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Sample records for justice kathleen lynch

  1. The Course of Law: State Intervention in Southern Lynch Mob Violence 1882–1930

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    Kinga Makovi

    2016-09-01

    Full Text Available Collective violence when framed by its perpetrators as "citizen" justice is inherently a challenge to state legitimacy. To properly account for such violence, it is necessary to consider an opportunity structure incorporating the actions of both vigilantes and agents of the state. The motivation and lethality of lynch mobs in the South cannot be understood without considering how the state reacted to the legitimacy challenges posed by lynching. We trace the shifting orientation of state agents to lynching attempts between the end of Reconstruction and the start of the Great Depression. Analyzing an inventory of more than 1,000 averted and completed lynching events in three Southern states, we model geographic and temporal patterns in the determinants of mob formation, state intervention, and intervention success. Opponents of lynching often pled with mobs to "let the law take its course." This article examines the course followed by the law itself, as state actors moved between encouraging, accommodating, and in many instances averting mob violence.

  2. Interview with Kathleen Fitzpatrick

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    Andrés Lomeña Cantos

    2012-12-01

    Full Text Available Kathleen Fitzpatrick, born in 1967, teaches Media Studies in Pomona University (California, coordinator of the MediaCommons plattaform and one of the most remarkable Digital Humantties academic. His first book The Anxiety of Obsolescence (http://www.anxietyofobsolescence.com reflects on some novelist technophilia as a mecanism to maintain his privilege status inside a media ecology increasingly comptetive. His next essay, Planned obsolecence (http://www.plannedobsolescence.net, extends his critics to the old humanities role and meditate about pressent and future of academic publications.

  3. Extracolonic Manifestations of Lynch Syndrome

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    Bansidhar, Brian J.

    2012-01-01

    Lynch syndrome has classically been defined by several predominant malignancies. Initial clinical criteria for diagnosis of Lynch syndrome would miss 40% of affected individuals. As time has passed, our understanding of Lynch syndrome has evolved and will continue to do so. The number of cancer types that are included in the Lynch phenotype is growing. This has allowed clinicians to redefine Lynch syndrome, at risk populations, screening needs, and diagnostic criteria. Inclusion of extracolon...

  4. LYNCHING IN RUSSIAN COUNTRYSIDE (late XIX-early XX

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    Vladimir Borisovich Bezgin

    2013-08-01

    Full Text Available Research actuality is due to the frequent attempts of extrajudicial killings of criminals in the country as a result of the citizens' law enforcement distrust, their doubt of deserved retribution.Such phenomenon of legal life of the Russian countryside as a lynch mob is studied in the article on the basis of a wide range of archival and ethnographic sources. The author analyzes the crimes for which the perpetrators are arbitrarily subjected to massacre in the village. The role of the peasant community in the punishment implementation of criminals was found out. The causes of the stability of this tradition in rural society were set.Lynching played an effective means of suppression of unlawful acts of the peasants. The collective nature of the spontaneously created killings of criminals was the result of mutual responsibility of community members and rural solidarity preservation condition. According to farmers gathering verdict gave legal force to massacre and left no doubt about the justice of the decision.DOI: http://dx.doi.org/10.12731/2218-7405-2013-8-1

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

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    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.

  6. Lynch syndrome: the patients' perspective

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    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

  7. Lynch Syndrome: An Updated Review

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    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. Lynch syndrome-related small intestinal adenocarcinomas.

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    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.

  9. Rehabilitation programme for the Mary Kathleen uranium mine

    International Nuclear Information System (INIS)

    Duffield, I.R.; Ward, T.A.

    1989-01-01

    The Mary Kathleen uranium deposit was located in the North West region of the state of Queensland, Australia. It was discovered in 1954 and mined in two phases for a total of twelve years between 1958 and 1982. In October 1982 operations at the site ceased with the deposit virtually exhausted and all contractual commitments completed. From the outset, a site specific approach was adopted in developing the rehabilitation plan. Other sites'experience was evaluated but was adopted only if appropriate for Mary Kathleen. As a result of this approach a conceptual solution was established for each area within the site. Each solution was then used as the basis for detailed planning for rehabilitation of that area. The rehabilitation program commenced in mid 1982 and was completed in late 1985. Results of monitoring provided a strong basis for confidence that the objectives of the plan have been met, and allowed for the relinquishment of all the remaining mining leases in August 1987

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

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    Carethers, John M; Stoffel, Elena M

    2015-01-01

    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. PMID:26309352

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

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    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.

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

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    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.

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

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    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.

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

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    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.

  15. Lynch syndrome-associated neoplasms

    DEFF Research Database (Denmark)

    Shia, Jinru; Holck, Susanne; Depetris, Giovanni

    2013-01-01

    It was a century ago that Warthin, a pathologist, first described the clinical condition now known as Lynch syndrome. One hundred years later, our understanding of this syndrome has advanced significantly. Much of the progress took place over the last 25 years and was marked by a series...... of interacting developments from the disciplines of clinical oncology, pathology, and molecular genetics, with each development serving to guide or enhance the next. The advancement of our understanding about the pathology of Lynch syndrome associated tumors exemplifies such intimate interplay among disciplines....... Today, accumulative knowledge has enabled surgical pathologists to detect tumors that are likely to be associated with Lynch syndrome, and the pathologist is playing an increasingly more important role in the care of these patients. The pathologist's ability is afforded primarily by information gained...

  16. 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.

  17. Three molecular pathways model colorectal carcinogenesis in Lynch syndrome.

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    Ahadova, Aysel; Gallon, Richard; Gebert, Johannes; Ballhausen, Alexej; Endris, Volker; Kirchner, Martina; Stenzinger, Albrecht; Burn, John; von Knebel Doeberitz, Magnus; Bläker, Hendrik; Kloor, Matthias

    2018-07-01

    Lynch syndrome is caused by germline mutations of DNA mismatch repair (MMR) genes. MMR deficiency has long been regarded as a secondary event in the pathogenesis of Lynch syndrome colorectal cancers. Recently, this concept has been challenged by the discovery of MMR-deficient crypt foci in the normal mucosa. We aimed to reconstruct colorectal carcinogenesis in Lynch syndrome by collecting molecular and histology evidence from Lynch syndrome adenomas and carcinomas. We determined the frequency of MMR deficiency in adenomas from Lynch syndrome mutation carriers by immunohistochemistry and by systematic literature analysis. To trace back the pathways of pathogenesis, histological growth patterns and mutational signatures were analyzed in Lynch syndrome colorectal cancers. Literature and immunohistochemistry analysis demonstrated MMR deficiency in 491 (76.7%) out of 640 adenomas (95% CI: 73.3% to 79.8%) from Lynch syndrome mutation carriers. Histologically normal MMR-deficient crypts were found directly adjacent to dysplastic adenoma tissue, proving their role as tumor precursors in Lynch syndrome. Accordingly, mutation signature analysis in Lynch colorectal cancers revealed that KRAS and APC mutations commonly occur after the onset of MMR deficiency. Tumors lacking evidence of polypous growth frequently presented with CTNNB1 and TP53 mutations. Our findings demonstrate that Lynch syndrome colorectal cancers can develop through three pathways, with MMR deficiency commonly representing an early and possibly initiating event. This underlines that targeting MMR-deficient cells by chemoprevention or vaccines against MMR deficiency-induced frameshift peptide neoantigens holds promise for tumor prevention in Lynch syndrome. © 2018 UICC.

  18. Milestones of Lynch syndrome: 1895-2015.

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    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. Modernization and Lynching in the New South

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    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.

  20. Lynch Syndrome: A Primer for Urologists and Panel Recommendations.

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    Mork, Maureen; Hubosky, Scott G; Rouprêt, Morgan; Margulis, Vitaly; Raman, Jay; Lotan, Yair; O'Brien, Timothy; You, Nancy; Shariat, Shahrokh F; Matin, Surena F

    2015-07-01

    Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer, is a common genetic disease. The predisposition of patients with Lynch syndrome to urological cancer, particularly upper tract urothelial carcinoma, is underappreciated. Urologists may be involved in several aspects of care involving Lynch syndrome, including identifying undiagnosed patients, surveillance of those with established Lynch syndrome or screening family members, in addition to treating patients with Lynch syndrome in whom upper tract urothelial carcinoma develops. We sought to increase awareness in the urological community about Lynch syndrome and provide some guidance where little currently exists. Using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement we reviewed the available published literature and guidelines from 1998 to 2014 on Lynch syndrome and its association with upper tract urothelial carcinoma. Recommendations based on the literature and the consensus of expert opinion are provided. No randomized or prospective study has been done to evaluate Lynch syndrome in the setting of urological cancer. All data were based on retrospective studies. Lynch syndrome is an autosomal dominant genetic disease caused by germline mutations in 4 mismatch repair genes, leading to the accumulation of DNA errors in microsatellite regions. Upper tract urothelial carcinoma develops in up to 28% of patients with known Lynch syndrome. The diagnosis of Lynch syndrome is established by clinical criteria, tumor tissue testing and genetic evaluation. Urologists should suspect Lynch syndrome when a patient with upper tract urothelial carcinoma presents before age 60 years or meets the 3-2-1 rule. Screening patients with Lynch syndrome for upper tract urothelial carcinoma presents a particular challenge. While no ideal screening test exists, at a minimum routine urinalysis is recommended using the American Urological Association guideline of 3 or more red

  1. Lynch Syndrome: Genomics Update and Imaging Review.

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    Cox, Veronica L; Saeed Bamashmos, Anas A; Foo, Wai Chin; Gupta, Shiva; Yedururi, Sireesha; Garg, Naveen; Kang, Hyunseon Christine

    2018-01-01

    Lynch syndrome is the most common hereditary cancer syndrome, the most common cause of heritable colorectal cancer, and the only known heritable cause of endometrial cancer. Other cancers associated with Lynch syndrome include cancers of the ovary, stomach, urothelial tract, and small bowel, and less frequently, cancers of the brain, biliary tract, pancreas, and prostate. The oncogenic tendency of Lynch syndrome stems from a set of genomic alterations of mismatch repair proteins. Defunct mismatch repair proteins cause unusually high instability of regions of the genome called microsatellites. Over time, the accumulation of mutations in microsatellites and elsewhere in the genome can affect the production of important cellular proteins, spurring tumorigenesis. Universal testing of colorectal tumors for microsatellite instability (MSI) is now recommended to (a) prevent cases of Lynch syndrome being missed owing to the use of clinical criteria alone, (b) reduce morbidity and mortality among the relatives of affected individuals, and (c) guide management decisions. Organ-specific cancer risks and associated screening paradigms vary according to the sex of the affected individual and the type of germline DNA alteration causing the MSI. Furthermore, Lynch syndrome-associated cancers have different pathologic, radiologic, and clinical features compared with their sporadic counterparts. Most notably, Lynch syndrome-associated tumors tend to be more indolent than non-Lynch syndrome-associated neoplasms and thus may respond differently to traditional chemotherapy regimens. The high MSI in cases of colorectal cancer reflects a difference in the biologic features of the tumor, possibly with a unique susceptibility to immunotherapy. © RSNA, 2018.

  2. Upper urinary tract carcinoma in Lynch syndrome cases.

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    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.

  3. 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.

  4. Molecular subtype classification of urothelial carcinoma in Lynch syndrome.

    Science.gov (United States)

    Therkildsen, Christina; Eriksson, Pontus; Höglund, Mattias; Jönsson, Mats; Sjödahl, Gottfrid; Nilbert, Mef; Liedberg, Fredrik

    2018-05-23

    Lynch syndrome confers an increased risk for urothelial carcinoma (UC). Molecular subtypes may be relevant to prognosis and therapeutic possibilities, but have to date not been defined in Lynch syndrome-associated urothelial cancer. We aimed to provide a molecular description of Lynch syndrome-associated UC. Thus, Lynch syndrome-associated UC of the upper urinary tract and the urinary bladder were identified in the Danish hereditary non-polyposis colorectal cancer (HNPCC) register and were transcriptionally and immunohistochemically profiled and further related to data from 307 sporadic urothelial carcinomas. Whole genome mRNA expression profiles of 41 tumors and immunohistochemical stainings against FGFR3, KRT5, CCNB1, RB1, and CDKN2A (p16) of 37 tumors from Lynch syndrome patients were generated. Pathological data, microsatellite instability, anatomic location, and overall survival data was analyzed and compared with sporadic bladder cancer. The 41 Lynch syndrome-associated UC developed at a mean age of 61 years with 59% women. mRNA expression profiling and immunostaining classified the majority of the Lynch syndrome-associated UC as Urothelial-like tumors with only 20% being Genomically Unstable, Basal/SCC-like or other subtypes. The subtypes were associated with stage, grade, and microsatellite instability. Comparison to larger data sets revealed that Lynch syndrome-associated UC share molecular similarities with sporadic UC. In conclusion, transcriptomic and immunohistochemical profiling identifies a predominance of the Urothelial-like molecular subtype in Lynch syndrome and reveals that the molecular subtypes of sporadic bladder cancer are relevant also within this hereditary, mismatch-repair defective subset. This article is protected by copyright. All rights reserved. Molecular Oncology (2018) © 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

  5. 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. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  6. Molecular subtype classification of urothelial carcinoma in Lynch syndrome

    DEFF Research Database (Denmark)

    Therkildsen, Christina; Eriksson, Pontus; Höglund, Mattias

    2018-01-01

    Lynch syndrome confers an increased risk for urothelial carcinoma (UC). Molecular subtypes may be relevant to prognosis and therapeutic possibilities, but have to date not been defined in Lynch syndrome-associated urothelial cancer. We aimed to provide a molecular description of Lynch syndrome......-associated UC. Thus, Lynch syndrome-associated UC of the upper urinary tract and the urinary bladder were identified in the Danish hereditary non-polyposis colorectal cancer (HNPCC) register and were transcriptionally and immunohistochemically profiled and further related to data from 307 sporadic urothelial...... carcinomas. Whole genome mRNA expression profiles of 41 tumors and immunohistochemical stainings against FGFR3, KRT5, CCNB1, RB1, and CDKN2A (p16) of 37 tumors from Lynch syndrome patients were generated. Pathological data, microsatellite instability, anatomic location, and overall survival data was analyzed...

  7. Diagnosis of Lynch Syndrome: Genetic Testing Identifies a Potentially Deadly Hereditary Disease

    Science.gov (United States)

    ... of Lynch Syndrome Follow us A Diagnosis of Lynch Syndrome Genetic testing identifies a potentially deadly hereditary disease ... helped Jack learn what was wrong. Jack had Lynch Syndrome—an inherited disorder. Lynch Syndrome increases the risk ...

  8. Factors affecting groundwater quality at the rehabilitated Mary Kathleen Tailings Dam, Australia

    International Nuclear Information System (INIS)

    Ward, T.A.; Hart, K.P.; Morton, W.H.; Levins, D.M.

    1984-01-01

    The Mary Kathleen uranium mine and treatment plant ceased operation in late 1982 and a plan for the closure and rehabilitation of the area was developed by Mary Kathleen Uranium Ltd in association with consultants. This paper describes some of the groundwater quality studies undertaken in support of the rehabilitation program including sampling within the tailings dam to determine the profile of radionuclides, accelerated leaching tests on tailings to estimate long-term release rates of radium, monitoring of piezometers to determine the rate of movement of contaminants, and disposal of acidic effluent by neutralization and ion exchange through infiltration trenches. From accelerated leaching tests, it is estimated that a maximum of 0.13% of 226 Ra will be leached from the tailings in the first 1,000 years. There is no evidence that uranium or any of its daughters is moving away from the waste disposal area. The movement of heavy metals, radionuclides and acidity is strongly retarded by the alkaline soils

  9. 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.

  10. 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.

  11. Mismatch repair genes in Lynch syndrome: a review

    Directory of Open Access Journals (Sweden)

    Felipe Cavalcanti Carneiro da Silva

    Full Text Available 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; and postmeiotic segregation increased 1 (PMS1. It has been proposed that one additional mismatch repair gene, mutL homolog 3 (MLH3, also plays a role in Lynch syndrome predisposition, but the clinical significance of mutations in this gene is less clear. According to the InSiGHT database (International Society for Gastrointestinal Hereditary Tumors, approximately 500 different LS-associated mismatch repair gene mutations are known, primarily involving MLH1 (50% and MSH2 (40%, while others account for 10%. Much progress has been made in understanding the molecular basis of Lynch Syndrome. Molecular characterization will be the most accurate way of defining Lynch syndrome and will provide predictive information of greater accuracy regarding the risks of colon and extracolonic cancer and enable optimal cancer surveillance regimens.

  12. PMS2 involvement in patients suspected of Lynch syndrome.

    Science.gov (United States)

    Niessen, Renée 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

    2009-04-01

    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, PMS2, play a far more important role in Lynch syndrome than initially thought. To explore this further, we determined the prevalence of pathogenic germline PMS2 mutations in a series of Lynch syndrome-suspected patients. Ninety-seven patients who had early-onset microsatellite instable colorectal or endometrial cancer, or multiple Lynch syndrome-associated tumors and/or were from an Amsterdam Criteria II-positive family were selected for this study. These patients carried no pathogenic germline mutation in MLH1, MSH2, or MSH6. When available, tumors were investigated for immunohistochemical staining (IHC) for PMS2. PMS2 was screened in all patients by exon-by-exon sequencing. We identified four patients with a pathogenic PMS2 mutation (4%) among the 97 patients we selected. IHC of PMS2 was informative in one of the mutation carriers, and in this case, the tumor showed loss of PMS2 expression. In conclusion, our study confirms the finding of previous studies that PMS2 is more frequently involved in Lynch syndrome than originally expected.

  13. Immunohistochemical Pitfalls: Common Mistakes in the Evaluation of Lynch Syndrome.

    Science.gov (United States)

    Markow, Michael; Chen, Wei; Frankel, Wendy L

    2017-12-01

    At least 15% of colorectal cancers diagnosed in the United States are deficient in mismatch repair mechanisms. Most of these are sporadic, but approximately 3% of colorectal cancers result from germline alterations in mismatch repair genes and represent Lynch syndrome. It is critical to identify patients with Lynch syndrome to institute appropriate screening and surveillance for patients and their families. Exclusion of Lynch syndrome in sporadic cases is equally important because it reduces anxiety for patients and prevents excessive spending on unnecessary surveillance. Immunohistochemistry is one of the most widely used screening tools for identifying patients with Lynch syndrome. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. [A Case of Ascending Colon Cancer with Lynch Syndrome Who Underwent XELOX Adjuvant Chemotherapy].

    Science.gov (United States)

    Takase, Koki; Murata, Kohei; Kagawa, Yoshinori; Nose, Yohei; Kawai, Kenji; Sakamoto, Takuya; Naito, Atsushi; Murakami, Kohei; Katsura, Yoshiteru; Omura, Yoshiaki; Takeno, Atsushi; Nakatsuka, Shinichi; Takeda, Yutaka; Kato, Takeshi; Tamura, Shigeyuki

    2018-01-01

    Lynch syndrome is an inherited syndrome with the development of the colorectal and various other cancers. Lynch syndrome is caused by mutations in the mismatch repair genes. A 33 year-old male underwent XELOX adjuvant chemotherapy for ascending colon cancer with Lynch syndrome. Although efficacy of 5-FU is not demonstrated in Lynch syndrome, MOSAIC trial had suggested a benefit from FOLFOX compared with 5-FU in patients who have colorectal cancer with Lynch syndrome. Oxaliplatin-based adjuvant chemotherapy can be a therapeutic option for colorectal cancer in lynch syndrome patients.

  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. 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....... The effect remained when cancers diagnosed at surveillance were excluded, applied to maternal as well as paternal inheritance, and was independent of the MMR gene mutated. CONCLUSION: The effect from anticipation demonstrated in this large, population-based Lynch syndrome cohort underscores the need...

  17. 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....

  18. Management of extracolonic tumours in patients with Lynch syndrome

    NARCIS (Netherlands)

    Koornstra, Jan J; Mourits, Marian Je; Sijmons, Rolf H; Leliveld-Kors, Anna; Hollema, Harry; Kleibeuker, Jan H

    Hereditary nonpolyposis colorectal cancer, or Lynch syndrome, is responsible for 2-3% of all colorectal cancers. Lynch syndrome is also associated with a high risk of extracolonic cancers, including endometrial, stomach, small bowel, pancreas, biliary tract, ovary, urinary tract, brain, and skin

  19. 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.

  20. 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.

  1. 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.

  2. 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,

  3. DNA mismatch repair protein deficient non-neoplastic colonic crypts: a novel indicator of Lynch syndrome.

    Science.gov (United States)

    Pai, Rish K; Dudley, Beth; Karloski, Eve; Brand, Randall E; O'Callaghan, Neil; Rosty, Christophe; Buchanan, Daniel D; Jenkins, Mark A; Thibodeau, Stephen N; French, Amy J; Lindor, Noralane M; Pai, Reetesh K

    2018-06-08

    Lynch syndrome is the most common form of hereditary colorectal carcinoma. However, establishing the diagnosis of Lynch syndrome is challenging, and ancillary studies that distinguish between sporadic DNA mismatch repair (MMR) protein deficiency and Lynch syndrome are needed, particularly when germline mutation studies are inconclusive. The aim of this study was to determine if MMR protein-deficient non-neoplastic intestinal crypts can help distinguish between patients with and without Lynch syndrome. We evaluated the expression of MMR proteins in non-neoplastic intestinal mucosa obtained from colorectal surgical resection specimens from patients with Lynch syndrome-associated colorectal carcinoma (n = 52) and patients with colorectal carcinoma without evidence of Lynch syndrome (n = 70), including sporadic MMR protein-deficient colorectal carcinoma (n = 30), MMR protein proficient colorectal carcinoma (n = 30), and "Lynch-like" syndrome (n = 10). MMR protein-deficient non-neoplastic colonic crypts were identified in 19 of 122 (16%) patients. MMR protein-deficient colonic crypts were identified in 18 of 52 (35%) patients with Lynch syndrome compared to only 1 of 70 (1%) patients without Lynch syndrome (p Lynch-like" syndrome and harbored two MSH2-deficient non-neoplastic colonic crypts. MMR protein-deficient non-neoplastic colonic crypts were not identified in patients with sporadic MMR protein-deficient or MMR protein proficient colorectal carcinoma. Our findings suggest that MMR protein-deficient colonic crypts are a novel indicator of Lynch syndrome, and evaluation for MMR protein-deficient crypts may be a helpful addition to Lynch syndrome diagnostics.

  4. TumorNext-Lynch-MMR: a comprehensive next generation sequencing assay for the detection of germline and somatic mutations in genes associated with mismatch repair deficiency and Lynch syndrome.

    Science.gov (United States)

    Gray, Phillip N; Tsai, Pei; Chen, Daniel; Wu, Sitao; Hoo, Jayne; Mu, Wenbo; Li, Bing; Vuong, Huy; Lu, Hsiao-Mei; Batth, Navanjot; Willett, Sara; Uyeda, Lisa; Shah, Swati; Gau, Chia-Ling; Umali, Monalyn; Espenschied, Carin; Janicek, Mike; Brown, Sandra; Margileth, David; Dobrea, Lavinia; Wagman, Lawrence; Rana, Huma; Hall, Michael J; Ross, Theodora; Terdiman, Jonathan; Cullinane, Carey; Ries, Savita; Totten, Ellen; Elliott, Aaron M

    2018-04-17

    The current algorithm for Lynch syndrome diagnosis is highly complex with multiple steps which can result in an extended time to diagnosis while depleting precious tumor specimens. Here we describe the analytical validation of a custom probe-based NGS tumor panel, TumorNext-Lynch-MMR, which generates a comprehensive genetic profile of both germline and somatic mutations that can accelerate and streamline the time to diagnosis and preserve specimen. TumorNext-Lynch-MMR can detect single nucleotide variants, small insertions and deletions in 39 genes that are frequently mutated in Lynch syndrome and colorectal cancer. Moreover, the panel provides microsatellite instability status and detects loss of heterozygosity in the five Lynch genes; MSH2 , MSH6 , MLH1 , PMS2 and EPCAM . Clinical cases are described that highlight the assays ability to differentiate between somatic and germline mutations, precisely classify variants and resolve discordant cases.

  5. Lynch Syndrome-Related Clear Cell Carcinoma of the Cervix: A Case Report.

    Science.gov (United States)

    Nakamura, Kohei; Nakayama, Kentaro; Minamoto, Toshiko; Ishibashi, Tomoka; Ohnishi, Kaori; Yamashita, Hitomi; Ono, Ruriko; Sasamori, Hiroki; Razia, Sultana; Hossain, Mohammad Mahmud; Kamrunnahar, Shanta; Ishikawa, Masako; Ishikawa, Noriyoshi; Kyo, Satoru

    2018-03-25

    Lynch syndrome, a hereditary cancer syndrome, occurs because of germline mutations in at least one of four DNA mismatch repair genes (MutL Homolog 1 ( MLH1 ), MutS Homolog 2 ( MSH2 ), MutS Homolog 6 ( MSH6 ), and PMS1 Homolog 2 ( PMS2 )). The disorder is associated with colorectal, endometrial, and other epithelial malignancies, but not cervical cancer. We report a woman with Lynch syndrome with synchronous cervical cancer. This is the first report of Lynch syndrome-related clear cell carcinoma of the cervix, which indicates the possibility of an association between cervical cancer and Lynch syndrome. Suitable genetic tests are required to determine whether common genetics can account for synchronous or subsequent malignancies in Lynch syndrome patients and their families. Such knowledge will also enhance our understanding of the genetic mechanisms governing the development of apparently unrelated cancers.

  6. 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

    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...... 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...

  7. 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.

  8. Hegemonic Masculinity and the Position of Men in Kathleen Winter’s Annabel

    OpenAIRE

    Tay Lai Kit; Wan Roselezam Wan Yahya

    2016-01-01

    Emerging from the1980s, the concept of masculinity has slowly started to make its way towards social studies. Instead of a singular fixed identity, masculinity has now been claimed to be branching into several types – hegemonic masculinity, complicit masculinity, marginalized masculinity, and subordinated masculinity. By utilizing the notion of hegemonic masculinity, this paper observes the thoughts and decisions made by men in Kathleen Winter’s Annabel. This paper explores and re-examines th...

  9. Lynch Syndrome-Related Clear Cell Carcinoma of the Cervix: A Case Report

    Science.gov (United States)

    Nakamura, Kohei; Nakayama, Kentaro; Minamoto, Toshiko; Ishibashi, Tomoka; Ohnishi, Kaori; Yamashita, Hitomi; Ono, Ruriko; Sasamori, Hiroki; Razia, Sultana; Hossain, Mohammad Mahmud; Kamrunnahar, Shanta; Ishikawa, Masako; Ishikawa, Noriyoshi; Kyo, Satoru

    2018-01-01

    Lynch syndrome, a hereditary cancer syndrome, occurs because of germline mutations in at least one of four DNA mismatch repair genes (MutL Homolog 1 (MLH1), MutS Homolog 2 (MSH2), MutS Homolog 6 (MSH6), and PMS1 Homolog 2 (PMS2)). The disorder is associated with colorectal, endometrial, and other epithelial malignancies, but not cervical cancer. We report a woman with Lynch syndrome with synchronous cervical cancer. This is the first report of Lynch syndrome-related clear cell carcinoma of the cervix, which indicates the possibility of an association between cervical cancer and Lynch syndrome. Suitable genetic tests are required to determine whether common genetics can account for synchronous or subsequent malignancies in Lynch syndrome patients and their families. Such knowledge will also enhance our understanding of the genetic mechanisms governing the development of apparently unrelated cancers. PMID:29587389

  10. Lynch Syndrome-Related Clear Cell Carcinoma of the Cervix: A Case Report

    Directory of Open Access Journals (Sweden)

    Kohei Nakamura

    2018-03-01

    Full Text Available Lynch syndrome, a hereditary cancer syndrome, occurs because of germline mutations in at least one of four DNA mismatch repair genes (MutL Homolog 1 (MLH1, MutS Homolog 2 (MSH2, MutS Homolog 6 (MSH6, and PMS1 Homolog 2 (PMS2. The disorder is associated with colorectal, endometrial, and other epithelial malignancies, but not cervical cancer. We report a woman with Lynch syndrome with synchronous cervical cancer. This is the first report of Lynch syndrome-related clear cell carcinoma of the cervix, which indicates the possibility of an association between cervical cancer and Lynch syndrome. Suitable genetic tests are required to determine whether common genetics can account for synchronous or subsequent malignancies in Lynch syndrome patients and their families. Such knowledge will also enhance our understanding of the genetic mechanisms governing the development of apparently unrelated cancers.

  11. 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.

  12. 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.

  13. Leaching and solvent extraction at Mary Kathleen Uranium Ltd

    International Nuclear Information System (INIS)

    Richmond, G.D.

    1978-01-01

    Mary Kathleen Uranium Ltd. recommenced operations in early 1976 following a twelve year period of care and maintenance. Several sections of the plant were modified or completely changed for the second operation. The most important change was the replacement of ion exchange with solvent extraction as the means of purifying and upgrading uranium rich solutions. Most of the problems experienced in the solvent extraction system originate from the leach liquor which has a strong tendency to form stable emulsions. This has been countered by some careful control of leaching conditions and by closer observation of operations in the solvent extraction area. Most problems have now been resolved and plant recoveries are quite satisfactory

  14. Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database

    OpenAIRE

    Moller, Pal; Seppala, Toni; Bernstein, Inge; Holinski-Feder, Elke; Sala, Paola; Evans, D. Gareth; Lindblom, Annika; Macrae, Finlay; Blanco, Ignacio; Sijmons, Rolf; Jeffries, Jacqueline; Vasen, Hans; Burn, John; Nakken, Sigve; Hovig, Eivind

    2017-01-01

    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.\\ud \\ud 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 rela...

  15. Early onset of colorectal cancer in a 13-year-old girl with Lynch syndrome.

    Science.gov (United States)

    Ahn, Do Hee; Rho, Jung Hee; Tchah, Hann; Jeon, In-Sang

    2016-01-01

    Lynch syndrome is the most common inherited colon cancer syndrome. Patients with Lynch syndrome develop a range of cancers including colorectal cancer (CRC) and carry a mutation on one of the mismatched repair (MMR) genes. Although CRC usually occurs after the fourth decade in patients with Lynch syndrome harboring a heterozygous MMR gene mutation, it can occur in children with Lynch syndrome who have a compound heterozygous or homozygous MMR gene mutation. We report a case of CRC in a 13-year-old patient with Lynch syndrome and congenital heart disease. This patient had a heterozygous mutation in MLH1 (an MMR gene), but no compound MMR gene defects, and a K-RAS somatic mutation in the cancer cells.

  16. Recurrence and Variability of Germline EPCAM Deletions in Lynch Syndrome

    NARCIS (Netherlands)

    Kuiper, Roland P.; Vissers, Lisenka E. L. M.; Venkatachalam, Ramprasath; Bodmer, Danielle; Hoenselaar, Eveline; Goossens, Monique; Haufe, Aline; Kamping, Eveline; Niessen, Renee 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.

    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

  17. 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.

  18. Genetics Home Reference: Lynch syndrome

    Science.gov (United States)

    ... Genetic Changes Variations in the MLH1 , MSH2 , MSH6 , PMS2 , or EPCAM gene increase the risk of developing Lynch syndrome . The MLH1 , MSH2 , MSH6 , and PMS2 genes are involved in the repair of errors ...

  19. 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 individual episodes oscillate between carefully plotted psychology and lurid plot-holes. In other words: taken at face value, Luther is as interesting as it is messy. This paper proposes a reading of Luther that reconciles its many inconsistencies by treating it as if it was a David Lynch movie. If one...

  20. 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

  1. 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.

  2. 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

  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...... Lynch syndrome families. These mutations affected MLH1 in 40%, MSH2 in 36%, MSH6 in 18% and PMS2 in 6% of the families. A large variety of mutations were identified with splice site mutations being the most common mutation type in MLH1 and frameshift mutations predominating in MSH2 and MSH6. Large...... deletions of one or several exons accounted for 21% of the mutations in MLH1 and MSH2 and 22% in PMS2, but were rare (4%) in MSH6. In 66% of the Lynch syndrome families the variants identified were private and the effect from founder mutations was limited and predominantly related to a Finnish founder...

  4. The recommissioning of the treatment plant at Mary Kathleen Uranium Ltd

    International Nuclear Information System (INIS)

    Thomas, J.

    1978-01-01

    The recommissioning of the plant at Mary Kathleen involved several distinct phases. The previous plant process was modified significantly, the plant capacity was increased by the addition of new equipment and the existing equipment was in most cases overhauled. This equipment was either reused in its original duty or relocated. Maintenance requirements after the plant was commissioned were high because of the amount of modified equipment and also because some old items of equipment were deliberately not overhauled during recommissioning. The equipment that was overhauled has operated reliably. However some new equipment has not been as satisfactory

  5. 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...

  6. 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.

  7. 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.

  8. 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"

  9. 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

  10. 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.

  11. 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

  12. 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

    BACKGROUND: When compared to the other mismatch repair genes involved in Lynch syndrome, the identification of mutations within PMS2 has been limited (Lynch syndrome cases...... on immunohistochemical analysis. RESULTS: We have identified a frequently occurring frame-shift mutation (c.736_741del6ins11) in 12 ostensibly unrelated Lynch syndrome patients (20% of patients we have identified with a deleterious mutation in PMS2, n=61). These individuals all display the rare allele (population...... 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...

  13. Fertility and apparent genetic anticipation in Lynch syndrome.

    Science.gov (United States)

    Stupart, Douglas; Win, Aung Ko; Jenkins, Mark; Winship, Ingrid M; Goldberg, Paul; Ramesar, Rajkumar

    2014-09-01

    Genetic anticipation is the phenomenon in which age of onset of an inherited disorder decreases in successive generations. Inconsistent evidence suggests that this occurs in Lynch syndrome. A possible cause for apparent anticipation is fecundity bias, which occurs if the disease adversely affects fertility. The purpose of this study was to determine the effect of age of diagnosis of colorectal cancer (CRC) on lifetime fertility in Lynch syndrome, and whether this can falsely create the appearance of genetic anticipation. A computer model simulated age of diagnosis of CRC in hypothetical Lynch syndrome carriers and their offspring. The model assumed similar age distribution of CRC across generations (i.e. that there was no true anticipation). Age distribution of CRC diagnosis, and lifetime fertility rates (grouped by age of diagnosis of CRC) were determined from the Australasian Colorectal Cancer Family Registry (ACCFR). Apparent anticipation was calculated by comparing ages of diagnosis of CRC in affected parent-child pairs. A total of 1,088 patients with CRC were identified from the ACCFR. Total lifetime (cohort) fertility was related to age of diagnosis of CRC (correlation coefficient 0.13, P = 0.0001). In the simulation, apparent anticipation was 1.8 ± 0.54 years (P = 0.0044). Observed apparent anticipation in the ACCFR cohort was 4.8 ± 1.73 years (P = 0.0064). There was no difference in apparent anticipation between the simulate d and observed parent-child pairs (P = 0.89). The appearance of genetic anticipation in Lynch syndrome can be falsely created due to changes in fertility.

  14. The genetic basis of Lynch syndrome and its implications for clinical practice and risk management

    Science.gov (United States)

    Cohen, Stephanie A; Leininger, Anna

    2014-01-01

    Lynch syndrome is the most common cause of hereditary colon cancer, and accounts for as much as 3% of all colon and endometrial cancers. The identification and management of individuals with Lynch syndrome have evolved over the past 20 years, yet the syndrome remains vastly underdiagnosed. It is important for clinicians to recognize individuals and families who are at risk in order to be able to manage them appropriately and reduce their morbidity and mortality from this condition. This review will touch on the history of Lynch syndrome, the current knowledge of genotype–phenotype correlations, the cancers associated with Lynch syndrome, and management of individuals who are gene carriers. PMID:25161364

  15. 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

  16. 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.

  17. 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 Lynch 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.

  18. [Colorectal Carcinoma with Suspected Lynch Syndrome: A Multidisciplinary Algorithm].

    Science.gov (United States)

    Schneider, R; Schneider, C; Büttner, R; Reinacher-Schick, A; Tannapfel, A; Fürst, A; Rüschoff, J; Jakobeit, C; Royer-Pokora, B; Möslein, G

    2015-12-01

    Lynch syndrome is the most frequent hereditary cancer syndrome, accounting for approximately 3-5 % of all colorectal cancers. In addition, it is the most frequent predisposing hereditary cause of endometrial cancer and is also associated with gastric cancer, ovarian cancer, cancer of the urinary tract as well as several other cancers. In clinical practise Lynch syndrome is frequently not detected and many clinicians admit uncertainties regarding diagnostic procedures. Also, counselling of patients is considered difficult regarding therapeutic - especially prophylactic surgical and chemopreventive options and recommendations. Based on a review of available literature we discuss optimized strategies for improved detection of suspected Lynch syndrome patients. The aim of this review is to establish a clinical algorithm of how to proceed on a diagnostic level and to discuss surgical options at the time of a colorectal cancer. In order to identify patients with Lynch syndrome, family history should be ascertained and evaluated in regards to fulfilment of the Amsterdam-II- and/or the revised Bethesda criteria. Subsequently immunohistochemical staining for the mismatch-repair-genes, BRAF testing for MLH1 loss of expression, as well as testing for microsatellite instability in some, followed by genetic counselling and mutation analysis when indicated, is recommended. Pathological identification of suspected Lynch syndrome is readily feasible and straightforward. However, the need of performing these analyses in the tumor biopsy at the time of (gastroenterological) diagnosis of CRC neoplasia is essential, in order to offer patients the option of a prophylactically extended surgery and - as recommended in the German S3 guidelines - to discuss the option of a merely prophylactical hysterectomy and oophorectomy (if postmenopausal) in women. Close cooperation between gastroenterologists, pathologists and surgeons is warranted, so that patients may benefit from options of

  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. 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

    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...... and for diagnosis of Lynch syndrome, and perhaps other hereditary diseases....

  1. 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.

  2. 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...

  3. Screening for Lynch syndrome using risk assessment criteria in patients with ovarian cancer.

    Science.gov (United States)

    Takeda, Takashi; Tsuji, Kosuke; Banno, Kouji; Yanokura, Megumi; Kobayashi, Yusuke; Tominaga, Eiichiro; Aoki, Daisuke

    2018-05-01

    Lynch syndrome is a cancer predisposition syndrome caused by germline mutation of DNA mismatch repair (MMR) genes. Lynch syndrome only causes about 0.4% of cases of ovarian cancer, which suggests that universal screening may not be cost-efficient. However, the frequency of Lynch syndrome in ovarian cancer is unclear in the Asian population. The goal of the study was to investigate a screening strategy using family history. The subjects were 129 patients with ovarian cancer. Clinical and family history were collected using a self-administered questionnaire, and Society of Gynecologic Oncology (SGO) criteria 2007 and PREMM₅ were used for risk assessment. Microsatellite instability, immunohistochemistry, and methylation of MMR genes were analyzed. Of the 129 cases, 25 (19.4%) met the SGO criteria, and 4 of these 25 had MSI-high and MMR deficiency. Two cases had loss of MSH2 and MSH6, indicating MSH2 mutation, and the other two had loss of MLH1 and PMS2, including one without MLH1 methylation indicating MLH1 mutation. These results show that screening using family history can detect Lynch syndrome in 12.0% (3/25) of ovarian cancer cases. The 3 cases were positive for PREMM₅, but negative for Amsterdam II criteria and revised Bethesda guidelines. Genetic testing in one case with MSH2 and MSH6 deficiency confirmed the diagnosis of Lynch syndrome with MSH2 mutation. This is the first study of screening for Lynch syndrome in ovarian cancer using clinical and family history in an Asian population. This approach may be effective for diagnosis in these patients. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.

