledge on determinants of

  12. Determinants of adherence to recommendations for cancer prevention among Lynch Syndrome mutation carriers: a qualitative exploration.

    NARCIS (Netherlands)

    Visser, A.; Vrieling, A.; Murugesu, L.; Hoogerbrugge, N.; Kampman, E.; Hoedjes, M.

    2017-01-01

    Background: Lynch Syndrome (LS) mutation carriers are at high risk for various cancer types, particularly colorectal cancer. Adherence to lifestyle and body weight recommendations for cancer prevention may lower this risk. To promote adherence to these recommendations, knowledge on determinants of

  13. Determinants of adherence to recommendations for cancer prevention among Lynch Syndrome mutation carriers

    NARCIS (Netherlands)

    Visser, Annemiek; Vrieling, Alina; Murugesu, Laxsini; Hoogerbrugge, Nicoline; Kampman, Ellen; Hoedjes, Meeke

    2017-01-01

    Background: Lynch Syndrome (LS) mutation carriers are at high risk for various cancer types, particularly colorectal cancer. Adherence to lifestyle and body weight recommendations for cancer prevention may lower this risk. To promote adherence to these recommendations, knowledge on determinants

  14. Underutilization of microsatellite instability analysis in colorectal cancer patients at high risk for Lynch syndrome.

    NARCIS (Netherlands)

    Lier, M.G. Van; Wilt, J.H.W. de; Wagemakers, J.J.; Dinjens, W.N.; Damhuis, R.A.; Wagner, A.; Kuipers, E.J.; Leerdam, M.E. van

    2009-01-01

    OBJECTIVE: The revised Bethesda Guidelines were published to improve the efficiency of recognizing Lynch syndrome (LS) by identifying LS-related malignancies that should be analyzed for microsatellite instability (MSI). The aim of this study was to evaluate whether MSI analysis was performed in

  15. Validation of a Self-Concept Scale for Lynch Syndrome in Different Nationalities

    DEFF Research Database (Denmark)

    Petersen, Helle Vendel; Domanska, Katarina; Bendahl, Pär-Ola

    2011-01-01

    Learning about hereditary cancer may influence an individual's self-concept, which otherwise represents a complex but stable cognitive structure. Recently, a 20-statement self-concept scale, with subscales related to stigma-vulnerability and bowel symptom-related anxiety, was developed for Lynch...

  16. HEREDITARY NON-POLYPOSIS COLORECTAL CANCER (LYNCH SYNDROME PADA WANITA UMUR 16 TAHUN

    Directory of Open Access Journals (Sweden)

    Asril Zahari

    2011-09-01

    Full Text Available AbstrakKanker kolorektal menduduki peringkat ketiga jenis kanker yang paling sering terjadi di dunia. Sekitar 3% kasus kanker kolorektal merupakan jenis hereditary non polyposis colorectal cancer (HNPCC/Lynch syndrome, yang sering muncul pada usia muda. Dilaporkan satu kasus di rumah sakit Dr. M. Djamil Padang, wanita berumur 16 tahun dengan keluhan nyeri perut kanan bawah. Didapatkan riwayat penyakit serupa pada kakek, bibi pasien dan enam anggota keluarga yang lain. Pada pemeriksaan fisik abdomen teraba massa dengan konsistensi keras dan terfiksir. Pada kolonoskopi dan biopsi ditemukan tumor jenis adenocarcinoma colon moderatly differentiated di fleksura hepatika dan polip di kolon sigmoid. Berdasarkan kriteria Amsterdam pasien didiagnosa Lynch syndrome. Pada Pasien dilakukan subtotal kolektomi, anastomose ileorectal dan kemoterapi ajuvan. Identifikasi genetik sedang dikerjakan untuk melihat adanya kelainan genetik pada pasien. Pasien melakukan skrining berkala untuk mencegah kanker HNPCC jenis yang lain.Kata kunci : Hereditary non polyposis colorectal cancer, Lynch syndrome, Microsatellite instability, skrining.AbstractCarcinoma colorectal is the third most common type of cancer that occurs in the world. About 2% -3% of cases of colorectal cancer is hereditary non-polyposis colorectal cancer (HNPCC/Lynch syndrome, which often appear at a young age. Amsterdam and Bethesda criteria have been used to identify patients with Lynch syndrome.one case was reported at the Dr. M. Djamil Padang hospital, a 16-year-old girl with right lower abdominal pain. Obtained a history of similar disease in grandparents, aunts and six other family members. On physical examination found palpable fixed abdominal mass with hard consistency in the lower right abdomen. At colonoscopy and biopsy found a moderatly differentiated adenocarcinoma colon type at the hepatic flexure and the sigmoid colon polyp. Based on the Amsterdam criteria, patients diagnosed with HNPCC/Lynch

  17. The Contributions - and Collapse - of Lamarckian Heredity in Pasteurian Molecular Biology: 1. Lysogeny, 1900-1960.

    Science.gov (United States)

    Loison, Laurent; Gayon, Jean; Burian, Richard M

    2017-02-01

    This article shows how Lamarckism was essential in the birth of the French school of molecular biology. We argue that the concept of inheritance of acquired characters positively shaped debates surrounding bacteriophagy and lysogeny in the Pasteurian tradition during the interwar period. During this period the typical Lamarckian account of heredity treated it as the continuation of protoplasmic physiology in daughter cells. Félix d'Hérelle applied this conception to argue that there was only one species of bacteriophage and Jules Bordet applied it to develop an account of bacteriophagy as a transmissible form of autolysis and to analyze the new phenomenon of lysogeny. In a long-standing controversy with Bordet, Eugène Wollman deployed a more morphological understanding of the inheritance of acquired characters, yielding a particulate, but still Lamarckian, account of lysogeny. We then turn to André Lwoff who, with several colleagues, completed Wollman's research program from 1949 to 1953. We examine how he gradually set aside the Lamarckian background, finally removing inheritance of acquired characters from the resulting account of bacteriophagy and lysogeny. In the conclusion, we emphasize the complex dual role of Lamarckism as it moved from an assumed explanatory framework to a challenge that the nascent molecular biology had to overcome.

  18. Heredity, evolution and development in their (epistemic) environment at the turn of the nineteenth century.

    Science.gov (United States)

    Colonna, Federica Turriziani

    2016-03-01

    During the early 1870s a young zoologist who worked as a Privatdozent delivering lectures at different Prussian universities invested much of his family wealth and solicited his fellows' contributions to establish a research facility by the sea. The young zoologist happened to be called Anton Dohrn. From the time it opened its doors, the Anton Dohrn Zoological Station - or Naples Zoological Station, as it was originally called - played a crucial role in shaping life sciences as it facilitated research aimed at explaining the mechanics of inheritance. During the last quarter of the nineteenth century and the first decades of the twentieth, zoologists attempted to explain how evolutionary changes occur within a population and become stabilized. In so doing, they looked at developmental processes as well as environmental pressure, coming up with different hypotheses to explain inheritance. In some cases, their research was highly speculative, whereas in other cases they conducted cytological observations to identify the material basis of heredity. Research on evolution and development has been carried out in different places, and zoological stations like the one in Naples have played a major role in this story. However, numerous biological institutions active at the turn of the twentieth century have not received much attention from historians.

  19. Conventional, emerging, heredity, lifestyle, and psychosocial coronary risk factors: relationships to subclinical atherosclerosis.

    Science.gov (United States)

    Taylor, Allen J; Arora, Navin S; Bindeman, Jody; Bhattari, Saroj; Feuerstein, Irwin M; O'malley, Patrick G

    2006-01-01

    The authors examined the relationship between calcified coronary atherosclerosis and an array of cardiovascular risk factors in sequential logistic models to determine the extent to which these markers overlap in their identification of patients at risk for developing coronary heart disease. The prevalence of coronary artery calcium using electron beam computed tomography was 19.4% in this cross-sectional study of a prospective, consecutive, screening cohort of 1999 healthy United States Army personnel (aged 39-50 years). The proportion of the total variance of coronary artery calcium explained by sequential logistic models incorporating conventional, emerging, hereditary, lifestyle, and psychosocial cardiovascular risk variables increased progressively from 9.7% to 14.5%. The best-fit logistic model for the prediction of coronary artery calcium identified age, male gender, Framingham risk score, total cholesterol, high-density lipoprotein cholesterol, triglycerides, smoking, a family history of coronary heart disease, white race, physical inactivity, and lower depression scores as significant independent correlates of coronary artery calcium. These data indicate that the explanatory power of models for atherosclerosis can be significantly improved with the use of emerging, heredity, lifestyle, and psychosocial factors. The large residual variance, however, supports the potential of atherosclerosis imaging to incrementally and independently identify coronary heart disease risk.

  20. Paradox of the Moving Boundary: Legal Heredity of River Accretion and Avulsion

    Directory of Open Access Journals (Sweden)

    John W. Donaldson

    2011-06-01

    Full Text Available International boundaries – the divisions between state jurisdictions – are characterised in law by their inherent rigidity. Yet recent research has revealed that well over one-third of the total length of international boundaries follow rivers or streams that are inherently dynamic natural features. The tension between legal staticity and fluid dynamism manifests along international river boundaries both in terms of the problematic definition of the line itself and the disparity in water management regulations. The actions of accretion and avulsion have been used to resolve disputes over river boundary movement since Roman times, but they contain an inherent paradox. Tracing the heredity of these two legal mechanisms, this paper will expose that paradox by focusing on the relationship between boundary and water. State practice will reveal how the continued application of these mechanisms is reinforcing a land bias in international law that becomes problematic when addressing a dynamic fluid resource that is concurrently divided and shared. Rather than emphasising the rigidity of jurisdictional division, this paper will suggest that deterring the risks inherent in the definition of river boundaries requires challenging some of the foundational legal tenets of territorial sovereignty; tenets that continue to influence the development of international water law.

  1. [Current status of heredity role in development of allergies among the children].

    Science.gov (United States)

    Saakadze, V; Metreveli, M

    2006-12-01

    The study of the role of compromised allergic heredity among the patients' parents in frequency of allergic illnesses among the children was conducted. Through the accurate analysis were selected two groups of patients. The first group - different allergic diseases (345 sick children from 0 to 17 years old); the second (control) group - different somatic diseases of non-allergic genesis (251 patients of the same age without any records in the anamnesis on development of allergy and signs of accompanied allergic pathologies during the examination period and clinical medication for somatic illnesses of non-allergic genesis. The study of allergic and family anamnesis of patients in both groups-right immediately during the clinical research and therapy, and the retrospective specification of required data via different source of communication certain regularity was revealed that allowed to conclude that among the risk factors that define formation of allergic disposition among the children, the hereditary compromised patients' parents take an important role in development of so called biological defects among their children in pre-natal period of life. These so-called biological defects provide formation and development of allergic status and different allergic diseases among the posterity (risk factor coefficient PR is 2,49 and waves from 1,8 up to 2,73).

  2. The post-perspectival: screens and time in David Lynch's Inland Empire

    Directory of Open Access Journals (Sweden)

    Anne Jerslev

    2012-03-01

    Full Text Available Taking Anne Friedberg's notion of the post-perspectival as the point of departure for her analysis of David Lynch's digitally shot and edited Inland Empire from 2006, Anne Jerslev argues that the film deconstructs continuous time and coherent space by constructing multiple planes of representation, multiple layerings of screens and, hence, multiple and fractured modes of perception. The article further suggests that the film's enigmatic structure might best be understood with reference to a new media genre like the website with its hyperlink structure. Finally, the article discusses how a sense of ubiquitous surveillance coalesces with the screen logic.Author Biography Anne Jerslev (PhD is Professor of Film and Media Studies at the Department of Media, Cognition and Communication, University of Copenhagen. Anne Jerslev has published and edited books in Danish and English and published dozens of articles in journals and anthologies in Danish, Scandinavian languages, German and English. Her first book was titled David Lynch i vore øjne (David Lynch in our eyes (1991; it was published in German in 1995 under the title David Lynch—mentale Landschaften. After the Lynch book she published books about cult movies, youth and media and media and intimacy. She has edited two volumes in English, Realism and Reality in Film and Media (2002, where she contributed a piece about Lars von Trier's The Idiots, and Performative Realism (co-edited with Rune Gade (2005. Her latest edited volume (co-edited with Christa Lykke Christensen is Hvor går grænsen? Brudflader i den moderne mediekultur [Are there no limits? The crossing of boundaries in contemporary media culture] (Copenhagen 2010. She is currently editing a volume about “Impure Cinema” together with professor Lúcia Nagib from the University of Leeds, which will appear in 2013. Her own contribution to the book is an article about David Lynch's Interview Project.

  3. Microsatellite instability and DNA mismatch repair protein deficiency in Lynch syndrome colorectal polyps.

    Science.gov (United States)

    Yurgelun, Matthew B; Goel, Ajay; Hornick, Jason L; Sen, Ananda; Turgeon, Danielle Kim; Ruffin, Mack T; Marcon, Norman E; Baron, John A; Bresalier, Robert S; Syngal, Sapna; Brenner, Dean E; Boland, C Richard; Stoffel, Elena M

    2012-04-01

    Colorectal cancers associated with Lynch syndrome are characterized by deficient DNA mismatch repair (MMR) function. Our aim was to evaluate the prevalence of microsatellite instability (MSI) and loss of MMR protein expression in Lynch syndrome-associated polyps. Sixty-two colorectal polyps--37 adenomatous polyps, 23 hyperplastic polyps, and 2 sessile serrated polyps (SSP)--from 34 subjects with germline MMR gene mutations were tested for MSI using a single pentaplex PCR for five mononucleotide repeat microsatellite markers, and also for expression of MLH1, MSH2, MSH6, and PMS2 proteins by immunohistochemistry. High-level MSI (MSI-H) was seen in 15 of 37 (41%) adenomatous polyps, one of 23 (4%) hyperplastic polyps, and one of two (50%) SSPs. Loss of MMR protein expression was seen in 18 of 36 (50%) adenomatous polyps, zero of 21 hyperplastic polyps, and zero of two SSPs. Adenomatous polyps 8 mm or larger in size were significantly more likely to show MSI-H [OR, 9.98; 95% confidence interval (CI), 1.52-65.65; P = 0.02] and deficient MMR protein expression (OR, 3.17; 95% CI, 1.20-8.37; P = 0.02) compared with those less than 8 mm in size. All (six of six) adenomatous polyps 10 mm or larger in size showed both MSI-H and loss of MMR protein expression by immunohistochemistry. Our finding that the prevalence of MMR deficiency increases with the size of adenomatous polyps suggests that loss of MMR function is a late event in Lynch syndrome-associated colorectal neoplasia. Although testing large adenomatous polyps may be of value in the diagnostic evaluation of patients with suspected Lynch syndrome, the absence of an MMR-deficient phenotype in an adenoma cannot be considered as a strong evidence against Lynch syndrome, as it is with colorectal carcinomas. 2012 AACR

  4. Henry's law constants of chlorinated solvents at elevated temperatures.

    Science.gov (United States)

    Chen, Fei; Freedman, David L; Falta, Ronald W; Murdoch, Lawrence C

    2012-01-01

    Henry's law constants for 12 chlorinated volatile organic compounds (CVOCs) were measured as a function of temperature ranging from 8 to 93°C, using the modified equilibrium partitioning in closed system (EPICS) method. The chlorinated compounds include tetrachloroethylene, trichloroethylene, cis-1,2-dichloroethylene, vinyl chloride, 1,1,1-trichloroethane, 1,1-dichloroethane, 1,2-dichloroethane, chloroethane, carbon tetrachloride, chloroform, dichloromethane, and chloromethane. The variation in Henry's constants for these compounds as a function of temperature ranged from around 3-fold (chloroethane) to 30-fold (1,2-dichloroethane). Aqueous solubilities of the pure compounds were measured over the temperature range of 8-75°C. The temperature dependence of Henry's constant was predicted using the ratio of pure vapor pressure to aqueous solubility, both of which are functions of temperature. The calculated Henry's constants are in a reasonable agreement with the measured results. With the improved data on Henry's law constants at high temperatures measured in this study, it will be possible to more accurately model subsurface remediation processes that operate near the boiling point of water. Published by Elsevier Ltd.

  5. Science Advisor and Applied Physicist: Joseph Henry Serves His Country

    Science.gov (United States)

    Rothenberg, Marc

    1997-04-01

    When Joseph Henry accepted the postion of secretary of the Smithsonian in 1846, his career changed radically. Although he never ceased thinking of himself as a research scientist and educator, thereafter his chief roles were those of science administrator and advisor to both the executive and legislative branches of the federal government for both science and technology. His effectiveness as an advocate became more important than his skill as an experimental physicist. Even when he entered the laboratory, his role had changed. No longer was he concerned with basic research. As a member of various government boards and committees, Henry spent the last three decades of his life concerned with the application of fundamental knowledge for the improvement of the human condition. This paper will discuss Henry's service on behalf of his country.

  6. Comprehensive population-wide analysis of Lynch syndrome in Iceland reveals founder mutations in MSH6 and PMS2

    DEFF Research Database (Denmark)

    Haraldsdottir, Sigurdis; Rafnar, Thorunn; Frankel, Wendy L

    2017-01-01

    Lynch syndrome, caused by germline mutations in the mismatch repair genes, is associated with increased cancer risk. Here using a large whole-genome sequencing data bank, cancer registry and colorectal tumour bank we determine the prevalence of Lynch syndrome, associated cancer risks...... and pathogenicity of several variants in the Icelandic population. We use colorectal cancer samples from 1,182 patients diagnosed between 2000-2009. One-hundred and thirty-two (11.2%) tumours are mismatch repair deficient per immunohistochemistry. Twenty-one (1.8%) have Lynch syndrome while 106 (9.0%) have somatic...... hypermethylation or mutations in the mismatch repair genes. The population prevalence of Lynch syndrome is 0.442%. We discover a translocation disrupting MLH1 and three mutations in MSH6 and PMS2 that increase endometrial, colorectal, brain and ovarian cancer risk. We find thirteen mismatch repair variants...

  7. Limited impact on self-concept in individuals with Lynch syndrome; results from a national cohort study

    DEFF Research Database (Denmark)

    Petersen, Helle Vendel; Esplen, Mary Jane; Ladelund, Steen

    2011-01-01

    An increasing number of individuals seek genetic counseling and hereby learn about hereditary cancer in the family. Lynch syndrome is associated with an inherited high risk for colorectal and gynecological cancer, but knowledge about how family members at risk perceive their situation is limited....... We used the national Danish HNPCC register to collect data on self-concept from 413 individuals with Lynch syndrome. The recently developed Lynch syndrome self-concept scale contains 20 items within two subscales related to stigma-vulnerability and bowel symptom-related anxiety. Significantly higher...... more often reported by women (odds ratio 1.8) and by individuals with less education (OR 1.8). This study provides the first extended use of the Lynch syndrome self-concept scale and suggests that the majority of the Danish mutation carriers adapt well to the situation, though knowledge about...

  8. Exploring Henri Meschonnic’s Poetics of Translating

    OpenAIRE

    Kadiu, Silvia

    2015-01-01

    Henri Meschonnic (1932–2009) is a relatively unknown figure in the Anglophone world. A French poet, linguist, and translator, he has authored several texts about translation, only one of which has been translated into English: Ethics and Politics of Translating (2011). Dr Marko Pajević’s exploration of Henri Meschonnic’s philosophy of language, given as a part of the UCL Translation in History lecture series on 23 October 2014, provided an informative introduction to the translation theory of...

  9. A cohort analysis of men with a family history of BRCA1/2 and Lynch mutations for prostate cancer.

    Science.gov (United States)

    Kerr, Lynne; Rewhorn, Matthew J; Longmuir, Mark; Fraser, Sioban; Walsh, Shaun; Andrew, Nicola; Leung, Hing Y

    2016-07-25

    Prostate cancer (PC) is a major health concern for men worldwide, with an estimated lifetime risk of ~14 %. A recent comprehensive analysis of mutational processes revealed ageing and mismatch repair as the only altered processes in PC. We wish to test if a cohort of men with inherited risk of mismatch repair defect through BRCA1/2 or Lynch Syndrome mutations represents a target population for prostate cancer testing. Fifty-eight men (aged 40-69 years) from families with a history of BRCA1/2 or HNPCC/Lynch mutations were invited to take part. Men with PSA >3.0 ng/ml were recommended to have transrectal ultrasound-guided prostatic biopsies. Overall 1 of 7 (14 %) and 1 of 20 (5 %) men with BRCA1/2 mutations were positive for a diagnosis of prostate cancer. In men with Lynch syndrome, 1 of 4 (25 %) was diagnosed to have prostate cancer. The index case with Lynch syndrome harbours a heterozygous mutation in the mismatch repair MSH6 gene. Near to complete loss of MSH6 immunoreactivity in the prostate tumour supports silencing of the remaining MSH6 allele during prostate carcinogenesis. The finding of near-to-complete loss of MSH6 expression in affected men with a family history of Lynch Syndrome supports its mechanistic involvement during prostate carcinogenesis. This work therefore contributes to the argument that, in certain male populations, Lynch Syndrome mutations are biologically implicated in men with prostate cancer.

  10. Identification of MSH2 inversion of exons 1-7 in clinical evaluation of families with suspected Lynch syndrome.

    Science.gov (United States)

    Mork, Maureen E; Rodriguez, Andrea; Taggart, Melissa W; Rodriguez-Bigas, Miguel A; Lynch, Patrick M; Bannon, Sarah A; You, Y Nancy; Vilar, Eduardo

    2017-07-01

    Traditional germline sequencing and deletion/duplication analysis does not detect Lynch syndrome-causing mutations in all individuals whose colorectal or endometrial tumors demonstrate mismatch repair (MMR) deficiency. Unique inversions and other rearrangements of the MMR genes have been reported in families with Lynch syndrome. In 2014, a recurrent inversion of MSH2 exons 1-7 was identified in five families suspected to have Lynch syndrome. We aimed to describe our clinical experience in identifying families with this specific inversion. Four probands whose Lynch syndrome-associated tumors demonstrated absence of MSH2/MSH6 staining and who had negative MMR germline testing were evaluated for the MSH2 inversion of exons 1-7, offered during initial genetic workup or upon routine clinical follow-up. All four probands tested positive for the MSH2 inversion. Proband cancer diagnoses included colon and endometrial adenocarcinoma and sebaceous adenoma. A variety of Lynch syndrome-associated cancers were reported in the family histories, although only one family met Amsterdam II criteria. Thirteen at-risk relatives underwent predictive testing. MSH2 inversion of exons 1-7 was found in four probands previously suspected to have Lynch syndrome based on family history and tumor testing. This testing should be offered routinely to patients with tumors demonstrating loss of MSH2/MSH6 staining.

  11. Leaves imitate trees: Minnesota Hmong concepts of heredity and applications to genomics research.

    Science.gov (United States)

    Culhane-Pera, Kathleen A; Moua, MaiKia; Vue, Pachia; Xiaaj, Kang; Lo, May Xia; Straka, Robert J

    2017-01-01

    Historically, Hmong refugees in the USA were distrustful of Western medicine, medicines, and medical research due to concerns about harm and experimentation. Current Hmong concerns about genomics research are not well known. Our research aims were to identify cultural and ethical issues about conducting genomic studies in the Hmong community. Using a community-based participatory action process, the West Side Hmong Genomics Research Board conducted a qualitative exploratory research study that included semistructured interviews with five Hmong key informants and five focus groups with 42 Hmong adults near Saint Paul, Minnesota. We used a thematic analysis approach to qualitatively analyze the data. Identified concepts of heredity included characteristics that are passed between the generations: physical features; character traits; some behaviors; some diseases; and probably not response to medicines, although individual variations to medicines are known. Most participants were willing to join genomic research projects to help themselves and community. Others refused to participate: they did not want to know future disease risk; did not want doctors to know their genes; did not trust doctors with their blood; and did not know if they would benefit from results. Ethically, many participants were in favor of confidentiality, but wanted to know their personal results; many were willing to agree to genetic storage of anonymous samples; all agreed with individual consent, not family or community consent; and none were concerned about social stigma from genetic testing about chronic diseases and medications. The Hmong Genomics Board will build upon these concepts to create, conduct, and evaluate culturally-appropriate genomic and pharmacogenomic research projects relevant to community interests.

  12. Henry Giroux on Democracy Unsettled: From Critical Pedagogy to the War on Youth--An Interview

    Science.gov (United States)

    Peters, Michael A.

    2012-01-01

    This interview conducted with Henry Giroux begins by probing Henry's childhood, upbringing and undergraduate years to discover where his sense of social justice took hold. It also questions Henry about his working-class background and the major influences on his thought, including his relationships with Paulo Freire and Howard Zinn. The interview…

  13. Differential expression of CK20, β-catenin, and MUC2/5AC/6 in Lynch syndrome and familial colorectal cancer type X

    DEFF Research Database (Denmark)

    Haraldsson, Stefan; Klarskov, Louise; Nilbert, Mef

    2017-01-01

    BACKGROUND: Hereditary non-polyposis colorectal cancer comprises Lynch syndrome and familial colorectal cancer type X (FCCTX). Differences in genetics, demographics and histopathology have been extensively studied. The purpose of this study is to characterize their immunoprofile of markers other...... than MMR proteins. METHODS: We compared the expression patterns of cytokeratins (CK7 and CK20), mucins (MUC2/5 AC/6), CDX2 and β-catenin in Lynch syndrome and FCCTX. RESULTS: Differences were identified for CK20 and nuclear β-catenin, which were significantly more often expressed in FCCTX than in Lynch...... syndrome (p Lynch syndrome tumors compared with FCCTX tumors (p = 0.001,

  14. Writing, Self-realization and Community: Henry Muoria and the ...

    African Journals Online (AJOL)

    This paper traces the career of the Kenyan publicist and intellectual, Henry Muoria (1914-1997). Muoria was an active journalist, a friend and press secretary of Kenya's future president Jomo Kenyatta and, from 1945 to 1952, the editor of a nationalist newspaper Mumenyereri, written in Gikuyu, one of Kenya's major ...

  15. Comparison of the acute effects of Tulbaghia violacea William Henry ...

    African Journals Online (AJOL)

    Purpose: To assess the effect of the crude methanol leaf extracts of Tulbaghia violacea William Henry Harvey (Alliaceae) on blood pressure (BP) and heart rate in ageing normotensive Wistar Kyoto rats (WKY), and compare the results obtained with those for adult spontaneously hypertensive rats (SHR). Methods: T.

  16. Driving into the Heart of Henry Giroux's Pedagogy.

    Science.gov (United States)

    Rhodes, Keith

    1996-01-01

    Muses on the power and intelligence of Henry Giroux as a composition theorist and pedagogue. Recounts Giroux's presentation at the 1993 Penn State Conference on Rhetoric and Composition and his categorizing of the "power dynamics" present at most institutions. Opts for "expressivist" pedagogy. (PA)

  17. The Transformative Intellectual: An Examination of Henry Giroux's Ethics

    Science.gov (United States)

    Kashani, Tony

    2012-01-01

    This article explores Henry Giroux's contributions to critical pedagogy. The author demonstrates how Giroux, as a public intellectual, has found his Ethics in the right place. The author further argues that Giroux's Ethics of virtue are present not only in the public person but also in his transformative writing.

  18. The Hope of Radical Education: A Conversation with Henry Giroux.

    Science.gov (United States)

    Journal of Education, 1988

    1988-01-01

    Radical education is questioning institutions and assumptions about education. An interview presents ideas of the spokesperson, Henry Giroux. They include the following: (1) traditional thinkers have the wrong perception of education; (2) education should engender empowerment; (3) radical education goes beyond a Marxist perspective; and (4)…

  19. Kesknoored tegid visiidi Šveitsi / Henri Kaselo

    Index Scriptorium Estoniae

    Kaselo, Henri

    2005-01-01

    Keskerakonna noorte esindus külastas 20.-25. aprillini 2005 Šveitsi, et osaleda sealsete noorte liberaalide Jungfreisinnige Schweizi kongressil. Delegatsiooni kuulusid esimees Tarmo Lausing, välissekretär Olga Sõtnik, endine pressisekretär Raimond Kaljulaid ja noortekogu esimees Henri Kaselo

  20. George Henry Hepting: Pioneer Leader in Forest Pathology

    Science.gov (United States)

    Ellis B. Cowling; Arthur Kelman; Harry R. Powers

    1999-01-01

    George Henry Hepting grew up in the city environment of Brooklyn, but early in his life developed a deep love and scientific interest in forestry. He became America's most skilled scientist in the theory and practice of forest pathology. He studied how long-lived forest trees, unlike most plants, cope with the long-term changes in their biological, physical, and...

  1. Henri Poincaré: A Scientific Biography [Book Review

    OpenAIRE

    Sauer, Tilman

    2014-01-01

    It must have taken some courage to undertake the task of writing a scientific biography of a towering figure like Henri Poincaré. Jeremy Gray took on the challenge and has delivered a wonderful book. Poincaré (1854–1912) is considered one of the most influential mathematicians of the late nineteenth and early twentieth centuries. His oeuvre is vast and formidable.

  2. The John Henry wars | Berman | Marang: Journal of Language and ...

    African Journals Online (AJOL)

    academics, the former accusing the latter of ruining the legend through endless analysis. As the title suggests, these 'wars' over this national icon unearth the subtleties of the political economy of labor, the ironies of racial identity, and the intricate relationship between folklore and fiction. Keywords:folklore, John Henry

  3. Henri Poincaré a biography through the daily papers

    CERN Document Server

    Ginoux, Jean-Marc

    2014-01-01

    On July 17, 2012, the centenary of Henri Poincaré's death was commemorated; his name being associated with so many fields of knowledge that he was considered as the Last Universalist. In Pure and Applied Mathematics, Physics, Astronomy, Engineering and Philosophy, his works have had a great impact all over the world. Poincaré acquired in his lifetime such a reputation that, both nationally and internationally, his life and career were made the object of various articles in the daily papers not only in France, but also in the USA. Some of his philosophical concepts have even caused sharp controversies in the Press (as we will discover in this book).This work presents an original portrait of Henri Poincaré based on various press cuttings from The New York Times, The San Francisco Sunday Call, The Times, The Sun, The Washington Post that chronicled unknown anecdotes of his life (for example, his first name was actually not Henri, but Henry; he obtained his high school diploma in sciences with a zero in mathem...

  4. The Failed Educations of John Stuart Mill and Henry Adams.

    Science.gov (United States)

    Crossley, Robert

    1979-01-01

    Analyzes and contrasts Mill's "Autobiography" and Adams'"The Education of Henry Adams" in order to present two approaches to the nature of education and of failure. Maintains that their perspectives may serve as catalysts and cautions for contemporary theories of education and its utility and relevance. (CAM)

  5. A special issue for Henri Poincaré

    NARCIS (Netherlands)

    Verhulst, Ferdinand|info:eu-repo/dai/nl/068380437; Wepster, S.A.|info:eu-repo/dai/nl/304831565

    One hundred years ago, on 17 July 1912, Henri Poincare died at the age of only 58 years. He had been unusually productive with fundamental results in mathematics, physics and astronomy, and he can be regarded as one of the most important mathematical physicists of all times; his work had a major

  6. Henry's law constants for dimethylsulfide in freshwater and seawater

    Science.gov (United States)

    Dacey, J. W. H.; Wakeham, S. G.; Howes, B. L.

    1984-01-01

    Distilled water and several waters of varying salinity were subjected, over a 0-32 C temperature range, to measurements for Henry's law constants for dimethylsulfide. Values for distilled water and seawater of the solubility parameters A and C are obtained which support the concept that the concentration of dimethylsulfide in the atmosphere is far from equilibrium with seawater.

  7. Potential Beneficial Effects of Tulbaghia violacea William Henry ...

    African Journals Online (AJOL)

    Tulbaghia violacea William Henry Harvey (Harv. Alliaceae) is a small bulbous herb belonging to the family Alliaceae. It is used in South Africa to treat fever, colds, asthma, paralysis, and hypertension. Meanwhile, cardiovascular disease accounts for about 30 % of total global death, with most of these deaths occurring in low ...

  8. Unlikely reformer: Dr Henry Calvert Barnett (1832-1897).

    Science.gov (United States)

    Martyr, Philippa

    2017-10-01

    To provide a brief biography of Western Australian colonial lunacy superintendent Dr Henry Calvert Barnett. A range of primary sources were consulted. Barnett was a complex man: a caring and forward-thinking practitioner who had a colourful and turbulent private life. Barnett's contribution to mental health service development in Western Australia was genuine and worthwhile, and should be recognised.

  9. Henry Odera Oruka, Ecophilosophy and Climate Change | Attfield ...

    African Journals Online (AJOL)

    The purpose of this paper is to explore what Henry Odera Oruka, a renowned ecophilosopher and Director designate of an Ecophilosophy Centre, would have thought and argued in the sphere of climate change if he had remained alive beyond 1995 and up to the present time. The methodology of the paper combines an ...

  10. Sir William Henry Perkin: The Man and his 'Mauve'

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 15; Issue 9. Sir William Henry Perkin: The Man and his 'Mauve'. G Nagendrappa. General Article Volume 15 Issue 9 September 2010 pp 779-793. Fulltext. Click here to view fulltext PDF. Permanent link:

  11. Henry the Seventh and Italy, an historiographical account

    Directory of Open Access Journals (Sweden)

    Gian Maria Varanini

    2014-06-01

    Full Text Available The article represents an introduction to the contributions published in the monographic section dedicated to the expedition of Henry VII of Luxembourg in Italy (1310-1313. It provides an historiographic overview and some insightful clues.

  12. Philosophic sagacity and intercultural philosophy : beyond Henry Odera Oruka

    NARCIS (Netherlands)

    Mosima, P.M.

    2016-01-01

    In this work, I attempt to contribute to the future of African and intercultural philosophy. This is undertaken by a comparative appraisal of the late lamented Kenyan philosopher Henry Odera Oruka's (1944-1995) philosophic sagacity, and intercultural philosophy as conceived by Dutch intercultural

  13. William Henry Bragg (1862-1942) William Lawrence Bragg (1890 ...

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 19; Issue 12. William Henry Bragg (1862-1942) William Lawrence Bragg (1890-1971). Featured Scientist Volume 19 Issue 12 December 2014 pp 1210-1210. Fulltext. Click here to view fulltext PDF. Permanent link:

  14. In praise of the literary eponym--Henry V sign.

    LENUS (Irish Health Repository)

    Shanahan, F

    2013-01-01

    The use of eponyms in medicine is often discouraged. However, the literary eponym should be an exception as it is not linked with many of the difficulties associated with conventional eponyms and offers descriptive brevity and accuracy. Here, we illustrate the point with Henry V sign, which will be familiar to many who have cared for patients in the terminal stage of illness.

  15. One case of endometrial cancer occurrence: Over 10 years after colon cancer in Lynch family.

    Science.gov (United States)

    Lee, Jee Yeon; Kim, Hyun Joo; Lee, Eun Hee; Lee, Hyoun Wook; Kim, Jong-Won; Kim, Min Kyu

    2013-11-01

    We have recently experienced an endometrial cancer 12 years after the diagnosis of colon cancer with Lynch syndrome. A 49-year-old Korean woman had a family history of colon cancer. Her mother had colon cancer at 56-year-old, and her brother had colon cancer at 48 years old. The patient received surgery for endometrial cancer at the same hospital 12 years after being treated for colon cancer. Immunohistochemistry showed that her endometrial tissue stained negative for MSH2. A microsatellite instability test was performed and showed the presence of instability high microsatellite instability. An hMLH2 gene mutation was detected at codon 629 codon of exon 12, in which a glutamine was replaced with an arginine (1886A>G [p.Gln629Arg]). To our knowledge, this is the first case of metachronous cancer in a Lynch syndrome family in Korea with a gap of more than ten years between cancer diagnoses.

  16. Expression defect size among unclassified MLH1 variants determines pathogenicity in Lynch syndrome diagnosis

    DEFF Research Database (Denmark)

    Hinrichsen, Inga; Brieger, Angela; Trojan, Jörg

    2013-01-01

    Lynch syndrome is caused by a germline mutation in a mismatch repair gene, most commonly the MLH1 gene. However, one third of the identified alterations are missense variants with unclear clinical significance. The functionality of these variants can be tested in the laboratory, but the results c...... cannot be used for clinical diagnosis. We therefore aimed to establish a laboratory test that can be applied clinically.......Lynch syndrome is caused by a germline mutation in a mismatch repair gene, most commonly the MLH1 gene. However, one third of the identified alterations are missense variants with unclear clinical significance. The functionality of these variants can be tested in the laboratory, but the results...

  17. Urinary Tract Cancer in Lynch Syndrome; Increased Risk in Carriers of MSH2 Mutations

    DEFF Research Database (Denmark)

    Joost, Patrick; Therkildsen, Christina; Dominguez-Valentin, Mev

    2015-01-01

    OBJECTIVE: To evaluate the risk of urothelial cancer in the upper urinary tract and the bladder, determine the contribution from the different mismatch-repair genes, and define clinical characteristics of urothelial cancer in Lynch syndrome. MATERIALS AND METHODS: The national hereditary...... lifetime risks were determined. RESULTS: In total, 48 cancers of the ureter, 34 cancers of the renal pelvis, and 54 urinary bladder cancers developed at a mean age of 61 (24-89) years. The tumors were typically of high grade, showed loss of mismatch-repair protein expression in 90% of the tumors...... and the urinary bladder are included in the Lynch syndrome tumor spectrum. Urothelial cancers are predominantly linked to MSH2 mutations, which suggest that surveillance should be targeted at individuals with mutations herein....

  18. From lynching to gay bashing: the elusive connection between economic conditions and hate crime.

    Science.gov (United States)

    Green, D P; Glaser, J; Rich, A

    1998-07-01

    Trends in bigoted violence are often explained by reference to frustrations arising from macroeconomic downturns. Historical and recent time-series studies have turned up significant links between economic conditions and lynchings of Blacks in the pre-Depression South (e.g., Hepworth & West, 1988; Hovland & Sears, 1940). However, replicating the time-series analyses of lynching, extending them through the Great Depression, and applying similar techniques to contemporary data fail to provide robust evidence of a link between economic performance and intolerant behavior directed against minorities. The authors speculate that the predictive force of macroeconomic fluctuation is undermined by the rapid rate of decay in the frustration-bred aggressive impulse and the absence of prominent political actors affixing economic blame on target groups.

