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The intensity of the language contact belongs to numerous sociodemographic variables that influence the language competence of preschool children. This study aimed to examine associations between 16 variables related to the language contact and German language competence of multilingual children. Four-year-old kindergarten children (N = 824) were examined with the language test “Kindersprachscreening” (KiSS.2; Holler-Zittlau/Euler/Neumann 2011). Correlations between children’s and their parents’ age of contact to German and children’s language competence were weak to moderate. The same is valid for the use of German at home. Weak German language skills of children speaking Turkish and Arabic were associated with their limited contact to German both in the family and beyond. Their German language competence depended predominantly on how often German was used at home. All other children acquired German predominantly in day care facilities. Therefore, their German language skills did not depend much on the language input in the family. To sum up, intensive language contact was, at best, moderately associated with age-appropriate German language skills. Significant differences in the command of the German language among largest ethnic or linguistic subgroups could be traced back to sociodemographic differences in the children’s and their families’ characteristics. Active use of German at home was more important for those immigrant subgroups that do not attend any day care facilities before kindergarten age.

The relevance is due to the expansion of the practice of including chess into school as an academic subject. At the same time, there are very few studies devoted to the analysis of the influence of chess on the development and academic performance of students studying chess as a school subject. This diagnostic study is being carried out as part of the Chess for Overall Development project, which has been implemented in the city of Satka, Chelyabinsk Region, from 2004 to the present. The aim of the study is to establish a relationship between teaching chess in elementary school using the «Chess for Overall Development» technology and the dynamics of the development of higher mental functions of students playing chess using the «Chess for Overall Development» technology (N=331), not playing chess (N=146) or engaged in other methods (N=160). In a cross-sectional longitudinal study, methods are used to diagnose the development of attention, memory, verbal and non-verbal intelligence, performance, and the ability to act in the mind. In total, three cross-sectional studies were conducted: with students in the second grade, in high school and in the ninth grade. The results of a comparative study show that in the second grade, students who played chess using the «Chess for Overall Development» technology for a year were ahead of their peers from the comparison groups in almost all indicators. According to some indicators, the advance in development remained until the ninth grade. In terms of academic performance, students who studied using the «Chess for Overall Development» technology showed significantly higher results than their peers from the two control groups: every third graduate from those who entered the tenth grade became a gold medalist. The conclusion is made about the expediency of using the «Chess for Overall Development» technology in elementary school for cognitive development and growth in academic performance in middle and high school.

To overcome the crisis of the modern school institution, it is necessary to qualitatively rethink its foundations and to design fundamentally new approaches to implementing the educational program. The theoretical and methodological bases of the concept of a new type of school as a development practice, based on the provisions of Russian cultural-historical psychology and the activity approach are presented. The purpose of the work is to consider in the modern context the key theoretical provisions of Russian psychology and to formulate the methodological principles arising from them, which set the conditions for organizing the educational process, thus ensuring the transition from theory to practice. The key concepts of the school model are development, agency and collaboration: infinite development is formulated as the supreme goal and value of the school, the development of the position of agency is considered as the main productive process, and collaboration is the main professional principle. Eight basic principles are formulated as follows: intent - implementation - reflection as a methodological scheme for organizing school processes, the principle of multidimensional development, the principle of equal importance of school activities, the principle of congruence, the principle of organizing the educational space as a space for growing up, the principle of fellowship of practices and the development-oriented approach to evaluation. Thus, the article presents the authors view of the school as a scientifically grounded anthropological practice. The implementation of the concept, which has already begun in Russia, is an experiment that will make it possible to verify these theoretical and methodological provisions.