  4. Targeted Screening With Combined Age- and Morphology-Based Criteria Enriches Detection of Lynch Syndrome in Endometrial Cancer.

    Science.gov (United States)

    Lin, Douglas I; Hecht, Jonathan L

    2016-06-01

    Endometrial cancer is associated with Lynch syndrome in 2% to 6% of cases. Adequate screening may prevent of a second cancer and incident cancers in family members via risk-reducing strategies. The goal of the study was to evaluate the detection rate of Lynch syndrome via a targeted screening approach. In 2009, we incorporated targeted Lynch syndrome screening via immunohistochemistry for MLH1, PMS2, MSH2, and MSH6, followed by MLH1 promoter hypermethylation, in select cases of endometrial carcinoma. Criteria for patient selection included (1) all patients Lynch syndrome. Therefore, targeted screening with combined age and morphology based criteria enriches detection of Lynch syndrome in endometrial cancer. However, the detection rate is lower than the rates from published series that offer universal screening. © The Author(s) 2016.

  5. 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.

  6. Value-based healthcare in Lynch syndrome

    NARCIS (Netherlands)

    Hennink, Simone D; Hofland, N.; Gopie, J.P.; van der Kaa, C.; de Koning, K.; Nielsen, M.; Tops, C.; Morreau, H.; de Vos Tot Nederveen Cappel, W.H.; Langers, A.M.; Hardwick, J.C.; Gaarenstroom, K.N.; Tollenaar, R.A.; Veenendaal, R.A.; Tibben, A.; Wijnen, J.; van Heck, M.; van Asperen, C.; Roukema, J.A.; Hommes, D.W.; Hes, F.J.; Vasen, H.F.A.

    2013-01-01

    Lynch syndrome (LS), one of the most frequent forms of hereditary colorectal cancer (CRC), is caused by a defect in one of the mismatch repair (MMR) genes. Carriers of MMR defects have a strongly increased risk of developing CRC and endometrial cancer. Over the last few years, value-based healthcare

  7. 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...... on the incidence of colorectal adenoma or carcinoma among carriers of the Lynch syndrome. (Current Controlled Trials number, ISRCTN59521990.)...

  8. What the physician needs to know about Lynch syndrome: an update.

    Science.gov (United States)

    Lynch, Henry T; Lynch, Jane F

    2005-04-01

    The Lynch syndrome (hereditary nonpolyposis colorectal cancer [HNPCC]), is the most common form of hereditary colorectal cancer (CRC), accounting for 2% to 7% of all CRC cases. The next most common hereditary CRC syndrome is familial adenomatous polyposis (FAP), which accounts for less than 1% of all CRC. Lynch syndrome is of crucial clinical importance due to the fact that it predicts the lifetime risk for CRC and a litany of extra-CRC cancers (of the endometrium, ovary, stomach, small bowel, hepatobiliary tract, upper uroepithelial tract, and brain) through assessment of a well-orchestrated family history. A Lynch syndrome diagnosis is almost certain when a mutation in a mismatch repair gene--most commonly MSH2, MLHI, or, to a lesser degree, MSH6--is identified. Once diagnosed, the potential for significant reduction in cancer-related morbidity and mortality through highly targeted surveillance may be profound. Particularly important is colonoscopy initiated at an early age (ie, 25 years) and repeated annually due to accelerated carcinogenesis. In women, endometrial aspiration biopsy and transvaginal ultrasound are important given the extraordinarily high risk for endometrial and ovarian carcinoma. These cancer control strategies have a major impact on at-risk family members once they have been counseled and educated thoroughly about Lynch syndrome's natural history and their own hereditary cancer risk.

  9. The B-Lynch uterine brace suture, and a bit of this and a bit of that...

    Science.gov (United States)

    Karoshi, Mahantesh

    2010-03-01

    The widespread application of the B-Lynch brace suture to control postpartum hemorrhage has sparked interest in a variety of adjunctive methods, used alone or in combination, to control uterine bleeding. Although the B-Lynch brace suture has been used with good results throughout the world, failures can and do occur in rare instances, especially when the suture is incorrectly placed for use for an inappropriate indication. Four reports of additional methods to control postpartum hemorrhage are published in this issue of IJGO. Three use the B-Lynch brace suture combined with other techniques. The need for additional techniques reminds the reader of the importance of proper suture application for proper indication. Potential reasons for failure of the B-Lynch suture are provided.

  10. How does genetic risk information for Lynch syndrome translate to risk management behaviours?

    Science.gov (United States)

    Steel, Emma; Robbins, Andrew; Jenkins, Mark; Flander, Louisa; Gaff, Clara; Keogh, Louise

    2017-01-01

    There is limited research on why some individuals who have undergone predictive genetic testing for Lynch syndrome do not adhere to screening recommendations. This study aimed to explore qualitatively how Lynch syndrome non-carriers and carriers translate genetic risk information and advice to decisions about risk managment behaviours in the Australian healthcare system. Participants of the Australasian Colorectal Cancer Family Registry who had undergone predictive genetic testing for Lynch syndrome were interviewed on their risk management behaviours. Transcripts were analysed thematically using a comparative coding analysis. Thirty-three people were interviewed. Of the non-carriers ( n  = 16), 2 reported having apparently unnecessary colonoscopies, and 6 were unsure about what population-based colorectal cancer screening entails. Of the carriers ( n  = 17), 2 reported they had not had regular colonoscopies, and spoke about their discomfort with the screening process and a lack of faith in the procedure's ability to reduce their risk of developing colorectal cancer. Of the female carriers ( n  = 9), 2 could not recall being informed about the associated risk of gynaecological cancers. Non-carriers and female carriers of Lynch syndrome could benefit from further clarity and advice about appropriate risk management options. For those carriers who did not adhere to colonoscopy screening, a lack of faith in both genetic test results and screening were evident. It is essential that consistent advice is offered to both carriers and non-carriers of Lynch syndrome.

  11. The clinical phenotype of Lynch syndrome due to germline PMS2 mutations

    Science.gov (United States)

    Senter, Leigha; Clendenning, Mark; Sotamaa, Kaisa; Hampel, Heather; Green, Jane; Potter, John D.; Lindblom, Annika; Lagerstedt, Kristina; Thibodeau, Stephen N.; Lindor, Noralane M.; Young, Joanne; Winship, Ingrid; Dowty, James G.; White, Darren M.; Hopper, John L.; Baglietto, Laura; Jenkins, Mark A.; de la Chapelle, Albert

    2009-01-01

    Background and Aims Although the clinical phenotype of Lynch syndrome (also known as Hereditary Nonpolyposis Colorectal Cancer) has been well described, little is known about disease in PMS2 mutation carriers. Now that mutation detection methods can discern mutations in PMS2 from mutations in its pseudogenes, more mutation carriers have been identified. Information about the clinical significance of PMS2 mutations is crucial for appropriate counseling. Here, we report the clinical characteristics of a large series of PMS2 mutation carriers. Methods We performed PMS2 mutation analysis using long range PCR and MLPA for 99 probands diagnosed with Lynch syndrome-associated tumors showing isolated loss of PMS2 by immunohistochemistry. Penetrance was calculated using a modified segregation analysis adjusting for ascertainment. Results Germline PMS2 mutations were detected in 62% of probands (n = 55 monoallelic; 6 biallelic). Among families with monoallelic PMS2 mutations, 65.5% met revised Bethesda guidelines. Compared with the general population, in mutation carriers, the incidence of colorectal cancer was 5.2 fold higher and the incidence of endometrial cancer was 7.5 fold higher. In North America, this translates to a cumulative cancer risk to age 70 of 15–20% for colorectal cancer, 15% for endometrial cancer, and 25–32% for any Lynch syndrome-associated cancer. No elevated risk for non-Lynch syndrome-associated cancers was observed. Conclusions PMS2 mutations contribute significantly to Lynch syndrome but the penetrance for monoallelic mutation carriers appears to be lower than that for the other mismatch repair genes. Modified counseling and cancer surveillance guidelines for PMS2 mutation carriers are proposed. PMID:18602922

  12. Rehabilitation of the Mary Kathleen uranium mining and processing site

    International Nuclear Information System (INIS)

    Ward, T.A.

    1985-09-01

    A detailed plan for the rehabilitation of the Mary Kathleen mining and processing site was developed prior to the closure of operations in late 1982. The plan was based on three basic principles of: making all areas safe for public access; removing all structures which could deteriorate and become unsightly or unsafe with time; and encouraging natural revegetation on erosion resistant surfaces. The aim was to leave the site in a safe and satisfactory condition, consistent with future land use in the area, requiring no foreseeable ongoing maintenance and a minimum of precautionary monitoring. When the programme has been completed, the only constraint on future land use will be the need to control building construction in the tailings/ evaporation, dumps and mine areas as a precaution against possible exposure to radon daughters. Appropriate radiation and water quality monitoring programmes were incorporated in the plan

  13. Strategies to Identify the Lynch Syndrome Among Patients With Colorectal Cancer

    Science.gov (United States)

    Ladabaum, Uri; Wang, Grace; Terdiman, Jonathan; Blanco, Amie; Kuppermann, Miriam; Boland, C. Richard; Ford, James; Elkin, Elena; Phillips, Kathryn A.

    2013-01-01

    Background Testing has been advocated for all persons with newly diagnosed colorectal cancer to identify families with the Lynch syndrome, an autosomal dominant cancer-predisposition syndrome that is a paradigm for personalized medicine. Objective To estimate the effectiveness and cost-effectiveness of strategies to identify the Lynch syndrome, with attention to sex, age at screening, and differential effects for probands and relatives. Design Markov model that incorporated risk for colorectal, endometrial, and ovarian cancers. Data Sources Published literature. Target Population All persons with newly diagnosed colorectal cancer and their relatives. Time Horizon Lifetime. Perspective Third-party payer. Intervention Strategies based on clinical criteria, prediction algorithms, tumor testing, or up-front germline mutation testing, followed by tailored screening and risk-reducing surgery. Outcome Measures Life-years, cancer cases and deaths, costs, and incremental cost-effectiveness ratios. Results of Base-Case Analysis The benefit of all strategies accrued primarily to relatives with a mutation associated with the Lynch syndrome, particularly women, whose life expectancy could increase by approximately 4 years with hysterectomy and salpingo-oophorectomy and adherence to colorectal cancer screening recommendations. At current rates of germline testing, screening, and prophylactic surgery, the strategies reduced deaths from colorectal cancer by 7% to 42% and deaths from endometrial and ovarian cancer by 1% to 6%. Among tumor-testing strategies, immunohistochemistry followed by BRAF mutation testing was preferred, with an incremental cost-effectiveness ratio of $36 200 per life-year gained. Results of Sensitivity Analysis The number of relatives tested per proband was a critical determinant of both effectiveness and cost-effectiveness, with testing of 3 to 4 relatives required for most strategies to meet a threshold of $50 000 per life-year gained. Immunohistochemistry

  14. Mike Lynch

    DEFF Research Database (Denmark)

    Horst, Maja; Irwin, Alan

    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...... jobs, this presentation will discuss the relationship between vacation, work, professional ethos and personal contribution in the context of STS.......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...

  15. A model-based assessment of the cost-utility of strategies to identify Lynch syndrome in early-onset colorectal cancer patients.

    Science.gov (United States)

    Snowsill, Tristan; Huxley, Nicola; Hoyle, Martin; Jones-Hughes, Tracey; Coelho, Helen; Cooper, Chris; Frayling, Ian; Hyde, Chris

    2015-04-25

    Lynch syndrome is an autosomal dominant cancer predisposition syndrome caused by mutations in the DNA mismatch repair genes MLH1, MSH2, MSH6 and PMS2. Individuals with Lynch syndrome have an increased risk of colorectal cancer, endometrial cancer, ovarian and other cancers. Lynch syndrome remains underdiagnosed in the UK. Reflex testing for Lynch syndrome in early-onset colorectal cancer patients is proposed as a method to identify more families affected by Lynch syndrome and offer surveillance to reduce cancer risks, although cost-effectiveness is viewed as a barrier to implementation. The objective of this project was to estimate the cost-utility of strategies to identify Lynch syndrome in individuals with early-onset colorectal cancer in the NHS. A decision analytic model was developed which simulated diagnostic and long-term outcomes over a lifetime horizon for colorectal cancer patients with and without Lynch syndrome and for relatives of those patients. Nine diagnostic strategies were modelled which included microsatellite instability (MSI) testing, immunohistochemistry (IHC), BRAF mutation testing (methylation testing in a scenario analysis), diagnostic mutation testing and Amsterdam II criteria. Biennial colonoscopic surveillance was included for individuals diagnosed with Lynch syndrome and accepting surveillance. Prophylactic hysterectomy with bilateral salpingo-oophorectomy (H-BSO) was similarly included for women diagnosed with Lynch syndrome. Costs from NHS and Personal Social Services perspective and quality-adjusted life years (QALYs) were estimated and discounted at 3.5% per annum. All strategies included for the identification of Lynch syndrome were cost-effective versus no testing. The strategy with the greatest net health benefit was MSI followed by BRAF followed by diagnostic genetic testing, costing £5,491 per QALY gained over no testing. The effect of prophylactic H-BSO on health-related quality of life (HRQoL) is uncertain and could outweigh

  16. 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...

  17. 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.

  18. Common mutations identified in the MLH1 gene in familial Lynch syndrome

    OpenAIRE

    Jisha Elias; Coral Karunakaran; Snigdha Majumder; Malini Manoharan; Rakshit Shah; Yogesh Mistry; Rajesh Ramanuj; Niraj Bhatt; Arati Khanna- Gupta

    2017-01-01

    Lynch syndrome (Hereditary Non Polyposis Colorectal Cancer, HNPCC) is one of the most common hereditary familial colorectal cancers (CRC) with an autosomal dominant pattern of inheritance. It accounts for 2-5% of the total CRCs reported worldwide. Although a lower incidence for CRCs have been observed in India, the last decade has shown a remarkable increase of CRC incidences (2-4 %). Features of Lynch syndrome associated colorectal cancer include early age of cancer onset, accelerated car...

  19. 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.

  20. 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).

  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

    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...

  2. 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....

  3. Caring Is Activism: Black Southern Womanist Teachers Theorizing and the Careers of Kathleen Crosby and Bertha Maxwell-Roddey, 1946-1986

    Science.gov (United States)

    Ramsey, Sonya

    2012-01-01

    This article, based on archival research and oral interviews, examines the personal and professional impact of desegregation on African American teachers in an urban southern setting by focusing on the life stories of two public school teachers, Kathleen Crosby and Bertha Maxwell-Roddey. Both taught in segregated schools, helped to desegregate…

  4. Rehabilitation of the Mary Kathleen uranium mine site after closure

    International Nuclear Information System (INIS)

    Ward, T.A.; Flannagan, J.C.; Hubery, R.W.

    1983-01-01

    The Mary Kathleen uranium mine and treatment plant ceased operation in late 1982 and a plan for the closure and rehabilitation of the area was developed. The object of the plan is to make all areas safe, remove all non-permanent structures and encourage natural revegetation. The plan has been accepted by the Queensland Mines Department. The mine pit will be left stable, inaccessible to vehicles, and containing about 50 metres of water. Mine waste and borrow areas will be contoured, ripped and seeded to encourage revegetation. The treatment plant area will be cleared of all equipment and light structures, decontaminated and revegetated. The evaporation ponds will be dried out, precipitate and contaminated soil will be removed to the tailings dam, and the area will be contoured and revegetated. The tailings will be covered with one metre of waste rock and boreholes will be used to recover groundwater containing salts for storage in the pit

  5. A model-based assessment of the cost–utility of strategies to identify Lynch syndrome in early-onset colorectal cancer patients

    International Nuclear Information System (INIS)

    Snowsill, Tristan; Huxley, Nicola; Hoyle, Martin; Jones-Hughes, Tracey; Coelho, Helen; Cooper, Chris; Frayling, Ian; Hyde, Chris

    2015-01-01

    Lynch syndrome is an autosomal dominant cancer predisposition syndrome caused by mutations in the DNA mismatch repair genes MLH1, MSH2, MSH6 and PMS2. Individuals with Lynch syndrome have an increased risk of colorectal cancer, endometrial cancer, ovarian and other cancers. Lynch syndrome remains underdiagnosed in the UK. Reflex testing for Lynch syndrome in early-onset colorectal cancer patients is proposed as a method to identify more families affected by Lynch syndrome and offer surveillance to reduce cancer risks, although cost-effectiveness is viewed as a barrier to implementation. The objective of this project was to estimate the cost–utility of strategies to identify Lynch syndrome in individuals with early-onset colorectal cancer in the NHS. A decision analytic model was developed which simulated diagnostic and long-term outcomes over a lifetime horizon for colorectal cancer patients with and without Lynch syndrome and for relatives of those patients. Nine diagnostic strategies were modelled which included microsatellite instability (MSI) testing, immunohistochemistry (IHC), BRAF mutation testing (methylation testing in a scenario analysis), diagnostic mutation testing and Amsterdam II criteria. Biennial colonoscopic surveillance was included for individuals diagnosed with Lynch syndrome and accepting surveillance. Prophylactic hysterectomy with bilateral salpingo-oophorectomy (H-BSO) was similarly included for women diagnosed with Lynch syndrome. Costs from NHS and Personal Social Services perspective and quality-adjusted life years (QALYs) were estimated and discounted at 3.5% per annum. All strategies included for the identification of Lynch syndrome were cost-effective versus no testing. The strategy with the greatest net health benefit was MSI followed by BRAF followed by diagnostic genetic testing, costing £5,491 per QALY gained over no testing. The effect of prophylactic H-BSO on health-related quality of life (HRQoL) is uncertain and could

  6. 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

  7. 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

  8. 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.

  9. The clinical phenotype of Lynch syndrome due to germ-line PMS2 mutations.

    Science.gov (United States)

    Senter, Leigha; Clendenning, Mark; Sotamaa, Kaisa; Hampel, Heather; Green, Jane; Potter, John D; Lindblom, Annika; Lagerstedt, Kristina; Thibodeau, Stephen N; Lindor, Noralane M; Young, Joanne; Winship, Ingrid; Dowty, James G; White, Darren M; Hopper, John L; Baglietto, Laura; Jenkins, Mark A; de la Chapelle, Albert

    2008-08-01

    Although the clinical phenotype of Lynch syndrome (also known as hereditary nonpolyposis colorectal cancer) has been well described, little is known about disease in PMS2 mutation carriers. Now that mutation detection methods can discern mutations in PMS2 from mutations in its pseudogenes, more mutation carriers have been identified. Information about the clinical significance of PMS2 mutations is crucial for appropriate counseling. Here, we report the clinical characteristics of a large series of PMS2 mutation carriers. We performed PMS2 mutation analysis using long-range polymerase chain reaction and multiplex ligation-dependent probe amplification for 99 probands diagnosed with Lynch syndrome-associated tumors showing isolated loss of PMS2 by immunohistochemistry. Penetrance was calculated using a modified segregation analysis adjusting for ascertainment. Germ-line PMS2 mutations were detected in 62% of probands (n = 55 monoallelic; 6 biallelic). Among families with monoallelic PMS2 mutations, 65.5% met revised Bethesda guidelines. Compared with the general population, in mutation carriers, the incidence of colorectal cancer was 5.2-fold higher, and the incidence of endometrial cancer was 7.5-fold higher. In North America, this translates to a cumulative cancer risk to age 70 years of 15%-20% for colorectal cancer, 15% for endometrial cancer, and 25%-32% for any Lynch syndrome-associated cancer. No elevated risk for non-Lynch syndrome-associated cancers was observed. PMS2 mutations contribute significantly to Lynch syndrome, but the penetrance for monoallelic mutation carriers appears to be lower than that for the other mismatch repair genes. Modified counseling and cancer surveillance guidelines for PMS2 mutation carriers are proposed.

  10. 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

    BACKGROUND: When compared to the other mismatch repair genes involved in Lynch syndrome, the identification of mutations within PMS2 has been limited (Lynch syndrome cases...... on immunohistochemical analysis. RESULTS: We have identified a frequently occurring frame-shift mutation (c.736_741del6ins11) in 12 ostensibly unrelated Lynch syndrome patients (20% of patients we have identified with a deleterious mutation in PMS2, n=61). These individuals all display the rare allele (population...... 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...

  11. 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

  12. 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...

  13. 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...... in one of the three main mismatch repair (MMR) genes. In contrast to the clinic-based population, we re-analyze data on a population-based Lynch syndrome cohort, derived from the Danish HNPCC-register. Both datasets indicate evidence of genetic anticipation in Lynch syndrome. We then expand our review...

  14. 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

  15. Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance : first report from the prospective Lynch syndrome database

    NARCIS (Netherlands)

    Moller, Pal; Seppala, Toni; Bernstein, Inge; Holinski-Feder, Elke; Sala, Paola; Evans, D. Gareth; Lindblom, Annika; Macrae, Finlay; Blanco, Ignacio; Sijmons, Rolf; Jeffries, Jacqueline; Vasen, Hans; Burn, John; Nakken, Sigve; Hovig, Eivind; Rodland, Einar Andreas; Tharmaratnam, Kukatharmini; Cappel, Wouter H. de Vos Tot Nederveen; Hill, James; Wijnen, Juul; Green, Kate; Lalloo, Fiona; Sunde, Lone; Mints, Miriam; Bertario, Lucio; Pineda, Marta; Navarro, Matilde; Morak, Monika; Renkonen-Sinisalo, Laura; Frayling, Ian M.; Plazzer, John-Paul; Pylvanainen, Kirsi; Sampson, Julian R.; Capella, Gabriel; Mecklin, Jukka-Pekka; Moslein, Gabriela

    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

  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)

    Salloum, Ramzi G; Guo, Yi; Wang, Mo; Prosperi, Mattia; Zhang, Hansi; Du, Xinsong; Ramirez-Diaz, Laura J; He, Zhe

    2017-01-01

    Background 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. Objective 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. Methods 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. Results Of all tweets (N=16,667), 87.38% (14,564/16,667) were related to Lynch syndrome. Of the Lynch syndrome–related tweets, 81

  17. 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...

  18. 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....

  19. 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.

  20. Utility of MLH1 methylation analysis in the clinical evaluation of Lynch Syndrome in women with endometrial cancer.

    Science.gov (United States)

    Bruegl, Amanda S; Djordjevic, Bojana; Urbauer, Diana L; Westin, Shannon N; Soliman, Pamela T; Lu, Karen H; Luthra, Rajyalakshmi; Broaddus, Russell R

    2014-01-01

    Clinical screening criteria, such as young age of endometrial cancer diagnosis and family history of signature cancers, have traditionally been used to identify women with Lynch Syndrome, which is caused by mutation of a DNA mismatch repair gene. Immunohistochemistry and microsatellite instability analysis have evolved as important screening tools to evaluate endometrial cancer patients for Lynch Syndrome. A complicating factor is that 15-20% of sporadic endometrial cancers have immunohistochemical loss of the DNA mismatch repair protein MLH1 and high levels of microsatellite instability due to methylation of MLH1. The PCR-based MLH1 methylation assay potentially resolves this issue, yet many clinical laboratories do not perform this assay. The objective of this study was to determine if clinical and pathologic features help to distinguish sporadic endometrial carcinomas with MLH1 loss secondary to MLH1 methylation from Lynch Syndrome-associated endometrial carcinomas with MLH1 loss and absence of MLH1 methylation. Of 337 endometrial carcinomas examined, 54 had immunohistochemical loss of MLH1. 40/54 had MLH1 methylation and were designated as sporadic, while 14/54 lacked MLH1 methylation and were designated as Lynch Syndrome. Diabetes and deep myometrial invasion were associated with Lynch Syndrome; no other clinical or pathological variable distinguished the 2 groups. Combining Society of Gynecologic Oncology screening criteria with these 2 features accurately captured all Lynch Syndrome cases, but with low specificity. In summary, no single clinical/pathologic feature or screening criteria tool accurately identified all Lynch Syndrome-associated endometrial carcinomas, highlighting the importance of the MLH1 methylation assay in the clinical evaluation of these patients.

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    Watkins Kathy E

    2011-09-01

    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusions 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.

  3. Same MSH2 Gene Mutation But Variable Phenotypes in 2 Families With Lynch Syndrome: Two Case Reports and Review of Genotype-Phenotype Correlation.

    Science.gov (United States)

    Liccardo, Raffaella; De Rosa, Marina; Duraturo, Francesca

    2018-01-01

    Lynch syndrome is an autosomal dominant syndrome that can be subdivided into Lynch syndrome I, or site-specific colonic cancer, and Lynch syndrome II, or extracolonic cancers, particularly carcinomas of the stomach, endometrium, biliary and pancreatic systems, and urinary tract. Lynch syndrome is associated with point mutations and large rearrangements in DNA MisMatch Repair ( MMR ) genes. This syndrome shows a variable phenotypic expression in people who carry pathogenetic mutations. So far, a correlation in genotype-phenotype has not been definitely established. In this study, we describe 2 Lynch syndrome cases presenting with the same genotype but different phenotypes and discuss possible reasons for this.

  4. 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...

  5. Worldwide Practice Patterns in Lynch Syndrome Diagnosis and Management, Based on Data From the International Mismatch Repair Consortium.

    Science.gov (United States)

    Pan, Jennifer Y; Haile, Robert W; Templeton, Allyson; Macrae, Finlay; Qin, FeiFei; Sundaram, Vandana; Ladabaum, Uri

    2018-04-24

    Families with a history of Lynch syndrome often do not adhere to guidelines for genetic testing and screening. We investigated practice patterns related to Lynch syndrome worldwide, to ascertain potential targets for research and public policy efforts. We collected data from the International Mismatch Repair Consortium (IMRC), which comprises major research and clinical groups engaged in the care of families with Lynch syndrome worldwide. IMRC institutions were invited to complete a questionnaire to characterize diagnoses of Lynch syndrome and management practice patterns. Fifty-five providers, representing 63 of 128 member institutions (49%) in 21 countries, completed the questionnaire. For case finding, 55% of respondents reported participating in routine widespread population tumor testing among persons with newly diagnosed Lynch syndrome-associated cancers, whereas 27% reported relying on clinical criteria with selective tumor and/or germline analyses. Most respondents (64%) reported using multigene panels for germline analysis, and only 28% reported testing tumors for biallelic mutations for cases in which suspected pathogenic mutations were not confirmed by germline analysis. Respondents reported relying on passive dissemination of information to at-risk family members, and there was variation in follow through of genetic testing recommendations. Reported risk management practices varied-nearly all programs (98%) recommended colonoscopy every 1 to 2 years, but only 35% recommended chemoprevention with aspirin. There is widespread heterogeneity in management practices for Lynch syndrome worldwide among IMRC member institutions. This may reflect the rapid pace of emerging technology, regional differences in resources, and the lack of definitive data for many clinical questions. Future efforts should focus on the large numbers of high-risk patients without access to state-of-the-art Lynch syndrome management. Copyright © 2018 AGA Institute. Published by

  6. Thyroid cancer in a patient with Lynch syndrome – case report and literature review

    Directory of Open Access Journals (Sweden)

    Fazekas-Lavu M

    2017-07-01

    Full Text Available Monika Fazekas-Lavu,1 Andrew Parker,2 Allan D Spigelman,3,4 Rodney J Scott,5 Richard J Epstein,6 Michael Jensen,7 Katherine Samaras1,8 1Department of Endocrinology, 2Department of Pathology, St Vincent’s Hospital, Darlinghurst, NSW, Australia; 3Hereditary Cancer Clinic, St Vincent’s Cancer Genetics Service, Darlinghurst, NSW, Australia; 4University of NSW, St Vincent’s Clinical School, Darlinghurst, NSW, Australia; 5Division of Molecular Medicine, Pathology North, John Hunter Hospital and The Hunter Medical Research Institute, Newcastle, NSW, Australia; 6Department of Oncology, 7Department of Oncological Surgery/General Surgery, St Vincent’s Hospital, Darlinghurst, NSW, Australia; 8Diabetes and Metabolism Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia Abstract: 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

  7. 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.

  8. The effectiveness of the double B-lynch suture as a modification in the treatment of intractable postpartum haemorrhage.

    Science.gov (United States)

    Şahin, Hanifi; Soylu Karapınar, Oya; Şahin, Eda Adeviye; Dolapçıoğlu, Kenan; Baloğlu, Ali

    2018-03-20

    A broader range of more effective compression techniques are needed in the patients who have an intractable postpartum haemorrhage due to uterine atony despite medical treatment and B-Lynch sutures. The aim of this study was to report the outcome of a series of patients with haemorrhage who were managed by double B-Lynch suture. Fourteen patients who were treated in a tertiary hospital between July 2010 and February 2015 were included in the study. The intractable haemorrhage rate was 0.35% over 5 years (14/4000 births). Bleeding was controlled in all the patients with a double B-Lynch suture. The mean age of the patients was 24 ± 3.4 years. The mean estimated blood loss was 1696 ± 272.075 mL, and the mean transfusion rate was 4.2 ± 2.5 units. Pregnancy was observed in five patients at follow up. The double B-Lynch suture seems to be an effective and reliable solution to an intractable postpartum haemorrhage resulting from uterine atony and has no unfavourable impacts on fertility. It should be considered before the use of any aggressive surgical techniques such as a hypogastric artery ligation or a hysterectomy. This the first study to investigate the effectiveness of the double B-Lynch suture, and we showed that the hysterectomy and/or hypogastric artery ligation rate can be decreased by adding a second B-Lynch suture in cases where the medical treatment or a single B-Lynch has failed. Impact statement What is already known on the subject? Uterine atony is the most common cause of a primary postpartum haemorrhage. When a simple massage of the uterus and medication failed to manage this condition, various surgical solutions have been sought, including uterine compression sutures, uterine artery ligation, devascularisation of the uterus, internal iliac artery ligation and, ultimately, a hysterectomy. The B-Lynch suturing technique is particularly useful because of its simplicity of application, life-saving potential, relative safety and capacity

  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. 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

  11. 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.

  12. Laboratory Assays in Evaluation of Lynch Syndrome in Patients with Endometrial Carcinoma.

    Science.gov (United States)

    Djordjevic, Bojana; Broaddus, Russell R

    2016-06-01

    This article reviews the main tissue testing modalities for Lynch Syndrome in the pathology laboratory, such as immunohistochemistry and PCR based analyses, and discusses their routine application, interpretation pitfalls, and troubleshooting of common technical performance issues. Discrepancies between laboratory and genetic testing may arise, and are examined in the context of the complexity of molecular abnormalities associated with Lynch Syndrome. The merits of targeted versus universal screening in a changing healthcare climate are addressed. In the absence of comprehensive screening programs, specific tumor topography and histological features that may prompt pathologist-initiated molecular tumor testing are outlined. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. 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....

  14. 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.

  15. Molecular changes preceding endometrial and ovarian cancer: a study of consecutive endometrial specimens from Lynch syndrome surveillance.

    Science.gov (United States)

    Niskakoski, Anni; Pasanen, Annukka; Lassus, Heini; Renkonen-Sinisalo, Laura; Kaur, Sippy; Mecklin, Jukka-Pekka; Bützow, Ralf; Peltomäki, Päivi

    2018-03-27

    Molecular alterations preceding endometrial and ovarian cancer and the sequence of events are unknown. Consecutive specimens from lifelong surveillance for Lynch syndrome provides a natural setting to address such questions. To molecularly define the multistep gynecological tumorigenesis, DNA mismatch repair gene mutation carriers with endometrial or ovarian carcinoma or endometrial hyperplasia were identified from a nation-wide registry and endometrial biopsy specimens taken from these individuals during 20 years of screening were collected. A total of 213 endometrial and ovarian specimens from Lynch syndrome individuals and 197 histology-matched (non-serous) samples from sporadic cases were available for this investigation. The specimens were profiled for markers linked to endometrial and ovarian tumorigenesis, including ARID1A protein expression, mismatch repair status, and tumor suppressor gene promoter methylation. In Lynch syndrome-associated endometrial and ovarian carcinomas, ARID1A protein was lost in 61-100% and mismatch repair was deficient in 97-100%, compared to 0-17% and 14-44% in sporadic cases (P = 0.000). ARID1A loss appeared in complex hyperplasia and deficient mismatch repair and tumor suppressor gene promoter methylation in histologically normal endometrium. Despite quantitative differences between Lynch syndrome and sporadic cases, ARID1A expression, mismatch repair, and tumor suppressor gene promoter methylation divided endometrial samples from both patient groups into three categories of increasing abnormality, comprising normal endometrium and simple hyperplasia (I), complex hyperplasia with or without atypia (II), and endometrial cancer (III). Complex hyperplasias without vs. with atypia were molecularly indistinguishable. In conclusion, surveillance specimens from Lynch syndrome identify mismatch repair deficiency, tumor suppressor gene promoter methylation, and ARID1A loss as early changes in tumor development. Our findings are

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

    Science.gov (United States)

    Haraldsdottir, Sigurdis; Rafnar, Thorunn; Frankel, Wendy L; Einarsdottir, Sylvia; Sigurdsson, Asgeir; Hampel, Heather; Snaebjornsson, Petur; Masson, Gisli; Weng, Daniel; Arngrimsson, Reynir; Kehr, Birte; Yilmaz, Ahmet; Haraldsson, Stefan; Sulem, Patrick; Stefansson, Tryggvi; Shields, Peter G; Sigurdsson, Fridbjorn; Bekaii-Saab, Tanios; Moller, Pall H; Steinarsdottir, Margret; Alexiusdottir, Kristin; Hitchins, Megan; Pritchard, Colin C; de la Chapelle, Albert; Jonasson, Jon G; Goldberg, Richard M; Stefansson, Kari

    2017-05-03

    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 of uncertain significance that are not associated with cancer risk. We find that founder mutations in MSH6 and PMS2 prevail in Iceland unlike most other populations.

  17. 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,

  18. 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

  19. 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

  20. Physical activity and the risk of colorectal cancer in Lynch syndrome.

    Science.gov (United States)

    Dashti, S Ghazaleh; Win, Aung Ko; Hardikar, Sheetal S; Glombicki, Stephen E; Mallenahalli, Sheila; Thirumurthi, Selvi; Peterson, Susan K; You, Y Nancy; Buchanan, Daniel D; Figueiredo, Jane C; Campbell, Peter T; Gallinger, Steven; Newcomb, Polly A; Potter, John D; Lindor, Noralane M; Le Marchand, Loic; Haile, Robert W; Hopper, John L; Jenkins, Mark A; Basen-Engquist, Karen M; Lynch, Patrick M; Pande, Mala

    2018-06-14

    Greater physical activity is associated with a decrease in risk of colorectal cancer for the general population; however, little is known about its relationship with colorectal cancer risk for people with Lynch syndrome, carriers of inherited pathogenic mutations in genes affecting DNA mismatch repair (MMR). We studied a cohort of 2,042 MMR gene mutations carriers (n=807, diagnosed with colorectal cancer), from the Colon Cancer Family Registry. Self-reported physical activity in three age-periods (20-29, 30-49, and ≥50 years) was summarized as average metabolic equivalent of task hours per week (MET-h/week) during the age-period of cancer diagnosis or censoring (near-term exposure), and across all age-periods preceding cancer diagnosis or censoring (long-term exposure). Weighted Cox regression was used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) for the association between physical activity and colorectal cancer risk. Near-term physical activity was associated with a small reduction in the risk of colorectal cancer (HR ≥35 vs. Lynch syndrome, however, further confirmation is warranted. The potential modifying effect of physical activity on colorectal cancer risk for people with Lynch syndrome could be useful for risk prediction and support counseling advice for lifestyle modification to reduce cancer risk. This article is protected by copyright. All rights reserved. © 2018 UICC.

  1. Adrenocortical carcinoma, an unusual extracolonic tumor associated with Lynch II syndrome.

    Science.gov (United States)

    Medina-Arana, V; Delgado, L; González, L; Bravo, A; Díaz, H; Salido, E; Riverol, D; González-Aguilera, J J; Fernández-Peralta, A M

    2011-06-01

    Lynch syndrome (LS) is an autosomal dominant condition that predisposes to colorectal cancer and specific other tumors. Extracolonic tumors occur mainly in the endometrium, stomach, ovary, small intestine and urinary tract. The presence of rare tumors in patients belonging to families who have Lynch syndrome is always interesting, because the question arises whether these tumors should be considered as a coincidence or are related with the syndrome. In this last case, they are also the result of the defect in the mismatch repair system, opening the possibility of extending the tumor spectrum associated with the syndrome. Here we describe a patient from a Lynch syndrome family with a germline mutation c.2063T>G (p.M688R) in the MSH2 gene, who developed an adrenal cortical carcinoma, a tumor not usually associated with LS. We analyzed the adrenocortical tumour for microsatellite instability (MSI), LOH and the presence of the germline c.2063T>G (M688R) mutation. The adrenal cortical carcinoma showed the MSH2 mutation, loss of heterozygosity of the normal allele in the MSH2 gene and loss of immunohistochemical expression for MSH2 protein, but no microsatellite instability. Additionally, the adrenal cortical carcinoma did not harbour a TP53 mutation. The molecular study indicates that this adrenal cortical cancer is probably due to the mismatch repair defect.

  2. 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

  3. 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...

  4. 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...... 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...

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

    Science.gov (United States)

    Haraldsdottir, Sigurdis; Rafnar, Thorunn; Frankel, Wendy L.; Einarsdottir, Sylvia; Sigurdsson, Asgeir; Hampel, Heather; Snaebjornsson, Petur; Masson, Gisli; Weng, Daniel; Arngrimsson, Reynir; Kehr, Birte; Yilmaz, Ahmet; Haraldsson, Stefan; Sulem, Patrick; Stefansson, Tryggvi; Shields, Peter G.; Sigurdsson, Fridbjorn; Bekaii-Saab, Tanios; Moller, Pall H.; Steinarsdottir, Margret; Alexiusdottir, Kristin; Hitchins, Megan; Pritchard, Colin C.; de la Chapelle, Albert; Jonasson, Jon G.; Goldberg, Richard M.; Stefansson, Kari

    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 of uncertain significance that are not associated with cancer risk. We find that founder mutations in MSH6 and PMS2 prevail in Iceland unlike most other populations. PMID:28466842

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

    Science.gov (United States)

    Clendenning, M; Senter, L; Hampel, H; Robinson, K Lagerstedt; Sun, S; Buchanan, D; Walsh, M D; Nilbert, M; Green, J; Potter, J; Lindblom, A; de la Chapelle, A

    2008-06-01

    When compared to the other mismatch repair genes involved in Lynch syndrome, the identification of mutations within PMS2 has been limited (PMS2. This disparity is primarily due to complications in the study of this gene caused by interference from pseudogene sequences. Using a recently developed method for detecting PMS2 specific mutations, we have screened 99 patients who are likely candidates for PMS2 mutations based on immunohistochemical analysis. We have identified a frequently occurring frame-shift mutation (c.736_741del6ins11) in 12 ostensibly unrelated Lynch syndrome patients (20% of patients we have identified with a deleterious mutation in PMS2, n = 61). These individuals all display the rare allele (population frequency 10 000 carriers of this mutation in the USA 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 in the probands' families, would suggest that this is a prevalent mutation with reduced penetrance.

  7. Freshwater and Saline Loads of Dissolved Inorganic Nitrogen to Hood Canal and Lynch Cove, Western Washington

    Science.gov (United States)

    Paulson, Anthony J.; Konrad, Christopher P.; Frans, Lonna M.; Noble, Marlene; Kendall, Carol; Josberger, Edward G.; Huffman, Raegan L.; Olsen, Theresa D.

