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Resource Teachers: Learning and Behaviour (RTLB) work with teachers to identify learning and behaviour needs of students who experience barriers to educational success. The language RTLB use can have a significant impact on teachers’ response to the inclusion of students with special learning needs and is key to improving educational outcomes for all learners. We examined the extent to which RTLB in New Zealand used inclusive, strengths-based language in initial meetings with teachers and whether shifts could be made through professional learning and development (PLD). Data collected included audio recordings, transcripts of initial meetings pre- and post-PLD, RTLB reflections on both transcripts, and questionnaires. Results indicate limited use of inclusive, strengths-based language prior to PLD. However, PLD that provided targeted opportunities to reflect on evidence of language behaviour and to practise requisite skills markedly increased RTLB awareness, knowledge, and skills with respect to inclusive, strengths-based language. Findings indicate that change often requires disrupting long-held beliefs and practices and a need for evidence of these to be able to do so. The findings have implications for the type of in-depth PLD needed to facilitate change in the language RTLB use when working with teachers.

While the link between self-perceptions of aging (SPA) and healthy aging is well established, less is known about how SPA relate to social factors. The present study investigated whether higher social network diversity is associated with more gain-related SPA and less loss-related SPA and whether this association is moderated by chronological age. We examined data from the German Ageing Survey of 2008 (DEAS; N = 6,205, 40–85 years, 49.5% female). Network diversity was assessed as the number of social roles in an individual’s social network. Three dimensions of SPA were measured with the Aging-Related Cognitions Scale (AgeCog; ongoing development, social losses, physical losses). We conducted multiple linear regression models and tested for a moderator effect of chronological age using an interaction term of age and network diversity. Results showed that at higher ages older adults with higher network diversity reported more gain-related SPA in the dimension of ongoing development than those with less diverse networks, supporting a moderating effect of age. Loss-related SPA in the dimension of social losses showed a small positive association with network diversity while loss-oriented SPA in the dimension of physical losses did not appear to be related to network diversity. Age had no relevance for either relationship. The present study adds to evidence on the role of social relationships for SPA. Our findings suggest that in certain dimensions and partly depending on age, social network diversity is both related to more gain-related and more loss-related SPA.

Neighbourhood effects research has benefited from the application of sequence analysis which, together with cluster analysis, identifies the main temporal patterns of exposure to residential contexts experienced by different groups of people, such as children. However, given that this is a relatively new approach to measuring exposure to neighbourhood deprivation, studies that have utilised sequence analysis to model residential trajectories and test for neighbourhood effects do not contextualise these population-level findings at the individual-level. The current study sought to investigate the patterns of exposure to neighbourhood deprivation experienced by children in Aotearoa New Zealand over the first eight years of life by utilising two different methodological approaches: at the macro-level, the results of the sequence and cluster analysis suggest that in general, children experienced little neighbourhood mobility; at the micro-level, children experienced greater levels of movement between different levels of neighbourhood deprivation in middle childhood, compared to early childhood, while children in the least and most deprived neighbourhoods experienced less mobility than their peers. Together, these findings provide a comprehensive description of the ways in which children are exposed to different residential contexts over time and advance our understandings of how to document these experiences effectively within quantitative research.

This study sheds light on the relationship between cognition and patience by documenting that the correlation between cognitive abilities and delay discounting is weaker for the same group of individuals if choices are incentivized. This study conjectures that higher cognitive effort, which induces higher involvement of the cognitive system, moderates the relationship between patience and cognition. For 107 participants drawn from the adult population in Tbilisi, this study examines the relationship between various measures of cognitive ability and that of patience. Specifically, we consider the relationship between the Cognitive Reflection Test, a numeracy test, self-reported math ability measure, enumerators’ assessments, and incentivized and hypothetical trade-offs between smaller-sooner and larger-later payments.

Little is known about the relations between principals’ effectiveness in specific leadership tasks and student achievement. The purpose of this study is to explore principal task effectiveness, as ...