  19. Validation of a self-concept scale for Lynch syndrome in different nationalities.

    Science.gov (United States)

    Petersen, Helle Vendel; Domanska, Katarina; Bendahl, Pär-Ola; Wong, Jiahui; Carlsson, Christina; Bernstein, Inge; Esplen, Mary Jane; Nilbert, Mef

    2011-06-01

    Learning about hereditary cancer may influence an individual's self-concept, which otherwise represents a complex but stable cognitive structure. Recently, a 20-statement self-concept scale, with subscales related to stigma-vulnerability and bowel symptom-related anxiety, was developed for Lynch syndrome. We compared the performance of this scale in 591 mutation carriers from Denmark, Sweden and Canada. Principal component analysis identified two sets of linked statements-the first related to feeling different, isolated and labeled, and the second to concern and worry about bowel changes. The scale performed consistently in the three countries. Minor differences were identified, with guilt about passing on a defective gene and feelings of losing one's privacy being more pronounced among Canadians, whereas Danes more often expressed worries about cancer. Validation of the Lynch syndrome self-concept scale supports its basic structure, identifies dependence between the statements in the subscales and demonstrates its applicability in different Western populations.

  20. Effect of aspirin or resistant starch on colorectal neoplasia in the Lynch syndrome

    DEFF Research Database (Denmark)

    Burn, John; Bishop, D Timothy; Mecklin, Jukka-Pekka

    2008-01-01

    BACKGROUND: Observational and epidemiologic data indicate that the use of aspirin reduces the risk of colorectal neoplasia; however, the effects of aspirin in the Lynch syndrome (hereditary nonpolyposis colon cancer) are not known. Resistant starch has been associated with an antineoplastic effect...... on the colon. METHODS: In a randomized, placebo-controlled trial, we used a two-by-two design to investigate the effects of aspirin, at a dose of 600 mg per day, and resistant starch (Novelose), at a dose of 30 g per day, in reducing the risk of adenoma and carcinoma among persons with the Lynch syndrome...... developed in 141 participants. Of 693 participants randomly assigned to receive aspirin or placebo, neoplasia developed in 66 participants receiving aspirin (18.9%), as compared with 65 receiving placebo (19.0%) (relative risk, 1.0; 95% confidence interval [CI], 0.7 to 1.4). There were no significant...

  1. Phenotypic and genotypic heterogeneity of Lynch syndrome: a complex diagnostic challenge.

    Science.gov (United States)

    Lynch, Henry T; Lanspa, Stephen; Shaw, Trudy; Casey, Murray Joseph; Rendell, Marc; Stacey, Mark; Townley, Theresa; Snyder, Carrie; Hitchins, Megan; Bailey-Wilson, Joan

    2017-10-25

    Lynch syndrome is the hereditary disorder that most frequently predisposes to colorectal cancer as well as predisposing to a number of extracolonic cancers, most prominently endometrial cancer. It is caused by germline mutations in the mismatch repair genes. Both its phenotype and genotype show marked heterogeneity. This review gives a historical overview of the syndrome, its heterogeneity, its genomic landscape, and its implications for complex diagnosis, genetic counseling and putative implications for immunotherapy.

  2. Compression of weather charts by the segmented Lynch-Davisson code.

    Science.gov (United States)

    Lynch, T. J.

    1973-01-01

    The Lynch-Davisson (L-D) code is shown to be efficient for compressing line-scanned weather charts wherein each line is divided into equal-length segments, and a separate L-D code is generated for each segment. As the number of segments increases, the L-D code length decreases appreciably, thereby simplifying the encoding and decoding operations. However, the accompanying decrease in the overall compression ratio is relatively small.

  3. Field performance of timber bridges. 8, Lynches Woods Park stress-laminated deck bridge

    Science.gov (United States)

    J. P. Wacker; M. A. Ritter; D. Conger

    The Lynches Woods Park bridge was constructed during the summer of 1990 in Newberry, South Carolina. It is a single-span, single-lane, stress-laminated deck superstructure that measures approximately 30 ft long, 16 ft wide, and 14 in. deep. The bridge is unique in that is one of the first known stress-laminated deck bridges to be constructed of Southern Pine lumber...

  4. Lynch syndrome: barriers to and facilitators of screening and disease management.

    Science.gov (United States)

    Watkins, Kathy E; Way, Christine Y; Fiander, Jacqueline J; Meadus, Robert J; Esplen, Mary Jane; Green, Jane S; Ludlow, Valerie C; Etchegary, Holly A; Parfrey, Patrick S

    2011-09-07

    Lynch syndrome is a hereditary cancer with confirmed carriers at high risk for colorectal (CRC) and extracolonic cancers. The purpose of the current study was to develop a greater understanding of the factors influencing decisions about disease management post-genetic testing. The study used a grounded theory approach to data collection and analysis as part of a multiphase project examining the psychosocial and behavioral impact of predictive DNA testing for Lynch syndrome. Individual and small group interviews were conducted with individuals from 10 families with the MSH2 intron 5 splice site mutation or exon 8 deletion. The data from confirmed carriers (n = 23) were subjected to re-analysis to identify key barriers to and/or facilitators of screening and disease management. Thematic analysis identified personal, health care provider and health care system factors as dominant barriers to and/or facilitators of managing Lynch syndrome. Person-centered factors reflect risk perceptions and decision-making, and enduring screening/disease management. The perceived knowledge and clinical management skills of health care providers also influenced participation in recommended protocols. The health care system barriers/facilitators are defined in terms of continuity of care and coordination of services among providers. Individuals with Lynch syndrome often encounter multiple barriers to and facilitators of disease management that go beyond the individual to the provider and health care system levels. The current organization and implementation of health care services are inadequate. A coordinated system of local services capable of providing integrated, efficient health care and follow-up, populated by providers with knowledge of hereditary cancer, is necessary to maintain optimal health.

  5. Universal tumor screening for Lynch syndrome: Assessment of the perspectives of patients with colorectal cancer regarding benefits and barriers.

    Science.gov (United States)

    Hunter, Jessica Ezzell; Zepp, Jamilyn M; Gilmore, Mari J; Davis, James V; Esterberg, Elizabeth J; Muessig, Kristin R; Peterson, Susan K; Syngal, Sapna; Acheson, Louise S; Wiesner, Georgia L; Reiss, Jacob A; Goddard, Katrina A B

    2015-09-15

    Universal tumor screening for Lynch syndrome, the most common form of hereditary colorectal cancer (CRC), has been recommended among all patients newly diagnosed with CRC. However, there is limited literature regarding patient perspectives of tumor screening for Lynch syndrome among patients with CRC who are not selected for screening based on family history criteria. A total of 145 patients aged 39 to 87 years were administered surveys assessing perceived risk, patient perspectives, and potential benefits of and barriers to tumor screening for Lynch syndrome. Associations between patient-specific and cancer-specific factors and survey responses were analyzed. The majority of participants perceived their risk of developing Lynch syndrome as being low, with 9 participants (6.2%) anticipating an abnormal screening result. However, most participants endorsed the potential benefits of screening for themselves and their families, with 84.8% endorsing ≥6 benefits and 50.3% endorsing all 8 benefits. Participants also endorsed few potential barriers to screening, with 89.4% endorsing ≤4 of 9 potential barriers. A common barrier was worry about the cost of additional testing and surveillance, which was endorsed by 54.5% of participants. The level of distress associated with tumor screening for Lynch syndrome, which was very low, was not associated with age or CRC stage. The results of the current study indicate that patients with CRC overall have a positive attitude toward tumor screening for Lynch syndrome, endorse the benefits of screening, and experience low levels of distress. These findings provide insight into patient attitudes toward tumor screening for Lynch syndrome among unselected patients with CRC to inform educational approaches that assist in patient decision-making and guide the successful implementation of screening programs. © 2015 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

  6. Implementation of routine screening for Lynch syndrome in university and safety-net health system settings: successes and challenges.

    Science.gov (United States)

    Marquez, Evelyn; Geng, Zhuo; Pass, Sarah; Summerour, Pia; Robinson, Linda; Sarode, Venetia; Gupta, Samir

    2013-12-01

    Routine screening for evidence of DNA mismatch repair abnormalities can identify colorectal cancer patients with Lynch syndrome, but impact in usual care settings requires study. After implementing routine screening at our university and safety-net health systems as usual practice, our aims were to determine outcomes, including screening process quality. We conducted a retrospective cohort study from 1 May 2010 to 1 May 2011. Screening included reflexive immunohistochemistry to evaluate DNA mismatch repair protein expression for patients with colorectal cancer aged ≤70 years, with a cancer genetics team following up results. Screening outcomes, as well as challenges to a high-quality screening process were evaluated. We included 129 patients (mean age 56 years, 36% female); 100 had immunohistochemistry screening completed. Twelve patients had abnormal immunohistochemistry: four with definite Lynch syndrome, four with probable Lynch syndrome, and three without Lynch syndrome; one patient had an incomplete work-up. Lynch syndrome was confirmed for 6/13 asymptomatic relatives tested. Screening process quality was optimal for 77.5% of patients. Barriers to optimal quality screening included ensuring reflexive immunohistochemistry completion, complete follow-up of abnormal immunohistochemistry, and timely incorporation of results into clinical decision making. Usual care implementation of routine screening for Lynch syndrome can result in significant rates of detection, even in a largely safety-net setting. To optimize implementation, challenges to high-quality Lynch syndrome screening, such as ensuring reflexive screening completion and clinically indicated genetic testing and follow-up for abnormal screens, must be identified and addressed.

  7. Obituary: Roy Henry Garstang (1925-2009)

    Science.gov (United States)

    Malville, J.

    2011-12-01

    Roy Henry Garstang 84 passed away on November 1, 2009 in Boulder Colorado. He was born in Southport, England in September of 1925 to Percy Brocklehurst and Eunice (Gledhill) Garstang. He won a scholarship to Caius College in Cambridge University. Because it was wartime, he could spend only two years at his studies. However, he managed to complete three years of required work during that time, and then spent 1945-46 as a Junior Scientific Officer at the Royal Aircraft Establishment at Farnborough. He received his BA in 1946 from Cambridge, his MA in 1950, and his PhD in Mathematics in 1954, with a thesis: "Atomic Transitions in Astrophysics," working under D. R. Hartree. He also received a ScD from Cambridge in Physics and Chemistry in 1983. He married Ann in August 1959. She and two daughters, Jennifer and Susan, survive him. While still pursuing his PhD, Roy Garstang served as a Research Associate at the Yerkes Observatory, from 1951-1952, working under Subrahmanyan Chandrasekhar. During that time he continued with his own calculations of atomic structure and transition probabilities, although these were not part of Chandra's research interests. After earning his PhD, he went to teach at the University of London, where he also served as the Assistant Director of the University of London Observatory (1959-1964). He was editor of "The Observatory" Magazine form 1953-1960. The continuing theme of this research was to help meet the needs of astrophysicists for atomic data. In 1964, he left England for the United States, where he joined the faculty at the University of Colorado, Boulder, where he would remain for the rest of his professional career. It was entirely fitting, considering his interest in performing calculations of interest to astrophysicists, that soon after arriving in Boulder he was appointed Chairman of JILA - Joint Institute for Laboratory Astrophysics (1966-1967). He was Director of the Division of Physics and AstroGeophysics (1979-80), acting

  8. INOVATION AND ANTREPRENEURIAL CREATIVITY BUSINESS DURING HENRY FORD

    Directory of Open Access Journals (Sweden)

    GHICAJANU MIHAELA

    2015-03-01

    Full Text Available In this paper I presented the innovation and entrepeneurial creativity as a basis in the process of business redesign. I chose as a case study the the Ford brand products, because it is considered that Henry Ford is one of the greatest innovators and entrepreneurs of all time and I decided to present and to analyze these things. The first part of the paper will include theoretical approaches on the innovation and creativity business concepts and premises, and then I showed the ways in which four types of economic innovation under the leadership of Henry Ford (innovation in product, in process, market and organizational were achieved, with the purpose to recognize them in other companies, nowadays .

  9. Employees Perception Towards Implication Of Henry Fayols Principles

    OpenAIRE

    Kumari, Dr. Sunil; Arora, Madhu

    2013-01-01

    Human wants are unlimited and resources to fulfill them are limited. Art of getting unlimited results from limited resources is called Management. Henry Fayol is called the father of principles of Management who derived 14 milestones called principles to the area of Management. Present study aims to know whether Feyols principles are being adopted at Fairfield Institute of management Technology in their routine functioning. 36 employees perceptions were gathered through a questionnaire and fo...

  10. W. Henry Robinson: Popularising astronomy in Victorian Walsall and Birmingham

    Science.gov (United States)

    Williams, S.

    William Henry Robinson was one of the most prominent citizens of Walsall, then part of Staffordshire, in the Victorian and Edwardian periods. An influential businessman, he managed to combine printing, publishing, editing a newspaper, writing books and poetry, maintaining a library and retail trading with founding the town's literary institute, and bringing the scientists, explorers, authors and cultural pursuits of the day to his home town. An amateur astronomer in his own right, Robinson was instrumental in setting up the BAA's Midland Branch.

  11. Sarcophilia, cremation and Sir Henry Thompson (1820-1904).

    Science.gov (United States)

    Jellinek, E H

    2009-11-01

    Sarcophilia, a neologism for an attachment to human remains, is set in a review of the history of the disposal of the dead. The ancient practice of cremation was relaunched late in the 19th century by the urological surgeon cum social reformer Sir Henry Thompson. He was stimulated by Edwin Chadwick and Charles Dickens, and by Charles Darwin's observations on the earthworm. Sarcophilia is the reason for the controversial Human Tissue Act of 2004.

  12. Iraagi olukorral on poliitiline lahendus / Henry A. Kissinger

    Index Scriptorium Estoniae

    Kissinger, Henry, 1923-

    2007-01-01

    USA endine riigisekretär Henry Kissinger kirjutab, et Ameerika Ühendriikide eesmärgiks peaks olema riikidevaheline kokkulepe, mis tunnistaks Iraagi rahvusvahelist staatust. See oleks vägivalla lõpetamiseks hea alus ja eeltingimuseks vägede väljaviimisele. Vt. samas: Ameerika Ühendriikide vahekokkuvõte Iraagi sõja kohta oli suhteliselt pessimistlik

  13. Differential expression of CK20, β-catenin, and MUC2/5AC/6 in Lynch syndrome and familial colorectal cancer type X.

    Science.gov (United States)

    Haraldsson, Stefan; Klarskov, Louise; Nilbert, Mef; Bernstein, Inge; Bonde, Jesper; Holck, Susanne

    2017-01-01

    Hereditary non-polyposis colorectal cancer comprises Lynch syndrome and familial colorectal cancer type X (FCCTX). Differences in genetics, demographics and histopathology have been extensively studied. The purpose of this study is to characterize their immunoprofile of markers other than MMR proteins. We compared the expression patterns of cytokeratins (CK7 and CK20), mucins (MUC2/5 AC/6), CDX2 and β-catenin in Lynch syndrome and FCCTX. Differences were identified for CK20 and nuclear β-catenin, which were significantly more often expressed in FCCTX than in Lynch syndrome (p Lynch syndrome tumors compared with FCCTX tumors (p = 0.001, Lynch syndrome with a more sporadic-like profile in the former group and a more distinct profile with frequent MUC6 positivity in the latter group.

  14. BOOK REVIEW: Joseph Henry: The Rise of an American Scientist

    Science.gov (United States)

    Crawford, Elspeth

    1998-09-01

    Albert Moyer has clearly done his research into the events of Joseph Henry's life. The personal, professional, sociological and scientific aspects have been meticulously detailed throughout and the ordering, as in the chapter headings, is chronological, so that there is some element of each of these aspects in each chapter. This is unfortunately both the strength and the weakness of the biography, as the detail seemed to me to be the most remarkable characteristic of the writing. But, the bigger stories, or the themes, which might have been possible, seemed to get lost. Hence, I found this a book for those who are seriously interested in Joseph Henry; but for those whose interest might be more general, say having an interest in nineteenth century growth of scientific institutions, or wanting to understand the conceptual development of electromagnetism, there seemed to be too much which came from the Henry point of view, rather than locating Henry within his time and context. This is a remark about style, rather than omission of content, as the myriad of details in each paragraph certainly inform the reader about the context. For instance, some sociology of the USA in the nineteenth century could be inferred, say showing how a young man from a modest background might make his way into a professional life, but the information is so particularly a description of Henry's experience that one has to rely on prior knowledge or make assumptions in order to create a sociological perspective. That is, I now know, what happened to Henry, but I do not know if his case was in any sense typical or atypical. Similarly there is information about education in general at that time, and scientific education, research and its publication, as it applied to Henry. The relationships between science in the USA and in Europe have a place, and there is quite a bit of information about the institutions in which Henry worked, particularly Albany Academy, Princeton and the Smithsonian. Henry

  15. The forgotten first career of Doctor Henry Van Dyke Carter.

    Science.gov (United States)

    Hiatt, J R; Hiatt, N

    1995-11-01

    While Henry Gray's Anatomy: Descriptive and Surgical, first published in 1858, is distinguished by superb illustrations, its original illustrator is remembered for an entirely different set of accomplishments, notably significant contributions to tropical medicine. Literature review. Dr. Henry Van Dyke Carter, Professor of Anatomy and Physiology and subsequently Dean of the Grant Medical College in Bombay, India, was a skillful researcher and keen clinician who made significant contributions to tropical medicine, including the discovery of Spirillum minus, the spirochetal organism that causes relapsing fever. For his discoveries he was honored by both the British Medical Association and the English government. Before his departure for India in 1858, however, he and Henry Gray worked at St. George's Hospital Medical School and collaborated on the first edition of the text that is still the "Bible" of anatomy to many medical students. His drawings have appeared in every subsequent edition, up to the present day. During his first career as a medical illustrator, Carter was responsible for the drawings that have helped generations of physicians to master the intricacies of human anatomy.

  16. Prospective study of combined colon and endometrial cancer screening in women with lynch syndrome: a patient-centered approach.

    Science.gov (United States)

    Huang, Marilyn; Sun, Charlotte; Boyd-Rogers, Stephanie; Burzawa, Jennifer; Milbourne, Andrea; Keeler, Elizabeth; Yzquierdo, Rebecca; Lynch, Patrick; Peterson, Susan K; Lu, Karen

    2011-01-01

    Endometrial and colorectal cancers are the most common cancers in Lynch syndrome. Consensus guidelines recommend annual endometrial biopsy (EMB) and regular colonoscopies. We assessed the feasibility of concurrently performing EMB and colonoscopy and evaluated women's perception of pain, satisfaction, and acceptability. From July 2002 to December 2009, women who had a gene mutation for Lynch syndrome, met the Amsterdam II criteria, or had a high-risk situation that required screening were prospectively enrolled. After conscious sedation, the procedures were sequentially performed. Patients completed pre- and postprocedure questionnaires assessing pain, level of satisfaction, and acceptability. The Wilcoxon rank test and Mann-Whitney test were used to compare pain scores. Forty-two women completed the study. Median age was 37 years (range, 25 to 73). Nineteen had previously had an EMB in the office setting. Women reported significantly lower median levels of pain in the combined procedure compared with previous office setting biopsies (P Lynch syndrome screening recommendations.

  17. Which uterine sparing technique should be used for uterine atony during cesarean section? The Bakri balloon or the B-Lynch suture?

    Science.gov (United States)

    Kaya, Baris; Guralp, Onur; Tuten, Abdullah; Unal, Orhan; Celik, Melih Ozgur; Dogan, Askın

    2016-09-01

    To evaluate various aspects of two popular uterine sparing techniques, the B-Lynch uterine compression suture and Bakri balloon tamponade, in severe postpartum hemorrhage (PPH). 21 women who underwent the Bakri balloon procedure and 24 women who underwent the B-Lynch suture as primary uterus-sparing methods, due to PPH not responding to medical treatment, were retrospectively evaluated. The success rates of the B-Lynch procedure and the Bakri balloon were 79.1 and 80 %, respectively. The success rates of the B-Lynch + IIAL and the Bakri balloon + IIAL were 91.6 and 95 %, respectively. There was no significant difference in success rates, mean duration of time to stop bleeding, estimated blood loss, transfused packed red blood cells or mean duration of hospital stay between the B-Lynch and the Bakri balloon groups. The duration of operation was significantly longer in the Bakri balloon compared to the B-Lynch group (p = 0.01). In our study, the Bakri balloon and the B-Lynch suture had similar success rates in uterine atony during CS. The advantages of the B-Lynch suture include rapid application with no need for lithotomy position or extra material; whereas the Bakri balloon is less invasive and easier to learn, but more time consuming and expensive compared to the B-Lynch suture. We suggest that the B-Lynch suture may be preferred in uterine atony during CS in low resource settings; however, the less invasive Bakri balloon should be the first line in full resource settings. Further studies are needed to evaluate the advantages and disadvantages of the two methods.

  18. Cancer spectrum in DNA mismatch repair gene mutation carriers: results from a hospital based Lynch syndrome registry.

    Science.gov (United States)

    Pande, Mala; Wei, Chongjuan; Chen, Jinyun; Amos, Christopher I; Lynch, Patrick M; Lu, Karen H; Lucio, Laura A; Boyd-Rogers, Stephanie G; Bannon, Sarah A; Mork, Maureen E; Frazier, Marsha L

    2012-09-01

    The spectrum of cancers seen in a hospital based Lynch syndrome registry of mismatch repair gene mutation carriers was examined to determine the distribution of cancers and examine excess cancer risk. Overall there were 504 cancers recorded in 368 mutation carriers from 176 families. These included 236 (46.8 %) colorectal and 268 (53.2 %) extracolonic cancers. MLH1 mutation carriers had a higher frequency of colorectal cancers whereas MSH2, MSH6 and PMS2 mutation carriers had more extracolonic cancers although these differences were not statistically significant. Men had fewer extracolonic cancers than colorectal (45.3 vs. 54.7 %), whereas women had more extracolonic than colorectal cancers (59.0 vs. 41.0 %). The mean age at diagnosis overall for extracolonic cancers was older than for colorectal, 49.1 versus 44.8 years (P ≤ 0.001). As expected, the index cancer was colorectal in 58.1 % of patients and among the extracolonic index cancers, endometrial was the most common (13.8 %). A significant number of non-Lynch syndrome index cancers were recorded including breast (n = 5) prostate (n = 3), thyroid (n = 3), cervix (n = 3), melanoma (n = 3), and 1 case each of thymoma, sinus cavity, and adenocarcinoma of the lung. However, standardized incidence ratios calculated to assess excess cancer risk showed that only those cancers known to be associated with Lynch syndrome were significant in our sample. We found that Lynch syndrome patients can often present with cancers that are not considered part of Lynch syndrome. This has clinical relevance both for diagnosis of Lynch syndrome and surveillance for cancers of different sites during follow-up of these patients.

  19. Achieving behaviour change for detection of Lynch syndrome using the Theoretical Domains Framework Implementation (TDFI) approach: a study protocol.

    Science.gov (United States)

    Taylor, Natalie; Long, Janet C; Debono, Deborah; Williams, Rachel; Salisbury, Elizabeth; O'Neill, Sharron; Eykman, Elizabeth; Braithwaite, Jeffrey; Chin, Melvin

    2016-03-12

    Lynch syndrome is an inherited disorder associated with a range of cancers, and found in 2-5 % of colorectal cancers. Lynch syndrome is diagnosed through a combination of significant family and clinical history and pathology. The definitive diagnostic germline test requires formal patient consent after genetic counselling. If diagnosed early, carriers of Lynch syndrome can undergo increased surveillance for cancers, which in turn can prevent late stage cancers, optimise treatment and decrease mortality for themselves and their relatives. However, over the past decade, international studies have reported that only a small proportion of individuals with suspected Lynch syndrome were referred for genetic consultation and possible genetic testing. The aim of this project is to use behaviour change theory and implementation science approaches to increase the number and speed of healthcare professional referrals of colorectal cancer patients with a high-likelihood risk of Lynch syndrome to appropriate genetic counselling services. The six-step Theoretical Domains Framework Implementation (TDFI) approach will be used at two large, metropolitan hospitals treating colorectal cancer patients. Steps are: 1) form local multidisciplinary teams to map current referral processes; 2) identify target behaviours that may lead to increased referrals using discussion supported by a retrospective audit; 3) identify barriers to those behaviours using the validated Influences on Patient Safety Behaviours Questionnaire and TDFI guided focus groups; 4) co-design interventions to address barriers using focus groups; 5) co-implement interventions; and 6) evaluate intervention impact. Chi square analysis will be used to test the difference in the proportion of high-likelihood risk Lynch syndrome patients being referred for genetic testing before and after intervention implementation. A paired t-test will be used to assess the mean time from the pathology test results to referral for high

  20. Clinical problems of colorectal cancer and endometrial cancer cases with unknown cause of tumor mismatch repair deficiency (suspected Lynch syndrome

    Directory of Open Access Journals (Sweden)

    Buchanan DD

    2014-10-01

    Full Text Available Daniel D Buchanan,1,2 Christophe Rosty,1,3,4 Mark Clendenning,1 Amanda B Spurdle,5 Aung Ko Win2 1Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, VIC, Australia; 2Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, Australia; 3Envoi Specialist Pathologists, Herston, QLD, Australia; 4School of Medicine, University of Queensland, Herston, QLD, Australia; 5Molecular Cancer Epidemiology Laboratory, Genetics and Computational Biology Division, QIMR Berghofer Medical Research Institute, Herston, QLD, AustraliaAbstract: Carriers of a germline mutation in one of the DNA mismatch repair (MMR genes have a high risk of developing numerous different cancers, predominantly colorectal cancer and endometrial cancer (known as Lynch syndrome. MMR gene mutation carriers develop tumors with MMR deficiency identified by tumor microsatellite instability or immunohistochemical loss of MMR protein expression. Tumor MMR deficiency is used to identify individuals most likely to carry an MMR gene mutation. However, MMR deficiency can also result from somatic inactivation, most commonly methylation of the MLH1 gene promoter. As tumor MMR testing of all incident colorectal and endometrial cancers (universal screening is becoming increasingly adopted, a growing clinical problem is emerging for individuals who have tumors that show MMR deficiency who are subsequently found not to carry an MMR gene mutation after genetic testing using the current diagnostic approaches (Sanger sequencing and multiplex ligation-dependent probe amplification and who also show no evidence of MLH1 methylation. The inability to determine the underlying cause of tumor MMR deficiency in these "Lynch-like" or "suspected Lynch syndrome" cases has significant implications on the clinical management of these individuals and their relatives. When the

  1. Limited impact on self-concept in individuals with Lynch syndrome; results from a national cohort study

    DEFF Research Database (Denmark)

    Petersen, Helle Vendel; Esplen, Mary Jane; Ladelund, Steen

    2011-01-01

    . We used the national Danish HNPCC register to collect data on self-concept from 413 individuals with Lynch syndrome. The recently developed Lynch syndrome self-concept scale contains 20 items within two subscales related to stigma-vulnerability and bowel symptom-related anxiety. Significantly higher...... total scores, indicating a greater impact on self-concept, were reported by females and by individuals with experience from cancer in close relatives, whereas individuals with less formal education scored significantly higher on the stigma and vulnerability subscale. Scores in the upper quartile were...

  2. Family history of cancer predicts endometrial cancer risk independently of Lynch Syndrome: Implications for genetic counselling.

    Science.gov (United States)

    Johnatty, Sharon E; Tan, Yen Y; Buchanan, Daniel D; Bowman, Michael; Walters, Rhiannon J; Obermair, Andreas; Quinn, Michael A; Blomfield, Penelope B; Brand, Alison; Leung, Yee; Oehler, Martin K; Kirk, Judy A; O'Mara, Tracy A; Webb, Penelope M; Spurdle, Amanda B

    2017-11-01

    To determine endometrial cancer (EC) risk according to family cancer history, including assessment by degree of relatedness, type of and age at cancer diagnosis of relatives. Self-reported family cancer history was available for 1353 EC patients and 628 controls. Logistic regression was used to quantify the association between EC and cancer diagnosis in ≥1 first or second degree relative, and to assess whether level of risk differed by degree of relationship and/or relative's age at diagnosis. Risk was also evaluated for family history of up to three cancers from known familial syndromes (Lynch, Cowden, hereditary breast and ovarian cancer) overall, by histological subtype and, for a subset of 678 patients, by EC tumor mismatch repair (MMR) gene expression. Report of EC in ≥1 first- or second-degree relative was associated with significantly increased risk of EC (P=3.8×10-7), independent of lifestyle risk factors. There was a trend in increasing EC risk with closer relatedness and younger age at EC diagnosis in relatives (PTrend=4.43×10-6), and with increasing numbers of Lynch cancers in relatives (PTrend≤0.0001). EC risk associated with family history did not differ by proband tumor MMR status, or histological subtype. Reported EC in first- or second-degree relatives remained associated with EC risk after conservative correction for potential misreported family history (OR 2.0; 95% CI, 1.24-3.37, P=0.004). The strongest predictor of EC risk was closer relatedness and younger EC diagnosis age in ≥1 relative. Associations remained significant irrespective of proband MMR status, and after excluding MMR pathogenic variant carriers, indicating that Lynch syndrome genes do not fully explain familial EC risk. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Universal molecular screening does not effectively detect Lynch syndrome in clinical practice.

    Science.gov (United States)

    Brennan, Beatrice; Hemmings, Christine T; Clark, Ian; Yip, Desmond; Fadia, Mitali; Taupin, Douglas R

    2017-04-01

    Lynch syndrome (LS) due to an inherited damaging mutation in mismatch repair (MMR) genes comprises 3% of all incident colorectal cancer (CRC). Molecular testing using immunohistochemistry (IHC) for MMR proteins is a recommended screening tool to identify LS in incident CRC. This study assessed outcomes of population-based routine molecular screening for diagnosis of LS in a regional center. We conducted a prospective, consecutive case series study of universal IHC testing on cases of resected CRC from September 2004-December 2013. Referred cases with abnormal IHC results that attended a familial cancer clinic were assessed according to modified Bethesda criteria (until 2009) or molecular criteria (from 2009). 1612 individuals underwent resection for CRC in the study period and had MMR testing by IHC. Of these, 274 cases (16.9%) exhibited loss of expression of MMR genes. The mean age at CRC diagnosis was 68.1 years (± standard deviation 12.7) and the mean age of those with an IHC abnormality was 71.6 (± 11.8). A total of 82 (29.9%) patients with an abnormal result were seen in a subspecialty familial cancer clinic. Patients aged under 50 (p = 0.009) and those with loss of MSH6 staining (p = 0.027) were more likely to be referred and to attend. After germ-line sequencing, 0.6% (10 of 82) were identified as having a clinically significant abnormality. A further eight probands with pathogenic germ-line mutations were identified from other referrals to the service over the same time period. While technically accurate, the yield of 'universal' IHC in detecting new Lynch probands is limited by real-world factors that reduce referrals and genetic testing. We propose an alternative approach for universal, incident case detection of Lynch syndrome with 'one-stop' MMR testing and sequencing.

  4. Subtotal Colectomy for Colon Cancer Reduces the Need for Subsequent Surgery in Lynch Syndrome.

    Science.gov (United States)

    Renkonen-Sinisalo, Laura; Seppälä, Toni T; Järvinen, Heikki J; Mecklin, Jukka-Pekka

    2017-08-01

    The risk of metachronous colorectal cancer is high after surgical resection for first colon cancer in Lynch syndrome. This study aimed to examine whether extended surgery decreases the risk of subsequent colorectal cancer and improves long-term survival. This was a retrospective study. Data were collected from a nationwide registry. Two hundred forty-two Lynch syndrome pathogenic variant carriers who underwent surgery for a first colon cancer from 1984 to 2009 were included. Patients underwent standard segmental colectomy (n = 144) or extended colectomy (n = 98) for colon cancer. Patients were followed a median of 14.6 up to 25 years. Risk of subsequent colorectal cancer in either group, overall and disease-specific survival, and operative mortality were the primary outcomes measured. Subtotal colectomy decreased the risk of subsequent colorectal cancer (HR, 0.20; 95% CI, 0.08-0.52; p = 0.001), compared with segmental resection. Subsequent colorectal cancer decreased in MLH1 carriers. The MSH2 carriers showed no statistical difference, possibly because of their small number. Disease-specific and overall survival within 25 years did not differ between the standard and extended surgeries (82.7% vs 87.2%, p = 0.76 and 47.2% vs 41.4%, p = 0.83). The cumulative risk of subsequent colorectal cancer was 20% in 10 years and 47% within 25 years after standard resection and 4% and 9% after extended surgery. The cumulative risk of metachronous colorectal cancer was 7% within 25 years after subtotal colectomy with ileosigmoidal anastomosis. One patient died of postoperative septicemia within 30 days after segmental colectomy. Data on surgical procedures were primarily collected retrospectively. Lynch syndrome pathogenic variant carriers may undergo subtotal colectomy to manage first colon cancer and avoid repetitive abdominal surgery and to reduce the remaining bowel to facilitate easier endoscopic surveillance. It provides no survival benefit, compared with segmental colon

  5. Risks of less common cancers in proven mutation carriers with lynch syndrome.

    Science.gov (United States)

    Engel, Christoph; Loeffler, Markus; Steinke, Verena; Rahner, Nils; Holinski-Feder, Elke; Dietmaier, Wolfgang; Schackert, Hans K; Goergens, Heike; von Knebel Doeberitz, Magnus; Goecke, Timm O; Schmiegel, Wolff; Buettner, Reinhard; Moeslein, Gabriela; Letteboer, Tom G W; Gómez García, Encarna; Hes, Frederik J; Hoogerbrugge, Nicoline; Menko, Fred H; van Os, Theo A M; Sijmons, Rolf H; Wagner, Anja; Kluijt, Irma; Propping, Peter; Vasen, Hans F A

    2012-12-10

    Patients with Lynch syndrome are at high risk for colon and endometrial cancer, but also at an elevated risk for other less common cancers. The purpose of this retrospective cohort study was to provide risk estimates for these less common cancers in proven carriers of pathogenic mutations in the mismatch repair (MMR) genes MLH1, MSH2, and MSH6. Data were pooled from the German and Dutch national Lynch syndrome registries. Seven different cancer types were analyzed: stomach, small bowel, urinary bladder, other urothelial, breast, ovarian, and prostate cancer. Age-, sex- and MMR gene-specific cumulative risks (CRs) were calculated using the Kaplan-Meier method. Sex-specific incidence rates were compared with general population incidence rates by calculating standardized incidence ratios (SIRs). Multivariate Cox regression analysis was used to estimate the impact of sex and mutated gene on cancer risk. The cohort comprised 2,118 MMR gene mutation carriers (MLH1, n = 806; MSH2, n = 1,004; MSH6, n = 308). All cancers were significantly more frequent than in the general population. The highest risks were found for male small bowel cancer (SIR, 251; 95% CI, 177 to 346; CR at 70 years, 12.0; 95% CI, 5.7 to 18.2). Breast cancer showed an SIR of 1.9 (95% CI, 1.4 to 2.4) and a CR of 14.4 (95% CI, 9.5 to 19.3). MSH2 mutation carriers had a considerably higher risk of developing urothelial cancer than MLH1 or MSH6 carriers. The sex- and gene-specific differences of less common cancer risks should be taken into account in cancer surveillance and prevention programs for patients with Lynch syndrome.

  6. The risk of extra-colonic, extra-endometrial cancer in the Lynch syndrome

    DEFF Research Database (Denmark)

    Watson, Patrice; Vasen, Hans F A; Mecklin, Jukka-Pekka

    2008-01-01

    Persons with the Lynch syndrome (LS) are at high risk for cancer, including cancers of the small bowel, stomach, upper urologic tract (renal pelvis and ureter), ovary, biliary tract and brain tumors, in addition to the more commonly observed colorectal and endometrial cancers. Cancer prevention...... strategies for these less common cancers require accurate, age-specific risk estimation. We pooled data from 4 LS research centers in a retrospective cohort study, to produce absolute incidence estimates for these cancer types, and to evaluate several potential risk modifiers. After elimination of 135...

  7. Spectrum of MLH1 and MSH2 mutations in Chilean families with suspected Lynch syndrome.

    Science.gov (United States)

    Alvarez, Karin; Hurtado, Claudia; Hevia, Montserrat A; Wielandt, Ana Maria; de la Fuente, Marjorie; Church, James; Carvallo, Pilar; López-Köstner, Francisco

    2010-04-01

    Lynch syndrome is the most common inherited syndrome of colorectal cancer, caused principally by germline mutations in MLH1 and MSH2. We report our experience with genetic screening in the diagnosis of Lynch syndrome in Chile, a country previously underserved in the capacity to diagnose hereditary colorectal cancer. Families from our Familial Colorectal Cancer Registry were selected for this study if they fulfilled either Amsterdam I/II or Bethesda criteria for classification of Lynch syndrome. Analysis of colorectal tumors from probands included a microsatellite instability study and immunohistochemical evaluation for MLH1 and MSH2. Screening of germline mutations was performed by single-strand conformation polymorphism analysis and DNA sequencing. A total of 21 families were evaluated, 14 meeting Amsterdam criteria and 7 meeting Bethesda criteria. Tumors in 20 families (95%) showed microsatellite instability (19 high and 1 low) and 9 of these 20 families (45%) harbored a germline mutation (7 of 13 Amsterdam and 2 of 7 Bethesda families). Of the 9 mutations identified, 6 were in MLH1 and 3 in MSH2. Two of the mutations were novel, 3 were previously found in 1 to 2 European populations, and 4 were previously found in various ethnic populations worldwide. Only 2 mutations were previously found in another Latin American population (Colombia). In our probands, colorectal cancer was located mainly (57%) in the right or transverse colon. Pedigree information from 104 family affected members of 21 studied families showed endometrial cancer to be the most frequent primary extracolonic tumor, accounting for 15.1% of total cases, followed by stomach (13.2%) and breast cancer (11.3%). Analysis of mitochondrial DNA haplotypes showed a strong Amerindian genetic component in 15 (71.4%) of the 21 families analyzed. The study of Lynch syndrome in families of different ethnic origins contributes to the definition of genetic and clinical differences among populations. Wide

  8. Early colonization with a group of Lactobacilli decreases the risk for allergy at five years of age despite allergic heredity.

