Regression Towards the Mean Artifacts and Matthew Effects in multilevel analyses of value-added of individual schools

League tables are a problematic approach to inferring school effectiveness, but traditional value-added approaches are fraught with statistical complexities. According to the Regression Towards the Mean Artifacts (RTMA), students with initially high or low scores tend to regress towards the mean in subsequent testing, resulting in biased estimates of school growth (Marsh & Hau, 2002). The Matthews Effect is an apparently counter-balancing artifact in growth in achievement gains is systematically larger for students who are initially more able. (i.e., the rich becomes richer). Mathematical proof shows that although the Matthew and the RTMA artifacts work in opposite direction and tend to cancel each other, they share a similar mechanism and can be rectified. In this study, mathematical derivations and Monte Carlo simulated data are used to compare four models, namely: (i) without any remedy, (ii) with remedy for Matthew effect only, (iii) with remedy for RTMA only, (iv) remedies for both Matthew and RTMA effects. The conditional strategy with individual assignment test scores (used in assigning students to different schools) as covariate remedies artifacts, consistent with Marsh & Hau's (2002) conclusion for RTMA. The associated problems with the two effects in estimating school value-added information are discussed.published_or_final_versio

Control of Single Molecule Fluorescence Dynamics by Stimulated Emission Depletion

The feasibility of manipulating the single molecule absorption-emission cycle using picosecond stimulated emission depletion (STED) is investigated using a stochastic computer simulation. In the simulation the molecule is subjected to repeated excitation and depletion events using time delayed pairs of excitation (PUMP) and depletion (DUMP) pulses derived from a high repetition rate pulsed laser system. The model is used to demonstrate that a significant and even substantial reduction in the occurrence of 'dark states' in the fluorescence emission can be achieved using stimulated emission depletion. Variation in the PUMP-DUMP window allows precise control of the fluorescence yield with substantial increases in the fluorescence intensity observed at early PUMP-DUMP delays

Investigating State Restriction in Fluorescent Protein FRET Using Time-Resolved Fluorescence and Anisotropy

Most fluorescent proteins exhibit multiexponential fluorescence decays, indicating a heterogeneous excited state population. FRET between fluorescent proteins should therefore involve multiple energy transfer pathways. We recently demonstrated the FRET pathways between EGFP and mCherry (mC), upon the dimerization of 3-phosphoinositide dependent protein kinase 1 (PDK1), to be highly restricted. A mechanism for FRET restriction based on a highly unfavorable κ(2) orientation factor arising from differences in donor-acceptor transition dipole moment angles in a far from coplanar and near static interaction geometry was proposed. Here this is tested via FRET to mC arising from the association of glutathione (GSH) and glutathione S-transferase (GST) with an intrinsically homogeneous and more mobile donor Oregon Green 488 (OG). A new analysis of the acceptor window intensity, based on the turnover point of the sensitized fluorescence, is combined with donor window intensity and anisotropy measurements which show that unrestricted FRET to mC takes place. However, a long-lived anisotropy decay component in the donor window reveals a GST-GSH population in which FRET does not occur, explaining previous discrepancies between quantitative FRET measurements of GST-GSH association and their accepted values. This reinforces the importance of the local donor-acceptor environment in mediating energy transfer and the need to perform spectrally resolved intensity and anisotropy decay measurements in the accurate quantification of fluorescent protein FRET

Polarised stimulated emission depletion studies of two-photon excited states

Stimulated emission depletion (STED) population and polarisation dynamics following two-photon excitation are investigated for rhodamine 6G in ethylene glycol. Time resolved fluorescence intensity and polarisation measurements were made using picosecond time-correlated single photon counting (TCSPC). Cross-sections for the stimulated transition were measured between 614nm (2.32 X 10(-16) cm(2)) and 663.5nm (6.05 X 10(-17) cm(2)), ground state vibrational lifetimes were found to vary between 314fs and 467fs. A collinear (180degrees) excitation-detection geometry was employed to investigate re-polarisation of the excited state array yielding fluorescence anisotropies above the two-photon limit. The circumvention of single-photon selection rules is demonstrated allowing the measurement of higher order parameters and correlation functions that are wholly inaccessible to 'conventional' (spontaneous) time resolved fluorescence techniques

