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2. Biological basis of extensive pleiotropy between blood traits and cancer risk

Author

Pardo-Cea, Miguel Angel, Farré, Xavier, Esteve, Anna, Palade, Joanna, Espín, Roderic, Mateo, Francesca, Alsop, Eric, Alorda, Marc, Blay, Natalia, Baiges, Alexandra, Shabbir, Arzoo, Comellas, Francesc, Gómez, Antonio, Arnan, Montserrat, Teulé, Alex, Salinas, Monica, Berrocal, Laura, Brunet, Joan, Rofes, Paula, Lázaro, Conxi, Conesa, Miquel, Rojas, Juan Jose, Velten, Lars, Fendler, Wojciech, Smyczynska, Urszula, Chowdhury, Dipanjan, Zeng, Yong, He, Housheng Hansen, Li, Rong, Van Keuren-Jensen, Kendall, de Cid, Rafael, and Pujana, Miquel Angel

Published
2024
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3. A multimodal approach for Parkinson disease analysis

Author

Faundez-Zanuy, Marcos, Satue-Villar, Antonio, Mekyska, Jiri, Arreola, Viridiana, Sanz, Pilar, Paul, Carles, Guirao, Luis, Serra, Mateu, Rofes, Laia, Clavé, Pere, Sesa-Nogueras, Enric, and Roure, Josep

Subjects
Quantitative Biology - Neurons and Cognition, Computer Science - Machine Learning
Abstract

Parkinson's disease (PD) is the second most frequent neurodegenerative disease with prevalence among general population reaching 0.1-1 %, and an annual incidence between 1.3-2.0/10000 inhabitants. The mean age at diagnosis of PD is 55 and most patients are between 50 and 80 years old. The most obvious symptoms are movement-related; these include tremor, rigidity, slowness of movement and walking difficulties. Frequently these are the symptoms that lead to the PD diagnoses. Later, thinking and behavioral problems may arise, and other symptoms include cognitive impairment and sensory, sleep and emotional problems. In this paper we will present an ongoing project that will evaluate if voice and handwriting analysis can be reliable predictors/indicators of swallowing and balance impairments in PD. An important advantage of voice and handwritten analysis is its low intrusiveness and easy implementation in clinical practice. Thus, if a significant correlation between these simple analyses and the gold standard video-fluoroscopic analysis will imply simpler and less stressing diagnostic test for the patients as well as the use of cheaper analysis systems., Comment: 10 pages

Published
2022
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4. What Drives Task Performance in Animal Fluency in Individuals Without Dementia? The SMART-MR Study

Author

Adrià Rofes, Magdalena Beran, Roel Jonkers, Mirjam I. Geerlings, and Jet M. J. Vonk

Abstract

Purpose: In this study, we aim to understand whether and how performance in animal fluency (i.e., total correct word count) relates to linguistic levels and/or executive functions by looking at sequence information and item-level metrics (i.e., clusters, switches, and word properties). Method: Seven hundred thirty-one Dutch-speaking individuals without dementia from the Second Manifestations of ARTerial disease-Magnetic Resonance study responded to an animal fluency task (120 s). We obtained cluster size and number of switches for the task, and eight different word properties for each correct word produced. We detected variables that determine total word count with random forests, and used conditional inference trees to assess points along the scales of such variables, at which total word count changes significantly. Results: Number of switches, average cluster size, lexical decision response times, word frequency, and concreteness determined total correct word count in animal fluency. People who produced more correct words produced more switches and bigger clusters. People who produced fewer words produced fewer switches and more frequent words. Conclusions: Concurrent with existing literature, individuals without dementia rely on language and executive functioning to produce words in animal fluency. The novelty of our work is that such results were shown based on a data-driven approach using sequence information and item-level metrics.

Published
2023
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12. How Are School Districts Responding to Charter Laws and Charter Schools? A Study of Eight States and the District of Columbia.

Author

Policy Analysis for California Education, Berkeley, CA. and Rofes, Eric

Abstract

This report provides findings from a study that aimed to identity: (1) the impact of charter schools on school districts; (2) the ways school districts had responded; and (3) whether districts had experienced systemic change as a result of charter laws and the opening of charter schools. The study was conducted in 1997, six years into the nation's experiment with charter schools. It focused on eight states and the District of Columbia and included case studies of 25 school districts affected by charter schools. The study revealed the following primary impacts: (1) the loss of students and often an accompanying loss of financing; (2) the loss of a particular kind of student to niche-focused charter schools; (3) the departure of significant numbers of disgruntled parents; (4) shifts in staff morale; (5) the redistribution of some central office administrators' time and increased challenges predicting student enrollment and planning grade-level placement. Of the 25 case-study districts in this research study, almost half (12 or 48%) had experienced either strong (five or 20%) or moderate (seven or 28%) impact from charter schools and slightly more than half (13 or 52%) had experienced either no impact (nine or 36%) or mild impact (four or 16%). Large urban districts had experienced significantly less impact from charters than rural, suburban, and small urban districts. (AA)

Published
1998

13. Transgression and the Situated Body: Gender, Sex, and the Gay Male Teacher.

Author

Rofes, Eric

Abstract

This paper begins by examining representations of gay male school teachers in discourses produced by gay men, illustrating the ways gay men represent themselves in public discourse. The literature is reviewed for answers to questions about the role of the gay male teacher in education and the responsibility of the gay male teacher to gay liberationist politics while working as an educator. Events from the author's own classroom are used to illustrate dilemmas he has faced as a gay male college teacher and ways he has responded. Ways are then suggested within discourses on gender, the body, and sexuality that offer opportunities for gay male teachers to recognize their potential contributions to the field of education and the lives of children more fully. The review of the literature shows that the personal narratives of gay male teachers reveal the tradeoffs lesbian, gay, bisexual, and transgender people are forced to make as they move in the public sphere. Many gay men maintain sharp divides between their sex lives and classroom lives. They usually face the choice between a committed couple relationship and desexualized behavior. There is really no room for a type of gay male identity that acknowledges the value some gay men place on the erotic. Questions that the teacher may encounter include: if the teacher believes that there are many diverse and ethical ways for people to structure their social and sexual practices, is it acceptable to affirm this in the classroom?; and, if the teacher believes in casual, nonmonogamous sex, what responsibility does he have toward gay male students? Questions the gay male teacher faces in classroom situations and other encounters with students have implications for democratic education and social change. (Contains 22 references.) (SLD)

