Statistical Analysis Plan: SMART Spaces: Spaced Learning Revision Programme

This statistical analysis plan sets out the planned analysis for the evaluation of SMART Spaces: Spaced Learning Revision Programme (SMART Spaces Revision), an efficacy trial funded by the Education Endowment Foundation (EEF), to investigate the effect of the intervention on the chemistry element of the GCSE double award science. The SMART Spaces revision programme uses spaced learning within chemistry revision for the AQA GCSE double award science examinations. Evidence from neuroscience and cognitive psychology (e.g. Fields, 2009) indicates that including spaces – time intervals - between learning sessions can improve factual recall. It is anticipated that improved factual recall will have a positive impact on the application and analysis as well as knowledge elements of the chemistry score in GCSE double award science. An earlier pilot study (O’Hare, Stark, McGuinness, Biggart & Thurston, 2017), also funded by the EEF, suggested that a combination of short (10 minute) and longer (approximately 24 hour or night-time sleep) spaces provides a promising model of spacing. The intervention comprises both continuing professional development (CPD) and support for teachers to deliver the SMART Spaces revision programme and teacher implementation of the programme in Year 11 science lessons. The programme consists of six lessons delivered over two weeks and is designed to space the revision of content both between and within lessons. The chemistry topics for AQA Paper 1 are covered in one SMART Spaces lesson. This lesson is repeated three times in the same week, with spaces which allow pupils a nighttime sleep between lessons. After at least one further night-time sleep, but ideally the following week, the process is repeated for content associated with AQA Paper 2. Within lessons, chemistry topics are revised using the SMART spaces materials in three short ~12- minute sessions with 10-minute spaces between each topic. During the 10-minute spaces, pupils take part in a sensorimotor activity (such as juggling). The evaluation is structured as a two-armed school-level cluster randomised controlled trial involving 125 secondary schools. Fifty-four schools were allocated to receive the intervention and 71 to a business as usual control group. Recruitment occurred in Spring-Autumn 2018 with the aim of initiating training for teachers in intervention schools in November 2018. The evaluation will look at the impact of the programme on pupils’ performance on the chemistry element of the AQA GCSE double award science

Using Single loxP Sites to Enhance Homologous Recombination: ts Mutants in Sec1 of Dictyostelium discoideum

Dictyostelium discoideum amoebae are haploid and, as they share many features with animal cells, should be an ideal creature for studying basic processes such as cell locomotion. Isolation of mutants in this amoeba has largely been limited to non-essential genes: nsfA-the gene for NEM-sensitive factor-remains the only essential gene for which conditional (ts) mutants exist. These ts mutants were generated by gene replacement using a library of mutagenised nsfA containing a selectable marker: transformants were then screened for temperature sensitivity. The success of this approach depended on the high level of homologous recombination prevailing at this locus: approximately 95% of selected clones were homologous recombinants. This is unusually high for Dictyostelium: homologous recombination at other loci is usually much less, usually between 0-30%, making the isolation of ts mutants much more tedious.In trying to make ts mutants in sec1A, homologous recombination was found to be only approximately 25%. A new approach, involving single loxP sites, was investigated. LoxP sites are 34 bp sequences recognised by Cre recombinase and between which this enzyme catalyses recombination. A Dictyostelium line containing a single loxP site adjacent to the 3' end of the sec1A gene was engineered. A sec1A replacement DNA also containing a single loxP site in a homologous position was then introduced into this cell line. In the presence of CRE recombinase, homologous recombination increased to approximately 80% at this locus, presumably largely driven by intermolecular recombination between the two single loxP sites.A route to increase the rate of homologous recombination at a specific locus, sec1A, is described which enabled the isolation of 30 ts mutants in sec1A. One of these, sec1Ats1,has been studied and found to cease moving at the restrictive temperature. The approach described here may be valuable for enhancing homologous recombination at specified loci and thus for introducing mutations into specific genes in Dictyostelium and other creatures

Measurement of Plasmodium falciparum transmission intensity using serological cohort data from Indonesian schoolchildren.

BACKGROUND: As malaria transmission intensity approaches zero, measuring it becomes progressively more difficult and inefficient because parasite-positive individuals are hard to detect. This situation may arise shortly before achieving local elimination, or during surveillance post-elimination to prevent reintroduction. Antibody responses against the parasite last longer than the infections themselves. This "footprint" of infection may thus be used for assessing transmission intensity. A statistical approach is presented for measuring the seroconversion rate (SCR), a correlate of the force of infection, from individual-level longitudinal data on antibody titres in an area of low Plasmodium falciparum transmission. METHODS: Blood samples were collected from 160 Indonesian schoolchildren every month for six months. Titres of antibodies against AMA-1 and MSP-1(19) antigens of P. falciparum were measured using ELISA. The distribution of antibody titres among seronegative and -positive individuals, respectively, was estimated by comparing the titres from the study data (a mixture of both seropositive and -negative individuals) with titres from a (unexposed) negative control group of Indonesian individuals. Two Markov-Chain models for the transition of individuals between serological states were fitted to individual anti-PfAMA-1 or anti-PfMSP-1 titre time series using Bayesian Markov-Chain-Monte-Carlo (MCMC). This yielded estimates of SCR as well as of the duration of seropositivity. RESULTS: A posterior median SCR of 0.02 (Pf AMA-1) and 0.09 (PfMSP-1) person(-1) year(-1) was estimated, with credible intervals ranging from 1E-4 to 0.2 person(-1) year(-1). This level of transmission intensity is at the lower range of what can reliably be measured with the present study size. A Bayesian test for seroconversion of an individual between two observations is presented and used to identify the subjects who have most likely experienced an infection. Furthermore, the theoretical limits of measuring transmission intensity, and how these depend on duration and size of a study as well as on transmission intensity itself, is illustrated. CONCLUSIONS: This analysis shows that it is possible to measure SCR's from individual-level longitudinal data on antibody titres. In addition, individual seroconversion events can be identified, which can be useful in assessing interruption of transmission. Analyses of further serological datasets using the present method are required to improve and validate it. This includes measurement of the duration of antibody responses, how it depends on host age or cumulative exposure, or on the particular antigen used

