Genomic and clinical characterization of early T-cell precursor lymphoblastic lymphoma

Early T-cell precursor phenotype acute lymphoblastic leukemia (ETP-ALL) is a subtype of T-ALL with a unique immunophenotype and genetic abnormalities distinct from conventional T-ALL. A subset of T lymphoblastic lymphoma (T-LLy) also demonstrates the early T-cell precursor immunophenotype and may be a counterpart of ETP-ALL. Unlike ETP-ALL, the incidence, clinical features, and genomic features of ETP-LLy are unknown. We reviewed the immunophenotyping data of 218 T-LLy patients who enrolled in the Children’s Oncology Group AALL0434 clinical trial and identified 9 cases (4%) exhibiting a definitive ETP immunophenotype. We performed single-nucleotide polymorphism array profiling on 9 ETP-LLy and 15 non-ETP T-LLy cases. Compared with non-ETP T-LLy, ETP-LLy showed less frequent deletion of 9p (CKDN2A/B), more frequent deletion of 12p (ETV6) and 1p (RPL22), and more frequent absence of biallelic T-cell receptor γ deletions. Recurrent abnormalities previously described in ETP-ALL such as deletions of 5q and 13q and gain of 6q were not observed in ETP-LLy cases. There were no failures of therapy among the ETP-LLy subtype with a 4-year event-free survival of 100%. Overall, ETP-LLy does not exhibit unifying genetic alterations but shows some distinct genomic features from non-ETP T-LLy suggesting that ETP-LLy may be a distinct entity from non-ETP T-LLy.

The Application of International Law in the Court of Justice of the European Union: Proportionality Rising

Application of international treaty and customary international law at the Court of Justice of the European Union (CJEU) is increasingly recognized by scholars as problematic regarding legal certainty. This Article seeks to illustrate why this is and to propose reform. Through comparing judicial approaches in the application of international law at the CJEU to its approach in internal case law, it is argued that in the frequent absence of proportionality in external case law the Court has utilized, redeployed, or varied other judicial devices in an effort to retain the discretion which proportionality affords. These are argued to effect legal certainty and established concepts of justice within the EU legal system. Accordingly, it is submitted that proportionality should be transplanted fully and openly to external relations case law and that support for this can be extrapolated from existing literature.

“Old” and “new” probiotics in the treatment of gastroenterological diseases in children and adults: how to increase effectiveness?

The purpose of the review is to analyze the real benefits of the use of traditional probiotics and to highlight the issues of the possibility of creating and using new generation probiotics in the treatment of gastroenterological pathology. Questions of effectiveness of therapy with traditional probiotics of functional and organic diseases of the gastrointestinal tract in children and adults from the points of view of evidence-based medicine are analyzed, insufficient number of studies in children and frequent absence of significant differences in the effect of probiotics compared to placebo are emphasized. New generation probiotic candidates are described, which could become potential sources of new drugs for various diseases, including gastroenterological pathology. The main problems in the way of creation and introduction of new probiotics are outlined. Data on an alternative approach of probiotic therapy based on use to restore microbiocenosis of own bacteria, which are grown as pure genetically characterized cultures and can be used as probiotic products, are presented.

Glioblastomas with primitive neuronal component harbor a distinct methylation and copy-number profile with inactivation of TP53, PTEN, and RB1

Glioblastoma IDH-wildtype presents with a wide histological spectrum. Some features are so distinctive that they are considered as separate histological variants or patterns for the purpose of classification. However, these usually lack defined (epi-)genetic alterations or profiles correlating with this histology. Here, we describe a molecular subtype with overlap to the unique histological pattern of glioblastoma with primitive neuronal component. Our cohort consists of 63 IDH-wildtype glioblastomas that harbor a characteristic DNA methylation profile. Median age at diagnosis was 59.5 years. Copy-number variations and genetic sequencing revealed frequent alterations inTP53,RB1andPTEN,with fewer gains of chromosome 7 and homozygousCDKN2A/Bdeletions than usually described for IDH-wildtype glioblastoma. Gains of chromosome 1 were detected in more than half of the cases. A poorly differentiated phenotype with frequent absence of GFAP expression, high proliferation index and strong staining for p53 and TTF1 often caused misleading histological classification as carcinoma metastasis or primitive neuroectodermal tumor. Clinically, many patients presented with leptomeningeal dissemination and spinal metastasis. Outcome was poor with a median overall survival of only 12 months. Overall, we describe a new molecular subtype of IDH-wildtype glioblastoma with a distinct histological appearance and genetic signature.

