Interdisciplinary risk counseling for hereditary breast and ovarian cancer: real-world data from a specialized center

Purpose Hereditary breast and ovarian cancer has long been established to affect a considerable number of patients and their families. By identifying those at risk ideally before they have been diagnosed with breast and/or ovarian cancer, access to preventive measures, intensified screening and special therapeutic options can be obtained, and thus, prognosis can be altered beneficially. Therefore, a standardized screening and counseling process has been established in Germany under the aegis of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC). As one of these specialized clinics, the HBOC-Center at Charite offers genetic counseling as well as genetic analysis based on the GC-HBOC standards. This analysis aims first at depicting this process from screening through counseling to genetic analysis as well as the patient collective and second at correlating the results of genetic analysis performed. Thus, real-world data from an HBOC-Center with a substantial patient collective and a high frequency of pathogenic variants in various genes shall be presented. Methods The data of 2531 people having been counseled at the HBOC-Center at Charite in 2016 and 2017 were analyzed in terms of patient and family history as well as pathogenic variants detected during genetic analysis with the TruRisk (R) gene panel when genetic analysis was conducted. This standardized analysis is compiled and regularly adjusted by the GCHBOC. The following genes were included at time of research: BRCA1, BRCA2, ATM, CDH1, CHEK2, PALB2, RAD51C, RAD51D, NBN, and TP53. Results Genetic analysis was conducted in 59.8% of all cases meeting the criteria for genetic analysis and 286 pathogenic variants were detected among 278 (30.3%) counselees tested using the TruRisk (R) gene panel. These were primarily found in the genes BRCA1 (44.8%) and BRCA2 (28.3%) but also in CHEK2 (12.2%), ATM (5.6%) and PALB2 (3.5%). The highest prevalence of pathogenic variants was seen among the families with both ovarian and breast cancer (50.5%), followed by families with ovarian cancer only (43.2%) and families with breast cancer only (35.6%)-these differences are statistically significant (p < 0.001). Considering breast cancer subtypes, the highest rate of pathogenic variants was detected among patients with triple-negative breast cancer (40.7%) and among patients who had had been diagnosed with triple-negative breast cancer before the age of 40 (53.4%)-both observations proved to be statistically significant (p = 0.003 and p = 0.001). Conclusion Genetic counseling and analysis provide the foundation in the prevention and therapy of hereditary breast and ovarian cancer. The rate of pathogenic variants detected is associated with family history as well as breast cancer subtype and age at diagnosis, and can reach considerable dimensions. Therefore, a standardized process of identification, genetic counseling and genetic analysis deems mandatory

Paradigmatic Approach to Support Personalized Counseling With Digital Health (iKNOW)

iKNOW is the first evidence-based digital tool to support personalized counseling for women in Germany with a hereditary cancer risk. The counseling tool is designed for carriers of pathogenic gBRCA (germline breast cancer gene) variants that increase the lifetime risk of breast and ovarian cancer. Carriers of pathogenic variants are confronted with complex, individualized risk information, and physicians must be able to convey this information in a comprehensible way to enable preference-sensitive health decisions. In this paper, we elaborate on the clinical, regulatory, and practical premises of personalized counseling in Germany. By operationalizing these premises, we formulate 5 design principles that, we suggest, are specific enough to develop a digital tool (eg, iKNOW), yet wide-ranging enough to inform the development of counseling tools for personalized medicine more generally: (1) digital counseling tools should implement the current standard of care (eg, based on guidelines); (2) digital counseling tools should help to both standardize and personalize the counseling process (eg, by enabling the preference-sensitive selection of counseling contents from a common information base); (3) digital counseling tools should make complex information easy to access both cognitively (eg, by using evidenced-based risk communication formats) and technically (eg, by means of responsive design for various devices); (4) digital counseling tools should respect the counselee's data privacy rights (eg, through strict pseudonymization and opt-in consent); and (5) digital counseling tools should be systematically and iteratively evaluated with the users in mind (eg, using formative prototype testing to ensure a user-centric design and a summative multicenter, randomized controlled trial). On the basis of these paradigmatic design principles, we hope that iKNOW can serve as a blueprint for the development of more digital innovations to support personalized counseling approaches in cancer medicine