    2006-01-01

    Hood Canal is a long (110 kilometers), deep (175 meters) and narrow (2 to 4 kilometers wide) fjord of Puget Sound in western Washington. The stratification of a less dense, fresh upper layer of the water column causes the cold, saltier lower layer of the water column to be isolated from the atmosphere in the late summer and autumn, which limits reaeration of the lower layer. In the upper layer of Hood Canal, the production of organic matter that settles and consumes dissolved oxygen in the lower layer appears to be limited by the load of dissolved inorganic nitrogen (DIN): nitrate, nitrite, and ammonia. Freshwater and saline loads of DIN to Hood Canal were estimated from available historical data. The freshwater load of DIN to the upper layer of Hood Canal, which could be taken up by phytoplankton, came mostly from surface and ground water from subbasins, which accounts for 92 percent of total load of DIN to the upper layer of Hood Canal. Although DIN in rain falling on land surfaces amounts to about one-half of the DIN entering Hood Canal from subbasins, rain falling directly on the surface of marine waters contributed only 4 percent of the load to the upper layer. Point-source discharges and subsurface flow from shallow shoreline septic systems contributed less than 4 percent of the DIN load to the upper layer. DIN in saline water flowing over the sill into Hood Canal from Admiralty Inlet was at least 17 times the total load to the upper layer of Hood Canal. In September and October 2004, field data were collected to estimate DIN loads to Lynch Cove - the most inland marine waters of Hood Canal that routinely contain low dissolved-oxygen waters. Based on measured streamflow and DIN concentrations, surface discharge was estimated to have contributed about one-fourth of DIN loads to the upper layer of Lynch Cove. Ground-water flow from subbasins was estimated to have contributed about one-half of total DIN loads to the upper layer. In autumn 2004, the relative

  8. Elisa Alicia Lynch: a Dama de Aço do Paraguai * Elisa Alicia Lynch: the Steel ‘S Lady of Paraguay

    OpenAIRE

    Frota, Luciara Silveira de Aragão e

    2015-01-01

    Este trabalho mostra uma nova visão da irlandesa Elisa Alicia Lynch, longe da figura de prostituta manipuladora que incitou o Marechal Solano López no começo da Guerra do Paraguai. Dentro de uma corrente revisionista histórica, apoiada em Marc Bloch, propõe uma nova análise de seu papel na vida de Solano López e do Paraguai, comentando a literatura sobre o assunto.

  9. 'Where are your intelligent mothers to come from?': marriage and family in the scientific career of Dame Kathleen Lonsdale FRS (1903-71).

    Science.gov (United States)

    Baldwin, Melinda

    2009-03-20

    Although she was one of the most successful female scientists in twentieth-century Britain, the X-ray crystallographer Kathleen Yardley Lonsdale (1903-71) has received relatively little attention from historians of science. This paper, based on material from the recently opened Dame Kathleen Lonsdale Papers, argues that Lonsdale's scientific career was shaped in particular ways by her identity not just as a woman, but as a married woman and a mother. When interacting with her scientific colleagues, Lonsdale frequently had to confront the assumption that married women should not pursue scientific careers, an attitude shaped by British concerns about reasserting traditional gender roles after the World Wars I and II. Furthermore, although Lonsdale's husband, Thomas, was an ardent supporter of her career, in the early 1930s Lonsdale left research temporarily to care for her small children. Her desire to work from home during this period led her to pursue one of her most significant scientific projects: the creation of crystallographic reference tables. Lonsdale's own experiences, and those of her female students, led her to focus on issues of marriage and family when she began speaking and writing about women in science during the late 1960s.

  10. Lynch syndrome-associated endometrial carcinoma with MLH1 germline mutation and MLH1 promoter hypermethylation: a case report and literature review.

    Science.gov (United States)

    Yokoyama, Takanori; Takehara, Kazuhiro; Sugimoto, Nao; Kaneko, Keika; Fujimoto, Etsuko; Okazawa-Sakai, Mika; Okame, Shinichi; Shiroyama, Yuko; Yokoyama, Takashi; Teramoto, Norihiro; Ohsumi, Shozo; Saito, Shinya; Imai, Kazuho; Sugano, Kokichi

    2018-05-21

    Lynch syndrome is an autosomal dominant inherited disease caused by germline mutations in mismatch repair genes. Analysis for microsatellite instability (MSI) and immunohistochemistry (IHC) of protein expressions of disease-associated genes is used to screen for Lynch syndrome in endometrial cancer patients. When losses of both MLH1 and PMS2 proteins are observed by IHC, MLH1 promoter methylation analysis is conducted to distinguish Lynch syndrome-associated endometrial cancer from sporadic cancer. Here we report a woman who developed endometrial cancer at the age of 49 years. She had a family history of colorectal cancer (first-degree relative aged 52 years) and stomach cancer (second-degree relative with the age of onset unknown). No other family history was present, and she failed to meet the Amsterdam II criteria for the diagnosis of Lynch syndrome. Losses of MLH1 and PMS2, but not MSH2 and MSH6, proteins were observed by IHC in endometrial cancer tissues. Because MLH1 promoter hypermethylation was detected in endometrial cancer tissue samples, the epigenetic silencing of MLH1 was suspected as the cause of the protein loss. However, because of the early onset of endometrial cancer and the positive family history, a diagnosis of Lynch syndrome was also suspected. Therefore, we provided her with genetic counseling. After obtaining her consent, MLH1 promoter methylation testing and genetic testing of peripheral blood were performed. MLH1 promoter methylation was not observed in peripheral blood. However, genetic testing revealed a large deletion of exon 5 in MLH1; thus, we diagnosed the presence of Lynch syndrome. Both MLH1 germline mutation and MLH1 promoter hypermethylation may be observed in endometrial cancer. Therefore, even if MLH1 promoter hypermethylation is detected, a diagnosis of Lynch syndrome cannot be excluded.

  11. 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

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

    Science.gov (United States)

    Buchanan, Daniel D; Rosty, Christophe; Clendenning, Mark; Spurdle, Amanda B; Win, Aung Ko

    2014-01-01

    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 data from published studies are combined, 59% (95% confidence interval [CI]: 55% to 64%) of colorectal cancers and 52% (95% CI: 41% to 62%) of endometrial cancers with MMR deficiency were identified as suspected Lynch syndrome. Recent studies estimated that colorectal cancer risk for relatives of suspected Lynch syndrome cases is lower than for relatives of those with MMR gene mutations, but higher than for relatives of those with tumor MMR deficiency resulting from methylation of the MLH1 gene promoter. The cause of tumor MMR deficiency in suspected Lynch syndrome cases is likely due to either unidentified germline MMR gene mutations, somatic cell mosaicism, or biallelic somatic

  13. Genetic anticipation in Swedish Lynch syndrome families

    OpenAIRE

    von Salomé, Jenny; Boonstra, Philip S.; Karimi, Masoud; Silander, Gustav; Stenmark-Askmalm, Marie; Gebre-Medhin, Samuel; Aravidis, Christos; Nilbert, Mef; Lindblom, Annika; Lagerstedt-Robinson, Kristina

    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, ha...

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

    DEFF Research Database (Denmark)

    Rasmussen, Lene Juel; Heinen, Christopher D.

    2014-01-01

    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....

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

    Science.gov (United States)

    Tan, Yen Y.; Fitzgerald, Lisa J.

    2014-01-01

    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. PMID:25562140

  16. 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.

  17. Serum antibodies against frameshift peptides in microsatellite unstable colorectal cancer patients with Lynch syndrome.

    Science.gov (United States)

    Reuschenbach, Miriam; Kloor, Matthias; Morak, Monika; Wentzensen, Nicolas; Germann, Anja; Garbe, Yvette; Tariverdian, Mirjam; Findeisen, Peter; Neumaier, Michael; Holinski-Feder, Elke; von Knebel Doeberitz, Magnus

    2010-06-01

    High level microsatellite instability (MSI-H) occurs in about 15% of colorectal cancer (CRCs), either as sporadic cancers or in the context of hereditary non-polyposis cancer or Lynch syndrome. In MSI-H CRC, mismatch repair deficiency leads to insertion/deletion mutations at coding microsatellites and thus to the translation of frameshift peptides (FSPs). FSPs are potent inductors of T cell responses in vitro and in vivo. The present study aims at the identification of FSP-specific humoral immune responses in MSI-H CRC and Lynch syndrome. Sera from patients with history of MSI-H CRC (n = 69), healthy Lynch syndrome mutation carriers (n = 31) and healthy controls (n = 52) were analyzed for antibodies against FSPs using peptide ELISA. Reactivities were measured against FSPs derived from genes frequently mutated in MSI-H CRCs, AIM2, TGFBR2, CASP5, TAF1B, ZNF294, and MARCKS. Antibody reactivity against FSPs was significantly higher in MSI-H CRC patients than in healthy controls (P = 0.036, Mann-Whitney) and highest in patients with shortest interval between tumor resection and serum sampling. Humoral immune responses in patients were most frequently directed against FSPs derived from mutated TAF1B (11.6%, 8/69) and TGFBR2 (10.1%, 7/69). Low level FSP-specific antibodies were also detected in healthy mutation carriers. Our results show that antibody responses against FSPs are detectable in MSI-H CRC patients and healthy Lynch syndrome mutation carriers. Based on the high number of defined FSP antigens, measuring FSP-specific humoral immune responses is a highly promising tool for future diagnostic application in MSI-H cancer patients.

  18. Serum antibodies against frameshift peptides in microsatellite unstable colorectal cancer patients with Lynch syndrome

    Science.gov (United States)

    Reuschenbach, Miriam; Kloor, Matthias; Morak, Monika; Wentzensen, Nicolas; Germann, Anja; Garbe, Yvette; Tariverdian, Mirjam; Findeisen, Peter; Neumaier, Michael; Holinski-Feder, Elke; Doeberitz, Magnus von Knebel

    2014-01-01

    High level microsatellite instability (MSI-H) occurs in about 15% of colorectal cancer (CRCs), either as sporadic cancers or in the context of hereditary non-polyposis cancer (HNPCC) or Lynch syndrome. In MSI-H CRC, mismatch repair deficiency leads to insertion/deletion mutations at coding microsatellites (cMS) and thus to the translation of frameshift peptides (FSPs). FSPs are potent inductors of T cell responses in vitro and in vivo. The present study aims at the identification of FSP-specific humoral immune responses in MSI-H CRC and Lynch syndrome. Sera from patients with history of MSI-H CRC (n=69), healthy Lynch syndrome mutation carriers (n=31) and healthy controls (n=52) were analyzed for antibodies against FSPs using peptide ELISA. Reactivities were measured against FSPs derived from genes frequently mutated in MSI-H CRCs, AIM2, TGFBR2, CASP5, TAF1B, ZNF294, and MARCKS. Antibody reactivity against FSPs was significantly higher in MSI-H CRC patients than in healthy controls (p=0.036, Mann-Whitney) and highest in patients with shortest interval between tumor resection and serum sampling. Humoral immune responses in patients were most frequently directed against FSPs derived from mutated TAF1B (11.6%, 8/69) and TGFBR2 (10.1%, 7/69). Low level FSP-specific antibodies were also detected in healthy mutation carriers. Our results show that antibody responses against FSPs are detectable in MSI-H CRC patients and healthy Lynch syndrome mutation carriers. Based on the high number of defined FSP antigens, measuring FSP-specific humoral immune responses is a highly promising tool for future diagnostic application in MSI-H cancer patients. PMID:19957108

  19. 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...

  20. 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.

  1. Comparison of clinical features between suspected familial colorectal cancer type X and Lynch syndrome in Japanese patients with colorectal cancer: a cross-sectional study conducted by the Japanese Society for Cancer of the Colon and Rectum.

    Science.gov (United States)

    Yamaguchi, Tatsuro; Furukawa, Yoichi; Nakamura, Yusuke; Matsubara, Nagahide; Ishikawa, Hideki; Arai, Masami; Tomita, Naohiro; Tamura, Kazuo; Sugano, Kokichi; Ishioka, Chikashi; Yoshida, Teruhiko; Moriya, Yoshihiro; Ishida, Hideyuki; Watanabe, Toshiaki; Sugihara, Kenichi

    2015-02-01

    The characteristics of familial colorectal cancer type X are poorly defined. Here we aimed to clarify the differences in clinical features between suspected familial colorectal cancer type X and Lynch syndrome in Japanese patients. We performed germline mutation analyses of mismatch repair genes in 125 patients. Patients who met the Amsterdam Criteria I but lacked mismatch repair gene mutations were diagnosed with suspected familial colorectal cancer type X. We identified 69 patients with Lynch syndrome and 25 with suspected familial colorectal cancer type X. The frequencies of gastric and extracolonic Lynch syndrome-associated cancers were lower with suspected familial colorectal cancer type X than with Lynch syndrome. The number of organs with Lynch syndrome-associated cancer was significantly lower with suspected familial colorectal cancer type X than with Lynch syndrome. The cumulative incidence of extracolonic Lynch syndrome-associated cancer was significantly lower with suspected familial colorectal cancer type X than with Lynch syndrome. We estimated that the median cancer risk in 60-year-old patients with Lynch syndrome was 89, 36 and 24% for colorectal, endometrial and gastric cancers, respectively. Analyses of family members, including probands, revealed that the median age at diagnosis of extracolonic Lynch syndrome-associated cancer was significantly older with suspected familial colorectal cancer type X than with Lynch syndrome. The frequency of extracolonic Lynch syndrome-associated cancer was significantly lower with suspected familial colorectal cancer type X than with Lynch syndrome. A significant difference in extracolonic Lynch syndrome-associated cancer was evident between suspected familial colorectal cancer type X and Lynch syndrome. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. The Germline MLH1 K618A Variant and Susceptibility to Lynch Syndrome-Associated Tumors

    Science.gov (United States)

    Medeiros, Fabiola; Lindor, Noralane M.; Couch, Fergus J.; Highsmith, W. Edward

    2013-01-01

    Missense variants discovered during sequencing of cancer susceptibility genes can be problematic for clinical interpretation. MLH1 K618A, which results from a 2-bp alteration (AAG→GCG) leading to a substitution of lysine to alanine in codon 618, has variously been interpreted as a pathogenic mutation, a variant of unknown significance, and a benign polymorphism. We evaluated the role of MLH1 K618A in predisposition to cancer by genotyping 1512 control subjects to assess its frequency in the general population. We also reviewed the literature concerning MLH1 K618A in families with colorectal cancer. The measured allele frequency of the K618A variant was 0.40%, which is remarkably close to the 0.44% summarized from 2491 control subjects in the literature. K618A was over-represented in families with suspected Lynch syndrome. In 1366 families, the allele frequency was 0.88% (OR = 2.1, 95% CI = 1.3 to 3.5; P = 0.006). In studies of sporadic cancers of the type associated with Lynch syndrome, K618A was over-represented in 1742 cases (allele frequency of 0.83) (OR = 2.0, 95% CI = 1.2 to 3.2; P = 0.008). We conclude that MLH1 K618A is not a fully penetrant Lynch syndrome mutation, although it is not without effect, appearing to increase the risk of Lynch syndrome-associated tumors approximately twofold. Our systematic assessment approach may be useful for variants in other genes. PMID:22426235

  3. 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.

  4. 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

  5. Lynch syndrome associated with two MLH1 promoter variants and allelic imbalance of MLH1 expression.

    Science.gov (United States)

    Hesson, Luke B; Packham, Deborah; Kwok, Chau-To; Nunez, Andrea C; Ng, Benedict; Schmidt, Christa; Fields, Michael; Wong, Jason W H; Sloane, Mathew A; Ward, Robyn L

    2015-06-01

    Lynch syndrome is a hereditary cancer syndrome caused by a constitutional mutation in one of the mismatch repair genes. The implementation of predictive testing and targeted preventative surveillance is hindered by the frequent finding of sequence variants of uncertain significance in these genes. We aimed to determine the pathogenicity of previously reported variants (c.-28A>G and c.-7C>T) within the MLH1 5'untranslated region (UTR) in two individuals from unrelated suspected Lynch syndrome families. We investigated whether these variants were associated with other pathogenic alterations using targeted high-throughput sequencing of the MLH1 locus. We also determined their relationship to gene expression and epigenetic alterations at the promoter. Sequencing revealed that the c.-28A>G and c.-7C>T variants were the only potentially pathogenic alterations within the MLH1 gene. In both individuals, the levels of transcription from the variant allele were reduced to 50% compared with the wild-type allele. Partial loss of expression occurred in the absence of constitutional epigenetic alterations within the MLH1 promoter. We propose that these variants may be pathogenic due to constitutional partial loss of MLH1 expression, and that this may be associated with intermediate penetrance of a Lynch syndrome phenotype. Our findings provide further evidence of the potential importance of noncoding variants in the MLH1 5'UTR in the pathogenesis of Lynch syndrome. © 2015 The Authors. **Human Mutation published by Wiley Periodicals, Inc.

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

    African Journals Online (AJOL)

    DR Nneka

    the United State America treasury securities market. Ahimie (2008) ... Thus, the above school of thought considered a bank failure as not when it ceases .... Lynch had further confirmed the historical fact that, no bank or financial institution is.

  7. 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.

  8. Transitional Justice as Elite Justice? Compromise Justice and Transition in Tunisia

    NARCIS (Netherlands)

    Lamont, Christopher; Pannwitz, Hannah

    2016-01-01

    This article reflects upon the ways in which transitional justice debates and processes impacted Tunisia's transition. It explores key questions such as what demands for justice emerged in the aftermath of the Tunisian revolution? Did Tunisia's transitional justice process reflect these demands?

  9. 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

  10. Special Justice for Peace: A Transitional Justice Model According to Modern Tendencies and Orientations of Law and Justice

    Directory of Open Access Journals (Sweden)

    Carlos Arturo Gómez Pavajeau

    2016-06-01

    Full Text Available The article analyses the constitutional implications of the peace agreement about Colombia’s armed conflict. It examines constitutional rules and international instruments about human rights, confronting the agreement with justice criteria in the national and international context, to underline the role of justice for the definitive solution of the conflict. By using the methodology of opposing concepts, it reviews the implications of formal justice and material justice, to establish the superiority of the last one and it’s relation with social justice; it analyses the differences between individual justice and global justice, to demonstrate the need to obtain an integral justice; it contrasts alternative justice and traditional justice, to propose an integrated justice; it explains that justice based upon the formal syllogism should be overcome by a justice based upon equity, to obtain a justice anchored in the Constitution, universal and concentrated in the human rights; it hypothesizes that justice supported in the atonement and retribution should be overcome by a justice that is preventive and restorative, that allows the construction of a justice focused in the future, without ignoring the past; it clarifies that justice with one jurisdiction and special justice are the components of a integrative transitional justice; it explains the presence of justice in different institutions with different functions and justice concentrated in one institution, although with different functions, because there is a search for an integrative justice; it exposes the search for a constitutional and political justice, discussing the vision of justice as a triumph of the force or the scandalous concession of benefits; it exalts that it is a justice in search of a positive discrimination, not a negative discrimination, overcoming the discussion between justice for the powerful and justice for the weak; finally, it considers that it is a justice

  11. 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 (PREMM 1,2,6 ) 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 PREMM 1,2,6 . PREMM 1,2,6 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 PREMM 1,2,6 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 PREMM 1,2,6 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 PREMM 1,2,6 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 PREMM 1,2,6 scores of 5% or higher who underwent germline testing, and 3 of the 28 patients (10.7%) recruited during study initiation with PREMM 1,2,6 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

  12. 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.

  13. Dietary patterns and colorectal adenomas in Lynch syndrome: the GEOLynch cohort study

    NARCIS (Netherlands)

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

    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

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

    NARCIS (Netherlands)

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

    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

  15. 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

  16. 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

    Whereas the generally accepted carcinogenesis pathway of the microsatellite instabile high (MSI-H) colorectal carcinoma (CRC) involves the traditional adenoma in patients with Lynch syndrome, a serrate pathway involving serrate adenomas (SA) and sessile serrate polyps (SSP) characterize...... 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...... (FCF) is addressed. Polyps coded as hyperplastic polyps (HP) from subjects with Lynch syndrome and FCF enrolled in the HNPCC-register at the Hvidovre University Hospital as well as adenomas from this population were retrieved and reviewed for features of SSP. Ninety-eight polyps coded as HP and 41...

  17. Endoscopic detection rate of sessile serrated lesions in Lynch syndrome patients is comparable with 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

    2018-05-01

    Carcinogenesis in Lynch syndrome involves fast progression of adenomas to colorectal cancer (CRC) because of 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 with 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. Control subjects 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 1 colonoscopy. Of these, 223 Lynch syndrome patients (mean age, 49.3; 59% women; index colonoscopy, 56%) were matched to 223 control subjects. SSLs were detected in 7.6% (95% confidence interval, 4.8-11.9) of colonoscopies performed in Lynch syndrome patients and in 6.7% (95% confidence interval, 4.1-10.8) of control subjects (P = .86). None of the detected SSLs in Lynch syndrome patients contained dysplasia. The detection rate of SSLs in Lynch syndrome patients undergoing colonoscopy is comparable with a matched population. These findings suggest that the role of the serrated neoplasia pathway in CRC development in Lynch syndrome seems to be comparable with that in the general population. Copyright © 2018 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

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

    DEFF Research Database (Denmark)

    Therkildsen, Christina; Timshel, Susanne; Nilbert, Mef

    2008-01-01

    The Danish Hereditary Nonpolyposis Colorectal Cancer (HNPCC) Register is a national resource that registers families with hereditary colorectal cancer. HNPCC is the most common type of hereditary colorectal cancer and carries an increased risk of other tumor types. Genetic diagnostics has...... 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....

  19. Transitional Justice

    DEFF Research Database (Denmark)

    Gissel, Line Engbo

    This presentation builds on an earlier published article, 'Contemporary Transitional Justice: Normalising a Politics of Exception'. It argues that the field of transitional justice has undergone a shift in conceptualisation and hence practice. Transitional justice is presently understood to be th...... to be the provision of ordinary criminal justice in contexts of exceptional political transition.......This presentation builds on an earlier published article, 'Contemporary Transitional Justice: Normalising a Politics of Exception'. It argues that the field of transitional justice has undergone a shift in conceptualisation and hence practice. Transitional justice is presently understood...

  20. Germ-line variants identified by next generation sequencing in a panel of estrogen and cancer associated genes correlate with poor clinical outcome in Lynch syndrome patients.

    Science.gov (United States)

    Jóri, Balazs; Kamps, Rick; Xanthoulea, Sofia; Delvoux, Bert; Blok, Marinus J; Van de Vijver, Koen K; de Koning, Bart; Oei, Felicia Trups; Tops, Carli M; Speel, Ernst Jm; Kruitwagen, Roy F; Gomez-Garcia, Encarna B; Romano, Andrea

    2015-12-01

    The risk to develop colorectal and endometrial cancers among subjects testing positive for a pathogenic Lynch syndrome mutation varies, making the risk prediction difficult. Genetic risk modifiers alter the risk conferred by inherited Lynch syndrome mutations, and their identification can improve genetic counseling. We aimed at identifying rare genetic modifiers of the risk of Lynch syndrome endometrial cancer. A family based approach was used to assess the presence of genetic risk modifiers among 35 Lynch syndrome mutation carriers having either a poor clinical phenotype (early age of endometrial cancer diagnosis or multiple cancers) or a neutral clinical phenotype. Putative genetic risk modifiers were identified by Next Generation Sequencing among a panel of 154 genes involved in endometrial physiology and carcinogenesis. A simple pipeline, based on an allele frequency lower than 0.001 and on predicted non-conservative amino-acid substitutions returned 54 variants that were considered putative risk modifiers. The presence of two or more risk modifying variants in women carrying a pathogenic Lynch syndrome mutation was associated with a poor clinical phenotype. A gene-panel is proposed that comprehends genes that can carry variants with putative modifying effects on the risk of Lynch syndrome endometrial cancer. Validation in further studies is warranted before considering the possible use of this tool in genetic counseling.

  1. “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.

  2. 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...

  3. 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

  4. 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

    Background: 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. Methods: 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. Results: 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. PMID:21532810

  5. 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.

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

    NARCIS (Netherlands)

    Broeke, S.W. ten; Brohet, R.M.; Tops, C.M.; Klift, H.M. van der; Velthuizen, M.E.; Bernstein, I.; Capella Munar, G.; Garcia, E.; Hoogerbrugge, N.; Letteboer, T.G.; Menko, F.H.; Lindblom, A.; Mensenkamp, A.R.; Moller, P.; Os, T.A. van; Rahner, N.; Redeker, B.J.; Sijmons, R.H.; Spruijt, L.; Suerink, M.; Vos, Y.J.; Wagner, A.; Hes, F.J.; Vasen, H.F.A.; Nielsen, M.; Wijnen, J.T.

    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

  7. RNF43 is mutated less frequently in Lynch Syndrome compared with sporadic microsatellite unstable colorectal cancers.

    Science.gov (United States)

    Fennell, Lochlan J; Clendenning, Mark; McKeone, Diane M; Jamieson, Saara H; Balachandran, Samanthy; Borowsky, Jennifer; Liu, John; Kawamata, Futoshi; Bond, Catherine E; Rosty, Christophe; Burge, Matthew E; Buchanan, Daniel D; Leggett, Barbara A; Whitehall, Vicki L J

    2018-01-01

    The WNT signaling pathway is commonly altered during colorectal cancer development. The E3 ubiquitin ligase, RNF43, negatively regulates the WNT signal through increased ubiquitination and subsequent degradation of the Frizzled receptor. RNF43 has recently been reported to harbor frequent truncating frameshift mutations in sporadic microsatellite unstable (MSI) colorectal cancers. This study assesses the relative frequency of RNF43 mutations in hereditary colorectal cancers arising in the setting of Lynch syndrome. The entire coding region of RNF43 was Sanger sequenced in 24 colorectal cancers from 23 patients who either (i) carried a germline mutation in one of the DNA mismatch repair genes (MLH1, MSH6, MSH2, PMS2), or (ii) showed immunohistochemical loss of expression of one or more of the DNA mismatch repair proteins, was BRAF wild type at V600E, were under 60 years of age at diagnosis, and demonstrated no promoter region methylation for MLH1 in tumor DNA. A validation cohort of 44 colorectal cancers from mismatch repair germline mutation carriers from the Australasian Colorectal Cancer Family Registry (ACCFR) were sequenced for the most common truncating mutation hotspots (X117 and X659). RNF43 mutations were found in 9 of 24 (37.5%) Lynch syndrome colorectal cancers. The majority of mutations were frameshift deletions in the G659 G7 repeat tract (29%); 2 cancers (2/24, 8%) from the one patient harbored frameshift mutations at codon R117 (C6 repeat tract) within exon 3. In the ACCFR validation cohort, RNF43 hotspot mutations were identified in 19/44 (43.2%) of samples, which was not significantly different to the initial series. The proportion of mutant RNF43 in Lynch syndrome related colorectal cancers is significantly lower than the previously reported mutation rate found in sporadic MSI colorectal cancers. These findings identify further genetic differences between sporadic and hereditary colorectal cancers. This may be because Lynch Syndrome cancers

  8. Finding the needle in a haystack: identification of cases of Lynch syndrome with MLH1 epimutation.

    Science.gov (United States)

    Hitchins, Megan P

    2016-07-01

    Constitutional epimutation of the DNA mismatch repair gene, MLH1, represents a minor cause of Lynch syndrome. MLH1 epimutations are characterized by the soma-wide distribution of methylation of a single allele of the MLH1 promoter accompanied by constitutive allelic loss of transcription. 'Primary' MLH1 epimutations, considered pure epigenetic defects, tend to arise de novo in patients without a family history or any apparent genetic mutation. These demonstrate non-Mendelian inheritance. 'Secondary' MLH1 epimutations have a genetic basis and have been linked to non-coding genetic alterations in the vicinity of MLH1. These demonstrate autosomal dominant inheritance. Despite convincing evidence of their role in causing Lynch-type cancers, routine screening for MLH1 epimutations has not been widely adopted. Complicating factors may include: the need to perform additional methylation-based testing beyond the standard genetic screening for a germline mutation; the lack of a consensus algorithm for the selection of patients warranting MLH1 epimutation testing; overlapping molecular pathology features of MLH1 methylation and loss of MLH1 expression with more prevalent sporadic MSI cancers; the rarity of MLH1 epimutation; the variable inter-generational inheritance patterns; and the cost-effectiveness of screening. Nevertheless, a positive molecular diagnosis of MLH1 epimutation is clinically important because carriers have a high personal risk of developing metachronous Lynch-type cancers, and their relatives may also be at risk of carriage. Extending existing universal and clinic-based screening algorithms for Lynch syndrome to include an additional arm of selection criteria for cases warranting MLH1 epimutation testing could provide a cost-effective means of diagnosing these cases.

  9. 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.

  10. Informing family members of individuals with Lynch syndrome: a guideline for clinical geneticists

    NARCIS (Netherlands)

    Menko, Fred H.; Aalfs, Cora M.; Henneman, Lidewij; Stol, Yrrah; Wijdenes, Miranda; Otten, Ellen; Ploegmakers, Marleen M. J.; Legemaate, Johan; Smets, Ellen M. A.; de Wert, Guido M. W. R.; Tibben, Aad

    2013-01-01

    The diagnosis of Lynch syndrome can lead to the prevention of colorectal cancer through periodic colonoscopies and removal of premalignant lesions in susceptible individuals. Therefore, predisposed individuals identified by mutation analysis are advised to inform their at-risk relatives about the

  11. Informing family members of individuals with Lynch syndrome : a guideline for clinical geneticists

    NARCIS (Netherlands)

    Menko, Fred H.; Aalfs, Cora M.; Henneman, Lidewij; Stol, Yrrah; Wijdenes, Miranda; Otten, Ellen; Ploegmakers, Marleen M. J.; Legemaate, Johan; Smets, Ellen M. A.; de Wert, Guido M. W. R.; Tibben, Aad

    The diagnosis of Lynch syndrome can lead to the prevention of colorectal cancer through periodic colonoscopies and removal of premalignant lesions in susceptible individuals. Therefore, predisposed individuals identified by mutation analysis are advised to inform their at-risk relatives about the

  12. Lynch Syndrome Caused by Germline PMS2 Mutations: Delineating the Cancer Risk

    NARCIS (Netherlands)

    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.

    2015-01-01

    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

  13. Lynch Syndrome Caused by Germline PMS2 Mutations : Delineating the Cancer Risk

    NARCIS (Netherlands)

    ten Broeke, Sanne W.; Brohet, Richard M.; Tops, Carli M.; van der Klift, Heleen M.; Velthuizen, Mary E.; Bernstein, Inge; Capella Munar, Gabriel; Garcia, Encarna Gomez; 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.

    2015-01-01

    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

  14. Efficacy of b-lynch brace suture in postpartum haemorrhage

    International Nuclear Information System (INIS)

    Tarique, S.; Wazir, S.; Moeen, G.

    2011-01-01

    Massive uncontrolled haemorrhage after childbirth is the leading cause of maternal death in developing countries. Postpartum haemorrhage is traditionally defined as blood loss of more than 500 ml after vaginal delivery and more than 1000 ml after caesarean section, but intraoperative estimation of blood loss is inaccurate. Uterine atony alone accounts for 75 - 90% of PPH. To estimate the effectiveness and safety of B-Lynch brace Suture in the management of primary postpartum haemorrhage (PPH). (author)

  15. Diagnostic Strategies for Early Lynch Syndrome Detection: From Molecular Testing to Economic Evaluation

    NARCIS (Netherlands)

    C.H.M. Leenen (Celine)

    2015-01-01

    markdownabstract__Abstract__ Lynch syndrome (LS) is an autosomal dominant inherited syndrome that predisposes to multiple malignancies, in particular colorectal cancer (CRC) and endometrial cancer (EC). The lifetime risk of developing CRC for a LS mutation carrier is 25 to 70%, while women

  16. Prevalence of small-bowel neoplasia in Lynch syndrome assessed by video capsule endoscopy

    NARCIS (Netherlands)

    Haanstra, Jasmijn F.; Al-Toma, Abdul; Dekker, Evelien; Vanhoutvin, Steven A. L. W.; Nagengast, Fokko M.; Mathus-Vliegen, Elisabeth M.; van Leerdam, Monique E.; Cappel, Wouter H. de Vos tot Nederveen; Sanduleanu, Silvia; Veenendaal, Roeland A.; Cats, Annemieke; Vasen, Hans F. A.; Kleibeuker, Jan H.; Koornstra, Jan J.

    2015-01-01

    Objective The aim was to determine the prevalence of small-bowel neoplasia in asymptomatic patients with Lynch syndrome (LS) by video capsule endoscopy (VCE). Design After obtaining informed consent, asymptomatic proven gene mutation carriers aged 3570 years were included in this prospective

  17. 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

  18. Haematuria in association with Lynch syndrome

    Directory of Open Access Journals (Sweden)

    Marwan Ma'ayeh

    2012-04-01

    Full Text Available A 40-year-old Caucasian male presented to the Emergency Department complaining of intermittent painless frank haematuria. Past medical history was significant for Hereditary Non-Polyposis Colon Cancer (HNPCC and a prophylactic total colectomy. Computed tomography urogram showed thickening in the posterior wall of the bladder. Cystoscopy showed a small bladder mass. Histology showed a papillary urothelial neoplasm of low malignant potential. HNPCC, also known as Lynch Syndrome, is an autosomal dominant disorder responsible for 3-5% of colorectal cancers. There are certain cancers known to be associated with HNPCC; colorectal cancer, endometrial, ovarian, stomach, pancreas, biliary tract, small bowel, brain, renal pelvic and ureteric tumours, sebaceous gland adenomas and keratocanthomas. An association with bladder tumours is not well established.

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

    DEFF Research Database (Denmark)

    Møller, Pål; Seppälä, Toni; Bernstein, Inge

    2017-01-01

    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...... carriers. Among first cancer detected in each patient the colorectal cancer cumulative incidences at 70 years by gene were 46%, 35%, 20% and 10% for MLH1, MSH2, MSH6 and PMS2 mutation carriers, respectively. The equivalent cumulative incidences for endometrial cancer were 34%, 51%, 49% and 24......%; 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...

  20. SNP association study in PMS2-associated Lynch syndrome.

    Science.gov (United States)

    Ten Broeke, Sanne W; Elsayed, Fadwa A; Pagan, Lisa; Olderode-Berends, Maran J W; Garcia, Encarna Gomez; Gille, Hans J P; van Hest, Liselot P; Letteboer, Tom G W; van der Kolk, Lizet E; Mensenkamp, Arjen R; van Os, Theo A; Spruijt, Liesbeth; Redeker, Bert J W; Suerink, Manon; Vos, Yvonne J; Wagner, Anja; Wijnen, Juul T; Steyerberg, E W; Tops, Carli M J; van Wezel, Tom; Nielsen, Maartje

    2017-11-17

    Lynch syndrome (LS) patients are at high risk of developing colorectal cancer (CRC). Phenotypic variability might in part be explained by common susceptibility loci identified in Genome Wide Association Studies (GWAS). Previous studies focused mostly on MLH1, MSH2 and MSH6 carriers, with conflicting results. We aimed to determine the role of GWAS SNPs in PMS2 mutation carriers. A cohort study was performed in 507 PMS2 carriers (124 CRC cases), genotyped for 24 GWAS SNPs, including SNPs at 11q23.1 and 8q23.3. Hazard ratios (HRs) were calculated using a weighted Cox regression analysis to correct for ascertainment bias. Discrimination was assessed with a concordance statistic in a bootstrap cross-validation procedure. Individual SNPs only had non-significant associations with CRC occurrence with HRs lower than 2, although male carriers of allele A at rs1321311 (6p21.31) may have increased risk of CRC (HR = 2.1, 95% CI 1.2-3.0). A polygenic risk score (PRS) based on 24 HRs had an HR of 2.6 (95% CI 1.5-4.6) for the highest compared to the lowest quartile, but had no discriminative ability (c statistic 0.52). Previously suggested SNPs do not modify CRC risk in PMS2 carriers. Future large studies are needed for improved risk stratification among Lynch syndrome patients.

  1. 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.

  2. Prevalence of small-bowel neoplasia in Lynch syndrome assessed by video capsule endoscopy

    NARCIS (Netherlands)

    Haanstra, Jasmijn F.; Al-Toma, Abdul; Dekker, Evelien; Vanhoutvin, Steven A. L. W.; Nagengast, Fokko M.; Mathus-Vliegen, Elisabeth M.; van Leerdam, Monique E.; de Vos tot Nederveen Cappel, Wouter H.; Sanduleanu, Silvia; Veenendaal, Roeland A.; Cats, Annemieke; Vasen, Hans F. A.; Kleibeuker, Jan H.; Koornstra, Jan J.

    2015-01-01

    The aim was to determine the prevalence of small-bowel neoplasia in asymptomatic patients with Lynch syndrome (LS) by video capsule endoscopy (VCE). After obtaining informed consent, asymptomatic proven gene mutation carriers aged 35-70 years were included in this prospective multicentre study in

  3. Hegemonic Masculinity and the Position of Men in Kathleen Winter’s Annabel

    Directory of Open Access Journals (Sweden)

    Tay Lai Kit

    2016-01-01

    Full Text Available Emerging from the1980s, the concept of masculinity has slowly started to make its way towards social studies. Instead of a singular fixed identity, masculinity has now been claimed to be branching into several types – hegemonic masculinity, complicit masculinity, marginalized masculinity, and subordinated masculinity. By utilizing the notion of hegemonic masculinity, this paper observes the thoughts and decisions made by men in Kathleen Winter’s Annabel. This paper explores and re-examines the position of men in their society with reference to the effect of hegemonic masculinity, as proposed by Connell. It is also within the scope of the study to trace the position of men in the novel through a series of negotiations made within themselves. This study reveals the typical behavior of an alpha male of hegemonic masculinity in Annabel. For hegemony to pan out, all members of society should have respective social duties in order for the entire mechanism to function. The paper demonstrated that male characters of the novel exude the position of men in the hegemonic masculine setting by showcasing the firmness in making decisions, having knowledge on faith, religion, and monetary issues. Keywords: Annabel; Alpha Male, Hegemonic Masculinity, Hermaphrodite

  4. A novel deletion in the splice donor site of MLH1 exon 6 in a Japanese colon cancer patient with Lynch syndrome.

    Science.gov (United States)

    Yamaguchi, Junya; Sato, Yuri; Kita, Mizuho; Nomura, Sachio; Yamamoto, Noriko; Kato, Yo; Ishikawa, Yuichi; Arai, Masami

    2015-10-01

    Lynch syndrome is an autosomal dominantly inherited disease that is characterized by a predisposition to cancers, mainly colorectal cancer. Germline mutations of DNA mismatch repair genes such as MLH1, MSH2, MSH6 and PMS2 have been described in patients with Lynch syndrome. Here, we report deletion of 2 bp in the splice donor site of the MLH1 exon 6 (c.545+4_545+5delCA) in a 48-year-old Japanese woman with Lynch syndrome. RT-PCR direct sequencing analysis revealed that this mutation led to an increase in the level of an MLH1 transcript in which exon 6 was skipped, and may cause a frameshift (p.E153FfsX8). Therefore, this mutation appears to be pathogenic and is responsible for Lynch syndrome. Additionally, analysis of the patient's tumor cells indicated microsatellite instability high phenotype and loss of the MLH1 and PMS2 proteins. To our knowledge, this is a germline splice site mutation of MLH1 that has not been reported previously. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Characterization of a rare variant (c.2635-2A>G) of the MSH2 gene in a family with Lynch syndrome.

