Approaches to consider heterogeneity - task adaptation for inclusive mathematics education in a professional development program

Der Adaption von Aufgaben kommt im inklusiven Unterricht eine besondere Bedeutung zu. In diesem Beitrag werden Maßnahmen zur Berücksichtigung von Heterogenität vorgestellt, die Lehrkräfte bei der Anforderung, Aufgaben für den Einsatz im inklusiven Mathematikunterricht zu adaptieren, nutzen können. Sowohl die theoretische und empirische Fundierung der Maßnahmen als auch ihr vielseitiger Einsatz in einer digitalen Fortbildung für Lehrkräfte der Sekundarstufe I werden erläutert. Die beispielhaften Konkretisierungen, wie die Maßnahmen in der Fortbildung verwendet wurden, zeigen auf, wie die Adaption von Aufgaben für inklusiven Mathematikunterricht in einer Fortbildung thematisiert werden kann. Es wird dargestellt, wie die Maßnahmen in der Fortbildung im Kontext einer Geometrieaufgabe erläutert wurden, wie diese auf eine Lernumgebung zur Einführung in Wahrscheinlichkeit angewendet wurden und inwiefern die Lehrkräfte die Maßnahmen für die weitere Adaption von Aufgaben auch vor dem Hintergrund ihres eigenen Unterrichts nutzten. Dabei wird durchweg eine Verbindung von Fach- und Entwicklungsorientierung herausgearbeitet, indem fachlich-fachdidaktische Überlegungen und entwicklungsorientierte Ausführungen insbesondere in den Bereichen Lernentwicklung sowie Entwicklung des sprachlichen und kommunikativen Handelns verknüpft werden. (DIPF/Orig.)The adaptation of tasks is particularly important in inclusive settings. This article presents approaches to consider heterogeneity, which teachers can use to adapt tasks for inclusive mathematics settings. The theoretical and empirical foundation of the approaches as well as their versatile use in a digital professional development (PD) program for secondary teachers are explained. The exemplarily concretion of how the approaches were used in the PD program focus on how the adaptation of tasks for inclusive mathematics teaching can be addressed in a PD program. It is shown how the approaches were explained in the PD program in the context of a geometry task, how these were applied to a learning environment on introducing probability and to what extent the teachers used the approaches for the further adaptation of tasks also against the background of their own teaching practice. Throughout, a connection between a subject-specific view and a developmental orientation is considered by linking subject-specific considerations and development-oriented explanations especially concerning students with special needs regarding learning difficulties and low (academic) language proficiency. (DIPF/Orig.

Inhibitors of Bcl-2 and Bruton's tyrosine kinase synergize to abrogate diffuse large B-cell lymphoma growth in vitro and in orthotopic xenotransplantation models

Numerous targeted therapies have been developed for diffuse large B-cell lymphoma, but the results of late-stage clinical trials were mostly disappointing and have led to very few new regulatory approvals. Here, we use single and combinatorial drug response profiling to show that the combined inhibition of the anti-apoptotic protein Bcl-2 and of the tyrosine kinase BTK with the small molecules venetoclax and ibrutinib efficiently kills DLBCL cells in vitro. High Bcl-2 expression due to either BCL2 amplifications or translocations, in conjunction with chronic active BCR signaling accurately predict responses to dual Bcl-2/BTK inhibition. Orthotopic xenotransplantation and patient-derived xenograft models confirm that the combinatorial is superior to single-agent treatment in reducing the lymphoma burden. Combinatorial treatment further efficiently overcomes both primary and acquired resistance to venetoclax, which we could link to reduced expression of the Bcl-2 family members Bcl-X$_{L}$ and Bcl-2A1 under ibrutinib. We found in a Swiss DLBCL cohort that ~15% of patients are projected to respond to the venetoclax/ibrutinib combination based on their high Bcl-2 expression and nuclear NF-κB localization. Our data show that drug sensitivities exposed by drug response profiling can be attributed to specific mutational signatures and immunohistochemical biomarkers, and point to combined Bcl-2/BTK inhibition as a promising therapeutic strategy in DLBCL

