Mean-field equations for stochastic firing-rate neural fields with delays: Derivation and noise-induced transitions

In this manuscript we analyze the collective behavior of mean-field limits of large-scale, spatially extended stochastic neuronal networks with delays. Rigorously, the asymptotic regime of such systems is characterized by a very intricate stochastic delayed integro-differential McKean-Vlasov equation that remain impenetrable, leaving the stochastic collective dynamics of such networks poorly understood. In order to study these macroscopic dynamics, we analyze networks of firing-rate neurons, i.e. with linear intrinsic dynamics and sigmoidal interactions. In that case, we prove that the solution of the mean-field equation is Gaussian, hence characterized by its two first moments, and that these two quantities satisfy a set of coupled delayed integro-differential equations. These equations are similar to usual neural field equations, and incorporate noise levels as a parameter, allowing analysis of noise-induced transitions. We identify through bifurcation analysis several qualitative transitions due to noise in the mean-field limit. In particular, stabilization of spatially homogeneous solutions, synchronized oscillations, bumps, chaotic dynamics, wave or bump splitting are exhibited and arise from static or dynamic Turing-Hopf bifurcations. These surprising phenomena allow further exploring the role of noise in the nervous system.Comment: Updated to the latest version published, and clarified the dependence in space of Brownian motion

A systems approach to evaluate One Health initiatives

Challenges calling for integrated approaches to health, such as the One Health (OH) approach, typically arise from the intertwined spheres of humans, animals, and ecosystems constituting their environment. Initiatives addressing such wicked problems commonly consist of complex structures and dynamics. As a result of the EU COST Action (TD 1404) “Network for Evaluation of One Health” (NEOH), we propose an evaluation framework anchored in systems theory to address the intrinsic complexity of OH initiatives and regard them as subsystems of the context within which they operate. Typically, they intend to influence a system with a view to improve human, animal, and environmental health. The NEOH evaluation framework consists of four overarching elements, namely: (1) the definition of the initiative and its context, (2) the description of the theory of change with an assessment of expected and unexpected outcomes, (3) the process evaluation of operational and supporting infrastructures (the “OH-ness”), and (4) an assessment of the association(s) between the process evaluation and the outcomes produced. It relies on a mixed methods approach by combining a descriptive and qualitative assessment with a semi-quantitative scoring for the evaluation of the degree and structural balance of “OH-ness” (summarised in an OH-index and OH-ratio, respectively) and conventional metrics for different outcomes in a multi-criteria-decision-analysis. Here, we focus on the methodology for Elements (1) and (3) including ready-to-use Microsoft Excel spreadsheets for the assessment of the “OH-ness”. We also provide an overview of Element (2), and refer to the NEOH handbook for further details, also regarding Element (4) (http://neoh.onehealthglobal.net). The presented approach helps researchers, practitioners, and evaluators to conceptualise and conduct evaluations of integrated approaches to health and facilitates comparison and learning across different OH activities thereby facilitating decisions on resource allocation. The application of the framework has been described in eight case studies in the same Frontiers research topic and provides first data on OH-index and OH-ratio, which is an important step towards their validation and the creation of a dataset for future benchmarking, and to demonstrate under which circumstances OH initiatives provide added value compared to disciplinary or conventional health initiatives

A comparative analysis of the Libyan national essential medicines list and the WHO model list of essential medicines

Aim and Objectives: To examine the concordance of the Libyan Pharmaceutical List of Essential Medicines (LPLEM) with the World Health Organization Model List of Essential Medicines 2009 (WMLEM 2009). Methods: The concordance between generic medicines listed in the WMLEM 2009 (standard reference list) and the LPLEM 2006 (comparator list) was evaluated. Results: The total number of Basic Essential Medicines (BEMs) listed on the WMLEM 2009 was 347. The total number of generic medicines listed on the LPLEM was 584. Although the LPLEM has more listed medicines, only 270 (77.6%) of BEMs from the WMLEM were listed as available. However, 25 of the 77 missing medicines were deemed to have appropriate alternatives. A total of 52 medicines from the WMLEM 2009 were therefore missing from the LPLEM. Discrepancies compared to the WMLEM 2009 were identified in 15 out of 29 therapeutic sections. The highest discrepancy rate from the WMLEM 2009 was in the anti-infective section (35 missing medicines). Missing BEMs were noted in many subclassifications of the anti-infective medicines section, but omissions were particularly prevalent in the antibacterial medicines subsection (11 missing medicines). Antituberculosis medications had the highest discrepancy rate for antibacterial BEMs with one-third of the single medicines recommended by the WHO in the WMLEM 2009 not listed on the LPLEM. Of the 314 additional medicines on the LPLEM, 18 were deemed to be irrational non-essential medicines. Conclusion: The LPLEM does not include several essential medicines recommended by the WHO in the WMLEM 2009. These discrepancies may have serious public health implications for management of some infectious diseases, particularly, tuberculosis and HIV