Published
1998

15. AIDS Education under Democracy: Gay Men, Sexual Dissent, and the Limits of Prevention.

Author

Rofes, Eric

Abstract

This paper reviews past and current Acquired Immune Deficiency Syndrome (AIDS) education and prevention efforts, describes three specific phases of efforts, and analyzes AIDS education and prevention in relation to emancipatory models of education. First the paper reviews data measuring the transmission of Human Immunodeficiency Virus (HIV) among gay and bisexual men in the United States and critiques studies that found that gay men in epicenter cities had halted the spread of HIV. More recent data are presented showing increased unprotected sex among gay men and analyzing public response. Next the paper sketches HIV prevention programs that target gay and bisexual men: early pioneering work initiated by grassroots activities, first generation education programs launched in most cities from 1985 to 1990, and post-1990 responses to the dawning recognition of escalating incidence of unprotected sex. Finally, the paper raises questions about the "ownership" of HIV education and prevention programs by public health and social marketing professionals and criticizes the limited involvement by individuals in the education field. Following "gay liberation and queer theory" that have conceptualized gay men as a colonized population, the paper argues for emancipatory education based on the theories of Paulo Freire. Such education might offer important new possibilities for HIV prevention rooted in resistance, knowledge, and empowerment. (Contains 57 references.) (JB)

Published
1995

16. Queers, Education Schools, and Sex Panic.

Author

Rofes, Eric

Abstract

This paper examines education's role in addressing lesbian, gay, and bisexual issues, focusing on the role of graduate schools of education. It discusses the mission of schools of education and reviews points of conflict concerning the purpose of such schools. It then provides evidence of the vast array of contemporary lesbian and gay issues which confront educators, pointing out that if education schools were to fulfill the essence of their missions, considerable resources would be channeled into research, theory, and analysis of lesbian and gay issues in the educational arena. The paper also examines bulletins, course catalogs, and application materials from 16 graduate schools of education in order to assess the stated relationship between schools of education and lesbian and gay issues. It then discusses the personal experiences of an education graduate student interested in the study of gay and lesbian issues, as well as historical accounts of sex scandals and moral panics in educational institutions. It concludes by stating that the linkage of gay educators and children triggers real or imagined sex panic which functions to police many aspects of academic life. However, it urges educational leaders to find the courage to fulfill the mission and preserve the integrity of the discipline by interrogating controversial and vexing questions. An appendix lists the bulletins, course catalogs, and application materials reviewed. (Contains 99 references.) (MDM)

Published
1995

18. Imaging practice in low-grade gliomas among European specialized centers and proposal for a minimum core of imaging

Author

Freyschlag, Christian F., Krieg, Sandro M., Kerschbaumer, Johannes, Pinggera, Daniel, Forster, Marie-Therese, Cordier, Dominik, Rossi, Marco, Miceli, Gabriele, Roux, Alexandre, Reyes, Andrés, Sarubbo, Silvio, Smits, Anja, Sierpowska, Joanna, Robe, Pierre A., Rutten, Geert-Jan, Santarius, Thomas, Matys, Tomasz, Zanello, Marc, Almairac, Fabien, Mondot, Lydiane, Jakola, Asgeir S., Zetterling, Maria, Rofes, Adrià, von Campe, Gord, Guillevin, Remy, Bagatto, Daniele, Lubrano, Vincent, Rapp, Marion, Goodden, John, De Witt Hamer, Philip C., Pallud, Johan, Bello, Lorenzo, Thomé, Claudius, Duffau, Hugues, and Mandonnet, Emmanuel

Published
2018
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19. Imageability ratings across languages

Author

Rofes, Adrià, Zakariás, Lilla, Ceder, Klaudia, Lind, Marianne, Johansson, Monica Blom, de Aguiar, Vânia, Bjekić, Jovana, Fyndanis, Valantis, Gavarró, Anna, Simonsen, Hanne Gram, Sacristán, Carlos Hernández, Kambanaros, Maria, Kraljević, Jelena Kuvač, Martínez-Ferreiro, Silvia, Mavis, İlknur, Orellana, Carolina Méndez, Sör, Ingrid, Lukács, Ágnes, Tunçer, Müge, Vuksanović, Jasmina, Ibarrola, Amaia Munarriz, Pourquie, Marie, Varlokosta, Spyridoula, and Howard, David

Published
2018
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21. Survey on current cognitive practices within the European Low-Grade Glioma Network: towards a European assessment protocol

Author

Rofes, Adrià, Mandonnet, Emmanuel, Godden, John, Baron, Marie Hélène, Colle, Henry, Darlix, Amelie, de Aguiar, Vânia, Duffau, Hugues, Herbet, Guillaume, Klein, Martin, Lubrano, Vincent, Martino, Juan, Mathew, Ryan, Miceli, Gabriele, Moritz-Gasser, Sylvie, Pallud, Johan, Papagno, Costanza, Rech, Fabien, Robert, Erik, Rutten, Geert-Jan, Santarius, Thomas, Satoer, Djaina, Sierpowska, Joanna, Smits, Anja, Skrap, Miran, Spena, Giannantonio, Visch, Evy, De Witte, Elke, Zetterling, Maria, and Wager, Michel

Published
2017
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25. Canada: A Videotape Collection Focused on Bullying, Homophobia, and Queer Youth

Author

Rofes, Eric

Abstract

This first essay presents and reviews a collection of six videotapes produced over the past decade that focus primarily on bullying, homophobia, and LGBTQ youth. The second review details a video resource for librarians and those supportive of non-censorship of library resources to provide materials and services to GLBT&Q adolescents.

Published
2005
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27. Young Adult Reflections on Having an Openly Gay Teacher during Early Adolescence.

