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Early Childhood Matters documents the rapid development of early years education and care from the late 1990s into the new millennium. It chronicles the unique contribution of the EPPE research to our understanding of the importance of pre-school. The Effective Pre-school and Primary Education (EPPE) project is the largest European study of the impact of early years education and care on children’s developmental outcomes. Through this ground-breaking project a team of internationally-recognised experts provide insights into how home learning environments interact with pre-school and primary school experiences to shape children’s progress. The findings of this fascinating project: provide new evidence of the importance of early childhood experiences show how these experiences influence children’s cognitive, social and behavioural development give new insights on the importance of early years education will be relevant to a wide audience who are interested in policy development, early years education and care, and ‘effectiveness’ research examine how the combined effects of pre-school, primary school and the family interact to shape children’s educational outcomes. This insightful book is essential reading for all those interested in innovative research methodology and policy development in early childhood education and care. It provides new evidence on good practice in early years settings and will have a wide appeal for students and those engaged in providing accredited courses of study at a range of levels in early childhood. Selected Contents: Chapter 1 Introduction: Why EPPE? Kathy Sylva and the EPPE Team Chapter 2 The EPPE settings in the context of English pre-schools Iram Siraj-Blatchford Chapter 3 The EPPE Research design: An educational effectiveness focus Pam Sammons Chapter 4 Why children, parents and home learning are important Edward Melhuish Chapter 5 Quality in Early Childhood settings Kathy Sylva Chapter 6 Does pre-school make a difference?: Results over the pre-school period (to aged 5) Pam Sammons Chapter 7 Do the benefits of pre-school last? Investigating pupil outcomes to the end of Key Stage 2 (aged 11) Pam Sammons Chapter 8 A focus on pedagogy: Case studies of effective practice Iram Siraj-Blatchford Chapter 9 Vulnerable children: Identifying children ‘at risk’ Brenda Taggart Chapter 10 A linked study: Effective Pre-school Provision in Northern Ireland Edward Melhuish Chapter 11 Making a difference: How research can inform policy Brenda Taggart Chapter 12 Re-thinking the evidence-base for Early Years policy and practice Kathy Sylva Glossary of terms Appendix 1 How children were assessed at different time points throughout the study Appendix 2 The Home Learning Environment at different time points Appendix 3 The EPPE Technical Papers Appendix 4 Social/behavioural dimensions at different time points (items associated with dimensions) Appendix 5 The Multiple Disadvantage Index Appendix 6 Results from analyses of pre-school effects compared with those of family income and parents’ employment status Kathy Sylva is Professor of Educational Psychology, University of Oxford. Edward Melhuish is Professor of Human Development, Birkbeck College, University of London. Pam Sammons is Professor of Education, University of Oxford. Iram Siraj-Blatchford is Professor of Education, Institute of Education, University of London. Brenda Taggart is Senior Research Officer, Institute of Education, University of London.

Children spend more time in school than in any social institution outside the home. And schools probably exert more influence on children's development and life chances than any environment beyond the home and neighbourhood. The purpose of this book is to document some important ways schools influence children's development and to describe various models and methods for studying schooling effects. Key features include: Comprehensive Coverage - this is the first book to provide a comprehensive review of what is known about schools as a context for human development. Topical coverage ranges from theoretical foundations to investigative methodologies and from classroom-level influences such as teacher-student relations to broader influences such as school organization and educational policies. Cross-Disciplinary - this volume brings together the divergent perspectives, methods and findings of scholars from a variety of disciplines, among them educational psychology, developmental psychology, school psychology, social psychology, psychiatry, sociology, and educational policy. Chapter Structure - to ensure continuity, chapter authors describe 1) how schooling influences are conceptualized 2) identify their theoretical and methodological approaches 3) discuss the strengths and weaknesses of existing research and 4) highlight implications for future research, practice, and policy. Methodologies - chapters included in the text feature various methodologies including longitudinal studies, hierarchical linear models, experimental and quasi-experimental designs, and mixed methods.