    Science.gov (United States)

    Cariola, Filomena; Disciglio, Vittoria; Valentini, Anna M; Lotesoriere, Claudio; Fasano, Candida; Forte, Giovanna; Russo, Luciana; Di Carlo, Antonio; Guglielmi, Floranna; Manghisi, Andrea; Lolli, Ivan; Caruso, Maria L; Simone, Cristiano

    2018-04-01

    Lynch syndrome is caused by germline mutations in one of the mismatch repair genes ( MLH1, MSH2, MSH6, and PMS2) or in the EPCAM gene. Lynch syndrome is defined on the basis of clinical, pathological, and genetic findings. Accordingly, the identification of predisposing genes allows for accurate risk assessment and tailored screening protocols. Here, we report a family case with three family members manifesting the Lynch syndrome phenotype, all of which harbor the rare variant c.2635-2A>G affecting the splice site consensus sequence of intron 15 of the MSH2 gene. This mutation was previously described only in one family with Lynch syndrome, in which mismatch repair protein expression in tumor tissues was not assessed. In this study, we report for the first time the molecular characterization of the MSH2 c.2635-2A>G variant through in silico prediction analysis, microsatellite instability, and mismatch repair protein expression experiments on tumor tissues of Lynch syndrome patients. The potential effect of the splice site variant was revealed by three splicing prediction bioinformatics tools, which suggested the generation of a new cryptic splicing site. The potential pathogenic role of this variant was also revealed by the presence of microsatellite instability and the absence of MSH2/MSH6 heterodimer protein expression in the tumor cells of cancer tissues of the affected family members. We provide compelling evidence in favor of the pathogenic role of the MSH2 variant c.2635-2A>G, which could induce an alteration of the canonical splice site and consequently an aberrant form of the protein product (MSH2).

  6. 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

  7. A rare case of choroid plexus carcinoma that led to the diagnosis of Lynch syndrome (hereditary nonpolyposis colorectal cancer).

    Science.gov (United States)

    Zhu, Viola W; Hinduja, Sanjay; Knezevich, Stevan R; Silveira, William R; DeLozier, Celia D

    2017-07-01

    Lynch syndrome (hereditary nonpolyposis colorectal cancer) is an autosomal dominant disorder characterized by a significant risk of colorectal and endometrial cancers. A variety of other epithelial cancers may be associated with this syndrome. Brian tumors are infrequent, but have been reported in series. Here, we report a case of a 34-year-old Caucasian woman with WHO grade III choroid plexus carcinoma (CPC). Comprehensive genomic profiling of the patient's resected brain tumor revealed mutations in six genes: PTEN, VHL, MSH6, NOTCH1, RB1, and TP53. Family history is significant for endometrial cancer in her mother and sister as well as colon cancer in her maternal grandfather suggestive of Lynch syndrome. Site-specific mutational analysis showed the MSH6 mutation (p.R482*) in peripheral lymphocytes. Subsequently we performed immunohistochemical staining of the tumor tissue which demonstrated widespread loss of MSH6 with intact MSH2, MLH1, and PMS2. The diagnosis of Lynch syndrome due to a mutation in MSH6 was therefore established. Our patient elected to have adjuvant radiation to the surgical bed only followed by prophylactic total abdominal hysterectomy and bilateral salpingo-oophorectomy and is doing very well. To our knowledge, this is the first case report of CPC in an adult patient with a germline MSH6 mutation. We believe our data have provided molecular evidence to suggest that CPC could potentially be part of the Lynch syndrome spectrum. Published by Elsevier B.V.

  8. Marilyn Nelson: Poetic Justice

    Science.gov (United States)

    Pierpont, Katherine

    2006-01-01

    This article features some of the books written by Marilyn Nelson. Here, the author discusses how she has written a children's book of poetry about lynching, entitled "A Wreath for Emmitt Till." The author discusses how her books for children honor and memorialize history-changing African Americans. Among other things, the author discusses some of…

  9. Association of Mismatch Repair Mutation With Age at Cancer Onset in Lynch Syndrome: Implications for Stratified Surveillance Strategies.

    Science.gov (United States)

    Ryan, Neil A J; Morris, Julie; Green, Kate; Lalloo, Fiona; Woodward, Emma R; Hill, James; Crosbie, Emma J; Evans, D Gareth

    2017-12-01

    Lynch syndrome is caused by dominantly inherited germline mutations that predispose individuals to colorectal, endometrial, ovarian, and other cancers through inactivation of the cellular mismatch repair system. Lynch syndrome–associated cancers are amenable to surveillance strategies that may improve survival. The age at which surveillance should start is disputed. To determine whether mutated gene and type of mutation influence age at onset of Lynch syndrome–associated cancers. A retrospective cohort study of individuals with Lynch syndrome–associated colorectal, endometrial, and/or ovarian cancers whose medical records were included in the clinical database of a large quaternary referral center for genomic medicine in the Northwest of England. Mutated gene (MLH1, MSH2, MSH6, and/or PMS2) and type of mutation (truncating, splicing, or large rearrangement). Age at cancer diagnosis. A total of 1063 individuals with proven Lynch syndrome were included, 495 male and 568 female (mean age 52 years; age range, 10-93 years [children were included in the database, but no children developed cancer]). There were 546 men and women with colorectal cancer, 162 women with endometrial cancer, and 49 women with ovarian cancer; mean follow-up was 68.2 months. Among MLH1 mutation carriers, mutations in MLH1 were associated with colorectal cancer in 249 (61%) of 409 men and women; endometrial cancer in 53 of 196 (27%) women; and ovarian cancer in 15 (8%) of 196 women. Among MSH2 mutation carriers, mutations in MSH2 (the most prevalent mutations overall) were most commonly associated with female-specific cancers: endometrial cancer in 83 (30%) of 279 women; ovarian cancer in 28 (10%) of 279 women; and colorectal cancer in 239 (50%) 479 men and women. Mutations in MSH6 were less prevalent, and MSH6 mutation carriers presented with colorectal and endometrial cancer at later ages than carriers of mutations in MSH2 or MLH1. When stratified by mutation type, women with truncating

  10. Contiguous gene deletion of chromosome 2p16.3-p21 as a cause of Lynch syndrome.

    Science.gov (United States)

    Salo-Mullen, Erin E; Lynn, Patricio B; Wang, Lu; Walsh, Michael; Gopalan, Anuradha; Shia, Jinru; Tran, Christina; Man, Fung Ying; McBride, Sean; Schattner, Mark; Zhang, Liying; Weiser, Martin R; Stadler, Zsofia K

    2018-01-01

    Lynch syndrome is an autosomal dominant condition caused by pathogenic mutations in the DNA mismatch repair (MMR) genes. Although commonly associated with clinical features such as intellectual disability and congenital anomalies, contiguous gene deletions may also result in cancer predisposition syndromes. We report on a 52-year-old male with Lynch syndrome caused by deletion of chromosome 2p16.3-p21. The patient had intellectual disability and presented with a prostatic adenocarcinoma with an incidentally identified synchronous sigmoid adenocarcinoma that exhibited deficient MMR with an absence of MSH2 and MSH6 protein expression. Family history was unrevealing. Physical exam revealed short stature, brachycephaly with a narrow forehead and short philtrum, brachydactyly of the hands, palmar transverse crease, broad and small feet with hyperpigmentation of the soles. The patient underwent total colectomy with ileorectal anastomosis for a pT3N1 sigmoid adenocarcinoma. Germline genetic testing of the MSH2, MSH6, and EPCAM genes revealed full gene deletions. SNP-array based DNA copy number analysis identified a deletion of 4.8 Mb at 2p16.3-p21. In addition to the three Lynch syndrome associated genes, the deleted chromosomal section encompassed genes including NRXN1, CRIPT, CALM2, FBXO11, LHCGR, MCFD2, TTC7A, EPAS1, PRKCE, and 15 others. Contiguous gene deletions have been described in other inherited cancer predisposition syndromes, such as Familial Adenomatous Polyposis. Our report and review of the literature suggests that contiguous gene deletion within the 2p16-p21 chromosomal region is a rare cause of Lynch syndrome, but presents with distinct phenotypic features, highlighting the need for recognition and awareness of this syndromic entity.

  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. Biallelic MLH1 SNP cDNA expression or constitutional promoter methylation can hide genomic rearrangements causing Lynch syndrome.

    Science.gov (United States)

    Morak, Monika; Koehler, Udo; Schackert, Hans Konrad; Steinke, Verena; Royer-Pokora, Brigitte; Schulmann, Karsten; Kloor, Matthias; Höchter, Wilhelm; Weingart, Josef; Keiling, Cortina; Massdorf, Trisari; Holinski-Feder, Elke

    2011-08-01

    A positive family history, germline mutations in DNA mismatch repair genes, tumours with high microsatellite instability, and loss of mismatch repair protein expression are the hallmarks of hereditary non-polyposis colorectal cancer (Lynch syndrome). However, in ~10-15% of cases of suspected Lynch syndrome, no disease-causing mechanism can be detected. Oligo array analysis was performed to search for genomic imbalances in patients with suspected mutation-negative Lynch syndrome with MLH1 deficiency in their colorectal tumours. A deletion in the LRRFIP2 (leucine-rich repeat flightless-interacting protein 2) gene flanking the MLH1 gene was detected, which turned out to be a paracentric inversion on chromosome 3p22.2 creating two new stable fusion transcripts between MLH1 and LRRFIP2. A single-nucleotide polymorphism in MLH1 exon 8 was expressed from both alleles, initially pointing to appropriate MLH1 function at least in peripheral cells. In a second case, an inherited duplication of the MLH1 gene region resulted in constitutional MLH1 promoter methylation. Constitutional MLH1 promoter methylation may therefore in rare cases be a heritable disease mechanism and should not be overlooked in seemingly sporadic patients.

  13. 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

  14. Lynch syndrome patients' views of and preferences for return of results following whole exome sequencing.

    Science.gov (United States)

    Hitch, Kelly; Joseph, Galen; Guiltinan, Jenna; Kianmahd, Jessica; Youngblom, Janey; Blanco, Amie

    2014-08-01

    Whole exome sequencing (WES) uses next generation sequencing technology to provide information on nearly all functional, protein-coding regions in an individual's genome. Due to the vast amount of information and incidental findings that can be generated from this technology, patient preferences must be investigated to help clinicians consent and return results to patients. Patients (n = 19) who were previously clinically diagnosed with Lynch syndrome, but received uninformative negative Lynch syndrome genetic results through traditional molecular testing methods participated in semi-structured interviews after WES testing but before return of results to explore their views of WES and preferences for return of results. Analyses of interview results found that nearly all participants believed that the benefits of receiving all possible results generated from WES outweighed the undesirable effects. The majority of participants conveyed that relative to coping with a cancer diagnosis, information generated from WES would be manageable. Importantly, participants' experience with Lynch syndrome influenced their notions of genetic determinism, tolerance for uncertain results, and family communication plans. Participants would prefer to receive WES results in person from a genetic counselor or medical geneticist so that an expert could help explain the meaning and implications of the potentially large quantity and range of complicated results. These results underscore the need to study various populations with regard to the clinical use of WES in order to effectively and empathetically communicate the possible implications of this new technology and return results.

  15. 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.

  16. Justice orientation as a moderator of the framing effect on procedural justice perception.

    Science.gov (United States)

    Sasaki, Hiroyuki; Hayashi, Yoichiro

    2014-01-01

    Justice orientation is a justice-relevant personality trait, which is referred to as the tendency to attend to fairness issues and to internalize justice as a moral virtue. This study examined the moderating role of justice orientation in the relationship between justice perception and response to a decision problem. The authors manipulated procedural justice and the outcome valence of the decision frame within a vignette, and measured justice orientation of 174 Japanese participants. As hypothesized, the results indicated an interaction between procedural justice and framing manipulation, which was moderated by individual differences in justice orientation. In negative framing, justice effects were larger for individuals with high rather than low justice orientation. The results are explained from a social justice perspective, and the contributions and limitations of this study are also discussed with respect to our sample and framing manipulation.

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

    International Nuclear Information System (INIS)

    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

  18. Retributive and restorative justice.

    Science.gov (United States)

    Wenzel, Michael; Okimoto, Tyler G; Feather, Norman T; Platow, Michael J

    2008-10-01

    The emergence of restorative justice as an alternative model to Western, court-based criminal justice may have important implications for the psychology of justice. It is proposed that two different notions of justice affect responses to rule-breaking: restorative and retributive justice. Retributive justice essentially refers to the repair of justice through unilateral imposition of punishment, whereas restorative justice means the repair of justice through reaffirming a shared value-consensus in a bilateral process. Among the symbolic implications of transgressions, concerns about status and power are primarily related to retributive justice and concerns about shared values are primarily related to restorative justice. At the core of these processes, however, lies the parties' construal of their identity relation, specifically whether or not respondents perceive to share an identity with the offender. The specific case of intergroup transgressions is discussed, as are implications for future research on restoring a sense of justice after rule-breaking.

  19. Civilisation of Criminal Justice: Restorative Justice amongst other strategies

    NARCIS (Netherlands)

    J.R. Blad (John)

    2013-01-01

    markdownabstract__Abstract__ Is criminal justice becoming more and uncivilised if so, how could this be explained? Could Is criminal justice becoming more and uncivilised if so, how could this be explained? Could Is criminal justice becoming more and uncivilised if so, how could this be

  20. 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...

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

    NARCIS (Netherlands)

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

  2. 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...... 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 ... parents using the paired t-test and 5.5 years (P anticipation with 7.2 years earlier age at onset was identified also in the oldest cohort, in which the children were observed until they were older than 80 years...

  3. Universal screening for Lynch syndrome in endometrial cancers: frequency of germline mutations and identification of patients with Lynch-like syndrome.

    Science.gov (United States)

    Dillon, Jessica L; Gonzalez, Jorge L; DeMars, Leslie; Bloch, Katarzyna J; Tafe, Laura J

    2017-12-01

    Lynch syndrome (LS) is an inherited clinical syndrome characterized by a high risk of colorectal, endometrial (lifetime risk of up to 60%), ovarian, and urinary tract cancers. The diagnosis is confirmed by identification of germline mutations in the DNA mismatch repair genes MLH1, PMS2, MSH2, MSH6, or EPCAM. In 2015, our institution implemented universal screening of endometrial cancer (EC) hysterectomy specimens by mismatch repair immunohistochemistry (IHC) with reflex MLH1 promoter hypermethylation analysis for tumors with loss of MLH1/PMS2 expression. Patients with tumors negative for MLH1 methylation and those with a loss of the heterodimer pair MSH2 and MSH6, or isolated loss of either PMS2 or MSH6 were referred to the Familial Cancer Program for genetic counseling and consideration of germline testing. Between May 2015 to Dec 2016, 233 EC patients were screened by IHC for LS with a median age of 63 years. Sixty tumors (27%) had abnormal IHC staining results. Fifty-one (22%) harbored heterodimeric loss of MLH1 and PMS2, 49 of which showed MLH1 promoter methylation (1 failure, 1 negative). One showed loss of MLH1/PMS2 and MSH6, 2 showed loss of MSH2/MSH6, and 6 had isolated loss of MSH6 only. Ten patients underwent genetic counseling, and germline testing was performed in 8; LS was confirmed in 5 patients (2.1%). In addition, 3 patients with negative germline testing and presumed Lynch-like syndrome were identified and offered additional somatic testing. Universal screening for LS in EC patients has yielded positive results for identification of patients at risk for this inherited syndrome. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. [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.

  5. Common mutations identified in the MLH1 gene in familial Lynch syndrome

    Directory of Open Access Journals (Sweden)

    Jisha Elias

    2017-12-01

    In this study we identified three families with Lynch syndrome from a rural cancer center in western India (KCHRC, Goraj, Gujarat, where 70-75 CRC patients are seen annually. DNA isolated from the blood of consented family members of all three families (8-10 members/family was subjected to NGS sequencing methods on an Illumina HiSeq 4000 platform. We identified unique mutations in the MLH1 gene in all three HNPCC family members. Two of the three unrelated families shared a common mutation (154delA and 156delA. Total 8 members of a family were identified as carriers for 156delA mutation of which 5 members were unaffected while 3 were affected (age of onset: 1 member <30yrs & 2 were>40yr. The family with 154delA mutation showed 2 affected members (>40yr carrying the mutations.LYS618DEL mutation found in 8 members of the third family showed that both affected and unaffected carried the mutation. Thus the common mutations identified in the MLH1 gene in two unrelated families had a high risk for lynch syndrome especially above the age of 40.

  6. 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.

  7. Corrective Justice vs. Social Justice in the Aftermath of War

    Directory of Open Access Journals (Sweden)

    Pablo Kalmanovitz

    2010-11-01

    Full Text Available How do we justify the practice of corrective justice for losses suffered during armed conflicts? This article seeks to show the force and relevance of this question, and to argue that, in cases of massively destructive wars, social justice should gain priority over corrective justice. Starting from a liberal Rawlsian conception of the relationship between corrective and social justice, it is argued that, paradoxically, the more destructive a war is, the less normative force corrective rights have and the higher priority policies of social justice, which guarantee basic rights to all citizens, should have.

  8. 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

    2018-07-01

    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.

  9. Contemporary Transitional Justice

    DEFF Research Database (Denmark)

    Gissel, Line Engbo

    2017-01-01

    This article studies the contemporary expression of transitional justice, a field of practice through which global governance is exercised. It argues that transitional justice is being normalised, given the normative and empirical de-legitimisation of its premise of exceptionalism. The article...... theorises exceptionalism and normalcy in transitional justice and identifies three macro-level causes of normalisation: the legalisation, internationalisation, and professionalization of the field. This argument is illustrated by a study of Uganda’s trajectory of transitional justice since 1986. Across five...... phases of transitional justice, processes of legalisation, internationalisation, and professionalization have contributed to the gradual dismantling of the country’s exceptional justice. The case demonstrates, further, that normalization is a contested and incomplete process....

  10. 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.

  11. Contribution of Large Genomic Rearrangements in Italian Lynch Syndrome Patients: Characterization of a Novel Alu-Mediated Deletion

    Directory of Open Access Journals (Sweden)

    Francesca Duraturo

    2013-01-01

    Full Text Available Lynch syndrome is associated with germ-line mutations in the DNA mismatch repair (MMR genes, mainly MLH1 and MSH2. Most of the mutations reported in these genes to date are point mutations, small deletions, and insertions. Large genomic rearrangements in the MMR genes predisposing to Lynch syndrome also occur, but the frequency varies depending on the population studied on average from 5 to 20%. The aim of this study was to examine the contribution of large rearrangements in the MLH1 and MSH2 genes in a well-characterised series of 63 unrelated Southern Italian Lynch syndrome patients who were negative for pathogenic point mutations in the MLH1, MSH2, and MSH6 genes. We identified a large novel deletion in the MSH2 gene, including exon 6 in one of the patients analysed (1.6% frequency. This deletion was confirmed and localised by long-range PCR. The breakpoints of this rearrangement were characterised by sequencing. Further analysis of the breakpoints revealed that this rearrangement was a product of Alu-mediated recombination. Our findings identified a novel Alu-mediated rearrangement within MSH2 gene and showed that large deletions or duplications in MLH1 and MSH2 genes are low-frequency mutational events in Southern Italian patients with an inherited predisposition to colon cancer.

  12. Special Justice for Peace: A Transitional Justice Model According to Modern Tendencies and Orientations of Law and Justice

    OpenAIRE

    Carlos Arturo Gómez Pavajeau

    2016-01-01

    The article analyses the constitutional implications of the peace agreement about Colombia’s armed conflict. It examines constitutional rules and international instruments about human rights, confronting the agreement with justice criteria in the national and international context, to underline the role of justice for the definitive solution of the conflict. By using the methodology of opposing concepts, it reviews the implications of formal justice and material justice, to establish the supe...

  13. 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...

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

    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 of

  15. 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

  16. 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.

  17. 2015 Military Investigation and Justice Experience Survey (MIJES). Overview Report

    Science.gov (United States)

    2016-03-16

    consisting of Ms. Natalie Namrow, Ms. Sarah De Silva, Ms. Kathleen Dippold, SRA International, Inc., a CSRA Company, Dr. Samantha Daniel, Dr. Paul Cook ...construed as substantiated allegations of professional reprisal, ostracism, or maltreatment. General Satisfaction With Individuals/Resources... Professional Reprisal, Ostracism, and Maltreatment The Department strives to create an environment where military members feel comfortable and safe

  18. RESTORATIVE JUSTICE DALAM SISTEM PERADILAN PIDANA ANAK / Restorative Justice In Juvenile Justice System

    Directory of Open Access Journals (Sweden)

    Randy Pradityo

    2016-11-01

    Full Text Available Anak sebagai generasi penerus bangsa sudah selayaknya mendapatkan perhatian khusus. Hal tersebut bertujuan dalam rangka pembinaan anak untuk mewujudkan sumber daya manusia yang berkualitas. Maka dari itu, diperlukan pula sarana dan prasarana hukum yang mengantisipasi segala permasalahan yang timbul. Sarana hukum ini bertujuan untuk mengantisipasi stigma atau cap jahat yang ditimbulkan ketika anak berhadapan dengan hukum, sekaligus memulihkan dan memasyarakatkan kembali anak tersebut. Salah satu solusinya adalah dengan mengalihkan atau menempatkan pelaku tindak pidana anak keluar dari sistem peradilan pidana serta memberikan alternatif bagi penyelesaian dengan pendekatan keadilan demi kepentingan terbaik bagi anak, yang kemudian dikenal dengan pendekatan restorative justice. Restorative justice yang merupakan implementasi konsep dari diversi telah dirumuskan dalam sistem peradilan pidana anak, namun sistem yang baik haruslah diiringi dengan suatu sikap yang dijiwai kehendak untuk memandang dan berkeyakinan bahwa dunia ini selalu menjadi lebih baik. Selain itu, hendaknya prinsip the best interest of the children selalu diutamakan ketika menangani anak yang berhadapan dengan hukum.   Children as the nation's next generation is already deserve special attention. It aims in order to develop the child to realize the quality of human resources. Therefore, it is also necessary legal infrastructure to anticipate any problems that arise. The legal means to anticipate stigma or stamp evil inflicted when the child against the law, as well as restoring and re-socialize the child. One solution is to divert or placing the offender children out of the criminal justice system as well as providing an alternative to the settlement with justice approach in the best interests of the child, who was then known as restorative justice approach. Restorative justice which is the implementation of the concept of diversion has been formulated in the juvenile justice system

  19. 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.

  20. Changes in screening behaviors and attitudes toward screening from pre-test genetic counseling to post-disclosure in Lynch syndrome families

    Science.gov (United States)

    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

  1. 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.

  2. Germline Hypermethylation of MLH1 and EPCAM Deletions Are a Frequent Cause of Lynch Syndrome

    NARCIS (Netherlands)

    Niessen, Renee C.; Hofstra, Robert M. W.; Westers, Helga; Ligtenberg, Marjolijn J. L.; Kooi, Krista; Jager, Paul O. J.; de Groote, Marloes L.; Dijkhuizen, Trijnie; Olderode-Berends, Maran J. W.; Hollema, Harry; Kleibeuker, Jan H.; Sijmons, Rolf H.

    It was shown that Lynch syndrome can be caused by germline hypermethylation of the MLH1 and MSH2 promoters. Furthermore, it has been demonstrated very recently that germline deletions of the 3' region of EPCAM cause transcriptional read-through which results in silencing of MSH2 by hypermethylation.

  3. Germline hypermethylation of MLH1 and EPCAM deletions are a frequent cause of Lynch syndrome.

    NARCIS (Netherlands)

    Niessen, R.C.; Hofstra, R.M.; Westers, H.; Ligtenberg, M.J.L.; Kooi, K.; Jager, P.O.; Groote, M.L. de; Dijkhuizen, T.; Olderode-Berends, M.J.; Hollema, H.; Kleibeuker, J.H.; Sijmons, R.H.

    2009-01-01

    It was shown that Lynch syndrome can be caused by germline hypermethylation of the MLH1 and MSH2 promoters. Furthermore, it has been demonstrated very recently that germline deletions of the 3' region of EPCAM cause transcriptional read-through which results in silencing of MSH2 by hypermethylation.

  4. Bayesian Modeling for Genetic Anticipation in Presence of Mutational Heterogeneity: A Case Study in Lynch Syndrome

    DEFF Research Database (Denmark)

    Boonstra, Philip S; Mukherjee, Bhramar; Taylor, Jeremy M G

    2011-01-01

    to cause hereditary nonpolyposis colorectal cancer, also called Lynch syndrome (LS). We find evidence for a decrease in AOO between generations in this article. Our model predicts family-level anticipation effects that are potentially useful in genetic counseling clinics for high-risk families....

  5. Justice and Negotiation.

    Science.gov (United States)

    Druckman, Daniel; Wagner, Lynn M

    2016-01-01

    This review article examines the literature regarding the role played by principles of justice in negotiation. Laboratory experiments and high-stakes negotiations reveal that justice is a complex concept, both in relation to attaining just outcomes and to establishing just processes. We focus on how justice preferences guide the process and outcome of negotiated exchanges. Focusing primarily on the two types of principles that have received the most attention, distributive justice (outcomes of negotiation) and procedural justice (process of negotiation), we introduce the topic by reviewing the most relevant experimental and field or archival research on the roles played by these justice principles in negotiation. A discussion of the methods used in these studies precedes a review organized in terms of a framework that highlights the concept of negotiating stages. We also develop hypotheses based on the existing literature to point the way forward for further research on this topic.

  6. 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

    2018-06-01

    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.

  7. Justice seems not to be for all: Exploring the scope of justice

    OpenAIRE

    Lima-Nunes, Aline; Pereira, Cícero Roberto; Correia, Isabel

    2013-01-01

    The idea that “justice is for everyone” seems to be over. A justice perception can have unfair consequences for those who are perceived not to be included within the boundaries of fairness. This is what the scope of justice is all about: who is within and who is outside of the “justice boundaries”. This paper intends to clarify the concept and explain how social psychologists work with it in real-life contexts. We argue that the scope of justice is a key concept that helps us to understand a ...

  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

    . 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. 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

  10. Prospective, Multi-center Randomized Intermediate Biomarker Study of Oral Contraceptive vs. 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.

    2013-01-01

    Women with Lynch syndrome have a 40–60% 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 demonstrated that progestin-containing oral contraceptives (OCP) reduce the risk of endometrial cancer by 50% in women at general population risk. It is unknown if they are effective in women with Lynch syndrome. Asymptomatic women age 25–50 with Lynch syndrome were randomized to receive the progestin compounds depo-Provera (depoMPA) or OCP for three months. An endometrial biopsy and transvaginal ultrasound were performed 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 depoMPA 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 demonstrate that women with Lynch syndrome do show an endometrial response to short term exogenous progestins, suggesting that OCP and depoMPA may be reasonable chemopreventive agents in this high-risk patient population. PMID:23639481

  11. Justice delayed is justice denied: Protecting Miners against ...

    African Journals Online (AJOL)

    Justice delayed is justice denied: Protecting Miners against Occupational ... of section 35 of Compensation for Occupational Injuries and Diseases Act 130 of ... of the Mankayi case for the system of occupational health and safety in South Africa. ... KEYWORDS: Occupational health; diseases; injuries; employees; protection; ...

  12. 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

  13. Co-workers' Justice Judgments, own Justice Judgments and Employee Commitment: A multi-foci approach

    Directory of Open Access Journals (Sweden)

    Florence Stinglhamber

    2008-06-01

    Full Text Available Using a sample of 212 employees, we conducted a study to examine whether employees use their co-workers' fairness perceptions to generate their own justice judgments and to develop their subsequent affective commitment. The conceptual framework used to investigate these linkages is social exchange theory combined with a multiple foci approach. Results of the structural equation modeling analyses revealed that co-workers' procedural justice judgments strengthened employee's own procedural justice judgments, which in turn influenced their affective commitment to the organisation. Similarly, co-workers' interactional justice judgments increased employee's own interactional justice judgments, which in turn impacted on their affective commitment to both the supervisor and the organisation. As a whole, findings suggest that coworkers' justice judgments strengthened employee's affective attachments toward the justice sources by reinforcing employee's own justice perceptions.

  14. Uncertainties in the Management of a Lynch Syndrome Patient: A Case Report

    OpenAIRE

    Campos, Sara; Amaro, Pedro; Cunha, Inês; Fraga, João; Cipriano, Maria Augusta; Tomé, Luís

    2017-01-01

    Introduction: Lynch syndrome (LS), the most common hereditary colorectal cancer syndrome, is characterized by mutations in mismatch repair (MMR) genes leading to an increased cancer risk, namely colorectal cancer. Case: In the context of surveillance colonoscopy, a 40-mm flat lesion (0-IIa+b, Paris classification) was identified and submitted to piecemeal mucosal endoscopic resection in a 64-year-old LS patient with an MLH1 germline mutation (262delATC) and two previous segmental resections d...

  15. A Systematic Review on the Existing Screening Pathways for Lynch Syndrome Identification

    OpenAIRE

    Tognetto, Alessia; Michelazzo, Maria Benedetta; Calabró, Giovanna Elisa; Unim, Brigid; Di Marco, Marco; Ricciardi, Walter; Pastorino, Roberta; Boccia, Stefania

    2017-01-01

    Background Lynch 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 ...

  16. Models for Immune Response and Immune Evasion in MSI Cancer and Lynch Syndrome

    OpenAIRE

    Özcan, Mine

    2017-01-01

    Microsatellite-unstable (MSI) cancers occurring in the context of the hereditary Lynch syndrome or as sporadic cancers elicit pronounced tumor-specific immune responses. The pronounced immune response was shown to be closely associated with frameshift peptides (FSP) that are generated as a result of deficiency in DNA mismatch repair system leading to insertion/deletion mutations in coding microsatellites (cMS). FSP neoantigens are long antigenic amino acid stretches that bear m...

  17. Lynch syndrome-associated extracolonic tumors are rare in two extended families with the same EPCAM deletion

    NARCIS (Netherlands)

    Lynch, H.T.; Riegert-Johnson, D.L.; Snyder, C.; Lynch, J.F.; Hagenkord, J.; Boland, C.R.; Rhees, J.; Thibodeau, S.N.; Boardman, L.A.; Davies, J.; Kuiper, R.P.; Hoogerbrugge, N.; Ligtenberg, M.J.L.

    2011-01-01

    OBJECTIVES: The Lynch syndrome (LS) is an inherited cancer syndrome showing a preponderance of colorectal cancer (CRC) in context with endometrial cancer and several other extracolonic cancers, which is due to pathogenic mutations in the mismatch repair (MMR) genes, MLH1, MSH2, MSH6, and PMS2. Some

  18. 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 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.

  19. Geographies of justice: preschool-childcare provision and the conceptualisation of social justice

    OpenAIRE

    S L Holloway

    1998-01-01

    During the 1990s geographers of diverse philosophical orientations have shown a renewed interest in questions of justice. The author draws on empirical work on childcare provision in Sheffield, England, in order to evaluate two different approaches to the geography of justice and hence the theories of social justice which lie behind these; in particular she explores the different geographies of childcare produced by the territorial-justice approach, which is based on a liberal conception of s...

  20. Justice Globalism

    NARCIS (Netherlands)

    Wilson, Erin; Steger, Manfred; Siracusa, Joseph; Battersby, Paul

    2014-01-01

    The pursuit of a global order founded on universal rules extends beyond economics into the normative spheres of law, politics and justice. Justice globalists claim universal principles applicable to all societies irrespective of religion or ideology. This view privileges human rights, democracy and

  1. Justice at the millennium: a meta-analytic review of 25 years of organizational justice research.

    Science.gov (United States)

    Colquitt, J A; Conlon, D E; Wesson, M J; Porter, C O; Ng, K Y

    2001-06-01

    The field of organizational justice continues to be marked by several important research questions, including the size of relationships among justice dimensions, the relative importance of different justice criteria, and the unique effects of justice dimensions on key outcomes. To address such questions, the authors conducted a meta-analytic review of 183 justice studies. The results suggest that although different justice dimensions are moderately to highly related, they contribute incremental variance explained in fairness perceptions. The results also illustrate the overall and unique relationships among distributive, procedural, interpersonal, and informational justice and several organizational outcomes (e.g., job satisfaction, organizational commitment, evaluation of authority, organizational citizenship behavior, withdrawal, performance). These findings are reviewed in terms of their implications for future research on organizational justice.

  2. 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

    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

  3. 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.

  4. From distributive to procedural justice. Justice as a constitutive value of public administration

    Directory of Open Access Journals (Sweden)

    Antonio SANDU

    2016-07-01

    Full Text Available The justice as an ethical value can be considered constitutive for contemporary administrative systems. These ones are asked to transpose into practice the ideal of justice in the community. The functioning of a modern state cannot be conceived without a series of institutions that would guarantee the achievement of justice. The legal system was established specifically to administer justice. Modern democratic systems felt the need for certain courts and extrajudicial procedures to create justice. The institutions required to implement the extrajudicial distribution of justice are part of the public administration, representing a central element of it. The model of a political system based on justice is a minimalist one; the role of the state is limited to making it possible for individuals to follow their own ideal of welfare. Opposed to justice, the ideal of welfare requests the state, and implicitly the administration, to ensure the individual the minimum conditions to live in that community. The minimal state centered on justice is the result of a modern paradigm with post-Kantian reverberations, which emphasize the rationality of human action. If the individual is rational, he only needs fair conditions in order to pursue his own welfare. The role of the administration is to ensure those conditions and to oversee the distribution of goods and services, as well as the distribution and redistribution of added value.

  5. Environmental justice: a criminological perspective

    Science.gov (United States)

    Lynch, Michael J.; Stretesky, Paul B.; Long, Michael A.

    2015-08-01

    This article examines studies related to environmental justice in the criminological literature and from a criminological perspective. Criminologists have long been concerned with injustices in the criminal justice system related to the enforcement of criminal law. In the 1990s, following the emergence of green criminology, a handful of criminologists have drawn attention to environmental justice as an extension of more traditional criminological studies of justice and injustice. Relevant criminological studies of environmental justice are reviewed, and suggestions for future environmental justice research are offered.

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

    OpenAIRE

    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.

    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). 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...

  7. Justice and medical ethics.

    Science.gov (United States)

    Gillon, R

    1985-07-20

    Justice, in the sense of fair adjudication between conflicting claims, is held to be relevant to a wide range of issues in medical ethics. Several differing concepts of justice are briefly described, including Aristotle's formal principle of justice, libertarian theories, utilitarian theories, Marxist theories, the theory of John Rawls, and the view--held, for example, by W.D. Ross--that justice is essentially a matter of reward for individual merit.

  8. 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

  9. 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.

  10. OUTLAWING AMNESTY: THE RETURN OF CRIMINAL JUSTICE IN TRANSITIONAL JUSTICE SCHEMES*

    Directory of Open Access Journals (Sweden)

    Lisa J. Laplante, University of Connecticut-School of Law, Estados Unidos

    2012-11-01

    Full Text Available Abstract: This Article responds to an apparent gap in the scholarly literature which fails to merge the fields of human rights law and international criminal law—a step that would resolve the current debate as to whether any amnesty in transitional justice settings is lawful. More specifically, even though both fields are a subset of transitional justice in general, the discipline of international criminal law still supports the theory of “qualified amnesties” in transitional justice schemes, while international human rights law now stands for the proposition that no amnesty is lawful in those settings. This Article brings attention to this new development through a discussion of the Barrios Altos case. This Article seeks to reveal how an international human rights decision can dramatically impact state practice, thus also contributing to a pending question in international human rights law as to whether such jurisprudence is effective in increasing human rights protections. The Article concludes by looking at the implications of this new legal development in regard to amnesties in order to encourage future research regarding the role of criminal justice in transitional justice schemes. Keywords: Amnesty in the Americas. Transitional Justice. Human Rights Violations

  11. The Space for Restorative Justice in the Ethiopian Criminal Justice System

    Directory of Open Access Journals (Sweden)

    Endalew Lijalem Enyew

    2014-12-01

    Full Text Available Restorative Justice (RJ is an alternative way of apprehending crime and justice which views crime as a violation of a relationship among victims, offenders and community, and which allows the active participation of the crime’s stakeholders. It has the objective of ‘putting right’ the wrong done, to restore the broken relationship and to reintegrate the offender back into society. The Ethiopian criminal justice system views crime primarily as a violation of the state’s criminal laws, either in the form of a commission or omission. It excludes the community from participation, and gives no opportunity to the victim to fully participate in the process. Nor is there a satisfactory legal procedure which enables the public prosecutor to adequately protect the victim’s interest. The focus of the public prosecutor is to have the accused convicted and punished, instead of encouraging them to take responsibility to undo the wrong they have committed. This article thus examines whether restorative justice has a place in the formal legal framework of the existing Ethiopian criminal justice system; and analyses the prospects for, and the challenges that may hinder, the implementation of restorative justice practice in this framework.

  12. ECONOMIC EQUALITY OR JUSTICE

    Directory of Open Access Journals (Sweden)

    Ekrem Tufan

    2017-12-01

    Full Text Available From the beginning of economic life, equality has been a matter for human. Intrinsically human has two legs: Selfish and Groupish. Our selfish side does not care equality while Groupish side cares. What about the justice? Does human wants justice more than equalities in economic life? In this research, we have applied a questionnaire to find these two questions answer. As a result we can report that respondents prefer equality rather than justice in negative outcomes. On the other hand, they tend to prefer justice if there is possibility for positive outcomes. We cannot give evidence about gender, education and age differences effect on equality and justice preference.

  13. Organisational justice and change in justice as predictors of employee health: the Whitehall II study.

    Science.gov (United States)

    Kivimäki, Mika; Ferrie, Jane E; Head, Jenny; Shipley, Martin J; Vahtera, Jussi; Marmot, Michael G

    2004-11-01

    Organisational justice has been proposed as a new way to examine the impact of psychosocial work environment on employee health. This article studied the justice of interpersonal treatment by supervisors (the relational component of organisational justice) as a predictor of health. Prospective cohort study. Phase 1 (1985-88) measured relational justice, job demands, job control, social support at work, effort-reward imbalance, and self rated health. Relational justice was assessed again at phase 2 (1989-90) and self rated health at phase 2 and phase 3 (1991-93). 20 civil service departments originally located in London. 10 308 civil servants (6895 men, 3413 women) aged 35-55. Self rated health. Men exposed to low justice at phase 1 or adverse change in justice between phase 1 and phase 2 were at higher risk of poor health at phase 2 and phase 3. A favourable change in justice was associated with reduced risk. Adjustment for other stress indicators had little effect on results. In women, low justice at phase 1 predicted poor health at phase 2 and phase 3 before but not after adjustment for other stress indicators. Adverse change in justice was associated with worse health prospects irrespective of adjustments. The extent to which people are treated with justice in workplaces seems to predict their health independently of established stressors at work. Evidence on reduced health risk after favourable change in organisational justice implies a promising area for health interventions at workplace.

  14. Organizational Justice

    Science.gov (United States)

    Burns, Travis

    2013-01-01

    Helping principals understand the importance of organizational justice is the first step in enhancing learning outcomes for all learners, regardless of their social class, race, abilities, sex, or gender. In schools, organizational justice may be defined as teachers' perceptions of fairness, respect, and equity that relate to their interactions…

  15. Equality in the Framework of Justice

    OpenAIRE

    Aşik, Kübra

    2015-01-01

    This thesis assesses the relation between equality and justice by exploring and identifying the relation between equality and justice in Rawls's theory of justice, Sandel's communitarian account of Justice and Sen's capability approach. And these accounts of justice are evaluated from an egalitarian point of view. The main argument defended in the thesis is that justice requires equality. Accordingly, these three accounts of justice are evaluated by taking their understanding of equality into...