Contingent Behavior and Asymmetric Preferences for Baltic Sea Coastal Recreation

In this study, we augment the traditional travel cost approach with contingent behavior data for coastal recreation. The objective is to analyze the welfare implications of future changes in the conditions of the Baltic Sea due to climate change and eutrophication. Adding to the literature, we assess the symmetricity of welfare effects caused by improvements and deteriorations in environmental conditions for a set of quality attributes. Responses are derived from identical online surveys in Finland, Germany and Latvia. We estimate recreational benefits using linear and non-linear negative binomial random-effects models. The calculated annual consumer surpluses are considerably influenced by the magnitude of the environmental changes in the three countries. We also observe asymmetries in the effects of environmental improvements and deteriorations on the expected number of visits. In particular, the results indicate that deteriorations lead to larger or more significant impacts than improvements in the case of blue-green algal blooms and algae onshore for Finland, water clarity for Germany, and water clarity and blue-green algal blooms for Latvia. For the remaining attributes, the effects are ambiguous.202

Inactivation of CREBBP expands the germinal center B cell compartment, down-regulates MHCII expression and promotes DLBCL growth

The genes encoding the histone acetyl-transferases (HATs) CREB binding protein (CREBBP) and EP300 are recurrently mutated in the activated B cell-like and germinal center (GC) B cell-like subtypes of diffuse large B cell lymphoma (DLBCL). Here, we introduced a patient mutation into a human DLBCL cell line using CRISPR and deleted Crebbp and Ep300 in the GC B cell compartment of mice. CREBBP-mutant DLBCL clones exhibited reduced histone H3 acetylation, expressed significantly less MHCII, and grew faster than wild-type clones in s.c. and orthotopic xenograft models. Mice lacking Crebbp in GC B cells exhibited hyperproliferation of their GC compartment upon immunization, had reduced MHCII surface expression on GC cells, and developed accelerated MYC-driven lymphomas. Ep300 inactivation reproduced some, but not all, consequences of Crebbp inactivation. MHCII deficiency phenocopied the effects of CREBBP loss in spontaneous and serial transplantation models of MYC-driven lymphomagenesis, supporting the idea that the mutational inactivation of CREBBP promotes immune evasion. Indeed, the depletion of CD4(+) T cells greatly facilitated the engraftment of lymphoma cells in serial transplantation models. In summary, we provide evidence that both HATs are bona fide tumor suppressors that control MHCII expression and promote tumor immune control; mutational inactivation of CREBBP, but not of EP300, has additional cell-intrinsic engraftment and growth-promoting effects

Key insights for the future of urban ecosystem services research

Understanding the dynamics of urban ecosystem services is a necessary requirement for adequate planning, management, and governance of urban green infrastructure. Through the three-year Urban Biodiversity and Ecosystem Services (URBES) research project, we conducted case study and comparative research on urban biodiversity and ecosystem services across seven cities in Europe and the United States. Reviewing > 50 peer-reviewed publications from the project, we present and discuss seven key insights that reflect cumulative findings from the project as well as the state-of-the-art knowledge in urban ecosystem services research. The insights from our review indicate that cross-sectoral, multiscale, interdisciplinary research is beginning to provide a solid scientific foundation for applying the ecosystem services framework in urban areas and land management. Our review offers a foundation for seeking novel, nature-based solutions to emerging urban challenges such as wicked environmental change issues

Recommendations for Kidney Disease Guideline Updating: A Report by the KDIGO Methods Committee

Updating rather than de novo guideline development now accounts for the majority of guideline activities for many guideline development organizations, including Kidney Disease: Improving Global Outcomes (KDIGO), an international kidney disease guideline development entity that has produced guidelines on kidney diseases since 2008. Increasingly, guideline developers are moving away from updating at fixed intervals in favor of more flexible approaches that use periodic expert assessment of guideline currency (with or without an updated systematic review) to determine the need for updating. Determining the need for guideline updating in an efficient, transparent, and timely manner is challenging, and updating of systematic reviews and guidelines is labor intensive. Ideally, guidelines should be updated dynamically when new evidence indicates a need for a substantive change in the guideline based on a priori criteria. This dynamic updating (sometimes referred to as a living guideline model) can be facilitated with the use of integrated electronic platforms that allow updating of specific recommendations. This report summarizes consensus-based recommendations from a panel of guideline methodology professionals on how to keep KDIGO guidelines up to date

Airport emission particles:Exposure characterization and toxicity following intratracheal instillation in mice