Plain English summary In the UK, more patients go to primary care than other parts of the health service. Therefore it is important for research into primary care to include the insights and views of people who receive these services. To explore the extent, quality and impact of patient and public involvement (PPI) in primary care research, we examined documents of 200 projects and surveyed 191 researchers. We found that about half of studies included PPI to develop research ideas and during the study itself. Common activities included designing study materials, advising on methods, and managing the research. Some studies did not undertake the PPI activities initially planned and funded for. PPI varied by study design, health condition and study population. We found pockets of good practice: having a PPI budget, supporting PPI contributors, and PPI informing recruitment issues. However, good practice was lacking in other areas. Few projects offered PPI contributors training, used PPI to develop information for participants about study progress and included PPI to advise on publishing findings. Researchers reported beneficial impacts of PPI. Most impact was reported when the approach to PPI included more indicators of good practice. The main cost of PPI for researchers was their time. Many reported difficulties providing information about PPI. In partnership with PPI contributors, we have used these findings to develop: a new Cost and Consequences Framework for PPI highlighting financial and non-financial costs, benefits and harms of PPI Fifteen co-produced recommendations to improve the practice and delivery of PPI. Background: To improve the lives of patients in primary care requires the involvement of service users in primary care research. We aimed to explore the extent, quality and impact of patient and public involvement (PPI) in primary care research. Methods: We extracted information about PPI from grant applications, reports and an electronic survey of researchers of studies funded by the NIHR School for Primary Care Research (SPCR). We applied recognised quality indicators to assess the quality of PPI and assessed its impact on research. Results: We examined 200 grant applications and reports of 181 projects. PPI was evident in the development of 47 (24%) grant applications. 113 (57%) grant applications included plans for PPI during the study, mostly in study design, oversight, and dissemination. PPI during projects was reported for 83 (46%) projects, including designing study materials and managing the research. We identified inconsistencies between planned and reported PPI. PPI varied by study design, health condition and study population. Of 46 (24%) of 191 questionnaires completed, 15 reported PPI activity. Several projects showed best practice according to guidelines, in terms of having a PPI budget, supporting PPI contributors, and PPI informing recruitment issues. However few projects offered PPI contributors training, used PPI to develop information for participants about study progress, and had PPI in advising on dissemination. Beneficial impacts of PPI in designing studies and writing participant information was frequently reported. Less impact was reported on developing funding applications, managing or carrying out the research. The main cost of PPI for researchers was their time. Many researchers found it difficult to provide information about PPI activities. Our findings informed: a new Cost and Consequences Framework for PPI in primary care research highlighting financial and non-financial costs, plus the benefits and harms of PPI Fifteen co-produced recommendations to improve PPI in research and within the SPCR. Conclusions: The extent, quality and impact of PPI in primary care research is inconsistent across research design and topics. Pockets of good practice were identified making a positive impact on research. The new Cost and Consequences Framework may help others assess the impact of PPI.

Background Psychological disorders including depression and anxiety are not rare in primary care clinics. The Patient Health Questionnaire (PHQ) is a clinical diagnostic tool that is widely utilized by primary health care physicians worldwide because it provides a practical in-clinic tool to screen for psychological disorders. This study evaluated the validity of the Arabic version of the PHQ in all six modules including depression, anxiety, somatic, panic, eating, and alcohol abuse disorders. Methods This is a quantitative observational cross-sectional study that was conducted by administrating the translated Arabic version of PHQ to a sample of King Saud University students in Riyadh, Saudi Arabia. Results The sample was 731 university students who participated in this study including 376 (51.6%) females and 354 (48.4%) males with a mean age of 21.30 years. Eight mental health experts carried out the face validation process of the PHQ Arabic version. The internal consistency reliability was measured using Cronbach’s alpha for the PHQ9, GAD7, PHQ15, and panic disorder modules. The results were 0.857, 0.763, 0.826, and 0.696, respectively. In comparison, the eating disorders and alcohol abuse modules demonstrated poor internal consistency due to small number of participants in these modules. Conclusion This study demonstrates that the Arabic version of the PHQ is a valid and reliable tool to screen for depression, anxiety, somatic, and panic disorders in a Saudi sample.

Background Cancer stem cells (CSCs) play crucial role in tumor progression, drug resistance and relapse in various cancers. CSC niche is comprised of various stromal cell types including Tumor-associated macrophages (TAMs). Extrinsic ques derived from these cells help in maintenance of CSC phenotype. TAMs have versatile roles in tumor progression however their function in enrichment of CSC is poorly explored. Methods Mouse macrophages (RAW264.7) cells were activated by interaction with conditioned media (CM) of murine breast cancer cells (4T1) into TAMs and the effect of activated macrophage (TAM) derived factors was examined on enrichment of cancer stem cells (CSCs) and tumor growth using in vitro and in vivo models. Results In this study, we report that macrophages upon interaction with breast cancer cells activate tumor promoting function and exhibit differential expression of various proteins as shown by secretome analysis using proteomics studies. Based on secretome data, we found that Interleukin-6 (IL-6) is one of the up-regulated genes expressed in activated macrophages. Further, we confirm that TAMs produce high levels of IL-6 and breast cancer cell derived factors induce IL-6 production in activated macrophages via p38-MAPK pathway. Furthermore, we demonstrate that tumor activated macrophages induce enrichment of CSCs and expression of CSC specific transcription factors such as Sox-2, Oct-3/4 and Nanog in breast cancer cells. We further prove that TAM derived IL-6 plays a key role in TAM mediated CSC enrichment through activation of Signal transducer and activator of transcription 3 (STAT-3) signaling. TAM derived IL-6 influences breast cancer cell migration and angiogenesis. Moreover, our in vivo findings indicated that TAM derived IL-6 induces CSC population and resulting tumor growth in breast cancer. Conclusion These finding provide evidence that TAM derived IL-6 plays a major role in CSC enrichment and tumor progression in breast cancer and IL-6 and its regulated signalling network may act as potential therapeutic target for management of breast cancer.