    Directory of Open Access Journals (Sweden)

    Maria A Johansson

    Full Text Available BACKGROUND: Microbial deprivation early in life can potentially influence immune mediated disease development such as allergy. The aims of this study were to investigate the influence of parental allergy on the infant gut colonization and associations between infant gut microbiota and allergic disease at five years of age. METHODS AND FINDINGS: Fecal samples were collected from 58 infants, with allergic or non-allergic parents respectively, at one and two weeks as well as at one, two and twelve months of life. DNA was extracted from the fecal samples and Real time PCR, using species-specific primers, was used for detection of Bifidobacterium (B. adolescentis, B. breve, B. bifidum, Clostridium (C. difficile, a group of Lactobacilli (Lactobacillus (L. casei, L. paracasei and L. rhamnosus as well as Staphylococcus (S. aureus. Infants with non-allergic parents were more frequently colonized by Lactobacilli compared to infants with allergic parents (p = 0.014. However, non-allergic five-year olds acquired Lactobacilli more frequently during their first weeks of life, than their allergic counterparts, irrespectively of parental allergy (p = 0.009, p = 0.028. Further the non-allergic children were colonized with Lactobacilli on more occasions during the first two months of life (p = 0.038. Also, significantly more non-allergic children were colonized with B. bifidum at one week of age than the children allergic at five years (p = 0.048. CONCLUSION: In this study we show that heredity for allergy has an impact on the gut microbiota in infants but also that early Lactobacilli (L. casei, L. paracasei, L. rhamnosus colonization seems to decrease the risk for allergy at five years of age despite allergic heredity.

  9. Compilation of Henry's law constants (version 4.0) for water as solvent

    Science.gov (United States)

    Sander, R.

    2015-04-01

    Many atmospheric chemicals occur in the gas phase as well as in liquid cloud droplets and aerosol particles. Therefore, it is necessary to understand the distribution between the phases. According to Henry's law, the equilibrium ratio between the abundances in the gas phase and in the aqueous phase is constant for a dilute solution. Henry's law constants of trace gases of potential importance in environmental chemistry have been collected and converted into a uniform format. The compilation contains 17 350 values of Henry's law constants for 4632 species, collected from 689 references. It is also available at law.org"target="_blank">http://www.henrys-law.org.

  10. [From apprenticeship to Nobel Prize: Henri Moissan's fabulous destiny].

    Science.gov (United States)

    Lafont, O

    2008-01-01

    Born in Paris on September 28, 1852, son of an eastern railways' employee and of a dressmaker, Henri Moissan's secondary schooling in Meaux did not allow him to get access to the sesame diploma "baccalauréat" (GCE). In 1869, he did obtain a special certificate of secondary schooling so that he could become an apprentice in watch making. That could have been the end of the story, but dreadful event for France appeared to have beneficial effects for Moissan. Under the threat of the Prussian army, Moissan's family took refuge near Paris. This gave the young Henri the opportunity to register as a student for the second-class pharmacy diploma, which did not need, at the time, the GCE. Moissan became then a trainee in pharmacy in 1871. Meanwhile, he followed the special schooling of "Ecole de chimie" founded by E. Frémy, and then joined the laboratory of Dehérain at the Museum, where he worked in plant physiology. He finally obtained the famous "baccalauréat" (GCE) and could register as a student in first-class pharmacy. He became a pharmacist as well as a doctor in sciences. In 1883, Moissan was named professor at the school of pharmacy in Paris. In 1886, he isolated fluorine by electrolysis of fluorhydric acid, in the presence of potassium fluoride, at a low temperature. He then studied diamond synthesis and gave a start to high temperature chemistry, designing his famous furnace. These findings and many others allowed Moissan to rise to membership in many learned academies around the world. Crowning achievement, Moissan won the Nobel Prize in 1906. A man of culture, collector of autographs and paintings, he died in 1907. Nothing of that would have been possible if there had not been a second-class pharmacist diploma. The history of Henri Moissan is one of a rise from apprenticeship to the Nobel Prize.

  11. An 57Fe Mössbauer study of the ordinary chondrite meteorite Lynch 001

    Science.gov (United States)

    Elewa, Nancy N.; Cadogan, J. M.

    2017-11-01

    The Lynch 001 meteorite was found in the Nullarbor Plain region of Western Australia in 1977. This meteorite is classified as an ordinary chondrite of the petrologic group L5/6 that has undergone `minor to moderate' terrestrial weathering. Here, we characterize the Fe-bearing phases in this chondrite using 57Fe Mössbauer spectroscopy carried out over the temperature range 13 K to room temperature (295 K). The paramagnetic doublets of olivine, pyroxene and a superparamagnetic ferric phase dominate the room temperature Mössbauer spectrum. On the basis of the room temperature quadrupole splitting of the olivine component, we estimate its composition to be Fa 30(5). Besides the paramagnetic ferric component, accounting for ˜15 % of the spectral area at room temperature, magnetically ordered ferric phases were also detected. The total relative proportion of the Fe 3+ components allows us to estimate the terrestrial age of Lynch 001 to be 6,500 ± 1,500 yr, consistent with the value of 6,700 ± 1,300 yr determined by 14C dating.

  12. Screening adherence and cancer risk perceptions in colorectal cancer survivors with Lynch-like syndrome.

    Science.gov (United States)

    Katz, L H; Burton-Chase, A M; Advani, S; Fellman, B; Polivka, K M; Yuan, Y; Lynch, P M; Peterson, S K

    2016-03-01

    Cancer screening recommendations for patients with Lynch-like syndrome (LLS) are not well defined. We evaluated adherence to Lynch syndrome (LS) screening recommendations, cancer risk perceptions, and communication within the families among colorectal cancer (CRC) survivors with LLS. Thirty-four participants with LLS completed a questionnaire about risk perception, adherence to LS screening recommendations, and communication with relatives. Clinical data were obtained from medical records. Most participants (76%) believed they should undergo colonoscopy every 1-2 years. Only 41% correctly interpreted their genetic tests as uninformative negative or as variant of unknown significance for LS. Less than half had had an upper gastrointestinal endoscopy for screening purpose. Among female participants, 86% had been screened for endometrial cancer (EC) and 71% for ovarian cancer. Most participants had informed relatives about the CRC diagnosis and advised them to undergo CRC screening, but only 50% advised female relatives to be screened for EC and only one-third advised relatives to have genetic counseling. Most CRC survivors with LLS follow the same cancer screening recommended for LS patients but do not understand the meaning of LLS. Greater care must be devoted to communicating the implications of nondiagnostic germline mutation testing among patients with LLS. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Comparison of extended colectomy and limited resection in patients with Lynch syndrome.

    Science.gov (United States)

    Natarajan, Nagendra; Watson, Patrice; Silva-Lopez, Edibaldo; Lynch, Henry T

    2010-01-01

    The purpose of the study was to determine the advantages and disadvantages of prophylactic/extended colectomy (subtotal colectomy) in patients with Lynch syndrome who manifest colorectal cancer. A retrospective cohort using Creighton University's hereditary cancer database was used to identify cases and controls. Cases are patients who underwent subtotal colectomy, either with no colorectal cancer diagnosis (prophylactic) or at diagnosis of first colorectal cancer; controls for these 2 types of cases were, respectively, patients who underwent no colon surgery or those having limited resection at time of diagnosis of first colorectal cancer. The Kaplan-Meier and proportional hazard regression models from the Statistical Analysis Software program was used to calculate the difference in survival, time to subsequent colorectal cancer, and subsequent abdominal surgery between cases and controls. The event-free survival of our study did not reach 50%, so we used the event-free survival at 5 years as our parameter to compare the 2 groups. The event-free survival for subsequent colorectal cancer, subsequent abdominal surgery, and death was 94%, 84%, and 93%, respectively, for cases and 74%, 63%, and 88%, respectively, for controls. Times to subsequent colorectal cancer and subsequent abdominal surgery were significantly shorter in the control group (P Lynch syndrome.

  14. Locating inputs of freshwater to Lynch Cove, Hood Canal, Washington, using aerial infrared photography

    Science.gov (United States)

    Sheibley, Rich W.; Josberger, Edward G.; Chickadel, Chris

    2010-01-01

    The input of freshwater and associated nutrients into Lynch Cove and lower Hood Canal (fig. 1) from sources such as groundwater seeps, small streams, and ephemeral creeks may play a major role in the nutrient loading and hydrodynamics of this low dissolved-oxygen (hypoxic) system. These disbursed sources exhibit a high degree of spatial variability. However, few in-situ measurements of groundwater seepage rates and nutrient concentrations are available and thus may not represent adequately the large spatial variability of groundwater discharge in the area. As a result, our understanding of these processes and their effect on hypoxic conditions in Hood Canal is limited. To determine the spatial variability and relative intensity of these sources, the U.S. Geological Survey Washington Water Science Center collaborated with the University of Washington Applied Physics Laboratory to obtain thermal infrared (TIR) images of the nearshore and intertidal regions of Lynch Cove at or near low tide. In the summer, cool freshwater discharges from seeps and streams, flows across the exposed, sun-warmed beach, and out on the warm surface of the marine water. These temperature differences are readily apparent in aerial thermal infrared imagery that we acquired during the summers of 2008 and 2009. When combined with co-incident video camera images, these temperature differences allow identification of the location, the type, and the relative intensity of the sources.

  15. The Use of Social Media to Recruit Participants With Rare Conditions: Lynch Syndrome as an Example.

    Science.gov (United States)

    Burton-Chase, Allison M; Parker, Wendy M; Hennig, Kelsey; Sisson, Faith; Bruzzone, Linda L

    2017-01-23

    Social media is increasingly being used as a means of recruiting participants, particularly for investigators whose areas of interest involve rare conditions or hard-to-reach populations. However, much of the literature to date has focused on paid advertisement recruitment. We used Lynch syndrome (LS), a rare hereditary cancer syndrome, as a model to demonstrate the successful partnership between researchers and a Web-based patient education and advocacy organization to facilitate participant recruitment. Recruitment was undertaken in partnership with Lynch Syndrome International (LSI), an advocacy organization with a strong social media presence. After LSI published our study information, participants followed up via email or phone call. Following prescreening and consent, interested and eligible participants were then sent a secure survey link. Within 36 hours of a single Facebook post by the site administrators for LSI, over 150 individuals responded via phone or email. Sixty-five individuals were sent the survey link and 57 individuals completed the survey (88% response rate). Of note, these 57 individuals were geographically diverse within the Unites States, representing LS patients from 26 different states. This approach has several advantages, including recruitment through a trusted source outside of a clinical setting, higher response rates, and cost-effectiveness with a small research team in a relatively short amount of time. Overall, social media recruitment with a trusted online partner can be highly effective in hard-to-reach clinical populations, such as patients with LS. However, this approach requires additional effort for eligibility screening.

  16. Predicting the impact of Lynch syndrome-causing missense mutations from structural calculations.

    Directory of Open Access Journals (Sweden)

    Sofie V Nielsen

    2017-04-01

    Full Text Available Accurate methods to assess the pathogenicity of mutations are needed to fully leverage the possibilities of genome sequencing in diagnosis. Current data-driven and bioinformatics approaches are, however, limited by the large number of new variations found in each newly sequenced genome, and often do not provide direct mechanistic insight. Here we demonstrate, for the first time, that saturation mutagenesis, biophysical modeling and co-variation analysis, performed in silico, can predict the abundance, metabolic stability, and function of proteins inside living cells. As a model system, we selected the human mismatch repair protein, MSH2, where missense variants are known to cause the hereditary cancer predisposition disease, known as Lynch syndrome. We show that the majority of disease-causing MSH2 mutations give rise to folding defects and proteasome-dependent degradation rather than inherent loss of function, and accordingly our in silico modeling data accurately identifies disease-causing mutations and outperforms the traditionally used genetic disease predictors. Thus, in conclusion, in silico biophysical modeling should be considered for making genotype-phenotype predictions and for diagnosis of Lynch syndrome, and perhaps other hereditary diseases.

  17. Genealogical tree study as screening method in the Lynch syndrome prior to genetic test.

    Science.gov (United States)

    Delgado-Plasencia, Luciano; Medina-Arana, Vicente; Barrios Del Pino, Ysamar; Fernández-Peralta, Antonia; González-Aguilera, Juan J

    2010-08-01

    Despite genetic advances in the study of Lynch syndrome (LS), difficulties remain in the diagnosis of the syndrome. The aim of this study was to assess the usefulness of a detailed genealogical tree as a screening method to identify Tenerife island families with a high probability of LS. We elaborated complete genealogical trees of the families. According to the degree of fulfillment of the Amsterdam Criteria II, the genealogical trees were classified as high or low probability of LS. Additionally, we analyzed the level of tumor microsatellite instability (MSI+) and identified a mutation in exon 13 of the MSH2 gene by single-strand conformation polymorphism, sequencing, and PCR-RFLP. According the genealogical trees, we found 10 families with high probability of LS and 30 families with low probability of LS. The families with high probability of LS showed high MSI+ in all cases. Conversely, families with low probability were MSS (microsatellite stable). In 5 of the 10 families with high probability, we discovered a T-->G mutation in position 688 of exon 13 of MSH2, which appeared in all the family members with the tumor, except 1 patient with a retinoblastoma. Our results indicate that genealogical tree is a highly effective tool for classifying families with a high probability of Lynch Syndrome prior to genetic test.

  18. [Management and Nursing care for a patient with Lynch syndrome: A case report].

    Science.gov (United States)

    Pacheco-Pérez, Luis Arturo; Guevara Valtier, Milton Carlos

    2016-01-01

    Colorectal cancer is one of the leading causes of death from cancer worldwide. Main interventions to reduce the impact are aimed to enhance prevention and early detection. Results of several studies show that tests such as the fecal occult blood test and colonoscopy are effective for early diagnosis. There are hereditary syndromes such as Lynch Syndrome that can lead to certain types of cancers, including bowel neoplasms, therefore early detection needs to be included as part of the treatment. In these cases, family genetic testing is recommended if the bowel cancer is diagnosed before 50 years old. A care plan including the NANDA (North American Nursing Diagnosis Association), NOC (Nursing Outcomes Classification) and NIC (Nursing Interventions Classification) was developed for a patient with suspected Lynch Syndrome. Nurses should be qualified to identify potential cases of cancer associated with this syndrome, and thus, reduce the likelihood that family members develop the disease, through genetic counseling and education of environmental risk factors. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  19. Coexisting somatic promoter hypermethylation and pathogenic MLH1 germline mutation in Lynch syndrome.

    Science.gov (United States)

    Rahner, N; Friedrichs, N; Steinke, V; Aretz, S; Friedl, W; Buettner, R; Mangold, E; Propping, P; Walldorf, C

    2008-01-01

    Somatic epimutations in the MLH1 promoter mimic the phenotype of Lynch syndrome. To date, no somatic hypermethylation of the MLH1 promoter in the carrier of a pathogenic MLH1 germline mutation has been identified, prompting the recommendation that a germline mutation in MLH1 should only be sought in the absence of tumour tissue methylation. We aimed to determine whether methylation of the MLH1 promoter may coexist in carriers of a pathogenic germline mutation in MLH1. We examined the methylation status of the MLH1 promoter in 123 tumour tissue samples, demonstrating high microsatellite instability and loss of expression of a mismatch repair protein (60 cases with MLH1 germline mutation, 25 cases without mutation, 38 cases with MSH2 mutations), using combined bisulphite restriction analysis (COBRA) and SNaPshot analysis. Methylation of the MLH1 promoter was found in two patients with pathogenic germline mutations, one a carrier of a MLH1 mutation and the other a carrier of a MSH2 mutation. Our results demonstrate that methylation of the MLH1 promoter region does not exclude the presence of a germline mutation in a mismatch repair (MMR) gene. Hypermethylation of the MLH1 promoter may be present in most cases of sporadic colorectal cancers, but this does not exclude a diagnosis of Lynch syndrome.

  20. An {sup 57}Fe Mössbauer study of the ordinary chondrite meteorite Lynch 001

    Energy Technology Data Exchange (ETDEWEB)

    Elewa, Nancy N., E-mail: nancy.elewa@student.unsw.edu.au; Cadogan, J. M. [The University of New South Wales at the Australian Defence Force Academy, School of Physical, Environmental and Mathematical Sciences (Australia)

    2017-11-15

    The Lynch 001 meteorite was found in the Nullarbor Plain region of Western Australia in 1977. This meteorite is classified as an ordinary chondrite of the petrologic group L5/6 that has undergone ‘minor to moderate’ terrestrial weathering. Here, we characterize the Fe-bearing phases in this chondrite using {sup 57}Fe Mössbauer spectroscopy carried out over the temperature range 13 K to room temperature (295 K). The paramagnetic doublets of olivine, pyroxene and a superparamagnetic ferric phase dominate the room temperature Mössbauer spectrum. On the basis of the room temperature quadrupole splitting of the olivine component, we estimate its composition to be Fa {sub 30(5)}. Besides the paramagnetic ferric component, accounting for ∼15 % of the spectral area at room temperature, magnetically ordered ferric phases were also detected. The total relative proportion of the Fe {sup 3+} components allows us to estimate the terrestrial age of Lynch 001 to be 6,500 ± 1,500 yr, consistent with the value of 6,700 ± 1,300 yr determined by {sup 14}C dating.

  1. Teoria das representações em Henri Lefebvre

    Directory of Open Access Journals (Sweden)

    Angelo Serpa

    2014-12-01

    Full Text Available This article looks for to clear one theory of representations in Henri Lefebvre’s work, taking his seminal book on the thematic: The presence and the absence as support. It is aimed to clear one theory and one concept of representation that can support one cultural and multidimensional boarding for Geography, with the articulation of the fields of dialectic and phenome- nology. The articulation between phenomenology and dialectic is justified in this context as a method necessity for understanding the processes of pro- duction of the space in the contemporary times, as basis for a Geography of the Lived Spaces. 

  2. O pensamento crítico de Henri Lefebvre

    Directory of Open Access Journals (Sweden)

    William Gómez Soto

    2012-12-01

    Full Text Available Este trabalho é uma análise da presença de Henri Lefebvre na sociologia brasileira. Lefebvre faz uma leitura crítica de Marx, recuperando o método dialético e propondo uma teoria da vida cotidiana. José de Souza Martins influenciado por Lefebvre e utilizando o método dialético, analisa o processo histórico da constituição do capitalismo brasileiro. Apesar de que há certa presença de Lefebvre na sociologia brasileira, ainda a riqueza de sua obra está para ser descoberta.

  3. Barriers and Motivators for Referral of Patients with Suspected Lynch Syndrome to Cancer Genetic Services: A Qualitative Study

    Directory of Open Access Journals (Sweden)

    Yen Y. Tan

    2014-02-01

    Full Text Available This article explores the views of general practitioners and specialists on their referral of patients with suspected Lynch syndrome to cancer genetic services. Using a purposive maximum variation sampling strategy, we conducted semi-structured interviews face-to-face with 28 general practitioners and specialists in public or private hospitals and specialist clinics between March and August 2011. General practitioners and specialists were recruited in a major metropolitan area in Australia. Interview transcripts were reviewed by two independent researchers, and thematic analysis was performed using NVivo10 software. The main barriers and motivators identified were: (1 clinician-related (e.g., familiarity with Lynch syndrome and family history knowledge; (2 patient-related (e.g., patients’ interests and personal experience with cancer; and (3 organizational-related (e.g., access to services, guidelines and referral pathway. Referral of patients with suspected Lynch syndrome to cancer genetic services is motivated and hindered by a range of individual, interpersonal and organizational factors. In order to improve the care and quality of life of patients and family with suspected Lynch syndrome, further research is needed to develop supportive tools for clinicians.

  4. Body Mass Index Increases Risk of Colorectal Adenomas in Men With Lynch Syndrome : The GEOLynch Cohort Study

    NARCIS (Netherlands)

    Botma, Akke; Nagengast, Fokko M.; Braem, Marieke G. M.; Hendriks, Jan C. M.; Kleibeuker, Jan H.; Vasen, Hans F. A.; Kampman, Ellen

    2010-01-01

    Purpose High body mass index (BMI) is an established risk factor for sporadic colorectal cancer. Still, the influence of BMI on hereditary colorectal cancer (eg, Lynch syndrome [LS]), is unknown. The objective of this study was to assess whether BMI is associated with colorectal adenoma occurrence

  5. Revised guidelines for the clinical management of Lynch syndrome (HNPCC) : Recommendations by a group of European experts

    NARCIS (Netherlands)

    Vasen, Hans F. A.; Blanco, Ignacio; Aktan-Collan, Katja; Gopie, Jessica P.; Alonso, Angel; Aretz, Stefan; Bernstein, Inge; Bertario, Lucio; Burn, John; Capella, Gabriel; Colas, Chrystelle; Engel, Christoph; Frayling, Ian M.; Genuardi, Maurizio; Heinimann, Karl; Hes, Frederik J.; Hodgson, Shirley V.; Karagiannis, John A.; Lalloo, Fiona; Lindblom, Annika; Mecklin, Jukka-Pekka; Moller, Pal; Myrhoj, Torben; Nagengast, Fokko M.; Parc, Yann; de Leon, Maurizio Ponz; Renkonen-Sinisalo, Laura; Sampson, Julian R.; Stormorken, Astrid; Sijmons, Rolf H.; Tejpar, Sabine; Thomas, Huw J. W.; Rahner, Nils; Wijnen, Juul T.; Jaervinen, Heikki Juhani; Moeslein, Gabriela; Jarvinen, H.J.; Moslein, G.

    Lynch 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

  6. A frame-shift mutation of PMS2 is a widespread cause of Lynch syndrome

    DEFF Research Database (Denmark)

    Clendenning, Mark; Senter, Leigha; Hampel, Heather

    2008-01-01

    and Swedish ancestry. We estimate that there are >10,000 carriers of this mutation in the United States alone. The identification of both the mutation and the common haplotype in one Swedish control sample (n = 225), along with evidence that Lynch syndrome associated cancers are rarer than expected...

  7. Out of Amazonia: the unexpected trans-Andean distribution of Cochranella resplendens (Lynch and Duellman, 1978) (Anura: Centrolenidae).

    Science.gov (United States)

    Molina-Zuluaga, Claudia; Cano, Estefany; Restrepo, Adriana; Rada, Marco; Daza, Juan M

    2017-03-02

    The glassfrog genus Cochranella, with nine recognized species, is distributed in the lowlands and mid elevation of the Neotropical forests, from Nicaragua to Bolivia (Guayasamin et al. 2009; Twomey et al. 2014). Four species are trans-Andean-C. granulosa (Taylor 1949) occurs in the lowlands and mountains, at mid elevation, of Central America, C. litoralis (Ruiz-Carranza & Lynch 1996) and C. mache Guayasamin & Bonaccorso 2004 occur in the Pacific lowlands and the western cloud forests of Colombia and Ecuador, and C. euknemos (Savage & Starrett 1967) occurs both in Central America and South America (northwestern Colombia).-The other five species have cis-Andean distributions in the Amazonian slopes and lowlands, from Colombia to Bolivia: C. nola Harvey 1996, C. guayasamini Twomey, Delia & Castroviejo-Fisher 2014, C. resplendens (Lynch & Duellman 1973), C. erminea Torres-Gastello, Suárez-Segovia & Cisneros-Heredia 2007, and C. phryxa Aguayo-Vedia & Harvey 2006. In Colombia, C. resplendens is known from the foothills of the Amazon versant in Caquetá (Malambo et al. 2013) and Putumayo (Lynch & Duellman 1973; Ruiz-Carranza et al. 1996). The species is also known from Ecuador (Lynch & Duellman 1973) and Peru (Twomey et al. 2014). Here, we report two new records of Cochranella resplendens, extending the species distribution beyond the Amazonian lowlands into the northern Cordillera Central in Colombia.

  8. Sessile serrated polyps of the colorectum are rare in patients with Lynch syndrome and in familial colorectal cancer families

    DEFF Research Database (Denmark)

    Andersen, S H; Lykke, E; Folker, M B

    2008-01-01

    the sporadic MSI-H counterpart. Recent studies have, however, challenged such simple one-pathway models, inviting the consideration of alternative, unexpected pathways. Here, the issue as to the possible role of SSP, primarily in the context of Lynch syndrome, but also in subjects from familial CRC families...

  9. The additional value of endometrial sampling in the early detection of endometrial cancer in women with Lynch syndrome

    NARCIS (Netherlands)

    Helder-Woolderink, J. M.; De Bock, G. H.; Sijmons, R. H.; Hollema, H.; Mourits, M. J. E.

    2013-01-01

    Objective. Based on previous studies, standard gynecological screening consisting of annual transvaginal ultrasonography (TVU) was added with endometrial sampling in women with Lynch syndrome (LS). The aim of this study was to evaluate the additional value of endometrial sampling in detecting

  10. Targeted Next-Generation Sequencing for Hereditary Cancer Syndromes: A Focus on Lynch Syndrome and Associated Endometrial Cancer.

    Science.gov (United States)

    Tafe, Laura J

    2015-09-01

    Lynch syndrome is a hereditary cancer syndrome that results from germline mutations in one of the DNA mismatch repair genes, leading to an increased lifetime risk of cancer. Colorectal cancer is most commonly identified with Lynch syndrome; however, women with Lynch syndrome have an increased risk of developing endometrial cancer (up to 60%), which is the sentinel diagnosis in approximately one-half of the cases. Current screening algorithms are developed on family history and laboratory-based tests, including immunohistochemistry for mismatch repair proteins and microsatellite instability testing. Next-generation sequencing assays are rapidly being incorporated into clinical laboratory practices and have diagnostic applications for hereditary cancer syndromes. Important challenges of next-generation sequencing include interpreting incidental and uncertain findings, counseling before and after testing, and informed consent of patients. Here, with the use of Lynch syndrome in endometrial cancer as a model, some of the applications and intricacies of next-generation sequencing testing for hereditary cancer syndromes are reviewed. Copyright © 2015 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  11. Patient-reported disease knowledge and educational needs in Lynch syndrome: findings of an interactive multidisciplinary patient conference.

    Science.gov (United States)

    Bannon, Sarah A; Mork, Maureen; Vilar, Eduardo; Peterson, Susan K; Lu, Karen; Lynch, Patrick M; Rodriguez-Bigas, Miguel A; You, Yiqian Nancy

    2014-02-05

    Patients with Lynch Syndrome, the most common hereditary colorectal cancer syndrome, benefit from genetic education and family counseling regarding diagnostic testing and cancer surveillance/prevention recommendations. Although genetic counseling is currently the most common venue where such education and counseling takes place, little is known about the level of disease knowledge and education needs as directly reported by patients and families with Lynch Syndrome. Furthermore, experiences with forums for larger-scale knowledge transfer have been limited in the current literature. We conducted a one-day interactive multidisciplinary patient conference, designed to complement individual genetic counseling for updating disease knowledge, supportive networking and needs assessment among Lynch Syndrome patients and their family members. The patient conference was designed utilizing the conceptual framework of action research. Paired pre- and post-conference surveys were administered to 44 conference participants anonymously to assess patient-reported disease knowledge and education needs. A multidisciplinary team of expert providers utilized a variety of educational formats during the one-day conference. Four main focus areas were: genetic testing, surveillance/prevention, living with Lynch Syndrome, and update on research. Thirty-two participants (73%) completed the pre-conference, and 28 (64%) participants completed the post-conference surveys. Nineteen respondents were affected and the remaining were unaffected. The scores of the disease-knowledge items significantly increased from 84% pre- to 92% post-conference (p = 0.012). Patients reported a high level of satisfaction and identified further knowledge needs in nutrition (71%), surveillance/prevention options (71%), support groups (36%), cancer risk assessment (32%), active role in medical care (32%), and research opportunities (5%). Our experience with a dedicated patient education conference focused on

  12. Genetic variants in the cell cycle control pathways contribute to early onset colorectal cancer in Lynch syndrome.

    Science.gov (United States)

    Chen, Jinyun; Etzel, Carol J; Amos, Christopher I; Zhang, Qing; Viscofsky, Nancy; Lindor, Noralane M; Lynch, Patrick M; Frazier, Marsha L

    2009-11-01

    Lynch syndrome is an autosomal dominant syndrome of familial malignancies resulting from germ line mutations in DNA mismatch repair (MMR) genes. Our goal was to take a pathway-based approach to investigate the influence of polymorphisms in cell cycle-related genes on age of onset for Lynch syndrome using a tree model. We evaluated polymorphisms in a panel of cell cycle-related genes (AURKA, CDKN2A, TP53, E2F2, CCND1, TP73, MDM2, IGF1, and CDKN2B) in 220 MMR gene mutation carriers from 129 families. We applied a novel statistical approach, tree modeling (Classification and Regression Tree), to the analysis of data on patients with Lynch syndrome to identify individuals with a higher probability of developing colorectal cancer at an early age and explore the gene-gene interactions between polymorphisms in cell cycle genes. We found that the subgroup with CDKN2A C580T wild-type genotype, IGF1 CA-repeats >or=19, E2F2 variant genotype, AURKA wild-type genotype, and CCND1 variant genotype had the youngest age of onset, with a 45-year median onset age, while the subgroup with CDKN2A C580T wild-type genotype, IGF1 CA-repeats >or=19, E2F2 wild-type genotype, and AURKA variant genotype had the latest median age of onset, which was 70 years. Furthermore, we found evidence of a possible gene-gene interaction between E2F2 and AURKA genes related to CRC age of onset. Polymorphisms in these cell cycle-related genes work together to modify the age at the onset of CRC in patients with Lynch syndrome. These studies provide an important part of the foundation for development of a model for stratifying age of onset risk among those with Lynch syndrome.

  13. From Classrooms to Careers: The Senior Mastery Process at Henry Ford Academy.

    Science.gov (United States)

    Parizek, Deborah; Kesavan, Sandy

    The Henry Ford Academy is the nations first charter school developed jointly by a global corporation, public education, and a non-profit cultural institution. The Senior Mastery Process at Henry Ford Academy is an innovative, challenging program of career exploration and research project for high school seniors. Beginning with initial job…

  14. VoxHenry: FFT-Accelerated Inductance Extraction for Voxelized Geometries

    KAUST Repository

    Yucel, Abdulkadir C.

    2018-01-18

    VoxHenry, a fast Fourier transform (FFT)-accelerated integral-equation-based simulator for extracting frequency-dependent inductances and resistances of structures discretized by voxels, is presented. VoxHenry shares many features with the popular inductance extractor, FastHenry. Just like FastHenry, VoxHenry solves a combination of the electric volume integral equation and the current continuity equation, but with three distinctions that make VoxHenry suitable and extremely efficient for analyzing voxelized geometries: 1) it leverages a carefully selected set of piecewise-constant and piecewise-linear basis functions; 2) it exploits FFTs to accelerate the matrix-vector multiplications during the iterative solution of system of equations; and 3) it employs a sparse preconditioner to ensure the rapid convergence of iterative solution. VoxHenry is capable of accurately computing frequency-dependent inductances and resistances of arbitrarily shaped and large-scale structures on a desktop computer. The accuracy, efficiency, and applicability of VoxHenry are demonstrated through inductance analysis of various structures, including square and circular coils as well as arrays of RF inductors (situated over ground planes).

  15. Mutation spectrum and risk of colorectal cancer in African American families with Lynch syndrome.

    Science.gov (United States)

    Guindalini, Rodrigo Santa Cruz; Win, Aung Ko; Gulden, Cassandra; Lindor, Noralane M; Newcomb, Polly A; Haile, Robert W; Raymond, Victoria; Stoffel, Elena; Hall, Michael; Llor, Xavier; Ukaegbu, Chinedu I; Solomon, Ilana; Weitzel, Jeffrey; Kalady, Matthew; Blanco, Amie; Terdiman, Jonathan; Shuttlesworth, Gladis A; Lynch, Patrick M; Hampel, Heather; Lynch, Henry T; Jenkins, Mark A; Olopade, Olufunmilayo I; Kupfer, Sonia S

    2015-11-01

    African Americans (AAs) have the highest incidence of and mortality resulting from colorectal cancer (CRC) in the United States. Few data are available on genetic and nongenetic risk factors for CRC among AAs. Little is known about cancer risks and mutations in mismatch repair (MMR) genes in AAs with the most common inherited CRC condition, Lynch syndrome. We aimed to characterize phenotype, mutation spectrum, and risk of CRC in AAs with Lynch syndrome. We performed a retrospective study of AAs with mutations in MMR genes (MLH1, MSH2, MSH6, and PMS2) using databases from 13 US referral centers. We analyzed data on personal and family histories of cancer. Modified segregation analysis conditioned on ascertainment criteria was used to estimate age- and sex-specific CRC cumulative risk, studying members of the mutation-carrying families. We identified 51 AA families with deleterious mutations that disrupt function of the MMR gene product: 31 in MLH1 (61%), 11 in MSH2 (21%), 3 in MSH6 (6%), and 6 in PMS2 (12%); 8 mutations were detected in more than 1 individual, and 11 have not been previously reported. In the 920 members of the 51 families with deleterious mutations, the cumulative risks of CRC at 80 years of age were estimated to be 36.2% (95% confidence interval [CI], 10.5%-83.9%) for men and 29.7% (95% CI, 8.31%-76.1%) for women. CRC risk was significantly higher among individuals with mutations in MLH1 or MSH2 (hazard ratio, 13.9; 95% CI, 3.44-56.5). We estimate the cumulative risk for CRC in AAs with MMR gene mutations to be similar to that of individuals of European descent with Lynch syndrome. Two-thirds of mutations were found in MLH1, some of which were found in multiple individuals and some that have not been previously reported. Differences in mutation spectrum are likely to reflect the genetic diversity of this population. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  16. Effect of aspirin or resistant starch on colorectal neoplasia in the Lynch syndrome.

    Science.gov (United States)

    Burn, John; Bishop, D Timothy; Mecklin, Jukka-Pekka; Macrae, Finlay; Möslein, Gabriela; Olschwang, Sylviane; Bisgaard, Marie-Luise; Ramesar, Raj; Eccles, Diana; Maher, Eamonn R; Bertario, Lucio; Jarvinen, Heikki J; Lindblom, Annika; Evans, D Gareth; Lubinski, Jan; Morrison, Patrick J; Ho, Judy W C; Vasen, Hans F A; Side, Lucy; Thomas, Huw J W; Scott, Rodney J; Dunlop, Malcolm; Barker, Gail; Elliott, Faye; Jass, Jeremy R; Fodde, Ricardo; Lynch, Henry T; Mathers, John C

    2008-12-11

    Observational and epidemiologic data indicate that the use of aspirin reduces the risk of colorectal neoplasia; however, the effects of aspirin in the Lynch syndrome (hereditary nonpolyposis colon cancer) are not known. Resistant starch has been associated with an antineoplastic effect on the colon. In a randomized, placebo-controlled trial, we used a two-by-two design to investigate the effects of aspirin, at a dose of 600 mg per day, and resistant starch (Novelose), at a dose of 30 g per day, in reducing the risk of adenoma and carcinoma among persons with the Lynch syndrome. Among 1071 persons in 43 centers, 62 were ineligible to participate in the study, 72 did not enter the study, and 191 withdrew from the study. These three categories were equally distributed across the study groups. Over a mean period of 29 months (range, 7 to 74), colonic adenoma or carcinoma developed in 141 participants. Of 693 participants randomly assigned to receive aspirin or placebo, neoplasia developed in 66 participants receiving aspirin (18.9%), as compared with 65 receiving placebo (19.0%) (relative risk, 1.0; 95% confidence interval [CI], 0.7 to 1.4). There were no significant differences between the two groups with respect to the development of advanced neoplasia (7.4% and 9.9%, respectively; P=0.33). Among the 727 participants receiving resistant starch or placebo, neoplasia developed in 67 participants receiving starch (18.7%), as compared with 68 receiving placebo (18.4%) (relative risk, 1.0; 95% CI, 0.7 to 1.4). Advanced adenomas and colorectal cancers were evenly distributed in the two groups. The prevalence of serious adverse events was low, and the events were evenly distributed. The use of aspirin, resistant starch, or both for up to 4 years has no effect on the incidence of colorectal adenoma or carcinoma among carriers of the Lynch syndrome. (Current Controlled Trials number, ISRCTN59521990.) 2008 Massachusetts Medical Society

  17. Henry Mayhew: jornalista, investigador social e precursor da pesquisa qualitativa Henry Mayhew: journalist, social investigator, and foreshadower of qualitative research

    Directory of Open Access Journals (Sweden)

    Everardo Duarte Nunes

    2012-09-01

    Full Text Available Henry Mayhew serviu-se de sua profissão, o jornalismo, para registrar o dia a dia da Londres da segunda metade do século XIX de uma forma que até hoje interessa historiadores e cientistas sociais, como obra precursora da pesquisa qualitativa. Este artigo destaca aspectos metodológicos das investigações de Mayhew e analisa dois de seus relatos: sobre o surto de cólera e sobre uma vendedora de rua. Aborda também trabalhos críticos que tomam sua obra como referência.As a journalist, Henry Mayhew recorded daily life in London in the latter half of the nineteenth century. His approach remains of interest to historians and social scientists today in that it foreshadowed qualitative research. The article highlights methodological aspects of Mayhew's investigations and analyzes two of his reports, one on a cholera outbreak and the other on a female street vendor. It also addresses some analyses that have critiqued his work.

