Evaluation of Year 1 of the Tuition Partners Programme: Impact Evaluation for Primary Schools. Evaluation Report

The National Tutoring Programme (NTP) Tuition Partners (TP) programme was designed to provide additional support to schools and teachers to supplement classroom teaching through subsidised high-quality tutoring for pupils from an approved list of tutoring organisations, the Tuition Partners. This evaluation covers the TP programme as delivered in its first year by the Education Endowment Foundation (EEF), from November 2020 to August 2021. Tuition Partners was one arm of the NTP. The NTP aimed to support teachers and schools in providing a sustained response to the Covid-19 pandemic and to provide a longer term contribution to closing the attainment gap between disadvantaged pupils and their peers. The NTP was part of a wider government response to the pandemic, funded by the Department for Education and originally developed by the EEF, Nesta, Impetus, The Sutton Trust, and Teach First, and with the support of the KPMG Foundation. The EEF appointed 33 approved ‘Tuition Partners’ that schools could select from to deliver tuition. Schools could access 15 hours of tutoring per selected pupil (with a minimum of 12 hours being considered a completed block of tuition). Tuition was provided online and/or face-to-face; and was 1:1, or in small groups (1:2 or 1:3); and available in English, maths, science, humanities and modern foreign languages. Tuition was expected to be delivered in schools (before, during and after school), in addition to usual teaching; and, in certain circumstances, at home. The programme was targeted at disadvantaged pupils attending state-maintained schools in England, including those eligible for Pupil Premium funding (PP-eligible), Free School Meals (FSM), or those identified by schools as having an equivalent need for support. Participating schools had discretion to identify which of their pupils they felt would most benefit from additional tuition support. Pupils in Years 1–11 were eligible (5–16 years old). The programme aimed to reach 215,000 to 265,000 pupils, across 6000 state-maintained schools in England, and it was expected that approximately 20,000 tutors would be recruited by Tuition Partners. The TP programme was set up and delivered during the Covid-19 pandemic, requiring continued responsiveness to the challenges faced by schools including restricted attendance, remote teaching, and ongoing widespread staff and pupil absences. During the school closures to most pupils from January – March 2021, the EEF approved TPs to deliver online tuition at home, however many schools chose to wait to commence tutoring until schools reopened fully, and therefore started tutoring later than planned. This evaluation report covers the analysis on the impact of the TP programme on the maths and English attainment outcomes for primary school pupils (Years 1–6) using standardised classroom assessments. Separate reports relate to analysis on Year 11 pupils and an implementation and process evaluation (IPE). The evaluation findings for the TP programme are brought together in a summary and interpretation report that is available here. This evaluation uses a quasi-experimental design (QED), involving a group of intervention schools that participated in the TP programme, and a group of comparison schools that did not receive the programme. The evaluation relies on a propensity score matching and re-weighting approach to ensure that the intervention and comparison schools are similar to each other in important, observable regards. As pupils who would have received TP in comparison schools were difficult to identify, the evaluation focused on pupils eligible for Pupil Premium and on all pupils, as these groups can be identified in both TP and comparison schools. For English, the analysis is based on 165 primary schools with 7073 pupils eligible for Pupil Premium and for maths, 126 primary schools with 5102 pupils eligible for Pupil Premium3. An additional instrumental variable (IV) analysis, based on the sample of TP schools only, looked at the impact of TP in schools that signed up to the TP programme earlier (and that delivered more tutoring) compared to schools that signed up later. On average, pupils eligible for Pupil Premium in schools that received TP made similar progress in English and maths compared to pupils eligible for Pupil Premium in comparison schools (no evidence of an effect in English or in maths). This result has a low security rating. A particular challenge is that, on average, only approximately 20% of pupils eligible for Pupil Premium were selected for tutoring, meaning a large proportion of pupils eligible for Pupil Premium were included in the analysis who did not receive tutoring. Therefore, this estimated impact of TP is diluted and it is hard to detect any effect that may (or may not) be present. Similar analysis on all pupils found that pupils in schools that received TP made, on average, similar progress in English compared to all pupils in comparison schools (no evidence of an effect), and an additional one month’s progress in maths compared to pupils in comparison schools. However, there is uncertainty around these estimates, with the positive maths result being consistent with a null (0 months) or slightly larger positive effect (2 months) and the English result being consistent with small positive (1 month) or small negative effect (−1 months). Furthermore, this analysis was subject to even further dilution: on average, only 12% (for maths) and 14% (for English) of pupils in the analysed schools were selected for tutoring. Given this context, it is unlikely that any of these differences were due to TP. In the sample of TP schools, completing a 12-hour block of tutoring (compared to zero hours) was related to higher English scores amongst pupils eligible for Pupil Premium that received more tutoring due to the early sign-up of the school. An equivalent analysis for maths was not able to proceed. A different analysis within TP schools showed that pupils who received more hours of tutoring were associated with higher English scores on average than pupils who received fewer hours of tutoring. However, this was not the case for maths, where receiving more hours of tutoring was not associated with higher maths scores. These results are associations and are not necessarily causal estimates of impact; there may be other explanations for the results