Academic resilience captures academic success despite adversity and thus is an important concept for promoting equity within education. However, our understanding of how and why rates of academic resilience differ between contexts is currently limited by variation in the ways that the construct has been operationalised in quantitative research. Similarly, comparing the strength of protective factors that promote academic resilience is hindered by differing approaches to the measurement of academic resilience. This methodological variation has complicated attempts to reconcile disparate findings about academic resilience. The current study applied six commonly used operationalisations of academic resilience that combined different thresholds of high risk and high achievement, to three international large-scale assessments, to explore how these different operationalisations impacted the findings produced. The context of Aotearoa New Zealand was chosen as a case study to further academic resilience research within this context and investigate how academic resilience manifests in an education system with relatively high levels of average achievement alongside low levels of educational equity. Within international large-scale assessment datasets, prevalence rates differed markedly across subject areas, grade levels, and collection cycles, as a function of the measure of academic resilience employed, while the strength of protective factors was more consistent. Thresholds that were norm-referenced produced more consistent findings across the different datasets compared to thresholds that were criterion-referenced. High levels of missing data prevented the analysis of some datasets, and differences in the way that key constructs were measured undermined the comparability of findings across international large-scale assessments. The findings emphasise the strengths and limitations of utilising international large-scale assessment data for the study of academic resilience, particularly within the Aotearoa New Zealand context. Furthermore, the study highlights that researchers' methodological decisions have important impacts on the conclusions drawn about academic resilience.The online version contains supplementary material available at 10.1007/s11092-022-09384-0.

Tyrosine kinase inhibitors (TKI) targeting the epidermal growth factor receptor (EGFR) like the third-generation TKI osimertinib have substantially improved the treatment of patients with advanced non-small cell lung cancer (NSCLC) harboring sensitizing EGFR mutations. However, there is a subset of patients that do not benefit from these therapies in terms of response rate or progression-free-survival (PFS). It has been shown that persistence of EGFR mutations in circulating tumor DNA (ctDNA) at weeks 3 and 6 after start of osimertinib predicts shorter PFS. These patients may benefit from additional chemotherapy. While combination therapies with older TKI have been demonstrated effective in improving outcome, they are associated with a significant increase in toxicity.PACE-LUNG is a multicenter, single-arm, investigator initiated, phase II trial conducted with the German national Network Genomic Medicine (nNGM). Patients with stage IIIB or IV NSCLC and exon 19 deletion or p.L858R EGFR mutation not amenable to curative treatment with persisting ctDNA after 3 to 4 weeks of first-line osimertinib monotherapy will receive additional chemotherapy (4 cycles of either cisplatin/pemetrexed or carboplatin/pemetrexed). Afterwards, osimertinib will be continued as standard of care until disease progression or intolerable toxicity. The primary endpoint is PFS. Secondary endpoints include overall survival, response rate, safety, and quality of life. Concomitant translational research will be performed to identify patterns of mutational evolution in ctDNA upon disease progression or ctDNA persistence. Enrollment started in December 2021.The PACE-LUNG trial is designed to evaluate the efficacy and safety of a biomarker-driven strategy for therapy escalation in patients at high risk for early treatment failure. This approach aims not only to improve treatment outcomes, but also to limit the anticipated additional toxicity to high-risk patients.2019-004757-88 (EudraCT).

Many studies claim the importance of goal-setting for school improvement but few outline specific practices. This study highlights specific goal-setting practices associated with successful school improvement efforts. It reports on a 2-year collaborative research project, which closely examined three principals’ goal-setting practices in the context of their schools. It documents principals’ and staffs’ efforts to improve equity in outcomes through detailed case studies. Case studies drew on principal and teacher interview data, workshop artifacts and discussion recordings, observations, school reports and school achievement data. The in-depth case and cross-case analyses focused on micro-level leadership practices and their impact on school-wide practices. This study highlights four key leadership drivers for improvement. These include: justifying goals in ways that challenge teachers’ beliefs about current achievement to raise commitment; embedding tight and rigourous monitoring practices with a focus on problem-solving and improvement; distributing responsibility and leadership; and developing the capability and collective responsibility of middle leaders. Our discussion highlights how leaders’ belief systems can enable or constrain their ability to influence their schools’ cultures.

Solving complex problems is critical to educational leaders’ ability to achieve improvement in schools. Much of this problem-solving is carried out in conversations with staff. This paper draws on ...

PurposeThe purpose of this research is to use a collective responsibility theoretical lens to examine the work of three school principals as they focussed on school-wide goal-setting processes to achieve valued student achievement goals. The tensions principals face in creating collective responsibility are examined so that these might be intentionally navigated.Design/methodology/approachQualitative case studies of three New Zealand schools include data from interviews with principals, middle leaders and teachers. An inductive and deductive thematic analysis approach was employed.FindingsPrincipals face four key tensions: (1) whether to promote self or centrally directed and voluntary or mandatory professional learning; (2) how to balance a top-down versus a middle-up process for accountability; (3) ways to integrate both educator and student voice and (4) the complexity of both challenging teachers' beliefs and providing support. These challenges seemed inherent in the work of developing collective responsibility and leaders tended to move along response continuum.Research limitations/implicationsThis research highlights the importance of being intentional and transparent with staff members about both the nature of these tensions and their navigation, and opens up further questions in relation to leader, and teacher perceptions of tensions in creating collective responsibility for achieving school-improvement goals.Practical implicationsAn understanding of the tensions that need to be navigated can help leaders and other educators to take effective action, scrutinize the reasoning behind decisions, and understand the inherent challenges faced.Originality/valueLeadership tensions in creating collective responsibility are explored and implications for leadership practice and learning considered.