  18. Direct-to-patient disclosure of results of mismatch repair screening for Lynch syndrome via electronic personal health record: a feasibility study

    National Research Council Canada - National Science Library

    Hall, Michael J; Herda, Meagan M; Handorf, Elizabeth A; Rybak, Christina C; Keleher, Cindy A; Siemon, Mark; Daly, Mary B

    2014-01-01

    The adoption of universal mismatch repair screening of colorectal and endometrial cancers has the potential to improve detection of Lynch syndrome, as well as to improve health outcomes among cancer...

  19. Human Heredity and Health (H3) in Africa Kidney Disease Research Network: A Focus on Methods in Sub-Saharan Africa

    OpenAIRE

    Osafo, Charlotte; Raji, Yemi Raheem; Burke, David; Tayo, Bamidele O.; Tiffin, Nicki; Moxey-Mims, Marva M.; Rasooly, Rebekah S.; Kimmel, Paul L; Ojo, Akinlolu; Adu, Dwomoa; Parekh, Rulan S.

    2015-01-01

    CKD affects an estimated 14% of adults in sub-Saharan Africa, but very little research has been done on the cause, progression, and prevention of CKD there. As part of the Human Heredity and Health in Africa (H3Africa) Consortium, the H3Africa Kidney Disease Research Network was established to study prevalent forms of kidney disease in sub-Saharan Africa and increase the capacity for genetics and genomics research. The study is performing comprehensive phenotypic characterization and analyzin...

  20. Henri Pirenne: Historian and Man of the World.

    Directory of Open Access Journals (Sweden)

    S. Keymeulen

    2016-12-01

    Full Text Available Henri Pirenne (1862-1935 is generally recognised as one of the most influential European historians of the late nineteenth- and early twentieth-century. The combination of his scholarly activity with the social mission that he set himself earned him an extraordinarily successful career and a double reputation: at least in Belgium, he was regarded not only as a ‘father of history’, but also as great citizen. Although his influence was unmistakably large, there is no consensus about the existence or the nature of a ‘Pirennian persona’. He combined the ideal collection of skills, values and standards required of historians with very specific personal characteristics. At the same time he was inextricably linked to a certain era and a certain Belgium that died with him. Pirenne therefore, did not so much represent a new type of scientific persona as the prestige of an idealised, long-vanished Belgium and its corresponding academic culture. Henri Pirenne. Historicus en man van de wereld. Henri Pirenne (1862-1935 wordt beschouwd als één van de meest invloedrijke Europese geschiedschrijvers van de laatnegentiende en vroegtwintigste eeuw. Het verband tussen zijn wetenschappelijke activiteit en de maatschappelijke taak die hij voor zichzelf zag weggelegd, leverde hem een uitzonderlijk succesvolle carrière en een dubbele reputatie op. Pirenne staat, althans in België, immers niet alleen geboekstaafd als een ‘vader van de geschiedenis’, maar ook als een groot staatsburger. Hoewel de invloed van Pirenne onmiskenbaar groot is geweest, is er geen consensus over het bestaan of de aard van een ‘pirenniaanse persona’. Hij combineerde het ideaalpakket van vaardigheden, normen en waarden die historici werden geacht te bezitten met zeer specifieke karaktereigenschappen. Tegelijk was hij onlosmakelijk verknoopt met een zeker tijdsgewricht en een zeker België, dat samen met hem ter ziele ging. Pirenne stond dan ook niet zozeer model voor een nieuw

  1. Henri Pirenne: Historian and Man of the World

    Directory of Open Access Journals (Sweden)

    Sarah Keymeulen

    2016-12-01

    Full Text Available Henri Pirenne (1862-1935 is generally recognised as one of the most influential European historians of the late nineteenth- and early twentieth-century. The combination of his scholarly activity with the social mission that he set himself earned him an extraordinarily successful career and a double reputation: at least in Belgium, he was regarded not only as a ‘father of history’, but also as great citizen. Although his influence was unmistakably large, there is no consensus about the existence or the nature of a ‘Pirennian persona’. He combined the ideal collection of skills, values and standards required of historians with very specific personal characteristics. At the same time he was inextricably linked to a certain era and a certain Belgium that died with him. Pirenne therefore, did not so much represent a new type of scientific persona as the prestige of an idealised, long-vanished Belgium and its corresponding academic culture. Henri Pirenne. Historicus en man van de wereldHenri Pirenne (1862-1935 wordt beschouwd als één van de meest invloedrijke Europese geschiedschrijvers van de laatnegentiende en vroegtwintigste eeuw. Het verband tussen zijn wetenschappelijke activiteit en de maatschappelijke taak die hij voor zichzelf zag weggelegd, leverde hem een uitzonderlijk succesvolle carrière en een dubbele reputatie op. Pirenne staat, althans in België, immers niet alleen geboekstaafd als een ‘vader van de geschiedenis’, maar ook als een groot staatsburger. Hoewel de invloed van Pirenne onmiskenbaar groot is geweest, is er geen consensus over het bestaan of de aard van een ‘pirenniaanse persona’. Hij combineerde het ideaalpakket van vaardigheden, normen en waarden die historici werden geacht te bezitten met zeer specifieke karaktereigenschappen. Tegelijk was hij onlosmakelijk verknoopt met een zeker tijdsgewricht en een zeker België, dat samen met hem ter ziele ging. Pirenne stond dan ook niet zozeer model voor een nieuw

  2. Human genetics and politics as mutually beneficial resources: The case of the Kaiser Wilhelm Institute for Anthropology, Human Heredity and Eugenics during the Third Reich.

    Science.gov (United States)

    Weiss, Sheila Faith

    2006-01-01

    This essay analyzes one of Germany's former premier research institutions for biomedical research, the Kaiser Wilhelm Institute for Anthropology, Human Heredity and Eugenics (KWIA) as a test case for the way in which politics and human heredity served as resources for each other during the Third Reich. Examining the KWIA from this perspective brings us a step closer to answering the questions at the heart of most recent scholarship concerning the biomedical community under the swastika: (1) How do we explain why the vast majority of German human geneticists and eugenicists were willing to work for the National Socialist state and, at the very least, legitimized its exterminationist racial policy; and (2) what accounts for at least some of Germany's most renowned medically trained professionals' involvement in forms of morally compromised science that wholly transcend the bounds of normal scientific practice? Although a complete answer to this question must await an examination of other German biological research centers, the present study suggests that during the Nazi period the symbiotic relationship between human genetics and politics served to radicalize both. The dynamic between the science of human heredity and Nazi politics changed the research practice of some of the biomedical sciences housed at the KWIA. It also simultaneously made it easier for the Nazi state to carry out its barbaric racial program leading, finally, to the extermination of millions of so-called racial undesirables.

  3. HNPCC (Lynch Syndrome): Differential Diagnosis, Molecular Genetics and Management - a Review

    Science.gov (United States)

    2003-01-01

    HNPCC (Lynch syndrome) is the most common form of hereditary colorectal cancer (CRC), wherein it accounts for between 2-7 percent of the total CRC burden. When considering the large number of extracolonic cancers integral to the syndrome, namely carcinoma of the endometrium, ovary, stomach, hepatobiliary system, pancreas, small bowel, brain tumors, and upper uroepithelial tract, these estimates of its frequency are likely to be conservative. The diagnosis is based upon its natural history in concert with a comprehensive cancer family history inclusive of all anatomic sites. In order for surveillance and management to be effective and, indeed, lifesaving, among these high-risk patients, the linchpin to cancer control would be the physician, who must be knowledgeable about hereditary cancer syndromes, their molecular and medical genetics, genetic counseling, and, most importantly, the natural history of the disorders, so that the entirety of this knowledge can be melded to highly-targeted management.

  4. Predicting the impact of Lynch syndrome-causing missense mutations from structural calculations

    DEFF Research Database (Denmark)

    Nielsen, Sofie V,; Stein, Amelie; Dinitzen, Alexander B.

    2017-01-01

    inherent loss of function, and accordingly our in silico modeling data accurately identifies disease-causing mutations and outperforms the traditionally used genetic disease predictors. Thus, in conclusion, in silico biophysical modeling should be considered for making genotype-phenotype predictions......Accurate methods to assess the pathogenicity of mutations are needed to fully leverage the possibilities of genome sequencing in diagnosis. Current data-driven and bioinformatics approaches are, however, limited by the large number of new variations found in each newly sequenced genome, and often...... selected the human mismatch repair protein, MSH2, where missense variants are known to cause the hereditary cancer predisposition disease, known as Lynch syndrome. We show that the majority of disease-causing MSH2 mutations give rise to folding defects and proteasome-dependent degradation rather than...

  5. The risk of extra-colonic, extra-endometrial cancer in the Lynch syndrome

    DEFF Research Database (Denmark)

    Watson, Patrice; Vasen, Hans F A; Mecklin, Jukka-Pekka

    2008-01-01

    Persons with the Lynch syndrome (LS) are at high risk for cancer, including cancers of the small bowel, stomach, upper urologic tract (renal pelvis and ureter), ovary, biliary tract and brain tumors, in addition to the more commonly observed colorectal and endometrial cancers. Cancer prevention...... strategies for these less common cancers require accurate, age-specific risk estimation. We pooled data from 4 LS research centers in a retrospective cohort study, to produce absolute incidence estimates for these cancer types, and to evaluate several potential risk modifiers. After elimination of 135...... persons missing crucial information, cohort included 6,041 members of 261 families with LS-associated MLH1 or MSH2 mutations. All were either mutation carriers by test, probable mutation carriers (endometrial/colorectal cancer-affected), or first-degree relatives of these. Among mutation carriers...

  6. "The cancer bond": exploring the formation of cancer risk perception in families with Lynch syndrome.

    Science.gov (United States)

    Palmquist, Aunchalee E L; Koehly, Laura M; Peterson, Susan K; Shegog, Margarette; Vernon, Sally W; Gritz, Ellen R

    2010-10-01

    This study explores the social context of hereditary cancer risk perception in three families, an African-American family, a Mexican-American family, and a Caucasian family, each with Lynch Syndrome documented by a mismatch repair gene mutation. Communication network assessments measured family communication about cancer experiences and genetic testing information among a total of 26 participants. Participant narratives were evaluated to gain insight into how family cancer experiences and genetic testing information have shaped perceptions of cancer risk. Analysis of communication networks indicated that some families discussed cancer experiences to a greater extent than genetic testing information, and vice-versa. Interviews elucidated that sharing both types of health information led participants to conceptualize linkages among a strong family history of cancer, genetic testing information, and cancer prevention strategies. Understanding how different types of family communication influence the formation of perceived hereditary disease risk may enhance efforts to tailor genetic counseling services for families.

  7. A review of statistical methods for testing genetic anticipation: looking for an answer in Lynch syndrome

    DEFF Research Database (Denmark)

    Boonstra, Philip S; Gruber, Stephen B; Raymond, Victoria M

    2010-01-01

    the issue of multiplex ascertainment and its effect on the different methods. We then focus on exploring genetic anticipation in Lynch syndrome and analyze new data on the age of onset in affected parent-child pairs from families seen at the University of Michigan Cancer Genetics clinic with a mutation...... to a recently proposed random effects model which includes extended pedigree data and unaffected family members [Larsen et al., 2009]. A naive use of the paired t-test is biased for the simple reason that age of onset has to be less than the age at ascertainment (interview) for both affected parent and child......, and this right truncation effect is more pronounced in children than in parents. In this study, we first review different statistical methods for testing genetic anticipation in affected parent-child pairs that address the issue of bias due to right truncation. Using affected parent-child pair data, we compare...

  8. Structure of the human MLH1 N-terminus: implications for predisposition to Lynch syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Hong; Zeng, Hong; Lam, Robert; Tempel, Wolfram [University of Toronto, 101 College Street, Toronto, ON M5G 1L7 (Canada); Kerr, Iain D., E-mail: ikerr@myriad.com [Myriad Genetic Laboratories Inc., 320 Wakara Way, Salt Lake City, UT 84108 (United States); Min, Jinrong, E-mail: ikerr@myriad.com [University of Toronto, 101 College Street, Toronto, ON M5G 1L7 (Canada); University of Toronto, Toronto, ON M5G 1L7 (Canada)

    2015-07-28

    The crystal structure of the human MLH1 N-terminus is reported at 2.30 Å resolution. The overall structure is described along with an analysis of two clinically important mutations. Mismatch repair prevents the accumulation of erroneous insertions/deletions and non-Watson–Crick base pairs in the genome. Pathogenic mutations in the MLH1 gene are associated with a predisposition to Lynch and Turcot’s syndromes. Although genetic testing for these mutations is available, robust classification of variants requires strong clinical and functional support. Here, the first structure of the N-terminus of human MLH1, determined by X-ray crystallography, is described. The structure shares a high degree of similarity with previously determined prokaryotic MLH1 homologs; however, this structure affords a more accurate platform for the classification of MLH1 variants.

  9. Assessing Genetic Variants of Uncertain Significance: The Example of Lynch Syndrome

    DEFF Research Database (Denmark)

    Rasmussen, Lene Juel; Heinen, Christopher D.

    2014-01-01

    A significant fraction of cancer is the result of genetic predisposition. Frequently, in patients with suspected cancer predisposition, subtle variations are found in predisposing genes. Currently, it is often not possible to determine whether such variants are pathogenic, thus they are termed...... variants of uncertain significance (VUS). This leads to anxiety in carriers and noncarrying relatives alike, as well as to an unnecessary burden to preventive healthcare. The establishment of procedures that enable the diagnostic assessment of VUSs in individuals are discussed and hereditary colorectal...... cancer syndrome, Lynch syndrome, is used as an example. This challenge is addressed by illustrating the importance of combining genetic and functional data in future strategies to assess VUS. The proposed strategies combine clinical genetic, analytical, functional and in silico approaches....

  10. Revised Bethesda Guidelines for Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome) and Microsatellite Instability

    Science.gov (United States)

    Umar, Asad; Boland, C. Richard; Terdiman, Jonathan P.; Syngal, Sapna; de la Chapelle, Albert; Rüschoff, Josef; Fishel, Richard; Lindor, Noralane M.; Burgart, Lawrence J.; Hamelin, Richard; Hamilton, Stanley R.; Hiatt, Robert A.; Jass, Jeremy; Lindblom, Annika; Lynch, Henry T.; Peltomaki, Païvi; Ramsey, Scott D.; Rodriguez-Bigas, Miguel A.; Vasen, Hans F. A.; Hawk, Ernest T.; Barrett, J. Carl; Freedman, Andrew N.; Srivastava, Sudhir

    2010-01-01

    Hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is a common autosomal dominant syndrome characterized by early age at onset, neoplastic lesions, and microsatellite instability (MSI). Because cancers with MSI account for approximately 15% of all colorectal cancers and because of the need for a better understanding of the clinical and histologic manifestations of HNPCC, the National Cancer Institute hosted an international workshop on HNPCC in 1996, which led to the development of the Bethesda Guidelines for the identification of individuals with HNPCC who should be tested for MSI. To consider revision and improvement of the Bethesda Guidelines, another HNPCC workshop was held at the National Cancer Institute in Bethesda, MD, in 2002. In this commentary, we summarize the Workshop presentations on HNPCC and MSI testing; present the issues relating to the performance, sensitivity, and specificity of the Bethesda Guidelines; outline the revised Bethesda Guidelines for identifying individuals at risk for HNPCC; and recommend criteria for MSI testing. PMID:14970275

  11. H3ABioNet, a sustainable pan-African bioinformatics network for human heredity and health in Africa

    Science.gov (United States)

    Mulder, Nicola J.; Adebiyi, Ezekiel; Alami, Raouf; Benkahla, Alia; Brandful, James; Doumbia, Seydou; Everett, Dean; Fadlelmola, Faisal M.; Gaboun, Fatima; Gaseitsiwe, Simani; Ghazal, Hassan; Hazelhurst, Scott; Hide, Winston; Ibrahimi, Azeddine; Jaufeerally Fakim, Yasmina; Jongeneel, C. Victor; Joubert, Fourie; Kassim, Samar; Kayondo, Jonathan; Kumuthini, Judit; Lyantagaye, Sylvester; Makani, Julie; Mansour Alzohairy, Ahmed; Masiga, Daniel; Moussa, Ahmed; Nash, Oyekanmi; Ouwe Missi Oukem-Boyer, Odile; Owusu-Dabo, Ellis; Panji, Sumir; Patterton, Hugh; Radouani, Fouzia; Sadki, Khalid; Seghrouchni, Fouad; Tastan Bishop, Özlem; Tiffin, Nicki; Ulenga, Nzovu

    2016-01-01

    The application of genomics technologies to medicine and biomedical research is increasing in popularity, made possible by new high-throughput genotyping and sequencing technologies and improved data analysis capabilities. Some of the greatest genetic diversity among humans, animals, plants, and microbiota occurs in Africa, yet genomic research outputs from the continent are limited. The Human Heredity and Health in Africa (H3Africa) initiative was established to drive the development of genomic research for human health in Africa, and through recognition of the critical role of bioinformatics in this process, spurred the establishment of H3ABioNet, a pan-African bioinformatics network for H3Africa. The limitations in bioinformatics capacity on the continent have been a major contributory factor to the lack of notable outputs in high-throughput biology research. Although pockets of high-quality bioinformatics teams have existed previously, the majority of research institutions lack experienced faculty who can train and supervise bioinformatics students. H3ABioNet aims to address this dire need, specifically in the area of human genetics and genomics, but knock-on effects are ensuring this extends to other areas of bioinformatics. Here, we describe the emergence of genomics research and the development of bioinformatics in Africa through H3ABioNet. PMID:26627985

  12. Thyroid cancer in a patient with a germline MSH2 mutation. Case report and review of the Lynch syndrome expanding tumour spectrum

    Directory of Open Access Journals (Sweden)

    Stulp Rein P

    2008-02-01

    Full Text Available Abstract Lynch syndrome (HNPCC is a dominantly inherited disorder characterized by germline defects in DNA mismatch repair (MMR genes and the development of a variety of cancers, predominantly colorectal and endometrial. We present a 44-year-old woman who was shown to carry the truncating MSH2 gene mutation that had previously been identified in her family. Recently, she had been diagnosed with an undifferentiated carcinoma of the thyroid and an adenoma of her coecum. Although the thyroid carcinoma was not MSI-high (1 out of 5 microsatellites instable, it did show complete loss of immunohistochemical expression for the MSH2 protein, suggesting that this tumour was not coincidental. Although the risks for some tumour types, including breast cancer, soft tissue sarcoma and prostate cancer, are not significantly increased in Lynch syndrome, MMR deficiency in the presence of a corresponding germline defect has been demonstrated in incidental cases of a growing range of tumour types, which is reviewed in this paper. Interestingly, the MSH2-associated tumour spectrum appears to be wider than that of MLH1 and generally the risk for most extra-colonic cancers appears to be higher for MSH2 than for MLH1 mutation carriers. Together with a previously reported case, our findings show that anaplastic thyroid carcinoma can develop in the setting of Lynch syndrome. Uncommon Lynch syndrome-associated tumour types might be useful in the genetic analysis of a Lynch syndrome suspected family if samples from typical Lynch syndrome tumours are unavailable.

  13. Role of microsatellite instability-low as a diagnostic biomarker of Lynch syndrome in colorectal cancer.

    Science.gov (United States)

    Vilar, Eduardo; Mork, Maureen E; Cuddy, Amanda; Borras, Ester; Bannon, Sarah A; Taggart, Melissa W; Ying, Jun; Broaddus, Russell R; Luthra, Rajyalakshmi; Rodriguez-Bigas, Miguel A; Lynch, Patrick M; You, Yi-Qian Nancy

    2014-01-01

    Lynch syndrome is the most common Mendelian disorder predisposing persons to hereditary colorectal cancer. Carriers of MSH6 mutations constitute less than 10% of the total of cases with Lynch syndrome and present with a weaker clinical phenotype, including low levels of microsatellite instability (MSI-L) in colorectal tumors. The frequency of MSH6 mutation carriers among patients presenting with MSI-L colorectal cancer has yet to be determined, as has the appropriate genetic workup in this context. We have reviewed here the clinicopathologic characteristics, immunohistochemistry, and genetic testing results for 71 patients at a single institution diagnosed with MSI-L colorectal cancers. Of 71 patients with MSI-L tumors, 21 underwent genetic testing for MSH6 mutations, three of whom presented with loss of staining of MSH6 and only one of whom carried a pathogenic germline MSH6 mutation in exon 4 (c.2677_2678delCT; p.Leu893Alafs*6). This latter patient had a significant family history of cancer and had a rectal primary tumor that showed instability only in mononucleotide markers. In this cohort of MSI-L patients, we detected no notable clinicopathologic or molecular characteristic that would help to distinguish a group most likely to harbor germline MSH6 mutations. Therefore, we conclude that the prevalence of MSH6 mutations among patients with MSI-L tumors is very low. Microsatellite instability analysis combined with immunohistochemistry of mismatch repair proteins adequately detects potential MSH6 mutation carriers among MSI-L colorectal cancers. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Linkage analysis in familial non-Lynch syndrome colorectal cancer families from Sweden.

    Directory of Open Access Journals (Sweden)

    Vinaykumar Kontham

    Full Text Available Family history is a major risk factor for colorectal cancer and many families segregate the disease as a seemingly monogenic trait. A minority of familial colorectal cancer could be explained by known monogenic genes and genetic loci. Familial polyposis and Lynch syndrome are two syndromes where the predisposing genes are known but numerous families have been tested without finding the predisposing gene. We performed a genome wide linkage analysis in 121 colorectal families with an increased risk of colorectal cancer. The families were ascertained from the department of clinical genetics at the Karolinska University Hospital in Stockholm, Sweden and were considered negative for Familial Polyposis and Lynch syndrome. In total 600 subjects were genotyped using single nucleotide polymorphism array chips. Parametric- and non-parametric linkage analyses were computed using MERLIN in all and subsets of families. No statistically significant result was seen, however, there were suggestive positive HLODs above two in parametric linkage analysis. This was observed in a recessive model for high-risk families, at locus 9q31.1 (HLOD=2.2, rs1338121 and for moderate-risk families, at locus Xp22.33 (LOD=2.2 and HLOD=2.5, rs2306737. Using families with early-onset, recessive analysis suggested one locus on 4p16.3 (LOD=2.2, rs920683 and one on 17p13.2 (LOD/HLOD=2.0, rs884250. No NPL score above two was seen for any of the families. Our linkage study provided additional support for the previously suggested region on chromosome 9 and suggested additional loci to be involved in colorectal cancer risk. Sequencing of genes in the regions will be done in future studies.

  15. Linkage analysis in familial non-Lynch syndrome colorectal cancer families from Sweden.

    Science.gov (United States)

    Kontham, Vinaykumar; von Holst, Susanna; Lindblom, Annika

    2013-01-01

    Family history is a major risk factor for colorectal cancer and many families segregate the disease as a seemingly monogenic trait. A minority of familial colorectal cancer could be explained by known monogenic genes and genetic loci. Familial polyposis and Lynch syndrome are two syndromes where the predisposing genes are known but numerous families have been tested without finding the predisposing gene. We performed a genome wide linkage analysis in 121 colorectal families with an increased risk of colorectal cancer. The families were ascertained from the department of clinical genetics at the Karolinska University Hospital in Stockholm, Sweden and were considered negative for Familial Polyposis and Lynch syndrome. In total 600 subjects were genotyped using single nucleotide polymorphism array chips. Parametric- and non-parametric linkage analyses were computed using MERLIN in all and subsets of families. No statistically significant result was seen, however, there were suggestive positive HLODs above two in parametric linkage analysis. This was observed in a recessive model for high-risk families, at locus 9q31.1 (HLOD=2.2, rs1338121) and for moderate-risk families, at locus Xp22.33 (LOD=2.2 and HLOD=2.5, rs2306737). Using families with early-onset, recessive analysis suggested one locus on 4p16.3 (LOD=2.2, rs920683) and one on 17p13.2 (LOD/HLOD=2.0, rs884250). No NPL score above two was seen for any of the families. Our linkage study provided additional support for the previously suggested region on chromosome 9 and suggested additional loci to be involved in colorectal cancer risk. Sequencing of genes in the regions will be done in future studies.

  16. Lynch syndrome caused by germline PMS2 mutations: delineating the cancer risk.

    Science.gov (United States)

    ten Broeke, Sanne W; Brohet, Richard M; Tops, Carli M; van der Klift, Heleen M; Velthuizen, Mary E; Bernstein, Inge; Capellá Munar, Gabriel; Gomez Garcia, Encarna; Hoogerbrugge, Nicoline; Letteboer, Tom G W; Menko, Fred H; Lindblom, Annika; Mensenkamp, Arjen R; Moller, Pal; van Os, Theo A; Rahner, Nils; Redeker, Bert J W; Sijmons, Rolf H; Spruijt, Liesbeth; Suerink, Manon; Vos, Yvonne J; Wagner, Anja; Hes, Frederik J; Vasen, Hans F; Nielsen, Maartje; Wijnen, Juul T

    2015-02-01

    The clinical consequences of PMS2 germline mutations are poorly understood compared with other Lynch-associated mismatch repair gene (MMR) mutations. The aim of this European cohort study was to define the cancer risk faced by PMS2 mutation carriers. Data were collected from 98 PMS2 families ascertained from family cancer clinics that included a total of 2,548 family members and 377 proven mutation carriers. To adjust for potential ascertainment bias, a modified segregation analysis model was used to calculate colorectal cancer (CRC) and endometrial cancer (EC) risks. Standardized incidence ratios (SIRs) were calculated to estimate risks for other Lynch syndrome-associated cancers. The cumulative risk (CR) of CRC for male mutation carriers by age 70 years was 19%. The CR among female carriers was 11% for CRC and 12% for EC. The mean age of CRC development was 52 years, and there was a significant difference in mean age of CRC between the probands (mean, 47 years; range, 26 to 68 years) and other family members with a PMS2 mutation (mean, 58 years; range, 31 to 86 years; P < .001). Significant SIRs were observed for cancers of the small bowel, ovaries, breast, and renal pelvis. CRC and EC risks were found to be markedly lower than those previously reported for the other MMR. However, these risks embody the isolated risk of carrying a PMS2 mutation, and it should be noted that we observed a substantial variation in cancer phenotype within and between families, suggesting the influence of genetic modifiers and lifestyle factors on cancer risks. © 2014 by American Society of Clinical Oncology.

  17. [Determination of Henry's law constants for dimethyl sulfide in seawater].

    Science.gov (United States)

    Wang, Y H; Wong, P K

    2001-07-01

    The article presents the method of determination of Henry's Law Constant(K) for dimethyl sulfide (DMS) in seawater using multiple phase equilibration/headspace gas chromatography. The method is based on the demonstration that analysis of only one phase after multiple phase equilibration give all necessary data. The values of K of DMS in seawater determined by this method was 0.089 with relative standard deviation(RSD) of 5.50% at 22 degrees C. The linear relationship between log K and w (NaCl) was log K = 0.0688.w (NaCl) - 1.3568 with correlation coefficient(r) of 0.997. The regression equation of log K against reciprocal of absolute temperature(T) was log K = -1,544.8/T + 4.2112 with r of 0.996.

  18. Henry's law constants of diacids and hydroxy polyacids: recommended values

    Science.gov (United States)

    Compernolle, S.; Müller, J.-F.

    2014-03-01

    In spite of the importance of diacids and functionalised diacids for organic aerosol formation through aqueous-phase processes in droplets and aerosol water, there seems to be no reliable set of experimental values for their Henry's law constants (HLCs). We show that their estimation through the use of infinite dilution activity coefficients is also prone to error. Here we present HLC values for diacids and hydroxy polyacids determined from solubilities, water activities and vapour pressures of solids or solutions, by employing thermodynamic relationships. The vapour pressures are found to be the largest source of error, but the analysis of the obtained HLC points to inconsistencies among specific vapour pressure data sets. Although there is considerable uncertainty, the HLC defined as aqueous concentration per unit gaseous partial pressure of linear α- and ω-diacids appear to be higher than estimated by the often cited review work of Saxena and Hildemann (1996).

  19. História e psicologia em Henri Berr

    OpenAIRE

    Waeny, Maria Fernanda Costa

    2017-01-01

    O artigo aborda algumas das idéias de Henri Berr; trata de sua proposta em história, especialmente no que ela se opõe à filosofia da história e à história alemãs; e examina como esta concepção de história à la francesa introduz a psicologia nas pesquisas em história e inaugura a psicologia histórica.Palavras-chave: História da Psicologia; Psicologia Histórica; História das Ciências Humanas; História das Idéias; Annales

  20. Thinking in time an introduction to Henri Bergson

    CERN Document Server

    Guerlac, Suzanne

    2006-01-01

    "In recent years, we have grown accustomed to philosophical language that is intensely self-conscious and rhetorically thick, often tragic in tone. It is enlivening to read Bergson, who exerts so little rhetorical pressure while exacting such a substantial effort of thought. . . . Bergson's texts teach the reader to let go of entrenched intellectual habits and to begin to think differently—to think in time. . . . Too much and too little have been said about Bergson. Too much, because of the various appropriations of his thought. Too little, because the work itself has not been carefully studied in recent decades."—from Thinking in TimeHenri Bergson (1859–1941), whose philosophical works emphasized motion, time, and change, won the Nobel Prize for Literature in 1927. His work remains influential, particularly in the realms of philosophy, cultural studies, and new media studies. In Thinking in Time, Suzanne Guerlac provides readers with the conceptual and contextual tools necessary for informed appreciati...

  1. W.E. Henry Symposium compendium: The importance of magnetism in physics and material science

    Energy Technology Data Exchange (ETDEWEB)

    Carwell, H.

    1997-09-19

    This compendium contains papers presented at the W. E. Henry Symposium, The Importance of Magnetism in Physics and Material Science. The one-day symposium was conducted to recognize the achievements of Dr. Warren Elliot Henry as educator, scientist, and inventor in a career spanning almost 70 years. Dr. Henry, who is 88 years old, attended the symposium. Nobel Laureate, Dr. Glenn Seaborg, a friend and colleague for over 40 years, attended the event and shared his personal reminiscences. Dr. Seaborg is Associate Director-At-Large at the Lawrence Berkeley National Laboratory. The Compendium begins with three papers which demonstrate the ongoing importance of magnetism in physics and material science. Other contributions cover the highlights of Dr. Henry`s career as a researcher, educator, and inventor. Colleagues and former students share insights on the impact of Dr. Henry`s research in the field of magnetism, low temperature physics, and solid state physics; his influence on students as an educator; and his character, intellect and ingenuity, and passion for learning and teaching. They share a glimpse of the environment and times that molded him as a man, and the circumstances under which he made his great achievements despite the many challenges he faced.

  2. Using extrathermodynamic relationships to model the temperature dependence of Henry's law constants of 209 PCB congeners.

    Science.gov (United States)

    Bamford, Holly A; Poster, Dianne L; Huie, Robert E; Baker, Joel E

    2002-10-15

    Our previous measurements of the temperature dependencies of Henry's law constants of 26 polychlorinated biphenyls (PCBs) showed a well-defined linear relationship between the enthalpy and the entropy of phase change. Within a homologue group, the Henry's law constants converged to a common value at a specific isoequilibrium temperature. We use this relationship to model the temperature dependencies of the Henry's law constants of the remaining PCB congeners. By using experimentally measured Henry's law constants at 11 degrees C for 61 PCB congeners described in this paper combined with the isoequilibrium temperatures from our previous measurements of Henry's law constants of 26 PCB congeners, we have derived an empirical relationship between the enthalpies and the entropies of phase change for these additional PCB congeners. A systematic variation in the enthalpies and entropies of phase change was found to be partially dependent on the chlorine number and substitution patterns on the biphenyl rings, allowing further estimation of the temperature dependence of Henry's law constants for the remaining 122 PCB congeners. The enthalpies of phase change for all 209 PCB congeners ranged between 10 and 169 kJ mol(-1), where the enthalpies of phase change decreased as the number of ortho chlorine substitutions on the biphenyl rings increased within homologue groups. These data are used to predict the temperature dependence of Henry's law constants for all 209 PCB congeners.

  3. Lynching Luther

    DEFF Research Database (Denmark)

    Backe, Hans-Joachim

    2016-01-01

    . The improbabilities of the series, from the docile Ian Reed turning homicidal maniac to the vigilante who needlessly kills a cop, as well as the downright odd moments (such as the hero’s wardrobe of six identical suits), all fall into place if read as the struggles of Luther’s mind to regain its sanity. From...

  4. Lynch Syndrome

    Science.gov (United States)

    ... cancer, kidney cancer, stomach cancer, small intestine cancer, liver cancer, sweat gland cancer (sebaceous carcinoma) and other cancers When to see a doctor If you have concerns about your family history of colon or endometrial cancer, bring it up ...

  5. Lynching Luther

    DEFF Research Database (Denmark)

    Backe, Hans-Joachim

    2016-01-01

    , cerebral detective – two character-types traditionally rather juxtaposed as irreconcilable opposites. In this fashion, the overall story arc meshes together elements from Thomas Harris-style serial killer fiction and intuitive detection in the tradition of George Simenon’s Maigret. Similarly....... The improbabilities of the series, from the docile Ian Reed turning homicidal maniac to the vigilante who needlessly kills a cop, as well as the downright odd moments (such as the hero’s wardrobe of six identical suits), all fall into place if read as the struggles of Luther’s mind to regain its sanity. From...

  6. Analysis and Comparison of the Ideas and Later Influences of Henri Jomini and Carl von Clausewitz

    Science.gov (United States)

    1985-04-01

    INFLUENCES OF HENRI JOiINI AND CARL VON CLAUSEWITZ AUTHOR(S) MAJIOR FRANC[S S. JONES, USAF FACULTYADVISOR DR. DONALD D. CHIIPMAN, SOS/CAE SPNO TCOL...INFLUENCES OF HENRI JOMINI AND CARL VON CLAUSEWITZ 17 COSATI CODES 18. SUBJECT TERMS (Continue on reverse if necessary and Identify by block number) FIELD...GROUP SUB. GR. 19. ABSTRACT (Continue on reuerse if necessary and identify by block number) This paper reviews the lives of Henri Jomini and Carl von Clausewitz . It

  7. Development and validation of an instrument to measure the impact of genetic testing on self-concept in Lynch syndrome

    DEFF Research Database (Denmark)

    Esplen, M J; Stuckless, N; Gallinger, S

    2011-01-01

    with two dimensions identified through factor analysis: stigma/vulnerability and bowel symptom-related anxiety. The scale showed excellent reliability (Cronbach's α = 0.93), good convergent validity by a high correlation with impact of event scale (r(102) = 0.55, p self-esteem scale......Esplen MJ, Stuckless N, Gallinger S, Aronson M, Rothenmund H, Semotiuk K, Stokes J, Way C, Green J, Butler K, Petersen HV, Wong J. Development and validation of an instrument to measure the impact of genetic testing on self-concept in Lynch syndrome. A positive genetic test result may impact...... on a person's self-concept and affect quality of life. The purpose of the study was to develop a self-concept scale to measure such impact for individuals carrying mutations for a heritable colorectal cancer Lynch syndrome (LS). Two distinct phases were involved: Phase 1 generated specific colorectal self...

  8. Lynch Syndrome Associated Colon Adenocarcinoma Resembling Lymphoma on Fluoro-Deoxyglucose-Positron Emission Tomography/Computed Tomography.

    Science.gov (United States)

    Aparici, Carina Mari; Win, Aung Zaw

    2015-01-01

    The patient was a 46-year-old Asian male diagnosed with lynch syndrome associated colon adenocarcinoma in the right ascending colon. A presurgical staging 18-fluoro-deoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) found increased metabolic activity in the cervical, axillary, mediastinal, supraclavicular, para-aortic and mesenteric lymph nodes. This pattern of metastasis was very unusual for lynch syndrome associated colon adenocarcinoma and the involvement of those lymph nodes resembles the pattern of spread of lymphoma. He underwent right hemicolectomy and he was subsequently treated with 12 cycles of folinic acid (leucovorin), fluorouracil (5-FU), irinotecan. A restaging FDG-PET/CT at the end of the chemotherapy showed interval decrease in size and metabolic activity in the affected lymph nodes. FDG-PET/CT is a useful imaging modality in following-up the treatment response in colon adenocarcinoma.

  9. Caracterización molecular de las mutaciones presentes en los genes responsables del síndrome de Lynch

    Directory of Open Access Journals (Sweden)

    Luis Isaza

    2001-04-01

    Full Text Available

    Debido a la alta frecuencia del CCR (cáncer colorrectal en menores de 40 años de nuestra población y sabiendo que su principal origen en jóvenes es genético, especialmente por el síndrome de Lynch,
    la Universidad de Antioquia inició un programa multicéntrico en el
    país, con el fin de determinar las mutaciones presentes en los genes
    hMLH1 y hMSH2 en colombianos con CCR, sospechosos del síndrome
    de Lynch, con el fin de desarrollar programas de aproximación
    diagnóstica tanto para afectados como para sus familiares (1-2.

     

     

  10. Mismatch repair-deficient crypt foci in Lynch syndrome--molecular alterations and association with clinical parameters.

    Directory of Open Access Journals (Sweden)

    Laura Staffa

    Full Text Available Lynch syndrome is caused by germline mutations of DNA mismatch repair (MMR genes, most frequently MLH1 and MSH2. Recently, MMR-deficient crypt foci (MMR-DCF have been identified as a novel lesion which occurs at high frequency in the intestinal mucosa from Lynch syndrome mutation carriers, but very rarely progress to cancer. To shed light on molecular alterations and clinical associations of MMR-DCF, we systematically searched the intestinal mucosa from Lynch syndrome patients for MMR-DCF by immunohistochemistry. The identified lesions were characterised for alterations in microsatellite-bearing genes with proven or suspected role in malignant transformation. We demonstrate that the prevalence of MMR-DCF (mean 0.84 MMR-DCF per 1 cm2 mucosa in the colorectum of Lynch syndrome patients was significantly associated with patients' age, but not with patients' gender. No MMR-DCF were detectable in the mucosa of patients with sporadic MSI-H colorectal cancer (n = 12. Microsatellite instability of at least one tested marker was detected in 89% of the MMR-DCF examined, indicating an immediate onset of microsatellite instability after MMR gene inactivation. Coding microsatellite mutations were most frequent in the genes HT001 (ASTE1 with 33%, followed by AIM2 (17% and BAX (10%. Though MMR deficiency alone appears to be insufficient for malignant transformation, it leads to measurable microsatellite instability even in single MMR-deficient crypts. Our data indicate for the first time that the frequency of MMR-DCF increases with patients' age. Similar patterns of coding microsatellite instability in MMR-DCF and MMR-deficient cancers suggest that certain combinations of coding microsatellite mutations, including mutations of the HT001, AIM2 and BAX gene, may contribute to the progression of MMR-deficient lesions into MMR-deficient cancers.