Evaluation of Year 1 of the Tuition Partners Programme: Impact Evaluation Report for Year 11. Evaluation Report: An exploration of impact in Year 11

The National Tutoring Programme (NTP) Tuition Partners (TP) programme was designed to provide additional support to schools and teachers to supplement classroom teaching through subsidised, high quality tutoring for pupils from an approved list of tutoring organisations, the Tuition Partners. This evaluation covers the TP programme as delivered in its first year by the Education Endowment Foundation (EEF), from November 2020 to August 2021. Tuition Partners was one arm of the NTP. The NTP aimed to support teachers and schools in providing a sustained response to the Covid-19 pandemic and to provide a longer term contribution to closing the attainment gap between disadvantaged pupils and their peers. The NTP was part of a wider government response to the pandemic, funded by the Department for Education and originally developed by the EEF, Nesta, Impetus, The Sutton Trust, and Teach First, and with the support of the KPMG Foundation. The EEF appointed 33 approved ‘Tuition Partners’ that schools could select from to deliver tuition. Schools could access 15 hours of tutoring per selected pupil (with a minimum of 12 hours being considered a completed block of tuition). Tuition was provided online and/or face-to-face; and was 1:1, or in small groups (1:2 or 1:3); and available in English, maths, science, humanities and modern foreign languages. Tuition was expected to be delivered in schools (before, during and after school), in addition to usual teaching; and in certain circumstances, at home. The programme was targeted at disadvantaged pupils attending state-maintained schools in England, including those eligible for Pupil Premium funding (PP-eligible), Free School Meals (FSM), or those identified by schools as having an equivalent need for support. Participating schools had discretion to identify which of their pupils they felt would most benefit from additional tuition support. Pupils in Years 1–11 were eligible (5–16 years old). The programme aimed to reach 215,000 to 265,000 pupils, across 6,000 state-maintained schools in England, and it was expected that approximately 20,000 tutors would be recruited by Tuition Partners. The TP programme was set up and delivered during the Covid-19 pandemic, requiring continued responsiveness to the challenges faced by schools including restricted attendance, remote teaching, and ongoing widespread staff and pupil absences. During school closures to most pupils from January – March 2021, the EEF approved TPs to deliver online tuition at home, however many schools chose to wait to commence tutoring until schools reopened fully, and therefore started tutoring later than planned. The usual summer exams process for Year 11 pupils could not go ahead as planned in summer 2021, and GCSEs were determined by TAGs instead. This evaluation report covers the analysis on the impact of the TP programme on the maths and English attainment outcomes for Year 11 pupils only. Separate reports relate to analysis on a sample of primary schools and an implementation and process evaluation (IPE). The evaluation findings for the TP programme are brought together in a summary and interpretation report that is available here. This evaluation uses a quasi-experimental design (QED), involving a group of intervention schools that participated in the TP programme, and a group of comparison schools that did not receive the programme. The evaluation relies on a propensity score matching approach to ensure that the intervention and comparison schools are similar to each other in important, observable regards. As pupils who would have received TP in comparison schools were difficult to identify, the evaluation focused on pupils eligible for Pupil Premium and on all pupils, as these groups can be identified in both TP and non-TP schools. The analysis is based on 1,464 secondary schools with a total of 62,024 pupils eligible for Pupil Premium. The evaluation assessed impact in English and maths using Teacher Assessed Grades (TAGs) from 2021. Year 11 pupils eligible for Pupil Premium in schools that received TP made similar progress in English and maths compared to pupils eligible for Pupil Premium in comparison schools (there was no evidence of an effect in English or maths). A particular challenge is that, on average, only 12% of pupils eligible for Pupil Premium were selected for tutoring in maths and 9% were selected for tutoring in English, meaning the vast majority of the pupils included in the analysis did not receive tutoring. Therefore, this estimated impact of TP is diluted and it is hard to detect any effect that may (or may not) be present. When looking at all pupils in Year 11, pupils in schools that received TP made, on average, similar progress in English compared to all Year 11 pupils in comparison schools (there was no evidence of an effect). In maths, Year 11 pupils in schools that received TP made slightly less progress than all Year 11 pupils in comparison schools (though this effect was very small and equivalent to zero months ’ additional progress). However, this analysis was subject to even further dilution than the PPeligible analysis: only 7% of Year 11 pupils were selected for tutoring in maths and 6% in English. Given this context, it is unlikely that any of these differences were due to TP. Additional analysis restricted the sample of schools to those that targeted higher proportions of pupils eligible for Pupil Premium to receive tutoring, to reduce the issue of dilution and bring the group of analysed pupils closer to those that were selected for the intervention. In schools that selected over 50% of pupils eligible for Pupil Premium for tutoring, pupils eligible for Pupil Premium made similar progress in TP and comparison schools in English and maths. However, when the sample was restricted to schools that selected over 70% of pupils eligible for Pupil Premium for tutoring (and reducing dilution further), the impact of TP on pupils eligible for Pupil Premium is positive. In these schools, pupils eligible for Pupil Premium made, on average, the equivalent of two months additional progress in English and two months additional progress in maths, compared to pupils eligible for Pupil Premium in comparison schools. This analysis was based on a smaller sample of schools that were rematched to a comparison sample. However, different characteristics to the rest of the TP population of schools remained (more ‘Outstanding’ schools, lower percentage of FSM students), so this finding may not necessarily be generalisable to all TP schools. Within schools that participated in TP, pupils who received more hours of tutoring in maths obtained higher maths TAGs, and pupils who received more hours of tutoring in English obtained higher English TAGs, than pupils who received fewer hours of tutoring in the respective subjects. These results are associations and are not necessarily causal estimates of impact; there may be other explanations for the higher grades among these pupils