Author

Rofes, Eric

Abstract

Presents one teacher's story of being openly gay from 1978-83. He surveyed his former students, now in their 30s, about their experience as young adolescents with a gay teacher. Results showed that students did not necessarily confront intense concerns about it. Many noted the disparity between the intensity of the controversy and their lived experience with a gay teacher. (SM)

Published
2000

28. The Catalyst Role of Charter Schools.

Author

Rofes, Eric

Abstract

Some superintendents successfully exploit competitive intentions of the charter-school movement to improve district schools. A 1997 study of randomly selected districts found that half had experienced little financial effects from charters. Districts often lose certain ethnic groups and disgruntled parents. Ripple effects and policy recommendations are discussed. (MLH)

Published
1999

32. White Men and Affirmative Action: A Conversation.

Author

Rofes, Eric, Keiser, David, Smith, Tony, and Wray, Matt

Abstract

Presents the views of four white graduate students at the University of California, Berkeley who do not support the recent elimination of affirmative action policies for job applicants and student admissions. Their opinions argue that white men should support equity in education and society. (SLD)

Published
1997

33. Public Law, Private School: Choice, the Constitution, and Some Emerging Issues.

Author

Rofes, Peter K.

Abstract

Among types of school choice plans, most important distinction is between plans within preexisting public schools and plans that provide opportunities for students to move, at government expense, into otherwise private schools. Discusses five developments that have moved different but overlapping constituencies behind school choice. Discusses role played by Constitution in school choice programs, citing Milwaukee, Wisconsin, program. (MLF)

Published
1992

38. Toronto, Canada

Author

Rofes, Eric

Abstract

This article introduces Karleen Pendleton Jimenez's book for young children, "Are You a Boy or a Girl?", represents a landmark achievement in queer literature in the early childhood classroom and deserves special attention by pre-school and primary teachers, academics working in early childhood education, and parents, particularly parents with gender nonconforming children. It takes a great step beyond books like "William's Doll" (Zolotow, 1985) and "Oliver Button Is a Sissy" (DePaola, 1990) and opens up a conversation among young children about the rigidity of gender roles and "appropriate" activities and behavior for boys and girls. This book is important because it could be the start of classroom-based interventions to support gender nonconforming children in schools. At this point, throughout the United States and Canada, classroom teachers must take their own initiative in creating resources and support for these children. At best, gender nonconformity is addressed through new, anti-bullying curriculum or through a discussion of "tomboys" in gym class. Jimenez's book has seen strong utilization in Toronto area schools and one can hope that this classroom practice will result in program and curriculum development in the near future.

Published
2003
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39. Christchurch, New Zealand

Author

Rofes, Eric

Abstract

Out of the moral panic surrounding the education of boys comes at least one good resource: this valuable book for teachers. While work on gender theory, queer theory, and the social construction of identity (Davies, 1995) have made huge inroads within the academy over the past dozen years, such theoretical thinking often seems exiled from K-12 schools. What materials are available placing Butler (1990), Grosz (1994), Connell (1995), and Rubin (1982) at the service of schoolteachers attempting to make sense of rapidly shifting cultural understandings of sex and gender as well as the rapidly diversifying gender performances among students? "Exploring the Construction of Gender in Schools: Analysis and Action" will prove to be a hugely beneficial resource to educators seeking to initiate pioneering action research in their classrooms and schools. This small guidebook is divided in two parts. Part A provides an accessible analysis of the ways in which gender is constructed Part B, entitled "Exploring the Social Construction of Gender in Schools: A Pilot Study," presents an outline of a research project the author and colleagues have conducted, one that may be replicated by educators in local schools.

Published
2003
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41. Comprehensive analysis and ACMG-based classification ofCHEK2variants in hereditary cancer patients

Author

Vargas-Parra, G, del Valle, J, Rofes, P, Gausachs, M, Stradella, A, Moreno-Cabrera, JM, Velasco, A, Tornero, E, Menendez, M, Munoz, X, Iglesias, S, Lopez-Doriga, A, Azuara, D, Campos, O, Cuesta, R, Darder, E, de Cid, R, Gonzalez, S, Teule, A, Navarro, M, Brunet, J, Capella, G, Pineda, M, Feliubadalo, L, and Lazaro, C

Subjects
hereditary cancer, low penetrance, molecular diagnosis, variant classification, CHEK2, risk allele
Abstract

CHEK2variants are associated with intermediate breast cancer risk, among other cancers. We aimed to comprehensively describeCHEK2variants in a Spanish hereditary cancer (HC) cohort and adjust the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP) guidelines for their classification. First, threeCHEK2frequent variants were screened in a retrospective Hereditary Breast and Ovarian Cancer cohort of 516 patients. After, the wholeCHEK2coding region was analyzed by next-generation sequencing in 1848 prospective patients with HC suspicion. We refined ACMG-AMP criteria and applied different combined rules to classifyCHEK2variants and define risk alleles. We identified 10CHEK2null variants, 6 missense variants with discordant interpretation in ClinVar database, and 35 additional variants of unknown significance. Twelve variants were classified as (likely)-pathogenic; two can also be considered "established risk-alleles" and one as "likely risk-allele." The prevalence of (likely)-pathogenic variants in the HC cohort was 0.8% (1.3% in breast cancer patients and 1.0% in hereditary nonpolyposis colorectal cancer patients). Here, we provide ACMG adjustment guidelines to classifyCHEK2variants. We hope that this study would be useful for variant classification of other genes with low effect variants.

Published
2020

42. The Aftercare Survey: Assessment and intervention practices after brain tumor surgery in Europe

Author

Sierpowska, Joanna, Rofes, Adrià, Dahlslätt, Kristoffer, Mandonnet, Emmanuel, ter Laan, Mark, Połczyńska, Monika, Hamer, Philip De Witt, Halaj, Matej, Spena, Giannantonio, Meling, Torstein R, Motomura, Kazuya, Reyes, Andrés Felipe, Campos, Alexandre Rainha, Robe, Pierre A, Zigiotto, Luca, Sarubbo, Silvio, Freyschlag, Christian F, Broen, Martijn P G, Stranjalis, George, Papadopoulos, Konstantinos, Liouta, Evangelia, Rutten, Geert-Jan, Viegas, Catarina Pessanha, Silvestre, Ana, Perrote, Federico, Brochero, Natacha, Cáceres, Cynthia, Zdun-Ryżewska, Agata, Kloc, Wojciech, Satoer, Djaina, Dragoy, Olga, Hendriks, Marc P H, Alvarez-Carriles, Juan C, and Piai, Vitória

Published
2022
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43. Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification.