A variety of genetic techniques have been devised to determine cell lineage relationships during tissue development. Some of these systems monitor cell lineages spatially and/or temporally without regard to gene expression by the cells, whereas others correlate gene expression with the lineage under study. The GAL4 Technique for Real-time and Clonal Expression (G-TRACE) system allows for rapid, fluorescent protein-based visualization of both current and past GAL4 expression patterns and is therefore amenable to genome-wide expression-based lineage screens. Here we describe the results from such a screen, performed by undergraduate students of the University of California, Los Angeles (UCLA) Undergraduate Research Consortium for Functional Genomics (URCFG) and high school summer scholars as part of a discovery-based education program. The results of the screen, which reveal novel expression-based lineage patterns within the brain, the imaginal disc epithelia, and the hematopoietic lymph gland, have been compiled into the G-TRACE Expression Database (GED), an online resource for use by the Drosophila research community. The impact of this discovery-based research experience on student learning gains was assessed independently and shown to be greater than that of similar programs conducted elsewhere. Furthermore, students participating in the URCFG showed considerably higher STEM retention rates than UCLA STEM students that did not participate in the URCFG, as well as STEM students nationwide.

Neoantigen-specific T cells are increasingly viewed as important immunotherapy effectors, but physically isolating these rare cell populations is challenging. Here, we describe a sensitive method for the enumeration and isolation of neoantigen-specific CD8+ T cells from small samples of patient tumor or blood. The method relies on magnetic nanoparticles that present neoantigen-loaded major histocompatibility complex (MHC) tetramers at high avidity by barcoded DNA linkers. The magnetic particles provide a convenient handle to isolate the desired cell populations, and the barcoded DNA enables multiplexed analysis. The method exhibits superior recovery of antigen-specific T cell populations relative to literature approaches. We applied the method to profile neoantigen-specific T cell populations in the tumor and blood of patients with metastatic melanoma over the course of anti-PD1 checkpoint inhibitor therapy. We show that the method has value for monitoring clinical responses to cancer immunotherapy and might help guide the development of personalized mutational neoantigen-specific T cell therapies and cancer vaccines.

PurposeSeveral biomarkers have been individually associated with response to PD-1 blockade, including PD-L1 and tumor mutational burden (TMB) in non-small cell lung cancer (NSCLC), and CD8 cells in melanoma. We sought to examine the relationship between these distinct variables with response to PD-1 blockade and long-term benefit.Experimental designWe assessed the association between baseline tumor characteristics (TMB, PD-L1, CD4, and CD8) and clinical features and outcome in 38 patients with advanced NSCLC treated with pembrolizumab (median follow-up of 4.5 years, range 3.8-5.5 years).ResultsPD-L1 expression and CD8 infiltration correlated with each other and each significantly associated with objective response rate (ORR) and progression-free survival (PFS). TMB was independent of PD-L1 and CD8 expression, and trended towards association with ORR and PFS. There was no association between CD4 infiltration and outcomes. Only PD-L1 expression was correlated with overall survival (OS). Among 5 patients with long-term survival >3 years with no additional systemic therapy, PD-L1 expression was the only discriminating feature. The increased predictive value for PFS and OS of composite biomarker inclusive of PD-L1, CD8, CD4, and TMB was limited.ConclusionsIn patients with NSCLC treated with PD-1 blockade with long-term follow up, TMB, PD-L1, and CD8 were each associated with benefit from PD-1 blockade. Pretreatment PD-L1 expression was correlated with T lymphocyte infiltration and OS, whereas models incorporating TMB and infiltrating CD4 and CD8 lymphocytes did not substantially add to the predictive value of PD-L1 alone for OS.

BACKGROUND:Open maternal-fetal surgery for fetal myelomeningocele results in reduction in neonatal morbidity related to spina bifida but may be associated with fetal, neonatal, and maternal complications in subsequent pregnancies. OBJECTIVE:The objective of this study was to ascertain obstetric risk in subsequent pregnancies after open maternal-fetal surgery for fetal myelomeningocele closure. STUDY DESIGN:An international multicenter prospective observational registry created to track and report maternal, obstetric, fetal/neonatal, and subsequent pregnancy outcomes following open maternal-fetal surgery for fetal myelomeningocele was evaluated for subsequent pregnancy outcome variables. Institutional Review Board approval was obtained for the registry. RESULTS:From 693 cases of open maternal-fetal surgery for fetal myelomeningocele closure entered into the registry, 77 subsequent pregnancies in 60 women were identified. The overall live birth rate was 96.2%, with 52 pregnancies delivering beyond 20 weeks gestational age and median gestational age at delivery of 37 (36.3-37.1) weeks. The uterine rupture rate was 9.6% (n = 5), resulting in 2 fetal deaths. Maternal transfusion was required in 4 patients (7.7%). CONCLUSION:The risk of uterine rupture or dehiscence in subsequent pregnancies with associated fetal morbidity after open maternal-fetal surgery is significant, but is similar to that reported for subsequent pregnancies after classical cesarean deliveries. Future pregnancy considerations should be included in initial counseling for women contemplating open maternal-fetal surgery.