PurposeThis article investigates goal pursuit practices in a sample of 31 New Zealand high schools. It examines goal knowledge of middle and senior leaders, the alignment of this knowledge and factors related to improvement.Design/methodology/approachGoals from schools' annual improvement plans were identified and counted at the beginning of the academic year. Senior and middle leaders were asked to recall their school's academic goals from memory. Responses were scored against the goals in the schools' plans to produce an accuracy score for each leader and for each middle and senior leadership team (SLT). At the end of the academic year, leaders recounted their goals and rated and commented on their SLT’s goal focus. Data analysis examined goal knowledge, alignment of middle and senior leaders' goal knowledge and SLT's goal focus. Comments were analyzed thematically in regard to the number and clarity of the goals and how goals were communicated, enacted and monitored.FindingsOur findings show a lack of goal clarity, persistence across the year and effective strategy hampered the majority of schools in their goal pursuit. Only a few schools had a strong and aligned goal focus. Factors influencing perceived improvement included: fewer and greater clarity of goals, engagement of middle leaders in setting goals, establishing sound supporting structures and regular monitoring of progress.Originality/valueWhile annual improvement plans outlining multiple goals are often compulsory for schools, little is known about their impact on practice. This research clarifies the state of goal pursuit in a sample of high schools.

Despite research highlighting the negative impact of ability grouping on student outcomes in mathematics, the practice seems entrenched in New Zealand schools. The Ministry of Education launched a professional development initiative with the aim that mathematics lead teachers would drive change towards teaching in mixed-ability groups using a problem-solving pedagogy. Lead teachers were seen as uniquely positioned to promote change within schools. This study examined lead teachers’ changes in their own practice and that affected in their schools following the initiative. The study used a problem-based methodology. Through careful, in-depth interviews with lead teachers from six primary schools, the researchers examined lead teachers’ theories-of-action and the extent to which they were able to affect change. Findings showed different levels of change in lead teachers’ own and their school’s practice. Only two lead teachers made considerable changes in their own practice, and only one could fully incorporate mixed-ability grouping into school-wide practices. Analyses across the six cases revealed four factors impacting lead teachers’ ability to affect change: positional authority, senior leadership support, expertise in content and pedagogy, and changing teacher beliefs to bring about change. The study concludes that while the notion of lead teachers implementing change through working closely with their colleagues seems exciting and promising, the conditions for teacher leadership to be effective need to be met. Furthermore, the case of this national initiative shows that shortcuts in professional development are ineffective, especially for a matter so disputed and entrenched as ability grouping in mathematics.

Novice principals’ experiences and responses to challenges are important for understanding their sensemaking of their role, especially in view of the contextual complexity of leadership in small sc...

first_pagesettingsOrder Article ReprintsOpen AccessArticleDynamics and Heterogeneity of Environmental Attitude, Willingness and Behavior in Germany from 1993 to 2021by Frauke Meyer, Hawal Shamon* [ORCID] and Stefan Vögele[ORCID]Forschungszentrum Jülich GmbH, Institut für Energie- und Klimaforschung, Systemforschung und Technologische Entwicklung (IEK-STE), 52425 Jülich, Germany*Author to whom correspondence should be addressed.Sustainability 2022, 14(23), 16207; https://doi.org/10.3390/su142316207Received: 26 October 2022 / Revised: 23 November 2022 / Accepted: 24 November 2022 / Published: 5 December 2022(This article belongs to the Section Social Ecology and Sustainability)Download Browse FiguresVersions NotesAbstractThis paper analyzes environmental attitude, willingness, and behavior using a relatively broad range of survey items from the four Environment Modules of the International Social Survey Programme (ISSP) in Germany. The ISSP Environment Module is a repeated cross-sectional large-scale survey in Germany covering a period of nearly 30 years with four survey waves (1993, 2000, 2010, and 2020). We find that environmental attitude, willingness, and behavior are relatively stable between 1993 and 2010 in Germany. However, in the fourth wave, we find a significant upward trend in attitude and willingness compared to 2010—even though the COVID-19 pandemic was omnipresent at the time of the survey. This could indicate that climate change and environmental issues have gained such significance that they cannot easily be fully displaced by other major events, such as a pandemic. Moreover, we detect systematic heterogeneity in environmental attitude, willingness, and behavior predominantly with respect to respondents’ education, residential region, and political orientation but also some heterogeneity regarding gender, age, and income. Finally, we reveal that the dynamic of environmental attitude, willingness, and behavior also depends on certain socio-demographic characteristics, such as residential region, or political orientation. Our findings are essential for a better understanding of the social feasibility of transformation pathways towards a sustainable energy system.