  16. 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......-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...

  17. Pancreatic non-functioning neuroendocrine tumor: a new entity genetically related to Lynch syndrome

    OpenAIRE

    Serracant Barrera, Anna; Serra Pla, Sheila; Blázquez Maña, Carmen María; Salas, Rubén Carrera; García Monforte, Neus; Bejarano González, Natalia; Romaguera Monzonis, Andreu; Andreu Navarro, Francisco Javier; Bella Cueto, Maria Rosa; Borobia, Francisco G.

    2017-01-01

    Some pancreatic neuroendocrine tumors (P-NETs) are associated with hereditary syndromes. An association between Lynch syndrome (LS) and P-NETs has been suggested, however it has not been confirmed to date. We describe the first case associating LS and P-NETs. Here we report a 65-year-old woman who in the past 20 years presented two colorectal carcinomas (CRC) endometrial carcinoma (EC), infiltrating ductal breast carcinoma, small intestine adenocarcinoma, two non-functioning P-NETs and seboma...

  18. 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 (P Trend =4.43×10 -6 ), and with increasing numbers of Lynch cancers in relatives (P Trend ≤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.

  19. Health Law as Social Justice.

    Science.gov (United States)

    Wiley, Lindsay F

    2014-01-01

    Health law is in the midst of a dramatic transformation. From a relatively narrow discipline focused on regulating relationships among individual patients, health care providers, and third-party payers, it is expanding into a far broader field with a burgeoning commitment to access to health care and assurance of healthy living conditions as matters of social justice. Through a series of incremental reform efforts stretching back decades before the Affordable Care Act and encompassing public health law as well as the law of health care financing and delivery, reducing health disparities has become a central focus of American health law and policy. This Article labels, describes, and furthers a nascent "health justice" movement by examining what it means to view health law as an instrument of social justice. Drawing on the experiences of the reproductive justice, environmental justice, and food justice movements, and on the writings of political philosophers and ethicists on health justice, I propose that health justice offers an alternative to the market competition and patient rights paradigms that currently dominate health law scholarship, advocacy, and reform. I then examine the role of law in reducing health disparities through the health justice lens. I argue that the nascent health justice framework suggests three commitments for the use of law to reduce health disparities. First, to a broader inquiry that views access to health care as one among many social determinants of health deserving of public attention and resources. Second, to probing inquiry into the effects of class, racial, and other forms of social and cultural bias on the design and implementation of measures to reduce health disparities. And third, to collective action grounded in community engagement and participatory parity. In exploring these commitments, I highlight tensions within the social justice framework and between the social justice framework and the nascent health justice movement

  20. Student Perceptions of Social Justice and Social Justice Activities

    Science.gov (United States)

    Torres-Harding, Susan R.; Steele, Cheronda; Schulz, Erica; Taha, Farah; Pico, Chantal

    2014-01-01

    Encouraging students to engage in activities that actively seek to promote social justice is a goal of many educators. This study analyzed college student perceptions around social justice and related activities in a medium-sized, urban university in the United States. Students' open-ended responses to questions assessing their perceptions of…

  1. Towards gene-and gender-based risk estimates in Lynch syndrome; Age-specific incidences for 13 extra-colorectal cancer types

    DEFF Research Database (Denmark)

    Therkildsen, Christina; Ladelund, Steen; Smith-Hansen, Lars

    2017-01-01

    Background:In Lynch syndrome, inherited mismatch repair (MMR) defects predispose to colorectal cancer and to a wide spectrum of extra-colorectal tumours. Utilising a cohort study design, we aimed to determine the risk of extra-colorectal cancer and to identify yet unrecognised tumour types...... were identified for 13 cancer types with differences related to gender, age and disease-predisposing gene. The different cancer types showed variable peak age incidence rates (IRs) with the highest IRs for ovarian cancer at age 30-49 years, for endometrial cancer, breast cancer, renal cell cancer...... and brain tumours at age 50-69 years, and for urothelial cancer, small bowel cancer, gastric cancer, pancreatic cancer and skin tumours after age 70.Conclusions:The broad spectrum of tumour types that develop at an increased incidence defines Lynch syndrome as a multi-tumour syndrome. The variable...

  2. Environmental review of the Mary Kathleen uranium minesite, Northwest Queensland

    International Nuclear Information System (INIS)

    Costelloe, M.T.; Lottermoser, B.G.; Ashley, P.M.

    1999-01-01

    Full text: The Mary Kathleen uranium deposit, in northwest Queensland, was discovered in 1954 and mined in 19561963 and 1976-1982. Rehabilitation of the site was completed in 1985 and the work won an award for environmental excellence. In 1999 gamma-ray data, plus stream sediment, soil, rock chip, mineral efflorescence, vegetation and water samples were collected from selected sites to assist in the examination of the current environmental status of the rehabilitated area. This paper presents preliminary results and interpretations. In the Mark Kathleen open pit, skarn type U-Th-REE mineralisation is hosted in amphibolite grade metamorphosed calc-silicate, mafic to intermediate igneous and sedimentary rocks. Remnant ore zones are composed of medium to coarse grained garnet and clinopyroxene, with accessory allanite, plagioclase, pyrrhotite, chalcopyrite and uraninite. Later retrograde alteration to chlorite, calcite, sericite, epidote and scapolite occurs. Fine grained uraninite is enclosed in allanite, and is partly replaced by metamict products nd traces of galena. Elevated gamma-ray readings in the open pit correspond to exposed ore lenses, the former haul road and abandoned ore stockpiles (up to 16 mSv/year). Surficial oxidation of ore and adjacent sulphide-bearing calc-silicate rocks has led to contemporary precipitation of yellow, orange, green and white mineral efflorescences on the pit walls. Wallrock oxidation of reactive sulphides (mainly pyrrhotite breakdown) produces acidic solutions, however, buffering reactions of these fluids with gangue calc-silicates and carbonate phases prevent low pH conditions from developing. The open pit lake is approximately 40m deep and contains saline (0.15%) surface waters which are Ca-, SO 4 -rich with elevated Cu, Fe, Mn, Ni, U and Zn at a pH of 6.11. Waste rock piles are up to 30m thick and have been covered by a thin veneer of benign waste. However, there are high radiation levels on several waste rock piles (up to 20

  3. MSH6 and PMS2 mutation positive Australian Lynch syndrome families: novel mutations, cancer risk and age of diagnosis of colorectal cancer.

    Science.gov (United States)

    Talseth-Palmer, Bente A; McPhillips, Mary; Groombridge, Claire; Spigelman, Allan; Scott, Rodney J

    2010-05-21

    Approximately 10% of Lynch syndrome families have a mutation in MSH6 and fewer families have a mutation in PMS2. It is assumed that the cancer incidence is the same in families with mutations in MSH6 as in families with mutations in MLH1/MSH2 but that the disease tends to occur later in life, little is known about families with PMS2 mutations. This study reports on our findings on mutation type, cancer risk and age of diagnosis in MSH6 and PMS2 families. A total of 78 participants (from 29 families) with a mutation in MSH6 and 7 participants (from 6 families) with a mutation in PMS2 were included in the current study. A database of de-identified patient information was analysed to extract all relevant information such as mutation type, cancer incidence, age of diagnosis and cancer type in this Lynch syndrome cohort. Cumulative lifetime risk was calculated utilising Kaplan-Meier survival analysis. MSH6 and PMS2 mutations represent 10.3% and 1.9%, respectively, of the pathogenic mutations in our Australian Lynch syndrome families. We identified 26 different MSH6 and 4 different PMS2 mutations in the 35 families studied. We report 15 novel MSH6 and 1 novel PMS2 mutations. The estimated cumulative risk of CRC at age 70 years was 61% (similar in males and females) and 65% for endometrial cancer in MSH6 mutation carriers. The risk of developing CRC is different between males and females at age 50 years, which is 34% for males and 21% for females. Novel MSH6 and PMS2 mutations are being reported and submitted to the current databases for identified Lynch syndrome mutations. Our data provides additional information to add to the genotype-phenotype spectrum for both MSH6 and PMS2 mutations.

  4. Applying Social Justice Principles through School-Based Restorative Justice

    Science.gov (United States)

    von der Embse, Nathan; von der Embse, Daniel; von der Embse Meghan; Levine, Ian

    2009-01-01

    Social justice has recently received attention within the school psychology community. Yet, social justice is a nebulous term, as opined by Connelly (2009), who cautioned against searching for what is wrong and instead striving for the highest standards and recognizing needs of every unique child. Shriberg and colleagues (2008) have sought to…

  5. 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.

  6. On the relationship between justice and forgiveness: are all forms of justice made equal?

    Science.gov (United States)

    Wenzel, Michael; Okimoto, Tyler G

    2014-09-01

    This research investigates whether, following a wrongdoing, the restoration of justice promotes forgiveness. Three studies - one correlational recall study and two experimental scenario studies - provide evidence that while a restored sense of justice is overall positively related to forgiveness, forgiveness is highly dependent on the means of justice restoration being retributive (punitive) versus restorative (consensus-seeking) in nature. The findings showed that, overall, restorative but not retributive responses led to greater forgiveness. Although both retributive and restorative responses appeared to increase forgiveness indirectly through increased feelings of justice, for retributive responses these effects were counteracted by direct effects on forgiveness. Moreover, the experimental evidence showed that, while feelings of justice derived from restorative responses were positively related to forgiveness, feelings of justice derived from retributive responses were not. © 2013 The British Psychological Society.

  7. 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

    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...

  8. 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.

  9. Justice and feelings: Toward a new era in justice research

    NARCIS (Netherlands)

    D. de Cremer (David); K. van den Bos (Kees)

    2007-01-01

    textabstractIn this special issue, the relationship between feelings and justice and its consequences are highlighted. Five articles discuss the role that affect, feelings, and emotions play in justice processes across a variety of social settings. In the present introductory article, the position

  10. How does justice smell? Reflections on space and place, justice and the body

    Directory of Open Access Journals (Sweden)

    Jacob Meiring

    2016-11-01

    Full Text Available Flowing from a joint consultation on Spatial Justice and Reconciliation on 21–22 September 2015, hosted by the Centre for Contextual Ministry and the Ubuntu Research Project of the University of Pretoria, this article reflects on the notions of space and justice from the perspective of a contemporary theological anthropology as ‘embodied sensing’, where the making of meaning is sensed in the body. The argument is put forward that spatial justice is an embodied endeavour and that it cannot be achieved disconnected from the bodies of the persons in the concrete context where justice is strived for and where bodies can flourish. The relation between spatial justice, sense of place, human flourishing and the embodied sensing of meaning is explored.

  11. Justice on Both Sides: Transforming Education through Restorative Justice

    Science.gov (United States)

    Winn, Maisha T.

    2018-01-01

    Restorative justice represents "a paradigm shift in the way Americans conceptualize and administer punishment," says author Maisha T. Winn, from a focus on crime to a focus on harm, including the needs of both those who were harmed and those who caused it. Her book, "Justice on Both Sides," provides an urgently needed,…

  12. »Just cut them up like regular children.« : Eraserhead (USA 1977, David Lynch)

    OpenAIRE

    Höltgen, Stefan

    2010-01-01

    Zwischen 1970 und 1977 entsteht in fünfjähriger Dreharbeit mit Unterbrechungen und unter extrem schwierigen Produktionsbedingungen David Lynchs erster Spielfilm "Eraserhead". Vorbereitet wurde er in mehrfacher Hinsicht durch das Frühwerk des noch jungen Regisseurs. Seine kinetische Skulptur "Six Men getting sick", sowie seine Kurzfilme "The Alphabet" und "The Grandmother" verhalfen ihm nicht nur zu Stipendien (etwa der AFI für "The Grandmother"), sondern etablierten auch ein Motivinventar, au...

  13. Restorative justice as social justice for victims of gendered violence: a standpoint feminist perspective.

    Science.gov (United States)

    van Wormer, Katherine

    2009-04-01

    This article provides an overview of restorative justice as a process and examines its relevance to women who have been victimized by physical and sexual abuse. The starting point is the justice system with its roots in adversarial, offender-oriented practices of obtaining justice. The widespread dissatisfaction by battered women and rape victims and their advocates with the current system of mandatory law enforcement opens the door for consideration of alternative forms of dealing with domestic violence. Restorative justice strategies, as argued here, have several major advantages. Like social work, these strategies are solution-based rather than problem-based processes, give voice to marginalized people, and focus on healing and reconciliation. Moreover, restorative justice offers an avenue through which the profession of social work can re-establish its historic role in criminal justice. The four models most relevant to women's victimization are victim-offender conferencing, family group conferencing, healing circles, and community reparations. Each model is examined separately from a feminist standpoint. The discussion is informed by insights from the teachings of standpoint feminist theory and social work values, especially social justice.

  14. „FRAMES OF TRANSITIONAL JUSTICE: SOME APPLICATION IN INTERGENERATIONAL JUSTICE AND RETROACTIVITY”

    Directory of Open Access Journals (Sweden)

    GABRIEL RADU

    2011-04-01

    Full Text Available The article attempts to evaluate the concept of transitional justice in the sphere of public and academical debates, in different social environments during the transition period in the recent history. The approach will include an overflight over some definitions and interpretation of that concept and an assessment of possible applications of this concept in the reparative (corrective theories during the political transition. The evaluation of operational dimension of transitional justice will focus primarily the moral grounds invoked in political and juridical debates, and will pursue some applications of the transitional justice in intergenerational justice realm and at the level of the institution of retroactivity. Also, the assessment will focus the moral core of the motivation of judicial decisions in the space of positive law debates, concerning the constitutional and normative dimension.Examination of particular aspects of the transition has raised particular interest in the public agenda of romanian political change. Reparation issues in dealing with the past had always occupied a privileged role in public debate, in social and political problems. Justification for corrective measures during transition period were presented on various occasions in different points of view, but tools and proper institutions in generating legitimate formal-political obligations were absent, threatening the strength of the the political stability. Requirements for application of a corrective, reparative justice, appeared as a consequence of subjective awareness of rights and liberties that positive law of the communist system ignored or assign them like law infrigement. An approach of such rights, with their features should be evaluated in the context of both totalitarian and democratic state. A dialogue with the past becomes more necesary and will contribute to the success of any public policy designed for any possible reparation in the future

  15. Justice and Feelings: Toward a New Era in Justice Research

    NARCIS (Netherlands)

    Cremer, D. de; Bos, K. van den

    2007-01-01

    In this special issue, the relationship between feelings and justice and its consequences are highlighted. Five articles discuss the role that affect, feelings, and emotions play in justice processes across a variety of social settings. In the present introductory article, the position of past

  16. Implementation Of Law Number 11 Of 2012 Concerning Child Related Criminal Justice System Concept Restorative Justice

    Directory of Open Access Journals (Sweden)

    Intan Karangan

    2016-09-01

    Full Text Available This study aims to determine how the application of the concept of restorative justice in accordance with Law No. 11 of 2012 on Child Criminal Justice system. This study uses normative namely a study that discusses the problem based on the literature and legislation relating to the matter to be investigated. Law No. 11 of 2012 on the Criminal Justice System Child has provided a new concept in the criminal justice system, especially those in the juvenile justice system. Related to the concept of Restorative Justice or restorative justice is a resolution processes involving perpetrators, victims, families, and other relevant parties in a criminal act, jointly seek solutions to the offense and its implications by emphasizing restoration and not retribution

  17. Corrective justice and contract law

    OpenAIRE

    Martín Hevia

    2010-01-01

    This article suggests that the central aspects of contract law in various jurisdictions can be explained within the idea of corrective justice. The article is divided into three parts. The first part distinguishes between corrective justice and distributive justice. The second part describes contract law. The third part focuses on actions for breach of contract and within that context reflects upon the idea of corrective justice.

  18. Crippling Sexual Justice

    DEFF Research Database (Denmark)

    Stormhøj, Christel

    2015-01-01

    Exploring homosexuals' citizenship in Denmark from a justice perspective, this article critically interrogates society's supposed gay-friendliness by asking how far it has moved in achieving sexual justice, and inquiring into the gains and pains of the existing modes of achieving this end...... and representation within family law, civil society, and in the labour market. In conclusion, I suggest the possibility of different evaluations of the level of sexual justice reached, a mainly positive, partially negative one. Additionally, I discuss the gains and pains of the existing normalizing politics....

  19. Gendered Justice Gaps in Bosnia-Herzegovina

    DEFF Research Database (Denmark)

    Björkdahl, Annika; Mannergren Selimovic, Johanna

    2014-01-01

    , and reparations gaps-this article examines structural constraints for women to engage in shaping and implementing transitional justice, and unmasks transitional justice as a site for the long-term construction of the gendered post-conflict order. Thus, the gendered dynamics of peacebuilding and transitional...... justice have produced a post-conflict order characterized by gendered peace and justice gaps. Yet, we conclude that women are doing justice within the Bosnian-Herzegovina transitional justice project, and that their presence and participation is complex, multilayered, and constrained yet critical....

  20. Contribution of MLH1 constitutional methylation for Lynch syndrome diagnosis in patients with tumor MLH1 downregulation.

    Science.gov (United States)

    Pinto, Diana; Pinto, Carla; Guerra, Joana; Pinheiro, Manuela; Santos, Rui; Vedeld, Hege Marie; Yohannes, Zeremariam; Peixoto, Ana; Santos, Catarina; Pinto, Pedro; Lopes, Paula; Lothe, Ragnhild; Lind, Guro Elisabeth; Henrique, Rui; Teixeira, Manuel R

    2018-02-01

    Constitutional epimutation of the two major mismatch repair genes, MLH1 and MSH2, has been identified as an alternative mechanism that predisposes to the development of Lynch syndrome. In the present work, we aimed to investigate the prevalence of MLH1 constitutional methylation in colorectal cancer (CRC) patients with abnormal expression of the MLH1 protein in their tumors. In a series of 38 patients who met clinical criteria for Lynch syndrome genetic testing, with loss of MLH1 expression in the tumor and with no germline mutations in the MLH1 gene (35/38) or with tumors presenting the BRAF p.Val600Glu mutation (3/38), we screened for constitutional methylation of the MLH1 gene promoter using methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) in various biological samples. We found four (4/38; 10.5%) patients with constitutional methylation in the MLH1 gene promoter. RNA studies demonstrated decreased MLH1 expression in the cases with constitutional methylation when compared with controls. We could infer the mosaic nature of MLH1 constitutional hypermethylation in tissues originated from different embryonic germ layers, and in one family we could show that it occurred de novo. We conclude that constitutional MLH1 methylation occurs in a significant proportion of patients who have loss of MLH1 protein expression in their tumors and no MLH1 pathogenic germline mutation. Furthermore, we provide evidence that MLH1 constitutional hypermethylation is the molecular mechanism behind about 3% of Lynch syndrome families diagnosed in our institution, especially in patients with early onset or multiple primary tumors without significant family history. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  1. A tailored approach to BRAF and MLH1 methylation testing in a universal screening program for Lynch syndrome.

    Science.gov (United States)

    Adar, Tomer; Rodgers, Linda H; Shannon, Kristen M; Yoshida, Makoto; Ma, Tianle; Mattia, Anthony; Lauwers, Gregory Y; Iafrate, Anthony J; Chung, Daniel C

    2017-03-01

    To determine the correlation between BRAF genotype and MLH1 promoter methylation in a screening program for Lynch syndrome (LS), a universal screening program for LS was established in two medical centers. Tumors with abnormal MLH1 staining were evaluated for both BRAF V600E genotype and MLH1 promoter methylation. Tumors positive for both were considered sporadic, and genetic testing was recommended for all others. A total 1011 colorectal cancer cases were screened for Lynch syndrome, and 148 (14.6%) exhibited absent MLH1 immunostaining. Both BRAF and MLH1 methylation testing were completed in 126 cases. Concordant results (both positive or both negative) were obtained in 86 (68.3%) and 16 (12.7%) cases, respectively, with 81% concordance overall. The positive and negative predictive values for a BRAF mutation in predicting MLH1 promoter methylation were 98.9% and 41%, respectively, and the negative predictive value fell to 15% in patients ≥70 years old. Using BRAF genotyping as a sole test to evaluate cases with absent MLH1 staining would have increased referral rates for genetic testing by 2.3-fold compared with MLH1 methylation testing alone (31% vs 13.5%, respectively, PMLH1 methylation testing for BRAF wild-type cases only would significantly decrease the number of methylation assays performed and reduce the referral rate for genetic testing to 12.7%. A BRAF mutation has an excellent positive predictive value but poor negative predictive value in predicting MLH1 promoter methylation. A hybrid use of these tests may reduce the number of low-risk patients referred to genetic counseling and facilitate wider implementation of Lynch syndrome screening programs.

  2. Corrective justice and contract law

    Directory of Open Access Journals (Sweden)

    Martín Hevia

    2010-06-01

    Full Text Available This article suggests that the central aspects of contract law in various jurisdictions can be explained within the idea of corrective justice. The article is divided into three parts. The first part distinguishes between corrective justice and distributive justice. The second part describes contract law. The third part focuses on actions for breach of contract and within that context reflects upon the idea of corrective justice.

  3. The Value Of Justice In Child Criminal Justice System A Review Of Indonesian Criminal Law

    Directory of Open Access Journals (Sweden)

    Andi Sofyan

    2015-08-01

    Full Text Available The value of justice in Act No. 11 of 2012 concerns the Child Criminal Justice System Act No. SPPA confirms the Restorative Justice Approach as a method of disputes resolution. The method of research used was normative-legal research with philosophical approach. The results showed that the value of restorative justice through diversion contained in Act SPPA but the diversion limit for certain types of criminal acts and threats of punishment under seven 7 years and not a repetition criminal recidivists. This indicates that Act SPPA still contained a retributive justice not promote the interests of protection for child.

  4. Justice-based social assistance

    Science.gov (United States)

    Barrientos, Armando

    2016-01-01

    What are the main objectives of social protection institutions in developing countries? What should be their scope and reach? What is the source of their legitimacy? Finding appropriate answers to these questions is essential to understanding, and shaping, the emergence of welfare institutions in low- and middle-income countries. Most available answers rely on instrumental arguments. Few make reference to normative principles. This article draws on three concepts from Rawls – social justice as regulating cooperation, the social minimum, and the need for a freestanding political notion of social justice – to develop a coherent argument for grounding social assistance on social justice. In line with this argument, it identifies some parameters for a justice-based social assistance. This article then discusses, with examples, the tensions existing between a social justice-based social minimum and ‘real’ social assistance institutions emerging in developing countries. PMID:27708544

  5. Corporate accountability and transitional justice

    Directory of Open Access Journals (Sweden)

    Sabine Michalowski

    2015-10-01

    Full Text Available Traditionally, transitional justice processes do not address the role of corporations in dictatorships or in armed conflicts that give rise to the need for dealing with grave and systematic human rights violations. However, there is a growing awareness that in many contexts corporations contribute to these violations, often in the form of corporate complicity with the principal violators. An argument can therefore be made that to achieve the aims of transitional justice and establish a holistic narrative of the past as well as obtain justice and reparations for victims requires investigating and addressing the role of corporate actors. This article uses the example of Colombia’s Justice and Peace process to show some of the complexities, opportunities and challenges that arise if transitional justice measures focus primarily on criminal law and create a specific legal framework, outside of the ordinary justice systems, only for a limited group of primary perpetrators, in the Colombian case for members of the armed groups who demobilised. It is argued that the exclusion of corporate actors in contexts where their role is regarded as significant leads to victims seeking alternatives ways to obtain justice and that both victims and corporations would benefit if transitional justice mechanisms addressed the role of corporations.

  6. Setting standards of restorative justice

    Directory of Open Access Journals (Sweden)

    Kostić Miomira

    2007-01-01

    Full Text Available In the article the author deals with the basic theoretical statements and discussions about the practical use of restorative justice. She discusses the questions of introducing and application of restorative justice in order to reach the balance of interests between a victim, society and a delinquent. There is no unique statement about the restorative justice concept, so the authors make this concept by listing certain activities with rispect of standards and principles. Also she emphasizes the values of restorative justice process. A part of the article is dedicated to the standards for restorative justice that are harmonized with the international documents of human rights. .

  7. A hermeneutic of justice. Justice as discernment in Matthew ...

    African Journals Online (AJOL)

    In some important dictionaries for the study of the New Testament, δικαιοσύνη has two meanings: justice in the sense of distributive justice and righteousness as a relational notion. In Matthew, we discover that the word concerns a threefold loyalty: loyalty to the law, loyalty to fellow people, and loyalty to the will of God. In the ...

  8. Doing justice to social justice in South African higher education ...

    African Journals Online (AJOL)

    This paper attempts to develop a conceptualisation of social justice in higher education based on a close reading of the current literature in the field. An important assumption we make is that higher education is a valuable mechanism for social justice. We set the literature against policy documents that detail South African ...

  9. Functional characterization of MLH1 missense 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...... localization and protein-protein interaction with the dimer partner PMS2 and the MMR-associated exonuclease 1. We show that a significant proportion of examined variant proteins have functional defects in either subcellular localization or protein-protein interactions, which is suspected to lead to the cancer...

  10. 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.

  11. Restorative Justice as Social Justice for Victims of Gendered Violence: A Standpoint Feminist Perspective

    Science.gov (United States)

    van Wormer, Katherine

    2009-01-01

    This article provides an overview of restorative justice as a process and examines its relevance to women who have been victimized by physical and sexual abuse. The starting point is the justice system with its roots in adversarial, offender-oriented practices of obtaining justice. The widespread dissatisfaction by battered women and rape victims…

  12. Evaluation of current prediction models for Lynch syndrome: updating the PREMM5 model to identify PMS2 mutation carriers

    NARCIS (Netherlands)

    A. Goverde (Anne); M.C.W. Spaander (Manon); D. Nieboer (Daan); A.M.W. van den Ouweland (Ans); W.N.M. Dinjens (Winand); H.J. Dubbink (Erik Jan); C. Tops (Cmj); S.W. Ten Broeke (Sanne W.); M.J. Bruno (Marco); R.M.W. Hofstra (Robert); E.W. Steyerberg (Ewout); A. Wagner (Anja)

    2017-01-01

    textabstractUntil recently, no prediction models for Lynch syndrome (LS) had been validated for PMS2 mutation carriers. We aimed to evaluate MMRpredict and PREMM5 in a clinical cohort and for PMS2 mutation carriers specifically. In a retrospective, clinic-based cohort we calculated predictions for

  13. Some aspects of molecular diagnostics in Lynch syndrome

    Directory of Open Access Journals (Sweden)

    Kurzawski Grzegorz

    2006-12-01

    Full Text Available Abstract This manuscript is composed of five parts which summarize five publications in succession. Essentially, they are concerned with molecular diagnostics of Lynch syndrome and are based on studies in 238 families. The finding that young age at diagnosis is the key feature in patients with MSH2 and MLH1 mutations (Part 1 has helped to define simple criteria for the preliminary diagnosis of this syndrome. A cheaper method for the detection of mutations has been developed (Part 2 and applied to study the types of mutations and their prevalence in Poland (Part 3 and the Baltic States (Part 4. A specific feature of these mutations, i.e. presence of recurrent mutations in the majority of affected families with mutations, has suggested the feasibility of effective diagnostics with a single test disclosing all of them. An attempt to reveal other causes of familial aggregation of colorectal cancer has ruled out any association with C insertion in the NOD2 gene (Part 5.

  14. Effect of low B-Lynch suture on menstrual cycle recovery and sex hormone levels in patients after cesarean section for placenta previa

    Directory of Open Access Journals (Sweden)

    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.

  15. Functional analysis in mouse embryonic stem cells reveals wild-type activity for three MSH6 variants found in suspected Lynch syndrome patients.

    Directory of Open Access Journals (Sweden)

    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.

  16. Empowering Energy Justice

    Science.gov (United States)

    Finley-Brook, Mary; Holloman, Erica L.

    2016-01-01

    The U.S. is experiencing unprecedented movement away from coal and, to a lesser degree, oil. Burdened low-income communities and people of color could experience health benefits from reductions in air and water pollution, yet these same groups could suffer harm if transitions lack broad public input or if policies prioritize elite or corporate interests. This paper highlights how U.S. energy transitions build from, and contribute to, environmental injustices. Energy justice requires not only ending disproportionate harm, it also entails involvement in the design of solutions and fair distribution of benefits, such as green jobs and clean air. To what extent does the confluence of state, civic, and market processes assure “just” transitions to clean, low-carbon energy production involving equitable distribution of costs, benefits, and decision-making power? To explore this question we assess trends with (1) fossil fuel divestment; (2) carbon taxes and social cost of carbon measurements; (3) cap-and-trade; (4) renewable energy; and (5) energy efficiency. Current research demonstrates opportunities and pitfalls in each area with mixed or partial energy justice consequences, leading to our call for greater attention to the specifics of distributive justice, procedural justice, and recognition justice in research, policy, and action. Illustrative energy transition case studies suggest the feasibility and benefit of empowering approaches, but also indicate there can be conflict between “green” and “just”, as evident though stark inequities in clean energy initiatives. To identify positive pathways forward, we compile priorities for an energy justice research agenda based on interactive and participatory practices aligning advocacy, activism, and academics. PMID:27657101

  17. Empowering Energy Justice

    Directory of Open Access Journals (Sweden)

    Mary Finley-Brook

    2016-09-01

    Full Text Available The U.S. is experiencing unprecedented movement away from coal and, to a lesser degree, oil. Burdened low-income communities and people of color could experience health benefits from reductions in air and water pollution, yet these same groups could suffer harm if transitions lack broad public input or if policies prioritize elite or corporate interests. This paper highlights how U.S. energy transitions build from, and contribute to, environmental injustices. Energy justice requires not only ending disproportionate harm, it also entails involvement in the design of solutions and fair distribution of benefits, such as green jobs and clean air. To what extent does the confluence of state, civic, and market processes assure “just” transitions to clean, low-carbon energy production involving equitable distribution of costs, benefits, and decision-making power? To explore this question we assess trends with (1 fossil fuel divestment; (2 carbon taxes and social cost of carbon measurements; (3 cap-and-trade; (4 renewable energy; and (5 energy efficiency. Current research demonstrates opportunities and pitfalls in each area with mixed or partial energy justice consequences, leading to our call for greater attention to the specifics of distributive justice, procedural justice, and recognition justice in research, policy, and action. Illustrative energy transition case studies suggest the feasibility and benefit of empowering approaches, but also indicate there can be conflict between “green” and “just”, as evident though stark inequities in clean energy initiatives. To identify positive pathways forward, we compile priorities for an energy justice research agenda based on interactive and participatory practices aligning advocacy, activism, and academics.

  18. MSH6 and PMS2 mutation positive Australian Lynch syndrome families: novel mutations, cancer risk and age of diagnosis of colorectal cancer

    Directory of Open Access Journals (Sweden)

    Talseth-Palmer Bente A

    2010-05-01

    Full Text Available Abstract Background Approximately 10% of Lynch syndrome families have a mutation in MSH6 and fewer families have a mutation in PMS2. It is assumed that the cancer incidence is the same in families with mutations in MSH6 as in families with mutations in MLH1/MSH2 but that the disease tends to occur later in life, little is known about families with PMS2 mutations. This study reports on our findings on mutation type, cancer risk and age of diagnosis in MSH6 and PMS2 families. Methods A total of 78 participants (from 29 families with a mutation in MSH6 and 7 participants (from 6 families with a mutation in PMS2 were included in the current study. A database of de-identified patient information was analysed to extract all relevant information such as mutation type, cancer incidence, age of diagnosis and cancer type in this Lynch syndrome cohort. Cumulative lifetime risk was calculated utilising Kaplan-Meier survival analysis. Results MSH6 and PMS2 mutations represent 10.3% and 1.9%, respectively, of the pathogenic mutations in our Australian Lynch syndrome families. We identified 26 different MSH6 and 4 different PMS2 mutations in the 35 families studied. We report 15 novel MSH6 and 1 novel PMS2 mutations. The estimated cumulative risk of CRC at age 70 years was 61% (similar in males and females and 65% for endometrial cancer in MSH6 mutation carriers. The risk of developing CRC is different between males and females at age 50 years, which is 34% for males and 21% for females. Conclusion Novel MSH6 and PMS2 mutations are being reported and submitted to the current databases for identified Lynch syndrome mutations. Our data provides additional information to add to the genotype-phenotype spectrum for both MSH6 and PMS2 mutations.

  19. Organizational Justice Perception According to Generations

    Directory of Open Access Journals (Sweden)

    Zeki YÜKSEKBİLGİLİ

    2015-12-01

    Full Text Available Although there are many different researches on the subject of organizational justice, there is no research on organizational justice perception according to generations. In this study, the research subject is defined if there is a difference on the perception of organizational justice between x and y generations. After a conduct of 430 surveys the Organizational Justice Scale is used. As a result, it is proved that there is no significant difference between the organizational justice perceptions according to generations

  20. Screening for germline mutations of MLH1, MSH2, MSH6 and PMS2 genes in Slovenian colorectal cancer patients: implications for a population specific detection strategy of Lynch syndrome.

    Science.gov (United States)

    Berginc, Gasper; Bracko, Matej; Ravnik-Glavac, Metka; Glavac, Damjan

    2009-01-01

    Microsatellite instability (MSI) is present in more than 90% of colorectal cancers of patients with Lynch syndrome, and is therefore a feasible marker for the disease. Mutations in MLH1, MSH2, MSH6 and PMS2, which are one of the main causes of deficient mismatch repair and subsequent MSI, have been linked to the disease. In order to establish the role of each of the 4 genes in Slovenian Lynch syndrome patients, we performed MSI analysis on 593 unselected CRC patients and subsequently searched for the presence of point mutations, larger genomic rearrangements and MLH1 promoter hypermethylation in patients with MSI-high tumours. We detected 43 (7.3%) patients with MSI-H tumours, of which 7 patients (1.3%) harboured germline defects: 2 in MLH1, 4 in MSH2, 1 in PMS2 and none in MSH6. Twenty-nine germline sequence variations of unknown significance and 17 deleterious somatic mutations were found. MLH1 promoter methylation was detected in 56% of patients without detected germline defects and in 1 (14%) suspected Lynch syndrome. Due to the minor role of germline MSH6 mutations, we adapted the Lynch syndrome detection strategy for the Slovenian population of CRC patients, whereby germline alterations should be first sought in MLH1 and MSH2 followed by a search for larger genomic rearrangements in these two genes. When no germline mutations are found tumors should be further tested for the presence of germline defects in PMS2 and MSH6. The choice about which gene should be tested first can be guided more accurately by the immunohistochemical analysis. Our study demonstrates that the incidence of MMR mutations in a population should be known prior to the application of one of several suggested strategies for detection of Lynch syndrome.

  1. Trying to restore justice: bureaucracies, risk management, and disciplinary boundaries in New Zealand criminal justice.

    Science.gov (United States)

    Fox, Kathryn J

    2015-05-01

    New Zealand is well known for its restorative justice conferences in the youth justice system. However, restorative justice has yet to overwhelm the adult criminal justice system. Based on interviews in New Zealand with correctional staff, restorative justice providers, and others, this article explores the reason for the modest inroads that restorative practice has made, and suggests that the general context may explain the limits of restorative justice in other places. The article argues that bureaucratic silos make it challenging to determine if restorative practice might fit within a rehabilitation or reintegration framework. In addition, because of the dominance of psychological modes for assessing and treating criminal behavior, an overarching preoccupation with risk management orients correctional practice toward treatment. Moreover, restorative justice's affiliation with victims' perspectives has made its placement within offender reintegration difficult to imagine. Finally, the penal populism that frames correctional practice in New Zealand, and other Anglophone countries, makes alternative to punishment harder to sell. However, the current liminal state of correctional practice creates an opportunity to conceive of more humanistic ways of repairing the harm caused by crime. © The Author(s) 2013.

  2. Juvenile Justice

    OpenAIRE

    International Child Development Centre

    1998-01-01

    The third Innocenti Digest deals with the main issues connected with children and young people coming into conflict with the law and contact with the justice system. It looks at standards and problems from arrest through to the court hearing and sentencing, use of custodial measures and ways of avoiding the child’s unnecessary and counter-productive involvement with the formal justice system. It also covers prevention questions. Like previous publications in the series, it contains practical ...

  3. Smoking and colorectal cancer in Lynch syndrome: Results from the Colon Cancer Family Registry and The University of Texas M. D. Anderson Cancer Center

    Science.gov (United States)

    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.

    2009-01-01

    Purpose 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, but the association of smoking with CRC among those with Lynch syndrome is unknown. Experimental Design 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. Results Compared with never smokers, current smokers had a significantly increased CRC risk (adjusted hazard ratio [HR] = 1.62; 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 and light smokers are at decreased CRC risk, these findings need further confirmation, preferably using prospective designs. PMID:20145170

  4. In Defense of Freedom: Protection of Human Rights at Home and Abroad

    Science.gov (United States)

    2010-10-01

    October 2009): 1105-147 Gaskew, Tony . "Peacemaking Criminology and Counterterrorism: Muslim Americans and the War on Terror." Contemporary Justice...Buckley, eds. Urbanization and Growth. Washington: World Bank, 2009. (HT 321 .U338 2009) Staudt, Kathleen, Tony Payan, and Z. Anthony Kruszewski, eds...Barbara: ABC- CLIO, 2009. (HQ 1742 .R263 2009 v. 1-2) Robbins , Richard H. Global Problems and the Culture of Capitalism. 4th ed. Boston: Pearson/Allyn

  5. Criminal Justice System of Children in The Law Number 11 of 2012 (Restorative Justice

    Directory of Open Access Journals (Sweden)

    Ansori Ansori

    2014-01-01

    Full Text Available The future of the children will determine the future of the nation. The increasing problem of juvenile delinquency in this globalization and information technology era, requires the state to give more attention to the child's future. Application of the criminal justice system for children in Indonesia is as stipulated in Law Number 3 of 1997 potentially detrimental to the child's interests. In practice, the judicial system had many problems, among them is a violation of the rights of children, such as: physical and psychological violence, as well as deprivation of the right to education and welfare. It happened because the juvenile justice system is against to national and international regulations on the protection of children’s rights. Besides that, theory of punishment for the juvenile delinquency still refers to the concept of retribution for the crimes. This concept is not very useful for the development of the child, so the concept need to be repaired with the concept of restorative justice. With this concept, the criminal justice system for the juvenile delinquency, leads to the restoration of the state and the settlement pattern, involving the perpetrator, the victim, their families and engage with the community. This is done with consideration for the protection of children against the law. Whereas in line with this spirit of the restorative justice, it gives birth to the Law No. 11 of 2012 on The Criminal Justice System of Children. How To Cite: Ansori, A. (2014. Criminal Justice System of Children in The Law Number 11 of 2012 (Restorative Justice. Rechtsidee, 1(1, 11-26. doi:http://dx.doi.org/10.21070/jihr.v1i1.95

  6. Dietary patterns and colorectal adenomas in Lynch syndrome: the GEOLynch cohort study.

    Science.gov (United States)

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

    2013-02-01

    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 LS patients was assessed. In the GEOLynch cohort of 486 persons with LS, dietary information was collected, using a food frequency questionnaire. Dietary pattern scores were obtained by principal components analysis. Hazard ratios (HR) between dietary patterns and colorectal adenomas were calculated using Cox regression models. Robust sandwich variance estimates were used to control for dependency within families. Final models were adjusted for age, sex, smoking habits, colorectal adenoma history, and extent of colon resection. During a median follow-up of 20 months, colorectal adenomas were detected in 58 persons. Four dietary patterns were identified: a "Prudent," "Meat," "Snack," and "Cosmopolitan" pattern. Individuals within the highest tertile of the "Prudent" pattern had a HR of 0.73 (95% confidence interval [CI], 0.32-1.66) for colorectal adenomas, compared with the lowest tertile. Those with high "Meat" pattern scores had a HR of 1.70 (95% CI, 0.83-3.52). A high "Snack" pattern was associated with an increased risk of colorectal adenomas (HR, 2.16; 95% CI, 1.03-4.49). A HR of 1.25 (95% CI, 0.61-2.55) was observed for persons in the highest tertile of the "Cosmopolitan" pattern. These findings suggest that dietary patterns may be associated with development of colorectal adenoma in patients with Lynch syndrome. The directions of these findings are corroborative with those observed in studies investigating sporadic colorectal cancer. Copyright © 2012 American Cancer Society.