Author

Feroce I., Schoenwiese U., Seggewiss J., Solanes A., Steinemann D., Stiller M., Stoppa-Lyonnet D., Sullivan K.J., Susman R., Sutter C., Tavtigian S.V., Teo S.H., Teule A., Thomassen M., Tibiletti M.G., Tischkowitz M., Tognazzo S., Toland A.E., Tornero E., Torngren T., Torres-Esquius S., Toss A., Trainer A.H., Tucker K.M., van Asperen C.J., van Mackelenbergh M.T., Varesco L., Vargas-Parra G., Varon R., Vega A., Velasco A., Vesper A.-S., Viel A., Vreeswijk M.P.G., Wagner S.A., Waha A., Walker L.C., Walters R.J., Wang-Gohrke S., Weber B.H.F., Weichert W., Wieland K., Wiesmuller L., Witzel I., Wockel A., Woodward E.R., Zachariae S., Zampiga V., Zeder-Goss C., Investigators K., Lazaro C., De Nicolo A., Radice P., Engel C., Schmutzler R.K., Goldgar D.E., Spurdle A.B., Harris M., Parsons M.T., Tudini E., Li H., Hahnen E., Wappenschmidt B., Feliubadalo L., Aalfs C.M., Agata S., Aittomaki K., Alducci E., Alonso-Cerezo M.C., Arnold N., Auber B., Austin R., Azzollini J., Balmana J., Barbieri E., Bartram C.R., Blanco A., Blumcke B., Bonache S., Bonanni B., Borg A., Bortesi B., Brunet J., Bruzzone C., Bucksch K., Cagnoli G., Caldes T., Caliebe A., Caligo M.A., Calvello M., Capone G.L., Caputo S.M., Carnevali I., Carrasco E., Caux-Moncoutier V., Cavalli P., Cini G., Clarke E.M., Concolino P., Cops E.J., Cortesi L., Couch F.J., Darder E., de la Hoya M., Dean M., Debatin I., Del Valle J., Delnatte C., Derive N., Diez O., Ditsch N., Domchek S.M., Dutrannoy V., Eccles D.M., Ehrencrona H., Enders U., Evans D.G., Farra C., Faust U., Felbor U., Fine M., Foulkes W.D., Galvao H.C.R., Gambino G., Gehrig A., Gensini F., Gerdes A.-M., Germani A., Giesecke J., Gismondi V., Gomez C., Gomez Garcia E.B., Gonzalez S., Grau E., Grill S., Gross E., Guerrieri-Gonzaga A., Guillaud-Bataille M., Gutierrez-Enriquez S., Haaf T., Hackmann K., Hansen T.V.O., Hauke J., Heinrich T., Hellebrand H., Herold K.N., Honisch E., Horvath J., Houdayer C., Hubbel V., Iglesias S., Izquierdo A., James P.A., Janssen L.A.M., Jeschke U., Kaulfuss S., Keupp K., Kiechle M., Kolbl A., Krieger S., Kruse T.A., Kvist A., Lalloo F., Larsen M., Lattimore V.L., Lautrup C., Ledig S., Leinert E., Lewis A.L., Lim J., Loeffler M., Lopez-Fernandez A., Lucci-Cordisco E., Maass N., Manoukian S., Marabelli M., Matricardi L., Meindl A., Michelli R.D., Moghadasi S., Moles-Fernandez A., Montagna M., Montalban G., Monteiro A.N., Montes E., Mori L., Moserle L., Muller C.R., Mundhenke C., Naldi N., Nathanson K.L., Navarro M., Nevanlinna H., Nichols C.B., Niederacher D., Nielsen H.R., Ong K.-R., Pachter N., Palmero E.I., Papi L., Pedersen I.S., Peissel B., Perez-Segura P., Pfeifer K., Pineda M., Pohl-Rescigno E., Poplawski N.K., Porfirio B., Quante A.S., Ramser J., Reis R.M., Revillion F., Rhiem K., Riboli B., Ritter J., Rivera D., Rofes P., Rump A., Salinas M., Sanchez de Abajo A.M., Schmidt G., Feroce I., Schoenwiese U., Seggewiss J., Solanes A., Steinemann D., Stiller M., Stoppa-Lyonnet D., Sullivan K.J., Susman R., Sutter C., Tavtigian S.V., Teo S.H., Teule A., Thomassen M., Tibiletti M.G., Tischkowitz M., Tognazzo S., Toland A.E., Tornero E., Torngren T., Torres-Esquius S., Toss A., Trainer A.H., Tucker K.M., van Asperen C.J., van Mackelenbergh M.T., Varesco L., Vargas-Parra G., Varon R., Vega A., Velasco A., Vesper A.-S., Viel A., Vreeswijk M.P.G., Wagner S.A., Waha A., Walker L.C., Walters R.J., Wang-Gohrke S., Weber B.H.F., Weichert W., Wieland K., Wiesmuller L., Witzel I., Wockel A., Woodward E.R., Zachariae S., Zampiga V., Zeder-Goss C., Investigators K., Lazaro C., De Nicolo A., Radice P., Engel C., Schmutzler R.K., Goldgar D.E., Spurdle A.B., Harris M., Parsons M.T., Tudini E., Li H., Hahnen E., Wappenschmidt B., Feliubadalo L., Aalfs C.M., Agata S., Aittomaki K., Alducci E., Alonso-Cerezo M.C., Arnold N., Auber B., Austin R., Azzollini J., Balmana J., Barbieri E., Bartram C.R., Blanco A., Blumcke B., Bonache S., Bonanni B., Borg A., Bortesi B., Brunet J., Bruzzone C., Bucksch K., Cagnoli G., Caldes T., Caliebe A., Caligo M.A., Calvello M., Capone G.L., Caputo S.M., Carnevali I., Carrasco E., Caux-Moncoutier V., Cavalli P., Cini G., Clarke E.M., Concolino P., Cops E.J., Cortesi L., Couch F.J., Darder E., de la Hoya M., Dean M., Debatin I., Del Valle J., Delnatte C., Derive N., Diez O., Ditsch N., Domchek S.M., Dutrannoy V., Eccles D.M., Ehrencrona H., Enders U., Evans D.G., Farra C., Faust U., Felbor U., Fine M., Foulkes W.D., Galvao H.C.R., Gambino G., Gehrig A., Gensini F., Gerdes A.-M., Germani A., Giesecke J., Gismondi V., Gomez C., Gomez Garcia E.B., Gonzalez S., Grau E., Grill S., Gross E., Guerrieri-Gonzaga A., Guillaud-Bataille M., Gutierrez-Enriquez S., Haaf T., Hackmann K., Hansen T.V.O., Hauke J., Heinrich T., Hellebrand H., Herold K.N., Honisch E., Horvath J., Houdayer C., Hubbel V., Iglesias S., Izquierdo A., James P.A., Janssen L.A.M., Jeschke U., Kaulfuss S., Keupp K., Kiechle M., Kolbl A., Krieger S., Kruse T.A., Kvist A., Lalloo F., Larsen M., Lattimore V.L., Lautrup C., Ledig S., Leinert E., Lewis A.L., Lim J., Loeffler M., Lopez-Fernandez A., Lucci-Cordisco E., Maass N., Manoukian S., Marabelli M., Matricardi L., Meindl A., Michelli R.D., Moghadasi S., Moles-Fernandez A., Montagna M., Montalban G., Monteiro A.N., Montes E., Mori L., Moserle L., Muller C.R., Mundhenke C., Naldi N., Nathanson K.L., Navarro M., Nevanlinna H., Nichols C.B., Niederacher D., Nielsen H.R., Ong K.-R., Pachter N., Palmero E.I., Papi L., Pedersen I.S., Peissel B., Perez-Segura P., Pfeifer K., Pineda M., Pohl-Rescigno E., Poplawski N.K., Porfirio B., Quante A.S., Ramser J., Reis R.M., Revillion F., Rhiem K., Riboli B., Ritter J., Rivera D., Rofes P., Rump A., Salinas M., Sanchez de Abajo A.M., and Schmidt G.

