Recovering S1S^1-invariant metrics on S2S^2 from the equivariant spectrum

We prove an inverse spectral result for $S^1$-invariant metrics on $S^2$ based on the so-called asymptotic equivariant spectrum. This is roughly the spectrum together with large weights of the $S^1$ action on the eigenspaces. Our result generalizes an inverse spectral result of the first and last named authors, together with Victor Guillemin, concerning $S^1$-invariant metrics on $S^2$ which are invariant under the antipodal map. We use higher order terms in the asymptotic expansion of a natural spectral measure associated with the Laplacian and the $S^1$ action.Comment: 16 pages; minor revisions throughout following comments from referee

Hearing Delzant polytopes from the equivariant spectrum

Let M^{2n} be a symplectic toric manifold with a fixed T^n-action and with a toric K\"ahler metric g. Abreu asked whether the spectrum of the Laplace operator $\Delta_g$ on $\mathcal{C}^\infty(M)$ determines the moment polytope of M, and hence by Delzant's theorem determines M up to symplectomorphism. We report on some progress made on an equivariant version of this conjecture. If the moment polygon of M^4 is generic and does not have too many pairs of parallel sides, the so-called equivariant spectrum of M and the spectrum of its associated real manifold M_R determine its polygon, up to translation and a small number of choices. For M of arbitrary even dimension and with integer cohomology class, the equivariant spectrum of the Laplacian acting on sections of a naturally associated line bundle determines the moment polytope of M.Comment: 23 pages, 9 figures; v2 is published versio

The future is open – improving the utility of preclinical research

Keynote presentation for Dealing with Data 2018. There is a problem in preclinical research which results in published research not translating into successful clinical trials. The reasons for this may include the "perverse incentives" which researchers face to produce positive results at the expense of possibly more useful neutral or negative ones, and the drive to reduce the number of animals used in research resulting in underpowered studies. Whatever the cause of this translational failure institutions, funders, and researchers at all levels need to take steps to address their biases and improve the validity and usefulness of preclinical research. Adopting the tools of Open Science (open methods, registered reports, and published data), is one way to increase the rigour of research. Being more open to publishing results where the quality of the research is high but the results are neutral or negative is also useful in ensuring that other researchers get the full picture

Effects of MVA85A vaccine on tuberculosis challenge in animals: systematic review

Background The existing Bacillus Calmette–Guérin (BCG) vaccination provides partial protection against tuberculosis (TB). The modified vaccinia ankara virus-expressing antigen 85A (MVA85A) aims to boost BCG immunity. We evaluated the animal evidence supporting the testing of MVA85A in humans. Methods Our protocol included in vivo preclinical studies of the MVA85A booster with BCG compared with BCG alone, followed by a TB challenge. We used standard methods for systematic review of animal studies, and summarized mortality, measures of pathology and lung bacterial load. The comprehensive literature search was to September 2014. Two independent investigators assessed eligibility and performed data extraction. We assessed study quality and pooled bacteria load using random effect meta-analysis. Findings We included eight studies in 192 animals. Three experiments were in mice, two in guinea pigs, two in macaques and one in calves. Overall, study quality was low with no randomization, baseline comparability not described and blinding not reported. For animal death (including euthanasia due to severe morbidity), studies were underpowered, and overall no benefit demonstrated. No difference was shown for lung pathology measured on an ordinal scale or bacterial load. The largest mortality trial carried out in macaques had more deaths in the MVA85A vaccine group, and was published after a trial in South Africa had started recruiting children. Conclusions This independent assessment of the animal data does not provide evidence to support efficacy of MVA85A as a BCG booster. More rigorous conduct and reporting of preclinical research are warranted, and we believe the results of studies should be publicly available before embarking on trials in humans, irrespective of the findings