BackgroundDespite improvements in fetal survival for pregnancies affected by twin-twin transfusion syndrome since the introduction of laser photocoagulation, prematurity remains a major source of neonatal morbidity and mortality.ObjectiveTo investigate the indications and factors influencing the timing of delivery following laser treatment, we collected delivery information regarding twin-twin transfusion syndrome cases in a large multicenter cohort.Study designEleven North American Fetal Therapy Network (NAFTNet) centers conducted a retrospective review of twin-twin transfusion syndrome patients who underwent laser photocoagulation. Clinical, demographic and ultrasound variables including twin-twin transfusion syndrome stage, and gestational age at treatment and delivery were recorded. Primary and secondary maternal and fetal indications for delivery were identified. Univariate analysis was used to select candidate variables with significant correlation with latency and GA at delivery. Multivariable Cox regression with competing risk analysis was utilized to determine the independent associations.ResultsA total of 847 pregnancies were analyzed. After laser, the average latency to delivery was 10.11 ± 4.8 weeks and the mean gestational age at delivery was 30.7 ± 4.5 weeks. Primary maternal indications for delivery comprised 79% of cases. The leading indications included spontaneous labor (46.8%), premature rupture of membranes (17.1%), and placental abruption (8.4%). Primary fetal indications accounted for 21% of cases and the most frequent indications included donor non-reassuring status (20.5%), abnormal donor Dopplers (15.1%), and donor growth restriction (14.5%). The most common secondary indications for delivery were premature rupture of membranes, spontaneous labor and donor growth restriction. Multivariate modeling found gestational age at diagnosis, stage, history of prior amnioreduction, cerclage, interwin membrane disruption, procedure complications and chorioamniotic membrane separation as predictors for both gestational age at delivery and latency.ConclusionPremature delivery after laser therapy for twin-twin transfusion syndrome is primarily due to spontaneous labor, preterm premature rupture of membranes and non-reassuring status of the donor fetus. Placental abruption was found to be a frequent complication resulting in early delivery. Future research should be directed toward the goal of prolonging gestation after laser photocoagulation to further reduce morbidity and mortality associated with twin-twin transfusion syndrome.

CD8+ T cells recognize and eliminate tumors in an antigen-specific manner. Despite progress in characterizing the antitumor T cell repertoire and function, the identification of target antigens remains a challenge. Here we describe the use of chimeric receptors called signaling and antigen-presenting bifunctional receptors (SABRs) in a cell-based platform for T cell receptor (TCR) antigen discovery. SABRs present an extracellular complex comprising a peptide and major histocompatibility complex (MHC), and induce intracellular signaling via a TCR-like signal after binding with a cognate TCR. We devised a strategy for antigen discovery using SABR libraries to screen thousands of antigenic epitopes. We validated this platform by identifying the targets recognized by public TCRs of known specificities. Moreover, we extended this approach for personalized neoantigen discovery.