Abstract

The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification.Copyright © 2019 Wiley Periodicals, Inc.

Published
2019

44. Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

Author

Parsons, MT, Tudini, E, Li, H, Hahnen, E, Wappenschmidt, B, Feliubadalo, L, Aalfs, CM, Agata, S, Aittomaki, K, Alducci, E, Concepcion Alonso-Cerezo, M, Arnold, N, Auber, B, Austin, R, Azzollini, J, Balmana, J, Barbieri, E, Bartram, CR, Blanco, A, Bluemcke, B, Bonache, S, Bonanni, B, Borg, A, Bortesi, B, Brunet, J, Bruzzone, C, Bucksch, K, Cagnoli, G, Caldes, T, Caliebe, A, Caligo, MA, Calvello, M, Capone, GL, Caputo, SM, Carnevali, I, Carrasco, E, Caux-Moncoutier, V, Cavalli, P, Cini, G, Clarke, EM, Concolino, P, Cops, EJ, Cortesi, L, Couch, FJ, Darder, E, de la Hoya, M, Dean, M, Debatin, I, Del Valle, J, Delnatte, C, Derive, N, Diez, O, Ditsch, N, Domchek, SM, Dutrannoy, V, Eccles, DM, Ehrencrona, H, Enders, U, Evans, DG, Farra, C, Faust, U, Felbor, U, Feroce, I, Fine, M, Foulkes, WD, Galvao, HC, Gambino, G, Gehrig, A, Gensini, F, Gerdes, A-M, Germani, A, Giesecke, J, Gismondi, V, Gomez, C, Garcia, EBG, Gonzalez, S, Grau, E, Grill, S, Gross, E, Guerrieri-Gonzaga, A, Guillaud-Bataille, M, Gutierrez-Enriquez, S, Haaf, T, Hackmann, K, Hansen, TV, Harris, M, Hauke, J, Heinrich, T, Hellebrand, H, Herold, KN, Honisch, E, Horvath, J, Houdayer, C, Huebbel, V, Iglesias, S, Izquierdo, A, James, PA, Janssen, LA, Jeschke, U, Kaulfuss, S, Keupp, K, Kiechle, M, Koelbl, A, Krieger, S, Kruse, TA, Kvist, A, Lalloo, F, Larsen, M, Lattimore, VL, Lautrup, C, Ledig, S, Leinert, E, Lewis, AL, Lim, J, Loeffler, M, Lopez-Fernandez, A, Lucci-Cordisco, E, Maass, N, Manoukian, S, Marabelli, M, Matricardi, L, Meindl, A, Michelli, RD, Moghadasi, S, Moles-Fernandez, A, Montagna, M, Montalban, G, Monteiro, AN, Montes, E, Mori, L, Moserle, L, Mueller, CR, Mundhenke, C, Naldi, N, Nathanson, KL, Navarro, M, Nevanlinna, H, Nichols, CB, Niederacher, D, Nielsen, HR, Ong, K-R, Pachter, N, Palmero, E, Papi, L, Pedersen, IS, Peissel, B, Perez-Segura, P, Pfeifer, K, Pineda, M, Pohl-Rescigno, E, Poplawski, NK, Porfirio, B, Quante, AS, Ramser, J, Reis, RM, Revillion, F, Rhiem, K, Riboli, B, Ritter, J, Rivera, D, Rofes, P, Rump, A, Salinas, M, Sanchez de Abajo, AM, Schmidt, G, Schoenwiese, U, Seggewiss, J, Solanes, A, Steinemann, D, Stiller, M, Stoppa-Lyonnet, D, Sullivan, KJ, Susman, R, Sutter, C, Tavtigian, S, Teo, SH, Teule, A, Thomassen, M, Tibiletti, MG, Tischkowitz, M, Tognazzo, S, Toland, AE, Tornero, E, Torngren, T, Torres-Esquius, S, Toss, A, Trainer, AH, Tucker, KM, van Asperen, CJ, van Mackelenbergh, MT, Varesco, L, Vargas-Parra, G, Varon, R, Vega, A, Velasco, A, Vesper, A-S, Viel, A, Vreeswijk, MPG, Wagner, SA, Waha, A, Walker, LC, Walters, RJ, Wang-Gohrke, S, Weber, BHF, Weichert, W, Wieland, K, Wiesmueller, L, Witzel, I, Woeckel, A, Woodward, ER, Zachariae, S, Zampiga, V, Zeder-Goss, C, Lazaro, C, De Nicolo, A, Radice, P, Engel, C, Schmutzler, RK, Goldgar, DE, Spurdle, AB, Parsons, MT, Tudini, E, Li, H, Hahnen, E, Wappenschmidt, B, Feliubadalo, L, Aalfs, CM, Agata, S, Aittomaki, K, Alducci, E, Concepcion Alonso-Cerezo, M, Arnold, N, Auber, B, Austin, R, Azzollini, J, Balmana, J, Barbieri, E, Bartram, CR, Blanco, A, Bluemcke, B, Bonache, S, Bonanni, B, Borg, A, Bortesi, B, Brunet, J, Bruzzone, C, Bucksch, K, Cagnoli, G, Caldes, T, Caliebe, A, Caligo, MA, Calvello, M, Capone, GL, Caputo, SM, Carnevali, I, Carrasco, E, Caux-Moncoutier, V, Cavalli, P, Cini, G, Clarke, EM, Concolino, P, Cops, EJ, Cortesi, L, Couch, FJ, Darder, E, de la Hoya, M, Dean, M, Debatin, I, Del Valle, J, Delnatte, C, Derive, N, Diez, O, Ditsch, N, Domchek, SM, Dutrannoy, V, Eccles, DM, Ehrencrona, H, Enders, U, Evans, DG, Farra, C, Faust, U, Felbor, U, Feroce, I, Fine, M, Foulkes, WD, Galvao, HC, Gambino, G, Gehrig, A, Gensini, F, Gerdes, A-M, Germani, A, Giesecke, J, Gismondi, V, Gomez, C, Garcia, EBG, Gonzalez, S, Grau, E, Grill, S, Gross, E, Guerrieri-Gonzaga, A, Guillaud-Bataille, M, Gutierrez-Enriquez, S, Haaf, T, Hackmann, K, Hansen, TV, Harris, M, Hauke, J, Heinrich, T, Hellebrand, H, Herold, KN, Honisch, E, Horvath, J, Houdayer, C, Huebbel, V, Iglesias, S, Izquierdo, A, James, PA, Janssen, LA, Jeschke, U, Kaulfuss, S, Keupp, K, Kiechle, M, Koelbl, A, Krieger, S, Kruse, TA, Kvist, A, Lalloo, F, Larsen, M, Lattimore, VL, Lautrup, C, Ledig, S, Leinert, E, Lewis, AL, Lim, J, Loeffler, M, Lopez-Fernandez, A, Lucci-Cordisco, E, Maass, N, Manoukian, S, Marabelli, M, Matricardi, L, Meindl, A, Michelli, RD, Moghadasi, S, Moles-Fernandez, A, Montagna, M, Montalban, G, Monteiro, AN, Montes, E, Mori, L, Moserle, L, Mueller, CR, Mundhenke, C, Naldi, N, Nathanson, KL, Navarro, M, Nevanlinna, H, Nichols, CB, Niederacher, D, Nielsen, HR, Ong, K-R, Pachter, N, Palmero, E, Papi, L, Pedersen, IS, Peissel, B, Perez-Segura, P, Pfeifer, K, Pineda, M, Pohl-Rescigno, E, Poplawski, NK, Porfirio, B, Quante, AS, Ramser, J, Reis, RM, Revillion, F, Rhiem, K, Riboli, B, Ritter, J, Rivera, D, Rofes, P, Rump, A, Salinas, M, Sanchez de Abajo, AM, Schmidt, G, Schoenwiese, U, Seggewiss, J, Solanes, A, Steinemann, D, Stiller, M, Stoppa-Lyonnet, D, Sullivan, KJ, Susman, R, Sutter, C, Tavtigian, S, Teo, SH, Teule, A, Thomassen, M, Tibiletti, MG, Tischkowitz, M, Tognazzo, S, Toland, AE, Tornero, E, Torngren, T, Torres-Esquius, S, Toss, A, Trainer, AH, Tucker, KM, van Asperen, CJ, van Mackelenbergh, MT, Varesco, L, Vargas-Parra, G, Varon, R, Vega, A, Velasco, A, Vesper, A-S, Viel, A, Vreeswijk, MPG, Wagner, SA, Waha, A, Walker, LC, Walters, RJ, Wang-Gohrke, S, Weber, BHF, Weichert, W, Wieland, K, Wiesmueller, L, Witzel, I, Woeckel, A, Woodward, ER, Zachariae, S, Zampiga, V, Zeder-Goss, C, Lazaro, C, De Nicolo, A, Radice, P, Engel, C, Schmutzler, RK, Goldgar, DE, and Spurdle, AB

Abstract

The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification.