Background N6-methyladenosine (m 6 A) has emerged as a significant regulator of the progress of various cancers. However, its role in lung adenocarcinoma (LUAD) remains unclear. Here, we explored the biological function and underlying mechanism of methyltransferase-like 3 (METTL3), the main catalyst of m 6 A, in LUAD progression. Methods The expression of m 6 A, METTL3, YTHDF1 and SLC7A11 were detected by immunochemistry or/and online datasets in LUAD patients. The effects of METTL3 on LUAD cell proliferation, apoptosis and ferroptosis were assessed through in vitro loss-and gain-of-function experiments. The in vivo effect on tumorigenesis of METTL3 was evaluated using the LUAD cell xenograft mouse model. MeRIP-seq, RNA immunoprecipitation and RNA stability assay were conducted to explore the molecular mechanism of METTL3 in LUAD. Results The results showed that the m 6 A level, as well as the methylase METTL3 were both significantly elevated in LUAD patients and lung cancer cells. Functionally, we found that METTL3 could promote proliferation and inhibit ferroptosis in different LUAD cell models, while METTL3 knockdown suppressed LUAD growth in cell-derived xenografts. Mechanistically, solute carrier 7A11 (SLC7A11), the subunit of system Xc − , was identified as the direct target of METTL3 by mRNA-seq and MeRIP-seq. METTL3-mediated m 6 A modification could stabilize SLC7A11 mRNA and promote its translation, thus promoting LUAD cell proliferation and inhibiting cell ferroptosis, a novel form of programmed cell death. Additionally, we demonstrated that YTHDF1, a m 6 A reader, was recruited by METTL3 to enhance SLC7A11 m 6 A modification. Moreover, the expression of YTHDF1 and SLC7A11 were positively correlated with METTL3 and m 6 A in LUAD tissues. Conclusions These findings reinforced the oncogenic role of METTL3 in LUAD progression and revealed its underlying correlation with cancer cell ferroptosis; these findings also indicate that METTL3 is a promising novel target in LUAD diagnosis and therapy.

Background Hepatocellular carcinoma (HCC) remains a major challenge for public health worldwide. Considering the great heterogeneity of HCC, more accurate prognostic models are urgently needed. To identify a robust prognostic gene signature, we conduct this study. Materials and methods Level 3 mRNA expression profiles and clinicopathological data were obtained in The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC). GSE14520 dataset from the gene expression omnibus (GEO) database was downloaded to further validate the results in TCGA. Differentially expressed mRNAs between HCC and normal tissue were investigated. Univariate Cox regression analysis and lasso Cox regression model were performed to identify and construct the prognostic gene signature. Time-dependent receiver operating characteristic (ROC), Kaplan–Meier curve, multivariate Cox regression analysis, nomogram, and decision curve analysis (DCA) were used to assess the prognostic capacity of the six-gene signature. The prognostic value of the gene signature was further validated in independent GSE14520 cohort. Gene Set Enrichment Analyses (GSEA) was performed to further understand the underlying molecular mechanisms. The performance of the prognostic signature in differentiating between normal liver tissues and HCC were also investigated. Results A novel six-gene signature (including CSE1L, CSTB, MTHFR, DAGLA, MMP10, and GYS2) was established for HCC prognosis prediction. The ROC curve showed good performance in survival prediction in both the TCGA HCC cohort and the GSE14520 validation cohort. The six-gene signature could stratify patients into a high- and low-risk group which had significantly different survival. Cox regression analysis showed that the six-gene signature could independently predict OS. Nomogram including the six-gene signature was established and shown some clinical net benefit. Furthermore, GSEA revealed several significantly enriched oncological signatures and various metabolic process, which might help explain the underlying molecular mechanisms. Besides, the prognostic signature showed a strong ability for differentiating HCC from normal tissues. Conclusions Our study established a novel six-gene signature and nomogram to predict overall survival of HCC, which may help in clinical decision making for individual treatment.