Undergraduate research. Genomics Education Partnership

The Genomics Education Partnership offers an inclusive model for undergraduate research experiences incorporated into the academic year science curriculum, with students pooling their work to contribute to international data bases

Expression and Localization of CLC Chloride Transport Proteins in the Avian Retina

Members of the ubiquitously expressed CLC protein family of chloride channels and transporters play important roles in regulating cellular chloride and pH. The CLCs that function as Cl−/H+ antiporters, ClCs 3–7, are essential in particular for the acidification of endosomal compartments and protein degradation. These proteins are broadly expressed in the nervous system, and mutations that disrupt their expression are responsible for several human genetic diseases. Furthermore, knock-out of ClC3 and ClC7 in the mouse result in the degeneration of the hippocampus and the retina. Despite this evidence of their importance in retinal function, the expression patterns of different CLC transporters in different retinal cell types are as yet undescribed. Previous work in our lab has shown that in chicken amacrine cells, internal Cl− can be dynamic. To determine whether CLCs have the potential to participate, we used PCR and immunohistochemical techniques to examine CLC transporter expression in the chicken retina. We observed a high level of variation in the retinal expression levels and patterns among the different CLC proteins examined. These findings, which represent the first systematic investigation of CLC transporter expression in the retina, support diverse functions for the different CLCs in this tissue

Human ClC-6 Is a Late Endosomal Glycoprotein that Associates with Detergent-Resistant Lipid Domains