Discutindo a educação ambiental no cotidiano escolar: desenvolvimento de projetos na escola formação inicial e continuada de professores

A presente pesquisa buscou discutir como a Educação Ambiental (EA) vem sendo trabalhada, no Ensino Fundamental e como os docentes desta escola compreendem e vem inserindo a EA no cotidiano escolar., em uma escola estadual do município de Tangará da Serra/MT, Brasil. Para tanto, realizou-se entrevistas com os professores que fazem parte de um projeto interdisciplinar de EA na escola pesquisada. Verificou-se que o projeto da escola não vem conseguindo alcançar os objetivos propostos por: desconhecimento do mesmo, pelos professores; formação deficiente dos professores, não entendimento da EA como processo de ensino-aprendizagem, falta de recursos didáticos, planejamento inadequado das atividades. A partir dessa constatação, procurou-se debater a impossibilidade de tratar do tema fora do trabalho interdisciplinar, bem como, e principalmente, a importância de um estudo mais aprofundado de EA, vinculando teoria e prática, tanto na formação docente, como em projetos escolares, a fim de fugir do tradicional vínculo “EA e ecologia, lixo e horta”.Facultad de Humanidades y Ciencias de la Educació

Simulation der Exposition des menschlichen Körpers durch magnetoquasistatische Felder von induktiven Ladesystemen in Automobilen

Es wurden drei Zweischritt-Verfahren für elektromagnetische Umweltverträglichkeitsuntersuchungen der magneto-quasistatischen Feldexposition biologischer Organismen basierend auf der Scaled-Frequency FDTD Methode sowie der Scalar Potential Finite Difference Methode vorgestellt. Diese Verfahren wurden entwickelt und angewandt für magnetische Expositionsszenarien von Personen im Umfeld von Kraftfahrzeugen über induktiven Ladestationen. Die Verfahren erlauben die effiziente Verwendung hochrealistischer Modellgeometrien. Die Zweischritt-Verfahren erfordern geringerer Aufwand bei der erforderlichen Gitterauflösung und erzielten eine Reduktion des numerischen Simulationsaufwandes gegenüber monolithischen Simulationen

Paradigmatic Approach to Support Personalized Counseling With Digital Health (iKNOW)

iKNOW is the first evidence-based digital tool to support personalized counseling for women in Germany with a hereditary cancer risk. The counseling tool is designed for carriers of pathogenic gBRCA (germline breast cancer gene) variants that increase the lifetime risk of breast and ovarian cancer. Carriers of pathogenic variants are confronted with complex, individualized risk information, and physicians must be able to convey this information in a comprehensible way to enable preference-sensitive health decisions. In this paper, we elaborate on the clinical, regulatory, and practical premises of personalized counseling in Germany. By operationalizing these premises, we formulate 5 design principles that, we suggest, are specific enough to develop a digital tool (eg, iKNOW), yet wide-ranging enough to inform the development of counseling tools for personalized medicine more generally: (1) digital counseling tools should implement the current standard of care (eg, based on guidelines); (2) digital counseling tools should help to both standardize and personalize the counseling process (eg, by enabling the preference-sensitive selection of counseling contents from a common information base); (3) digital counseling tools should make complex information easy to access both cognitively (eg, by using evidenced-based risk communication formats) and technically (eg, by means of responsive design for various devices); (4) digital counseling tools should respect the counselee’s data privacy rights (eg, through strict pseudonymization and opt-in consent); and (5) digital counseling tools should be systematically and iteratively evaluated with the users in mind (eg, using formative prototype testing to ensure a user-centric design and a summative multicenter, randomized controlled trial). On the basis of these paradigmatic design principles, we hope that iKNOW can serve as a blueprint for the development of more digital innovations to support personalized counseling approaches in cancer medicine

