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11. Intestinal and extraintestinal neoplasms in patients with NTHL1 tumor syndrome:a systematic review

Author

Beck, S. H., Jelsig, A. M., Yassin, H. M., Lindberg, L. J., Wadt, K. A. W., Karstensen, J. G., Beck, S. H., Jelsig, A. M., Yassin, H. M., Lindberg, L. J., Wadt, K. A. W., and Karstensen, J. G.

Abstract

Germline biallelic pathogenic variants (PVs) in NTHL1 have since 2015 been associated with the autosomal recessive tumor predisposition syndrome: NTHL1 tumor syndrome or NTHL1-associated polyposis. In this systematic review, we aim to systematically investigate the phenotypic and genotypic spectrum of the condition including occurrence of both benign and malignant tumors. The databases PubMed, EMBASE, and Scopus were searched. The search was conducted the 25th of august 2021. We included patients with germline PVs, both heterozygous and homo-/compound heterozygous carriers. Twenty-one papers were selected including 47 patients with biallelic PVs in NTHL1 in 32 families. Twenty-three out of 47 patients (49%) were diagnosed with colorectal cancer (CRC) (mean age: 55, range: 31–73) and 12 out of 22 female patients (55%) were diagnosed with breast cancer (mean age: 49, range: 36–63). Apart from three, all patients who underwent a colonoscopy, had colonic adenomas (93%), and three patients (6%) had duodenal adenomatosis. We also identified 158 heterozygous carriers of germline PVs in NTHL1. Twenty-six out of 68 (38%) heterozygous carriers, who underwent colonoscopy, had colonic polyps or adenomas. Twenty-nine heterozygous carriers (18%) were diagnosed with CRC and 59 (49%) with breast cancer. We observed a high frequency of early onset CRC and breast cancer in patients with NTHL1 tumor syndrome. Subsequently, colorectal, breast, and endometrial cancer screening programs are recommended for NTHL1 biallelic carriers. Trial registry PROSPERO: CRD42021275159.

Published
2022

17. No Difference in Penetrance between Truncating and Missense/Aberrant Splicing Pathogenic Variants in MLH1 and MSH2: A Prospective Lynch Syndrome Database Study

Author

Dominguez-Valentin, M, Plazzer, J-P, Sampson, JR, Engel, C, Aretz, S, Jenkins, MA, Sunde, L, Bernstein, I, Capella, G, Balaguer, F, Macrae, F, Winship, IM, Thomas, H, Evans, DG, Burn, J, Greenblatt, M, Cappel, WHDVTN, Sijmons, RH, Nielsen, M, Bertario, L, Bonanni, B, Tibiletti, MG, Cavestro, GM, Lindblom, A, Della Valle, A, Lopez-Kostner, F, Alvarez, K, Gluck, N, Katz, L, Heinimann, K, Vaccaro, CA, Nakken, S, Hovig, E, Green, K, Lalloo, F, Hill, J, Vasen, HFA, Perne, C, Buettner, R, Goergens, H, Holinski-Feder, E, Morak, M, Holzapfel, S, Hueneburg, R, Doeberitz, MVK, Loeffler, M, Rahner, N, Weitz, J, Steinke-Lange, V, Schmiegel, W, Vangala, D, Crosbie, EJ, Pineda, M, Navarro, M, Brunet, J, Moreira, L, Sanchez, A, Serra-Burriel, M, Mints, M, Kariv, R, Rosner, G, Pinero, TA, Pavicic, WH, Kalfayan, P, ten Broeke, SW, Mecklin, J-P, Pylvanainen, K, Renkonen-Sinisalo, L, Lepisto, A, Peltomaki, P, Hopper, JL, Win, AK, Buchanan, DD, Lindor, NM, Gallinger, S, Le Marchand, L, Newcomb, PA, Figueiredo, JC, Thibodeau, SN, Therkildsen, C, Hansen, TVO, Lindberg, L, Rodland, EA, Neffa, F, Esperon, P, Tjandra, D, Moslein, G, Seppala, TT, Moller, P, Dominguez-Valentin, M, Plazzer, J-P, Sampson, JR, Engel, C, Aretz, S, Jenkins, MA, Sunde, L, Bernstein, I, Capella, G, Balaguer, F, Macrae, F, Winship, IM, Thomas, H, Evans, DG, Burn, J, Greenblatt, M, Cappel, WHDVTN, Sijmons, RH, Nielsen, M, Bertario, L, Bonanni, B, Tibiletti, MG, Cavestro, GM, Lindblom, A, Della Valle, A, Lopez-Kostner, F, Alvarez, K, Gluck, N, Katz, L, Heinimann, K, Vaccaro, CA, Nakken, S, Hovig, E, Green, K, Lalloo, F, Hill, J, Vasen, HFA, Perne, C, Buettner, R, Goergens, H, Holinski-Feder, E, Morak, M, Holzapfel, S, Hueneburg, R, Doeberitz, MVK, Loeffler, M, Rahner, N, Weitz, J, Steinke-Lange, V, Schmiegel, W, Vangala, D, Crosbie, EJ, Pineda, M, Navarro, M, Brunet, J, Moreira, L, Sanchez, A, Serra-Burriel, M, Mints, M, Kariv, R, Rosner, G, Pinero, TA, Pavicic, WH, Kalfayan, P, ten Broeke, SW, Mecklin, J-P, Pylvanainen, K, Renkonen-Sinisalo, L, Lepisto, A, Peltomaki, P, Hopper, JL, Win, AK, Buchanan, DD, Lindor, NM, Gallinger, S, Le Marchand, L, Newcomb, PA, Figueiredo, JC, Thibodeau, SN, Therkildsen, C, Hansen, TVO, Lindberg, L, Rodland, EA, Neffa, F, Esperon, P, Tjandra, D, Moslein, G, Seppala, TT, and Moller, P