  11. Interval colon cancer in a Lynch syndrome patient under annual colonoscopic surveillance: a case for advanced imaging techniques?

    Directory of Open Access Journals (Sweden)

    Oxentenko Amy S

    2012-05-01

    Full Text Available Abstract Background Lynch syndrome confers increased risk for various malignancies, including colorectal cancer. Colonoscopic surveillance programs have led to reduced incidence of colorectal cancer and reduced mortality from colorectal cancer. Colonoscopy every 1–2 years beginning at age 20–25, or 10 years earlier than the first diagnosis of colorectal cancer in a family, with annual colonoscopy after age 40, is the recommended management for mutation carriers. Screening programs have reduced colon cancer mortality, but interval cancers may occur. Case presentation We describe a 48-year-old woman with Lynch syndrome who was found to have an adenoma with invasive colorectal cancer within one year after a normal colonoscopy. Conclusion Our patient illustrates two current concepts about Lynch syndrome: 1 adenomas are the cancer precursor and 2 such adenomas may be “aggressive,” in the sense that the adenoma progresses more readily and more rapidly to carcinoma in this setting compared to usual colorectal adenomas. Our patient’s resected tumor invaded only into submucosa and all lymph nodes were negative; in that sense, she represents a success for annual colonoscopic surveillance. Still, this case does raise the question of whether advanced imaging techniques are advisable for surveillance colonoscopy in these high-risk patients.

  12. The Paradox of Being a Wounded Healer: Henri J.M. Nouwen's ...

    African Journals Online (AJOL)

    wounded healer'. It also shows that, in its utilisation by the Swiss psychiatrist Carl Jung, the concept became a metaphor. This insight leads to a discussion of how Henri Nouwen applied the significance of the metaphor to pastoral ministry.

  13. Hiina kompartei pole NLKP-ga võrreldav / Henri Kaselo

    Index Scriptorium Estoniae

    Kaselo, Henri

    2005-01-01

    20.-26. novembril Hiinas Pekingis ja sadamalinnas Tianjinis peetud Euroopa ja Aasia noorte kohtumisest, kus Eestit esindasid Keskerakonna noortekogu esimees Henri Kaselo ja Euroopa Noorte Sotsiaaldemokraatide aseesimees ning Toomas Hendrik Ilvese nõunik Rander Läntsi

  14. The personality of Henry Cavendish a great scientist with extraordinary peculiarities

    CERN Document Server

    McCormmach, Russell

    2014-01-01

    This book explores the 18th century natural philosopher Henry Cavendish, best known for his work in chemistry and physics. It traces aspects of his personality, views and interpretations of him, and explores notions of eccentricity and autism.

  15. Henry E. Hale. Patronal Politics: Eurasian Regime Dynamics in Comparative Perspective

    OpenAIRE

    Thomas F. Remington

    2016-01-01

    Henry E. Hale. Patronal Politics: Eurasian Regime Dynamics in Comparative Perspective. Problems of International Politics. Eds. Keith Darden and Ian Shapiro. New York: Cambridge University Press, 2015. xviii, 542 pp. References. Index. US$39.99, paper.

  16. Dual stereocontrol over the Henry reaction using a light- and heat-triggered organocatalyst

    NARCIS (Netherlands)

    Vlatkovic, Matea; Bernardi, Luca; Otten, Edwin; Feringa, Ben L.

    2014-01-01

    Here we present a novel dynamic organocatalyst, based on a first-generation molecular motor core, able to control the stereochemical outcome of the Henry reaction using both light and heat as external stimuli.

  17. 2008 USGS Lidar: Twelve County, Illinois (Grundy, Kane, McHenry only)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This LiDAR data is within Illinois Department of Transportation districts 1 and 3 covering Grundy, Kane and McHenry counties. The data is updated from its original...

  18. Dual stereocontrol over the Henry reaction using a light- and heat-triggered organocatalyst.

    Science.gov (United States)

    Vlatković, Matea; Bernardi, Luca; Otten, Edwin; Feringa, Ben L

    2014-07-25

    Here we present a novel dynamic organocatalyst, based on a first-generation molecular motor core, able to control the stereochemical outcome of the Henry reaction using both light and heat as external stimuli.

  19. Compilation of Henry's law constants (version 4.0) for water as solvent

    National Research Council Canada - National Science Library

    Sander, R

    2015-01-01

    .... Therefore, it is necessary to understand the distribution between the phases. According to Henry's law, the equilibrium ratio between the abundances in the gas phase and in the aqueous phase is constant for a dilute solution...

  20. Strelku vsjo ravno perevedut. No v kakuju storonu? / Henry Posner ; interv. Eteri Kekelidze

    Index Scriptorium Estoniae

    Posner, Henry

    2006-01-01

    Eesti Raudtee üks erastajaist, RDC juht Henry Posner III meenutab ER erastamist 2001. a., investeeringutest, reeglite muutmisest, Eesti Raudtee müümise põhjustest, Eesti transiidi tulevikust. Diagramm: Eesti Raudtee kasum 1998-2004

  1. NOAA Ship Henry B. Bigelow Underway Meteorological Data, Near Real Time

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA Ship Henry B. Bigelow Underway Meteorological Data (Near Real Time, updated daily) are from the Shipboard Automated Meteorological and Oceanographic System...

  2. Efficient molecular screening of Lynch syndrome by specific 3' promoter methylation of the MLH1 or BRAF mutation in colorectal cancer with high-frequency microsatellite instability.

    Science.gov (United States)

    Nakagawa, Hitoshi; Nagasaka, Takeshi; Cullings, Harry M; Notohara, Kenji; Hoshijima, Naoko; Young, Joanne; Lynch, Henry T; Tanaka, Noriaki; Matsubara, Nagahide

    2009-06-01

    It is sometimes difficult to diagnose Lynch syndrome by the simple but strict clinical criteria, or even by the definitive genetic testing for causative germline mutation of mismatch repair genes. Thus, some practical and efficient screening strategy to select highly possible Lynch syndrome patients is exceedingly desirable. We performed a comprehensive study to evaluate the methylation status of whole MLH1 promoter region by direct bisulfite sequencing of the entire MLH1 promoter regions on Lynch and non-Lynch colorectal cancers (CRCs). Then, we established a convenient assay to detect methylation in key CpG islands responsible for the silencing of MLH1 expression. We studied the methylation status of MLH1 as well as the CpG island methylator phenotype (CIMP) and immunohistochemical analysis of mismatch repair proteins on 16 cases of Lynch CRC and 19 cases of sporadic CRCs with high-frequency microsatellite instability (MSI-H). Sensitivity to detect Lynch syndrome by MLH1 (CCAAT) methylation was 88% and the specificity was 84%. Positive likelihood ratio (PLR) was 5.5 and negative likelihood ratio (NLR) was 0.15. Sensitivity by mutational analysis of BRAF was 100%, specificity was 84%, PLR was 6.3 and NLR was zero. By CIMP analysis; sensitivity was 88%, specificity was 79%, PLR was 4.2, and NLR was 0.16. BRAF mutation or MLH1 methylation analysis combined with MSI testing could be a good alternative to screen Lynch syndrome patients in a cost effective manner. Although the assay for CIMP status also showed acceptable sensitivity and specificity, it may not be practical because of its rather complicated assay.

  3. Initiation of universal tumor screening for Lynch syndrome in colorectal cancer patients as a model for the implementation of genetic information into clinical oncology practice.

    Science.gov (United States)

    Cohen, Stacey A; Laurino, Mercy; Bowen, Deborah J; Upton, Melissa P; Pritchard, Colin; Hisama, Fuki; Jarvik, Gail; Fichera, Alessandro; Sjoding, Britta; Bennett, Robin L; Naylor, Lorraine; Jacobson, Angela; Burke, Wylie; Grady, William M

    2016-02-01

    Lynch syndrome confers a hereditary predisposition to colorectal and other cancers. Universal tumor screening (UTS) for Lynch syndrome is recommended by several professional societies, but the implementation can be complex. This article describes the evaluation, process development, and initiation of Lynch syndrome UTS at a tertiary referral cancer center. A multidisciplinary team developed the new process design. Issues in 5 themes were noted: timing, funding, second-opinion patients, result processing, and the role of genetics providers. A committee approach was used to examine each issue for process-improvement development. The issues related to testing were addressed individually for the successful implementation of UTS at the institutional level. In the conventional-care period, 9 of 30 cases (30%) received Lynch syndrome screening, and 4 cases were referred to medical genetics. During the 6 months following the implementation of UTS, 32 of 44 patients (73%) received Lynch syndrome screening. The 13 unscreened patients all had identified reasons for nonscreening (eg, financial limitations). Ten patients were referred to medical genetics, which identified no new cases of Lynch syndrome, but a low-risk adenomatous polyposis coli (APC) variant was detected in 1 individual. The implementation of effective Lynch syndrome UTS can feasibly alter practice at the institutional level. This experience with the assessment and management of issues relevant to the successful implementation of a new clinical care paradigm based on emerging technology has implications for the uptake of advances across molecular oncology into clinical practice, and this is highly relevant in the current era of rapidly evolving genomic technology. © 2015 American Cancer Society.

  4. 46 CFR 7.55 - Cape Henry, VA to Cape Fear, NC.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Cape Henry, VA to Cape Fear, NC. 7.55 Section 7.55 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC BOUNDARY LINES Atlantic Coast § 7.55 Cape Henry, VA to Cape Fear, NC. (a) A line drawn from Rudee Inlet Jetty Light “2” to...

  5. Restauration de la statue de Henri IV

    Directory of Open Access Journals (Sweden)

    Stéphanie Celle

    2012-04-01

    Full Text Available Cette intervention de conservation du bronze de la statue de Henri IV était la première depuis sa création en 1818 : on héritait de la surface originale de l’œuvre altérée par les vicissitudes du temps et les événements historiques traversés. Le protocole de conservation se voulait respectueux de cette authenticité de la patine et a cherché à en laisser les marques tout en apportant une réponse pour contrer la corrosion active de l’alliage. C’est en conformité aux principes de conservation établis par Cesare Brandi, qu’ont été définis le nettoyage sélectif des surfaces et l’application de couches protectives sur le bronze. Par ailleurs, le moment du chantier est un moment privilégié pour observer un monument et mieux connaître son histoire particulière. Ce chantier nous a permis de redécouvrir deux ensembles de boîtes déposées dans l’antre du cheval dans des situations parfois surprenantes.This conservation treatment for the bronze statue of Henri IV is the first since its creation in 1818. While the original surface of the work remains, it has been altered by natural and human forces; including the weathering of the material from exposure to the elements and damage caused by historic events. The conservation protocol is respectful of this authenticity of the surface patina and the marks of damage due to historical events, while developing a treatment plan to counter the active corrosion of the alloy. In keeping with the principles of conservation established by Cesare Brandi, the treatment program defines the selective cleaning of the surface and the application of several layers of a protective coating on the bronze. In addition, the conservation project is an opportunity to carefully study a monument to better understand its unique history. This project allowed us to rediscover two sets of boxes placed inside the cavity of the horse; an unxpected discovery.

  6. Organocatalytic asymmetric assembly reactions for the syntheses of carbohydrate derivatives by intermolecular Michael-Henry reactions

    Science.gov (United States)

    Uehara, Hisatoshi; Imashiro, Ritsuo; Hernández-Torres, Gloria; Barbas, Carlos F.

    2010-01-01

    Given the significance of carbohydrates in life, medicine, and industry, the development of simple and efficient de novo methods to synthesize carbohydrates are highly desirable. Organocatalytic asymmetric assembly reactions are powerful tools to rapidly construct molecules with stereochemical complexity from simple precursors. Here, we present a simple and robust methodology for the asymmetric synthesis of pyranose derivatives with talo- and manno- configurations from simple achiral precursors through organocatalytic asymmetric intermolecular Michael–Henry reaction sequences. In this process, (tert-butyldimethylsilyloxy)acetaldehyde 1 was successfully utilized in two ways: as a donor in a highly selective anti-Michael reaction and as an acceptor in a consecutive Henry reaction. Varied nitroolefins served as Michael acceptors and varied aldehydes substituted for 1 as Henry acceptors providing for the construction of a wide range of carbohydrates with up to 5 stereocenters. In these reactions, a catalyst-controlled Michael reaction followed by a substrate-controlled Henry reaction provided 3,4-dideoxytalose derivatives 6 in a highly stereoselective manner. The Henry reaction was affected by addition of a simple base such as triethylamine: A complex chiral base was not necessary. 3,4-Dideoxymannose derivatives 7 were produced by simply changing the base from triethylamine to 1,8-diazabicyclo[5.4.0]undec-7-ene. Extension of this methodology to a syn-Michael initiated sequence was also successful. A mechanistic discussion is provided to explain the unusual substrate-induced stereoselectivity of the Henry reaction. PMID:20639468

  7. The head that wears the crown: Henry VIII and traumatic brain injury.

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    Ikram, Muhammad Qaiser; Sajjad, Fazle Hakim; Salardini, Arash

    2016-06-01

    Henry VIII of England is one of the most controversial figures in European history. He was born on 28 June 1491 as the second son of Henry VII and Elizabeth of York and became the heir to the English throne after his elder brother died prematurely. A contradictory picture of Henry's character emerges from history: the young Henry was a vigorous, generous and intelligent king who saw early military and naval successes. In contrast, in his later years he became cruel, petty and tyrannical. His political paranoia and military misjudgements are in direct contrast to his earlier successes and promise. Several hypotheses have been put forward regarding his transformation from a renaissance king to a later medieval tyrant, including endocrinopathies, psychiatric illnesses and traumatic brain injury. In this paper we examine the historical evidence linking the change in Henry's personality and health problems to traumatic brain injury. To our knowledge this is the first systematic neurological study of traumatic brain injury in Henry VIII. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Henry Fleming’s Inner Conflicts in Stephen Crane’s The Red Badge of Courage

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    Bambang Purwanto

    2017-04-01

    Full Text Available Stephen Crane is a famous novelist who puts his characters into the situation of war. One of the famous novels is The Red Badge of Courage in telling about war and psychological effects inside of it. The purpose of this research is finding internal conflicts in Henry Fleming as the main character in the novel. It is also finding the important of victory for Henry Fleming. It is not only the real victory in war but also the victory inside Henry Fleming to all internal conflicts. The methodology of this research is external method in which all references are taken from books and internet sources. Besides that, extrinsic approach is also being used especially about psychology of Henry Fleming. The result shows that Henry Fleming is a young boy who enlists the army because his imagination toward Greek epics. The winning in the Greek battleship makes him for being a hero in Civil War. He gains many conflicts inside of him as a soldier. He feels desperate in the battleship but all activities make him believe that he wants to conquer all his burdens. Finally, Henry Fleming can handle all the problems and he becomes the hero, a dream he wants to achieve.

  9. Syndrome de Lynch: à propos d'un cas et revue de la litterature

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    Bouguenouch, Laila; Samri, Imane; Belhassan, Khadija; Sayel, Hanane; Abbassi, Meriame; Bennis, Sanae; Benajah, Dafr Allah; Ibrahimi, Adil; Amarti, Afaf; Ouldim, Karim

    2016-01-01

    Le syndrome de Lynch, ou cancer colorectal héréditaire sans polypose ou HNPCC (hereditary non-polyposis colorectal cancer), est la forme la plus fréquente de cancer colorectal héréditaire. Il conduit à une augmentation de la susceptibilité à développer des cancers, au premier rang le cancer colorectal, le cancer de l'endomètre chez les femmes, et dans une moindre mesure, d'autres cancers (ovaire, intestin grêle, estomac, voies excrétrices urinaires et hépatobiliaires). Ainsi, le risque cumulé de développer un cancer colorectal ou de l'endomètre à l’âge de 80 ans s’élève respectivement à 20 et 40%. Ces cancers sont caractérisés par leur contexte d'atteinte familiale, leur survenue à un âge précoce, ainsi que par le développement de cancers métachrones chez un même individu. Ce syndrome se transmet de manière autosomique dominante. Les gènes dont l'altération est associée à l'existence d'un syndrome HNPCC appartiennent à la famille des gènes de réparation des mésappariements de l'ADN (DNA mismatch repair ou MMR): MSH2, MLH1 et MSH6 sont impliqués, par ordre décroissant de fréquence, dans respectivement 35%, 25% et 2% des cas. Une surveillance coloscopique et gynécologique est proposée aux personnes porteuses d'une mutation constitutionnelle du gène MSH2, MLH1 ou MSH6. Nous rapportons une des premières observations marocaines d'un syndrome de Lynch dont la mutation constitutionnelle du gène MLH1 a été identifiée chez un des membres de la famille atteint d'un cancer du côlon. Suite à la demande d'autres sujets sains de la même famille, un diagnostic presymptomatique a été effectué conduisant à une stratégie de surveillance adaptée. A travers notre observation nous illustrons le rôle de l'oncogénétique dans la prise en charge des patients cancéreux et de leurs familles. PMID:27642480

  10. Fenomenologiczna post-narracja. Szkic o fenomenologii Henri Maldineya

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    Monika MURAWSKA

    2013-12-01

    Full Text Available The paper attempts to outline the fundamental theses of Henri Maldiney’s new phenomenology. The first part presents the style of Maldiney’s discourse to emphasise its significance. The second outlines a rudimentary concept of subjectivity that can be “drawn” from Maldiney’s texts, and the basic categories of this phenomenology, including the concepts of “event” and “encounter”. The third part shows the complexity of this discourse and reconstructs Maldiney’s descriptions of selected phenomena, such as the Matterhorn and a 12th-century miniature depicting the enthroned Christ. Ultimately, the author of the article tries to demonstrate that Maldiney’s phenomenology focuses not only on the question of “what”, but also “how”. The form of his texts, their dispersion, and purposefully unsystematic construction all become a part of them. Just like a work of art, the form turns out to be inseparable from the content and becomes its very essence.

  11. Temperature dependence of Henry's law constants of metolachlor and diazinon.

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    Feigenbrugel, Valérie; Le Calvé, Stéphane; Mirabel, Philippe

    2004-10-01

    A dynamic system based on the water/air equilibrium at the interface within the length of a microporous tube has been used to determine experimentally the Henry's law constants (HLC) of two pesticides: metolachlor and diazinon. The measurements were conducted over the temperature range 283-301 K. At 293 K, HLCs values are (42.6+/-2.8) x 10(3) (in units of M atm(-1)) for metolachlor and (3.0+/-0.3)x10(3) for diazinon. The obtained data were used to derive the following Arrhenius expressions: HLC=(3.0+/-0.4) x 10(-11) exp((10,200+/-1,000)/T) for metolachlor and (7.2+/-0.5) x 10(-15) exp((11,900+/-700)/T) for diazinon. At a cumulus cloud temperature of 283 K, the fractions of metolachlor and diazinon in the atmospheric aqueous phase are about 57% and 11% respectively. In order to evaluate the impact of a cloud on the atmospheric chemistry of both studied pesticides, we compare also their atmospheric lifetimes under clear sky (tau(gas)), and cloudy conditions (tau(multiphase)). The calculated multiphase lifetimes (in units of hours) are significantly lower than those in gas phase at a cumulus temperature of 283 K (in parentheses): metolachlor, 0.4 (2.9); diazinon, 1.9 (5.0).

  12. Using an internal standard method to determine Henry's law constants.

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    Ji, Chang; Evans, Emily M

    2007-02-01

    An internal standard method is developed for the measurement of thermodynamic Henry's law constants (H). In this method, a mixture of the analytes and an internal standard is prepared and used to make a standard solution (organic solvent) and a dilute aqueous solution. Both the standard solution and the headspace samples above the aqueous solution at partitioning equilibrium in closed containers are subject to gas chromatographic (GC) analysis. Subsequently, the values of H for the analytes can be calculated from the known H of the internal standard and the GC peak-area ratios. Only approximate values of the concentrations of the compounds, the GC injection volumes, and the vapor-phase to liquid-phase volume ratios in the closed containers are needed in this approach. The method works particularly well for compounds that are highly soluble in water or that have low vapor pressures. Experimentally determined values of H are reported for some low-molecular-weight aldehydes, ketones, and nitriles, and their temperature dependencies are examined. The results also are compared with literature values. The applicability of this new approach is limited to compounds that have dimensionless H on the order of 10(-3) or less.

  13. A citation analysis of Henri Tajfel's work on intergroup relations.

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    Dumont, Kitty; Louw, Johann

    2009-02-01

    The late Henri Tajfel (1919-1982) is one of the central figures who shaped the development of post-war European social psychology. His contributions range from the establishment of an infrastructure for a European social psychology, and the start of a new intellectual movement within social psychology, to the formulation of a set of concepts addressing intergroup relations that were finally integrated into Social Identity Theory. The present study provides an empirical examination of Tajfel's contribution to intergroup research over the last 30 years via a citation analysis of five journals: the Journal of Personality and Social Psychology, the British Journal of Social Psychology, the European Journal of Social Psychology, the South African Journal of Psychology, and the German Journal of Social Psychology (Zeitschrift für Sozialpsychologie). The results indicate that Tajfel's work on intergroup relations is increasingly cited, especially since the 1990s, and the international recognition of his work is substantial. Three possible reasons for the recognition his work still enjoys are proposed: its potential to generate theoretical and empirical controversies; its explanatory power; and the extent to which his work is used as a referential framework.

  14. Henry Ingersoll Bowditch and Oliver Wendell Holmes: stethoscopists and reformers.

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    Felts, John H

    2002-01-01

    Two Bostonians, Henry Ingersoll Bowditch (1808-1892) and Oliver Wendell Holmes (1809-1894), went to Paris for advanced medical training and came home ardent disciples of Pierre Charles Alexandre Louis, leader of the French school that derived its eminence from expert auscultation and careful correlation of bedside and autopsy findings. Both Bowditch and Holmes became leaders in 19th-century American medicine. Bowditch, a successful practitioner and prolific medical writer, wrote the first important American text on physical examination and became our first specialist in pulmonary disease. He pioneered in the public health movement, was a charter member and later president of the American Medical Association, and was an abolitionist and an advocate for equal rights for women in medicine. Holmes left practice to become a medical educator. As Dean of Harvard Medical School, he tried unsuccessfully to admit white women and free black men to the school. Although his greatest fame came as a man of letters, Holmes considered himself first a physician and medical educator, and was justifiably proud of his definitive study, "The Contagiousness of Puerperal Fever" (1843). Today, Bowditch and Holmes are little appreciated as pioneers and reformers, but we remain in debt to them both.

  15. Genetic Analysis of the Henry Mountains Bison Herd.

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    Dustin H Ranglack

    Full Text Available Wild American plains bison (Bison bison populations virtually disappeared in the late 1800s, with some remnant animals retained in what would become Yellowstone National Park and on private ranches. Some of these private bison were intentionally crossbred with cattle for commercial purposes. This forced hybridization resulted in both mitochondrial and nuclear introgression of cattle genes into some of the extant bison genome. As the private populations grew, excess animals, along with their history of cattle genetics, provided founders for newly established public bison populations. Of the US public bison herds, only those in Yellowstone and Wind Cave National Parks (YNP and WCNP appear to be free of detectable levels of cattle introgression. However, a small free-ranging population (~350 animals exists on public land, along with domestic cattle, in the Henry Mountains (HM of southern Utah. This isolated bison herd originated from a founder group translocated from YNP in the 1940s. Using genetic samples from 129 individuals, we examined the genetic status of the HM population and found no evidence of mitochondrial or nuclear introgression of cattle genes. This new information confirms it is highly unlikely for free-living bison to crossbreed with cattle, and this disease-free HM bison herd is valuable for the long-term conservation of the species. This bison herd is a subpopulation of the YNP/WCNP/HM metapopulation, within which it can contribute significantly to national efforts to restore the American plains bison to more of its native range.

  16. Genetic Analysis of the Henry Mountains Bison Herd.

    Science.gov (United States)

    Ranglack, Dustin H; Dobson, Lauren K; du Toit, Johan T; Derr, James

    2015-01-01

    Wild American plains bison (Bison bison) populations virtually disappeared in the late 1800s, with some remnant animals retained in what would become Yellowstone National Park and on private ranches. Some of these private bison were intentionally crossbred with cattle for commercial purposes. This forced hybridization resulted in both mitochondrial and nuclear introgression of cattle genes into some of the extant bison genome. As the private populations grew, excess animals, along with their history of cattle genetics, provided founders for newly established public bison populations. Of the US public bison herds, only those in Yellowstone and Wind Cave National Parks (YNP and WCNP) appear to be free of detectable levels of cattle introgression. However, a small free-ranging population (~350 animals) exists on public land, along with domestic cattle, in the Henry Mountains (HM) of southern Utah. This isolated bison herd originated from a founder group translocated from YNP in the 1940s. Using genetic samples from 129 individuals, we examined the genetic status of the HM population and found no evidence of mitochondrial or nuclear introgression of cattle genes. This new information confirms it is highly unlikely for free-living bison to crossbreed with cattle, and this disease-free HM bison herd is valuable for the long-term conservation of the species. This bison herd is a subpopulation of the YNP/WCNP/HM metapopulation, within which it can contribute significantly to national efforts to restore the American plains bison to more of its native range.

  17. Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications

    Science.gov (United States)

    Lynch, HT; Lynch, PM; Lanspa, SJ; Snyder, CL; Lynch, JF; Boland, CR

    2010-01-01

    More than one million patients will manifest colorectal cancer (CRC) this year of which, conservatively, approximately 3% (~30,700 cases) will have Lynch syndrome (LS), the most common hereditary CRC predisposing syndrome. Each case belongs to a family with clinical needs that require genetic counseling, DNA testing for mismatch repair genes (most frequently MLH1 or MSH2) and screening for CRC. Colonoscopy is mandated, given CRC’s proximal occurrence (70–80% proximal to the splenic flexure). Due to its early age of onset (average 45 years of age), colonoscopy needs to start by age 25, and because of its accelerated carcinogenesis, it should be repeated every 1 to 2 years through age 40 and then annually thereafter. Should CRC occur, subtotal colectomy may be necessary, given the marked frequency of synchronous and metachronous CRC. Because 40–60% of female patients will manifest endometrial cancer, tailored management is essential. Additional extracolonic cancers include ovary, stomach, small bowel, pancreas, hepatobiliary tract, upper uroepithelial tract, brain (Turcot variant) and sebaceous adenomas/carcinomas (Muir-Torre variant). LS explains only 10–25% of familial CRC. PMID:19659756

  18. Rare mutations in RINT1 predispose carriers to breast and Lynch syndrome-spectrum cancers.

    Science.gov (United States)

    Park, Daniel J; Tao, Kayoko; Le Calvez-Kelm, Florence; Nguyen-Dumont, Tu; Robinot, Nivonirina; Hammet, Fleur; Odefrey, Fabrice; Tsimiklis, Helen; Teo, Zhi L; Thingholm, Louise B; Young, Erin L; Voegele, Catherine; Lonie, Andrew; Pope, Bernard J; Roane, Terrell C; Bell, Russell; Hu, Hao; Shankaracharya; Huff, Chad D; Ellis, Jonathan; Li, Jun; Makunin, Igor V; John, Esther M; Andrulis, Irene L; Terry, Mary B; Daly, Mary; Buys, Saundra S; Snyder, Carrie; Lynch, Henry T; Devilee, Peter; Giles, Graham G; Hopper, John L; Feng, Bing-Jian; Lesueur, Fabienne; Tavtigian, Sean V; Southey, Melissa C; Goldgar, David E

    2014-07-01

    Approximately half of the familial aggregation of breast cancer remains unexplained. A multiple-case breast cancer family exome-sequencing study identified three likely pathogenic mutations in RINT1 (NM_021930.4) not present in public sequencing databases: RINT1 c.343C>T (p.Q115X), c.1132_1134del (p.M378del), and c.1207G>T (p.D403Y). On the basis of this finding, a population-based case-control mutation-screening study was conducted that identified 29 carriers of rare (minor allele frequency Lynch syndrome-spectrum cancers [standardized incidence ratio (SIR), 3.35; 95% CI, 1.7-6.0; P = 0.005], particularly for relatives diagnosed with cancer under the age of 60 years (SIR, 10.9; 95% CI, 4.7-21; P = 0.0003). The work described in this study adds RINT1 to the growing list of genes in which rare sequence variants are associated with intermediate levels of breast cancer risk. Given that RINT1 is also associated with a spectrum of cancers with mismatch repair defects, these findings have clinical applications and raise interesting biological questions. ©2014 American Association for Cancer Research.

  19. Spectrum of mismatch repair gene mutations and clinical presentation of Hispanic individuals with Lynch syndrome.

    Science.gov (United States)

    Sunga, Annette Y; Ricker, Charité; Espenschied, Carin R; Castillo, Danielle; Melas, Marilena; Herzog, Josef; Bannon, Sarah; Cruz-Correa, Marcia; Lynch, Patrick; Solomon, Ilana; Gruber, Stephen B; Weitzel, Jeffrey N

    2017-04-01

    Lynch syndrome (LS), the most common hereditary colorectal cancer syndrome, is caused by mismatch repair (MMR) gene mutations. However, data about MMR mutations in Hispanics are limited. This study aims to describe the spectrum of MMR mutations in Hispanics with LS and explore ancestral origins. This case series involved an IRB-approved retrospective chart review of self-identified Hispanic patients (n = 397) seen for genetic cancer risk assessment at four collaborating academic institutions in California, Texas, and Puerto Rico who were evaluated by MMR genotyping and/or tumor analysis. A literature review was conducted for all mutations identified. Of those who underwent clinical genetic testing (n = 176), 71 had MMR gene mutations. Nine mutations were observed more than once. One third (3/9) of recurrent mutations and two additional mutations (seen only once) were previously reported in Spain, confirming the influence of Spanish ancestry on MMR mutations in Hispanic populations. The recurrent mutations identified (n = 9) included both previously reported mutations as well as unique mutations not in the literature. This is the largest report of Hispanic MMR mutations in North America; however, a larger sample and haplotype analyses are needed to better understand recurrent MMR mutations in Hispanic populations. Copyright © 2017. Published by Elsevier Inc.

  20. [Pancreatic-duodenectomy for invasive colon cancer in a patient with Lynch syndrome. Case report.].

    Science.gov (United States)

    Vergara-Fernández, O; Zamora-Valdés, D; Rodríguez-Zentner, H A; Tapia, H; Sánchez-Fernández, N; Gamboa-Domínguez, A; Medina-Franco, H; Chan-Núñez, C

    2009-01-01

    Despite the screening efforts in the general population and particularly in families with hereditary colon cancer, locally advanced colon cancer remains a common clinical problem. In block resection is considered mainstay therapy in these patients. The aim of this report is to present a case of right-sided colon cancer with a medullar phenotype invading the duodenum treated through in block resection. A case of a 54-year-old male with a family history of colon and pancreatic cancer with lower gastrointestinal tract bleeding is presented. Colonoscopy and computed tomography scan showed a tumor in the colonic hepatic flexure invading the duodenum. The patient underwent an in block resection of the right colon, duodenum, pancreas and antrum. The histopathological study showed a T4N0M0 adenocarcinoma invading the duodenum, pancreas and antrum with negative margins. His postoperative evolution was complicated with a pancreatic fistula, which resolved with conservative measures. In conclusion, in block resection is the treatment of choice for locally advanced colon cancer with invasion to duodenum and pancreas and should be performed in high-volume centers familiar with this type of procedures. Key words: pancreaticoduodenectomy, colon cancer, Lynch syndrome, pancreas, surgery, Mexico.

  1. Prevalence of Lynch Syndrome among Patients with Newly Diagnosed Endometrial Cancers

    Science.gov (United States)

    Egoavil, Cecilia; Alenda, Cristina; Castillejo, Adela; Paya, Artemio; Peiro, Gloria; Sánchez-Heras, Ana-Beatriz; Castillejo, Maria-Isabel; Rojas, Estefanía; Barberá, Víctor-Manuel; Cigüenza, Sonia; Lopez, Jose-Antonio; Piñero, Oscar; Román, Maria-Jose; Martínez-Escoriza, Juan-Carlos; Guarinos, Carla; Perez-Carbonell, Lucia; Aranda, Francisco-Ignacio; Soto, Jose-Luis

    2013-01-01

    Background Lynch syndrome (LS) is a hereditary condition that increases the risk for endometrial and other cancers. The identification of endometrial cancer (EC) patients with LS has the potential to influence life-saving interventions. We aimed to study the prevalence of LS among EC patients in our population. Methods Universal screening for LS was applied for a consecutive series EC. Tumor testing using microsatellite instability (MSI), immunohistochemistry (IHC) for mismatch-repair (MMR) protein expression and MLH1-methylation analysis, when required, was used to select LS-suspicious cases. Sequencing of corresponding MMR genes was performed. Results One hundred and seventy-three EC (average age, 63 years) were screened. Sixty-one patients (35%) had abnormal IHC or MSI results. After MLH1 methylation analysis, 27 cases were considered suspicious of LS. From these, 22 were contacted and referred for genetic counseling. Nineteen pursued genetic testing and eight were diagnosed of LS. Mutations were more frequent in younger patients (<50 yrs). Three cases had either intact IHC or MSS and reinforce the need of implement the EC screening with both techniques. Conclusion The prevalence of LS among EC patients was 4.6% (8/173); with a predictive frequency of 6.6% in the Spanish population. Universal screening of EC for LS is recommended. PMID:24244552

  2. Prevalence of Lynch syndrome among patients with newly diagnosed endometrial cancers.

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    Cecilia Egoavil

    Full Text Available Lynch syndrome (LS is a hereditary condition that increases the risk for endometrial and other cancers. The identification of endometrial cancer (EC patients with LS has the potential to influence life-saving interventions. We aimed to study the prevalence of LS among EC patients in our population.Universal screening for LS was applied for a consecutive series EC. Tumor testing using microsatellite instability (MSI, immunohistochemistry (IHC for mismatch-repair (MMR protein expression and MLH1-methylation analysis, when required, was used to select LS-suspicious cases. Sequencing of corresponding MMR genes was performed.One hundred and seventy-three EC (average age, 63 years were screened. Sixty-one patients (35% had abnormal IHC or MSI results. After MLH1 methylation analysis, 27 cases were considered suspicious of LS. From these, 22 were contacted and referred for genetic counseling. Nineteen pursued genetic testing and eight were diagnosed of LS. Mutations were more frequent in younger patients (<50 yrs. Three cases had either intact IHC or MSS and reinforce the need of implement the EC screening with both techniques.The prevalence of LS among EC patients was 4.6% (8/173; with a predictive frequency of 6.6% in the Spanish population. Universal screening of EC for LS is recommended.

  3. Gennemhullede myter – Jessica Lynch og den amerikanske ‘tilfangetagelses-fortælling’

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    Rikke Schubart

    2005-09-01

    Full Text Available I krig og kærlighed gælder alle kneb, siger man. Artiklen undersøger, hvorledes det amerikanske militær søgte at udnytte tilfangetagelsen af menig Jessica Lynch under Irakkrigen den 23. marts 2003 til at skabe en myte om en kvindelig soldat, der blev taget til fange, mishandlet og befriet under dramatiske omstændigheder. Forsøget mislykkedes, da journalister demonterede historien og viste, at de amerikanske soldater bl.a. brugte blanke skud ved angrebet på et irakisk hospital, at Jessica ikke som påstået havde skudsår, og at hun ikke var blevet mishandlet og voldtaget, men behandlet godt. Efter befrielsen blev historien et ek- sempel på magtens brug og misbrug af myter, og på mytens narrative funktion i kulturen. Artiklen argumenterer for, at myten kun kan bruges i samspil med omgivelserne, og at Pentagon desuden overså, hvilken myte Jessica passede ind i: Den amerikanske ‘tilfangetagelses-fortæl- ling’.

  4. Las cartas privadas de Wanda Morla Lynch: entre género discursivo y fuente documental

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    Carolina Miranda

    2016-11-01

    Full Text Available This essay is an approach to the private letters of Wanda Morla Lynch, a Chilean woman from the early XX century. This approach considers the epistolary genre as a complex and often contradictory genre, propitious to describe a feminine intimacy, feelings and subjectivity, due to the relationship of complicity between the letters and the historically acquired status of subordination, imposed by the patriarchal society. In this sense, this epistolary corpus will allow us establishing a characterization of these private letters as they have a formal/discursive singularity in relation to other genres that conform the corpus of autobiographic writing, as well as exploring and rescuing the value of those letters as a documentary source as they unveil the voice of a woman, who was a privileged witness of the changes that took place in Paris in the 1920’s, epicenter of the modernist avant-garde of the time. Regarding this last consideration, Wanda Morla Lynch’s letters can be also described as a “journey diary” (historically known as a particularly masculine experience, giving us the possibility of reading these letters as a secretly transgressor gesture towards the social conventions of an era.