The summer learning effect has been identified as a major barrier in creating equitable outcomes in the United States, especially in reading and mathematics. Less is known about the effect in other education systems and subject domains. This research draws on a large sample (N = 4390) to examine the summer learning effect in the comparatively under-researched domain of writing in New Zealand. Results indicate a considerable loss among students despite the relatively short summer break. The drop is substantially larger than the overall summer drop found previously across subjects, and for reading and mathematics specifically. Students from minority ethnic groups showed the greatest drops. Although indigenous students progressed at an equivalent rate than their European peers, the summer drop meant that the gap evident at the beginning of the academic year had widened by the beginning of the next year. At the school level, lower-income schools, which were over-represented by ethnic minority students, were also associated with a greater summer drop even after accounting for ethnicity. The growing inequities created by the effect underscore the importance of addressing this issue. Our findings point to the significance of supporting students’ literacy developments in and outside of school. They call for greater policy attention that would see an examination of the financial and educational resourcing to support schools and families, but also of the access and resourcing of communities in regard to education, libraries and community services.

The stability of extracellular matrices is in general ensured by cross-linking of its components. Previously, we had shown that the integrity of the layered Drosophila cuticle relies on the presence of a covalent cuticular dityrosine network. Production and composition of this structure remained unstudied. In this work, we present our analyses of the schlaff (slf) gene coding for a putative C-type lectin that is needed for the adhesion between the horizontal cuticle layers. The Slf protein mainly localizes between the two layers called epicuticle and procuticle that separate from each other when the function of Slf is reduced or eliminated paralleling the phenotype of a cuticle with reduced extracellular dityrosine. Localisation of the dityrosinylated protein Resilin to the epicuticle-procuticle interface suggests that the dityrosine network mediates the adhesion of the epicuticle to the procuticle. Ultimately, compromised Slf function is associated with massive water loss. In summary, we propose that Slf is implied in the stabilisation of a dityrosine layer especially between the epicuticle and the procuticle that in turn constitutes an outward barrier against uncontrolled water flow.

TPS9157 Background: Epidermal growth factor receptor (EGFR) – mutated non-small cell lung cancer (NSCLC) is susceptible to EGFR targeting tyrosine kinase inhibitors (TKI), such as the third generation TKI osimertinib. However, response rate and duration vary between patients. Among others, the specific subtype of EGFR-mutation, its co-occurrence with other genetic alterations, and the detection of phosphorylated EGFR (pEGFR) in the plasma, and its clearance upon treatment were previously identified as markers that predict therapy response. A high proportion of patients with early (3-6 weeks after start) pEGFR clearance from plasma show impressive survival upon single-agent TKI. However, failure to achieve early clearance upon Osimertinib is associated with unfavorable outcome. For these patients, treatment concepts are lacking. Here, we report about the initiation of a clinical trial that evaluates the combination of EGFR-directed TKI and platinum-based chemotherapy as an early treatment escalation strategy for this high-risk patient population. Methods: PACE is a prospective multicenter single-arm investigator-initiated phase II trial. Patients with NSCLC harboring L858R or del19 EGFR mutation, who are treated with first-line Osimertinib are subjected to liquid biopsy-based early response assessment three weeks after start of therapy. Failure to clear pEGFR from plasma at this time point triggers treatment escalation with the addition of platinum-based doublet chemotherapy to the Osimertinib treatment. The primary outcome measure of the trial is progression-free survival (PFS), with the objective to assess the efficacy of biomarker-driven escalation of osimertinib therapy with a combination platinum-based regimen. Secondary outcome measures are the overall response rate (ORR), overall survival (OS), and the Quality of life (QLQ-C30, CTCAE-PROs) of the treated patients. In exploratory analyses, we will assess whether specific patterns of co-mutations are associated with early treatment failure (upon TKI) and pEGFR persistence. Fig. 1 illustrates the trial concept. A sample of 46 subjects achieves 80% power at a 0.05 significance level to detect a PFS of 14.4 months in the experimental treatment group when the PFS of the historic control group is 9.1 months; a total of 400 patients need to be screened within the national Network Genomic Medicine. Enrollment started in 12/2021. The clinical trial is supported by AstraZeneca and Guardant. EudraCT registration number: 2019-004757-88 .