Abstract

BACKGROUND: Lynch syndrome is the most common genetic predisposition for hereditary cancer. Carriers of pathogenic changes in mismatch repair (MMR) genes have an increased risk of developing colorectal (CRC), endometrial, ovarian, urinary tract, prostate, and other cancers, depending on which gene is malfunctioning. In Lynch syndrome, differences in cancer incidence (penetrance) according to the gene involved have led to the stratification of cancer surveillance. By contrast, any differences in penetrance determined by the type of pathogenic variant remain unknown. OBJECTIVE: To determine cumulative incidences of cancer in carriers of truncating and missense or aberrant splicing pathogenic variants of the MLH1 and MSH2 genes. METHODS: Carriers of pathogenic variants of MLH1 (path_MLH1) and MSH2 (path_MSH2) genes filed in the Prospective Lynch Syndrome Database (PLSD) were categorized as truncating or missense/aberrant splicing according to the InSiGHT criteria for pathogenicity. RESULTS: Among 5199 carriers, 1045 had missense or aberrant splicing variants, and 3930 had truncating variants. Prospective observation years for the two groups were 8205 and 34,141 years, respectively, after which there were no significant differences in incidences for cancer overall or for colorectal cancer or endometrial cancers separately. CONCLUSION: Truncating and missense or aberrant splicing pathogenic variants were associated with similar average cumulative incidences of cancer in carriers of path MLH1 and path_MSH2.

Published
2021

18. Reduced evoked activity and cortical oscillations are correlated with anisometric amblyopia and impairment of visual acuity

Author

Julku, H. (Hanna), Rouhinen, S. (Santeri), Huttunen, H. J. (Henri J.), Lindberg, L. (Laura), Liinamaa, J. (Johanna), Saarela, V. (Ville), Karvonen, E. (Elina), Booms, S. (Sigrid), Mäkelä, J. P. (Jyrki P.), Uusitalo, H. (Hannu), Castrén, E. (Eero), Palva, J. M. (J. Matias), Palva, S. (Satu), Julku, H. (Hanna), Rouhinen, S. (Santeri), Huttunen, H. J. (Henri J.), Lindberg, L. (Laura), Liinamaa, J. (Johanna), Saarela, V. (Ville), Karvonen, E. (Elina), Booms, S. (Sigrid), Mäkelä, J. P. (Jyrki P.), Uusitalo, H. (Hannu), Castrén, E. (Eero), Palva, J. M. (J. Matias), and Palva, S. (Satu)