Using median survival in meta-analysis of experimental time-to-event data

Abstract Background Time-to-event data is frequently reported in both clinical and preclinical research spheres. Systematic review and meta-analysis is a tool that can help to identify pitfalls in preclinical research conduct and reporting that can help to improve translational efficacy. However, pooling of studies using hazard ratios (HRs) is cumbersome especially in preclinical meta-analyses including large numbers of small studies. Median survival is a much simpler metric although because of some limitations, which may not apply to preclinical data, it is generally not used in survival meta-analysis. We aimed to appraise its performance when compared with hazard ratio-based meta-analysis when pooling large numbers of small, imprecise studies. Methods We simulated a survival dataset with features representative of a typical preclinical survival meta-analysis, including with influence of a treatment and a number of covariates. We calculated individual patient data-based hazard ratios and median survival ratios (MSRs), comparing the summary statistics directly and their performance at random-effects meta-analysis. Finally, we compared their sensitivity to detect associations between treatment and influential covariates at meta-regression. Results There was an imperfect correlation between MSR and HR, although the opposing direction of treatment effects between summary statistics appeared not to be a major issue. Precision was more conservative for HR than MSR, meaning that estimates of heterogeneity were lower. There was a slight sensitivity advantage for MSR at meta-analysis and meta-regression, although power was low in all circumstances. Conclusions We believe we have validated MSR as a summary statistic for use in a meta-analysis of small, imprecise experimental survival studies—helping to increase confidence and efficiency in future reviews in this area. While assessment of study precision and therefore weighting is less reliable, MSR appears to perform favourably during meta-analysis. Sensitivity of meta-regression was low for this set of parameters, so pooling of treatments to increase sample size may be required to ensure confidence in preclinical survival meta-regressions

Hearing Delzant polytopes from the equivariant spectrum

Author's final manuscript June 18, 2012Let M[superscript 2n] be a symplectic toric manifold with a fixed T[superscript n]-action and with a toric Kähler metric g. Abreu (2003) asked whether the spectrum of the Laplace operator Δ[subscript g] on C∞ (M) determines the moment polytope of M, and hence by Delzant's theorem determines M up to symplectomorphism. We report on some progress made on an equivariant version of this conjecture. If the moment polygon of M[superscript 4] is generic and does not have too many pairs of parallel sides, the so-called equivariant spectrum of M and the spectrum of its associated real manifold M[subscript R] determine its polygon, up to translation and a small number of choices. For M of arbitrary even dimension and with integer cohomology class, the equivariant spectrum of the Laplacian acting on sections of a naturally associated line bundle determines the moment polytope of M

A Systematic Online Living Evidence Summary of experimental Alzheimer's disease research

BACKGROUND: Despite extensive investment, the development of effective treatments for Alzheimer's disease (AD) has been largely unsuccessful. To improve translation, it is crucial to ensure the quality and reproducibility of foundational evidence generated from laboratory models. Systematic reviews play a key role in providing an unbiased overview of the evidence, assessing rigour and reporting, and identifying factors that influence reproducibility. However, the sheer pace of evidence generation is prohibitive to evidence synthesis and assessment.NEW METHOD: To address these challenges, we have developed AD-SOLES, an integrated workflow of automated tools that collect, curate, and visualise the totality of evidence from in vivo experiments.RESULTS: AD-SOLES is a publicly accessible interactive dashboard aiming to surface and expose data from in vivo experiments. It summarises the latest evidence, tracks reporting quality and transparency, and allows research users to easily locate evidence relevant to their specific research question.COMPARISON WITH EXISTING METHODS: Using automated screening methodologies within AD-SOLES, systematic reviews can begin at an accelerated starting point compared to traditional approaches. Furthermore, through text-mining approaches within the full-text of publications, users can identify research of interest using specific models, outcomes, or interventions without relying on details in the title and/or abstract.CONCLUSIONS: By automating the collection, curation, and visualisation of evidence from in vivo experiments, AD-SOLES addresses the challenges posed by the rapid pace of evidence generation. AD-SOLES aims to offer guidance for research improvement, reduce research waste, highlight knowledge gaps, and support informed decision making for researchers, funders, patients, and the public.</p