While principal goal-setting has been shown to be an important leadership practice, there is little research examining principals’ goal-setting and goal-achievement. This research examined novice p...

Academic resilience research has the potential to improve the learning outcomes of students at risk of school failure, yet there is no standard approach to its measurement. This review aimed to provide an overview of the ways in which academic resilience has been measured and analysed within quantitative research over the last 20 years. Our findings extended upon those in existing reviews by focussing on how academic resilience has been operationalised as a specific construct. A systematic search of the literature returned 127 studies that drew conclusions about academic resilience based on quantitative data. Three distinct approaches to the measurement of academic resilience were identified using thematic analysis techniques: the definition-driven, process-driven, and latent construct approaches. Each of these approaches align with different types of analyses which, in turn, shape the inferences that researchers can make about academic resilience. The implications of these variations in measurement are discussed. At the macro-level, the utilisation of resilient characteristics and the omission of risk indicators within existing measures may undermine the validity of studies investigating the construct of academic resilience. At the micro-level, the purpose of the study, usability, and inclusivity of the measurement approach influence how researchers choose to operationalise academic resilience. This review emphasises the importance of considering the methodological decisions that researchers make and contributes to the ongoing refinement of academic resilience as a specific construct in resilience research.

Teacher judgments of student achievement are increasingly used for high-stakes decision-making, making it imperative that judgments be as fair and reliable as possible. Using a large national database from New Zealand, we explored the relation between psychometrically designed standardized achievement results and teacher judgments in reading ( N = 4771 students) and writing ( N = 11,765 students) using hierarchical linear modelling. Our findings indicated that judgments were systematically lower for marginalized learners after controlling for standardized achievement differences. Additionally, classroom and school achievement composition were inversely related to teacher judgments. These discrepancies are concerning, with important implications for equitable educational opportunities.

Purpose The notion of vulnerability underlies relationships of trust. Trust between leaders and staff is needed to solve concerns that hinder equity and excellence in teaching and learning. The purpose of this paper is to examine whether and how leaders show vulnerability by disclosing own possible contributions to concerns they try to resolve. Design/methodology/approach Data included transcripts of conversations held by 27 educational leaders about a concern with another staff and a questionnaire about the nature, causes and history of the concern. Questionnaire analysis identified if and how leaders described their own possible contribution prior to the conversation. Transcript analysis identified instances of leaders’ contribution disclosure. Findings Results indicate that while two-thirds of leaders identified an own contribution, when prompted prior to the conversation, one-third saw no own contribution. Leaders indicated contributing by not acting on the concern, by acting in ways inappropriate or insufficient to resolve the concern, or by not clearly communicating their concern in the past. Eight of the 27 leaders publicly disclosed their contribution in the actual conversation. In some conversations this disclosure prompted reciprocal disclosure of information about the concern and its causes by the other person, aiding a more effective concern resolution. Originality/value Through examining leaders’ interpersonal behavior in difficult conversations, the importance of leaders’ acknowledgments of own mistakes and communication of their own vulnerability is highlighted. A positive view of vulnerability is argued for, epistemic vulnerability, which manifests itself in the willingness to be honest and open to learning by accepting one’s own fallibility.

INTRODUCTION: Medulloblastoma is the most common malignant brain tumor of childhood and is a genetically heterogeneous disease. Amongst all medulloblastoma subgroups, MYC-amplified medulloblastomas are associated with a particularly poor prognosis as they are commonly metastatic and resistant to standard therapy. However, MYC amplification is restricted to a cellular subpopulation within MYC-amplified tumors. The underlying mechanisms mediating this cellular heterogeneity remain poorly understood. HYPOTHESIS: We hypothesize that a secretome-dependent crosstalk between MYC-amplified and non-MYC-amplified cells shapes an intratumoral microenvironment that promotes medulloblastoma aggressiveness. METHODS AND RESULTS: We first demonstrate that MYC overexpressing (high-MYC) cells induce proliferation and invasive growth patterns in their isogenic counterparts with low MYC expression (low-MYC) using contacting and non-contacting co-culture systems in three different medulloblastoma cell lines (ONS76, DAOY and UW228-3). Secondly, we demonstrate that exosomes from high-MYC cells promote the migratory propensity of low-MYC cells in vitro. Importantly, we confirmed the pro-tumorigenic interaction of high-MYC and low-MYC cells using two orthotopic medulloblastoma xenograft models. We further demonstrate that low-MYC cells promote tumor angiogenesis in vivo. Using an unbiased proteomic discovery approach and targeted validation by Western blotting, we identified and verified secreted proteins that may mediate this interaction. Rescue experiments validated the relevance of these candidates using functional genomics approaches in vitro, with in vivo validation being currently ongoing. CONCLUSION: We demonstrate that the crosstalk between cellular subclones in MYC-driven medulloblastoma may promote tumor growth, metastasis and angiogenesis. Understanding the underlying secretory signaling networks may elucidate novel therapeutic vulnerabilities in this prognostically poor subgroup of medulloblastoma.