Abstract

Amblyopia is a developmental disorder associated with abnormal visual experience during early childhood commonly arising from strabismus and/or anisometropia and leading to dysfunctions in visual cortex and to various visual deficits. The different forms of neuronal activity that are attenuated in amblyopia have been only partially characterized. In electrophysiological recordings of healthy human brain, the presentation of visual stimuli is associated with event-related activity and oscillatory responses. It has remained poorly understood whether these forms of activity are reduced in amblyopia and whether possible dysfunctions would arise from lower- or higher-order visual areas. We recorded neuronal activity with magnetoencephalography (MEG) from anisometropic amblyopic patients and control participants during two visual tasks presented separately for each eye and estimated neuronal activity from source-reconstructed MEG data. We investigated whether event-related and oscillatory responses would be reduced for amblyopia and localized their cortical sources. Oscillation amplitudes and evoked responses were reduced for stimuli presented to the amblyopic eye in higher-order visual areas and in parietal and prefrontal cortices. Importantly, the reduction of oscillation amplitudes but not that of evoked responses was correlated with decreased visual acuity in amblyopia. These results show that attenuated oscillatory responses are correlated with visual deficits in anisometric amblyopia.

Published
2021

23. 63MO Safety analysis of durvalumab following stereotactic body radiotherapy (SBRT) in early-stage non-small cell lung cancer (NSCLC) patients: A first report of a randomized phase II trial (ASTEROID)

Author

Hallqvist, A., primary, Koyi, H., additional, de Petris, L., additional, Lindberg, K., additional, Farooqi, S., additional, Helland, Å., additional, Wikström, A., additional, Johansson, M., additional, Planck, M., additional, Lindberg, L., additional, Yksnøy, Ø., additional, Grønberg, B.H., additional, Helbekkmo, N., additional, and Nyman, J., additional

Published
2021
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24. ESCOLA, REVOLUÇÃO 4.0, CONSERVADORISMO E A FORMAÇÃO DO PROFESSOR

Author

Christian Lindberg L. do Nascimento

Subjects
Escola, Professor, Revolução 4.0, General Engineering, Homeschooling, Conservadorismo
Abstract

O objetivo deste texto é analisar dois movimentos que tendem a impactar na formação do docente: a uberização das relações trabalhistas e as inciativas educacionais com caráter conservador. O ponto de partida é a atual situação política e educacional na qual se inserem as políticas públicas que visam impactar na formação do professor, marcadas pela Revolução 4.0, pela reforma trabalhista e por propostas educacionais que negam o papel da escola e do professor no processo educativo. Por ser uma pesquisa qualitativa, buscou-se utilizar fontes que pudessem subsidiar a argumentação. Além disso, a análise de conteúdo foi o procedimento metodológico adotado, tendo livros, estudos quantitativos e análise documental como fontes.

Published
2020
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25. Benefit from extended surveillance interval on colorectal cancer risk in Lynch syndrome

Author

Lindberg, L J, Rasmussen, M, Andersen, K K, Nilbert, M, Therkildsen, C, Lindberg, L J, Rasmussen, M, Andersen, K K, Nilbert, M, and Therkildsen, C

Abstract

AIM: Although patients with Lynch syndrome have an increased risk of developing colorectal cancer, surveillance can reduce morbidity and mortality. Whether or not affected individuals benefit from lifetime surveillance depends on individual factors and patient adherence, and these may vary, complicating risk modelling. The aim of this study was to identify individual factors which influence patient adherence to surveillance programmes and whether extended surveillance interval influenced their risk of developing colorectal cancer.METHOD: Demographics and survival data were obtained from patients (n = 1223) with Lynch syndrome, identified by interrogating the Danish Hereditary Non-Polyposis Colorectal Cancer Register. These data were linked to patient surveillance interval data which had been divided into three subsets (< 27 months, adherent to the recommended biennial programme; > 27 months, extended surveillance interval; and no surveillance) to estimate the cumulative risks and hazard ratios (HRs) for colorectal cancer.RESULTS: In all, 147 colorectal cancers (99 first; 48 metachronous) were identified in 1223 patients. Factors associated with adherence to surveillance were female sex, a previous history of cancer and age < 75 years. The cumulative incidence for colorectal cancer was 38% (95% CI 27%-50%) for surveillance intervals < 27 months, 48% (95% CI 29%-67%) for intervals > 27 months and 72% (95% CI 61%-83%) with no surveillance. Adjusted HRs were 0.22 for surveillance intervals < 27 months and 0.32 for surveillance intervals > 27 months. Extended surveillance intervals > 27 months had a non-significant benefit with an HR of 1.51 (95% CI 0.83-2.75) compared to surveillance intervals < 27 months.CONCLUSION: This study demonstrates that adherence to colonoscopic surveillance in Lynch syndrome varies with age, sex and cancer history and demonstrates a consistent benefit from colorectal cancer surveillance, thoug