T cell receptor (TCR) ligand discovery is essential for understanding and manipulating immune responses to tumors. We developed a cell-based selection platform for TCR ligand discovery that exploits a membrane transfer phenomenon called trogocytosis. We discovered that T cell membrane proteins are transferred specifically to target cells that present cognate peptide-major histocompatibility complex (MHC) molecules. Co-incubation of T cells expressing an orphan TCR with target cells collectively presenting a library of peptide-MHCs led to specific labeling of cognate target cells, enabling isolation of these target cells and sequencing of the cognate TCR ligand. We validated this method for two clinically employed TCRs and further used the platform to identify the cognate neoepitope for a subject-derived neoantigen-specific TCR. Thus, target cell trogocytosis is a robust tool for TCR ligand discovery that will be useful for studying basic tumor immunology and identifying new targets for immunotherapy.

The response of plane-parallel 2 mm thick samples of 47.3Ni-52.7Ti alloy was studied in two series of planar impact tests at temperatures between 300 and 473 K and between 473 and 318 K (heating to 473 K followed by cooling). In two additional series, the samples of 0.4–4 mm thickness were tested at 300 and 338 K (after preheating up to 473 K). In all the tests, the samples were loaded by 1 mm thick copper impactors having velocities equal to 314 ± 2 m/s. The velocity of the rear sample surface was continuously monitored by a laser Doppler velocimeter. It was shown that substantial, by an order of magnitude, variation of Hugoniot elastic limit σ H E L and compressive strength Y of the nitinol with temperature are caused by the martensite–austenite transformation and its reversal. The variation of the dynamic tensile (spall) strength σ s p of the nitinol along the heating–cooling path was found similar to that of σ H E L although the difference between σ s p values of austenite and martensite, ∼20%, is much more modest than in the case of σ H E L . The test series performed at constant temperatures with samples of different thicknesses allows one to conclude that the plastic deformation in shocked austenite is presumably realized by dislocation motion and multiplication controlled by phonon viscosity. In the shocked martensite, the plastic deformation mechanism at a stress lower than ∼0.3 GPa is likely a thermally activated combination of deformation twinning and slip of kinking dislocations. [ABSTRACT FROM AUTHOR]

Acquisition of oral English verb morphology presents difficulties for bilinguals, learners of EFL and English-speaking monolingual children with specific language impairment. This study aimed to identify challenging English verb inflections among sixth grade speakers of Arabic (N = 85) and Hebrew (N = 86) using an elicited oral narrative task, and EFL L1, L2, L3 skills that support oral production of English morphosyntactic structures and verb inflections. To understand potential universal versus language specific patterns, we compared performance of our sample with that of monolingual children with specific language impairment. Oral narratives were transcribed and analysed for obligatory use of four target tenses to assess the use of verb inflectional morphology. Results indicated that 3rd person singular presented most difficulties for both groups. Present progressive was more difficult for Hebrew speakers, as Arabic utilises this aspectual form in oral modality, while copula was more problematic for Arabic speakers. This error pattern aligns with use of verb inflections by English monolingual SLIs. Notable differences were seen in EFL/ L1/L2/L3 skills supporting EFL verb inflections: Hebrew speakers relied mostly on English reading comprehension, while Arabic speakers drew support from EFL, L1, and Hebrew morphological awareness. We attribute these differences to the multilingual status of Arabic speakers. [ABSTRACT FROM AUTHOR]

The role of verbal working memory (VWM) in early language and literacy development among typical and atypical monolingual children exposed to different orthographies is well established. Less is known how English Language Learners (ELLs) allocate their VWM resources in early stages of literacy acquisition in English (L2). This study examined the role of phonological (PM) and working memory (WM) in L2 decoding, sight word recognition and spelling among ELLs attending kindergarten in an urban Title I school. The results of ELLs' assessments across cognitive and linguistic reading pre-requisites were compared to the assessments on the same measures of typical and specific language impaired (SLI) monolingual peers. Despite decreased vocabulary and lower phonological awareness (PA) skills ELLs did not differ from typical monolingual peers on VWM skills and early literacy outcomes, but outperformed SLIs. However, ELLs relied exclusively on PM for decoding and spelling, which differed from typical monolingual peers. These results provide important information regarding L2 language and early literacy development among Spanish-speaking ELLs, and should help to conceptualize the educational strategies for supporting ELLs based on their L1 structure. Measure of PM may be discriminating criteria between ELLs and SLIs, as poor PM is an established marker for SLI.

