What can we do to reduce disciplinary school exclusion? A systematic review and meta-analysis

Objectives: To systematically review and quantitatively synthesize the evidence for the impact of different types of school-based interventions on the reduction of school exclusion. Methods: A systematic search of 27 databases including published and unpublished literature was carried out between September and December 2015. Eligible studies evaluated interventions intended to reduce the rates of exclusion; targeted children from ages four to 18 in mainstream schools; and reported results of interventions delivered from 1980 onwards. Only randomised controlled trials were included. Two independent reviewers determined study eligibility, extracted data and rated the methodological quality of studies. Results: Based on the thirty-seven studies eligible for meta-analysis, under a random effects model, results showed that school-based interventions significantly reduced school exclusion during the first six months after implementation SMD=.30, 95% CI [.20, .41], p<.001. The impact at follow-up (i.e., 12 or more months) was reduced by half and it was not statistically significant. Heterogeneity was mainly explained by the role of the evaluator: independent evaluators reported lower effect sizes than researchers involved in the design and/or delivery of the intervention. Four approaches presented promising and significant results in reducing exclusion: enhancement of academic skills, counselling, mentoring/monitoring, and skills training for teachers. Conclusions: Results suggest that school-based interventions can be effective in reducing school exclusion in the short term. Some specific types of interventions show more promising and stable results, but, based on the small number of studies involved in our calculations, we suggest that results are interpreted with caution.Nuffield Foundation Beca Chil

High-throughput spheroid screens using volume, resazurin reduction and acid phosphatase activity

Mainstream adoption of physiologically-relevant three-dimensional models has been slow in the last 50 years due to long, manual protocols with poor reproducibility, high price and closed commercial platforms. This chapter describes high-throughput, low-cost, open methods for spheroid viability assessment which use readily-available reagents and open-source software to analyse spheroid volume, metabolism and enzymatic activity. We provide two ImageJ macros for automated spheroid size determination - for both single images and for images in stacks. We also share an Excel template spreadsheet allowing users to rapidly process spheroid size data, analyse plate uniformity (such as edge effects and systematic seeding errors), detect outliers and calculate dose-response. The methods would be useful to researchers in preclinical and translational research planning to move away from simplistic monolayer studies and explore 3D spheroid screens for drug safety and efficacy without substantial investment in money or time

Spheroid arrays for high-throughput single-cell analysis of spatial patterns and biomarker expression in 3D

We describe and share a device, methodology and image analysis algorithms, which allow up to 66 spheroids to be arranged into a gel-based array directly from a culture plate for downstream processing and analysis. Compared to processing individual samples, the technique uses 11-fold less reagents, saves time and enables automated imaging. To illustrate the power of the technology, we showcase applications of the methodology for investigating 3D spheroid morphology and marker expression and for in vitro safety and efficacy screens. Firstly, spheroid arrays of 11 cell-lines were rapidly assessed for differences in spheroid morphology. Secondly, highly-positive (SOX-2), moderately-positive (Ki-67) and weakly-positive (βIII-tubulin) protein targets were detected and quantified. Third, the arrays enabled screening of ten media compositions for inducing differentiation in human neurospheres. Lastly, the application of spheroid microarrays for spheroid-based drug-screens was demonstrated by quantifying the dose-dependent drop in proliferation and increase in differentiation in etoposide-treated neurospheres

Decreasing intensity of open-ocean convection in the Greenland and Iceland seas

The air–sea transfer of heat and fresh water plays a critical role in the global climate system. This is particularly true for the Greenland and Iceland seas, where these fluxes drive ocean convection that contributes to Denmark Strait overflow water, the densest component of the lower limb of the Atlantic Meridional Overturning Circulation (AMOC). Here we show that the wintertime retreat of sea ice in the region, combined with different rates of warming for the atmosphere and sea surface of the Greenland and Iceland seas, has resulted in statistically significant reductions of approximately 20% in the magnitude of the winter air–sea heat fluxes since 1979. We also show that modes of climate variability other than the North Atlantic Oscillation (NAO) are required to fully characterize the regional air–sea interaction. Mixed-layer model simulations imply that further decreases in atmospheric forcing will exceed a threshold for the Greenland Sea whereby convection will become depth limited, reducing the ventilation of mid-depth waters in the Nordic seas. In the Iceland Sea, further reductions have the potential to decrease the supply of the densest overflow waters to the AMOC

Extended Follow-Up Following a Phase 2b Randomized Trial of the Candidate Malaria Vaccines FP9 ME-TRAP and MVA ME-TRAP among Children in Kenya