Given widespread acceptance of the role of teaching in improving student outcomes, it is not surprising that policy makers have turned to teaching standards as a lever for educational improvement. There are, however, long-standing critiques of standards that suggest they are reductionist and promote a dualism between theory and practice. Our purpose here is to propose a model of Teaching for Better Learning ( TBL) that responds to those critiques and that captures the complexity of teaching rather than focusing on discrete elements. Our model foregrounds the salience of teachers’ own situations and the active nature of teachers’ practice in a way that integrates practice with relevant theory. We outline how the TBL model can be used to derive inquiry-oriented teaching standards, an alternative approach that challenges widely accepted conventions for the design of standards and, we argue, might better support the improvement of teaching and learning.

Leseprobe ----- Zusammenfassung Der Beitrag richtet den Blick anhand der Leitfrage, was transnationale Bildung in einem postkolonialen Kontext von Asyl und Exil bedeuten kann, auf die seltener thematisierten Formen von Transnationalitat. Zunachst wird das Konzept transnationaler Bildung um eine postkoloniale Perspektive erweitert und dann ein erweiterter Bildungsbegriff vorgeschlagen, der es erlaubt, die in- und nonformalen Bildungsprozesse, wie sie im Kontext von Flucht und Asyl haufig sind, zu erfassen. Anhand zweier Fallbeispiele wird schlieslich illustriert, was transnationale Bildung unter den postkolonialen Bedingungen des Asyls bzw. Exils bedeuten kann. Schlagworter: Transnationalitat, Fluchtmigration, Bildung “Businessmen are everywhere useful”. Or: “I’d simply like to retreat.” – What Transnational ----- Education could mean in a Postcolonial Context of Asylum and Exile Abstract The paper focusses the less discussed forms of transnationalty guided by the question what transnational education (Bildung) could mean in a postcolonial context of asylum and exile. First, the concept of transnational Bildung is broaden by a postcolonial perspective. Then, an extended concept of Bildung is proposed which allows integrating in- and nonformal processes of Bildung being often characteristic for asylum and exile contexts. Finally, two case studies illustrate what transnational education could mean under the postcolonial conditions of asylum and exile. Keywords: transnationality, flight migration, education (Bildung) ----- Bibliographie: Meyer, Frauke: „Kaufleute kann man uberall brauchen.“ Oder: „Ich will mich einfach zuruckziehen.“ – Was transnationale Bildung in postkolonialen Kontexten von Asyl und Exil bedeuten kann, Diskurs Kindheits- und Jugendforschung / Discourse. Journal of Childhood and Adolescence Research, 4-2019, S. 405-416. https://doi.org/10.3224/diskurs.v14i4.03

Summary The current consensus recognizes four main medulloblastoma subgroups (wingless, Sonic hedgehog, group 3 and group 4). While medulloblastoma subgroups have been characterized extensively at the (epi-)genomic and transcriptomic levels, the proteome and phosphoproteome landscape remain to be comprehensively elucidated. Using quantitative (phospho)-proteomics in primary human medulloblastomas, we unravel distinct posttranscriptional regulation leading to highly divergent oncogenic signaling and kinase activity profiles in groups 3 and 4 medulloblastomas. Specifically, proteomic and phosphoproteomic analyses identify aberrant ERBB4-SRC signaling in group 4. Hence, enforced expression of an activated SRC combined with p53 inactivation induces murine tumors that resemble group 4 medulloblastoma. Therefore, our integrative proteogenomics approach unveils an oncogenic pathway and potential therapeutic vulnerability in the most common medulloblastoma subgroup.