  7. Psychology and criminal justice

    OpenAIRE

    Adler, Joanna R.

    2013-01-01

    This chapter is designed to give the reader a flavour of a few areas in which psychology has been applied to criminal justice. It begins by providing some historical context and showing the development of some applications of psychology to criminal justice. The chapter is broadly split into 3 sections: Pre Trial; Trial; and Post Trial. In most of this chapter, the areas considered assess how psychology has had an influence on the law and how psychologists work within criminal justice settings...

  8. Relationships are building blocks to social justice: Cases of biblical justice and African Ubuntu

    Directory of Open Access Journals (Sweden)

    Selaelo T. Kgatla

    2016-10-01

    Full Text Available The entire Bible is full of themes calling humans to live justly with one another and fear God who is the author of justice. The first book of the Bible, Genesis, carries the story of God’s relationship with his people. Their relationship is bound by social justice and mutual love in reciprocity. This article argues that African Ubuntu has an affinity with the Bible’s message of justice and mutual caring for one another. Ubuntu presupposes that humans were created in God’s image and indicates that characteristics such as kindness, charity, equality, love of one’s neighbours and voluntarily dispensing justice to others are present in human life. God created humans to be bound to one another in caring love, coexistence and total dependence. In today’s world, social justice requires good judgement from those who are in privileged positions to implement it.

  9. Understanding Education for Social Justice

    Science.gov (United States)

    Hytten, Kathy; Bettez, Silvia C.

    2011-01-01

    It has become increasingly common for education scholars to claim a social justice orientation in their work. At the same time, education programs seem to be adding statements about the importance of social justice to their mission, and a growing number of teacher education programs are fundamentally oriented around a vision of social justice.…

  10. 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.

  11. 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.

  12. Engineering justice transforming engineering education and practice

    CERN Document Server

    Leydens, Jon A

    2018-01-01

    Using social justice as a catalyst for curricular transformation, Engineering Justice presents an examination of how politics, culture, and other social issues are inherent in the practice of engineering. It aims to align engineering curricula with socially just outcomes, increase enrollment among underrepresented groups, and lessen lingering gender, class, and ethnicity gaps by showing how the power of engineering knowledge can be explicitly harnessed to serve the underserved and address social inequalities. This book is meant to transform the way educators think about engineering curricula through creating or transforming existing courses to attract, retain, and motivate engineering students to become professionals who enact engineering for social justice. Engineering Justice offers thought-provoking chapters on: why social justice is inherent yet often invisible in engineering education and practice; engineering design for social justice; social justice in the engineering sciences; social justice in human...

  13. La mujer en el radiador en Cabeza borradora (Eraserhead, 1972-1976) de David Lynch: disección utópica del ojo

    OpenAIRE

    Villaplana Ruiz, Virginia

    1998-01-01

    Villaplana, V. (1998). La mujer en el radiador en Cabeza borradora (Eraserhead, 1972-1976) de David Lynch: disección utópica del ojo. Banda aparte. (11):29-31. http://hdl.handle.net/10251/43165. 29 31 11

  14. Social justice in pandemic preparedness.

    Science.gov (United States)

    DeBruin, Debra; Liaschenko, Joan; Marshall, Mary Faith

    2012-04-01

    Pandemic influenza planning in the United States violates the demands of social justice in 2 fundamental respects: it embraces the neutrality of procedural justice at the expense of more substantive concern with health disparities, thus perpetuating a predictable and preventable social injustice, and it fails to move beyond lament to practical planning for alleviating barriers to accessing care. A pragmatic social justice approach, addressing both health disparities and access barriers, should inform pandemic preparedness. Achieving social justice goals in pandemic response is challenging, but strategies are available to overcome the obstacles. The public engagement process of one state's pandemic ethics project influenced the development of these strategies.

  15. The concept of energy justice across the disciplines

    International Nuclear Information System (INIS)

    Heffron, Raphael J.; McCauley, Darren

    2017-01-01

    Over the last decade, ‘Energy Justice’ is a concept that has emerged in research across many disciplines. This research explores the role and value of the energy justice concept across the disciplines. It provides the first critical account of the emergence of the energy justice concept in both research and practice. A diagrammatical image for examining the energy justice concepts is presented and this is a tool for interdisciplinary engagement with the concept. In this context, restorative justice is introduced and how it results in energy justice applying in practice is detailed. Energy research scholarship at universities is assessed and it is clear that through universities there is a platform for energy justice scholarship to build on the interdisciplinary energy scholarship at universities. Further, the role of education is vital to policy-making, and the understanding and development of the energy justice concept. Finally, in analysing how the energy justice concept can impact on policy-making, there is a critical examination of the energy justice and its relationship with economics, and how it can transfer directly into practice by assisting in balancing the competing aims of the energy trilemma. - Highlights: • Presents the value of the energy justice concept itself. • Introduces restorative justice as having a key role across the energy justice concept. • Expresses the need to develop a ‘common approach’ for the energy justice concept Advances the conceptual framework for energy justice – from theory to practice.

  16. Justice as Europe's Signifier

    NARCIS (Netherlands)

    Roy, Suryapratim; Kochenov, Dimitry; de Burca, Grainne; Williams, Andrew

    2015-01-01

    Drawing on the fact that justice is never explained in European legal discourse, but is used in conjunction with other principles and institutional decisions, this contribution argues that justice is used as a rhetorical tool to provide legitimacy to such principles and decisions. An analogous

  17. 28 CFR 0.92 - National Institute of Justice.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false National Institute of Justice. 0.92 Section 0.92 Judicial Administration DEPARTMENT OF JUSTICE ORGANIZATION OF THE DEPARTMENT OF JUSTICE 1-Office of Justice Programs and Related Agencies § 0.92 National Institute of Justice. The National...

  18. The Geography of Justice: Assessing Local Justice in Colombia’s Post-Conflict Phase

    Directory of Open Access Journals (Sweden)

    Mauricio García-Villegas

    2015-07-01

    Full Text Available This article combines descriptive empirical research with theoretical reflections to offer policy guidelines on what the role of local justice institutions in Colombia’s post-conflict phase should be. The article is divided into two parts. In the first, we present empirical evidence to illustrate the ways in which justice operates differently across the territory. In addition to illustrating these disparities, we also demonstrate the connection between these disparities and some phenomena relevant to understanding the Colombian conflict. Based on these findings, the second part of this article defines the state-building challenge confronted by the Colombian State during the post-conflict phase. Following this part, we propose a solution to this state-building challenge: the State must adopt a combination of efficacy and justice, and we provide guidelines on how a post-conflict justice system can operate to achieve that combination.

  19. Justice et miséricorde

    OpenAIRE

    Heyer, René

    2012-01-01

    On n’imagine pas de justice sans possibilité de faire miséricorde ; inversement, une miséricorde qui ne tiendrait pas compte de la justice ne serait plus la miséricorde. Les deux notions sont liées, mais sur un socle inégal : car la justice inspirée par la loi naturelle déborde la justice positive, de même que la misère des miséreux ne se laisse pas ramener au mal commis par le misérable. En découlent des variations où l’on peut voir se profiler trois moments : 1. La loi coutumière est bouscu...

  20. Restorative justice and victimology

    African Journals Online (AJOL)

    The growth of restorative justice has sparked debate over the future of the criminal justice system, which has historically adopted a retributive, punitive philosophy and advocated for an individualistic, treatment-orientated approach. This approach has over time failed to address the needs of crime victims, communities and.

  1. Comprehensive Mutation Analysis of PMS2 in a Large Cohort of Probands Suspected of Lynch Syndrome or Constitutional Mismatch Repair Deficiency Syndrome

    NARCIS (Netherlands)

    Klift, H.M. van der; Mensenkamp, A.R.; Drost, M.; Bik, E.C.; Vos, Y.J.; Gille, H.J.; Redeker, B.E.; Tiersma, Y.; Zonneveld, J.B.; Garcia, E.G.; Letteboer, T.G.; Olderode-Berends, M.J.; Hest, L.P. van; Os, T.A. van; Verhoef, S.; Wagner, A.; Asperen, C.J. van; Broeke, S.W. ten; Hes, F.J.; Wind, N. de; Nielsen, M.; Devilee, P.; Ligtenberg, M.J.L.; Wijnen, J.T.; Tops, C.M.

    2016-01-01

    Monoallelic PMS2 germline mutations cause 5%-15% of Lynch syndrome, a midlife cancer predisposition, whereas biallelic PMS2 mutations cause approximately 60% of constitutional mismatch repair deficiency (CMMRD), a rare childhood cancer syndrome. Recently improved DNA- and RNA-based strategies are

  2. Comprehensive Mutation Analysis of PMS2 in a Large Cohort of Probands Suspected of Lynch Syndrome or Constitutional Mismatch Repair Deficiency Syndrome

    NARCIS (Netherlands)

    van der Klift, Heleen M.; Mensenkamp, Arjen R.; Drost, Mark; Bik, Elsa C.; Vos, Yvonne J.; Gille, Hans J. J. P.; Redeker, Bert E. J. W.; Tiersma, Yvonne; Zonneveld, Jose B. M.; Garcia, Encarna Gomez; Letteboer, Tom G. W.; Olderode-Berends, Maran J. W.; van Hest, Liselotte P.; van Os, Theo A.; Verhoef, Senno; Wagner, Anja; van Asperen, Christi J.; ten Broeke, Sanne W.; Hes, Frederik J.; de Wind, Niels; Nielsen, Maartje; Devilee, Peter; Ligtenberg, Marjolijn J. L.; Wijnen, Juul T.; Tops, Carli M. J.

    Monoallelic PMS2 germline mutations cause 5%-15% of Lynch syndrome, a midlife cancer predisposition, whereas biallelic PMS2 mutations cause approximately 60% of constitutional mismatch repair deficiency (CMMRD), a rare childhood cancer syndrome. Recently improved DNA- and RNA-based strategies are

  3. Assessment for Social Justice: The Role of Assessment in Achieving Social Justice

    Science.gov (United States)

    McArthur, Jan

    2016-01-01

    This article provides a rationale for "assessment for social justice", through which a greater focus is given to the role of assessment in achieving the social justice aspirations of higher education. It takes inspiration from work on assessment for learning to propose that as assessment is a powerful driver of how and what students…

  4. Organization, relational justice and absenteeism.

    Science.gov (United States)

    Stoetzer, Ulrich; Åborg, Carl; Johansson, Gun; Svartengren, Magnus

    2014-01-01

    There is a need for more knowledge on how to manage companies towards healthier and more prosperous organizations with low levels of absenteeism. Relational Justice can be a useful concept when managing such organizations. Organizational factors can help to explain why some companies have relatively low absenteeism rates, even though they are equal to other companies in many other aspects. Previous studies suggest that management may be one important factor. Efficient management may depend on good relations between the leaders and the employees. The concept of Relational Justice is designed to capture these relations. Consequently, a Relational Justice framework may be used to understand why some companies have a low incidence of absenteeism. Managers from a representative body of Swedish companies. Interviews were analyzed to explore whether the items representing the concept of Relational Justice can be used to further understand the strategies, procedures and structures that characterize organizations and management in companies with a low incidence of absenteeism. Strategies, procedures or principles related to Relational Justice were common and highlighted in companies with an incidence of absenteeism. The most frequently occurring factors were; to be treated with kindness and consideration, personal viewpoint considered and to be treated impartially. The results suggested that a Relational Justice framework could be used to increase understanding of the organizational and managerial factors typical for companies with a low incidence of absenteeism. A Relational Justice approach to organizational management may be used to successfully lower absenteeism, change organizations and promote healthy and prosperous companies.

  5. Environmental justice: An issue for states

    Energy Technology Data Exchange (ETDEWEB)

    Murakami, L.K.; Davis, S.; Starkey, D. [National Conference of State Legislatures, Denver, CO (United States)

    1996-12-01

    Environmental justice combines the social justice and the environmental movements. The very term environmental justice is often and inaccurately used interchangeably with environmental racism and environmental equity. Environmental racism refers to any policy, practice or directive, intentional or not, that differentially affects the environment of individuals, groups or communities based on their race. The concept of environmental equity holds that all populations should bear a proportionate share of environmental pollution and health risks. Environmental justice is a broader term that encompasses both these concepts and connotes the laws must be applied with fairness and impartiality. Environmental justice is defined as the achievement of equal protection from environmental and health hazards for all people regardless of race, income, culture or social class.

  6. Environmental justice: An issue for states

    International Nuclear Information System (INIS)

    Murakami, L.K.; Davis, S.; Starkey, D.

    1996-01-01

    Environmental justice combines the social justice and the environmental movements. The very term environmental justice is often and inaccurately used interchangeably with environmental racism and environmental equity. Environmental racism refers to any policy, practice or directive, intentional or not, that differentially affects the environment of individuals, groups or communities based on their race. The concept of environmental equity holds that all populations should bear a proportionate share of environmental pollution and health risks. Environmental justice is a broader term that encompasses both these concepts and connotes the laws must be applied with fairness and impartiality. Environmental justice is defined as the achievement of equal protection from environmental and health hazards for all people regardless of race, income, culture or social class

  7. Military Justice Study Guide

    Science.gov (United States)

    1990-07-01

    statute within the military system, persons unfamiliar with the military justice system may find the procedure something of a paradox at first blush...Manual for Courts-Martial) Is RM Nemitafinuestlitimelf.(er- V. GRAD*: c. ORGANIZATION dDT FRPR ast eiRO t: fII) EPR LCDR/ Naval Justice School

  8. 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...

  9. Mathematics education for social justice

    Science.gov (United States)

    Suhendra

    2016-02-01

    Mathematics often perceived as a difficult subject with many students failing to understand why they learn mathematics. This situation has been further aggravated by the teaching and learning processes used, which is mechanistic without considering students' needs. The learning of mathematics tends to be just a compulsory subject, in which all students have to attend its classes. Social justice framework facilitates individuals or groups as a whole and provides equitable approaches to achieving equitable outcomes by recognising disadvantage. Applying social justice principles in educational context is related to how the teachers treat their students, dictates that all students the right to equal treatment regardless of their background and completed with applying social justice issues integrated with the content of the subject in order to internalise the principles of social justice simultaneously the concepts of the subject. The study examined the usefulness of implementing the social justice framework as a means of improving the quality of mathematics teaching in Indonesia involved four teacher-participants and their mathematics classes. The study used action research as the research methodology in which the teachers implemented and evaluated their use of social justice framework in their teaching. The data were collected using multiple research methods while analysis and interpretation of the data were carried out throughout the study. The findings of the study indicated that there were a number of challengesrelated to the implementation of the social justice framework. The findings also indicated that, the teachers were provided with a comprehensive guide that they could draw on to make decisions about how they could improve their lessons. The interactions among students and between the teachers and the students improved, they became more involved in teaching and learning process. Using social justice framework helped the teachers to make mathematics more

  10. Juvenile Justice in Mexico

    Directory of Open Access Journals (Sweden)

    Martha Frías Armenta

    2014-08-01

    Full Text Available The first tribunal in Mexico was established in the central state of San Luis Potosi in 1926. The Law Regarding Social Prevention and Juvenile Delinquency for the Federal District and Mexican territories was promulgated in 1928. In 2005, Article 18 of the Mexican Constitution was modified to establish a comprehensive system (“Sistema Integral de justicia” in Spanish of justice for juveniles between 12 and 18 years old who had committed a crime punishable under criminal law. Its objective was to guarantee juveniles all the due process rights established for adults, in addition to the special ones recognized for minors. The constitutional reform also provides a framework that includes special tribunals as well as alternative justice options for juveniles. With these reforms, institutionalization of minors was to be considered an extreme measure applicable only to felonies and to juveniles older than 14. In 2006, all states within the Mexican federation enacted the “Law of justice for adolescents”. This system, at both the federal and state levels, formalizes a new global paradigm with regard to the triangular relationship between children, the State and the Law. It recognizes that children are also bearers of the inherent human rights recognized for all individuals, instead of simply objects in need of protection. However, despite formally aligning Mexican juvenile justice law with the Convention on the Rights of the Child (CRC, issues of actual substantive rights remained and new ones have appeared. For example, juveniles younger than 14 who have not committed a felony are released from institutions without any rehabilitation or treatment options, and alternative forms of justice were included without evaluating their possibilities of application or their conditions for success. In addition, the economic status of most juvenile detainees continues to be one of the most important determining factors in the administration of justice

  11. New frontiers and conceptual frameworks for energy justice

    International Nuclear Information System (INIS)

    Sovacool, Benjamin K.; Burke, Matthew; Baker, Lucy; Kotikalapudi, Chaitanya Kumar; Wlokas, Holle

    2017-01-01

    This article explores how concepts from justice and ethics can inform energy decision-making and highlight the moral and equity dimensions of energy production and use. It defines “energy justice” as a global energy system that fairly distributes both the benefits and burdens of energy services, and one that contributes to more representative and inclusive energy decision-making. The primary contribution of the article is its focus on six new frontiers of future energy justice research. First is making the case for the involvement of non-Western justice theorists. Second is expanding beyond humans to look at the Rights of Nature or non-anthropocentric notions of justice. Third is focusing on cross-scalar issues of justice such as embodied emissions. Fourth is identifying business models and the co-benefits of justice. Fifth is better understanding the tradeoffs within energy justice principles. Sixth is exposing unjust discourses. In doing so, the article presents an agenda constituted by 30 research questions as well as an amended conceptual framework consisting of ten principles. The article argues in favor of “justice-aware” energy planning and policymaking, and it hopes that its (reconsidered) energy justice conceptual framework offers a critical tool to inform decision-making. - Highlights: • We need “justice-aware” energy policy. • A revised energy justice conceptual framework offers a critical tool to inform decision making. • New fields of inquiry for energy justice research and practice exist. • Tradeoffs and weighing competing justice claims occur in practice.

  12. Personality traits and perceptions of organisational justice.

    Science.gov (United States)

    Törnroos, Maria; Elovainio, Marko; Hintsa, Taina; Hintsanen, Mirka; Pulkki-Råback, Laura; Jokela, Markus; Lehtimäki, Terho; Raitakari, Olli T; Keltikangas-Järvinen, Liisa

    2018-01-04

    This study examined the association between five-factor model personality traits and perceptions of organisational justice. The sample for the study comprised 903 participants (35-50 years old; 523 women) studied in 2007 and 2012. Measures used were the Neuroticism, Extraversion, Openness, Five-Factor Inventory questionnaire and the short organisational justice measure. The results showed that high neuroticism was associated with low distributive, procedural and interactional justice. Furthermore, high agreeableness was associated with high procedural and interactional justice and high openness with high distributive justice. This study suggests that neuroticism, agreeableness and openness are involved in perceptions of organisational justice and that personality should be considered in research and in practices at the workplace. © 2018 International Union of Psychological Science.

  13. Restorative Justice: A Changing Community Response

    Science.gov (United States)

    Ryan, Thomas G.; Ruddy, Sean

    2015-01-01

    Our purpose herein is to demonstrate how restorative justice continues to unfold globally and we explain how the use of a restorative justice ideology and intervention leads to a common alternative, not only in criminal justice institutions, but also within social agencies, such as elementary schools, and the related social support systems. We…

  14. Rethinking Discussions of Justice in Educational Research: Formative Justice, Educational Liberalism, and Beyond

    Science.gov (United States)

    Thompson, Winston C.

    2016-01-01

    Background/Context: Educational research tends to borrow accounts of justice from scholarship embedded within the structures and commitments of other disciplines or fields of study. This has created a body of educational research that largely responds to the "justice" goals of those disciplines rather than education qua education.…

  15. Restorative Justice in Indonesia: Traditional Value

    Directory of Open Access Journals (Sweden)

    Eva Achjani Zulfa

    2011-05-01

    Full Text Available “Restorative Justice” is a model approach which emerged in the 1960s in an effort to solve criminal cases. Unlike the approach used in conventional criminal justice system, this approach focuses on the direct participation of perpetrators, victims and society in the settlement process. This theory of the approach is still debated, but the view is in fact growing and it exercises a lot of influence on legal policies and practices in several countries. The UN through its basic principles considers the approach of restorative justice as the approach which could be used in the rational criminal justice system. Restorative justice is a concept of thinking that supports the development of the criminal justice system with emphasis on the required involvement of the community. It is also involving the casualties who with the current criminal justice system are excluded. In several countries, restorative justice has been translated into a variety of formulations to accommodate a variety of values, philosophical basis, terms, strategies, mechanisms, and programs. Good consultation with the perpetrators and the victims themselves may provide the public with a different mindset in preventing emerging problems. This process can involve the police, prosecutorial institution or the traditional institutions. Therefore, without excluding the work in the formal legal system, the institutional mechanism for resolution through consultation was working in the community. In the various principles and models of the restorative justice approach, the process of dialogue between the perpetrator and the victim is a fundamental and the also the most important part of the application of the restorative justice. The direct dialogue between the perpetrator and the victim gave the victim the opportunity to express what he/she felt, hope for human rights and the desire to reach a criminal settlement.

  16. 83 CHALLENGES AND PROSPECTS OF THE JUVENILE JUSTICE ...

    African Journals Online (AJOL)

    Fr. Ikenga

    Juvenile justice administration in Nigeria is weak and has been given very .... The Nigerian criminal justice system, of which the juvenile justice system is an integral part, ... as instruments of security and justice but as weapons of oppression8.

  17. "The Path of Social Justice": A Human Rights History of Social Justice Education

    Science.gov (United States)

    Grant, Carl A.; Gibson, Melissa Leigh

    2013-01-01

    Although not often recognized, social justice education in the U.S. is historically and philosophically tied to the twentieth century's human rights initiatives. The efforts of human rights pioneers, such as those who authored the Universal Declaration of Human Rights, have indelibly shaped social justice efforts, including within education, in…

  18. Navigating the Meanings of Social Justice, Teaching for Social Justice, and Multicultural Education

    Science.gov (United States)

    Cho, Hyunhee

    2017-01-01

    This article uses well-received contemporary scholarship--works by Iris Young, Nancy Fraser, Morva McDonald, Connie North, and Geneva Gay--to illuminate a high degree of coherence among the substantive meanings of social justice, teaching for social justice, and multicultural education. Based on these relationships, the article suggests that…

  19. Genetics, criminal justice, and the minority community: An introduction for professionals in criminal justice. A report on the third annual convocation of the Justice George Lewis Ruffin Society

    Energy Technology Data Exchange (ETDEWEB)

    Croatti, R.D.

    1994-10-15

    The Justice George Lewis Ruffin Society is an organization founded in 1984 to support minority professionals in the Massachusetts criminal justice system. The Society began the sponsorship of statewide Convocations in 1992. These events provide minority criminal justice professionals with the opportunity to focus on pertinent topics through expert presentations, panel discussions, and peer interactions. Because of its increasing importance in the criminal justice process at large, and growing significance to the minority community in particular, the committee determined that the 1994 Convocation would focus on DNA. A decision was made to concentrate both on the science and the ethical and moral considerations pertinent to its application. The committee determined that along with expert presentations, a large portion of each day`s program should be devoted to workshops, designed to provide participants with an opportunity to review, test and discuss the material in a small group environment. Overall objectives of the Convocation were to provide minority and non-minority criminal justice professionals with a basic foundation in the science of genetics as well as current developments in genetic diagnostic technology, to highlight the actual and potential application of DNA technology to the criminal justice system and elsewhere, and to underscore the implications of these developments for criminal justice policy and the law.

  20. Justice In Granting Remission For Corruption Prisoners A Review Of Indonesian Criminal Justice System

    Directory of Open Access Journals (Sweden)

    Mispansyah

    2015-08-01

    Full Text Available Abstract Prisoners are entitled to have a reduction in criminal past remission as stipulated in the Indonesian Criminal Justice System still being debated to this day. This research reviews the essence of the implementation of the substantive law in granting remission against inmate corruption cases from the perspective of public and individual interests. The type of research used in this paper is socio-legal research reviewing remission policy from the perspective of the criminal law system with philosophical and statute approach. The outcomes of the research indicate that the implementation of granting remission for corruption prisoners does not provide justice both procedural and substantive does not provide legal expediency and arising imbalance of justice for individuals communities and countries. The need to implement remissions with impartial justice for corruption prisoners in granting remission to be useful for individuals communities and countries.

  1. Comprehensive Mutation Analysis of PMS2 in a Large Cohort of Probands Suspected of Lynch Syndrome or Constitutional Mismatch Repair Deficiency (CMMRD) Syndrome

    NARCIS (Netherlands)

    van der Klift, Heleen M; Mensenkamp, Arjen R; Drost, Mark; Bik, Elsa C; Vos, Yvonne J; Gille, Hans J J P; Redeker, Bert E J W; Tiersma, Yvonne; Zonneveld, José B M; García, Encarna Gómez; Letteboer, Tom G W; Olderode-Berends, Maran J W; van Hest, Liselotte P; van Os, Theo A; Verhoef, Senno; Wagner, Anja; van Asperen, Christi J; Ten Broeke, Sanne W; Hes, Frederik J; de Wind, Niels; Nielsen, Maartje; Devilee, Peter; Ligtenberg, Marjolijn J L; Wijnen, Juul T; Tops, Carli M J

    2016-01-01

    Monoallelic PMS2 germline mutations cause 5-15% of Lynch syndrome, a midlife cancer predisposition, whereas biallelic PMS2 mutations cause approximately 60% of constitutional MMR deficiency (CMMRD), a rare childhood cancer syndrome. Recently improved DNA and RNA-based strategies are applied to

  2. What is justice in education? Sketch of answer based on theories of justice and economics.

    OpenAIRE

    D. Waltenberg , Fábio

    2004-01-01

    D. Waltenberg, F. (2004). What is justice in education? Sketch of answer based on theories of justice and economics. Les Cahiers de Recherche du Girsef, 32.; What is justice in education? How can we evaluate whether given distributions of educational inputs or educational outcomes are just or not? How should a society distribute its educational resources? How can we evaluate the level of (un)fairness of a schooling system? In this paper, we try to provide a basic framework for thinking about ...

  3. Organization structure as a moderator of the relationship between procedural justice, interactional justice, perceived organizational support, and supervisory trust.

    Science.gov (United States)

    Ambrose, Maureen L; Schminke, Marshall

    2003-04-01

    Organizational justice researchers recognize the important role organization context plays in justice perceptions, yet few studies systematically examine contextual variables. This article examines how 1 aspect of context--organizational structure--affects the relationship between justice perceptions and 2 types of social exchange relationships, organizational and supervisory. The authors suggest that under different structural conditions, procedural and interactional justice will play differentially important roles in determining the quality of organizational social exchange (as evidenced by perceived organizational support [POS]) and supervisory social exchange (as evidenced by supervisory trust). In particular, the authors hypothesized that the relationship between procedural justice and POS would be stronger in mechanistic organizations and that the relationship between interactional justice and supervisory trust would be stronger in organic organizations. The authors' results support these hypotheses.

  4. The notion and basic principles of restorative justice

    Directory of Open Access Journals (Sweden)

    Ćopić Sanja

    2007-01-01

    Full Text Available One of the most important achievements of the contemporary criminal justice system and criminal policy is development of the concept of restorative justice. Contemporary concept of restorative justice was developed in 1970s on the basis of the criticism of the traditional criminal law and criminal justice system. Since that time, it has been developing through different programs in many countries. Reform of the criminal justice system in Serbia staring from 2002 went into direction of entering elements of restorative justice into existing criminal justice system. In that sense, development of restorative justice is still at the beginning in our country. However, it can be noticed that there is a low level of awareness on the nature and importance of restorative forms of response to crime among our professionals, as well as a lack of understanding of the concept itself. Due to that, the aim of the paper is to enable better understanding of restorative concept in general through defining restorative justice and basic principles it relies on. That may put a basis for further recognition of restorative elements in our criminal justice system, which may provide adequate implementation of relevant provisions of restorative character in practice. .

  5. The future of morality and international justice

    Directory of Open Access Journals (Sweden)

    Rakić Vojin

    2010-01-01

    Full Text Available The focus of this paper will be on the issue of justice, specifically in international relations. In that context, a number of existing theories of international justice will be briefly reviewed. Afterwards, I will turn to the question of what justice actually is. The assertion that justice is based on the idea of freedom will be substantiated. I will attempt to support my position with Doyle's and Kant's argumentation. It will be concluded that there are robust arguments in favor of the thesis that our historical development is marked by a gradual expansion of freedom and justice. Furthermore, we have strong reasons to aspire liberal internationalism based on the idea of humanity's gradual approximation of some form of global state because such a conception might be the best warrant of justice in international relations.

  6. What Justice for Rwanda? Gacaca versus Truth Commission?

    OpenAIRE

    Reuchamps, Min

    2008-01-01

    In post-genocide Rwanda, in addition to gacaca courts, a truth commission is needed in order to promote justice and foster reconciliation. In the context of transitional justice, retributive justice, which seeks justice and focuses on the perpetrators, appears to be inadequate to lead a society towards reconciliation. Therefore, some forms of restorative justice, which emphasize the healing of the whole society, seem necessary. In Rwanda, gacaca courts and a truth commission are complementary...

  7. Social and psychological aspects of criminal juvenile justice in the world practice (Anglo-Saxon model of juvenile justice

    Directory of Open Access Journals (Sweden)

    D.S. Oshevsky

    2013-10-01

    Full Text Available The article is the final part of the review of existing foreign models of juvenile criminal justice system. We analyze the principles of juvenile justice in the criminal trial: protective orientation, personalization and social richness of the trial, the emphasis on educational influences. We present the foreign experience of incorporating social, psychological and clinical special knowledge into specialized justice concerning juvenile offenders. We analyze modern trends in the development of juvenile justice in the United States and Canada. We present material related to methods of risk assessment of re-offending among adolescents. We highlight approaches to complex long-term follow-up of juvenile offenders in Anglo-Saxon juvenile justice. We describe some aspects of the probation service using the method of case management. In the context of the accepted “National Strategy for Action for the Benefit of Children for 2012-2017”, the prospects for the development of specialized criminal justice for young offenders in the Russian Federation are discussed

  8. The antecedents of buyers' perceived justice in online markets.

    Science.gov (United States)

    Chiu, Shun-Po; Chou, Huey-Wen; Chiu, Chao-Min

    2013-07-01

    The success of a business largely depends upon customers' intentions to continue to purchase, but this can be a challenge for vendors in online markets. This study proposes a model which identifies an initial set of justice antecedents and evaluates their relation to perceived justice, trust, and repurchase intention in online markets. The theoretical model is tested by using structural equation modeling on a data set of 424 buyers in Yahoo! Kimo online auction market. The results demonstrate that three dimensions of justice (distributive, procedural, and interactional) are positively and significantly related to trust, which in turn affects buyers' intention to repurchase. Moreover, among the three dimensions of justice judgments, distributive justice and interactional justice are relatively more important than procedural justice in predicting buyers' trust in sellers. In terms of the antecedents of justice, this study provides evidence that product quality and delivery performance are significantly related to distributive justice, while information quality and contact channel are important antecedents of procedural justice. This study also finds that responsiveness is important in enhancing buyers' judgments of interactional justice.

  9. Engaging Global Justice Through Internships (Penultimate Draft)

    OpenAIRE

    Ericka Tucker

    2014-01-01

    Engaging with Global Justice through InternshipsGlobal justice, on its face, seems like an impossible task. As individuals, even citizens of wealthy and powerful countries, the task of economic, social and political justice seems to outstrip our intellectual, practical and emotional abilities. Considering the scope of 'global' justice, it would appear that a massive coordinated effort would be necessary to overcome the problems of global injustice, yet it would seem such coordination may be i...

  10. Transgenerational epigenetics and environmental justice.

    Science.gov (United States)

    Rothstein, Mark A; Harrell, Heather L; Marchant, Gary E

    2017-07-01

    Human transmission to offspring and future generations of acquired epigenetic modifications has not been definitively established, although there are several environmental exposures with suggestive evidence. This article uses three examples of hazardous substances with greater exposures in vulnerable populations: pesticides, lead, and diesel exhaust. It then considers whether, if there were scientific evidence of transgenerational epigenetic inheritance, there would be greater attention given to concerns about environmental justice in environmental laws, regulations, and policies at all levels of government. To provide a broader perspective on environmental justice the article discusses two of the most commonly cited approaches to environmental justice. John Rawls's theory of justice as fairness, a form of egalitarianism, is frequently invoked for the principle that differential treatment of individuals is justified only if actions are designed to benefit those with the greatest need. Another theory, the capabilities approach of Amartya Sen and Martha Nussbaum, focuses on whether essential capabilities of society, such as life and health, are made available to all individuals. In applying principles of environmental justice the article considers whether there is a heightened societal obligation to protect the most vulnerable individuals from hazardous exposures that could adversely affect their offspring through epigenetic mechanisms. It concludes that unless there were compelling evidence of transgenerational epigenetic harms, it is unlikely that there would be a significant impetus to adopt new policies to prevent epigenetic harms by invoking principles of environmental justice.

  11. Asserting their Justice. The Shuar Vindicatory System and the Development of Indigenous Justice

    Directory of Open Access Journals (Sweden)

    Raúl Márquez Porras

    2018-06-01

    Full Text Available In Ecuador, the State’s recognition of indigenous justice systems takes place in a context where the legal framework is only partially made explicit, native communities debate their own legal model and their relationship with the State legal system remains ambiguous. This paper addresses the legal realities of one of these groups, the Shuar, drawing on a case study carried out in Nangaritza and on bibliographic work. First, a characterisation of the Shuar traditional justice is attempted. Then, certain dynamics of change, as well as the relationship between the Shuar and the State’s representatives, is described. Finally, hypotheses are proposed concerning the adaptation of Shuar justice to the new constitutional framework and its formalisation process.

  12. Love and justice's dialectical relationship: Ricoeur's contribution on the relationship between care and justice within care ethics.

    Science.gov (United States)

    Van Stichel, Ellen

    2014-11-01

    The relationship between love/care and justice was one of the key tensions from which care ethics originated; to this very day it is subject of debate between various streams of thought within care ethics. With some exceptions (e.g. Christa Schnabl) most approaches have in common the belief that care and justice are mutually exclusive concepts, or at least as so different that their application is situated on different levels. Hence, both are complementary, but distinct, so that there is no real interaction. This paper aims to investigate whether, and if so, how, a deeper understanding of Ricoeur's thoughts on this matter enriches the relationship between care and justice with respect to care ethics. This connection suggests itself from Ricoeur's interpretation of the relationship as a dialectical one in which the logic of superabundance (love) and the logic of equivalence (justice) meet. Care enables people to see the face and individuality of the one, 'le chacun,' within the anonymous structures of justice that tend to reduce all human beings to the anonymous each, 'le on'; justice in its turn is the precondition for love to become incarnated and made real. What may this view--of care and justice standing in close connection, in which they correct and strengthen each other--add to the understanding of concrete practices of care?

  13. Gendering agency in transitional justice

    DEFF Research Database (Denmark)

    Björkdahl, Annika; Selimovic, Johanna Mannergren

    2015-01-01

    -Herzegovina, where we point out instances of critical, creative, and transformative agency performed by women that challenge or negotiate patterns of gendered relations of domination. We collect women’s oral narratives and explore new sets of questions to capture women’s unique experiences in doing justice......Mainstream transitional justice and peacebuilding practices tend to re-entrench gendered hierarchies by ignoring women or circumscribing their presence to passive victims in need of protection. As a consequence we have limited knowledge about the multifaceted ways women do justice and build peace....... To address this lacuna we conceptualize and unpack the meaning of gendered agency, by identifying its critical elements and by locating it in space and in time. The conceptual work that we undertake is underpinned by empirical mapping of the transitional justice spaces in post-conflict Bosnia...

  14. Measuring Intergenerational Justice

    Directory of Open Access Journals (Sweden)

    Laurence J. Kotlikoff

    2017-12-01

    Full Text Available Concern with intergenerational justice has long been a focus of economics. This essay considers the effort, over the last three decades, to quantify generational fiscal burdens using label-free fiscal gap and generational accounting. It also points out that government debt -- the conventional metric for assessing generational fiscal justice,– has no grounding in economic theory. Instead, official debt is the result of economically arbitrary government labelling decisions: whether to call receipts “taxes” rather than “borrowing” and whether to call payments “transfer payments” rather than “debt service”. Via their choice of words, governments decide which obligations to put on, and which to keep off, the books. The essay also looks to the future of generational fiscal-justice analysis. Rapid computational advances are permitting economists to understand not just direct government intergenerational redistribution, but also how such policies impact the economy that future generations will inherit.

  15. Perception on justice, trust and tax compliance behavior in Malaysia

    Directory of Open Access Journals (Sweden)

    Sellywati Mohd Faizal

    2017-09-01

    Full Text Available The relationship between justice and trust with tax compliance behavior in Malaysia was studied. Previous studies have acknowledged the perception that justice does have an impact on tax compliance. This study distinguishes justice into procedural justice, distributive justice, and retributive justice. Therefore, this study examined the effect of these three types of justice on tax compliance. Trust also influences the act of tax compliance and it also has a relationship to the element of justice. Perceptions from individual taxpayers were gathered using questionnaires from previous studies. The findings suggest only procedural justice and trust affect tax compliance and procedural justice was positively and significantly correlated to trust. However, trust does not mediate the relationship between justice and compliance. This research will contribute to the tax literature with widened scope on justice in Malaysia.

  16. Quantification of sequence exchange events between PMS2 and PMS2CL provides a basis for improved mutation scanning of Lynch syndrome patients.

    NARCIS (Netherlands)

    Klift, H.M. van der; Tops, C.M.; Bik, E.C.; Boogaard, M.W.; Borgstein, A.M.; Hansson, K.B.; Ausems, M.G.E.M.; Gomez Garcia, E.; Green, A.; Hes, F.J.; Izatt, L.; Hest, L.P. van; Alonso, A.M.; Vriends, A.H.; Wagner, A.; Zelst-Stams, W.A.G. van; Vasen, H.F.; Morreau, H.; Devilee, P.; Wijnen, J.T.

    2010-01-01

    Heterozygous mutations in PMS2 are involved in Lynch syndrome, whereas biallelic mutations are found in Constitutional mismatch repair-deficiency syndrome patients. Mutation detection is complicated by the occurrence of sequence exchange events between the duplicated regions of PMS2 and PMS2CL. We

  17. 28 CFR 0.93 - Bureau of Justice Statistics.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Bureau of Justice Statistics. 0.93...-Office of Justice Programs and Related Agencies § 0.93 Bureau of Justice Statistics. The Bureau of Justice Statistics is headed by a Director appointed by the President. Under the general authority of the...

