Detecting pairwise correlations in spike trains: an objective comparison of methods and application to the study of retinal waves. Mathematical Details

Mathematical details, supplemental to the paper: "Detecting pairwise correlations in spike trains: an objective comparison of methods and application to the study of retinal waves."Wellcome Trust (SJE; grant number 083205) and EPSRC (CSC

The effect of distance on observed mortality, childhood pneumonia and vaccine efficacy in rural Gambia.

We investigated whether straight-line distance from residential compounds to healthcare facilities influenced mortality, the incidence of pneumonia and vaccine efficacy against pneumonia in rural Gambia. Clinical surveillance for pneumonia was conducted on 6938 children living in the catchment areas of the two largest healthcare facilities. Deaths were monitored by three-monthly home visits. Children living >5 km from the two largest healthcare facilities had a 2·78 [95% confidence interval (CI) 1·74-4·43] times higher risk of all-cause mortality compared to children living within 2 km of these facilities. The observed rate of clinical and radiological pneumonia was lower in children living >5 km from these facilities compared to those living within 2 km [rate ratios 0·65 (95% CI 0·57-0·73) and 0·74 (95% CI 0·55-0·98), respectively]. There was no association between distance and estimated pneumococcal vaccine efficacy. Geographical access to healthcare services is an important determinant of survival and pneumonia in children in rural Gambia

Using domiciliary non-invasive ventilator data downloads to inform clinical decision-making to optimise ventilation delivery and patient compliance

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted. Introduction Ventilation parameter data from patients receiving home mechanical ventilation can be collected via secure data cards and modem technology. This can then be reviewed by clinicians and ventilator prescriptions adjusted. Typically available measures include tidal volume (V T ), leak, respiratory rate, minute ventilation, patient triggered breaths, achieved pressures and patient compliance. This study aimed to assess the potential impact of ventilator data downloads on management of patients requiring home non-invasive ventilation (NIV). Methods A longitudinal within-group design with repeated measurements was used. Baseline ventilator data were downloaded, reviewed and adjustments made to optimise ventilation. Leak, V T and compliance data were collected for comparison at the first review and 3-7 weeks later. Ventilator data were monitored and amended remotely via a modem by a consultant physiotherapist between the first review and second appointment. Results Analysis of data from 52 patients showed increased patient compliance (% days used > 4 hours) from 90% to 96% (p=0.007), increased usage from 6.53 to 6.94 hours (p=0.211) and a change in V T (9.4 vs 8.7 mL/kg/ideal body weight, p=0.022). There was no change in leak following review of NIV prescriptions (mean (SD): 43 (23.4) L/min vs 45 (19.9)L/min, p=0.272). Conclusion Ventilator data downloads, via early remote assessment, can help optimise patient ventilation through identification of modifiable factors, in particular interface leak and ventilator prescriptions. However, a prospective study is required to assess whether using ventilator data downloads provides value in terms of patient outcomes and cost-effectiveness. The presented data will help to inform the design of such a study

Quantitative assessment of computational models for retinotopic map formation.

Molecular and activity-based cues acting together are thought to guide retinal axons to their terminal sites in vertebrate optic tectum or superior colliculus (SC) to form an ordered map of connections. The details of mechanisms involved, and the degree to which they might interact, are still not well understood. We have developed a framework within which existing computational models can be assessed in an unbiased and quantitative manner against a set of experimental data curated from the mouse retinocollicular system. Our framework facilitates comparison between models, testing new models against known phenotypes and simulating new phenotypes in existing models. We have used this framework to assess four representative models that combine Eph/ephrin gradients and/or activity-based mechanisms and competition. Two of the models were updated from their original form to fit into our framework. The models were tested against five different phenotypes: wild type, Isl2-EphA3(ki/ki), Isl2-EphA3(ki/+), ephrin-A2,A3,A5 triple knock-out (TKO), and Math5(-/-) (Atoh7). Two models successfully reproduced the extent of the Math5(-/-) anteromedial projection, but only one of those could account for the collapse point in Isl2-EphA3(ki/+). The models needed a weak anteroposterior gradient in the SC to reproduce the residual order in the ephrin-A2,A3,A5 TKO phenotype, suggesting either an incomplete knock-out or the presence of another guidance molecule. Our article demonstrates the importance of testing retinotopic models against as full a range of phenotypes as possible, and we have made available MATLAB software, we wrote to facilitate this process.Contract grant sponsors: Wellcome Trust; contract grant numbers: 083205, Engineering and Physical Sciences Research Council (EPSRC) (CSC).This is the published version. It's also available from Wiley at http://onlinelibrary.wiley.com/doi/10.1002/dneu.22241/abstract

Correlates of Complete Childhood Vaccination in East African Countries.