BACKGROUND: The mammalian CLC protein family comprises nine members (ClC-1 to -7 and ClC-Ka, -Kb) that function either as plasma membrane chloride channels or as intracellular chloride/proton antiporters, and that sustain a broad spectrum of cellular processes, such as membrane excitability, transepithelial transport, endocytosis and lysosomal degradation. In this study we focus on human ClC-6, which is structurally most related to the late endosomal/lysomal ClC-7. PRINCIPAL FINDINGS: Using a polyclonal affinity-purified antibody directed against a unique epitope in the ClC-6 COOH-terminal tail, we show that human ClC-6, when transfected in COS-1 cells, is N-glycosylated in a region that is evolutionary poorly conserved between mammalian CLC proteins and that is located between the predicted helices K and M. Three asparagine residues (N410, N422 and N432) have been defined by mutagenesis as acceptor sites for N-glycosylation, but only two of the three sites seem to be simultaneously N-glycosylated. In a differentiated human neuroblastoma cell line (SH-SY5Y), endogenous ClC-6 colocalizes with LAMP-1, a late endosomal/lysosomal marker, but not with early/recycling endosomal markers such as EEA-1 and transferrin receptor. In contrast, when transiently expressed in COS-1 or HeLa cells, human ClC-6 mainly overlaps with markers for early/recycling endosomes (transferrin receptor, EEA-1, Rab5, Rab4) and not with late endosomal/lysosomal markers (LAMP-1, Rab7). Analogously, overexpression of human ClC-6 in SH-SY5Y cells also leads to an early/recycling endosomal localization of the exogenously expressed ClC-6 protein. Finally, in transiently transfected COS-1 cells, ClC-6 copurifies with detergent-resistant membrane fractions, suggesting its partitioning in lipid rafts. Mutating a juxtamembrane string of basic amino acids (amino acids 71-75: KKGRR) disturbs the association with detergent-resistant membrane fractions and also affects the segregation of ClC-6 and ClC-7 when cotransfected in COS-1 cells. CONCLUSIONS: We conclude that human ClC-6 is an endosomal glycoprotein that partitions in detergent resistant lipid domains. The differential sorting of endogenous (late endosomal) versus overexpressed (early and recycling endosomal) ClC-6 is reminiscent of that of other late endosomal/lysosomal membrane proteins (e.g. LIMP II), and is consistent with a rate-limiting sorting step for ClC-6 between early endosomes and its final destination in late endosomes

A Cytoplasmic Domain Mutation in ClC-Kb Affects Long-Distance Communication Across the Membrane

BACKGROUND: ClC-Kb and ClC-Ka are homologous chloride channels that facilitate chloride homeostasis in the kidney and inner ear. Disruption of ClC-Kb leads to Bartter's Syndrome, a kidney disease. A point mutation in ClC-Kb, R538P, linked to Bartter's Syndrome and located in the C-terminal cytoplasmic domain was hypothesized to alter electrophysiological properties due to its proximity to an important membrane-embedded helix. METHODOLOGY/PRINCIPAL FINDINGS: Two-electrode voltage clamp experiments were used to examine the electrophysiological properties of the mutation R538P in both ClC-Kb and ClC-Ka. R538P selectively abolishes extracellular calcium activation of ClC-Kb but not ClC-Ka. In attempting to determine the reason for this specificity, we hypothesized that the ClC-Kb C-terminal domain had either a different oligomeric status or dimerization interface than that of ClC-Ka, for which a crystal structure has been published. We purified a recombinant protein corresponding to the ClC-Kb C-terminal domain and used multi-angle light scattering together with a cysteine-crosslinking approach to show that the dimerization interface is conserved between the ClC-Kb and ClC-Ka C-terminal domains, despite the fact that there are several differences in the amino acids that occur at this interface. CONCLUSIONS: The R538P mutation in ClC-Kb, which leads to Bartter's Syndrome, abolishes calcium activation of the channel. This suggests that a significant conformational change--ranging from the cytoplasmic side of the protein to the extracellular side of the protein--is involved in the Ca(2+)-activation process for ClC-Kb, and shows that the cytoplasmic domain is important for the channel's electrophysiological properties. In the highly similar ClC-Ka (90% identical), the R538P mutation does not affect activation by extracellular Ca(2+). This selective outcome indicates that ClC-Ka and ClC-Kb differ in how conformational changes are translated to the extracellular domain, despite the fact that the cytoplasmic domains share the same quaternary structure