Flight-to-quality, economic fundamentals, and stock returns

Due to copyright restrictions, the access to the full text of this article is only available via subscription.We find that the order flow differential (OFD), a flight-to-quality measure constructed as the difference between large- and small-cap stock order flows, strongly and negatively forecasts output growth and interest rates in the U.S. The predictive ability of OFD for future macroeconomic fundamentals is robust to the inclusion of return factors and business cycle predictors, and it is thus a state variable candidate in the spirit of Merton (1973). Consistent with this view, we document that OFD commands a statistically significant negative risk premium in cross-sectional asset pricing tests

Paradigmatic Approach to Support Personalized Counseling With Digital Health (iKNOW)

iKNOW is the first evidence-based digital tool to support personalized counseling for women in Germany with a hereditary cancer risk. The counseling tool is designed for carriers of pathogenic gBRCA (germline breast cancer gene) variants that increase the lifetime risk of breast and ovarian cancer. Carriers of pathogenic variants are confronted with complex, individualized risk information, and physicians must be able to convey this information in a comprehensible way to enable preference-sensitive health decisions. In this paper, we elaborate on the clinical, regulatory, and practical premises of personalized counseling in Germany. By operationalizing these premises, we formulate 5 design principles that, we suggest, are specific enough to develop a digital tool (eg, iKNOW), yet wide-ranging enough to inform the development of counseling tools for personalized medicine more generally: (1) digital counseling tools should implement the current standard of care (eg, based on guidelines); (2) digital counseling tools should help to both standardize and personalize the counseling process (eg, by enabling the preference-sensitive selection of counseling contents from a common information base); (3) digital counseling tools should make complex information easy to access both cognitively (eg, by using evidenced-based risk communication formats) and technically (eg, by means of responsive design for various devices); (4) digital counseling tools should respect the counselee’s data privacy rights (eg, through strict pseudonymization and opt-in consent); and (5) digital counseling tools should be systematically and iteratively evaluated with the users in mind (eg, using formative prototype testing to ensure a user-centric design and a summative multicenter, randomized controlled trial). On the basis of these paradigmatic design principles, we hope that iKNOW can serve as a blueprint for the development of more digital innovations to support personalized counseling approaches in cancer medicine

Targeting HSP90 dimerization via the C-terminus is effective in imatinib resistant CML and lacks heat shock response

Heat shock protein 90 (HSP90) stabilizes many client proteins including BCR-ABL1 oncoprotein. BCR-ABL1 is the hallmark of CML in which treatment-free remission (TFR) is limited with clinical and economic consequences. Thus, there is an urgent need for novel therapeutics, which synergize with current treatment approaches. Several inhibitors targeting the N-terminal domain (NTD) of HSP90 are under investigation; however, side effects such as induction of heat shock response (HSR) and toxicity have so far precluded their FDA approval. We have developed a novel inhibitor (referred to as aminoxyrone) of HSP90 function by targeting HSP90 dimerization via the C-terminal domain (CTD). This was achieved by structure-based molecular design, chemical synthesis, and functional pre-clinical in vitro and in vivo validation using CML cell lines and patient-derived CML cells. Aminoxyrone (AX) is a promising potential candidate, which induces apoptosis in leukemic stem cells (LSCs) fraction (CD34+CD38-) as well as the leukemic bulk (CD34+CD38+) of primary CML and in TKI-resistant cells. Furthermore, BCR-ABL1 oncoprotein and related pro-oncogenic cellular responses are downregulated and targeting HSP90 C-terminus by AX does not induce HSR in vitro and in vivo. We also probed the potential of AX in other therapy refractory leukemia such as BCR-ABL1+ BCP-ALL, FLT3-ITD+ AML and Ph-like BCP-ALL. Therefore, AX is the first peptidometic C-terminal HSP90 inhibitor with the potential to increase TFR in TKI sensitive and refractory CML patients and also offers a novel therapeutic option for patients with other therapy-refractory leukemia, due to its low toxicity profile and lack of HSR