EFL Female Students’ Perceptions towards Cheating in Distance Learning Programmes

Distance education is becoming more demanding at universities all around the world in general and in the Kingdom of Saudi Arabia (KSA) in particular, than ever before. This study aimed at highlighting the students’ perceptions of cheating on distance learning at King Abdulaziz University (KAU). The study will further explore the ways they use to cheat, causes for cheating, and some solutions to minimize cheating. This study was conducted at the end of the second semester in 2019. Data was collected from 57 female distance learning students who graduated from the English Language Department (ELD) at KAU. A mixed-methods research design was adopted in this study via a custom designed, fifteen closed ended and one, open ended item questionnaire. The quantitative section was analysed by frequency and percentages and the open-ended questions were analysed thematically. The results indicated that the majority of female students cheated by helping each other, obtain the correct answers from another student or send the correct responses to all their classmates. Another way which some students admitted they used was using electronic websites to copy and paste the answers in the test’s screen. The study further concluded that reasons for cheating in distance learning programs were due to technical problems, frequent absence of virtual classes, and wanting grades, not necessarily knowledge. Recommendations for the possible solutions to eliminate cheating, the participants recommended increasing the students’ awareness of cheating policy and finding solutions to technological issues.

L’analisi della conversazione per valutare l’autenticità dei materiali audio per l’insegnamento dell’italiano L2: una proposta metodologica

IT Questo studio di caso ispirato ai principi dell’analisi della conversazione prende in considerazione due conversazioni registrate tratte da un manuale per l’insegnamento dell’italiano L2 per analizzarne alcune caratteristiche salienti sulla base di quanto sappiamo sul parlato spontaneo a partire dagli studi dell’analisi della conversazione (Schegloff, 2007). L’analisi dettagliata delle registrazioni ne mette in luce il carattere a tratti problematico, soprattutto per ciò che concerne la sequenzialità dell’azione, fatto che si traduce nella frequente assenza di coordinamento tra i turni di parola dei parlanti. Altri fenomeni tipici dell’interazione verbale spontanea, quali sovrapposizioni e riparazioni, sono spesso assenti. In sostanza si tratta di conversazioni poco adatte ad un uso didattico che abbia tra i propri obiettivi anche quello di far riflettere gli apprendenti sulle specificità che caratterizzano il parlato in interazione. L’articolo vuole proporre un modello di analisi di questi supporti audio che prenda in considerazione la stretta relazione esistente tra lingua, struttura sequenziale del parlato e azione sociale. Parole chiave: ITALIANO L2, DIDATTICA, ANALISI DELLA CONVERSAZIONE, SEQUENZIALITÀ, PREFERENZA, COMPETENZA INTERAZIONALE EN This case study, inspired by the principles of conversation analysis, examines two recorded conversations from a manual for teaching Italian as a second language. It analyzes certain salient characteristics of these conversations based on what we know about spontaneous speech from conversation analysis studies (Schegloff, 2007). The detailed analysis of the conversations highlights their problematic nature, especially with regard to the sequentiality of actions, which results in the frequent absence of coordination between conversation shifts. Other phenomena typical of spontaneous verbal interaction, such as overlaps and reparations, are often absent. In essence, these are conversations that are not suitable for instructional approaches that encourage learners to reflect on the details of spoken interaction. The article proposes an analysis model of these audio scripts that takes into consideration the close relationship between language, the sequential structure of speech, and social interaction. Key words: L2 ITALIAN, TEACHING, CONVERSATION ANALYSIS, SEQUENTIALITY, PREFERENCE, INTERACTIONAL COMPETENCE ES Este estudio de caso, inspirado en los principios del análisis de conversaciones, se centra en dos conversaciones grabadas que fueron extraídas de un manual para la enseñanza del italiano L2 para analizar algunas características sobresalientes en base a lo que sabemos sobre el habla espontánea a partir de los estudios del análisis de la conversación (Schegloff, 2007). El análisis detallado de las grabaciones destaca el carácter a veces problemático, sobretodo en lo que respecta a la secuencialidad de la acción, lo que se traduce en la frecuente ausencia de coordinación entre los turnos de habla de los hablantes. Otros fenómenos típicos de la interacción verbal espontánea, como superposiciones y reparaciones, a menudo están ausentes. De hecho son conversaciones que no son aptas para el uso didáctico que tiene entre sus objetivos el de hacer reflexionar a sus discentes sobre las peculiaridades de la interacción hablada. El artículo tiene como objetivo proponer un modelo de análisis de estos soportes de audio que considere la estrecha relación entre la lengua, la estructura secuencial del habla y la acción social. Palabras clave: ITALIANO L2, DIDÁCTICA, ANALISIS DE LA CONVERSACIÓN, SECUENCIALIDAD, PREFERENCIA, COMPETENCIA INTERNACIONAL