X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes

X-linked intellectual disability (XLID) is a clinically and genetically heterogeneous disorder. During the past two decades in excess of 100 X-chromosome ID genes have been identified. Yet, a large number of families mapping to the X-chromosome remained unresolved suggesting that more XLID genes or loci are yet to be identified. Here, we have investigated 405 unresolved families with XLID. We employed massively parallel sequencing of all X-chromosome exons in the index males. The majority of these males were previously tested negative for copy number variations and for mutations in a subset of known XLID genes by Sanger sequencing. In total, 745 X-chromosomal genes were screened. After stringent filtering, a total of 1297 non-recurrent exonic variants remained for prioritization. Co-segregation analysis of potential clinically relevant changes revealed that 80 families (20%) carried pathogenic variants in established XLID genes. In 19 families, we detected likely causative protein truncating and missense variants in 7 novel and validated XLID genes (CLCN4, CNKSR2, FRMPD4, KLHL15, LAS1L, RLIM and USP27X) and potentially deleterious variants in 2 novel candidate XLID genes (CDK16 and TAF1). We show that the CLCN4 and CNKSR2 variants impair protein functions as indicated by electrophysiological studies and altered differentiation of cultured primary neurons from Clcn4−/− mice or after mRNA knock-down. The newly identified and candidate XLID proteins belong to pathways and networks with established roles in cognitive function and intellectual disability in particular. We suggest that systematic sequencing of all X-chromosomal genes in a cohort of patients with genetic evidence for X-chromosome locus involvement may resolve up to 58% of Fragile X-negative cases

Large-Scale Phenotyping of an Accurate Genetic Mouse Model of JNCL Identifies Novel Early Pathology Outside the Central Nervous System

Cln3Δex7/8 mice harbor the most common genetic defect causing juvenile neuronal ceroid lipofuscinosis (JNCL), an autosomal recessive disease involving seizures, visual, motor and cognitive decline, and premature death. Here, to more thoroughly investigate the manifestations of the common JNCL mutation, we performed a broad phenotyping study of Cln3Δex7/8 mice. Homozygous Cln3Δex7/8 mice, congenic on a C57BL/6N background, displayed subtle deficits in sensory and motor tasks at 10–14 weeks of age. Homozygous Cln3Δex7/8 mice also displayed electroretinographic changes reflecting cone function deficits past 5 months of age and a progressive decline of retinal post-receptoral function. Metabolic analysis revealed increases in rectal body temperature and minimum oxygen consumption in 12–13 week old homozygous Cln3Δex7/8mice, which were also seen to a lesser extent in heterozygous Cln3Δex7/8 mice. Heart weight was slightly increased at 20 weeks of age, but no significant differences were observed in cardiac function in young adults. In a comprehensive blood analysis at 15–16 weeks of age, serum ferritin concentrations, mean corpuscular volume of red blood cells (MCV), and reticulocyte counts were reproducibly increased in homozygous Cln3Δex7/8 mice, and male homozygotes had a relative T-cell deficiency, suggesting alterations in hematopoiesis. Finally, consistent with findings in JNCL patients, vacuolated peripheral blood lymphocytes were observed in homozygous Cln3Δex7/8 neonates, and to a greater extent in older animals. Early onset, severe vacuolation in clear cells of the epididymis of male homozygous Cln3Δex7/8 mice was also observed. These data highlight additional organ systems in which to study CLN3 function, and early phenotypes have been established in homozygous Cln3Δex7/8 mice that merit further study for JNCL biomarker development

Plasmid macro-evolution: selection of deletions during adaptation in a nutrient-limited environment

Under conditions where plasmid-carriage is deleterious to the cell, evolutionary changes may be expected which result in an attenuation of the deleterious effect of the plasmid. During long-term growth in glucose-limited continuous culture, initiated with a single clone of Escherichia coli containing a derivative of the plasmid pBR322, a structural change arose in the plasmid and predominated in the plasmid-containing sector of the population. This variant possessed a 2.25 kb deletion encompassing the tetracycline resistance operon as well as a region of about 1.5 kb upstream from this operon. Competition experiments involving strains carrying the plasmid with the spontancous deletion, and strains carrying plasmids with artificially constructed deletions, revealed that deletion of this region of the plasmid, involving loss of tetracycline resistance, resulted in an increment in fitness of between 10 and 20%. From the magnitude of the growth advantage, we conclude that the attenuation of the deleterious effect of the plasmid was mainly due to a reduction in the plasmid mediated interference in the metabolism of the cell caused by a deletion of the tetracycline resistance gene.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42797/1/10709_2004_Article_BF00127247.pd