A comprehensive multilevel model meta-analysis of self-concept interventions

The efficacy of self-concept interventions has previously been examined through traditional meta-analytic methods, and a host of moderators of intervention outcomes have been identified (O’Mara, Marsh, & Craven, 2004; Haney & Durlak, 1998; Hattie, 1992). However, traditional meta-analytic models have increasingly been criticized because they fail to account for the nested structure of effect sizes within studies, thereby violating statistical assumptions of independence. The multilevel model approach to meta-analysis takes into account the hierarchical structure of meta-analytic data, thus providing findings that are more statistically sound. Consequently, the present study applies the multilevel model technique to the analysis of the self-concept intervention literature. The overall mean effect size of .47 suggests a moderate impact of interventions on self-concept at post-test, and analyses show that intervention effects are maintained at follow-up. Other moderators examined include the construct validity approach to the multidimensionality of self-concept; the focus of the intervention on self-concept; the use of random assignment to treatment and control groups; the control group type; treatment type; and the treatment administrator. Intraclass correlations and the variance explained by each moderator model are presented to emphasise the importance of using a multilevel model approach to meta-analytic research. It is concluded that multilevel models provide a more accurate understanding of the self-concept intervention literature than traditional meta-analytic models. Suggestions for future self-concept intervention design and evaluation are provided

Stimulated emission depletion following two photon excitation

The technique of stimulated emission depletion of fluorescence (STED) from a two photon excited molecular population is demonstrated in the S, excited state of fluorescein in ethylene glycol and methanol. Two photon excitation (pump) is achieved using the partial output of a regeneratively amplified Ti:Sapphire laser in conjunction with an optical parametric amplifier whose tuneable output provides a synchronous depletion (dump) pulse. Time resolved fluorescence intensity and anisotropy measurements of the fluorescein emission are made using picosecond time-correlated single photon counting. Pump-dump time delayed fluorescence intensity measurements are used to characterise the response of the system and to provide additional data on saturation dynamics of the dump transition. Two photon STED is modelled using both approximate analytical techniques in the weak dump limit and by numerical solutions to the appropriate rate equations. The latter are used to fit experimental data from which it is possible to determine the cross-section for the stimulated transition and lifetime of the upper vibrational levels of the ground state

Unmasking the true effects of self-concept interventions and suggested guidelines for rectification

Over recent decades, traditional literature reviews have intimated that self-concept interventions have produced inconsistent or disappointing results (e.g., Marsh & Craven, 1997). It is put forth here that existing research practices, ranging from insufficient theoretical grounding to the use of inappropriate evaluation measures, have generally undermined the effectiveness of self-concept interventions to date. A brief rationale for the necessity of self-concept interventions for children and adolescents will be provided, followed by a review of self-concept enhancement research. This review will focus on the theoretical and methodological weaknesses that have typically resulted in an underestimation of the true effects of such interventions, as revealed by sophisticated meta-analytic techniques. A particular emphasis will be placed on the need for multidimensional approaches to intervention design and evaluation. Following from this, suggestions for improving self-concept intervention research will be posited, with the aim of increasing the consistency and effectiveness of such interventions, and thus unmasking the true effects of such interventions

Development and validation of broad-spectrum magnetic particle labelling processes for cell therapy manufacturing

Background Stem cells are increasingly seen as a solution for many health challenges for an ageing population. However, their potential benefits in the clinic are currently curtailed by technical challenges such as high cell dose requirements and point of care delivery, which pose sourcing and logistics challenges. Cell manufacturing solutions are currently in development to address the supply issue, and ancillary technologies such as nanoparticle-based labelling are being developed to improve stem cell delivery and enable post-treatment follow-up. Methods The application of magnetic particle (MP) labelling to potentially scalable cell manufacturing processes was investigated in a range of therapeutically relevant cells, including mesenchymal stromal cells (MSC), cardiomyocytes (CMC) and neural progenitor cells (ReN). The efficiency and the biological effect of particle labelling were analysed using fluorescent imaging and cellular assays. Results Flow cytometry and fluorescent microscopy confirmed efficient labelling of monolayer cultures. Viability was shown to be retained post labelling for all three cell types. MSC and CMC demonstrated higher tolerance to MP doses up to 100× the standard concentration. This approach was also successful for MP labelling of suspension cultures, demonstrating efficient MP uptake within 3 h, while cell viability was unaffected by this suspension labelling process. Furthermore, a procedure to enable the storing of MP-labelled cell populations to facilitate cold chain transport to the site of clinical use was investigated. When MP-labelled cells were stored in hypothermic conditions using HypoThermosol solution for 24 h, cell viability and differentiation potential were retained post storage for ReN, MSC and beating CMC. Conclusions Our results show that a generic MP labelling strategy was successfully developed for a range of clinically relevant cell populations, in both monolayer and suspension cultures. MP-labelled cell populations were able to undergo transient low-temperature storage whilst maintaining functional capacity in vitro. These results suggest that this MP labelling approach can be integrated into cell manufacturing and cold chain transport processes required for future cell therapy approaches