The stability of extracellular matrices is in general ensured by cross-linking of its components. Previously, we had shown that the integrity of the layeredDrosophilacuticle relies on the presence of a covalent cuticular dityrosine network. Production and composition of this structure remained unstudied. In this work, we present our analyses of theschlaff(slf) gene coding for a C-type lectin that is needed for the adhesion between the horizontal cuticle layers. The Slf protein mainly localizes between the two layers called epicuticle and procuticle that separate from each other when the function of Slf is reduced or eliminated paralleling the phenotype of a cuticle with reduced extracellular dityrosine. Localisation of the dityrosinylated protein Resilin to the epicuticle-procuticle interface suggests that the dityrosine network mediates the adhesion of the epicuticle to the procuticle. Ultimately, compromised Slf function is associated with massive water loss. In summary, we propose that Slf is implied in the stabilisation of a dityrosine layer especially between the epicuticle and the procuticle that in turn constitutes an outward barrier against uncontrolled water flow.Summary statementExtracellular matrices adopt a stereotypic organisation for function during development. The lectin Schlaff assists adhesion reactions to ensure compactness of the epidermal cuticle in Drosophila.

Pilocytic astrocytoma (PA) is the most common pediatric brain tumor. Aberrant MAPK signaling, typically mediated by BRAF alterations, drives PA formation. While five-year overall survival rates exceed 95%, incompletely resected tumors recur frequently despite treatment. Therefore, we used proteogenomics to discern the biological heterogeneity of PA to improve classification of this tumor entity and identify novel therapeutic targets. Our proteogenomics approach utilizes RNA sequencing and LC/MS-based proteomic profiling and Similarity Fusion Network (SNF) analysis reveals the biological heterogeneity of PA. Integrative genomics dissects aberrant pathway activation in biological subgroups. Lastly, we utilize a drug screening pipeline to evaluate selective therapeutic activity of conventional anti-cancer and phase III/IV clinical trial drugs in PA culture models. PAs segregate into three groups with distinct clinical and molecular features. Age and tumor location are significantly associated with the SNF groups. BRAF fusions were predominantly observed in Groups 1 and 2, while Group 3 PA largely harbored other alterations leading to MAPK activation. Pathway enrichment analyses reveals genesets involved in primary ciliogenesis in Group 3, while immune response signatures, many SYK-related, are associated with Group 1. Confirming this analysis, the SYK inhibitor R788 was specifically active in Group 1, and less active in other brain tumors models (n=27). In summary, our proteogenomic approach reveals important biological heterogeneity with novel therapeutic targets emerging in PA. These biological insights may improve biological classification and reveal novel therapeutic targets specifically useful for non-resectable tumors with high risk of progressive disease.

Harry Potter und der Gefangene von Askaban Wenn die Depression sich nähert, wird es plötzlich kalt. «Harry spürte seinen Atem in der Brust stocken. Die Kälte drang ihm unter die Haut. Sie drang in seine Brust, ins Innere seines Herzens … Harrys Augäpfel drehten sich nach innen. Er konnte nichts mehr sehen. Die Kälte ertränkte ihn. In seinen Ohren rauschte es, wie von Wasser. Etwas zog ihn in die Tiefe, das Rauschen wurde lauter … Und dann, aus weiter Ferne, hörte er Schreie, schreckliche, grauenerfüllte, flehende Schreie – er wollte helfen, wer immer es auch war, er versuchte die Arme zu bewegen, doch er konnte nicht – ein dichter weißer Nebel wirbelte um ihn auf, drang in sein Inneres–»

The ‘summer learning effect’ (SLE) is described as a stall or drop in achievement over summer, especially in schools serving poor or ‘minority’ communities. There has been little research in Europe on the effect, and research internationally has primarily focused on the effect in reading, with minimal focus on writing. This paper describes the extent and nature of the SLE in reading comprehension and writing in second grade classrooms in Germany. The SLE was evident in both subject areas with all students experiencing lower progress rates over summer. In reading, students attending the high-income school progressed significantly more over summer than their low-income peers, while there was no significant difference in writing progress over summer. Literacy logbooks over summer and interviews with a subset of students provided information on how home literacy practices influenced the effect.