  5. Suspected Lynch syndrome associated MSH6 variants: A functional assay to determine their pathogenicity.

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    Hellen Houlleberghs

    2017-05-01

    Full Text Available Lynch syndrome (LS is a hereditary cancer predisposition caused by inactivating mutations in DNA mismatch repair (MMR genes. Mutations in the MSH6 DNA MMR gene account for approximately 18% of LS cases. Many LS-associated sequence variants are nonsense and frameshift mutations that clearly abrogate MMR activity. However, missense mutations whose functional implications are unclear are also frequently seen in suspected-LS patients. To conclusively diagnose LS and enroll patients in appropriate surveillance programs to reduce morbidity as well as mortality, the functional consequences of these variants of uncertain clinical significance (VUS must be defined. We present an oligonucleotide-directed mutagenesis screen for the identification of pathogenic MSH6 VUS. In the screen, the MSH6 variant of interest is introduced into mouse embryonic stem cells by site-directed mutagenesis. Subsequent selection for MMR-deficient cells using the DNA damaging agent 6-thioguanine (6TG allows the identification of MMR abrogating VUS because solely MMR-deficient cells survive 6TG exposure. We demonstrate the efficacy of the genetic screen, investigate the phenotype of 26 MSH6 VUS and compare our screening results to clinical data from suspected-LS patients carrying these variant alleles.

  6. Novel Mutations in MLH1 and MSH2 Genes in Mexican Patients with Lynch Syndrome

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    Jose Miguel Moreno-Ortiz

    2016-01-01

    Full Text Available Background. Lynch Syndrome (LS is characterized by germline mutations in the DNA mismatch repair (MMR genes MLH1, MSH2, MSH6, and PMS2. This syndrome is inherited in an autosomal dominant pattern and is characterized by early onset colorectal cancer (CRC and extracolonic tumors. The aim of this study was to identify mutations in MMR genes in three Mexican patients with LS. Methods. Immunohistochemical analysis was performed as a prescreening method to identify absent protein expression. PCR, Denaturing High Performance Liquid Chromatography (dHPLC, and Sanger sequencing complemented the analysis. Results. Two samples showed the absence of nuclear staining for MLH1 and one sample showed loss of nuclear staining for MSH2. The mutations found in MLH1 gene were c.2103+1G>C in intron 18 and compound heterozygous mutants c.1852_1854delAAG (p.K618del and c.1852_1853delinsGC (p.K618A in exon 16. In the MSH2 gene, we identified mutation c.638dupT (p.L213fs in exon 3. Conclusions. This is the first report of mutations in MMR genes in Mexican patients with LS and these appear to be novel.

  7. Molecular profile of the Lynch Syndrome in the Republic of Macedonia

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    Marija Hiljadnikova-Bajro

    2012-12-01

    Full Text Available The most frequent type of hereditary colorectal cancer, the one occurring in the setting of the Lynch syndrome (LS is considered a phenotypic manifestation of a germline defect in the mismatch repair mechanism i.e. in the MLH1, MSH2, MSH6 or PMS2 gene. Aiming towards establishment of a standardized protocol involving molecular analyses for diagnosis of this syndrome and developing a unique national register of families with hereditary colorectal cancer syndromes in the Republic of Macedonia, we began a prospective study to reveal the genetic defects among Macedonian patients with colorectal cancer (CRC and identifying families with hereditary CRC. A total of 53 patients fulfilling the revised Bethesda criteria for MSI-genetic testing were compared to 350 patients with sporadic CRC. The results reveal significant differences in age at diagnosis (p=0.03, involvement of microsatellite instability (pG nonsense mutation with a possible founder effect in the Macedonian population, the MLH1 ex.3-12 deletion, as well as the c.244A>G mutation, IVS14- 19A>G and IVS4+65A>C changes in MLH1 without confirmed pathological significance. The observed high frequency (87.5% of the Ile219Val (c.655A>G variant in MLH1 among the LS suspects prompts further analyses to evaluate its involvement in the development of hereditary CRC by itself or as a risk modifying factor among the patients from the Republic of Macedonia.

  8. Recognition of Lynch Syndrome Amongst Newly Diagnosed Colorectal Cancers at St. Paul’s Hospital

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    Steven Pi

    2017-01-01

    Full Text Available Background. Lynch Syndrome (LS is the most common cause of inherited colorectal cancer (CRC. In British Columbia, most centres still use clinical criteria (Amsterdam II, Revised Bethesda, or the BC Cancer Agency’s criteria to determine who should undergo further first-line testing in the form of microsatellite instability or immunohistochemistry staining. Given the limitations with this strategy, LS is thought to be underrecognized. Objective. To investigate whether LS is truly underrecognized when compared to the reported prevalence. Methods. A retrospective chart review of all CRC cases diagnosed at St. Paul’s Hospital from 2010 to 2013 was conducted. Results. 246 patients met inclusion criteria. 76% (83/109 with a family history of malignancy were unable to recall the specific malignancy or age of diagnosis. 18% (43/235 were only asked about a history of gastrointestinal related malignancy and 26% (65/246 met at least one of the three criteria but only 21% (13/63 received further investigation. Only 1.6% (4/246 had LS compared to the reported prevalence of 2–5% of all CRC cases. Conclusion. This data supports our hypothesis that LS is underrecognized. Issues at the patient, physician, and systems level need to be evaluated to determine where the limitations preventing appropriate testing are occurring.

  9. Henry Daniel Cogswell, DDS (1819-1900): a temperance advocate, philanthropist and builder of ice-water fountains.

    Science.gov (United States)

    Christen, A G; Theobald, M S; Christen, J A

    1999-07-01

    Henry Daniel Cogswell (Fig. 1), the second of five children, was born in Tolland, Connecticut on March 3, 1819. His father, George Washington Cogswell, was a general carpenter, architect and builder of moderate circumstances. In 1827, when Henry was eight, his mother died. The following year, Henry's father moved to Orwell, (Oswego County) New York, in hopes of improving his financial condition. Henry was left behind in the care of his paternal grandfather, who died several months later, leaving the 10-year old boy, stranded and forced to rely upon his own resources. (In those times, when families were separated, individual members had limited means of locating one another.)

  10. Caracterização clínica e histomolecular de tumores de pacientes em risco para síndrome de Lynch

    OpenAIRE

    Silvia Liliana Cossio

    2009-01-01

    A síndrome de Lynch, também chamada HNPCC (Hereditary Non-Polyposis Colorectal Cancer), é uma doença com padrão de herança autossômica dominante onde se observam múltiplas gerações afetadas por câncer colorretal (CCR) em idade precoce (por volta dos 45 anos). Alem disso, pacientes com síndrome de Lynch possuem um risco aumentado de desenvolver múltiplos tumores sincrônicos ou metacrônicos. O segundo tipo de câncer mais freqüente na síndrome de Lynch é o câncer de endométrio (CE), que também é...

  11. Heredity of chronic bronchitis

    DEFF Research Database (Denmark)

    Meteran, Howraman; Backer, Vibeke; Kyvik, Kirsten Ohm

    2014-01-01

    -specific concordance rates and heritability of chronic bronchitis. The response rate was 75%. RESULTS: The prevalence of chronic bronchitis was 9.3% among men and 8.5% among women. The concordance rate for chronic bronchitis was higher in monozygotic twins than in dizygotic twins among women; 0.30 vs. 0...

  12. Heredity for triangular operators

    Directory of Open Access Journals (Sweden)

    Henry Crawford Rhaly Jr.

    2013-12-01

    Full Text Available A proof is given that if the lower triangular infinite matrix $T$ acts boundedly on $\\ell^2$ and U is the unilateral shift, the sequence $(U^*^nTU^n$ inherits from $T$ the following properties: posinormality, dominance, $M$-hyponormality, hyponormality, normality, compactness, and noncompactness.  Also, it is demonstrated that the upper triangular matrix $T^*$ is dominant if and only if $T$ is a diagonal matrix.

  13. Considerations and management of a patient with three metachronous cancers in association with Lynch syndrome and ileal Crohn’s disease: A case report

    Directory of Open Access Journals (Sweden)

    Kaleb Lourensz

    2015-01-01

    Conclusion: The surgical treatment of patients with Lynch syndrome requires a sound knowledge of the possible neoplastic conditions that can arise in the syndrome. Early detection is paramount, either by implementation of evidence based surveillance programs or at least by a heightened clinical awareness of the features of this disease. Ideally this will result in both reduced surgical morbidity and improved oncologic outcome. Furthermore, the medical treatment of Crohn’s disease in a patient with tumors arising from Lynch syndrome must be undertaken with at least a consideration of the possibility that the use of immunosuppressive medication might increase the risk of cancer recurrence.

  14. Recommendations from the EGAPP Working Group: genetic testing strategies in newly diagnosed individuals with colorectal cancer aimed at reducing morbidity and mortality from Lynch syndrome in relatives.

    Science.gov (United States)

    2009-01-01

    The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group found sufficient evidence to recommend offering genetic testing for Lynch syndrome to individuals with newly diagnosed colorectal cancer to reduce morbidity and mortality in relatives. We found insufficient evidence to recommend a specific genetic testing strategy among the several examined. Genetic testing to detect Lynch syndrome in individuals with newly diagnosed colorectal cancer (CRC) is proposed as a strategy to reduce CRC morbidity and mortality in their relatives (see Clinical Considerations section for definition of Lynch syndrome). The EGAPP Working Group (EWG) constructed a chain of evidence that linked genetic testing for Lynch syndrome in patients with newly diagnosed CRC with improved health outcomes in their relatives. We found that assessing patients who have newly diagnosed CRC with a series of genetic tests could lead to the identification of Lynch syndrome. Relatives of patients with Lynch syndrome could then be offered genetic testing, and, where indicated, colorectal, and possibly endometrial, cancer surveillance, with the expectation of improved health outcome. The EWG concluded that there is moderate certainty that such a testing strategy would provide moderate population benefit. The EWG found adequate evidence to conclude that the analytic sensitivity and specificity for preliminary and diagnostic tests were high. After accounting for the specific technologies and numbers of markers used, the EWG found at least adequate evidence to describe the clinical sensitivity and specificity for three preliminary tests, and for four selected testing strategies. These measures of clinical validity varied with each test and each strategy (see Clinical Considerations section). The EWG found adequate evidence for testing uptake rates, adherence to recommended surveillance activities, number of relatives approachable, harms associated with additional follow-up, and

  15. A TEST OF GRAHAM'S AND LYNCH'S STOCK SCREENING CRITERIA ON SHARES TRADED ON THE INDONESIAN STOCK EXCHANGE (IDX

    Directory of Open Access Journals (Sweden)

    Dwi Kartikasari

    2016-01-01

    Full Text Available Benjamin Graham and Peter Lynch listed criteria for screening stocks, which investors could use to identify undervalued stocks that would outperform the market. Numerous tests have been conducted in the United States and other countries, but not yet in Indonesia. Thus, the author aims to test the applicability of Graham’s and Lynch’s formulation on shares traded on the Indonesian Stock Exchange (IDX by screening stocks that meet the various sets of Graham's and Lynch's criteria and then measuring the performance of the portfolios over the years from 2010 to 2014. The author uses a simple linear regression to measure the performance of the portfolios against the IDX Composite (IHSG. The author discovered that investors who used the combined criteria of Lynch earned positive risk-adjusted returns, of 28.81 percent per year in 2010-2012 and 27.33 percent per year in 2012-2014. While investors who used a combination of two of Graham’s criteria obtained significant risk-adjusted returns of 47.55 percent annually in 2010-2012 and 5.92 percent annually in 2012-2014. However, investors who implemented a combination of three of Graham’s criteria did not earn positive risk-adjusted returns consistently during the research period. The increasingly complex criteria do not improve the performance of the portfolios, because when more criteria are used, less and less stocks can meet the criteria, hence the portfolios become more volatile and investors do not enjoy the benefits from diversification.

  16. A frame-shift mutation of PMS2 is a widespread cause of Lynch syndrome

    DEFF Research Database (Denmark)

    Clendenning, Mark; Senter, Leigha; Hampel, Heather

    2008-01-01

    are caused by PMS2. This disparity is primarily due to complications in the study of this gene caused by interference from pseudogene sequences. METHODS: Using a recently developed method for detecting PMS2 specific mutations, we have screened 99 patients who are likely candidates for PMS2 mutations based...... and Swedish ancestry. We estimate that there are >10,000 carriers of this mutation in the United States alone. The identification of both the mutation and the common haplotype in one Swedish control sample (n = 225), along with evidence that Lynch syndrome associated cancers are rarer than expected...

  17. Biochemical characterization of MLH3 missense mutations does not reveal an apparent role of MLH3 in Lynch syndrome

    DEFF Research Database (Denmark)

    Ou, Jianghua; Rasmussen, Merete; Westers, Helga

    2009-01-01

    for eight of these MLH3 UVs identified in suspected Lynch syndrome patients, we performed several biochemical tests. We determined the protein expression and stability, protein localization and interaction of the mutant MLH3 proteins with wildtype MLH1. All eight MLH3 UVs gave protein expression levels...... comparable with wildtype MLH3. Furthermore, the UV-containing proteins, in contrast to previous studies, were all localized normally in the nucleus and they interacted normally with wildtype MLH1. Our different biochemical assays yielded no evidence that the eight MLH3 UVs tested are the cause of hereditary...

  18. Iconografía, música y narración en Wild at Heart, de David Lynch

    OpenAIRE

    García Escrivá, Vicente

    2011-01-01

    El análisis del texto fílmico Corazón Salvaje (Wild at Heart, David Lynch, EEUU, 1990) permite localizar toda una serie de rasgos característicos de la narrativa y la estética cinematográfica posmoderna. Por un lado, el film presenta una notable descomposición narrativa, lo que se traduce en una sucesión de escenas un tanto inconexas, a modo de cuadros intensos pero poco trabados. Asimismo, en la película se produce una suerte de hibridación de géneros, aglutinados por un tono general de paro...

  19. Risk of colorectal and endometrial cancers in EPCAM deletion-positive Lynch syndrome: a cohort study.

    Science.gov (United States)

    Kempers, Marlies J E; Kuiper, Roland P; Ockeloen, Charlotte W; Chappuis, Pierre O; Hutter, Pierre; Rahner, Nils; Schackert, Hans K; Steinke, Verena; Holinski-Feder, Elke; Morak, Monika; Kloor, Matthias; Büttner, Reinhard; Verwiel, Eugene T P; van Krieken, J Han; Nagtegaal, Iris D; Goossens, Monique; van der Post, Rachel S; Niessen, Renée C; Sijmons, Rolf H; Kluijt, Irma; Hogervorst, Frans B L; Leter, Edward M; Gille, Johan J P; Aalfs, Cora M; Redeker, Egbert J W; Hes, Frederik J; Tops, Carli M J; van Nesselrooij, Bernadette P M; van Gijn, Marielle E; Gómez García, Encarna B; Eccles, Diana M; Bunyan, David J; Syngal, Sapna; Stoffel, Elena M; Culver, Julie O; Palomares, Melanie R; Graham, Tracy; Velsher, Lea; Papp, Janos; Oláh, Edith; Chan, Tsun L; Leung, Suet Y; van Kessel, Ad Geurts; Kiemeney, Lambertus A L M; Hoogerbrugge, Nicoline; Ligtenberg, Marjolijn J L

    2011-01-01

    Lynch syndrome is caused by germline mutations in MSH2, MLH1, MSH6, and PMS2 mismatch-repair genes and leads to a high risk of colorectal and endometrial cancer. We previously showed that constitutional 3' end deletions of EPCAM can cause Lynch syndrome through epigenetic silencing of MSH2 in EPCAM-expressing tissues, resulting in tissue-specific MSH2 deficiency. We aim to establish the risk of cancer associated with such EPCAM deletions. We obtained clinical data for 194 carriers of a 3' end EPCAM deletion from 41 families known to us at the Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands and compared cancer risk with data from a previously described cohort of 473 carriers from 91 families with mutations in MLH1, MSH2, MSH6, or a combined EPCAM-MSH2 deletion. 93 of the 194 EPCAM deletion carriers were diagnosed with colorectal cancer; three of the 92 women with EPCAM deletions were diagnosed with endometrial cancer. Carriers of an EPCAM deletion had a 75% (95% CI 65-85) cumulative risk of colorectal cancer before the age of 70 years (mean age at diagnosis 43 years [SD 12]), which did not differ significantly from that of carriers of combined EPCAM-MSH2 deletion (69% [95% CI 47-91], p=0·8609) or mutations in MSH2 (77% [64-90], p=0·5892) or MLH1 (79% [68-90], p=0·5492), but was higher than noted for carriers of MSH6 mutation (50% [38-62], p<0·0001). By contrast, women with EPCAM deletions had a 12% [0-27] cumulative risk of endometrial cancer, which was lower than was that noted for carriers of a combined EPCAM-MSH2 deletion (55% [20-90], p<0·0001) or of a mutation in MSH2 (51% [33-69], p=0·0006) or MSH6 (34% [20-48], p=0·0309), but did not differ significantly from that noted for MLH1 (33% [15-51], p=0·1193) mutation carriers. This risk seems to be restricted to deletions that extend close to the MSH2 gene promoter. Of 194 carriers of an EPCAM deletion, three had duodenal cancer and four had pancreatic cancer. EPCAM deletion carriers have

  20. Combined colonoscopy and endometrial biopsy cancer screening results in women with Lynch syndrome.

    Science.gov (United States)

    Nebgen, Denise R; Lu, Karen H; Rimes, Sue; Keeler, Elizabeth; Broaddus, Russell; Munsell, Mark F; Lynch, Patrick M

    2014-10-01

    Endometrial biopsy (EMBx) and colonoscopy performed under the same sedation is termed combined screening and has been shown to be feasible and to provide a less painful and more satisfactory experience for women with Lynch syndrome (LS). However, clinical results of these screening efforts have not been reported. The purpose of this study was to evaluate the long-term clinical outcomes and patient compliance with serial screenings over the last 10.5 years. We retrospectively analyzed the data for 55 women with LS who underwent combined screening every 1-2 years between 2002 and 2013. Colonoscopy and endometrial biopsy were performed by a gastroenterologist and a gynecologist, with the patient under conscious sedation. Out of 111 screening visits in these 55 patients, endometrial biopsies detected one simple hyperplasia, three complex hyperplasia, and one endometrioid adenocarcinoma (FIGO Stage 1A). Seventy-one colorectal polyps were removed in 29 patients, of which 29 were tubular adenomas. EMBx in our study detected endometrial cancer in 0.9% (1/111) of surveillance visits, and premalignant hyperplasia in 3.6% (4/111) of screening visits. No interval endometrial or colorectal cancers were detected. Combined screening under sedation is feasible and less painful than EMBx alone. Our endometrial pathology detection rates were comparable to yearly screening studies. Our results indicate that screening of asymptomatic LS women with EMBx every 1-2 years, rather than annually, is effective in the early detection of (pre)cancerous lesions, leading to their prompt definitive management, and potential reduction in endometrial cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. A comparison between Lynch syndrome and sporadic colorectal cancer survivors' satisfaction with their healthcare providers.

    Science.gov (United States)

    Burton-Chase, Allison M; Parker, Wendy M; Polivka, Katrina M; Gritz, Ellen R; Amos, Christopher I; Lu, Karen H; Lynch, Patrick M; Rodriguez-Bigas, Miguel A; Nancy You, Y; Peterson, Susan K

    2017-03-01

    This study evaluated provider satisfaction in a sample of colorectal cancer (CRC) survivors with and without Lynch syndrome (LS). Participants were case-case-matched CRC survivors with (n = 75) or without (n = 75) LS (mean age of 55; range: 27-93). Participants completed a mailed questionnaire assessing demographics, clinical characteristics, healthcare utilization, psychosocial variables, and provider satisfaction. LS CRC survivors reported lower provider satisfaction scores on three subscales of the Primary Care Assessment Survey: communication (78.14 vs. 83.96; P < 0.05), interpersonal treatment (78.58 vs. 85.30; P < 0.05), and knowledge of the patient (60.34 vs. 69.86; P < 0.01). Among LS CRC survivors, predictors for mean communication and trust subscale scores were location of treatment and socioeconomic status. Higher mean depression scores also were associated with trust, while social support predicted higher satisfaction with communication. Sporadic CRC survivor satisfaction is driven largely by age (communication, interpersonal treatment) and patient anxiety (communication), while seeing a provider more often was associated with increased satisfaction with knowledge of the patient. LS CRC survivors reported lower levels of provider satisfaction than sporadic CRC survivors. LS survivors who received care at The University of Texas MD Anderson Cancer Center, a comprehensive cancer center (CCC), reported higher satisfaction than those receiving care at other institutions. Depressive symptoms and socioeconomic status may impact provider satisfaction ratings. Exploration of other potential predictors of provider satisfaction should be examined in this population. Additionally, further research is needed to examine the potential impact of provider satisfaction on adherence to medical recommendations in LS CRC survivors, particularly those being treated outside of CCCs. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  2. The risk of extra-colonic, extra-endometrial cancer in the Lynch syndrome.

    Science.gov (United States)

    Watson, Patrice; Vasen, Hans F A; Mecklin, Jukka-Pekka; Bernstein, Inge; Aarnio, Markku; Järvinen, Heikki J; Myrhøj, Torben; Sunde, Lone; Wijnen, Juul T; Lynch, Henry T

    2008-07-15

    Persons with the Lynch syndrome (LS) are at high risk for cancer, including cancers of the small bowel, stomach, upper urologic tract (renal pelvis and ureter), ovary, biliary tract and brain tumors, in addition to the more commonly observed colorectal and endometrial cancers. Cancer prevention strategies for these less common cancers require accurate, age-specific risk estimation. We pooled data from 4 LS research centers in a retrospective cohort study, to produce absolute incidence estimates for these cancer types, and to evaluate several potential risk modifiers. After elimination of 135 persons missing crucial information, cohort included 6,041 members of 261 families with LS-associated MLH1 or MSH2 mutations. All were either mutation carriers by test, probable mutation carriers (endometrial/colorectal cancer-affected), or first-degree relatives of these. Among mutation carriers and probable carriers, urologic tract cancer (N = 98) had an overall lifetime risk (to age 70) of 8.4% (95% CI: 6.6-10.8); risks were higher in males (p < 0.02) and members of MSH2 families (p < 0.0001). Ovarian cancer (N = 72) had an lifetime risk of 6.7% (95% CI: 5.3-9.1); risks were higher in women born after the median year of birth (p < 0.008) and in members of MSH2 families (p < 0.006). Brain tumors and cancers of the small bowel, stomach, breast and biliary tract were less common. Urologic tract cancer and ovarian cancer occur frequently enough in some LS subgroups to justify trials to evaluate promising prevention interventions. Other cancer types studied occur too infrequently to justify strenuous cancer control interventions. (c) 2008 Wiley-Liss, Inc.

  3. A Systematic Review on the Existing Screening Pathways for Lynch Syndrome Identification

    Directory of Open Access Journals (Sweden)

    Alessia Tognetto

    2017-09-01

    Full Text Available BackgroundLynch syndrome (LS is the most common hereditary colon cancer syndrome, accounting for 3–5% of colorectal cancer (CRC cases, and it is associated with the development of other cancers. Early detection of individuals with LS is relevant, since they can take advantage of life-saving intensive care surveillance. The debate regarding the best screening policy, however, is far from being concluded. This prompted us to conduct a systematic review of the existing screening pathways for LS.MethodsWe performed a systematic search of MEDLINE, ISI Web of Science, and SCOPUS online databases for the existing screening pathways for LS. The eligibility criteria for inclusion in this review required that the studies evaluated a structured and permanent screening pathway for the identification of LS carriers. The effectiveness of the pathways was analyzed in terms of LS detection rate.ResultsWe identified five eligible studies. All the LS screening pathways started from CRC cases, of which three followed a universal screening approach. Concerning the laboratory procedures, the pathways used immunohistochemistry and/or microsatellite instability testing. If the responses of the tests indicated a risk for LS, the genetic counseling, performed by a geneticist or a genetic counselor, was mandatory to undergo DNA genetic testing. The overall LS detection rate ranged from 0 to 5.2%.ConclusionThis systematic review reported different existing pathways for the identification of LS patients. Although current clinical guidelines suggest to test all the CRC cases to identify LS cases, the actual implementation of pathways for LS identification has not been realized. Large-scale screening programs for LS have the potential to reduce morbidity and mortality for CRC, but coordinated efforts in educating all key stakeholders and addressing public needs are still required.

  4. Agreement between the Board of Trustees of Henry Ford Community College and the Henry Ford Community College Federation of Teachers, American Federation of Teachers Local 1650, 1987-1990.

    Science.gov (United States)

    Henry Ford Community Coll., Dearborn, MI.

    This collective bargaining agreement between the Board of Trustees of Henry Ford Community College and the Henry Ford Community College Federation of Teachers establishes conditions of employment for all full-time teachers, counselors, librarians, placement officers, and selected other professional personnel. The articles in the agreement set…

  5. Agreement Between the Board of Trustees of Henry Ford Community College and the Henry Ford Community College Federation of Teachers, American Federation of Teachers, Local 1650, 1973-75.

    Science.gov (United States)

    Henry Ford Community Coll., Dearborn, MI.

    This agreement between the Board of Trustees of Henry Ford Community College and the Henry Ford Community College Federation of Teachers, American Federation of Teachers, Local 1650 covers the period of 1973-1975. Contents of the agreement cover recognition, board of trustee rights, union-board relations, conditions of employment, seniority, the…

  6. The 'Overly-Broad' Selden Patent, Henry Ford and Development in the Early US Automobile Industry

    DEFF Research Database (Denmark)

    Howells, John; Katznelson, Ron D

    and show that there is no evidence that innovation was retarded. To better understand this result we follow Henry Ford’s investigation of the Selden patent’s scope during 1903, the year when the Ford Motor Co. was most vulnerable to “uncertainty” over the enforceability of the asserted broad construction...... of the Selden patent claims. We use new primary sources to show how Henry Ford and others engaged in what today is called “Freedom to Operate” patent analysis when it most mattered commercially. We show that Ford correctly anticipated that a future court adjudication of the Selden patent claims would...... public actions effectively induced the Selden patent owners to bring suit against the Ford Motor Company. Finally, we show that the Ford Motor Company litigation costs in its first year of operation were trivial yet litigation brought valuable market publicity. We find that Henry Ford’s investigative...

  7. «Ecuador» de Henri Michaux: fazer a viagem é que é a viagem

    Directory of Open Access Journals (Sweden)

    Vera Lúcia de Carvalho Casa Nova

    2011-10-01

    Full Text Available Resumo: Uma viagem que pode não ter acontecido, mas que merece o nome de viagem. Uma desconstrução do paradigma desse gênero. Relato que plasma a configuração de um eu imaginário à procura de um ultrapassamento e de estar en dehors de soi-même.Palavras-chave: Henri Michaux; Ecuador; gênero; viagem.Resúmé: Un voyage qui peut n’avoir existé, mais qui mérite le nom de voyage par son caractère de desconstruction d’une littérature de ce genre. Récit de voyage qui  montre une autre configuration d’un sujet imaginaire à la recherche d’être en dehors de soi-même.Mots-clés: Henri Michaux; Ecuador; genre; voyage.Keywords: Henri Michaux; Ecuador; gender; journey.

  8. Temperature-Dependent Henry's Law Constants of Atmospheric Amines.

    Science.gov (United States)

    Leng, Chunbo; Kish, J Duncan; Roberts, Jason E; Dwebi, Iman; Chon, Nara; Liu, Yong

    2015-08-20

    There has been growing interest in understanding atmospheric amines in the gas phase and their mass transfer to the aqueous phase because of their potential roles in cloud chemistry, secondary organic aerosol formation, and the fate of atmospheric organics. Temperature-dependent Henry's law constants (KH) of atmospheric amines, a key parameter in atmospheric chemical transport models to account for mass transfer, are mostly unavailable. In this work, we investigated gas-liquid equilibria of five prevalent atmospheric amines, namely 1-propylamine, di-n-propylamine, trimethylamine, allylamine, and 4-methylmorpholine using bubble column technique. We reported effective KH, intrinsic KH, and gas phase diffusion coefficients of these species over a range of temperatures relevant to the lower atmosphere for the first time. The measured KH at 298 K and enthalpy of solution for 1-propylamine, di-n-propylamine, trimethylamine, allylamine, and 4-methylmorpholine are 61.4 ± 4.9 mol L(-1) atm(-1) and -49.0 ± 4.8 kJ mol(-1); 14.5 ± 1.2 mol L(-1) atm(-1) and -72.5 ± 6.8 kJ mol(-1); 8.9 ± 0.7 mol L(-1) atm(-1) and -49.6 ± 4.7 kJ mol(-1); 103.5 ± 10.4 mol L(-1) atm(-1) and -42.7 ± 4.3 kJ mol(-1); and 952.2 ± 114.3 mol L(-1) atm(-1) and -82.7 ± 9.7 kJ mol(-1), respectively. In addition, we evaluated amines' characteristic times to achieve gas-liquid equilibrium for partitioning between gas and aqueous phases. Results show gas-liquid equilibrium can be rapidly established at natural cloud droplets surface, but the characteristic times may be extended substantially at lower temperatures and pHs. Moreover, our findings imply that atmospheric amines are more likely to exist in cloud droplets, and ambient temperature, water content, and pH of aerosols play important roles in their partitioning.

  9. Henri Lefebvre und der Begriff der Urbanisierung ohne Urbanität: Deutung eines missverstandenen Begriffs aus heutiger Sicht

    OpenAIRE

    Bocquet, Denis

    2012-01-01

    International audience; This article proposes a critical examination of the concept of urbanization without urbanity which Henri Lefebre developed in his seminal book The Right to the City.; Une critique de la notion d'urbanisation sans urbanité développée par Henri Lefebvre dans Le Droit à la ville.

  10. Henry constants in polymer solutions with the van der Waals equation of state

    DEFF Research Database (Denmark)

    Bithas, Sotiris; Kalospiros, Nikolaos; Kontogeorgis, Georgios

    1996-01-01

    is a corresponding-states correlation for a dimensionless Henry constant defined based on the van der Waals equation of state. Satisfactory results-often close to the ones from the one-parameter correlation-are obtained for all systems investigated in this work. Compared with literature models that have been applied......The simple der Waals equation of state, as extended to polymer systems, is applied to the correlation and prediction of Henry constants in polymer solutions comprising five polymers and many nonpolar and polar solvents, including supercritical gases. The correlation achieved with one adjustable...

  11. Re-membering surrealism in Charles Henri Ford’s Poem Posters (1964–5)

    OpenAIRE

    Pawlik, Joanna

    2017-01-01

    This article explores Charles Henri Ford’s Poem Posters series of 1964–5 and the ‘Having Wonderful Time Wish You Were Here’: Postcards to Charles Henri Ford exhibition at the Iolas Gallery (New York, 1976). Ford’s editorship of View magazine (1940–7) is well known in scholarship on surrealism’s reception in America, but less frequently explored are the ways in which his later artistic and curatorial practice self-consciously continued the publication’s mission of promoting a queer and partisa...

  12. Prediction of Henry's law constants of triazine derived herbicides from quantum chemical continuum solvation models.

    Science.gov (United States)

    Delgado, Eduardo J; Alderete, Joel B

    2003-01-01

    The Henry's law constants (H) for triazine derived herbicides are calculated using quantum chemical solvation models, SM2, SM3, PCM-DFT, and CPCM-DFT, and their performances are discussed. The results show considerable differences in performance among the different levels of theory. The values of H calculated by the semiempirical methods agree much better with the experimental values than those obtained at the DFT level. The differences are discussed in terms of the different contributions, electrostatic and no-electrostatic, to Gibbs free energy of solvation. In addition, the Henry's law constants of some triazine derived herbicides whose values have not been reported earlier are predicted as well.

  13. Taxing junk food: applying the logic of the Henry tax review to food.

    Science.gov (United States)

    Bond, Molly E; Williams, Michael J; Crammond, Brad; Loff, Bebe

    2010-10-18

    The recent review of taxation in Australia - the Henry tax review - has recommended that the federal government increase the taxes already levied on tobacco and alcohol. Tobacco and alcohol taxes are put forward as the best way of reducing the social harms caused by the use and misuse of these substances. Junk foods have the same pattern of misuse and the same social costs as tobacco and alcohol. The Henry tax review rejects the idea of taxing fatty foods, and to date the government has not implemented a tax on junk food. We propose that a tax on junk food be implemented as a tool to reduce consumption and address the obesity epidemic.

  14. The Royal Entries of Henry VI in a London Civic Manuscript

    DEFF Research Database (Denmark)

    Bourassa, Kristin

    2016-01-01

    London Metropolitan Archives, MS Letter Book K, contains descriptions of Henry VI’s royal entries into both Paris (1431) and London (1432). Their placement one after the other in a London Letter Book was likely the work of the city’s common clerk, John Carpenter, who was the author of the descrip......London Metropolitan Archives, MS Letter Book K, contains descriptions of Henry VI’s royal entries into both Paris (1431) and London (1432). Their placement one after the other in a London Letter Book was likely the work of the city’s common clerk, John Carpenter, who was the author...

  15. Henri Meschonnic entre langue et poésie, sous la direction de Marcella Leopizzi

    OpenAIRE

    Arena, Sara

    2016-01-01

    Come emerge dai due testi introduttivi alla silloge di interventi, riuniti in questo numero di «Studi di letteratura francese» quale ideale celebrazione dell’ottantesimo compleanno di Henri Meschonnic, scomparso nel 2009 (Giovanni Dotoli, Le Flambeau d’un message, pp. 11-14; Marcella Leopizzi, La Voix d’Henri Meschonnic: vivre-sentir poème, pp. 15-23), l’asse prescelto per la pubblicazione non si pone l’obiettivo di una presentazione esaustiva dell’opera di Meschonnic, ma di un’indagine unita...

  16. M. Pirgerou on D. Izzo and C. Martinez’s Revisionary Interventions into Henry James

    Directory of Open Access Journals (Sweden)

    2009-07-01

    Full Text Available Donatella Izzo and Carlo Martinez. Revisionary Interventions Into Henry James. Eds. Napoli, 2008. Revisionary Interventions into Henry James is a compilation of a series of papers presented at a colloquium which took place at Università Orientale in Naples, Italy, on October 27, 2006. In her introduction to the volume, Donatella Izzo acknowledges the “rather blatant plagiarism” (7 which lent the book its title.  The borrowing, of course, refers to Donald Pease’s landmark Revisionary Interve...

  17. Henri Fayol’un Yönetim Düşüncesi Üzerine Notlar(Notes on Managerial Thought of Henry Fayol)

    OpenAIRE

    Ramazan ŞENGÜL

    2007-01-01

    Henri Fayol, developed a managerial approach which is a perfect guide for both private and public sectors through focusing systematically upon managerial process. A major advantage of Fayol in creating a general managerial doctrine was his pratician side. His managerial thought which was developed in the early 20th century lasted up to our times. The distinguished characteristic of Fayol’s thought was studying the administrative reality through separating it into its functions, in that it hel...

  18. Efficacy of proximal colectomy for surgical management of right-sided first colorectal cancer in Lynch Syndrome mutation carriers.

    Science.gov (United States)

    Hiatt, Molly J; Casey, Murray Joseph; Lynch, Henry T; Snyder, Carrie L; Stacey, Mark; Walters, Ryan W

    2017-11-08

    This study analyzes the occurrence of colorectal cancer (CRC) in Lynch syndrome (LS) mutation carriers, interval until diagnosis of metachronous CRC, and survival after proximal colectomy (PC) compared with total (TC) and subtotal colectomy (STC) for right-sided first CRC in LS mutation carriers. Sixty-four LS mutation carriers with right-sided first CRC treated with PC or TC + STC were confirmed by clinical records. Bivariate analyses were examined for significance and life tables were generated for risk of metachronous CRC and survival estimates following surgery. One of 16 (6.3%) mutation carriers treated with TC + STC developed subsequent CRC compared with 13/48 (27%) treated by PC. There was no significant difference in survival estimates between PC compared with TC + STC through 25 years after surgery. Risk of subsequent CRC and survival estimates following PC and TC + STC should be considered in surgical management of right-sided first CRC in LS mutation carriers. Lynch syndrome mutation carriers are still at 27% risk for metachronous colorectal cancer after proximal colectomy for right-sided first colorectal cancers, but this study found no difference in survival through 25 years follow-up compared with those treated with total and subtotal colectomy. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Excluding Lynch syndrome in a female patient with metachronous DNA mismatch repair deficient colon- and ovarian cancer.

    Science.gov (United States)

    Crobach, Stijn; Jansen, Anne M L; Ligtenberg, Marjolein J L; Koopmans, Marije; Nielsen, Maartje; Hes, Frederik J; Wijnen, Juul T; Dinjens, Winand N M; van Wezel, Tom; Morreau, Hans

    2017-11-09

    Patients synchronously or metachronously presenting with ovarian and colon cancer can pose diagnostic challenges. A primary colon carcinoma can metastasize to one or both ovaries, two independent primary tumors can arise or an ovarian carcinoma can metastasize to the colon. Clinical and immunohistochemical characterization can aid the diagnosis. Recently, we reported that in difficult cases finding pathogenic APC variants supports a colonic origin.In this case report we describe the clinical history of a female patient suspected for Lynch syndrome. She was diagnosed with a bilateral ovarian cancer at age 44, followed by the detection of a colon carcinoma 12.5 months later. Lesions of both sites showed a DNA mismatch repair deficiency with immunohistochemical loss of MLH1 and PMS2 expression without MLH1 promoter hypermethylation. In absence of germline MMR gene variants identical somatic MLH1 and CTNNB1 gene variants were found, indicating a clonal relation. MMR germline mosaicism was made unlikely by ultra deep sequencing of the MLH1 variant in DNA isolated from normal mucosa, blood, urine and saliva. Although initially being suspect for Lynch syndrome it was eventually concluded that a metachronously diagnosed colon carcinoma that metastasized to both ovaries was most likely.