Published
2019

45. Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

Author

Parsons, M. T., Tudini, E., Li, H., Hahnen, E., Wappenschmidt, B., Feliubadalo, L., Aalfs, C. M., Agata, S., Aittomaki, K., Alducci, E., Alonso-Cerezo, M. C., Arnold, N., Auber, B., Austin, R., Azzollini, J., Balmana, J., Barbieri, E., Bartram, C. R., Blanco, A., Blumcke, B., Bonache, S., Bonanni, B., Borg, A., Bortesi, B., Brunet, J., Bruzzone, C., Bucksch, K., Cagnoli, G., Caldes, T., Caliebe, A., Caligo, M. A., Calvello, M., Capone, G. L., Caputo, S. M., Carnevali, I., Carrasco, E., Caux-Moncoutier, V., Cavalli, P., Cini, G., Clarke, E. M., Concolino, Paola, Cops, E. J., Cortesi, L., Couch, F. J., Darder, E., de la Hoya, M., Dean, M., Debatin, I., Del Valle, J., Delnatte, C., Derive, N., Diez, O., Ditsch, N., Domchek, S. M., Dutrannoy, V., Eccles, D. M., Ehrencrona, H., Enders, U., Evans, D. G., Farra, C., Faust, U., Felbor, U., Feroce, I., Fine, M., Foulkes, W. D., Galvao, H. C. R., Gambino, G., Gehrig, A., Gensini, F., Gerdes, A. -M., Germani, A., Giesecke, J., Gismondi, V., Gomez, C., Gomez Garcia, E. B., Gonzalez, S., Grau, E., Grill, S., Gross, E., Guerrieri-Gonzaga, A., Guillaud-Bataille, M., Gutierrez-Enriquez, S., Haaf, T., Hackmann, K., Hansen, T. V. O., Harris, M., Hauke, J., Heinrich, T., Hellebrand, H., Herold, K. N., Honisch, E., Horvath, J., Houdayer, C., Hubbel, V., Iglesias, S., Izquierdo, A., James, P. A., Janssen, L. A. M., Jeschke, U., Kaulfuss, S., Keupp, K., Kiechle, M., Kolbl, A., Krieger, S., Kruse, T. A., Kvist, A., Lalloo, F., Larsen, M., Lattimore, V. L., Lautrup, C., Ledig, S., Leinert, E., Lewis, A. L., Lim, J., Loeffler, M., Lopez-Fernandez, A., Lucci Cordisco, Emanuela, Maass, N., Manoukian, S., Marabelli, M., Matricardi, L., Meindl, A., Michelli, R. D., Moghadasi, S., Moles-Fernandez, A., Montagna, M., Montalban, G., Monteiro, A. N., Montes, E., Mori, L., Moserle, L., Muller, C. R., Mundhenke, C., Naldi, N., Nathanson, K. L., Navarro, M., Nevanlinna, H., Nichols, C. B., Niederacher, D., Nielsen, H. R., Ong, K. -R., Pachter, N., Palmero, E. I., Papi, L., Pedersen, I. S., Peissel, B., Perez-Segura, P., Pfeifer, K., Pineda, M., Pohl-Rescigno, E., Poplawski, N. K., Porfirio, B., Quante, A. S., Ramser, J., Reis, R. M., Revillion, F., Rhiem, K., Riboli, B., Ritter, J., Rivera, D., Rofes, P., Rump, A., Salinas, M., Sanchez de Abajo, A. M., Schmidt, G., Schoenwiese, U., Seggewiss, J., Solanes, A., Steinemann, D., Stiller, M., Stoppa-Lyonnet, D., Sullivan, K. J., Susman, R., Sutter, C., Tavtigian, S. V., Teo, S. H., Teule, A., Thomassen, M., Tibiletti, M. G., Tischkowitz, M., Tognazzo, S., Toland, A. E., Tornero, E., Torngren, T., Torres-Esquius, S., Toss, A., Trainer, A. H., Tucker, K. M., van Asperen, C. J., van Mackelenbergh, M. T., Varesco, L., Vargas-Parra, G., Varon, R., Vega, A., Velasco, A., Vesper, A. -S., Viel, A., Vreeswijk, M. P. G., Wagner, S. A., Waha, A., Walker, L. C., Walters, R. J., Wang-Gohrke, S., Weber, B. H. F., Weichert, W., Wieland, K., Wiesmuller, L., Witzel, I., Wockel, A., Woodward, E. R., Zachariae, S., Zampiga, V., Zeder-Goss, C., Investigators, K., Lazaro, C., De Nicolo, A., Radice, P., Engel, C., Schmutzler, R. K., Goldgar, D. E., Spurdle, A. B., Concolino P., Lucci