Parametric search and optimisation of fast displacement hull forms using rans simulations of full-scale flow

Abstract. A methodology to derive parametric hull design candidates with a specified displacement and initial stability is introduced. A gradient-free search and optimisation algorithm coupled to a RANS CFD solver is then used to identify efficient pure-displacement hull shapes with minimal hydrodynamic resistance operating in the transition speed region without relying on dynamic lift

Pilot Evaluation Protocol: SMART Spaces (Chemistry Teaching - Pilot Trial)

This evaluation protocol describes the pilot trial of the GCSE teaching version of the SMART Spaces programme (SMART Spaces: GCSE Chemistry Teaching), a pilot trial funded by the Education Endowment Foundation (EEF), designed to investigate whether the SMART Spaces approach has wider applicability beyond the previously trialled GCSE revision version. Specifically, the pilot will examine whether the teaching version has sufficient evidence of promise, feasibility and readiness to justify an efficacy trial. The trial will investigate the intervention group only (and there will be no control group). It will consist of a mixed methods implementation and process evaluation (IPE) together with an evaluation of the impact on students’ attitudes and on the teaching of chemistry. The trial will take place over the 2018/19 academic year. Final publication of the results will be in Summer 2020. This protocol outlines the rationale for the project, describes the intervention using the TIDieR framework and outlines the methods of data collection and analysis for the impact evaluation, the IPE and the cost evaluation. A separate evaluation protocol describes the SMART Spaces revision programme efficacy trial, which takes place concurrently to this pilo

Trial Evaluation Protocol: SMART Spaces (Spaced Learning Revision Programme)

This evaluation protocol describes the evaluation of SMART Spaces: Spaced Learning Revision Programme (SMART Spaces Revision), an efficacy trial funded by the Education Endowment Foundation (EEF), designed to investigate the effect of the intervention on the chemistry element of the GCSE double award science. The evaluation will consist of a twoarm randomised controlled trial testing the SMART Space Revision intervention against a ‘business as usual’ control and will include a mixed methods implementation and process evaluation (IPE). The trial will take place over the 2018/19 academic year, with randomisation taking place in two stages in October and December 2018 and the delivery of the intervention in schools during April and May 2019, following teacher training and coaching sessions over the period December 2018 to March 2019. Final publication of the results will be in Summer 2020. This protocol outlines the rationale for the project, describes the intervention using the TIDieR framework and outlines the methods of data collection and analysis for the impact evaluation, the IPE and the cost evaluation

Relative neutronic performance of proposed high-density dispersion fuels in water-moderated and D{sub 2}O-reflected research reactors

This paper provides an overview of the neutronic performance of an idealized research reactor using several high density LEU fuels that are being developed by the RERTR program. High-density LEU dispersion fuels are needed for new and existing high-performance research reactors and to extend the lifetime of fuel elements in other research reactors. This paper discusses the anticipated neutronic behavior of proposed advanced fuels containing dispersions of U{sub 3}Si{sub 2}, UN, U{sub 2}Mo and several uranium alloys with Mo, or Zr and Nb. These advanced fuels are ranked based on the results of equilibrium depletion calculations for a simplified reactor model having a small H{sub 2}O-cooled core and a D{sub 2}O reflector. Plans have been developed to fabricate and irradiate several uranium alloy dispersion fuels in order to test their stability and compatibility with the matrix material and to establish practical loading limits

A classification of tasks for the systematic study of immune response using functional genomics data

A full understanding of the immune system and its responses to infection by different pathogens is important for the development of anti-parasitic vaccines. A growing number of large-scale experimental techniques, such as microarrays, are being used to gain a better understanding of the immune system. To analyse the data generated by these experiments, methods such as clustering are widely used. However, individual applications of these methods tend to analyse the experimental data without taking publicly available biological and immunological knowledge into account systematically and in an unbiased manner. To make best use of the experimental investment, to benefit from existing evidence, and to support the findings in the experimental data, available biological information should be included in the analysis in a systematic manner. In this review we present a classification of tasks that shows how experimental data produced by studies of the immune system can be placed in a broader biological context. Taking into account available evidence, the classification can be used to identify different ways of analysing the experimental data systematically. We have used the classification to identify alternative ways of analysing microarray data, and illustrate its application using studies of immune responses in mice to infection with the intestinal nematode parasites Trichuris muris and Heligmosomoides polygyrus