The article is dedicated to the memory of the author's teachers in psychology, written in connection with the anniversaries of the outstanding Russian psychologists P.Ya. Galperin and N.G. Alekseev. Both scientists are the authors of the ideas underlying the reflective–activity approach (RAA) to assist students in overcoming learning difficulties, developed by the author. In 2022, practicians of the RAA celebrate 25 years since the birth of the approach, and this event prompts the author to turn to the origins of its occurrence, to the ideas on the basis of which the RAA technology is built. P.Ya. Galperin's ideas on internalization and the formation of mental actions are combined with N.G. Alekseev's ideas on reflection and reflective thinking based on the basic principles of cultural–historical psychology developed by L.S. Vygotskii. As a basis for uniting the ideas of L.S. Vygotskii, P.Ya. Galperin and N.G. Alekseev, their attitude to psychological practice becomes. The implementation of these ideas within the framework of the RAA is briefly considered on the example of three projects: summer schools, chess for general development, assistance to orphans with disabilities and severe somatic diseases.

We present an interview with Valentina V. Nikolaeva, Doctor of Psychology, Professor of the Department of Neuro- and Pathopsychology, Lomonosov Moscow State University (Moscow, Russia).

Abstract Background For infants with severe congenital diaphragmatic hernia (CDH) stabilized with extracorporeal membrane oxygenation (ECMO), early repair on ECMO improves outcome; however when compared to operative repair after ECMO, repair on ECMO is associated with increase bleeding risk and need for blood product transfusions. Methods A retrospective review of 54 patients with CDH placed on ECMO prior to CDH repair was performed. For the subset of patients repaired on ECMO, analysis comparing those repaired early (within 48 h of cannulation) and late (beyond 48 h) on ECMO was performed. Outcomes of interest included survival to discharge, days on ECMO, and postoperative blood product utilization. Results When compared to those patients repaired prior to 48 h of ECMO initiation, 57.7% of patients survived versus 40.9% of late repair patients. For those repaired early, blood product utilization was significantly less. Early repair patients received a median of 72 mL/kg packed red blood cells (PRBC) and 75 mL/kg platelets compared to 151.9 mL/kg and 98.7 mL/kg, respectively (p < 0.05 respectively). There was no difference in median days on ECMO (p = 0.38). Conclusion Our data supports prior reports of improved outcome with repair with 48 h of ECMO initiation and suggests early repair on ECMO is associated with less bleeding and decreased blood product requirement in the postoperative period.

To understand the genetic drivers of immune recognition and evasion in colorectal cancer, we analyzed 1,211 colorectal cancer primary tumor samples, including 179 classified as microsatellite instability-high (MSI-high). This set includes The Cancer Genome Atlas colorectal cancer cohort of 592 samples, completed and analyzed here. MSI-high, a hypermutated, immunogenic subtype of colorectal cancer, had a high rate of significantly mutated genes in important immune-modulating pathways and in the antigen presentation machinery, including biallelic losses of B2M and HLA genes due to copy-number alterations and copy-neutral loss of heterozygosity. WNT/β-catenin signaling genes were significantly mutated in all colorectal cancer subtypes, and activated WNT/β-catenin signaling was correlated with the absence of T-cell infiltration. This large-scale genomic analysis of colorectal cancer demonstrates that MSI-high cases frequently undergo an immunoediting process that provides them with genetic events allowing immune escape despite high mutational load and frequent lymphocytic infiltration and, furthermore, that colorectal cancer tumors have genetic and methylation events associated with activated WNT signaling and T-cell exclusion.Significance: This multi-omic analysis of 1,211 colorectal cancer primary tumors reveals that it should be possible to better monitor resistance in the 15% of cases that respond to immune blockade therapy and also to use WNT signaling inhibitors to reverse immune exclusion in the 85% of cases that currently do not. Cancer Discov; 8(6); 730-49. ©2018 AACR.This article is highlighted in the In This Issue feature, p. 663.