Cordisco E. (ORCID:0000-0002-6279-7604), Parsons, M. T., Tudini, E., Li, H., Hahnen, E., Wappenschmidt, B., Feliubadalo, L., Aalfs, C. M., Agata, S., Aittomaki, K., Alducci, E., Alonso-Cerezo, M. C., Arnold, N., Auber, B., Austin, R., Azzollini, J., Balmana, J., Barbieri, E., Bartram, C. R., Blanco, A., Blumcke, B., Bonache, S., Bonanni, B., Borg, A., Bortesi, B., Brunet, J., Bruzzone, C., Bucksch, K., Cagnoli, G., Caldes, T., Caliebe, A., Caligo, M. A., Calvello, M., Capone, G. L., Caputo, S. M., Carnevali, I., Carrasco, E., Caux-Moncoutier, V., Cavalli, P., Cini, G., Clarke, E. M., Concolino, Paola, Cops, E. J., Cortesi, L., Couch, F. J., Darder, E., de la Hoya, M., Dean, M., Debatin, I., Del Valle, J., Delnatte, C., Derive, N., Diez, O., Ditsch, N., Domchek, S. M., Dutrannoy, V., Eccles, D. M., Ehrencrona, H., Enders, U., Evans, D. G., Farra, C., Faust, U., Felbor, U., Feroce, I., Fine, M., Foulkes, W. D., Galvao, H. C. R., Gambino, G., Gehrig, A., Gensini, F., Gerdes, A. -M., Germani, A., Giesecke, J., Gismondi, V., Gomez, C., Gomez Garcia, E. B., Gonzalez, S., Grau, E., Grill, S., Gross, E., Guerrieri-Gonzaga, A., Guillaud-Bataille, M., Gutierrez-Enriquez, S., Haaf, T., Hackmann, K., Hansen, T. V. O., Harris, M., Hauke, J., Heinrich, T., Hellebrand, H., Herold, K. N., Honisch, E., Horvath, J., Houdayer, C., Hubbel, V., Iglesias, S., Izquierdo, A., James, P. A., Janssen, L. A. M., Jeschke, U., Kaulfuss, S., Keupp, K., Kiechle, M., Kolbl, A., Krieger, S., Kruse, T. A., Kvist, A., Lalloo, F., Larsen, M., Lattimore, V. L., Lautrup, C., Ledig, S., Leinert, E., Lewis, A. L., Lim, J., Loeffler, M., Lopez-Fernandez, A., Lucci Cordisco, Emanuela, Maass, N., Manoukian, S., Marabelli, M., Matricardi, L., Meindl, A., Michelli, R. D., Moghadasi, S., Moles-Fernandez, A., Montagna, M., Montalban, G., Monteiro, A. N., Montes, E., Mori, L., Moserle, L., Muller, C. R., Mundhenke, C., Naldi, N., Nathanson, K. L., Navarro, M., Nevanlinna, H., Nichols, C. B., Niederacher, D., Nielsen, H. R., Ong, K. -R., Pachter, N., Palmero, E. I., Papi, L., Pedersen, I. S., Peissel, B., Perez-Segura, P., Pfeifer, K., Pineda, M., Pohl-Rescigno, E., Poplawski, N. K., Porfirio, B., Quante, A. S., Ramser, J., Reis, R. M., Revillion, F., Rhiem, K., Riboli, B., Ritter, J., Rivera, D., Rofes, P., Rump, A., Salinas, M., Sanchez de Abajo, A. M., Schmidt, G., Schoenwiese, U., Seggewiss, J., Solanes, A., Steinemann, D., Stiller, M., Stoppa-Lyonnet, D., Sullivan, K. J., Susman, R., Sutter, C., Tavtigian, S. V., Teo, S. H., Teule, A., Thomassen, M., Tibiletti, M. G., Tischkowitz, M., Tognazzo, S., Toland, A. E., Tornero, E., Torngren, T., Torres-Esquius, S., Toss, A., Trainer, A. H., Tucker, K. M., van Asperen, C. J., van Mackelenbergh, M. T., Varesco, L., Vargas-Parra, G., Varon, R., Vega, A., Velasco, A., Vesper, A. -S., Viel, A., Vreeswijk, M. P. G., Wagner, S. A., Waha, A., Walker, L. C., Walters, R. J., Wang-Gohrke, S., Weber, B. H. F., Weichert, W., Wieland, K., Wiesmuller, L., Witzel, I., Wockel, A., Woodward, E. R., Zachariae, S., Zampiga, V., Zeder-Goss, C., Investigators, K., Lazaro, C., De Nicolo, A., Radice, P., Engel, C., Schmutzler, R. K., Goldgar, D. E., Spurdle, A. B., Concolino P., and Lucci Cordisco E. (ORCID:0000-0002-6279-7604)