Background: Little is known about the exposure levels and adverse health effects of occupational exposure to airplane emissions. Diesel exhaust particles are classified as carcinogenic to humans and jet engines produce potentially similar soot particles. Here, we evaluated the potential occupational exposure risk by analyzing particles from a non-commercial airfield and from the apron of a commercial airport. Toxicity of the collected particles was evaluated alongside NIST standard reference diesel exhaust particles (NIST2975) in terms of acute phase response, pulmonary inflammation, and genotoxicity after single intratracheal instillation in mice. Results: Particle exposure levels were up to 1 mg/m3 at the non-commercial airfield. Particulate matter from the non-commercial airfield air consisted of primary and aggregated soot particles, whereas commercial airport sampling resulted in a more heterogeneous mixture of organic compounds including salt, pollen and soot, reflecting the complex occupational exposure at an apron. The particle contents of polycyclic aromatic hydrocarbons and metals were similar to the content in NIST2975. Mice were exposed to doses 6, 18 and 54 μg alongside carbon black (Printex 90) and NIST2975 and euthanized after 1, 28 or 90 days. Dose-dependent increases in total number of cells, neutrophils, and eosinophils in bronchoalveolar lavage fluid were observed on day 1 post-exposure for all particles. Lymphocytes were increased for all four particle types on 28 days post-exposure as well as for neutrophil influx for jet engine particles and carbon black nanoparticles. Increased Saa3 mRNA levels in lung tissue and increased SAA3 protein levels in plasma were observed on day 1 post-exposure. Increased levels of DNA strand breaks in bronchoalveolar lavage cells and liver tissue were observed for both particles, at single dose levels across doses and time points. Conclusions: Pulmonary exposure of mice to particles collected at two airports induced acute phase response, inflammation, and genotoxicity similar to standard diesel exhaust particles and carbon black nanoparticles, suggesting similar physicochemical properties and toxicity of jet engine particles and diesel exhaust particles. Given this resemblance as well as the dose-response relationship between diesel exhaust exposure and lung cancer, occupational exposure to jet engine emissions at the two airports should be minimized.publishedVersionPeer reviewe

A Differential Network Approach to Exploring Differences between Biological States: An Application to Prediabetes

Background: Variations in the pattern of molecular associations are observed during disease development. The comprehensive analysis of molecular association patterns and their changes in relation to different physiological conditions can yield insight into the biological basis of disease-specific phenotype variation. Methodology: Here, we introduce a formal statistical method for the differential analysis of molecular associations via network representation. We illustrate our approach with extensive data on lipoprotein subclasses measured by NMR spectroscopy in 4,406 individuals with normal fasting glucose, and 531 subjects with impaired fasting glucose (prediabetes). We estimate the pair-wise association between measures using shrinkage estimates of partial correlations and build the differential network based on this measure of association. We explore the topological properties of the inferred network to gain insight into important metabolic differences between individuals with normal fasting glucose and prediabetes. Conclusions/Significance: Differential networks provide new insights characterizing differences in biological states. Based on conventional statistical methods, few differences in concentration levels of lipoprotein subclasses were found between individuals with normal fasting glucose and individuals with prediabetes. By performing the differential analysis of networks, several characteristic changes in lipoprotein metabolism known to be related to diabetic dyslipidemias were identified. The results demonstrate the applicability of the new approach to identify key molecular changes inaccessible to standard approaches

Werther

Johann Wolfgang Goethe'nin Malumat'ta yayımlanan Werther adlı romanının ilk ve son tefrikalarıTefrikanın devamına rastlanmamış, tefrika yarım kalmıştır

Genetic factors influencing a neurobiological substrate for psychiatric disorders

A retrospective meta-analysis of magnetic resonance imaging voxel-based morphometry studies proposed that reduced gray matter volumes in the dorsal anterior cingulate and the left and right anterior insular cortex-areas that constitute hub nodes of the salience network-represent a common substrate for major psychiatric disorders. Here, we investigated the hypothesis that the common substrate serves as an intermediate phenotype to detect genetic risk variants relevant for psychiatric disease. To this end, after a data reduction step, we conducted genome-wide association studies of a combined common substrate measure in four population-based cohorts (n = 2271), followed by meta-analysis and replication in a fifth cohort (n = 865). After correction for covariates, the heritability of the common substrate was estimated at 0.50 (standard error 0.18). The top single-nucleotide polymorphism (SNP) rs17076061 was associated with the common substrate at genome-wide significance and replicated, explaining 1.2% of the common substrate variance. This SNP mapped to a locus on chromosome 5q35.2 harboring genes involved in neuronal development and regeneration. In follow-up analyses, rs17076061 was not robustly associated with psychiatric disease, and no overlap was found between the broader genetic architecture of the common substrate and genetic risk for major depressive disorder, bipolar disorder, or schizophrenia. In conclusion, our study identified that common genetic variation indeed influences the common substrate, but that these variants do not directly translate to increased disease risk. Future studies should investigate gene-by-environment interactions and employ functional imaging to understand how salience network structure translates to psychiatric disorder risk