Published
2020

26. Method and education in John Locke

Author

Christian Lindberg L. do Nascimento

Subjects
lcsh:LC8-6691, lcsh:Special aspects of education, lcsh:Philosophy (General), lcsh:B1-5802
Abstract

The present text has as its main objective to analyze the impact of the educational method in obtaining knowledge, using as theoretical reference the philosophical thoughts of John Locke. The reflection developed by the autour is based, initially, on the criticism developed in the teaching of Logic and it ends in the moral reflection that runs through his whole work. The author of the Essay on Human Understanding realized that the teaching of the syllogism did not guarantee the production of knowledge. He understood that the education based on the teaching of logic and rhetoric formed pedantic children with encyclopedic knowledge with no use to their practical life.This matter, according to Locke, was related to the discussion about the most appropriate method for obtaining knowledge and the consequences that this new method of education propitiates. What this research seeks to develop is the relationship between epistemology and morality, with education as the fundamental link. This concern arises when is observed the relevance that the teaching method has had in contemporary educational processes, much of it with an end in itself. In selecting Locke as a theoretical reference, what it seeks is to give a moral sense to educational in concerns of methodological order, although the solution presented by the English philosopher requires a proper contextualization. Because it is an eminently qualitative research, the data analysis was done from the reading and summaring of the selected reference, having part of the work of Locke as primary source and those of the chosen commentators as secondary.

Published
2018

27. Locke e a educação do magistrado

Author

Christian Lindberg L. do Nascimento

Subjects
Educação, Gentleman, Locke, Política., Philosophy (General), B1-5802
Abstract

O objetivo deste texto é delimitar a relação entre educação e política na obra de John Locke, considerando as atribuições que o magistrado exerce. Nesse sentido, detalhar qual a função que o magistrado tem na manutenção dos direitos individuais e quais são as atribuições do poder legislativo e do poder executivo, torna-se necessário. Para tal intuito, iremos expor inicialmente a teoria lockeana da divisão dos poderes; em seguida, demonstraremos que o magistrado deve ser um indivíduo que elabora e execute as leis imparcialmente; e, por fim, relacionar esta argumentação com seus escritos sobre educação. Por ser resultado de uma pesquisa qualitativa e de cunho filosófico empregamos a hermenêutica como metodologia. Consequentemente, o procedimento metodológico adotado foi a análise de texto.

Published
2011
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34. Mechanical impedance of the human body in vertical direction

Author

Holmlund, P., Lundstrom, R., and Lindberg, L.

Subjects
Human mechanics -- Research, Sitting position -- Research, Vibration -- Physiological aspects, Engineering and manufacturing industries, Health, Human resources and labor relations
Abstract

The mechanical impedance of the human body in sitting posture and vertical direction was measured during different experimental conditions, such as vibration level (0.5-1.4 m/s(super 2)), frequency (2-100 Hz), body weight (57-92 kg), relaxed and erect upper body posture. The outcome shows that impedance increases with frequency up to a peak at about 5 Hz after which it decreases in a complex manner which includes two additional peaks. The frequency at which the first and second impedance peak occurs decreases with higher vibration level. Erect, compared with relaxed body posture resulted in higher impedance magnitudes and with peaks located at somewhat higher frequencies. Heavy persons show higher impedance magnitudes and peaks at lower frequencies. Keywords: Vibration; Whole-body; Biodynamics

Published
2000

40. A pedagogia histórico-crí­tica como abordagem metodológica para o ensino da filosofia

Author

Christian Lindberg L. do Nascimento

Subjects
Pedagogia histórico-crí­tica, Ensino de Filosofia, Metodologia de ensino
Abstract