Abstract

The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification.

Published
2019

46. Opening Up the Classroom Closet: Responding to the Educational Needs of Gay and Lesbian Youth.

Author

Rofes, Eric

Abstract

Argues that schools, denying the existence of gay and lesbian youth, have failed to meet their educational and social service needs. Presents two models: Project 10, a Los Angeles dropout prevention program offering education, counseling, and support services; and the Harvey Milk School, an alternative New York high school. (SK)

Published
1989

47. Improving Genetic Testing in Hereditary Cancer by RNA Analysis

Author

Rofes, Paula, Menéndez, Mireia, González, Sara, Tornero, Eva, Gómez, Carolina, Vargas-Parra, Gardenia, Montes, Eva, Salinas, Mónica, Solanes, Ares, Brunet, Joan, Teulé, Alex, Capellá, Gabriel, Feliubadaló, Lídia, del Valle, Jesús, Pineda, Marta, and Lázaro, Conxi

Abstract

RNA analyses are a potent tool to identify spliceogenic effects of DNA variants, although they are time-consuming and cannot always be performed. We present splicing assays of 20 variants that represent a variety of mutation types in 10 hereditary cancer genes and attempt to incorporate these results into American College of Medical Genetics and Genomics (ACMG) classification guidelines. Sixteen single-nucleotide variants, 3 exon duplications, and 1 single-exon deletion were selected and prioritized by in silicoalgorithms. RNA was extracted from short-term lymphocyte cultures to perform RT-PCR and Sanger sequencing, and allele-specific expression was assessed whenever possible. Aberrant transcripts were detected in 14 variants (70%). Variant interpretation was difficult, especially comparing old classification standards to generic ACMG guidelines and a proposal was devised to weigh functional analyses at RNA level. According to the ACMG guidelines, only 12 variants were reclassified as pathogenic/likely pathogenic because the other two variants did not gather enough evidence. This study highlights the importance of RNA studies to improve variant classification. However, it also indicates the challenge of incorporating these results into generic ACMG guidelines and the need to refine these criteria gene specifically. Nevertheless, 60% of variants were reclassified, thus improving genetic counseling and surveillance for carriers of these variants.

Published
2020
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48. Variability and temporality of lithic production in Epipaleolithic to Early Neolithic occupations at Cova del Vidre (Catalonia, Spain)

Author

Gironès-Rofes, Ivan, Bosch-Argilagós, Josep, Bach-Gómez, Anna, Molist, Miquel, and Pardo-Gordó, Salvador

Abstract

•The analysis of the lithic industry from Cova del Vidre defines its evolutionary changes between 10.800-5.000 cal. BC.•A new C14 date is presented in the Sauveterrian phase allowing it to model and fix its lithics to the chronological sequence.•The lithic production for each phase is in line with the traits of Western Mediterranean except for Late Mesolithic.

Published
2024
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49. Cognitive and language performance predicts effects of spelling intervention and tDCS in Primary Progressive Aphasia

Author

de Aguiar, Vânia, Zhao, Yi, Ficek, Bronte N., Webster, Kimberly, Rofes, Adrià, Wendt, Haley, Frangakis, Constantine, Caffo, Brian, Hillis, Argye E., Rapp, Brenda, and Tsapkini, Kyrana

Abstract

Predictors of treatment effects allow individual tailoring of treatment characteristics, thereby saving resources and optimizing outcomes. Electrical stimulation coupled with language intervention has shown promising results in improving language performance in individuals with Primary Progressive Aphasia (PPA). The current study aimed to identify language and cognitive variables associated with response to therapy consisting of language intervention combined with transcranial direct current stimulation (tDCS). Forty individuals with PPA received written naming/spelling intervention combined with anodal tDCS or Sham, using a between-subjects, randomized design, with intervention delivered over a period of 3 weeks. Participants were assessed using a battery of neuropsychological tests before and after each phase. We measured letter accuracy during spelling of trained and untrained words, before, immediately after, 2 weeks, and 2 months after therapy. We used step-wise regression methods to identify variables amongst the neuropsychological measures and experimental factors that were significantly associated with therapy outcomes at each time-point. For trained words, improvement was related to pre-therapy scores, in RAVLT (5 trials sum), pseudoword spelling, object naming, digit span backward, spatial span backward and years post symptom onset. Regarding generalization to untrained words, improvement in spelling was associated with pseudoword spelling, RAVLT proactive interference, RAVLT immediate recall. Generalization effects were larger under tDCS compared to Sham at the 2-month post training measurement. We conclude that, for trained words, patients who improve the most are those who retain for longer language skills such as sublexical spelling processes (phoneme-to-grapheme correspondences) and word retrieval, and other cognitive functions such as executive functions and working memory, and those who have a better learning capacity. Generalization to untrained words occurs through improvement in knowledge of phoneme-to-grapheme correspondences. Furthermore, tDCS enhances the generalizability and duration of therapy effects.

Published
2020
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