  20. Insertion of an SVA element, a nonautonomous retrotransposon, in PMS2 intron 7 as a novel cause of Lynch syndrome.

    Science.gov (United States)

    van der Klift, Heleen M; Tops, Carli M; Hes, Frederik J; Devilee, Peter; Wijnen, Juul T

    2012-07-01

    Heterozygous germline mutations in the mismatch repair gene PMS2 predispose carriers for Lynch syndrome, an autosomal dominant predisposition to cancer. Here, we present a LINE-1-mediated retrotranspositional insertion in PMS2 as a novel mutation type for Lynch syndrome. This insertion, detected with Southern blot analysis in the genomic DNA of the patient, is characterized as a 2.2 kb long 5' truncated SVA_F element. The insertion is not detectable by current diagnostic testing limited to MLPA and direct Sanger sequencing on genomic DNA. The molecular nature of this insertion could only be resolved in RNA from cultured lymphocytes in which nonsense-mediated RNA decay was inhibited. Our report illustrates the technical problems encountered in the detection of this mutation type. Especially large heterozygous insertions will remain unnoticed because of preferential amplification of the smaller wild-type allele in genomic DNA, and are probably underreported in the mutation spectra of autosomal dominant disorders. © 2012 Wiley Periodicals, Inc.

  1. The role of religious and existential well-being in families with Lynch syndrome: prevention, family communication, and psychosocial adjustment.

    Science.gov (United States)

    Morris, Bronwyn A; Hadley, Donald W; Koehly, Laura M

    2013-08-01

    This study explored the role of religious (RWB) and existential well-being (EWB) on psychosocial factors, support network characteristics, and screening practices in families with Lynch syndrome, also referred to as hereditary nonpolyposis colon cancer (HNPCC). Participants were individuals with Lynch syndrome associated cancers and their first-degree relatives at risk of inheriting an identified deleterious mutation. Analyses considered both family RWB and EWB norms and individual deviations from that norm. Analyses controlled for age, gender, cancer diagnosis, number of respondents, and network size. Higher family RWB was associated with increased depressive symptoms (p family EWB was related to decreased depression symptoms (p family EWB was associated with fecal occult blood testing (p family communication about genetic counselling and testing (p family-level effects. Individuals with lower EWB than their family had lower perceived risk for colorectal cancer (p communicated disease risk information to less family members (p family also had higher cancer worry (p family network and being aware of family characteristics which may impact individual adjustment to disease risk. Interventions considering family-level factors may provide efficient pathways to improving psychosocial factors, screening practices, communication about disease risk and genetic testing, and cancer prevention.

  2. Endoscopic detection rate of sessile serrated lesions in Lynch syndrome patients is comparable to an age- and gender-matched control population: case-control study with expert pathology review.

    Science.gov (United States)

    Vleugels, Jasper L A; Sahin, Husna; Hazewinkel, Yark; Koens, Lianne; van den Berg, Jose G; van Leerdam, Monique E; Dekker, Evelien

    2017-12-09

    Carcinogenesis in Lynch syndrome involves fast progression of adenomas to colorectal cancer (CRC) due to microsatellite instability. The role of sessile serrated lesions (SSLs) and the serrated neoplasia pathway in these patients is unknown. The aim of this matched case-control study was to compare endoscopic detection rates and distribution of SSLs in Lynch syndrome patients to a matched control population. We collected data of Lynch syndrome patients with a proven germline mutation who underwent colonoscopy between January 2011 and April 2016 in 2 tertiary referral hospitals. Controls undergoing elective colonoscopy from 2011 and onward for symptoms or surveillance were selected from a prospectively collected database. Patients were matched 1:1 for age, gender, and index versus surveillance colonoscopy. An expert pathology review of serrated polyps was performed. The primary outcomes included the detection rates and distribution of SSLs. We identified 321 patients with Lynch syndrome who underwent at least one colonoscopy. Of these, 223 Lynch patients (mean age 49.3, female 59%, index colonoscopy 56%) were matched to 223 controls. SSLs were detected in 7.6% (CI, 4.8-11.9) of colonoscopies performed in Lynch patients and in 6.7% (CI, 4.1-10.8) of controls (p = 0.86). None of the detected SSLs in Lynch patients contained dysplasia. The detection rate of SSLs in Lynch patients undergoing colonoscopy is comparable to a matched population. These findings suggest that the role of the serrated neoplasia pathway in CRC development in Lynch syndrome seems to be comparable to that in the general population. Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

  3. A putative Lynch syndrome family carrying MSH2 and MSH6 variants of uncertain significance-functional analysis reveals the pathogenic one

    DEFF Research Database (Denmark)

    Kantelinen, Jukka; Hansen, Thomas V O; Kansikas, Minttu

    2011-01-01

    Inherited pathogenic mutations in the mismatch repair (MMR) genes, MSH2, MLH1, MSH6, and PMS2 predispose to Lynch syndrome (LS). However, the finding of a variant or variants of uncertain significance (VUS) in affected family members complicates the risk assessment. Here, we describe a putative LS...

  4. Thyroid cancer in a patient with a germline MSH2 mutation. Case report and review of the Lynch syndrome expanding tumour spectrum

    NARCIS (Netherlands)

    Stulp, Rein P; Herkert, Johanna C; Karrenbeld, Arend; Mol, Bart; Vos, Yvonne J; Sijmons, Rolf H

    2008-01-01

    Lynch syndrome (HNPCC) is a dominantly inherited disorder characterized by germline defects in DNA mismatch repair (MMR) genes and the development of a variety of cancers, predominantly colorectal and endometrial. We present a 44-year-old woman who was shown to carry the truncating MSH2 gene

  5. Prospective multicenter randomized intermediate biomarker study of oral contraceptive versus depo-provera for prevention of endometrial cancer in women with Lynch syndrome.

    Science.gov (United States)

    Lu, Karen H; Loose, David S; Yates, Melinda S; Nogueras-Gonzalez, Graciela M; Munsell, Mark F; Chen, Lee-May; Lynch, Henry; Cornelison, Terri; Boyd-Rogers, Stephanie; Rubin, Mary; Daniels, Molly S; Conrad, Peggy; Milbourne, Andrea; Gershenson, David M; Broaddus, Russell R

    2013-08-01

    Women with Lynch syndrome have a 40% to 60% lifetime risk for developing endometrial cancer, a cancer associated with estrogen imbalance. The molecular basis for endometrial-specific tumorigenesis is unclear. Progestins inhibit estrogen-driven proliferation, and epidemiologic studies have shown that progestin-containing oral contraceptives (OCP) reduce the risk of endometrial cancer by 50% in women at general population risk. It is unknown whether they are effective in women with Lynch syndrome. Asymptomatic women ages 25 to 50 with Lynch syndrome were randomized to receive the progestin compounds Depo-Provera (depo-MPA) or OCP for three months. An endometrial biopsy and transvaginal ultrasound were conducted before and after treatment. Endometrial proliferation was evaluated as the primary endpoint. Histology and a panel of surrogate endpoint biomarkers were evaluated for each endometrial biopsy as secondary endpoints. A total of 51 women were enrolled, and 46 completed treatment. Two of the 51 women had complex hyperplasia with atypia at the baseline endometrial biopsy and were excluded from the study. Overall, both depo-MPA and OCP induced a dramatic decrease in endometrial epithelial proliferation and microscopic changes in the endometrium characteristic of progestin action. Transvaginal ultrasound measurement of endometrial stripe was not a useful measure of endometrial response or baseline hyperplasia. These results show that women with Lynch syndrome do show an endometrial response to short-term exogenous progestins, suggesting that OCP and depo-MPA may be reasonable chemopreventive agents in this high-risk patient population.

  6. Ovarian metastasis from uveal melanoma with MLH1/PMS2 protein loss in a patient with germline MLH1 mutated Lynch syndrome: consequence or coincidence?

    Science.gov (United States)

    Lobo, João; Pinto, Carla; Freitas, Micaela; Pinheiro, Manuela; Vizcaino, Rámon; Oliva, Esther; Teixeira, Manuel R; Jerónimo, Carmen; Bartosch, Carla

    2017-03-01

    Currently, uveal melanoma is not considered within the Lynch syndrome tumor spectrum. However, there are studies suggesting a contribution of microsatellite instability in sporadic uveal melanoma tumorigenesis. We report a 45-year-old woman who was referred for genetic counseling due to a family history of Lynch syndrome caused by a MLH1 mutation. She originally underwent enucleation of the right eye secondary to a uveal spindle cell melanoma diagnosed at age 25. The tumor recurred 22 years later presenting as an ovarian metastasis and concurrently a microscopic endometrial endometrioid carcinoma, grade 1/3 was diagnosed. Subsequent studies highlighted that the uveal melanoma showed high microsatellite instability and loss of MLH1 and PMS2 protein expression, with no MLH1 promoter methylation or BRAF mutation. Additionally, a GNAQ mutation was found. We conclude that our patient's uveal melanoma is most likely related to MLH1 germline mutation and thus Lynch syndrome related. To the best of our knowledge, this is the first report of uveal melanoma showing MLH1/PMS2 protein loss in the context of Lynch syndrome.

  7. A rapid and cell-free assay to test the activity of lynch syndrome-associated MSH2 and MSH6 missense variants

    DEFF Research Database (Denmark)

    Drost, Mark; Zonneveld, José B M; van Hees, Sandrine

    2012-01-01

    Lynch syndrome (LS) is an autosomal dominant disorder that predisposes to colon, endometrial, and other cancers. LS is caused by a heterozygous germline mutation in one of the DNA mismatch repair (MMR) genes. A significant proportion of all mutations found in suspected LS patients comprises single...

  8. Los actos tienen consecuencias. Lógicas del mind-game film en la trilogía de Los Ángeles de David Lynch

    NARCIS (Netherlands)

    Elsaesser, T.

    2013-01-01

    Actions Do Have Consequences. Logics of the Mind-Game Film in David Lynch’s Los Angeles-Trilogy. David Lynch is a director, along with other auteurs, notably Michael Haneke and Lars von Trier, whose authorial identity and creative authority —and the challenges these encounter in the 21st century—

  9. Development of in vitro and in vivo functional assays to enable diagnosis of Variants of Uncertain Significance in the common cancer predisposition Lynch syndrome

    NARCIS (Netherlands)

    Drost, Mark

    2014-01-01

    Lynch syndrome (LS) is caused by germline mutations in DNA mismatch repair (MMR) genes and is the most prevalent hereditary colorectal cancer syndrome. A significant proportion of variants identified in MMR and other common cancer susceptibility genes are missense or noncoding changes whose

  10. A prospective study of bowel preparation for colonoscopy with polyethylene glycol-electrolyte solution versus sodium phosphate in Lynch syndrome: a randomized trial

    NARCIS (Netherlands)

    Vugt-van Pinxteren, M.W.J. van; Kouwen, M.C.A. van; Oijen, M.G. van; Achterberg, T. van; Nagengast, F.M.

    2012-01-01

    Lynch gene carriers undergo regular surveillance colonoscopies. Polyethylene glycol-electrolyte solution (PEG) is routinely prescribed for bowel cleansing, but often poorly tolerated by patients. Sodium phosphate (NaP) may be an alternative. Prospective and random comparison of bowel preparation

  11. Equivalent Helicobacter pylori infection rates in Lynch syndrome mutation carriers with and without a first-degree relative with gastric cancer

    NARCIS (Netherlands)

    Soer, Eline C.; Leicher, Laura W.; Langers, Alexandra M. J.; van de Meeberg, Paul C.; van der Wouden, Egbert-Jan; Koornstra, Jan Jakob; Bigirwamungu-Bargeman, Marloes; Vasen, Hans F. A.; de Vos tot Nederveen Cappel, Wouter H.

    2016-01-01

    Patients with Lynch syndrome (LS) are at an increased risk of developing gastric cancer. In 2010, a guideline that recommended to screen all patients for Helicobacter pylori was implemented in the Netherlands. H. pylori is an important risk factor in the development of gastric cancer in the general

  12. Dietary B vitamin and methionine intake and MTHFR C677T genotype on risk of colorectal tumors in Lynch syndrome : the GEOLynch cohort study

    NARCIS (Netherlands)

    Jung, Audrey Y.; van Duijnhoven, Franzel J. B.; Nagengast, Fokko M.; Botma, Akke; Heine-Broring, Renate C.; Kleibeuker, Jan H.; Vasen, Hans F. A.; Harryvan, Jan L.; Winkels, Renate M.; Kampman, Ellen

    Dietary intake of B vitamins and methionine, essential components of DNA synthesis and methylation pathways, may influence colorectal tumor (CRT) development. The impact of B vitamins on colorectal carcinogenesis in individuals with Lynch syndrome (LS) is unknown but is important given their high

  13. Dietary B vitamin and methionine intake and MTHFR C677T genotype on risk of colorectal tumors in Lynch syndrome: the GEOLynch cohort study

    NARCIS (Netherlands)

    Jung, A.Y.; Duijnhoven, van F.J.B.; Nagengast, F.M.; Botma, A.; Heine-Bröring, R.C.; Kleibeuker, J.H.; Vasen, H.F.A.; Harryvan, J.L.; Winkels, R.M.; Kampman, E.

    2014-01-01

    Purpose Dietary intake of B vitamins and methionine, essential components of DNA synthesis and methylation pathways, may influence colorectal tumor (CRT) development. The impact of B vitamins on colorectal carcinogenesis in individuals with Lynch syndrome (LS) is unknown but is important given their

  14. Exploring clinicians' attitudes about using aspirin for risk reduction in people with Lynch Syndrome with no personal diagnosis of colorectal cancer.

    Science.gov (United States)

    Chen, Yanni; Peate, Michelle; Kaur, Rajneesh; Meiser, Bettina; Wong, Tim; Kirk, Judy; Ward, Robyn L; Goodwin, Annabel; Macrae, Finlay; Hiller, Janet; Trainer, Alison H; Mitchell, Gillian

    2017-01-01

    Recent research has shown that aspirin reduces the risk of cancers associated with Lynch Syndrome. However, uncertainty exists around the optimal dosage, treatment duration and whether the benefits of aspirin as a risk-reducing medication (RRM) outweigh adverse medication related side-effects. Little is known about clinicians' attitudes, current practice, and perceived barriers to recommending aspirin as a RRM. To explore the attitudes of clinicians who discuss risk management options with patients with Lynch Syndrome towards using aspirin as a RRM. Clinicians were invited through professional organisations to complete an online survey. Topics included their clinical experience with Lynch Syndrome, views and practice of recommending aspirin as a RRM, and knowledge about clinical risk management guidelines for Lynch Syndrome. Comparison of attitudes was made between three professional groups. 181 respondents were included in the analysis: 59 genetics professionals (genetic counsellors and clinical geneticists, medical oncologists with specialist training in familial cancer), 49 gastroenterologists and 73 colorectal surgeons. Most clinicians (76 %) considered aspirin to be an effective RRM and most (72 %) were confident about discussing it. In all professional categories, those who were confident about discussing aspirin with patients perceived it to be an effective RRM (OR = 2.8 [95 % CI = 1.8-4.2], p Lynch Syndrome patients compared to 69 % of gastroenterologists and 68 % of colorectal surgeons. Those who considered aspirin as an effective RRM or who felt confident in their knowledge of the aspirin literature were more likely (OR = 10 [95 % CI = 1.5-65], p = 0.010, OR = 6 [95 % CI = 2.2-16], p Lynch Syndrome per year were more likely to be confident in their knowledge of the aspirin literature and discussing it with patients (OR = 4.1 [95 % CI = 1.6-10.2], p = 0.003). Explicit recommendations to take aspirin, was reported by 65

  15. Community Practice Implementation of a Self-administered Version of PREMM1,2,6 to Assess Risk for Lynch Syndrome.

    Science.gov (United States)

    Luba, Daniel G; DiSario, James A; Rock, Colleen; Saraiya, Devki; Moyes, Kelsey; Brown, Krystal; Rushton, Kristen; Ogara, Maydeen M; Raphael, Mona; Zimmerman, Dayna; Garrido, Kimmie; Silguero, Evelyn; Nelson, Jonathan; Yurgelun, Matthew B; Kastrinos, Fay; Wenstrup, Richard J; Syngal, Sapna

    2018-01-01

    Lynch syndrome is a genetic disorder that greatly increases risk for colorectal and other cancers, although it is underdiagnosed. Prediction of MLH1, MSH2, and MSH6 (PREMM1,2,6) is a web-based tool that analyzes individuals' personal/family histories of cancer to quantify their likelihood of carrying a germline mutation associated with Lynch syndrome. We investigated the feasibility of systematic risk assessment for Lynch syndrome in a community gastroenterology practice using a patient-completed version of PREMM1,2,6. PREMM1,2,6 was adapted into a computer tablet version designed for self-administration by patients. Individuals presenting to a community gastroenterology office and endoscopy facility in California completed the PREMM1,2,6 assessment before their visit (n = 3134). The total study duration (8 months) comprised a 2-month initiation period (May 1-June 30, 2013) and a 6-month study period (July 1-December 31, 2013). Genetic counseling and germline analysis for mutations in genes associated with Lynch syndrome (MLH1, MSH2, MSH6, PMS2, and EPCAM) were offered to individuals with PREMM1,2,6 scores of 5% or higher. Patients and providers completed surveys to evaluate the feasibility and satisfaction with the process. Of the 3134 individuals assessed by PREMM1,2,6 during the 6-month study period, 177 individuals (5.6%) had scores of 5% or higher. Of these, 146 individuals underwent genetic testing, along with 28 additional participants recruited nonconsecutively during the initiation period. Mutations associated with Lynch syndrome were detected in 3 of the 146 individuals (2.1%) with PREMM1,2,6 scores of 5% or higher who underwent germline testing, and 3 of the 28 patients (10.7%) recruited during study initiation with PREMM1,2,6 scores of 5% or higher. Of the participants who underwent genetic analysis, 98.6% stated that they understood the information provided to them. All of the surveyed providers stated that they were satisfied with the incorporation

  16. Differences in histological features and PD-L1 expression between sporadic microsatellite instability and Lynch-syndrome-associated disease in Japanese patients with colorectal cancer.

    Science.gov (United States)

    Yamada, Rin; Yamaguchi, Tatsuro; Iijima, Takeru; Wakaume, Rika; Takao, Misato; Koizumi, Koichi; Hishima, Tsunekazu; Horiguchi, Shin-Ichiro

    2018-01-11

    The field of immunotherapy has recently focused on cancers with microsatellite instability (MSI). These cancers include both Lynch-syndrome-associated tumors, which are caused by mismatch repair (MMR) germline mutations, and sporadic MSI tumors, which are mainly attributed to MLH1 promoter methylation. The present study aimed to clarify differences in the histological and PD-L1 expression profiles between these two types of MSI cancers in Japanese patients. Among 908 cases of colorectal cancer treated via surgical resection from 2008 to 2014, we identified 64 MSI cancers, including 36 sporadic MSI and 28 Lynch-syndrome-associated cancers, using a BRAF V600E mutation analysis and MLH1 methylation analysis. Of the latter subgroup, 21 (75%) harbored MMR germline mutations. The following were more frequent with sporadic MSI than with Lynch syndrome associated cancers: poor differentiation (50.0 vs. 7.1%, P = 0.0002), especially solid type (30.6 vs. 3.6%, P = 0.0061); medullary morphology (19.4 and 0%, P = 0.015), Crohn-like lymphoid reaction (50.0 vs. 25.0%, P = 0.042), and PD-L1 expression (25.0 vs. 3.6%, P = 0.034). However, the groups did not differ in terms of the mean invasive front and intratumoral CD8-positive cell densities. In a logistic regression analysis, PD-L1 expression correlated with poor differentiation (odds ratio: 7.65, 95% confidence interval: 1.55-37.7, P = 0.012), but not with the difference between sporadic MSI cancer and Lynch-syndrome-associated cancer (odds ratio: 4.74, 95% confidence interval: 0.50-45.0, P = 0.176). Therefore, compared with Lynch-syndrome-associated cancers, sporadic MSI cancers are more frequently solid, poorly differentiated medullary cancers that express PD-L1.

  17. Ernest Henry Starling: the history of cardiovascular endocrinology and the continuous need for developing animal models

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl

    2014-01-01

    The English physiologist, Ernest Henry Starling (1866–1927) (Fig. 1) in 1896, provided a quantitative explanation of the transcapillary transport of fluid. Six years later, he discovered the first hormone and introduced the concept of hormones in 1905, and at the time of the First World War, he...

  18. BUBBLE STRIPPING TO DETERMINE HYDROGEN CONCENTRATIONS IN GROUND WATER: A PRACTICAL APPLICATION OF HENRY'S LAW

    Science.gov (United States)

    The Bubble Stripping Method is a chemical testing method that operates on the principle of Henry's Law. It is useful for determining concentrations of hydrogen in well water, and it is capable of detecting concentrations on the order of nanomoles per liter. The method provides ...

  19. Neoliberalism, Democracy and the University as a Public Sphere: An Interview with Henry A. Giroux

    Science.gov (United States)

    Harper, Victoria

    2014-01-01

    "Truthout" contributor, director of "Truthout's" Public Intellectual Project (truth-out.org/public-intellectual-project) and Truthout board member Henry A. Giroux responds to questions about how the excesses of neoliberal politics have reshaped and subverted the democratic mission of higher education.

  20. Henry Giroux and the Politics of Higher Education under George W. Bush: An Interview

    Science.gov (United States)

    Pozo, Mike Alexander

    2005-01-01

    In May of 2004 Henry Giroux, a creator of the field of critical pedagogy and a leading advocate for young people, democracy, and education in the United States, reluctantly left Penn State University after twelve years as a Distinguished Professor in the education department. He has been a critic of the corporatization of and conservative…

  1. Henry Carr on the Girl-Child and Women Education in Southern ...

    African Journals Online (AJOL)

    ... on the influence of non-indigenous educators. Again, Henry Carr was among the pioneers of Nigeria's educational system from its foundation stage. A system which had a consequential factor in the social, economic and political development of Nigeria. SOPHIA: An African Journal of Philosophy Vol. 9 (1) 2006: pp. 38-44 ...

  2. Paul Henry Latimer (1925-2011): discoverer of selective scattering in photosynthetic systems.

    Science.gov (United States)

    Latimer, Margaret Gwyn; Bannister, Thomas T; Govindjee

    2017-10-01

    We provide here a brief tribute to Paul Henry Latimer (November 25, 1925 to October 1, 2011), a dedicated biological physicist, discoverer of selective scattering in biological systems, a wonderful teacher, husband, and father. We provide here a glimpse of his personal and professional life, including reminiscences from F. Dudley Bryant, Dan A. Cross, Bobby E. Pyle, Bryan L. Seiber, and Bruce A. Seiber.

  3. Fin-de-Siecle Advances in Neuroeducation: Henry Herbert Donaldson and Reuben Post Halleck

    Science.gov (United States)

    Theodoridou, Zoe D.; Triarhou, Lazaros C.

    2009-01-01

    This article focuses on two early attempts at bridging neuroscience and education, made by Henry Herbert Donaldson (1857-1938), a neurologist, and Reuben Post Halleck (1859-1936), an educator. Their works, respectively entitled "The Growth of the Brain: A Study of the Nervous System in Relation to Education" (1895) and "The Education of the…

  4. The Imaginary World of Henri Rousseau. Teacher's Guide. School Arts: Looking/Learning.

    Science.gov (United States)

    Henderson, Anne

    While Henri Rousseau's work was not easily classified into any definitive artistic style of the time--impressionism, post-impressionism, fauvism, or cubism--it has been considered a forerunner of surrealism because of its dreamlike sensibility. This teaching guide provides information about Rousseau and his work, focusing on "Tropical Forest…

  5. Community Arts Programs: Cohesion and Difference Case Studies. Henry Street Settlement and El Museo del Barrio

    Science.gov (United States)

    Kiebert-Gruen, Cathleen

    2009-01-01

    A comparative case study of two cultural institutions, Henry Street Settlement and El Museo del Barrio, founded almost eighty years apart, were involved in social justice causes and community arts. Although both of these institutions participated in the political activism of their time, they also demonstrated an important adaptability. They were…

  6. Magie en wetenschap in de spektakelcultuur van de negentiende eeuw: Henri Robin in de Lage Landen

    NARCIS (Netherlands)

    Vanhoutte, Kurt; Wynants, Nele

    2017-01-01

    textabstractMagic and Science in the Nineteenth-century Culture of Spectacle: Henri Robin in the Low CountriesThe theatre of modernity served to illuminate scientific insight and discovery in a spectacular way. Astronomy, physics, and experiments with electricity were at the heart of a popular genre

  7. Henry's law constants of phenol and mononitrophenols in water and aqueous sulfuric acid.

    Science.gov (United States)

    Guo, X X; Brimblecombe, P

    2007-06-01

    Phenols are widely present in the atmosphere and nitration probably in the aerosol phase leads to nitrophenols. Nitration by nitric acid in sulfuric acid can be rapid, but little is known of the process under atmospheric conditions. The Henry's law constants K(H)(dagger) of phenol and 2-, 3- and 4-nitrophenol were all measured by a bubble stripping method as: 2820mol kg(-1) atm(-1) (at 298K), 147mol kg(-1) atm(-1) (at 298K), 1.6x10(4)mol kg(-1)atm(-1) (at 308K) and 2.1x10(4)mol kg(-1) atm(-1) (at 308K), respectively. The Henry's law constant of phenol in sulfuric acid systems is lower by more than a factor of two at 1020mol kg(-1) atm(-1) (at 298K) in 40wt% sulfuric acid, which is in line with salting-out of oxygen-containing aromatic compounds in water-sulfuric acid systems. The Henry's law constants of 2- and 4-nitrophenol behave differently and are almost independent of sulfuric acid concentration. The variation of K(H)(dagger) with temperature (T) described in terms of -dln(K(H)(dagger))/d(1/T) does not to vary with sulfuric acid concentration, suggesting enthalpy of dissolution for phenol is independent of sulfuric acid. The series of Henry's law constants measured here can describe the equilibrium situation for phenols in careful determinations of phase partitioning in the atmosphere.

  8. The Henry Reaction in [Bmim][PF6]-based Microemulsions Promoted by Acylase

    Directory of Open Access Journals (Sweden)

    Zhang-Gao Le

    2013-11-01

    Full Text Available An environmentally-friendly, enzyme-promoted procedure for the Henry reaction was first studied using water-in-[Bmim][PF6] microemulsions as reaction medium. The Amano acylase from Aspergillus oryzae showed better catalytic activity for the addition reactions of nitromethane with a series of aromatic aldehydes, and a highest yield of 90% was obtained.

  9. Pre-Education Programs: A Comprehensive Project at Henry Ford Community College.

    Science.gov (United States)

    Zopf, Deborah; Smyrski, Larry

    This document presents an overview of a four-year comprehensive pre-education project at Henry Ford Community College (HFCC) in Michigan. To meet the needs of school districts that preferred a 32-credit certificate program as well as districts that preferred a 60-unit associate degree, HFCC employed a career-ladder approach: A 32-credit…

  10. 2004 Foster G. McGaw Prize. Winner: Henry Ford Health System, Detroit, Michigan.

    Science.gov (United States)

    Rollins, Gina

    2005-04-01

    Henry Ford Health System's commitment to community service took root with its founding in 1915 and has been embraced by leaders ever since. Wide-ranging efforts of school health programs offering grief support for children earned it the 2004 McGaw Prize.

  11. The Henry Ford Academy: An Innovative Space for Teaching and Learning

    Science.gov (United States)

    n/a, n/a

    2005-01-01

    Edith Graybill, English instructor at the Henry Ford Academy in Dearborn, Michigan, speaks about her school's English language arts curriculum, the influence of the school on the role of English language arts, the theories of teaching and learning used at the Academy, and other related topics. She believes that most of the students appreciate…

  12. Detroit's Henry Ford Health System awarded Foster G. McGaw Prize.

    Science.gov (United States)

    Rees, Tom

    2005-01-01

    Henry Ford Health System, Detroit, is named winner of the prestigious Foster G. McGaw Prize for excellence in community service. The organization received 100,000 dollars from the sponsors, the American Hospital Association, The Baxter International Foundation and the Cardinal Health Foundation.

  13. Ernest Henry Starling (1866-1927): the scientist and the man

    DEFF Research Database (Denmark)

    Henriksen, Jens H

    2005-01-01

    The pre-eminent achievements of the English physician and physiologist Ernest Henry Starling were his quantitative explanation of the transcapillary transport of fluid, the discovery of the first hormone, secretin, and his formulation of the law of the heart. In some ways Starling was an outsider...

  14. Pornografia e transgressão na obra literária de Henry Miller

    Directory of Open Access Journals (Sweden)

    Raquel Catunda Pereira

    2016-07-01

    Full Text Available The North American writer Henry Miller was marginalized by literary critics since the first publications of his works in the 40s. Accused of being a pornographic text, the book Tropic of Cancer (1934 was forbidden in many countries. This article aims to analyze the obscene in Henry Miller’s work to prove that, beyond the erotic intention, Miller’s books are an expression of freedom and rejection of moral standards. In order to achieve our goal, we will use as theoretical basis the articles Criticismo e sexualidade: uma leitura de Tropico of Capricorn de Henry Miller, by Flávia Andréa Rodrigues Benfatt, and Literatura marginal americana: do épico confessional ao niilismo erótico, by Lainister de Oliveira. The texts mentioned above grant us the argumentation necessary to the analysis of pornographic discourse in Henry Miller’s literary works as the author’s aesthetics choice of taking himself as a transgressor in a decadent society.

  15. The Snake Charmer(ess intermedia dialogue between Henri Rousseau's Painting and Sylvia Plath's poetry

    Directory of Open Access Journals (Sweden)

    Milovanov Dajana

    2017-01-01

    Full Text Available The paper examines possible interpretations of poetry and poetic image analysing the dialogue between the arts of literature and painting. The paper studies the poet Sylvia Plath's referencing Henri Rousseau's painting The Snake Charmer in her poem 'Snakecharmer'. What is analysed is the creative superstructure based upon nonliterary reference, as well as the visual elements attained through two diverse artistic media.

  16. Fort McHenry National Monument and Historic Shrine. Teacher's Guide.

    Science.gov (United States)

    Rogers, Jim

    This teacher's guide explores Fort McHenry and the British attack on Baltimore Harbor (Maryland) in 1814. The guide contains 11 lessons: (1) "Where in the World Is Baltimore?" (no handout-use classroom resources); (2) "Why Baltimore?" (Handout-Why Baltimore?); (3) "Now Where Do We Place the Fort?" (Handout-Map of…

  17. ?18O signature of phytoliths from the last interglacial Lynch's Crater sediments (Qld, Australia): insights on changes in precipitation sources

    Science.gov (United States)

    Alexandre, A. E.; Pailles, C.; Sonzogni, C.; Kershaw, P.; Wust, R. A.; Turney, C. S.

    2013-12-01

    The 65 m continental sedimentary sequence from Lynch's Crater (17°37‧S, 145°70‧E; last 230 ka) has provided one of the main references for late Quaternary environmental changes in northeast Australia and in the Western Pacific area. The site is located at the southern limit of an area that is influenced by the Australian Summer Monsoon (ASM). The climate pattern is controlled by the position of the Intertropical Convergence Zone (ITCZ) and the monsoon circulation. Today, over 80% of mean annual precipitation falls during the November-March interval, supplied by NW monsoonal winds during the earlier phase of the ASM, by S-E trade winds during the later phase of the ASM and by occasional cyclones. Influence of Quaternary Northern Hemisphere glacial/inter-glacial changes on precipitation and rainforest dynamics at Lynch's crater has been previously evidenced from the pollen record. Here, we explore the oxygen isotopic composition of wood phytoliths (δ18Owood phytolith) recovered from 30 samples from the 70-130ka sedimentary section (core LC2-04). Reconstruction of a precise core chronology for the core is in progress. A recent calibration indicated the efficiency of δ18Owood phytolith signatures from Queensland rainforest phytolith assemblages in recording changes in mean annual δ18Osoil water values (assumed to be equivalent to the weighted mean annual δ18Oprecipitation values in rainforest environments) and mean annual temperature, provided these changes were on the order of several ‰ and/or several °C in magnitude. In parallel, through the morphological identification of phytolith types (d/p index), phytolith assemblages recovered from sediments have been shown to be a reliable tool for quantitatively estimating tree cover density at low elevation tropical sites. The Lynch's Crater phytolith record, although limited at this stage by the chronological framework, evidences several key features. 1) Increases in δ18Owood phytolith values are synchronous

  18. Temperature profiles from expendable bathythermograph (XBT) casts from the LYNCH in the North Atlantic Ocean in support of the Integrated Global Ocean Services System (IGOSS) from 1976-04-10 to 1976-04-12 (NODC Accession 7600921)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — XBT data were collected from the LYNCH in support of the Integrated Global Ocean Services System (IGOSS) project. Data were collected by the US Navy; Naval...

  19. Temperature profiles from expendable bathythermograph (XBT) casts from the LYNCH in the North Atlantic Ocean in support of the Integrated Global Ocean Services System (IGOSS) from 1972-04-15 to 1972-04-29 (NODC Accession 7300814)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — XBT data were collected from the LYNCH in support of the Integrated Global Ocean Services System (IGOSS). Data were collected by the US Navy; Naval Oceanographic...

  20. Temperature profiles from expendable bathythermograph (XBT) casts from the LYNCH in the North Atlantic Ocean in support of the Integrated Global Ocean Services System (IGOSS) from 1971-12-07 to 1971-12-12 (NODC Accession 8000360)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — XBT data were collected from the LYNCH in support of the Integrated Global Ocean Services System (IGOSS) project. Data were collected by the US Navy; Naval...

  1. “The Cancer Bond”: Exploring the Formation of Cancer Risk Perception in Families with Lynch Syndrome

    Science.gov (United States)

    Koehly, Laura M.; Peterson, Susan K.; Shegog, Margarette; Vernon, Sally W.; Gritz, Ellen R.

    2010-01-01

    This study explores the social context of hereditary cancer risk perception in three families, an African-American family, a Mexican-American family, and a Caucasian family, each with Lynch Syndrome documented by a mismatch repair gene mutation. Communication network assessments measured family communication about cancer experiences and genetic testing information among a total of 26 participants. Participant narratives were evaluated to gain insight into how family cancer experiences and genetic testing information have shaped perceptions of cancer risk. Analysis of communication networks indicated that some families discussed cancer experiences to a greater extent than genetic testing information, and vice-versa. Interviews elucidated that sharing both types of health information led participants to conceptualize linkages among a strong family history of cancer, genetic testing information, and cancer prevention strategies. Understanding how different types of family communication influence the formation of perceived hereditary disease risk may enhance efforts to tailor genetic counseling services for families. PMID:20401527

  2. [HNPCC (hereditary non-polyposis colorectal cancer) or Lynch syndrome: a syndrome related to a failure of DNA repair system].

    Science.gov (United States)

    Manceau, Gilles; Karoui, Mehdi; Charachon, Antoine; Delchier, Jean-Charles; Sobhani, Iradj

    2011-03-01

    The HNPCC syndrome (hereditary non polyposis colon cancer) or Lynch syndrome stands for an autosomic dominant condition leading to the most prevalent hereditary colo-rectal cancers (CCR). MMR (mismatch repair)'s genes are involved in carcinogenesis as they play a role in ADNA mismatch repair. Microsatellite instability (MSI+ phenotype) induced by germline mutations is characteristic of such tumors and is necessary to assert the diagnosis. The HNPCC syndrome is associated with a significant increased risk of CCR altogether with endometrium, upper urinary tract and small bowel carcinomas as well as ovarian, biliary system and gastric cancers although of lesser extent. It is of importance to diagnose HNPCC syndrome prior to the treatment starts because it may influence patient's (as well as her/his relatives) disease management (type of surgery, surveillance and screening exams). New French recommendations, developed in 2009, about prophylactic colo-rectal and gynecologic surgeries and monitoring update latest ones published on 2004.

  3. [Familial non-polyposis colorectal carcinoma (Lynch syndrome) in Germany - analysis of information, advisory service and family screening].

    Science.gov (United States)

    Schneider, R; Rümmele, P; Dechant, S; Hofstädter, F; Lorenz, W; Fürst, A

    2011-01-01

    Lynch syndrome is associated with an increased incidence of colorectal carcinomas and extracolonic neoplasms. Patients fulfilling the "Revised Bethesda criteria" or the Amsterdam Citeria I or II should be screened for DNA mismatch repair deficiency. Mutation carriers and high risk individuals should undergo intensified annual screening, as recommended by the S3 guideline for colorectal carcinoma. All families of the Regensburger study group with a verified mutation were included in this study. Data acquisition was conducted by telephone interviews. We determined the number of family members who had been informed about the diagnosis and how many of them participated in the recommended screening program. Additionally, an information letter was sent to family members providing information about the opportunity of a predictive mutation analysis. 90 family members of 12 families with a total of 42 carcinomas and a mean age of tumor diagnosis of 41.3 years were included. At the beginning of the study 97.4 % of the family members were informed about the diagnosis. In the course of the study the number of family members participating in the mutation analysis increased from 29.5 % to 42.3 %. The number of index patients complying with the recommended screening program was over 90 %, in contrast to the number of family members which varied between 30 - 60 %. Relatives of index patients are not sufficiently informed about the importance of predictive testing and the re-commended surveillance guidelines. An insufficient implementation of Lynch syndrome specific aspects of the S3-guideline can be assumed. For an improved implementation barriers of physicians' adherence must be systemically analyzed. It is essential for these high-risk families to establish and enforce awareness in order to create intensified surveillance. © Georg Thieme Verlag KG Stuttgart · New York.

  4. Volatility dependence of Henry's law constants of condensable organics: Application to estimate depositional loss of secondary organic aerosols

    National Research Council Canada - National Science Library

    Hodzic, A; Aumont, B; Knote, C; Lee‐Taylor, J; Madronich, S; Tyndall, G

    2014-01-01

    ...) is largely unconstrained in current chemistry‐climate models. We apply the Generator of Explicit Chemistry and Kinetics of Organics in the Atmosphere to calculate Henry's law constants for these intermediate species...