Despite the benefits of childhood vaccinations, vaccination rates in low-income countries (LICs) vary widely. Increasing coverage of vaccines to 90% in the poorest countries over the next 10 years has been estimated to prevent 426 million cases of illness and avert nearly 6.4 million childhood deaths worldwide. Consequently, we sought to provide a comprehensive examination of contemporary vaccination patterns in East Africa and to identify common and country-specific barriers to complete childhood vaccination. Using data from the Demographic and Health Surveys (DHS) for Burundi, Ethiopia, Kenya, Rwanda, Tanzania, and Uganda, we looked at the prevalence of complete vaccination for polio, measles, Bacillus Calmette-Guérin (BCG) and DTwPHibHep (DTP) as recommended by the WHO among children ages 12 to 23 months. We conducted multivariable logistic regression within each country to estimate associations between complete vaccination status and health care access and sociodemographic variables using backwards stepwise regression. Vaccination varied significantly by country. In all countries, the majority of children received at least one dose of a WHO recommended vaccine; however, in Ethiopia, Tanzania, and Uganda less than 50% of children received a complete schedule of recommended vaccines. Being delivered in a public or private institution compared with being delivered at home was associated with increased odds of complete vaccination status. Sociodemographic covariates were not consistently associated with complete vaccination status across countries. Although no consistent set of predictors accounted for complete vaccination status, we observed differences based on region and the location of delivery. These differences point to the need to examine the historical, political, and economic context of each country in order to maximize vaccination coverage. Vaccination against these childhood diseases is a critical step towards reaching the Millennium Development Goal of reducing under-five mortality by two-thirds by 2015 and thus should be a global priority

Challenging Perceptions of Disability through Performance Poetry Methods: The "Seen but Seldom Heard" Project.

This paper considers performance poetry as a method to explore lived experiences of disability. We discuss how poetic inquiry used within a participatory arts-based research framework can enable young people to collectively question society’s attitudes and actions towards disability. Poetry will be considered as a means to develop a more accessible and effective arena in which young people with direct experience of disability can be empowered to develop new skills that enable them to tell their own stories. Discussion of how this can challenge audiences to critically reflect upon their own perceptions of disability will also be developed

Report of the Beyond the MSSM Subgroup for the Tevatron Run II SUSY/Higgs Workshop

There are many low-energy models of supersymmetry breaking parameters which are motivated by theoretical and experimental considerations. Here, we discuss some of the lesser-known theories of low-energy supersymmetry, and outline their phenomenological consequences. In some cases, these theories have more gauge symmetry or particle content than the Minimal Supersymmetric Standard Model. In other cases, the parameters of the Lagrangian are unusual compared to commonly accepted norms (e.g., Wino LSP, heavy gluino LSP, light gluino, etc.). The phenomenology of supersymmetry varies greatly between the different models. Correspondingly, particular aspects of the detectors assume greater or lesser importance. Detection of supersymmetry and the determination of all parameters may well depend upon having the widest possible view of supersymmetry phenomenology.Comment: 78 pages, 49 figures, to appear in the Proceedings of the Tevatron Run II SUSY/Higgs Workshop. Editor: J. F. Gunion; BTMSSM Convenors: M. Chertok, H. Dreiner, G. Landsberg, J. F. Gunion, J.D. Well

Physics Beyond the Standard Model

I briefly summarize the prospects for extending our understanding of physics beyond the standard model within the next five years.Comment: 9 pages, 2 figures, LaTeX. Presented at the 1999 UK Phenomenology Workshop, Durham, September 1999. To be published in Journal of Physics

Utility of early circulating tumour DNA dynamics as a surrogate for progression free survival in the BEECH phase I/II trial in metastatic breast cancer

n/

A role for macrophages under cytokine control in mediating resistance to ADI-PEG20 (pegargiminase) in ASS1-deficient mesothelioma

Background Pegylated arginine deiminase (ADI-PEG20; pegargiminase) depletes arginine and improves survival outcomes for patients with argininosuccinate synthetase 1 (ASS1)-deficient malignant pleural mesothelioma (MPM). Optimisation of ADI-PEG20-based therapy will require a deeper understanding of resistance mechanisms, including those mediated by the tumor microenvironment. Here, we sought to reverse translate increased tumoral macrophage infiltration in patients with ASS1-deficient MPM relapsing on pegargiminase therapy. Methods Macrophage-MPM tumor cell line (2591, MSTO, JU77) co-cultures treated with ADI-PEG20 were analyzed by flow cytometry. Microarray experiments of gene expression profiling were performed in ADI-PEG20-treated MPM tumor cells, and macrophage-relevant genetic “hits” were validated by qPCR, ELISA, and LC/MS. Cytokine and argininosuccinate analyses were performed using plasma from pegargiminase-treated patients with MPM. Results We identified that ASS1-expressing macrophages promoted viability of ADI-PEG20-treated ASS1-negative MPM cell lines. Microarray gene expression data revealed a dominant CXCR2-dependent chemotactic signature and co-expression of VEGF-A and IL-1α in ADI-PEG20-treated MPM cell lines. We confirmed that ASS1 in macrophages was IL-1α-inducible and that the argininosuccinate concentration doubled in the cell supernatant sufficient to restore MPM cell viability under co-culture conditions with ADI-PEG20. For further validation, we detected elevated plasma VEGF-A and CXCR2-dependent cytokines, and increased argininosuccinate in patients with MPM progressing on ADI-PEG20. Finally, liposomal clodronate depleted ADI-PEG20-driven macrophage infiltration and suppressed growth significantly in the MSTO xenograft murine model. Conclusions Collectively, our data indicate that ADI-PEG20-inducible cytokines orchestrate argininosuccinate fuelling of ASS1-deficient mesothelioma by macrophages. This novel stromal-mediated resistance pathway may be leveraged to optimize arginine deprivation therapy for mesothelioma and related arginine-dependent cancers