  18. Globalization and Social Justice in OECD Countries

    OpenAIRE

    Björn Kauder; Niklas Potrafke

    2015-01-01

    Social justice is a topic of importance to social scientists and also political decision makers. We examine the relationship between globalization and social justice as measured by a new indicator for 31 OECD countries. The results show that countries that experienced rapid globalization enjoy social justice. When the KOF index of globalization increases by one standard deviation, the social justice indicator increases by about 0.4 points (on a scale from 1 to 10). The policy implication is t...

  19. Social Justice for Crossover Youth: The Intersection of the Child Welfare and Juvenile Justice Systems.

    Science.gov (United States)

    Kolivoski, Karen M; Goodkind, Sara; Shook, Jeffrey J

    2017-10-01

    Social workers are critical to promoting racial and social justice. "Crossover youth," a term used to describe youths who have contact with both the child welfare and juvenile justice systems, are an especially vulnerable but often overlooked population with whom social workers engage. A disproportionate number of crossover youth are African American. Empirical research on crossover youth is growing, but such scholarship rarely engages with a human rights and social justice perspective. African American children and youths have a distinct place within the history and current context of the child welfare and juvenile justice systems. These systems have historically excluded them or treated them differently; now, African American youths are overrepresented in each of them, and evidence suggests they are more likely to cross over. The purpose of this article is to describe the historical and current context of crossover youth, with a particular focus on African American youths, to provide the foundation for a discussion of what social workers can do to promote racial and social justice for crossover youth, including specific implications for practice and policy, as well as broader implications for human and civil rights. © 2017 National Association of Social Workers.

  20. 75 FR 9613 - Draft NIJ Restraints Standard for Criminal Justice

    Science.gov (United States)

    2010-03-03

    ... DEPARTMENT OF JUSTICE Office of Justice Programs [OJP (NIJ) Docket No. 1512] Draft NIJ Restraints Standard for Criminal Justice AGENCY: National Institute of Justice, Office of Justice Programs, DOJ. ACTION: Notice of Draft NIJ Restraints Standard for Criminal Justice and Certification Program...

  1. 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.

  2. Looking to Hume for justice: on the utility of Hume's view of justice for American health care reform.

    Science.gov (United States)

    Churchill, L R

    1999-08-01

    This essay argues that Hume's theory of justice can be useful in framing a more persuasive case for universal access in health care. Theories of justice derived from a Rawlsian social contract tradition tend to make the conditions for deliberation on justice remote from the lives of most persons, while religiously-inspired views require superhuman levels of benevolence. By contrast, Hume's theory derives justice from the prudent reflections of socially-encumbered selves. This provides a more accessible moral theory and a more realistic path to the establishment of universal access.

  3. Commentary: School Psychologists as Advocates for Racial Justice and Social Justice: Some Proposed Steps

    Science.gov (United States)

    Shriberg, David

    2016-01-01

    In this commentary, Shriberg acknowledges that social justice and racial justice are critical frameworks from which to view school psychology. Individually and collectively, the works in this special issue of "School Psychology Forum" have added a tremendous service to the field. In addition to advancing research, the articles challenge…

  4. Common Frame of Reference and social justice

    NARCIS (Netherlands)

    Hesselink, M.W.; Satyanarayana, R.

    2009-01-01

    The article "Common Frame of Reference and Social Justice" by Martijn W. Hesselink evaluates the Draft Common Frame of Reference (DCFR) of social justice. It discusses the important areas, namely a common frame of Reference in a broad sense, social justice and contract law, private law and

  5. Restorative Justice at Work: Examining the Impact of Restorative Justice Resolutions on Juvenile Recidivism

    Science.gov (United States)

    Rodriguez, Nancy

    2007-01-01

    Programs with restorative justice ideals attempt to incorporate victims and community members into the administration of justice. Although these programs have become increasingly popular, only a few programs in the United States have been the focus of prior studies. Using official juvenile court data from an urban, metropolitan area, this study…

  6. Climate Justice and the Paris Agreement

    International Nuclear Information System (INIS)

    Michelot, Agnes

    2016-01-01

    The concept of climate justice has been, for the first time, used in an international agreement - namely, the Paris Agreement. But this recognition of the notion of climate justice is extremely restricted by the very way it is formulated. Preamble of the Paris Agreement 'notes' that climate justice is recognized by 'certain cultures'. Does it mean that particular and concrete stakes of climate justice of the pre-COP21 agenda have been recognized or, on the contrary, that the notion so introduced is actually an empty shell without any genuine legal perspective? Considering this uncertainty, it appears relevant to analyze the Paris Agreement through the claims of various groups and coalitions, which influenced the COP21 negotiations

  7. Restorative justice: a changing community response

    Directory of Open Access Journals (Sweden)

    Thomas G Ryan

    2015-03-01

    Full Text Available Our purpose herein is to demonstrate how restorative justice continues to unfold globally and we explain how the use of a restorative justice ideology and intervention leads to a common alternative, not only in criminal justice institutions, but also within social agencies, such as elementary schools, and the related social support systems. We draw attention to this emerging trend via current research and resources that enable us to put forward a definition, theoretical background and list the characteristic traits of this alternative mode of life consequence. Finally, we argue that the use of restorative justice in schools is a focus that is really a paradigm shift within the landscape of the educational enterprise.

  8. 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

  9. 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.; van Duijnhoven, F.J.B.; Nagengast, F.M.; Botma, A.; Heine-Broring, 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

  10. 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.

  11. The Criminal justice system in Northern Ireland

    OpenAIRE

    Carr, Nicola

    2017-01-01

    As with any country, crime and justice and the contours of criminal justice have to be situated within the particular historical, social, and political context. Nowhere is this truer than in Northern Ireland, where the criminal justice system that has emerged has been shaped by a violent political conflict which spanned over three decades (from the late 1960s to the late 1990s). In the transition to peace, the reform of criminal justice agencies has been central—to a wider project of state le...

  12. Organizational Justice as an Antecedent of Job Performance

    Directory of Open Access Journals (Sweden)

    Aizzat Mohd. Nasurdin

    2013-06-01

    Full Text Available The present research examines the influence of organizational justice (distributive justice and procedural justice on predicting job performance (task performance and contextual performance. Survey data were drawn from a sample of 136 customer-contact employees within the telecommunications industry in Malaysia. Results of the regression analysis illustrate that distributive justice alone has a significant and positive relationship with task performance. On the other hand, only procedural justice is found to be significantly and positively related to contextual performance. Implications of the findings and directions for future research are highlighted.

  13. Restorative justice innovations in Canada.

    Science.gov (United States)

    Wilson, Robin J; Huculak, Bria; McWhinnie, Andrew

    2002-01-01

    As many jurisdictions move towards more retributive measures as a means to address public discontent with crime, a parallel movement has developed in regard to restorative justice. This article presents three restorative initiatives currently in use in Canada. Each initiative addresses offender behavior and community engagement at a different point in the justice continuum. The use of Sentencing Circles is an example of how restorative justice principles can be instituted at the front end, prior to an offender becoming lodged in the system. The Restorative Justice Options to Parole Suspension project demonstrates how community engagement can assist in preventing offenders from being returned to the system once they have achieved conditional release. The Circles of Support and Accountability project has enlisted the support of professionally supported volunteers in the community reintegration of high-risk sexual offenders. These initiatives are presented within a framework of effective correctional interventions and increased empowerment for a variety of stakeholders. Copyright 2002 John Wiley & Sons, Ltd.

  14. Leadership Education and Development for Justice Using the Canonical Framework of John Rawls's, "A Theory of Justice"

    Science.gov (United States)

    Kliewer, Brandon; Zacharakis, Jeff

    2015-01-01

    Higher education that presupposes a specific conception of justice does well in preparing students to make claims of justice from specific perspectives or positions. However, civic leadership students with a strong background in specific conceptions of justice are often not equipped with necessary skills, dispositions, and habits to exercise…

  15. Incidence of and survival after subsequent cancers in carriers of pathogenic MMR variants with previous cancer : a report from the prospective Lynch syndrome database

    NARCIS (Netherlands)

    Møller, Pål; Seppälä, Toni; Bernstein, Inge; Holinski-Feder, Elke; Sala, Paola; Evans, D Gareth; Lindblom, Annika; Macrae, Finlay; Blanco, Ignacio; Sijmons, Rolf; Jeffries, Jacqueline; Vasen, Hans; Burn, John; Nakken, Sigve; Hovig, Eivind; Rødland, Einar Andreas; Tharmaratnam, Kukatharmini; de Vos Tot Nederveen Cappel, Wouter H; Hill, James; Wijnen, Juul; Jenkins, Mark; Green, Kate; Lalloo, Fiona; Sunde, Lone; Mints, Miriam; Bertario, Lucio; Pineda, Marta; Navarro, Matilde; Morak, Monika; Renkonen-Sinisalo, Laura; Frayling, Ian M; Plazzer, John-Paul; Pylvanainen, Kirsi; Genuardi, Maurizio; Mecklin, Jukka-Pekka; Möslein, Gabriela; Sampson, Julian R; Capella, Gabriel

    2016-01-01

    Objective Today most patients with Lynch syndrome (LS) survive their first cancer. There is limited information on the incidences and outcome of subsequent cancers. The present study addresses three questions: (i) what is the cumulative incidence of a subsequent cancer; (ii) in which organs do

  16. Educational Justice and Big Data

    Science.gov (United States)

    Ben Shahar, Tammy Harel

    2017-01-01

    This article examines the effects of incorporating information and communication technologies in schools in terms of distributive justice. To do so, four issues that are central to educational justice are discussed: scarcity of resources, the positional nature of education, peer effects, and biases in educational decision-making. The discussion…

  17. Gender Justice and School Education

    Science.gov (United States)

    Gao, Desheng

    2009-01-01

    Gender justice includes three basic dimensions: gender equality, respect for difference, and free choice. In reality, schools construct and reproduce the gender injustice of the social culture through multiple dimensions that include the visible and the invisible curriculum, and the teacher's behaviour. In terms of gender justice, the social…

  18. Educational Administration and Social Justice

    Science.gov (United States)

    Bates, Richard

    2006-01-01

    After observing that texts in educational administration have largely failed to address the problem of the justice and fairness of social and educational arrangements, this article goes on to examine the necessary relationships between ethical leadership, community and the notion of social justice. Such relationships are argued to be necessarily…

  19. The Administration of Justice in al-Andalus and the Principles of Justice in Constitutional Democracies

    DEFF Research Database (Denmark)

    Abat Ninet, Antoni

    2018-01-01

    exanimating some of the distinctive elements of the Andalusian administration of justice and the role that specialized judges developed. The paper then exposes the meaning and scope of modern principles of justice, as prescribed by Article 10 of the Universal Declaration of Human Rights and in Article 14...

  20. “Judge-Only” Justice V. Collaborators: Introduction

    Directory of Open Access Journals (Sweden)

    Maria Cristina Reale

    2011-12-01

    Full Text Available Who and how many are the collaborators of judges? The answer may differ according to the perspective under which Justice is considered. In this introduction, and in the light of the papers submitted in the first session of the workshop, a distinction is proposed between “direct” and “indirect” collaborators of judges, according to the side of Justice observed. If Justice is confined simply to the classical function performed by courts, i.e. deciding cases according to the law, it seems quite obvious to remark that judges never act alone, since they normally benefit from the help of different kinds of assistants who, at different levels, help them in their daily work. But when paying attention to the facet of Justice concerning the concrete enforcement of decision, it becomes inevitable to take into account different categories of subjects involved in the “administration” of justice. Under this second perspective, justice is a matter for everyone: not only judges and prosecutors, but other professionals and bodies, including also Governments and other public institutions, since their decisions concerning, for example, human and material resources assigned to the judicial system have inevitably an impact on Justice considered as a public service. Lastly, the aptitude of the public opinion cannot be ignored: the degree of public satisfaction with the judicial system may influence the demand of justice as well as its material functioning. Accordingly, even common citizens could be seen as a very peculiar sort of “collaborators” of judges.

  1. Incorporating environmental justice into environmental decision making

    Energy Technology Data Exchange (ETDEWEB)

    Wolfe, A.K.; Vogt, D.P.; Hwang, Ho-Ling [Oak Ridge National Lab., TN (United States)] [and others

    1995-07-01

    Executive Order 12898, signed on February 11, 1994, broadly states that federal activities, programs, and policies should not produce disproportionately high and adverse impacts on minority and low-income populations. Moreover, the Order indicates that these populations should not be denied the benefits of, or excluded from participation in, these activities, programs, and policies. Because a presidential memorandum accompanying the order said that National Environmental Policy Act (NEPA) documents should begin to address environmental justice immediately, much attention has been paid to assessment-related issues. Also important, a topic that appears to have received relatively little attention, is how decision makers should be expected to use information about environmental justice in their decision making. This paper discusses issues surrounding the use of environmental justice information in the decision-making process by focusing on the following five main topics: (1) the importance, or weight, attached to environmental justice within larger decision-making contexts; (2) the potential tension between localized environmental justice issues and regional or national issues and needs; (3) the use of environmental justice information to develop (perhaps in concert with affected minority and low-income communities) appropriate mitigation strategies, or to establish conditions under which activities, programs, and policies may be accepted locally; (4) the general implications of shifting the distribution of broadly defined risks, costs, and benefits among different population groups; and (5) the implications of implementing environmental justice on an individual, ad hoc basis rather than within a larger environmental justice framework. This paper raises the issues and discusses the implications of alternative approaches to them.

  2. Environmental justice and healthy communities

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-12-01

    The environmental justice movement has come a long way since its birth a decade ago in rural and mostly African American Warren County, North Carolina. The selection of Warren County for a PCB landfill, they brought national attention to waste facility siting inequities and galvanized African American church and civil rights leaders` support for environmental justice. The demonstrations also put {open_quotes}environmental racism{close_quotes} on the map and challenged the myth that African Americans are not concerned about or involved in environmental issues. Grassroots groups, after decades of struggle, have grown to become the core of the multi-issue, multiracial, and multi-regional environmental justice movement. Diverse community-based groups have begun to organize and link their struggles to issues of civil and human rights, land rights and sovereignty, cultural survival , racial and social justice, and sustainable development. The impetus for getting environmental justice on the nations`s agenda has come from an alliance of grassroots activists, civil rights leaders, and a few academicians who questioned the foundation of the current environmental protection paradigm--where communities of color receive unequal protection. Whether urban ghettos and barrios, rural {open_quotes}poverty pockets,{close_quotes} Native American reservations, or communities in the Third World, grassroots groups are demanding an end to unjust and nonsustainable environmental and development policies.

  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. Privileged Pursuits of Social Justice: Exploring Privileged College Students' Motivation for Engaging in Social Justice

    Science.gov (United States)

    Howard, Adam

    2011-01-01

    The author of this article explores the motivation factors that lead privileged college students to be involved in social justice efforts. The students participating in this study identified multiple reasons for their initial and continued involvement in social justice work, but all students identified three main sources of motivation: responding…

  5. Mãori Customary Law: A Relational Approach to Justice

    Directory of Open Access Journals (Sweden)

    Stephanie Vieille

    2012-03-01

    Full Text Available This research paper examines the philosophy of justice embodied in tikanga Mãori, the Mãori traditional mechanism and approach to doing justice. Based on several months of fieldwork in New Zealand, this study contends that the Mãori approach to justice adopts a holistic and relational lens, which requires that justice be seen in the context of relationships and crimes dealt with in terms of the relationships they have affected. As a result, justice must be carried out within the community and the process owned by community members. Further discussion draws attention to the response of Mãori communities to the New Zealand government’s attempt to accommodate their traditions and warns against the global tendency to render traditional Indigenous approaches to justice ahistorical through their representation as restorative justice mechanisms.

  6. 44 CFR 11.17 - Referral to Department of Justice.

    Science.gov (United States)

    2010-10-01

    ... Justice. 11.17 Section 11.17 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY... Referral to Department of Justice. When Department of Justice approval or consultation is required under § 11.16, the referral or request shall be transmitted to the Department of Justice by the Chief Counsel...

  7. 28 CFR 0.85a - Criminal justice policy coordination.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Criminal justice policy coordination. 0.85a Section 0.85a Judicial Administration DEPARTMENT OF JUSTICE ORGANIZATION OF THE DEPARTMENT OF JUSTICE Federal Bureau of Investigation § 0.85a Criminal justice policy coordination. The Federal Bureau...

  8. Whole Gene Capture Analysis of 15 CRC Susceptibility Genes in Suspected Lynch Syndrome Patients.

    Science.gov (United States)

    Jansen, Anne M L; Geilenkirchen, Marije A; van Wezel, Tom; Jagmohan-Changur, Shantie C; Ruano, Dina; van der Klift, Heleen M; van den Akker, Brendy E W M; Laros, Jeroen F J; van Galen, Michiel; Wagner, Anja; Letteboer, Tom G W; Gómez-García, Encarna B; Tops, Carli M J; Vasen, Hans F; Devilee, Peter; Hes, Frederik J; Morreau, Hans; Wijnen, Juul T

    2016-01-01

    Lynch Syndrome (LS) is caused by pathogenic germline variants in one of the mismatch repair (MMR) genes. However, up to 60% of MMR-deficient colorectal cancer cases are categorized as suspected Lynch Syndrome (sLS) because no pathogenic MMR germline variant can be identified, which leads to difficulties in clinical management. We therefore analyzed the genomic regions of 15 CRC susceptibility genes in leukocyte DNA of 34 unrelated sLS patients and 11 patients with MLH1 hypermethylated tumors with a clear family history. Using targeted next-generation sequencing, we analyzed the entire non-repetitive genomic sequence, including intronic and regulatory sequences, of 15 CRC susceptibility genes. In addition, tumor DNA from 28 sLS patients was analyzed for somatic MMR variants. Of 1979 germline variants found in the leukocyte DNA of 34 sLS patients, one was a pathogenic variant (MLH1 c.1667+1delG). Leukocyte DNA of 11 patients with MLH1 hypermethylated tumors was negative for pathogenic germline variants in the tested CRC susceptibility genes and for germline MLH1 hypermethylation. Somatic DNA analysis of 28 sLS tumors identified eight (29%) cases with two pathogenic somatic variants, one with a VUS predicted to pathogenic and LOH, and nine cases (32%) with one pathogenic somatic variant (n = 8) or one VUS predicted to be pathogenic (n = 1). This is the first study in sLS patients to include the entire genomic sequence of CRC susceptibility genes. An underlying somatic or germline MMR gene defect was identified in ten of 34 sLS patients (29%). In the remaining sLS patients, the underlying genetic defect explaining the MMRdeficiency in their tumors might be found outside the genomic regions harboring the MMR and other known CRC susceptibility genes.

  9. Experiential Social Justice Judgment Processes

    NARCIS (Netherlands)

    Maas, M.

    2008-01-01

    Social justice can be thought of as an idea that exists within the minds of individuals and that concerns issues like what is right and wrong, what ought to be or not to be, and what is fair or unfair. This subjective quality of the justice judgment process makes it rather unpredictable how people

  10. 5 CFR 177.108 - Referral to Department of Justice.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Referral to Department of Justice. 177... ADMINISTRATIVE CLAIMS UNDER THE FEDERAL TORT CLAIMS ACT § 177.108 Referral to Department of Justice. When Department of Justice approval or consultation is required, or the advice of the Department of Justice is...

  11. 40 CFR 1620.8 - Referral to Department of Justice.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 32 2010-07-01 2010-07-01 false Referral to Department of Justice... ADMINISTRATIVE CLAIMS ARISING UNDER THE FEDERAL TORT CLAIMS ACT § 1620.8 Referral to Department of Justice. When Department of Justice approval or consultation is required, or the advice of the Department of Justice is...

  12. Social welfare and restorative justice

    OpenAIRE

    Fox, Darrell

    2009-01-01

    "This paper explores the links and connections between social work and restorative justice. After a brief description of social work, restorative justice and family group conferencing, I will explore some the complementary theoretical links and practice applications, critically examining the potential implications and opportunities for social work practitioners and academics in relation to practice." [author's abstract

  13. The design of a medical school social justice curriculum.

    Science.gov (United States)

    Coria, Alexandra; McKelvey, T Greg; Charlton, Paul; Woodworth, Michael; Lahey, Timothy

    2013-10-01

    The acquisition of skills to recognize and redress adverse social determinants of disease is an important component of undergraduate medical education. In this article, the authors justify and define "social justice curriculum" and then describe the medical school social justice curriculum designed by the multidisciplinary Social Justice Vertical Integration Group (SJVIG) at the Geisel School of Medicine at Dartmouth. The SJVIG addressed five goals: (1) to define core competencies in social justice education, (2) to identify key topics that a social justice curriculum should cover, (3) to assess social justice curricula at other institutions, (4) to catalog institutionally affiliated community outreach sites at which teaching could be paired with hands-on service work, and (5) to provide examples of the integration of social justice teaching into the core (i.e., basic science) curriculum. The SJVIG felt a social justice curriculum should cover the scope of health disparities, reasons to address health disparities, and means of addressing these disparities. The group recommended competency-based student evaluations and advocated assessing the impact of medical students' social justice work on communities. The group identified the use of class discussion of physicians' obligation to participate in social justice work as an educational tool, and they emphasized the importance of a mandatory, longitudinal, immersive, mentored community outreach practicum. Faculty and administrators are implementing these changes as part of an overall curriculum redesign (2012-2015). A well-designed medical school social justice curriculum should improve student recognition and rectification of adverse social determinants of disease.

  14. Psychometric properties of a four-component Norwegian Organizational Justice Scale.

    Science.gov (United States)

    Olsen, Olav Kjellevold; Myrseth, Helga; Eidhamar, Are; Hystad, Sigurd W

    2012-04-01

    Organizational justice has attracted attention as a predictor of employees' mental and physical health as well as commitment and work outcomes. The lack of a Norwegian translation of an organizational justice scale has precluded its use in Norway. Four dimensions of the organizational justice construct were examined in a Norwegian military context, including facet measures of distributional, interpersonal, and informational justice developed by Colquitt in 2001, in addition to procedural justice developed by Moorman in 1991. Confirmatory factor analyses supported a four-dimensional structure with good internal consistency. Follow-up analyses have suggested that the four dimensions were nested beneath a general, latent organizational justice factor. A positive relationship between organizational justice and self-sacrificial behavior was found, indicating satisfactory construct validity. The results demonstrate that the Norwegian Organizational Justice Scale is a reliable and construct-valid measure of organizational justice in a Norwegian setting.

  15. 24 CFR 17.9 - Referral to Department of Justice.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Referral to Department of Justice... Procedures § 17.9 Referral to Department of Justice. When Department of Justice approval or consultation is required under § 17.8, the referral or request shall be transmitted to the Department of Justice by the...

  16. Shame and Guilt in Restorative Justice

    DEFF Research Database (Denmark)

    Rodogno, Raffaele

    2008-01-01

    In this article, I examine the relevance and desirability of shame and guilt to restorative justice conferences. I argue that a careful study of the psychology of shame and guilt reveals that both emotions possess traits that can be desirable and traits that can be undesirable for restoration. More...... in particular, having presented the aims of restorative justice, the importance of face-to-face conferences in reaching these aims, the emotional dynamics that take place within such conferences, and the relevant parts of the empirical psychology of shame and guilt, I argue that restorative justice...

  17. The Ethics of Teaching for Social Justice: A Framework for Exploring the Intellectual and Moral Virtues of Social Justice Educators

    Science.gov (United States)

    Taylor, Rebecca M.

    2015-01-01

    Pursuing social justice in education raises ethical questions about teaching practice that have not been fully addressed in the social justice literature. Hytten (2015) initiated a valuable way forward in developing an ethics of social justice educators, drawing on virtue ethics. In this paper, I provide additional support to this effort by…

  18. 10 CFR 1014.7 - Referral to Department of Justice.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Referral to Department of Justice. 1014.7 Section 1014.7... § 1014.7 Referral to Department of Justice. (a) When Department of Justice approval or consultation is required under § 1014.6, the referral or request shall be transmitted to the Department of Justice by the...

  19. 34 CFR 21.1 - Equal Access to Justice Act.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Equal Access to Justice Act. 21.1 Section 21.1 Education Office of the Secretary, Department of Education EQUAL ACCESS TO JUSTICE General § 21.1 Equal Access to Justice Act. (a) The Equal Access to Justice Act (the Act) provides for the award of fees and...

  20. Restorative Justice: New Horizons in Juvenile Offender Counseling

    Science.gov (United States)

    Ryals, John S. Jr.

    2004-01-01

    Treatment strategies of the juvenile justice system focus singularly on rehabilitation of offenders, and victims and communities are excluded from the rehabilitative process. Restorative justice views victims and communities as essential components in rehabilitative efforts. In this article, the principles and practices of restorative justice,…

  1. Från outsiderfilmmakare till etablerad indieregissör : David Lynch, Jim Jarmusch och Steven Soderbergh

    OpenAIRE

    Simberg, Maximilian

    2014-01-01

    Det här arbetet behandlar kreativ frihet och konstnärligt oberoende i filmskapande, utgående från begreppet independent film och regissörerna David Lynch, Jim Jarmusch och Steven Soderbergh. Den centrala frågeställningen är hur det har varit möjligt för en filmkonstnär att uppnå konstnärligt oberoende och samtidigt ha en långlivad och framgångsrik karriär. Arbetets fokus ligger på de tre regissörernas genombrottsfilmer; Eraserhead, Stranger Than Paradise och sex, lies, and videotape, och förs...

  2. Screening of the DNA mismatch repair genes MLH1, MSH2 and MSH6 in a Greek cohort of Lynch syndrome suspected families

    International Nuclear Information System (INIS)

    Thodi, Georgia; Fountzilas, George; Yannoukakos, Drakoulis; Fostira, Florentia; Sandaltzopoulos, Raphael; Nasioulas, George; Grivas, Anastasios; Boukovinas, Ioannis; Mylonaki, Maria; Panopoulos, Christos; Magic, Mirjana Brankovic

    2010-01-01

    Germline mutations in the DNA mismatch repair genes predispose to Lynch syndrome, thus conferring a high relative risk of colorectal and endometrial cancer. The MLH1, MSH2 and MSH6 mutational spectrum reported so far involves minor alterations scattered throughout their coding regions as well as large genomic rearrangements. Therefore, a combination of complete sequencing and a specialized technique for the detection of genomic rearrangements should be conducted during a proper DNA-testing procedure. Our main goal was to successfully identify Lynch syndrome families and determine the spectrum of MLH1, MSH2 and MSH6 mutations in Greek Lynch families in order to develop an efficient screening protocol for the Greek colorectal cancer patients' cohort. Forty-two samples from twenty-four families, out of which twenty two of Greek, one of Cypriot and one of Serbian origin, were screened for the presence of germline mutations in the major mismatch repair genes through direct sequencing and MLPA. Families were selected upon Amsterdam criteria or revised Bethesda guidelines. Ten deleterious alterations were detected in twelve out of the twenty-four families subjected to genetic testing, thus our detection rate is 50%. Four of the pathogenic point mutations, namely two nonsense, one missense and one splice site change, are novel, whereas the detected genomic deletion encompassing exon 6 of the MLH1 gene has been described repeatedly in the LOVD database. The average age of onset for the development of both colorectal and endometrial cancer among mutation positive families is 43.2 years. The mutational spectrum of the MMR genes investigated as it has been shaped by our analysis is quite heterogeneous without any strong indication for the presence of a founder effect

  3. Social Justice, Research, and Adolescence.

    Science.gov (United States)

    Russell, Stephen T

    2016-03-01

    In what ways might research on adolescence contribute to social justice? My 2014 Presidential Address identified strategies for social justice in our field. First, we need research that is conscious of biases, power, and privilege in science, as well as in our roles as scholars. Second, we need research that attends to inequities in lives of adolescents, and as scholars we need to question the ways that our research may unwittingly reinforce those inequalities. Third, we need research that attends to urgencies, that is, issues or conditions that influence adolescents' well-being which demand attention and action. I draw from a range of concepts and theoretical perspectives to make the case for a framework of social justice in research on adolescence.

  4. Organizational Justice and Employee Satisfaction in Performance Appraisal

    Science.gov (United States)

    Palaiologos, Anastasios; Papazekos, Panagiotis; Panayotopoulou, Leda

    2011-01-01

    Purpose: This paper aims to explore the performance appraisal (PA) aspects that are connected with organizational justice, and more specifically three kinds of justice, namely distributive, procedural and interactional justice. Design/methodology/approach: The research is based on a sample of 170 respondents who answered a questionnaire giving…

  5. The Productivity of Criminology and Criminal Justice Faculty.

    Science.gov (United States)

    DeZee, Matthew R.

    The scholarly productivity of criminology and criminal justice faculty and programs was investigated. The methodologies that were used to rate journals that publish articles in the criminology/criminal justice field and to select 71 schools with graduate programs in criminology or criminal justice are described. Primary interest focused on…

  6. 76 FR 62434 - HUD Draft Environmental Justice Strategy

    Science.gov (United States)

    2011-10-07

    ... Justice Strategy AGENCY: Office of the Sustainable Housing and Communities, HUD. ACTION: Notice. SUMMARY: Through this notice, HUD announces the release of its draft Environmental Justice Strategy for review and... federal agency, with the law as its guide, should make environmental justice part of its mission. In this...

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

    Directory of Open Access Journals (Sweden)

    Lynch Henry T

    2003-12-01

    Full Text Available Abstract 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.

  8. From conditions of equality to demands of justice

    DEFF Research Database (Denmark)

    Hartz, Emily; Nielsen, Carsten Fogh

    2015-01-01

    Equal freedom is the common starting point for most contractual theories of justice from Hobbes and Rousseau to Rawls. But while equal freedom defines a common starting point for these theories, this does not result in a general consensus on the conception of justice. On the contrary, different...... ways of conceptualizing the contractual starting point leads to different conceptions of the demands of justice. To fully understand the relationship between equal freedom and justice we therefore first need to explicate how and why the initial condition of equality is transformed into demands...... of justice. In this paper we discuss how this transformation takes place in the theories of Hobbes, Rousseau and Rawls, with particular emphasis on the vexed relationship between motivation and justification....

  9. Water Justice

    NARCIS (Netherlands)

    Boelens, R.A.; Perreault, T.; Vos, J.M.C.

    2018-01-01

    Water justice is becoming an ever-more pressing issue in times of increasing water-based inequalities and discrimination. Megacities, mining, forestry, industry and agribusiness claim an increasingly large share of available surface and groundwater reserves. Water grabbing and pollution generate

  10. Teacher Activism: Enacting a Vision for Social Justice

    Science.gov (United States)

    Picower, Bree

    2012-01-01

    This qualitative study focused on educators who participated in grassroots social justice groups to explore the role teacher activism can play in the struggle for educational justice. Findings show teacher activists made three overarching commitments: to reconcile their vision for justice with the realities of injustice around them; to work within…

  11. In Pursuit of Educational Justice and Liberated Hearts

    Science.gov (United States)

    Mirci, Philip S.

    2008-01-01

    This article contributes to a discussion about educational leadership programs related to social justice and diversity. It focuses on the development of social justice leaders through a doctoral program that culminates in a Doctorate in Educational Justice. The program's design is intended to empower graduates to act with hearts liberated through…

  12. 32 CFR 989.33 - Environmental justice.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 6 2010-07-01 2010-07-01 false Environmental justice. 989.33 Section 989.33 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE ENVIRONMENTAL PROTECTION ENVIRONMENTAL IMPACT ANALYSIS PROCESS (EIAP) § 989.33 Environmental justice. During the preparation of...

  13. Religious Education towards Justice: What Kind of Justice Is to Be Taught in a Christian Context?

    Directory of Open Access Journals (Sweden)

    Monika Bobbert

    2017-02-01

    Full Text Available Education is a human right. It prepares human beings for life, helps to develop individual abilities and opens up social opportunities—e.g., earning one’s own living. Religion interprets our human existence in connection to a transcendental dimension. Religion can also influence moral values and behavior. The Christian religion established a basis for social life, and thus deals with religious and moral justice. As the Christian faith is understood as the identity of the qualities of love of God, of your neighbor and even of your enemy, it has to look for justice in the world. Modern Christian ethics does unfold interpersonal and global justice for all people and tries to give good reasons for moral claims. Religious education in a Christian context has to answer the question of what kind of justice is to be taught and by what means justice, as a goal of education, can be reached within such a setting. This article will unfold, from an ethical point of view, what kind of knowledge and competence teachers must have and what kind of goals can be followed with regard to their pupils or students. The results of this reflection imply certain pedagogical methods and means and exclude others—although it is not possible to go more deeply into a pedagogical discussion.

  14. A novel heterozygous germline deletion in MSH2 gene in a five generation Chinese family with Lynch syndrome

    OpenAIRE

    Wu, Bin; Ji, Wuyang; Liang, Shengran; Ling, Chao; You, Yan; Xu, Lai; Zhong, Min-Er; Xiao, Yi; Qiu, Hui-Zhong; Lu, Jun-Yang; Banerjee, Santasree

    2017-01-01

    Lynch syndrome (LS) is one of the most common familial forms of colorectal cancer predisposing syndrome with an autosomal dominant mode of inheritance. LS is caused by the germline mutations in DNA mismatch repair (MMR) genes including MSH2, MLH1, MSH6 and PMS2. Clinically, LS is characterized by high incidence of early-onset colorectal cancer as well as endometrial, small intestinal and urinary tract cancers, usually occur in the third to fourth decade of the life. Here we describe a five ge...

  15. Organizational justice and health: Contextual determinants and psychobiological consequences

    NARCIS (Netherlands)

    Herr, R.M.

    2015-01-01

    The research presented in this thesis entitled "Organizational Justice and Health: Contextual Determinants and Psychobiological Consequences" aimed to investigate associations between organizational justice and employee health and biological functioning. Organizational justice is an occupational

  16. Informal Justice Systems: Charting a Course for Human Rights-Based Engagement

    DEFF Research Database (Denmark)

    Kerrigan, Fergus; McKay, Anne Louise; Kristiansen, Annali

    engagement with informal justice systems can build greater respect and protection for human rights. It highlights the considerations that development partners should have when assessing whether to implement programmes involving informal justice systems, the primary consideration being that engagement......Providing accessible justice is a state obligation under international human rights standards, but this obligation does not require that all justice be provided through formal justice systems. If done in ways to respect and uphold human rights, the provision of justice through informal justice...... systems is not against human rights standards and can be a mechanism to enhance the fulfilment of human rights obligations by delivering accessible justice to individuals and communities where the formal justice system does not have the capacity or geographical reach. This study seeks to identify how...

  17. Editors' Introduction: Justice, Rights, Literature

    Directory of Open Access Journals (Sweden)

    Joxerramon Bengoetxea

    2014-12-01

    Full Text Available The articles gathered in this issue are the result of papers presented at the workshop held at the Oñati International Institute for the Sociology of Law on 20-21 May 2013 on Perspectives of Justice in Literature: Perspectives from Justice and Fundamental Rights in Literature: an Approach from Legal Culture in a European context. Literature and literary fiction can act as a thread that helps different disciplines to communicate with each other and can thus help go beyond the strictly legal field opening up to questions of justice and rights. These papers deal with issues of justice - mainly Fundamental Rights, but also procedural aspects of justice and its administration, philosophical perspectives of justice - and of legal culture - local, European, Universal - as reflected through and by literature. Los artículos que conforman este número son el resultado de las ponencias presentadas en el workshop celebrado en el Instituto Internacional de Sociología Jurídica de Oñati el 20 y 21 mayo de 2013 sobre las perspectivas de la justicia en la literatura: Perspectivas desde la Justicia y los Derechos Fundamentales en la Literatura: un Enfoque de Cultura Jurídica en el Contexto Europeo. La literatura y la ficción literaria pueden ser un hilo que favorece que diferentes disciplinas se comuniquen entre sí y pueden de esta forma ayudar a ir más allá del campo jurídico estricto, planteando cuestiones sobre justicia y derechos. Estos artículos tratan sobre aspectos de la justicia (principalmente derechos fundamentales, pero también sobre procedimiento judicial y administración de la justicia, perspectivas filosóficas de la justicia y de cultura jurídica (local, europea, universal, de la forma en la que se han reflejado en la literatura.DOWNLOAD THIS PAPER FROM SSRN: http://ssrn.com/abstract=2543450

  18. Restorative Justice: Principles, Practices, and Application

    Science.gov (United States)

    O'Brien, Sandra Pavelka

    2007-01-01

    A modern-day movement is transforming the way that communities and justice systems think about and respond to crime and wrongful occurrences. This response implements a holistic continuum of services, providing for prevention, intervention, diversion, commitment, probation, reentry, and aftercare. This approach--known as restorative justice--seeks…

  19. Restorative Justice as Strength-Based Accountability

    Science.gov (United States)

    Ball, Robert

    2003-01-01

    This article compares strength-based and restorative justice philosophies for young people and their families. Restorative justice provides ways to respond to crime and harm that establish accountability while seeking to reconcile members of a community. Restorative approaches are an important subset of strength-based interventions.

  20. Values and religiosity as predictors of engagement in social justice.

    Science.gov (United States)

    Torres-Harding, Susan R; Carollo, Olivia; Schamberger, Antú; Clifton-Soderstrom, Karl

    2013-01-01

    Some researchers have suggested that values, including religious values and motivations, might facilitate social justice work. Individuals might view social justice work as an expression of religious beliefs, values, and practices, or as an expression of their personal morals and values. The current study examined the role of religious variables and secular values to predict attitudes, intentions to engage in social justice, perceived norms around social justice, and perceived ability to engage in social justice within a culturally and religiously diverse student population. Implications of the study results for social justice education are presented and discussed.

  1. JUSTICE DRIVERS: THE SOCIO-COMMUNICATIVE FUNCTIONS OF YORUBA INDIGENOUS KNOWLEDGE

    Directory of Open Access Journals (Sweden)

    Ezekiel Bolaji

    2017-01-01

    Full Text Available Justice is a widely attested sacrosanct lifeblood of every human society which requires fair-play and impartial judgment and is often represented by a woman holding a balanced pair of scales in one hand and bearing a sword in the other, symbolising carefully weighed evidence and protection of the innocent, as well as punishment for the guilty; at times, justice is blindfolded, indicating impartiality. Though universal, justice is driven differently in different societies, as it is a derivative of the culture and tradition of the people with, often, a blend of some foreign touch, establishing its universality – universal justice – a source of which is expected to be divine or supreme, attesting to a human inborn tendency. If justice is divine, then the source of true justice transcends humans, which translates into the fact that all human societies draw principles from this higher source and apply the principles so drawn in line with the peculiarities of their culture and tradition. Hence, the extent to which justice is manifest or practiced in any society is contingent on how close or far away the society is to applying the divine justice. Since no human society has been able to abide by these principles perfectly, humans can attain no perfect justice. A discussion of perfect justice, as exemplified by a particular society and thus expected to be imitated by another, is beyond the scope of this paper. This paper investigates what drives justice and how justice is driven among the Yoruba. This paper argues that the Yoruba exploit the socio-communicative value of taboos, proverbs and àrokò to sustain justice in the society. The paper presents the issue through the frame of the principle of shared knowledge and socio-cultural competence.