  5. [Crusading and Chronicle Writing on the Medieval Baltic Frontier: A Companion to the Chronicle of Henry of Livonia] / Michael Amundsen

    Index Scriptorium Estoniae

    Amundsen, Michael

    2012-01-01

    Arvustus: Crusading and chronicle writing on the medieval Baltic frontier : a companion to the Chronicle of Henry of Livonia / edited by Marek Tamm, Linda Kaljundi, Carsten Selch Jensen. Farnham : Ashgate, 2011

  6. Henry's Constants of Persistent Organic Pollutants by a Group-Contribution Method Based on Scaled-Particle Theory.

    Science.gov (United States)

    Razdan, Neil K; Koshy, David M; Prausnitz, John M

    2017-10-09

    A group-contribution method based on scaled-particle theory was developed to predict Henry's constants for six families of persistent organic pollutants: polychlorinated benzenes, polychlorinated biphenyls, polychlorinated dibenzodioxins, polychlorinated dibenzofurans, polychlorinated naphthalenes, and polybrominated diphenyl ethers. The group-contribution model uses limited experimental data to obtain group-interaction parameters for an easy-to-use method to predict Henry's constants for systems where reliable experimental data are scarce. By using group-interaction parameters obtained from data reduction, scaled-particle theory gives the partial molar Gibbs energy of dissolution, Δg2, allowing calculation of Henry's constant, H2, for more than 700 organic pollutants. The average deviation between predicted values of log H2 and experiment is 4%. Application of an approximate van't Hoff equation gives the temperature dependence of Henry's constants for polychlorinated biphenyls, polychlorinated naphthalenes, and polybrominated diphenyl ethers in the environmentally-relevant range 0 to 40(o)C.

  7. Cardinal Henri De Lubac, Jacques Maritain, Correspondance et rencontres. Tome L.

    OpenAIRE

    Airiau, Paul

    2014-01-01

    La publication des œuvres complètes du cardinal Henri de Lubac suit son bonhomme de chemin. Elle prend ici la forme de l’édition de 17 lettres échangées entre le jésuite et Jacques Maritain (p. 43-80). Celle-ci est encadrée en ouverture d’une courte préface du cardinal archevêque de Lyon Philippe Barbarin (p. 9-12) et d’une longue introduction du fr. Jean-Miguel Garrigues, « Jacques Maritain et Henri de Lubac : distance, convergences et rapprochement » (p. 13-42, parue précédemment dans la Re...

  8. Monique VÉRITÉ, Henri Lhote – Une aventure scientifique au Sahara

    OpenAIRE

    Bruno LECOQUIERRE

    2015-01-01

    Auteur déjà en 1992 d’Odette du Puigaudeau : une bretonne au Sahara, Monique Vérité vient de livrer une nouvelle biographie passionnante, sur une personnalité saharienne haute en couleur, célèbre en France et au Sahara après-guerre et qui est aujourd’hui un peu oubliée : Henri Lhote (1903-1991). Henri Lhote peut être considéré comme l’un des plus grands explorateurs du Sahara au XXe siècle, aux côtés de Conrad Kilian et de Théodore Monod. Le parallèle avec ce dernier est assez fascinant car c...

  9. Henri Cartier Bresson's decisive instante and indexation: an exploratory study of photography indexing methods

    Directory of Open Access Journals (Sweden)

    Welington Rodrigo Zanon

    2017-08-01

    Full Text Available The research presents photography indexing methods from the perspective of Henri Cartier Bresson's work and the decisive instant. The methodology is exploratory and descriptive, with a qualitative approach, using documental research procedures, survey and content analysis. The research was based on the method of classification and indexing by studying the best indexing method for the photographs of Henri Cartier-Bresson, in order to extract as much information as possible from the visual representation of the document (photographs, and to minimize the losses in this transcription. For this, we used the four methods of indexing of photographs developed by the authors Panofsky (1986, Smit (1986, Manini (2002 and Rodrigues (2007, applying them to three (03 Bresson photographs. After the application, we performed a comparative analysis and discussion of the results.

  10. Henry's law constant for phosphine in seawater: determination and assessment of influencing factors

    Science.gov (United States)

    Fu, Mei; Yu, Zhiming; Lu, Guangyuan; Song, Xiuxian

    2013-07-01

    The Henry's Law constant ( k) for phosphine in seawater was determined by multiple phase equilibration combined with headspace gas chromatography. The effects of pH, temperature, and salinity on k were studied. The k value for phosphine in natural seawater was 6.415 at room temperature (approximately 23°C). This value increases with increases in temperature and salinity, but no obvious change was observed at different pH levels. At the same temperature, there was no significant difference between the k for phosphine in natural seawater and that in artificial seawater. This implies that temperature and salinity are major determining factors for k in marine environment. Double linear regression with Henry's Law constants for phosphine as a function of temperature and salinity confirmed our observations. These results provide a basis for the measurement of trace phosphine concentrations in seawater, and will be helpful for future research on the status of phosphine in the oceanic biogeochemical cycle of phosphorus.

  11. Prediction of the temperature dependency of Henry's law constant from chemical structure.

    Science.gov (United States)

    Kühne, Ralph; Ebert, Ralf-Uwe; Schüürmann, Gerrit

    2005-09-01

    A new model to estimate the temperature dependency of Henry's law constant in water for organic compounds from the two-dimensional structure is presented. Air/water partition enthalpies of 456 chemicals were fitted to 46 substructural parameters with a squared correlation coefficient r2 of 0.81 and a standard error of 7.1 kJ/mol. The compound set covers various organic compound classes with the atom types C, H, N, O, F, Cl, Br, I, and S. Application of the model together with experimental data for 25 degrees C to a set of 462 compounds with 2119 experimental Henry's law constants at temperatures below 20 degrees C yields a predictive squared correlation coefficient q2 of 0.99 and a standard error of 0.21 logarithmic units. The prediction capability is further evaluated using cross validation and permutation.

  12. A French description of German psychology laboratories in 1893 by Victor Henri, a collaborator of Binet.

    Science.gov (United States)

    Nicolas, Serge; Barnes, Marissa E; Murray, David J

    2015-05-01

    There is a rich tradition of writings about the foundation of psychology laboratories, particularly in the United States but also in France. Various documents exist concerning former German laboratories in American and French literature. But the most interesting French paper was certainly written by a young psychologist named Victor Henri (1872-1940) who was a close collaborator of Alfred Binet (1857-1911) in the 1890s. Visiting various psychology laboratories, he wrote, in 1893, a clear description of the laboratories of Wundt, G. E. Müller, Martius and Ebbinghaus. An English translation is given of Henri's paper and the historical importance of his contribution is here expounded by contrasting the German and French psychologies of the time.

  13. DNA-catalyzed Henry reaction in pure water and the striking influence of organic buffer systems.

    Science.gov (United States)

    Häring, Marleen; Pérez-Madrigal, Maria M; Kühbeck, Dennis; Pettignano, Asja; Quignard, Françoise; Díaz, David Díaz

    2015-03-04

    In this manuscript we report a critical evaluation of the ability of natural DNA to mediate the nitroaldol (Henry) reaction at physiological temperature in pure water. Under these conditions, no background reaction took place (i.e., control experiment without DNA). Both heteroaromatic aldehydes (e.g., 2-pyridinecarboxaldehyde) and aromatic aldehydes bearing strong or moderate electron-withdrawing groups reacted satisfactorily with nitromethane obeying first order kinetics and affording the corresponding β-nitroalcohols in good yields within 24 h. In contrast, aliphatic aldehydes and aromatic aldehydes having electron-donating groups either did not react or were poorly converted. Moreover, we discovered that a number of metal-free organic buffers efficiently promote the Henry reaction when they were used as reaction media without adding external catalysts. This constitutes an important observation because the influence of organic buffers in chemical processes has been traditionally underestimated.

  14. Keratin Protein-Catalyzed Nitroaldol (Henry) Reaction and Comparison with Other Biopolymers.

    Science.gov (United States)

    Häring, Marleen; Pettignano, Asja; Quignard, Françoise; Tanchoux, Nathalie; Díaz Díaz, David

    2016-08-25

    Here we describe a preliminary investigation on the ability of natural keratin to catalyze the nitroaldol (Henry) reaction between aldehydes and nitroalkanes. Both aromatic and heteroaromatic aldehydes bearing strong or moderate electron-withdrawing groups were converted into the corresponding β-nitroalcohol products in both DMSO and in water in the presence of tetrabutylammonium bromide (TBAB) as a phase transfer catalyst. Negligible background reactions (i.e., negative control experiment in the absence of keratin protein) were observed in these solvent systems. Aromatic aldehydes bearing electron-donating groups and aliphatic aldehydes showed poor or no conversion, respectively. In general, the reactions in water/TBAB required twice the amount of time than in DMSO to achieve similar conversions. Moreover, comparison of the kinetics of the keratin-mediated nitroaldol (Henry) reaction with other biopolymers revealed slower rates for the former and the possibility of fine-tuning the kinetics by appropriate selection of the biopolymer and solvent.

  15. Keratin Protein-Catalyzed Nitroaldol (Henry Reaction and Comparison with Other Biopolymers

    Directory of Open Access Journals (Sweden)

    Marleen Häring

    2016-08-01

    Full Text Available Here we describe a preliminary investigation on the ability of natural keratin to catalyze the nitroaldol (Henry reaction between aldehydes and nitroalkanes. Both aromatic and heteroaromatic aldehydes bearing strong or moderate electron-withdrawing groups were converted into the corresponding β-nitroalcohol products in both DMSO and in water in the presence of tetrabutylammonium bromide (TBAB as a phase transfer catalyst. Negligible background reactions (i.e., negative control experiment in the absence of keratin protein were observed in these solvent systems. Aromatic aldehydes bearing electron-donating groups and aliphatic aldehydes showed poor or no conversion, respectively. In general, the reactions in water/TBAB required twice the amount of time than in DMSO to achieve similar conversions. Moreover, comparison of the kinetics of the keratin-mediated nitroaldol (Henry reaction with other biopolymers revealed slower rates for the former and the possibility of fine-tuning the kinetics by appropriate selection of the biopolymer and solvent.

  16. DNA-Catalyzed Henry Reaction in Pure Water and the Striking Influence of Organic Buffer Systems

    Directory of Open Access Journals (Sweden)

    Marleen Häring

    2015-03-01

    Full Text Available In this manuscript we report a critical evaluation of the ability of natural DNA to mediate the nitroaldol (Henry reaction at physiological temperature in pure water. Under these conditions, no background reaction took place (i.e., control experiment without DNA. Both heteroaromatic aldehydes (e.g., 2-pyridinecarboxaldehyde and aromatic aldehydes bearing strong or moderate electron-withdrawing groups reacted satisfactorily with nitromethane obeying first order kinetics and affording the corresponding β-nitroalcohols in good yields within 24 h. In contrast, aliphatic aldehydes and aromatic aldehydes having electron-donating groups either did not react or were poorly converted. Moreover, we discovered that a number of metal-free organic buffers efficiently promote the Henry reaction when they were used as reaction media without adding external catalysts. This constitutes an important observation because the influence of organic buffers in chemical processes has been traditionally underestimated.

  17. Henry II of France (1519-1559) and His Death From Meningoencephalitis Following Cranial Trauma.

    Science.gov (United States)

    Markatos, Konstantinos; Karamanou, Marianna; Arkoudi, Konstantina; Androutsos, Georgios

    2017-10-01

    This historical review summarizes the most significant theories regarding the cause of death of King Henry II of France (1519-1559) and the circumstances under which it occurred. Although the historical testimonies are inconclusive and vague, postmortem analysis has shown that the King died of meningoencephalitis, caused by hematoma of a cerebral contusion, with effusion in the cerebral laminae and its surrounding tissue initiated by a periorbital fracture. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Henri Fayol, théoricien de l’entreprise innovante

    OpenAIRE

    Hatchuel, Armand; Segrestin, Blanche

    2016-01-01

    International audience; Have we correctly read Henri Fayol? His work is still reduced to general principles of administration that seem rigid and trivial. Yet, he has been a great innovative leader that considered scientific research as a major task of the business executive. A new reading of Fayol's masterpiece shows that he introduced sophisticated notions: " the unknown " , " the program of action " , " the advancement " , which meaning was erased by his translators or forgotten. Coming fr...

  19. Henry Fayol’s 14 Principles of Management: Implications for Libraries and Information Centres

    OpenAIRE

    Uzuegbu, C. P.; Nnadozie, C. O.

    2015-01-01

    This paper focuses generally on the ‘fourteen principles of management’ by Henri Fayol. However, it specifically analyses their application to and implications for libraries and information centres. An extensive review of published works on management generally, and library management in particular, was conducted. This yielded vital insights on the original meaning and later modifications of these principles, as well as their application in the management of various organisation...

  20. VIDEO: Dr. Henry Rodriguez - Proteogenomics in Cancer Medicine | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    Dr. Henry Rodriguez, director of the Office of Cancer Clinical Proteomics Research (OCCPR) at NCI, speaks with ecancer television at WIN 2017 about the translation of the proteins expressed in a patient's tumor into a map for druggable targets. By combining genomic and proteomic information (proteogenomics), leading scientists are gaining new insights into ways to detect and treat cancer due to a more complete and unified understanding of complex biological processes.

  1. Henry Ford Hospital dermatology experience with Levulan Kerastick and blue light photodynamic therapy.

    Science.gov (United States)

    Rivard, Jennifer; Ozog, David

    2006-06-01

    Photodynamic therapy (PDT) takes advantage of our understanding of the cutaneous response to topically applied porphyrins to selectively destroy malignant or premalignant cells. This type of therapy has been used to treat a variety of cutaneous diseases, including actinic keratoses, basal cell carcinoma, acne, and others. The treatment protocols are not standardized across institutions. We present the Henry Ford Dermatology protocol and early results of our first 150 treatments with PDT.

  2. [Henry Beecher and medical science: the 50th anniversary of a famous article].

    Science.gov (United States)

    Jacobs, N; Huisman, F G

    2017-01-01

    In 2016, it had been exactly half a century ago that Henry Beecher published his article 'Ethics and clinical research' in The New England Journal of Medicine. Today, this article is considered a turning point in the history of medical research ethics. On the occasion of the fiftieth anniversary of this famous article, we are looking back on this turbulent period in the history of medicine.

  3. Methylcarbonate and bicarbonate phosphonium salts as catalysts for the nitroaldol (Henry) reaction.

    Science.gov (United States)

    Fabris, Massimo; Noè, Marco; Perosa, Alvise; Selva, Maurizio; Ballini, Roberto

    2012-02-17

    Phosphonium ionic liquids exchanged with bicarbonate and methylcarbonate anions (CILs) exhibit catalytic performances comparable to those of sterically hindered (non nucleophilic) organosuperbases such as DBU. At 25-50 °C, under solventless conditions, CILs efficiently catalyze the Henry addition of different aldehydes and ketones to nitroalkanes: not only they allow the selective formation of nitroaldols but they unlock a novel high-yielding access to dinitromethyl derivatives of ketones.

  4. William Henry Welch (1850–1934): the road to Johns Hopkins

    OpenAIRE

    Silverman, Barry D.

    2011-01-01

    William Henry Welch's selection in 1884 as the first faculty member of the new medical school at Johns Hopkins created the invigorating atmosphere that generated the revolutionary changes in medical training and laboratory medicine that transformed medicine in America. Dr. Welch's family traditions, his New England upbringing, Yale education, and German university experience prepared a unique individual to lead American medicine into the 20th century.

  5. The last ride of Henry II of France: orbital injury and a king's demise.

    Science.gov (United States)

    Eftekhari, Kian; Choe, Christina H; Vagefi, M Reza; Eckstein, Lauren A

    2015-01-01

    Jousting was a popular pastime for royalty in the Renaissance era. Injuries were common, and the eye was particularly at risk from the splinters of the wooden lance. On June 30, 1559, Henry II of France participated in a jousting tournament to celebrate two royal weddings. In the third match, Gabriel de Montgomery struck Henry on the right shoulder and the lance splintered, sending wooden shards into his face and right orbit. Despite being cared for by the prominent physicians Ambroise Paré and Andreas Vesalius, the king died 10 days later and was found to have a cerebral abscess. The wound was not explored immediately after the injury; nevertheless, wooden foreign bodies were discovered in the orbit at the time of autopsy. The dura had not been violated, suggesting that an infection may have traveled from the orbit into the brain. Nostradamus and Luca Guarico, the astrologer to the Medici family, had prophesied the death of Henry II of France, but he ignored their warnings and thus changed the course of history in Renaissance Europe. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Transplant cost-report tracking at Henry Ford Transplant Institute and other centers nationwide.

    Science.gov (United States)

    Beach-Langlois, Marianne; Yankasky, Pamela

    2011-06-01

    The lack of uniformity in the reporting of direct and indirect costs by organ acquisition cost centers, diagnosis-related groups, and in physician reimbursement often results in Medicare overpayment and findings of unjustified charges in audits conducted by the Office of the Inspector General. Although it is true that organ transplantation costs vary widely, uniform cost-report accounting is needed. Henry Ford Transplant Institute has developed systematic auditing protocols that result in acceptable compliance with Medicare. The differences between those protocols and the methods used elsewhere are illustrated by the results of a national survey of transplant centers. The survey addresses 10 crucial questions, drawn from the cost-reporting model used at Henry Ford Transplant Institute. Setting-Surveys were distributed via the United Network for Organ Sharing listserv, with replies from 43 centers. The participants were transplant administrators. Several important practices that are audited by the Office of the Inspector General were not followed by a number of reporting institutions. About 30% did not account for pretransplant charges, 15% did not track pretransplant services, 40% do not use an external consultant, and the frequency of physician time studies varied. On the other hand, the vast majority of institutions perform frequent time studies and manually review pretransplant charges. These results suggest that most centers use accounting methods similar to those used at Henry Ford Transplant Institute, which will significantly improve recognition of pretransplantation costs.

  7. Temozolomide increases the number of mismatch repair-deficient intestinal crypts and accelerates tumorigenesis in a mouse model of Lynch syndrome.

    Science.gov (United States)

    Wojciechowicz, Kamila; Cantelli, Erika; Van Gerwen, Bastiaan; Plug, Mirjam; Van Der Wal, Anja; Delzenne-Goette, Elly; Song, Ji-Ying; De Vries, Sandra; Dekker, Marleen; Te Riele, Hein

    2014-11-01

    Lynch syndrome, a nonpolyposis form of hereditary colorectal cancer, is caused by inherited defects in DNA mismatch repair (MMR) genes. Most patients carry a germline mutation in 1 allele of the MMR genes MSH2 or MLH1. With spontaneous loss of the wild-type allele, cells with defects in MMR exist among MMR-proficient cells, as observed in healthy intestinal tissues from patients with Lynch syndrome. We aimed to create a mouse model of this situation to aid in identification of environmental factors that affect MMR-defective cells and their propensity for oncogenic transformation. We created mice in which the MMR gene Msh2 can be inactivated in a defined fraction of crypt base columnar stem cells to generate MSH2-deficient intestinal crypts among an excess of wild-type crypts (Lgr5-CreERT2;Msh2(flox/-) mice). Intestinal tissues were collected; immunohistochemical analyses were performed for MSH2, along with allele-specific PCR assays. We traced the fate of MSH2-deficient crypts under the influence of different external factors. Lgr5-CreERT2;Msh2(flox/-) mice developed more adenomas and adenocarcinomas than control mice; all tumors were MSH2 deficient. Exposure of Lgr5-CreERT2;Msh2(flox/-) mice to the methylating agent temozolomide caused MSH2-deficient intestinal stem cells to proliferate more rapidly than wild-type stem cells. The MSH2-deficient intestinal stem cells were able to colonize the intestinal epithelium and many underwent oncogenic transformation, forming intestinal neoplasias. We developed a mouse model of Lynch syndrome (Lgr5-CreERT2;Msh2(flox/-) mice) and found that environmental factors can modify the number and mutability of the MMR-deficient stem cells. These findings provide evidence that environmental factors can promote development of neoplasias and tumors in patients with Lynch syndrome. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  8. The Uterine Sandwich Method for Placenta Previa Accreta in Mullerian Anomaly: Combining the B-Lynch Compression Suture and an Intrauterine Gauze Tampon

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    Mustafa Kaplanoğlu

    2013-01-01

    Full Text Available Mullerian duct anomalies may cause obstetric complications, such as postpartum hemorrhage (PPH and placental adhesion anomalies. Uterine compression suture may be useful for controlling PPH (especially atony. In recent studies, uterine compression sutures have been used in placenta accreta. We report a case of PPH, a placenta accreta accompanying a large septae, treated with B-Lynch suture and intrauterine gauze tampon.

  9. Smoking and colorectal cancer in Lynch syndrome: results from the Colon Cancer Family Registry and the University of Texas M.D. Anderson Cancer Center.

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    Pande, Mala; Lynch, Patrick M; Hopper, John L; Jenkins, Mark A; Gallinger, Steve; Haile, Robert W; LeMarchand, Loic; Lindor, Noralane M; Campbell, Peter T; Newcomb, Polly A; Potter, John D; Baron, John A; Frazier, Marsha L; Amos, Christopher I

    2010-02-15

    Lynch syndrome family members with inherited germline mutations in DNA mismatch repair (MMR) genes have a high risk of colorectal cancer (CRC), and cases typically have tumors that exhibit a high level of microsatellite instability (MSI). There is some evidence that smoking is a risk factor for CRCs with high MSI; however, the association of smoking with CRC among those with Lynch syndrome is unknown. A multicentered retrospective cohort of 752 carriers of pathogenic MMR gene mutations was analyzed, using a weighted Cox regression analysis, adjusting for sex, ascertainment source, the specific mutated gene, year of birth, and familial clustering. Compared with never smokers, current smokers had a significantly increased CRC risk [adjusted hazard ratio (HR), 1.62; 95% confidence interval (95% CI), 1.01-2.57] and former smokers who had quit smoking for 2 or more years were at decreased risk (HR, 0.53; 95% CI, 0.35-0.82). CRC risk did not vary according to age at starting. However, light smoking (Lynch syndrome may be at increased risk of CRC if they smoke regularly. Although our data suggest that former smokers, short-term smokers, and light smokers are at decreased CRC risk, these findings need further confirmation, preferably using prospective designs.

  10. Changes in screening behaviors and attitudes toward screening from pre-test genetic counseling to post-disclosure in Lynch syndrome families

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    Burton-Chase, Allison M.; Hovick, Shelly R.; Peterson, Susan K.; Marani, Salma K.; Vernon, Sally W.; Amos, Christopher I.; Frazier, Marsha L.; Lynch, Patrick M.; Gritz, Ellen R.

    2013-01-01

    Purpose This study examined colonoscopy adherence and attitudes towards colorectal cancer (CRC) screening in individuals who underwent Lynch syndrome genetic counseling and testing. Methods We evaluated changes in colonoscopy adherence and CRC screening attitudes in 78 cancer-unaffected relatives of Lynch syndrome mutation carriers before pre-test genetic counseling (baseline) and at 6 and 12 months post-disclosure of test results (52 mutation-negative, 26 mutation-positive). Results While both groups were similar at baseline, at 12 months post-disclosure, a greater number of mutation-positive individuals had had a colonoscopy compared with mutation-negative individuals. From baseline to 12 months post-disclosure, the mutation-positive group demonstrated an increase in mean scores on measures of colonoscopy commitment, self-efficacy, and perceived benefits of CRC screening, and a decrease in mean scores for perceived barriers to CRC screening. Mean scores on colonoscopy commitment decreased from baseline to 6 months in the mutation-negative group. Conclusion Adherence to risk-appropriate guidelines for CRC surveillance improved after genetic counseling and testing for Lynch syndrome. Mutation-positive individuals reported increasingly positive attitudes toward CRC screening after receiving genetic test results, potentially reinforcing longer term colonoscopy adherence. PMID:23414081

  11. Cell cycle–related genes as modifiers of age of onset of colorectal cancer in Lynch syndrome: a large-scale study in non-Hispanic white patients

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    Chen, Jinyun; Pande, Mala

    2013-01-01

    Heterogeneity in age of onset of colorectal cancer in individuals with mutations in DNA mismatch repair genes (Lynch syndrome) suggests the influence of other lifestyle and genetic modifiers. We hypothesized that genes regulating the cell cycle influence the observed heterogeneity as cell cycle–related genes respond to DNA damage by arresting the cell cycle to provide time for repair and induce transcription of genes that facilitate repair. We examined the association of 1456 single nucleotide polymorphisms (SNPs) in 128 cell cycle–related genes and 31 DNA repair–related genes in 485 non-Hispanic white participants with Lynch syndrome to determine whether there are SNPs associated with age of onset of colorectal cancer. Genotyping was performed on an Illumina GoldenGate platform, and data were analyzed using Kaplan–Meier survival analysis, Cox regression analysis and classification and regression tree (CART) methods. Ten SNPs were independently significant in a multivariable Cox proportional hazards regression model after correcting for multiple comparisons (P Lynch syndrome. PMID:23125224

  12. Cell cycle-related genes as modifiers of age of onset of colorectal cancer in Lynch syndrome: a large-scale study in non-Hispanic white patients.

    Science.gov (United States)

    Chen, Jinyun; Pande, Mala; Huang, Yu-Jing; Wei, Chongjuan; Amos, Christopher I; Talseth-Palmer, Bente A; Meldrum, Cliff J; Chen, Wei V; Gorlov, Ivan P; Lynch, Patrick M; Scott, Rodney J; Frazier, Marsha L

    2013-02-01

    Heterogeneity in age of onset of colorectal cancer in individuals with mutations in DNA mismatch repair genes (Lynch syndrome) suggests the influence of other lifestyle and genetic modifiers. We hypothesized that genes regulating the cell cycle influence the observed heterogeneity as cell cycle-related genes respond to DNA damage by arresting the cell cycle to provide time for repair and induce transcription of genes that facilitate repair. We examined the association of 1456 single nucleotide polymorphisms (SNPs) in 128 cell cycle-related genes and 31 DNA repair-related genes in 485 non-Hispanic white participants with Lynch syndrome to determine whether there are SNPs associated with age of onset of colorectal cancer. Genotyping was performed on an Illumina GoldenGate platform, and data were analyzed using Kaplan-Meier survival analysis, Cox regression analysis and classification and regression tree (CART) methods. Ten SNPs were independently significant in a multivariable Cox proportional hazards regression model after correcting for multiple comparisons (P Lynch syndrome.

  13. Effect of low B-Lynch suture on menstrual cycle recovery and sex hormone levels in patients after cesarean section for placenta previa

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    Su-Lan Zhang

    2016-03-01

    Full Text Available Objective: To explore the effect of low B-Lynch suture on the menstrual cycle recovery and sex hormone levels in patients after cesarean section for placenta previa. Methods: A total of 40 patients who were admitted in our hospital from August, 2013 to August, 2015 for cesarean section due to placenta previa were included in the study and randomized into the observation group and the control group. The patients in the observation group were given low B-lynch suture, while in the control group, yarns were plugged in the uterus. The bleeding during operation and 24 h after operation, the postpartum lochia duration, and menstrual cycle recovery in the two groups were observed. The postpartum FSH, E2, and LH levels in the two groups were determined. Results: The amount of bleeding during operation and 24 h after operation in the observation group was significantly less than that in the control group (P0.05. The comparison of FSH, E2, and LH levels between the two groups was not statistically significant (P>0.05. Conclusions: Low B-Lynch suture can effectively reduce the amount of bleeding after cesarean section for placenta previa, and has no effect on the menstrual recovery and ovarian function with a simple operation and less postoperative complications; therefore, it deserves to be widely recommended in the clinic.

  14. “No Lynch, No Peaks!”: Auteurism, fan/actor campaigns and the challenges of Twin Peaks’ return(s

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    Rebecca Williams

    2016-12-01

    Full Text Available This article explores the return of Twin Peaks in 2017, exploring how the series’ revival may threaten fans’ sense of trust in the text and their own fan identity (Williams, 2015. Many fans welcome the return of beloved shows such as Twin Peaks and the involvement of original creators Mark Frost and David Lynch offers a ʻguaranteeʼ of authenticity, whilst the return of cast members presents the opportunity to re-visit favourite characters. This paper firstly explores how Twin Peaks’ resurrection allows consideration of fan responses to the continuation of an assumed dormant textual world by exploring the potential impact of the return of original actors and the series’ creators.Secondly, the paper considers the impact of Lynch’s temporary departure from the series in April 2015 and the subsequent actor-led campaign to encourage his return. The “No Lynch, No Peaks” campaign allows exploration of how the actors involved positioned themselves as both fans and potential employees. The paper thus analyses David Lynch’s enduring position as the auteur of Twin Peaks and how the campaign allows consideration of the actors as media professionals, fans of Lynch, and figures who display forms of cultural and symbolic capital (Bourdieu. 1984.

  15. LINCHAMENTO: O CRESCIMENTO DA (INJUSTIÇA COLETIVA DIANTE DA OMISSÃO DO ESTADO / LYNCHING: GROWTH OF PUBLIC (INJUSTICE FRONT THE FAILURE OF THE STATE

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    Sarah Ludmilla do Nascimento Félix

    2015-12-01

    Full Text Available This article presents the relationship between the increase in the number of lynching in Brazil and the omission of state to comply with its duty to punish and reintegrate of offenders into community. It is explained the origins and causes of the phenomenon and its use as a form of exhibitionism punishment. Additionally, it is showed how the state inaction in combating crime allows the occurrence of private punishment and encourages its practice. It is exposed the relationship between this lethargy and the growth in crime rates which creates a cycle of violence. It is used literature review as a research methodology and it is analyzed fundamental rights and constitutional guarantees and the intolerable disrespect in relation to the case of lynched people. It is indicated that these offenses are the main reason to start an effective combat against the practice of lynching. It is justified why government needs to work together with civil society in pursuing an effective security policies and investments to combat factors that cause violence in Brazil and the mechanisms to avoid these criminal offenses.

  16. Functional analysis in mouse embryonic stem cells reveals wild-type activity for three MSH6 variants found in suspected Lynch syndrome patients.

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    Eva A L Wielders

    Full Text Available Lynch syndrome confers an increased risk to various types of cancer, in particular early onset colorectal and endometrial cancer. Mutations in mismatch repair (MMR genes underlie Lynch syndrome, with the majority of mutations found in MLH1 and MSH2. Mutations in MSH6 have also been found but these do not always cause a clear cancer predisposition phenotype and MSH6-defective tumors often do not show the standard characteristics of MMR deficiency, such as microsatellite instability. In particular, the consequences of MSH6 missense mutations are challenging to predict, which further complicates genetic counseling. We have previously developed a method for functional characterization of MSH2 missense mutations of unknown significance. This method is based on endogenous gene modification in mouse embryonic stem cells using oligonucleotide-directed gene targeting, followed by a series of functional assays addressing the MMR functions. Here we have adapted this method for the characterization of MSH6 missense mutations. We recreated three MSH6 variants found in suspected Lynch syndrome families, MSH6-P1087R, MSH6-R1095H and MSH6-L1354Q, and found all three to behave like wild type MSH6. Thus, despite suspicion for pathogenicity from clinical observations, our approach indicates these variants are not disease causing. This has important implications for counseling of mutation carriers.

  17. Human Heredity and Health (H3) in Africa Kidney Disease Research Network: A Focus on Methods in Sub-Saharan Africa.

    Science.gov (United States)

    Osafo, Charlotte; Raji, Yemi Raheem; Burke, David; Tayo, Bamidele O; Tiffin, Nicki; Moxey-Mims, Marva M; Rasooly, Rebekah S; Kimmel, Paul L; Ojo, Akinlolu; Adu, Dwomoa; Parekh, Rulan S

    2015-12-07

    CKD affects an estimated 14% of adults in sub-Saharan Africa, but very little research has been done on the cause, progression, and prevention of CKD there. As part of the Human Heredity and Health in Africa (H3Africa) Consortium, the H3Africa Kidney Disease Research Network was established to study prevalent forms of kidney disease in sub-Saharan Africa and increase the capacity for genetics and genomics research. The study is performing comprehensive phenotypic characterization and analyzing environmental and genetic factors from nine clinical centers in four African countries (Ghana, Nigeria, Ethiopia, and Kenya) over a 5-year period. Approximately 4000 participants with specified kidney disease diagnoses and 4000 control participants will be enrolled in the four African countries. In addition, approximately 50 families with hereditary glomerular disease will be enrolled. The study includes both pediatric and adult participants age research infrastructure can be successfully established in Africa. This study will provide clinical, biochemical, and genotypic data that will greatly increase the understanding of CKD in sub-Saharan Africa. Copyright © 2015 by the American Society of Nephrology.

  18. Historical perspective on the Department of Neurosurgery at the Henry Ford Hospital.

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    Kole, M K; O'Leary, S T; Malik, G M; Rosenblum, M L

    2001-02-01

    The Henry Ford Hospital (HFH) was founded in 1915 as a philanthropic gift from Henry Ford, the automobile magnate and inventor of the Model T. The hospital and its organizational structure represented a nonsectarian facility that would provide care for all members of society. The system was patterned after the newest and most modern medical centers at the time in Europe, Canada, and the United States, including the German Krankenhauser, the Johns Hopkins Hospital, the Mayo Clinic, and the Peter Bent Brigham Hospital in Boston. The HFH grew into the Henry Ford Health System in the 1970s to 1990s, with the acquisition of other hospitals, the development of a multiple-region-based clinic system through southeastern Michigan, and the development of comprehensive, vertically integrated health care systems. The Division of Neurosurgery at HFH was established by Albert Crawford in 1926. The tradition of training residents in neurosurgery began in 1946, and the residency training program was accredited by the American Board of Neurosurgery in 1954. In 1970, the Division of Neurosurgery of the Department of Surgery was combined with the Division of Neurology to create the joint Department of Neurology and Neurosurgery. A separate Department of Neurosurgery was established in 1981. Four individuals have served as chairmen of the Department of Neurosurgery at HFH, i.e., Albert Crawford (1926-1952), Robert Knighton (1952-1978), James Ausman (1978-1991), and Mark Rosenblum (1992 to the present). During the 1980s and 1990s, HFH evolved into the vertically integrated, regionally distributed Henry Ford Health System. Under the current direction of Dr. Rosenblum, the Department of Neurosurgery at HFH has grown to include 11 full-time neurosurgeons, 2 neuro-oncologists, and 3 investigators with Ph.D. degrees and has recently expanded into three additional hospitals in southeastern Michigan, paralleling the growth of the system. The faculty annually treats more than 2,000 cases in

  19. Effectiveness of an implementation optimisation intervention aimed at increasing parent engagement in HENRY, a childhood obesity prevention programme - the Optimising Family Engagement in HENRY (OFTEN) trial: study protocol for a randomised controlled trial.

    Science.gov (United States)

    Bryant, Maria; Burton, Wendy; Cundill, Bonnie; Farrin, Amanda J; Nixon, Jane; Stevens, June; Roberts, Kim; Foy, Robbie; Rutter, Harry; Hartley, Suzanne; Tubeuf, Sandy; Collinson, Michelle; Brown, Julia

    2017-01-24

    Family-based interventions to prevent childhood obesity depend upon parents' taking action to improve diet and other lifestyle behaviours in their families. Programmes that attract and retain high numbers of parents provide an enhanced opportunity to improve public health and are also likely to be more cost-effective than those that do not. We have developed a theory-informed optimisation intervention to promote parent engagement within an existing childhood obesity prevention group programme, HENRY (Health Exercise Nutrition for the Really Young). Here, we describe a proposal to evaluate the effectiveness of this optimisation intervention in regard to the engagement of parents and cost-effectiveness. The Optimising Family Engagement in HENRY (OFTEN) trial is a cluster randomised controlled trial being conducted across 24 local authorities (approximately 144 children's centres) which currently deliver HENRY programmes. The primary outcome will be parental enrolment and attendance at the HENRY programme, assessed using routinely collected process data. Cost-effectiveness will be presented in terms of primary outcomes using acceptability curves and through eliciting the willingness to pay for the optimisation from HENRY commissioners. Secondary outcomes include the longitudinal impact of the optimisation, parent-reported infant intake of fruits and vegetables (as a proxy to compliance) and other parent-reported family habits and lifestyle. This innovative trial will provide evidence on the implementation of a theory-informed optimisation intervention to promote parent engagement in HENRY, a community-based childhood obesity prevention programme. The findings will be generalisable to other interventions delivered to parents in other community-based environments. This research meets the expressed needs of commissioners, children's centres and parents to optimise the potential impact that HENRY has on obesity prevention. A subsequent cluster randomised controlled pilot

  20. Linchamientos y conflicto político en Los Andes Lynchings and Political conflict in The Andes

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    Carlos M. Vilas

    2007-06-01

    Full Text Available En 2004, los alcaldes de dos municipalidades de la región aimara de los Andes fueron linchados en la aparente culminación de agudos conflictos políticos internos y entre las respectivas comunidades y el Estado central. En este artículo se discuten ambos casos con el fin de ilustrar las transformaciones experimentadas en años recientes en la organización y la dinámica interna de las comunidades andinas, y de la articulación conflictiva de la política local en los procesos e instituciones de más amplio alcance. Precariedad social e incapacidad o renuencia del Estado para responder con eficacia a demandas básicas de determinados grupos de población configuran enmarcamientos socioeconómicos e institucionales de los linchamientos. En contraste con enfoques que enfatizan en factores culturales tradicionales o en un supuesto nacionalismo indígena, en el artículo se destaca la gravitación de fenómenos y procesos político- institucionales recientes en la transformación cultural y política de las comunidades, en el modo en que éstas procesan sus conflictos internos y con el Estado central.In 2004, two municipalitys mayors form the aimara Andes of Peru and Bolivia were subjected to mass lynchings as a result of the apparent culmination of violent political confrontations. This paper deals with these events as dramatic illustrations of the transformations the Andean communities experienced during recent decades in their internal dynamics, as well as in the articulation of local politics to processes and institutions beyond the communal limits. Structural precariousness combined with the state's inability or reluctance to come to terms with social or political demands from relevant segments of the people in the communities set the socioeconomic and institutional stage for lynchings. In contrast with approaches relating these events to an alleged indigenous cultural identity, the analysis points to the impact of the communities' political