Pilocytic astrocytoma (PA) is a well-circumscribed, slow growing, low-grade brain tumor predominantly affecting children and considered a single-pathway disease with activation of MAPK signaling, typically driven by BRAF alterations. While five-year overall survival rates exceed 95%, incompletely resected tumors recur frequently despite radiation and/or chemotherapy. Less favorable responses to multimodal therapies are observed in adults compared to pediatric patients. Thus, we utilized a proteogenomics approach to discern the biological heterogeneity of PA across all age-groups to identify novel therapeutic targets. Our proteogenomic approach encompasses RNA sequencing (RNAseq) and LC/MS-based proteomic profiling in a cohort of pediatric (n=55) and adult cases (n=24). Unsupervised hierarchical clustering is used to determine the biological heterogeneity of the disease. Integrative genomics, combined with downstream pathway analysis, dissects aberrant pathway activation in biological subgroups. Lastly, we utilize a drug screening pipeline encompassing conventional chemotherapeutics and targeted therapeutics (n=211) currently evaluated in phase III and IV clinical trials to validate novel molecular targets in PA culture models (n=8). Pediatric and adult PA segregate into two subgroups identified by unsupervised hierarchical clustering using RNAseq and proteomic profiling (p=0.001). Adult tumors form a single entity, while we observed additional heterogeneity in pediatric tumors segregating into two subgroups (p=0.01). Initial analyses show that adult PA demonstrate an over-representation of genes involved in translation initiation and ciliogenesis according to GeneSet Enrichment Analysis, whereas pediatric PA show a significant enrichment of pathways involved in glycolysis, signal transmission and AKT signaling. In all, our proteogenomic approach reveals important biological heterogeneity in pediatric and adult PA. Ongoing drug profiling is used to determine therapeutics with preferential activity against pediatric and adult PA cultures compared to neural stem cells and astrocytes. These biological insights may improve biological classification and reveal novel therapeutic targets specifically useful for non-resectable tumors with high risk of progressive disease.

Pilocytic astrocytoma (PA) is the most common pediatric brain tumor. Aberrant MAPK signaling, typically mediated by BRAF alterations, drives PA tumorigenesis. While five-year overall survival rates exceed 95%, tumor recurrence constitutes a major clinical challenge in incompletely resected tumors despite chemotherapeutic or radiation based therapeutic approaches. Therefore, we used proteogenomics to discern the biological heterogeneity of PA to improve classification of this tumor entity and identify novel therapeutic targets. Our proteogenomics approach integrates RNA sequencing, DNA methylation profiling and LC/MS-based proteomic profiling data from a cohort of 75 primary PA samples. Similarity Fusion Network (SNF) analysis was conducted to discern the biological heterogeneity of PA. Integrative genomics was used to identify aberrant pathway activation in these biological subgroups. Lastly, we utilized a drug screening pipeline to evaluate selective therapeutic activity of conventional anti-cancer and phase III/IV clinical trial drugs in PA culture models. Pilocytic astrocytomas segregate into two groups with distinct clinical and molecular features. Age is significantly associated with the SNF groups. BRAF fusions were predominantly observed in Group 1, while Group 2 PAs largely harbored other alterations leading to MAPK activation. Importantly, we could confirm these two distinct biological subgroups in two independent, non-overlapping cohorts. Pathway enrichment analyses reveal genesets involved in ion channel activity, neurotransmitter signaling and cellular respiration, whereas largely SYK-related immune response signatures are associated with Group 1. Confirming this analysis, the SYK inhibitor R788 was specifically active in Group 1 PAs, and less active in other brain tumor models (n=13).

BACKGROUND Chitin produced by membrane-inserted chitin synthases is an important constituent of the arthropod cuticle and midgut peritrophic matrix. Chitin synthesis inhibitors are common insecticides in pest control. As the target of sulfonylurea-derived insecticides such as diflubenzuron, the ABC transporter sulfonylurea receptor (Sur) has been postulated to be an essential cofactor of chitin synthesis. However, direct evidence for this assumption is missing. RESULTS Here, a study has been made of the phenotype of Drosophila melanogaster larvae suffering completely eliminated Sur function. Taken together, it is found that cuticle architecture is normal and chitin amounts are not diminished in the cuticle of these animals, indicating that Sur is dispensable for chitin synthesis. CONCLUSION The data obtained suggest that there must exist another sulfonylurea-sensitive ABC transporter that either instead of Sur is the true sulfonylurea-sensitive transporter involved in chitin synthesis or is able to substitute Sur function during cuticle formation. Identification and characterisation of this factor is pivotal for understanding the mode of action of sulfonylurea as insecticide. © 2013 Society of Chemical Industry

In Deutschland hat die vollstationare kinder- und jugendpsychiatrische Versorgung in den letzten Jahrzehnten stetig zugenommen. Zurzeit werden knapp 20 Prozent der 3- bis 17-jahrigen Kinder und Jugendlichen der Risikogruppe fur ‚psychische Auffalligkeiten‘ zugeordnet (vgl. Holling et al. 2014, S. 811). Dass es sich hierbei um einen ansteigenden Trend handelt, zeigen u. a. Statistiken aus dem Stadtstaat Hamburg: Die Anzahl der vollstationar versorgten Kinder und Jugendlichen hat sich zwischen 2011 und 2014 um rund 37 Prozent auf ca. 1.900 Patienten und Patientinnen erhoht (vgl. BGV-HH 2016, S. 30).