Resumo: Os estudos historiográficos e filosóficos desenvolvidos por Dermeval Saviani têm apontado para a aplicação do materialismo-histórico-dialético ao debate educativo nacional. Neste sentido, a formação humana emerge como tema central das investigações educacionais, na qual se busca a superação da relação exploratória entre o Capital e o trabalho, marcada pela alienação e opressão do homem pelo homem. Como defende Saviani, "superar a alienação para alcançar-se o pleno desenvolvimento da individualidade livre e universal: essa é a perspectiva da sociedade comunista em Marx." (SAVIANI, 2015a, p.30). Isso posto, os objetivos deste artigo são: 1) Delimitar as linhas gerais do pensamento educacional de Saviani; 2) Expor a concepção metodológica defendida por ele; 3) Constituir uma abordagem metodológica para ensinar Filosofia a partir da Pedagogia Histórico-Crítica (PHC). Por ser um trabalho qualitativo, foi adotada a análise de conteúdo como procedimento metodológico, tendo as obras do próprio Saviani como fonte primária. Palavras-chave: Ensino de Filosofia. Metodologia de ensino. Pedagogia histórico-crítica. Abstract: Dermeval Saviani's historigraphic and philosophic studies have pointed to the application of the dialectical-historic-materialism to the national educational debate. In this sense, human formation emerges as the central theme of educational research, which seeks to overcome the exploratory relationship between Capital and work, marked by the alienation and oppression of men by men. As Saviani argues, "to overcome alienation in order to achieve the full development of free and universal individuality: this is the perspective of communist society in Marx." (SAVIANI, 2015a, p.30). Thus, the objectives of this article are: 1) Delimit the general lines of Saviani's educational thought; 2) Expose the methodological conception defended by him; 3) Constitute a methodological approach to teaching Philosophy from Historical-Critical Pedagogy (APS). As a qualitative work, content analysis was adopted as the methodological procedure, with Saviani's own works as the primary source. Keywords: Philosophy teaching. Educational methodology. Historical-critical pedagogy. REFERÊNCIAS ALMEIDA JÚNIOR, José Benedito. A avaliação em Filosofia. Revista Princípios, v.12, n.17-18, jan./dez. Natal, 2005, p.145-156. BRASIL. Ministério da Educação. Diretrizes Curriculares Nacionais para o Ensino Médio. Brasília, 2018. BRASIL. Ministério da Educação. Orientações curriculares para o ensino médio. v.3. Brasília: 2006. BRASIL. Ministério da Educação. Parâmetros Curriculares Nacionais Ensino Médio. Brasília, 2000. BRASIL. Ministério da Educação. PNLD 2018: Filosofia: guia de livros didáticos. Brasília, 2017. BRASIL. Palácio do Planalto. Lei nº 13.415/2017. Brasília, 2017. DUARTE, Newton.; SAVIANI, Dermeval. (org.). Pedagogia histórico-crítica e luta de classes na educação. Campinas: Autores Associados, 2012. EBY, Friedrich. História da educação moderna. 5.ed. Porto Alegre: Globo, 1978. GASPARIN, João Luiz. Uma didática para a pedagogia histórico-crítica. 5.ed. Campinas: Autores associados, 2009. GRAMSCI, Antônio. Cadernos do cárcere. Tradução Carlos Nelson Coutinho. 2.ed. Rio de Janeiro: Civilização Brasileira, 2001. v.2. p.11-53. GRAMSCI, Antônio. Concepção dialética da história. Tradução Carlos Nelson Coutinho. 2.ed. Rio de Janeiro: Civilização Brasileira, 1978. MARX, Karl. ENGELS, Friedrich. Teses sobre Feuerbach. In: MARX, Karl. ENGELS, Friedrich. A ideologia alemã. São Paulo: Editora Moraes, 1984. p. 107-111. SAVIANI, Dermeval. Educação: do senso comum à consciência filosófica. 12.ed. Autores Associados, 1996. SAVIANI, Dermeval. A nova lei da educação: trajetória, limites e perspectivas. Campinas: Autores Associados, 1997. SAVIANI, Dermeval. Escola e democracia. Campinas: Autores Associados, 2008. SAVIANI, Dermeval. Formação de professores: aspectos históricos e teóricos do problema no contexto brasileiro. Revista Brasileira de Educação v.14 n.40 jan./abr. 2009. p.143-155. SAVIANI, Dermeval. Pedagogia histórico-crítica: primeiras aproximações. 11.ed. Campinas: Autores Associados, 2013. SAVIANI, Dermeval. O conceito dialético de mediação na pedagogia histórico-crítica em intermediação com a psicologia histórico-cultural. Revista Germinal: Marxismo e Educação em Debate, v.7, n.01, jun. Salvador, 2015a. p. 26-43. SAVIANI, Dermeval. Sobre a natureza e especificidade da educação. Revista Germinal: Marxismo e Educação em Debate, v.7, n.01, jun. Salvador, 2015b. p. 286-293. VIGOTSKY, Lev Semenovitch; LURIA, Alexander Romanovich; LEONTIEV, Alexis Nikolaevich. Linguagem, desenvolvimento e aprendizagem. São Paulo: Ícone, 1988.

Published
2019
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