Background. "FFM ME-TRAP'' is sequential immunisation with two attenuated poxvirus vectors (FP9 and modified vaccinia virus Ankara) delivering the pre-erythrocytic malaria antigen ME-TRAP. Over nine months follow-up in our original study, there was no evidence that FFM ME-TRAP provided protection against malaria. The incidence of malaria was slightly higher in children who received FFM ME-TRAP, but this was not statistically significant (hazard ratio 1.5, 95% CI 1.0-2.3). Although the study was unblinded, another nine months follow-up was planned to monitor the incidence of malaria and other serious adverse events. Methods and Findings. 405 children aged 1-6 yrs were initially randomized to vaccination with either FFM ME-TRAP or control (rabies vaccine). 380 children were still available for follow-up after the first nine months. Children were seen weekly and whenever they were unwell for nine months monitoring. The axillary temperature was measured, and blood films taken when febrile. The primary analysis was time to parasitaemia >2,500/mu l. During the second nine months monitoring, 49 events met the primary endpoint (febrile malaria with parasites >2,500/mu l) in the Intention To Treat (ITT) group. 23 events occurred among the 189 children in the FFM ME-TRAP group, and 26 among the 194 children in the control group. In the full 18 months of monitoring, there were 63 events in the FFM ME-TRAP group and 60 in the control group (HR = 1.2, CI 0.84-1.73, p = 0.35). There was no evidence that the HR changed over the 18 months (test for interaction between time and vaccination p = 0.11). Conclusions. Vaccination with FFM ME-TRAP was not protective against malaria in this study. Malaria incidence during 18 months of surveillance was similar in both vaccine groups. Trial Registration. Controlled-Trials. com ISRCTN88335123

Improving Interpretation of Cardiac Phenotypes and Enhancing Discovery With Expanded Knowledge in the Gene Ontology

This work was funded through grants from the British Heart Foundation (BHF, SP/07/007/23671, RG/13/5/30112) and the National Institute for Health Research University College London Hospitals Biomedical Research Centre; The Zebrafish Model Organism Database: National Human Genome Research Institute (NHGRI, HG002659, HG004838, HG004834); The Rat Genome Database: National Heart, Lung, and Blood Institute on behalf of the NIH (HL64541); The Mouse Genome Database: NGHRI (HG003300); FlyBase: UK Medical Research Council (G1000968); and Gene Ontology Consortium: NIH NHGRI (U41 HG002273) to Drs Blake, Cherry, Lewis, Sternberg, and Thomas. Professor Riley received BHF personal chair award (CH/11/1/28798). Professors Lambiase and Tinker received support from BHF and UK Medical Research Council. Professor Tinker received National Institute for Health Research Biomedical Research Centre at Barts and BHF grant (RG/15/15/31742). Dr Roncaglia received EMBL-EBI Core funds

Early star-forming galaxies and the reionization of the Universe

Star forming galaxies represent a valuable tracer of cosmic history. Recent observational progress with Hubble Space Telescope has led to the discovery and study of the earliest-known galaxies corresponding to a period when the Universe was only ~800 million years old. Intense ultraviolet radiation from these early galaxies probably induced a major event in cosmic history: the reionization of intergalactic hydrogen. New techniques are being developed to understand the properties of these most distant galaxies and determine their influence on the evolution of the universe.Comment: Review article appearing in Nature. This posting reflects a submitted version of the review formatted by the authors, in accordance with Nature publication policies. For the official, published version of the review, please see http://www.nature.com/nature/archive/index.htm

LEDGF gene silencing impairs the tumorigenicity of prostate cancer DU145 cells by abating the expression of Hsp27 and activation of the Akt/ERK signaling pathway

Lens epithelium-derived growth factor (LEDGF) maintains survival pathways by augmenting the transcription of stress-response genes such as small heat-shock protein 27. Recently, aberrant expression of LEDGF was found in prostate cancer (PC). Herein, we showed that LEDGF overexpression upregulated Hsp27 in PC cells, DU145, PC-3 and LNCaP and promoted antiapoptotic pathways in PCs. We found that these cells had higher abundance of Hsp27, which was correlated with the levels of LEDGF expression. Transactivation assay in DU145 cells revealed that transactivation of Hsp27 was related to the magnitude of LEDGF expression. Silencing of LEDGF in DU145 cells abrogated Hsp27 expression and inhibited stimulated cell proliferation, invasiveness and migration. These cells were arrested in S and G2 phase, and failed to accumulate cyclin B1, and showed increased apoptosis. Furthermore, LEDGF-depleted DU145 cells displayed elevated Bax and cleaved caspase 9 expression and reduced levels of Bcl2, Bcl-XL. The activated survival pathway(s), ERK1/2 and Akt, were selectively decreased in these cells, which characteristically have lower tumorigenicity. Conversely, the depleted cells, when re-overexpressed with LEDGF or Hsp27, regained tumorigenic properties. Collectively, results reveal the involvement of LEDGF-mediated elevated expression of Hsp27-dependent survival pathway(s) in PC. Our findings suggest new lines of investigation aimed at developing therapies by targeting LEDGF or its aberrant expression-associated stimulated antiapoptotic pathway(s)

The MACHO Project Large Magellanic Cloud Variable Star Inventory. VIII. The Recent Star Formation History of the LMC from the Cepheid Period Distribution

We present an analysis of the period distribution of $\sim 1800$ Cepheids in the Large Magellanic Cloud, based on data obtained by the MACHO microlensing experiment and on a previous catalogue by Payne-Gaposchkin. Using stellar evolution and pulsation models, we construct theoretical period-frequency distributions that are compared to the observations. These models reveal that a significant burst of star formation has occurred recently in the LMC ($\sim 1.15\times 10^8$ years). We also show that during the last $\sim 10^8$ years, the main center of star formation has been propagating from SE to NW along the bar. We find that the evolutionary masses of Cepheids are still smaller than pulsation masses by $\sim 7$ % and that the red edge of the Cepheid instability strip could be slightly bluer than indicated by theory. There are $\sim 600$ Cepheids with periods below $\sim 2.5$ days cannot be explained by evolution theory. We suggest that they are anomalous Cepheids; a number of these stars are double-mode Cepheids