Una economía política y cultural de las subvenciones estatales a la educación privada en Argentina

In comparison with other forms of public-private partnerships (PPP) in education of more recent emergence such as voucher programs or charter schools inspired by the postulates of the theory of public choice, supply-side subsidies for private schools usually respond to less explicit theories of change. Indeed, most of these policies are addressed by specialized literature as unique and highly idiosyncratic arrangements, rather than examples of a particular variety of PPP. The frequent absence of a theory of change that explicitly presents the assumptions, objectives and mechanisms of this type of policy, makes it necessary to reconstruct it from a perspective of policy sociology based on the analysis of the behavior of agents and economic, political, institutional and cultural drivers that lie behind their adoption in each particular context. Based on a review of the literature and the analysis of the legislative debates of the 1947-2006 period, this article seeks to examine the process of adoption of the regulatory framework defined by the policy of supply-side subsidies for private schools in Argentina from an evolutionary perspective of political and cultural economy. The article distinguishes three periods for analytical purposes among which an evolutionary logic of nonlinear continuity prevails, subject to the contextual vagaries and driven by different actors in the field of ideas and political practice.

Metasubject Competencies in the Prevention of Delinquent Behavior in Adolescents

An attempt to establish the relationship between the formation of meta-subject competencies in delinquent adolescents in the framework of educational and extracurricular activities in an educational institution and the transition of forms of its behavioral manifestations from social disapproval to behavior regulated by legal norms was made. The authors outline that in order to structure knowledge about metasubject competencies, they are classified into meta-activities, meta-ways and meta-abilities that directly affect the rehabilitation of delinquent adolescents by means of educational and extracurricular activities organized in an educational institution. Methods of research: comparative and theoretical analysis of psychological and pedagogical literature, monographs and thesis works, documentation; generalization, comparison, systematization. Research result. The authors come to the conclusion that delinquent adolescent, due to the features of their socially disapproved forms of life, have well-defined formed competencies, but apply them in asocial behavioral manifestations. The article pays attention to the importance of improving the effectiveness of activity of educational institutions on the formation of delinquent adolescents’ metasubject competencies as a means of overcoming adolescent deviation. However, attention is drawn to the possible risks in this area of activity due to the delinquent adolescents’ frequent absence from school, so the authors also paid attention to the need to form academic motivation in delinquent adolescents to achieve the goals of forming metasubject competencies and overcoming delinquency.

Making Sense of Abstract Board Games: Toward a Cross-Ludic Theory

The frequent absence of culturally specific, figurative, or decorative markings in abstract board games has challenged theorizations that assume a meaningful representation in the study of games. In accepting this challenge, this article theorizes the historical phenomenon of abstract board games whose nonrepresentational board design and formal rules have transmitted with little change over millennia and across vast expanse. A theoretical framework is outlined for understanding abstract board games—a modular ontology of abstract board games and a typology of player meaning-making in abstract board games. It is argued that the reproducibility and transferability of abstract board games as self-sufficient and reliable formal systems that players share independently from culturally specific meanings and materials may contribute to their dispersal. It is in this interaction between the cross-cultural/reliable and local/variable semantic structures of abstract board games that game studies from a historical or archaeological perspective may meet literary and social science perspectives.

InferAMP, a python web app for copy number inference from discrete gene-level amplification signals noted in clinical tumor profiling reports

As somatic next-generation sequencing gene panel analysis in advanced cancer patients is becoming more routine, oncologists are frequently presented with reports containing lists of genes with increased copy number. Distinguishing which of these amplified genes, if any, might be driving tumor growth and might thus be worth considering targeting can be challenging. One particular issue is the frequent absence of genomic contextual information in clinical reports, making it very challenging to determine which reported genes might be co-amplified and how large any such amplicons might be. We describe a straightforward Python web app, InferAMP, into which healthcare professionals may enter lists of amplified genes from clinical reports. The tool reports (1) the likely size of amplified genomic regions, (2) which reported genes are co-amplified and (3) which other cancer-relevant genes that were not evaluated in the assay may also be co-amplified in the specimen. The tool is accessible for web queries at http://inferamp.org.