  2. The interface between the Mediation and Restorative Justice

    Directory of Open Access Journals (Sweden)

    Gustavo Rabay Guerra

    2016-06-01

    Full Text Available The present work starts stating the failure of the dominant paradigm of the penal system, retributive model, pointing to the emergence of restorative justice as a new paradigm of criminal justice, from the change in focus about the offender and in the rescue of victim’s role of conflict situations in the criminal orbit. In this sense, from the employment of mediation as restorative practice and identification of theoretical disagreements about the relationship between restorative justice and mediation, this article has the intention to investigate the existing interface between mediation and restorative justice in Brazil. Therefore, we start from the assumption that mediation and restorative justice are institutes with different origins and trajectories that at some moments have common destinations, presenting an intersection relationship when mediation is used in criminal matters as restorative practice. Thus, the research has as main aim to analyze similarities and differences between mediation and restorative justice in the Brazilian practice. From this perspective, we intend to make use of a comparative approach in the analysis of the institutes, to identify their origins and trajectories

  3. Green justice in the city

    DEFF Research Database (Denmark)

    Rutt, Rebecca Leigh; Gulsrud, Natalie Marie

    2016-01-01

    tIn this short communication, we discuss European urban green space (UGS) research from an environ-mental justice perspective. We show that European UGS scholarship primarily focuses on functionalvalues and managerial aspects of UGS, while paying less attention to equity in the enjoyment of andde...... of anddecision-making around UGS. On this basis we discuss potentials for European urban green space researchto take up a more explicit environmental justice framing to shed much-needed light on injustices inEuropean cities and inspire change in policy and practice.......tIn this short communication, we discuss European urban green space (UGS) research from an environ-mental justice perspective. We show that European UGS scholarship primarily focuses on functionalvalues and managerial aspects of UGS, while paying less attention to equity in the enjoyment...

  4. 75 FR 70293 - Meeting of the Federal Advisory Committee on Juvenile Justice

    Science.gov (United States)

    2010-11-17

    ... DEPARTMENT OF JUSTICE Office of Justice Programs [OJP (OJJDP) Docket No. 1532] Meeting of the Federal Advisory Committee on Juvenile Justice AGENCY: Office of Juvenile Justice and Delinquency Prevention, Office of Justice Programs, Justice. ACTION: Notice of Meeting. SUMMARY: The Office of Juvenile...

  5. Reflexivity and social justice

    DEFF Research Database (Denmark)

    Maksimovic, Tijana; Jakobsen, Helle Nordentoft

    2017-01-01

    Career practitioners’ reflexive understanding of their professional role as change agents in career guidance and counselling practices has a major impact on how social justice can be achieved. This entitles an awareness of the way in which guidance and counselling practices are embedded in the co......Career practitioners’ reflexive understanding of their professional role as change agents in career guidance and counselling practices has a major impact on how social justice can be achieved. This entitles an awareness of the way in which guidance and counselling practices are embedded...

  6. (Injustice contexts and work satisfaction: The mediating role of justice perceptions

    Directory of Open Access Journals (Sweden)

    Zhou, Q.

    2012-01-01

    Full Text Available This study explores the impact of the social context, namely (injustice climate and target, in workers' justice perceptions and satisfaction. Individual's justice judgments are expected to mediate the relationship of (injustice climate and target with work satisfaction. We found mediation effects of procedural justice in the relationship between justice climate and satisfaction, and interactional justice in the relationship between injustice target and satisfaction. Distributive justice does not affect the relationship between the (injustice context and satisfaction. Findings demonstrate the relevance of framing organizational justice in a socially contextualized perspective since they seem to influence individual justice reactions and work attitudes. Using an experimental methodology, it was possible to explore the role of seldom studied contextual variables.

  7. Environmental Justice Is a Social Justice Issue: Incorporating Environmental Justice into Social Work Practice Curricula

    Science.gov (United States)

    Beltrán, Ramona; Hacker, Alice; Begun, Stephanie

    2016-01-01

    Social justice education for social work practice is concerned with addressing issues of power and oppression as they impact intersections of identity, experience, and the social environment. However, little focus is directed toward the physical and natural environment despite overwhelming evidence that traditionally marginalized groups bear the…

  8. Social Justice, Disability, and Rehabilitation Education

    Science.gov (United States)

    Kelsey, Daniel; Smart, Julie F.

    2012-01-01

    The academic field and the professional practice of rehabilitation counseling focuses on one aspect of social justice, assisting individuals with disabilities to attain full community inclusion. Nonetheless, social justice focuses on many marginalized groups and in the related fields of counseling and psychology, those with disabilities are rarely…

  9. 76 FR 53965 - Meeting of the Federal Advisory Committee on Juvenile Justice

    Science.gov (United States)

    2011-08-30

    ... DEPARTMENT OF JUSTICE Office of Justice Programs [OJP (OJJDP) Docket No. 1556] Meeting of the Federal Advisory Committee on Juvenile Justice AGENCY: Office of Juvenile Justice and Delinquency Prevention, Office of Justice Programs, U. S. Department of Justice. ACTION: Notice of meeting. SUMMARY: The...

  10. 77 FR 61641 - Meeting of the Federal Advisory Committee on Juvenile Justice

    Science.gov (United States)

    2012-10-10

    ... DEPARTMENT OF JUSTICE Office of Justice Programs [OJP (OJJDP) Docket No. 1608] Meeting of the Federal Advisory Committee on Juvenile Justice AGENCY: Office of Juvenile Justice and Delinquency Prevention, Office of Justice Programs, U.S. Department of Justice. ACTION: Notice of meeting. SUMMARY: The...

  11. 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 J.; Lesueur, Fabienne; Tavtigian, Sean V.; Southey, Melissa C.; Goldgar, David E.

    2014-01-01

    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). Based on this finding, a population-based case-control mutation-screening study was conducted and identified 29 carriers of rare (MAF Lynch syndrome-spectrum cancers (SIR 3.35, 95% CI 1.7-6.0; P=0.005), particularly for relatives diagnosed with cancer under age 60 years (SIR 10.9, 95%CI 4.7-21; P=0.0003). PMID:25050558

  12. Distributive Justice and Free Market Economics: A Eudaimonistic Perspective

    Directory of Open Access Journals (Sweden)

    Michael F. Reber

    2010-11-01

    Full Text Available In today’s society, a peculiar understanding of distributive justice has developed which holds that “social justice must be distributed by the coercive force of government.” However, this is a perversion of the ideal of distributive justice. The perspective of distributive justice which should be considered is one with its roots in the school of thought referred to as self-actualization ethics or eudaimonism, which holds that each person is unique and each should discover whom he or she is—to actualize his or her true potential and to live the “good life” within the congeniality and complementarity of personal excellences of his or her fellow members of community. When a eudaimonistic perspective is considered, a definition of distributive of justice could be “the allocation of goods and utilities via the voluntary ubiquitous human interaction of self-actualizing individuals who not only recognize the human dignity of the self and other and the rights which flow from and guarantee it, but also actively will goods and utilities toward the self and other so as to manifest human dignity.” Therefore, with a eudaimonistic understanding of distributive justice, one can argue that the free market is the ubiquitous interactions of self-actualizing individuals who are giving and receiving goods and utilities for one and another’s own “happiness,” i.e. the free market is the socio-economic mechanism by which distributive justice operates. In this paper I first will overview the philosophical foundations of distributive justice. Next, I will propose a eudaimonistic definition of distributive justice. Finally, I will highlight examples of distributive justice operating in a free market economy.

  13. Social justice and religious participation: a qualitative investigation of Christian perspectives.

    Science.gov (United States)

    Todd, Nathan R; Rufa, Anne K

    2013-06-01

    This investigation examines how self-identified Christians in the Midwest U.S. understand and work for social justice, with a focus on their process of social justice development and the role of religious congregations in promoting social justice. Using a grounded theory analysis of 15 in-depth interviews, results indicated multiple understandings of social justice such as meeting basic needs, fixing social structures and systems to create equal distributions of resources, promoting human rights and dignity, and as a religious responsibility. Participants also described a process of social justice development facilitated by exposure to injustice, mentors, educating others, and the importance of finding a social justice community. Distinct personal barriers to social justice engagement were identified such as resources and negative emotions, whereas congregational leadership was important for congregational involvement. General frustration with congregations was expressed regarding low social justice engagement; however, participants balanced this frustration with hope for the positive potential of congregations to promote social justice. Together these findings show multifaceted understandings of social justice and a dynamic process of social justice development for these self-identified Christians. Implications for future research and partnership with religious individuals and congregations also are discussed.

  14. ADMINISTRATIVE JUSTICE IN FRANCE. BETWEEN SINGULARITY AND CLASSICISM

    Directory of Open Access Journals (Sweden)

    H. Flavier

    2016-01-01

    Full Text Available The administrative justice in France oscillates between classicism and singularity. Multiple factors explain how administrative justice has come to occupy a particular place in French administrative law. Administrative justice has not only settled disputes between administration and private persons, but as well, built the French administrative law. One of the main tasks during 19th and 20th century consisted in strengthen the independence from the executive branch and the efficiency in order to satisfy the idea of good justice. Many reforms have been led since the 1990’s. That is why we propose to depict the French system and evaluate the activity of French administrative justice concerning the judicial organization, its jurisdiction and the remedies before the administrative judge. We will enlighten also our paper with a comparative approach and some statistical elements.

  15. 22 CFR 213.37 - Referrals to the Department of Justice.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Referrals to the Department of Justice. 213.37... Department of Justice § 213.37 Referrals to the Department of Justice. (a) The CFO, through the FMS cross... of Justice's Nationwide Central Intake Facility as required by the Claims Collection Litigation...

  16. The first year of implementation of the Child Justice Act

    African Journals Online (AJOL)

    The Child Justice Act 75 of 2008 mandates the Minister of Justice and Constitutional Development to report annually on the implementation of the Child Justice Act to the Parliamentary Portfolio Committee on Justice and Constitutional Development. On 1 April 2011 a year had passed since the implementation of the Child ...

  17. Extending the multifoci perspective: The role of supervisor justice and moral identity in the relationship between customer justice and customer-directed sabotage.

    Science.gov (United States)

    Skarlicki, Daniel P; van Jaarsveld, Danielle D; Shao, Ruodan; Song, Young Ho; Wang, Mo

    2016-01-01

    The multifoci perspective of justice proposes that individuals tend to target their (in)justice reactions toward the perceived source of the mistreatment. Empirical support for target-specific reactions, however, has been mixed. To explore theoretically relevant reasons for these discrepant results and address unanswered questions in the multifoci justice literature, the present research examines how different justice sources might interactively predict target-specific reactions, and whether these effects occur as a function of moral identity. Results from a sample of North American frontline service employees (N = 314, Study 1) showed that among employees with lower levels of moral identity, low supervisor justice exacerbated the association between low customer justice and customer-directed sabotage, whereas this exacerbation effect was not observed among employees with higher levels of moral identity. This 3-way interaction effect was replicated in a sample of South Korean employees (N = 265, Study 2). (c) 2016 APA, all rights reserved).

  18. 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. ©Allison M Burton-Chase, Wendy M Parker, Kelsey Hennig, Faith Sisson, Linda L Bruzzone. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 23.01.2017.

  19. Organisational justice and employee perceptions on hospital management.

    Science.gov (United States)

    Wiili-Peltola, Erja; Kivimäki, Mika; Elovainio, Marko; Virtanen, Marianna

    2007-01-01

    The purpose to clarify what kind of managerial challenges employees experience regarding organisational justice in hospitals. This exploratory study of 8,971 employees working in 14 hospitals and examines the concept of organisational justice in management with qualitative and quantitative methods. An inductive content analysis of the comments revealed five integrative frames describing challenges in hospital management at respondents' workplaces. These frames should be regarded as major managerial challenges in hospitals. These findings illustrate important antecedents of organisational justice and suggest that work units tend to share the same perceptions of justice. They also reveal that individually produced comments reflect collective experiences in organisational justice. Further, the results indicate that problems in management and policies are often experienced in a complex way, and people making justice judgements do not separate procedural and interactional factors. Although the commentators producing qualitative data represented many organisational hierarchy levels, the results should not be generalised to apply to horizontal, informal social relationships. This paper gives useful information regarding challenges in human resources management in hospitals. The paper suggests that people making fairness judgements do not make a distinction between procedural and interpersonal factors. Instead, they use any information available to judge the righteousness of the management events. This paper serves to guide hospital managers towards a better understanding of the importance of organisational justice and its collective nature.

  20. Justice: A Problem for Military Ethics during Irregular War

    Science.gov (United States)

    2008-05-22

    101 See Hans Kelsen , What is Justice? Justice, Law, and Politics in the Mirror of Science...Publishing Company, 1983. Keegan, John, ed. Atlas of the Second World War. New York: Harper and Row, Publishers, 1989. Kelsen , Hans. What is Justice

  1. PERUSAHAAN TIDAK ADIL KEPADA SAYA! : GAMBARAN PERCEIVED JUSTICE PADA SITUASI PERUBAHAN

    Directory of Open Access Journals (Sweden)

    Vera Elisabeth

    2017-06-01

    Full Text Available Employees perceive the fairness of organization’s systems and procedure is called perceived justice. Some studies indicated that perceived justice affects many organizational attitudes and behaviors, such as job satisfaction, absenteeism, counterproductive behavior, and turnover. Therefore, organization needs to give attention on employees’ perceived justice. This study was taken in PT. EFG, where its employees have been complaining about  many changes happened. This study was conducted with mixed method approach. Quantiative data was collected through 114 online questionnaires. The questionnaire measures three dimensions which are distributive justice, procedural justice, and interactional justice. Qualitative data was collected through interview to five participants with high and low intensity of perceived justice. The findings show that supervisor play an important role in  determining other employees’ procedural and interactional justice. Other factors such as characteristics, previous experiences, perception about change and coworkers also affect employees’ perceived justice

  2. JUSTICE IN THE WORKPLACE: THE INFLUENCE OF PROCEDURAL,DISTRIBUTIVE AND INTERACTIONAL JUSTICE ONORGANISATIONAL CITIZENSHIP BEHAVIOUR AMONGEMPLOYEES IN THE POLICE SERVICE

    Directory of Open Access Journals (Sweden)

    H.J. van Vuuren

    2016-01-01

    Full Text Available Organisational justice has received a fair amount of attention in businessenvironments. The study investigated employees’ perceptions of organisationaljustice and their effects on organisational citizenship behaviour at the SAPSAcademy, Paarl, South Africa. Using a quantitative research paradigm and anexploratory research method, 226 employees were sampledthrough a structuredquestionnaire. Systematic sampling wasused to ensure that the sample accuratelyreflected the larger population (N=457.Thecorrelation analysis revealed that allthree dimensions of organisational justice are related significantly and positivelyto organisational citizenship behaviour.Through regression analysisorganisational justice showed a strong predictive relationship with organisationalcitizenship behaviour. The study demonstrated that employeesshow a greaterpropensityto engage in organisational citizenship behaviour when they are able toform positiveperceptions of procedural, distributive and interactional justice. Thestudy established that there are major differences between the expectations ofemployees and managerial actions, which suggest that there are differentareas toexplore and different types of activities to undertake in order to successfullyenhance employees’ perceptions of organisational justice and reinforceorganisational citizenship behaviourin the academy.

  3. The Uterine Sandwich Method for Placenta Previa Accreta in Mullerian Anomaly: Combining the B-Lynch Compression Suture and an Intrauterine Gauze Tampon

    Directory of Open Access Journals (Sweden)

    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.

  4. Global health justice and governance.

    Science.gov (United States)

    Ruger, Jennifer Prah

    2012-01-01

    While there is a growing body of work on moral issues and global governance in the fields of global justice and international relations, little work has connected principles of global health justice with those of global health governance for a theory of global health. Such a theory would enable analysis and evaluation of the current global health system and would ethically and empirically ground proposals for reforming it to more closely align with moral values. Global health governance has been framed as an issue of national security, human security, human rights, and global public goods. The global health governance literature is essentially untethered to a theorized framework to illuminate or evaluate governance. This article ties global health justice and ethics to principles for governing the global health realm, developing a theoretical framework for global and domestic institutions and actors.

  5. Spheres of Justice within Schools

    DEFF Research Database (Denmark)

    Sabbagh, Clara; Resh, Nura; Mor, Michal

    2006-01-01

    This article argues that there are distinct spheres of justice within education and examines a range of justice norms and distribution rules that characterize the daily life of schools and classrooms. Moving from the macro to micro level, we identify the following five areas: the right to education......, the allocation of (or selection into) learning places, teaching–learning practices, teachers’ treatment of students, and student evaluations of grade distribution. We discuss the literature on the beliefs by students and teachers about the just distribution of educational goods in these five domains......, and on the practices used in the actual allocation of these goods. In line with normative ‘spheres of justice’ arguments in social theory, we conclude that the ideals of social justice within schools vary strongly according to the particular resource to be distributed. Moreover, these ideals often do not correspond...

  6. 25 CFR 11.435 - Obstructing justice.

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Obstructing justice. 11.435 Section 11.435 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAW AND ORDER COURTS OF INDIAN OFFENSES AND LAW AND ORDER CODE Criminal Offenses § 11.435 Obstructing justice. A person commits a misdemeanor if, with...

  7. Constructing a justice model based on Sen's capability approach

    OpenAIRE

    Yüksel, Sevgi; Yuksel, Sevgi

    2008-01-01

    The thesis provides a possible justice model based on Sen's capability approach. For this goal, we first analyze the general structure of a theory of justice, identifying the main variables and issues. Furthermore, based on Sen (2006) and Kolm (1998), we look at 'transcendental' and 'comparative' approaches to justice and concentrate on the sufficiency condition for the comparative approach. Then, taking Rawls' theory of justice as a starting point, we present how Sen's capability approach em...

  8. 22 CFR 304.9 - Referral to the Department of Justice.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Referral to the Department of Justice. 304.9... Procedures § 304.9 Referral to the Department of Justice. When Department of Justice approval or consultation is required under § 304.8, the referral or request shall be transmitted to the Department of Justice...

  9. The Justice Dimension of Sustainability: A Systematic and General Conceptual Framework

    Directory of Open Access Journals (Sweden)

    Klara Helene Stumpf

    2015-06-01

    Full Text Available We discuss how the normative dimension of sustainability can be captured in terms of justice. We (i identify the core characteristics of the concept of sustainability and discuss underlying ethical, ontological and epistemological assumptions; (ii introduce a general conceptual structure of justice for the analysis and comparison of different conceptions of justice; and (iii employ this conceptual structure to determine the specific characteristics and challenges of justice in the context of sustainability. We demonstrate that sustainability raises specific and partly new challenges of justice regarding the community of justice, the judicandum, the informational base, the principles, and the instruments of justice.

  10. Organizational identification moderates the impact of organizational justice on job satisfaction.

    Science.gov (United States)

    Yuan, Guo; Jia, Libin; Zhao, Jian

    2016-03-09

    Few studies concern the moderator effect of organizational identification between organizational justice and job satisfaction. This study aimed to examine the trilateral relationship among organizational identification, organizational justice and job satisfaction, especially focus on the moderator effect of organizational identification. 354 staffs completed the measures of organizational justice, organizational identification and job satisfaction. Hierarchical regression analysis showed that organizational identification moderated the association between organizational justice and job satisfaction. When staffs reported a low level of organizational identification, those with high organizational justice reported higher scores in job satisfaction than those with low organizational justice. However, the impact of organizational justice on job satisfaction was not significant in high organizational identification group. Organizational identification can significantly moderate the impact of organizational justice on job satisfaction. The significance and limitations of the results are discussed.

  11. La representación de los personajes monstruosos en el cine de David Lynch: Cabeza Borradora y El Hombre Elefante

    OpenAIRE

    Suñer Royo, Iris

    2015-01-01

    Treball final de Grau en Comunicació Audiovisual. Codi: CA0932. Curs acadèmic 2014-2015 El universo creado por David Lynch es prácticamente inabarcable, sin embargo, con cada producto que realiza incorpora nuevas estrategias expresivas y formales que podemos desglosar y analizar para entender cada vez mejor como su mente y creatividad se desarrollan. Para ello hemos empezado desde el principio, por sus dos primeros largometrajes, los cuales son los únicos filmados en blanco ...

  12. Skepticism of the Western System on Justice

    Directory of Open Access Journals (Sweden)

    Noor Farihah Mohd Noor

    2013-06-01

    Full Text Available Justice is an elusive concept; it is controversial,yet very important to mankind. This paper seeks to explain the challenges found in the work of justice and to explore justice as defined by the West and by Islam. The findings show that there is stark difference especially in the philosophical aspect in how justice is interpreted and applied from the viewpoint of the West and Islam. Findings also show that Islamic approach to justice is more durable and dynamic as theguidance is deeply entrenched in the divine revelation of the Holy Quran; since no human being has the ability of creating, being by nature, fallible and as such produces excellent impact. The impact of justice in Islam can be seen from the Islamic history itself. Unfortunately, since the world has been dominated by the secularsystem; divine law has slowly been rejected and has been taken as irrelevant and backdated. The researcher also seeks to show why Muslims fail despite of the existence of rich and forceful Islamic ways. In order to overcome the setback, the researcher proposes some reforms for Muslims to return to its original state of Islam that encourages just and good governance. This finding is important as it can provide insights to the government as tools in combating acts ofinjustice more consistently and forcefully. As injustice is an endemic and the main reason for the collapse of society, this discussion attempts to show that Islamic idea of justice is actuallyable to solve all problems no matter how big the scale is. The positive and incredible impact not only will be enjoyed by the ruler and the governed, but also by the whole nation, Muslims and non-Muslims alike.

  13. Justice and the Human Genome Project

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, T.F.; Lappe, M. (eds.)

    1992-01-01

    Most of the essays gathered in this volume were first presented at a conference, Justice and the Human Genome, in Chicago in early November, 1991. The goal of the, conference was to consider questions of justice as they are and will be raised by the Human Genome Project. To achieve its goal of identifying and elucidating the challenges of justice inherent in genomic research and its social applications the conference drew together in one forum members from academia, medicine, and industry with interests divergent as rate-setting for insurance, the care of newborns, and the history of ethics. The essays in this volume address a number of theoretical and practical concerns relative to the meaning of genomic research.

  14. Justice and the Human Genome Project

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, T.F.; Lappe, M. [eds.

    1992-12-31

    Most of the essays gathered in this volume were first presented at a conference, Justice and the Human Genome, in Chicago in early November, 1991. The goal of the, conference was to consider questions of justice as they are and will be raised by the Human Genome Project. To achieve its goal of identifying and elucidating the challenges of justice inherent in genomic research and its social applications the conference drew together in one forum members from academia, medicine, and industry with interests divergent as rate-setting for insurance, the care of newborns, and the history of ethics. The essays in this volume address a number of theoretical and practical concerns relative to the meaning of genomic research.

  15. The Ambiguity of Justice: Paul Ricoeur on Universalism and Evil

    Directory of Open Access Journals (Sweden)

    Geoffrey Dierckxsens

    2016-01-01

    Full Text Available In this article I will examine Ricœur’s idea of the universal in his understanding of justice. Scholars recently discussed the extent to which Ricœur understands universal moral norms and universal rules of justice in his anthropology of human action (e.g., J. Michel, Paul Ricœur: une philosophie de l’agir humain, Paris: Les Éditions du Cerf, 2006, and argue that Ricœur stresses too much the idea of universal moral norms with regard to cultural and moral diversity (e.g., G. H. Taylor, “Ricoeur versus Ricoeur? Between the Universal and the Contextual,” From Ricoeur to Action. The Socio-Political Significance of Ricoeur’s Thinking, Todd S. Mei and David Lewin (eds., (London and New York: Bloomsbury, 2012. G. H. Taylor, “Reenvisioning Justice,” Lo Squarda 12 (2013: 65-80. In this article I will take part in the debate about universalism and approach Ricœur’s idea of the universal from a different angle, in placing it in light of his idea of evil. The point I will aim to make in this article is that Ricœur’s idea of the relation between justice and evil demonstrates what I understand as the ambiguity of justice, which highlights the difficulty of defining universal rules of justice. I will argue that this ambiguity is the following: justice aims at the establishment of social peace and in that sense it is the necessary remedy against human evil, but justice also implies power, and possibly violence, over others in that it relates to violent feelings of vengeance, to institutional mechanism of authority, and to a struggle of values. Yet if rules of justice relate to evil in the sense of power over others, so I argue, then it is problematic to define absolute criteria for rules of justice, i.e., for rules for social peace: because justice relates to particular values, which means that the risk of violence is inherent to institutional rules of justice, there is no ultimate universal set of such rules. This article therefore

  16. 28 CFR 16.76 - Exemption of Justice Management Division.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Exemption of Justice Management Division. 16.76 Section 16.76 Judicial Administration DEPARTMENT OF JUSTICE PRODUCTION OR DISCLOSURE OF MATERIAL OR INFORMATION Exemption of Records Systems Under the Privacy Act § 16.76 Exemption of Justice...

  17. Justice mechanisms and the question of legitimacy: the example of Rwanda's multi-layered justice mechanisms

    OpenAIRE

    Oomen, B.; Ambos, K.; Large, J.; Wierda, M.

    2009-01-01

    Legitimacy, this contribution argues, plays a key role in connecting transitional justice mechanisms to sustainable peace, and strengthening people's perceptions of legitimacy should be of concern to all those involved in these institutions. Here, it is important to take an empirical, people-based approach to legitimacy, with regard for its dynamic quality. This approach should focus on all three dimensions of legitimacy: the input into transitional justice mechanisms, the popular adherence t...

  18. The Law of Peoples and Global Justice

    Czech Academy of Sciences Publication Activity Database

    Hrubec, Marek

    2010-01-01

    Roč. 20, č. 2 (2010), s. 135-150 ISSN 1210-3055 R&D Projects: GA MŠk(CZ) LC06013 Institutional research plan: CEZ:AV0Z90090514 Keywords : international justice * global justice * Rawls * recognition Subject RIV: AA - Philosophy ; Religion

  19. Does organizational justice predict empowerment? Nurses assess their work environment.

    Science.gov (United States)

    Kuokkanen, Liisa; Leino-Kilpi, Helena; Katajisto, Jouko; Heponiemi, Tarja; Sinervo, Timo; Elovainio, Marko

    2014-09-01

    The purpose of the study was to explore how nurses assess their empowerment and clarify organizational justice compared to other work-related factors. In addition, we examined the major variables pertinent to empowerment. Cross-sectional survey data were used. A total of 2,152 nurses returned the completed questionnaire. The instruments consisted of nurse empowerment, organizational justice, job control, and possibilities for developing work. The data analysis was based on descriptive statistics and further statistical tests. Organizational justice and empowerment had a clear correlation. Job control, possibilities for developing work and organizational justice were statistically significant predictors of nurse empowerment. Organizational justice and the possibility to use one's individual skills at work are significant factors in staff activity and its development in nursing. They increase the level of empowerment and commitment as well as motivation to work. The results of this study confirm that nurses regard organizational justice as highly important. We can facilitate both work-related empowerment and organizational justice by creating and maintaining a culture of fairness and justice. Employees should be heard and involved more in the planning and decision making of work. © 2014 Sigma Theta Tau International.

  20. Energy decisions reframed as justice and ethical concerns

    Science.gov (United States)

    Sovacool, Benjamin K.; Heffron, Raphael J.; McCauley, Darren; Goldthau, Andreas

    2016-05-01

    All too often, energy policy and technology discussions are limited to the domains of engineering and economics. Many energy consumers, and even analysts and policymakers, confront and frame energy and climate risks in a moral vacuum, rarely incorporating broader social justice concerns. Here, to remedy this gap, we investigate how concepts from justice and ethics can inform energy decision-making by reframing five energy problems — nuclear waste, involuntary resettlement, energy pollution, energy poverty and climate change — as pressing justice concerns. We conclude by proposing an energy justice framework centred on availability, affordability, due process, transparency and accountability, sustainability, equity and responsibility, which highlights the futurity, fairness and equity dimensions of energy production and use.

  1. Environmental justice in Scotland: policy, pedagogy and praxis

    International Nuclear Information System (INIS)

    Scandrett, Eurig

    2007-01-01

    In the first decade of Scottish devolution, environmental justice became a significant component of environmental policy for the Scottish Executive, especially under First Minister Jack McConnell. This paper analyses how a discourse developed within policy narratives which separated environmental justice from economic growth and the interests of capital. In particular, it explores the role which research has played in justifying this discourse. By contrast, an alternative discourse has developed through reflexive and dialogical research associated with the praxis of the environmental organization Friends of the Earth Scotland. This alternative discourse is embedded in the embryonic environmental justice movement in Scotland, and identifies environmental justice as a social conflict which exposes negative externalities at the heart of economic development

  2. Environmental justice in Scotland: policy, pedagogy and praxis

    Energy Technology Data Exchange (ETDEWEB)

    Scandrett, Eurig [Queen Margaret University, Edinburgh (United Kingdom)

    2007-10-15

    In the first decade of Scottish devolution, environmental justice became a significant component of environmental policy for the Scottish Executive, especially under First Minister Jack McConnell. This paper analyses how a discourse developed within policy narratives which separated environmental justice from economic growth and the interests of capital. In particular, it explores the role which research has played in justifying this discourse. By contrast, an alternative discourse has developed through reflexive and dialogical research associated with the praxis of the environmental organization Friends of the Earth Scotland. This alternative discourse is embedded in the embryonic environmental justice movement in Scotland, and identifies environmental justice as a social conflict which exposes negative externalities at the heart of economic development.

  3. 77 FR 70473 - Office of Juvenile Justice and Delinquency Prevention; Agency Information Collection Activities...

    Science.gov (United States)

    2012-11-26

    ... DEPARTMENT OF JUSTICE [OMB Number 1121-0218] Office of Juvenile Justice and Delinquency Prevention... Justice (DOJ), Office of Justice Programs, Office of Juvenile Justice and Delinquency Prevention, will be... Justice and Delinquency Prevention, Office of Justice Programs, U.S. Department of Justice, 810 Seventh...

  4. Uncertainties in the Management of a Lynch Syndrome Patient: A Case Report

    Science.gov (United States)

    Campos, Sara; Amaro, Pedro; Cunha, Inês; Fraga, João; Cipriano, Maria Augusta; Tomé, Luís

    2017-01-01

    Introduction Lynch syndrome (LS), the most common hereditary colorectal cancer syndrome, is characterized by mutations in mismatch repair (MMR) genes leading to an increased cancer risk, namely colorectal cancer. Case In the context of surveillance colonoscopy, a 40-mm flat lesion (0-IIa+b, Paris classification) was identified and submitted to piecemeal mucosal endoscopic resection in a 64-year-old LS patient with an MLH1 germline mutation (262delATC) and two previous segmental resections due to metachronous colorectal cancer. Pathology raised the suspicion of superficial submucosal invasive carcinoma with poor differentiation. Immunochemistry showed heterogeneous MLH1 expression and PMS2 loss. In a short-term follow-up colonoscopy, another 30-mm advanced carcinoma was identified. The patient was referred to surgery. Conclusion This case raises several issues: (1) the potentially fast tumorigenesis and progression to carcinoma in LS and implications for endoscopic screening and surveillance; (2) pitfalls in the interpretation of MMR proteins immunochemistry; (3) the role of endoscopic resection in LS. PMID:29255760

  5. Uncertainties in the Management of a Lynch Syndrome Patient: A Case Report

    Directory of Open Access Journals (Sweden)

    Sara Campos

    2017-03-01

    Full Text Available Introduction: Lynch syndrome (LS, the most common hereditary colorectal cancer syndrome, is characterized by mutations in mismatch repair (MMR genes leading to an increased cancer risk, namely colorectal cancer. Case: In the context of surveillance colonoscopy, a 40-mm flat lesion (0-IIa+b, Paris classification was identified and submitted to piecemeal mucosal endoscopic resection in a 64-year-old LS patient with an MLH1 germline mutation (262delATC and two previous segmental resections due to metachronous colorectal cancer. Pathology raised the suspicion of superficial submucosal invasive carcinoma with poor differentiation. Immunochemistry showed heterogeneous MLH1 expression and PMS2 loss. In a short-term follow-up colonoscopy, another 30-mm advanced carcinoma was identified. The patient was referred to surgery. Conclusion: This case raises several issues: (1 the potentially fast tumorigenesis and progression to carcinoma in LS and implications for endoscopic screening and surveillance; (2 pitfalls in the interpretation of MMR proteins immunochemistry; (3 the role of endoscopic resection in LS.

  6. Integrating Deliberative Justice Theory into Social Work Policy Pedagogy

    Science.gov (United States)

    Morrow, Helen

    2011-01-01

    Deliberation that upholds the social work values of justice and inclusion is an essential component of the policy-making process; yet most social welfare policy curricula focus instead on the goals of distributive justice. This article presents a model that demonstrates how deliberative justice can be easily incorporated into beginning level…

  7. Challenges and prospects of the juvenile justice administration in ...

    African Journals Online (AJOL)

    Juvenile justice administration in Nigeria is weak and has been given very little priority, despite Nigeria being signatory to the major international instruments relevant to the administration of juvenile justice. This is attributable to the history of the penal system of Nigeria, with laws guiding juvenile justice administration having ...

  8. EUROPEAN UNION SUPPORT AND TRANSITIONAL JUSTICE PROCESSES IN KOSOVO

    Directory of Open Access Journals (Sweden)

    Remzije Istrefi

    2017-12-01

    Full Text Available The legacy of systematic human rights violations committed during 1999 violent conflict and the previous repressive rule still impact the everyday life of Kosovo citizens. That is why transitional justice processes are a necessary component in Kosovo’s state building efforts. With the end of the 1999 conflict, Kosovo has been administered by the United Nations Mission in Kosovo (UNMIK and also supported by European Union (EU presences: the EU Special Representative in Kosovo, and European Union Rule of Law Mission known as EULEX. In the course of implementation of their mandates transitional justice processes were not a priority for UNMIK and EU presences. With the signing of the Stabilization and Association Agreement (SAA the EU made transitional justice part of the Kosovo accession demands. In December 2015, the Government of Kosovo approved its National Action Plan for the Implementation of the Stabilization and Association Agreement (NAPISAA. The General Principles of the SAA, included within the NAPISAA oblige Kosovo Government to approve a National Transitional Justice Strategy. This paper analyses EU peace and institution-building support and their impact in transitional justice processes in Kosovo. Through analysing the mandate and actions on the ground it draws conclusions if EU is an active participant in transitional justice process in Kosovo or transitional justice policies are promoted by EU only as part of its enlargement strategy. Finally, the paper gives recommendations as a basis for future elaboration of an EU approach to transitional justice.

  9. 78 FR 43920 - Meeting (Webinar) of the Federal Advisory Committee on Juvenile Justice

    Science.gov (United States)

    2013-07-22

    ... DEPARTMENT OF JUSTICE Office of Justice Programs [OJP (OJJDP) Docket No. 1614] Meeting (Webinar) of the Federal Advisory Committee on Juvenile Justice AGENCY: Office of Juvenile Justice and Delinquency Prevention, Office of Justice Programs, U.S. Department of Justice. ACTION: Notice of Webinar...

  10. 77 FR 39511 - Meeting (Webinar) of the Federal Advisory Committee on Juvenile Justice

    Science.gov (United States)

    2012-07-03

    ... DEPARTMENT OF JUSTICE Office of Justice Programs [OJP (OJJDP) Docket No. 1594] Meeting (Webinar) of the Federal Advisory Committee on Juvenile Justice AGENCY: Office of Juvenile Justice and Delinquency Prevention, Office of Justice Programs, U.S. Department of Justice. ACTION: Notice of Webinar...

  11. 77 FR 20649 - Meeting (Webinar) of the Federal Advisory Committee on Juvenile Justice

    Science.gov (United States)

    2012-04-05

    ... DEPARTMENT OF JUSTICE Office of Justice Programs [OJP (OJJDP) Docket No. 1585] Meeting (Webinar) of the Federal Advisory Committee on Juvenile Justice AGENCY: Office of Juvenile Justice and Delinquency Prevention, Office of Justice Programs, U.S. Department of Justice. ACTION: Notice of meeting...

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

    International Nuclear Information System (INIS)

    Wu, Hong; Zeng, Hong; Lam, Robert; Tempel, Wolfram; Kerr, Iain D.; Min, Jinrong

    2015-01-01

    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

  13. 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.

  14. Social Justice and the “Green” City

    Directory of Open Access Journals (Sweden)

    Liette Gilbert

    2014-05-01

    Full Text Available A transition to a new, greener urbanism is increasingly imperative in the face of environmental crises. However, such a transition is not possible without considering social justice. This essay examines some ten¬sions between social justice and urban sustainability and some of the reasons why a social justice approach to urban sustainability is often marginalized by a neoliberal sustainability ontology. This essay first engages with various normative concepts of social justice and its long existing but unfulfilled claim in the city. It then considers some gains toward greener urbanism but contends that urban sustainability responses have ge¬nerally been more preoccupied with ecological modernization and the reproduction of best practices rather than with socio-spatial justice. In looking at some workings of green neoliberalism, the essay points to how the ecological is easily recuperated for neoliberal ends. The last section addresses some reasons why the social is de-privileged in the dominant sustainability discourses and practices, and how social justice serves, through citizenship practices, as a claim to urban change where participation is not a bureaucratized process but an everyday practice. Overall, the essay cautions against certain sustainability discourses and green neoliberalism without addressing its ingrained inequalities.

  15. 28 CFR 20.35 - Criminal Justice Information Services Advisory Policy Board.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Criminal Justice Information Services Advisory Policy Board. 20.35 Section 20.35 Judicial Administration DEPARTMENT OF JUSTICE CRIMINAL JUSTICE..., concept, and operational principles of various criminal justice information systems managed by the FBI's...

  16. Teaching for social justice education: the intersection between identity, critical agency, and social justice education

    OpenAIRE

    Dennis Francis; Adré le Roux

    2011-01-01

    In line with national policy requirements, educators are increasingly addressing forms of social justice education by focusing on classroom pedagogies and educational practices to combat different forms of oppression such as racism and sexism. As all educators have a role to play in dismantling oppression and generating a vision for a more socially just future, teacher education has the responsibility to capacitate pre-service teachers to work in areas of social justice education. It is, howe...

  17. Justice and Social Cohesion: Some conservative perspectives

    DEFF Research Database (Denmark)

    Pedersen, Søren Hviid

    2011-01-01

    In the wake of recent debates on multiculturalism and value-pluralism, the pressing questions now focuses on whether social cohesion and the notion of justice are sustainable and can be upheld, at least from a European perspective. There are many theoretical and academic responses, mainly from...... liberals, on how to accommodate the different demands of various ethnic and religious groups and at the same time sustain a minimum of social cohesion and justice. One voice is missing and that is a conservative perspective. The purpose of this paper is to formulate a modern conservative analysis...... of this problem. The argument presented in this paper will, first, take its point of departure from David Hume’s notion of sympathy and how this makes social cohesion possible. Second, it will be argued that social cohesion is a prerequisite for the existence of justice, and therefore justice is a derivative...

  18. 7 CFR 3.21 - Referrals of Debts to Justice.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Referrals of Debts to Justice. 3.21 Section 3.21... and Compromise of Claims § 3.21 Referrals of Debts to Justice. An agency shall promptly refer to Justice for litigation debts on which aggressive collection activity has been taken in accordance with...

  19. Ethical commitment to women's participation in transitional justice

    OpenAIRE

    Porter, Elisabeth

    2013-01-01

    Ethical issues of justice and human rights are central to countries emerging from conflict. Yet involving women in transitional justice processes rarely is articulated in ethical terms. To make a case for an ethical commitment to improving women’s participation in these processes, the paper begins by exploring why transitional justice strategies should bother with gender. Women and men often experience conflict and injustices differently which may require different responses to redress harms ...

  20. 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

    NARCIS (Netherlands)

    Vleugels, Jasper L. A.; Sahin, Husna; Hazewinkel, Yark; Koens, Lianne; van den Berg, Jose G.; van Leerdam, Monique E.; Dekker, Evelien

    2017-01-01

    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