Improving the use of research evidence in guideline development: 15. Disseminating and implementing guidelines

BACKGROUND: The World Health Organization (WHO), like many other organisations around the world, has recognised the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the 15(th )of a series of 16 reviews that have been prepared as background for advice from the WHO Advisory Committee on Health Research to WHO on how to achieve this. OBJECTIVES: In this review we address strategies for the implementation of recommendations in health care. METHODS: We examined overviews of systematic reviews of interventions to improve health care delivery and health care systems prepared by the Cochrane Effective Practice and Organisation of Care (EPOC) group. We also conducted searches using PubMed and three databases of methodological studies for existing systematic reviews and relevant methodological research. We did not conduct systematic reviews ourselves. Our conclusions are based on the available evidence, consideration of what WHO and other organisations are doing and logical arguments. KEY QUESTIONS AND ANSWERS: What should WHO do to disseminate and facilitate the uptake of recommendations? • WHO should choose strategies to implement their guidelines from among those which have been evaluated positively in the published literature on implementation research • Because the evidence base is weak and modest to moderate effects, at best, can be anticipated, WHO should promote rigorous evaluations of implementation strategies. What should be done at headquarters, by regional offices and in countries? • Adaptation and implementation of WHO guidelines should be done locally, at the national or sub-national level. • WHO headquarters and regional offices should support the development and evaluation of implementation strategies by local authorities

On the use of the group SO(4,2) in atomic and molecular physics

In this paper the dynamical noninvariance group SO(4,2) for a hydrogen-like atom is derived through two different approaches. The first one is by an established traditional ascent process starting from the symmetry group SO(3). This approach is presented in a mathematically oriented original way with a special emphasis on maximally superintegrable systems, N-dimensional extension and little groups. The second approach is by a new symmetry descent process starting from the noninvariance dynamical group Sp(8,R) for a four-dimensional harmonic oscillator. It is based on the little known concept of a Lie algebra under constraints and corresponds in some sense to a symmetry breaking mechanism. This paper ends with a brief discussion of the interest of SO(4,2) for a new group-theoretical approach to the periodic table of chemical elements. In this connection, a general ongoing programme based on the use of a complete set of commuting operators is briefly described. It is believed that the present paper could be useful not only to the atomic and molecular community but also to people working in theoretical and mathematical physics.Comment: 31 page

2-D Magnetohydrodynamic Simulations of Induced Plasma Dynamics in the Near-Core Region of a Galaxy Cluster

We present results from numerical simulations of the cooling-core cluster A2199 produced by the two-dimensional (2-D) resistive magnetohydrodynamics (MHD) code MACH2. In our simulations we explore the effect of anisotropic thermal conduction on the energy balance of the system. The results from idealized cases in 2-D axisymmetric geometry underscore the importance of the initial plasma density in ICM simulations, especially the near-core values since the radiation cooling rate is proportional to ${n_e}^2$. Heat conduction is found to be non-effective in preventing catastrophic cooling in this cluster. In addition we performed 2-D planar MHD simulations starting from initial conditions deliberately violating both thermal balance and hydrostatic equilibrium in the ICM, to assess contributions of the convective terms in the energy balance of the system against anisotropic thermal conduction. We find that in this case work done by the pressure on the plasma can dominate the early evolution of the internal energy over anisotropic thermal conduction in the presence of subsonic flows, thereby reducing the impact of the magnetic field. Deviations from hydrostatic equilibrium near the cluster core may be associated with transient activity of a central active galactic nucleus and/or remnant dynamical activity in the ICM and warrant further study in three dimensions.Comment: 16 pages, 13 figures, accepted for publication in MNRA

Clusters of galaxies : observational properties of the diffuse radio emission

Clusters of galaxies, as the largest virialized systems in the Universe, are ideal laboratories to study the formation and evolution of cosmic structures...(abridged)... Most of the detailed knowledge of galaxy clusters has been obtained in recent years from the study of ICM through X-ray Astronomy. At the same time, radio observations have proved that the ICM is mixed with non-thermal components, i.e. highly relativistic particles and large-scale magnetic fields, detected through their synchrotron emission. The knowledge of the properties of these non-thermal ICM components has increased significantly, owing to sensitive radio images and to the development of theoretical models. Diffuse synchrotron radio emission in the central and peripheral cluster regions has been found in many clusters. Moreover large-scale magnetic fields appear to be present in all galaxy clusters, as derived from Rotation Measure (RM) studies. Non-thermal components are linked to the cluster X-ray properties, and to the cluster evolutionary stage, and are crucial for a comprehensive physical description of the intracluster medium. They play an important role in the cluster formation and evolution. We review here the observational properties of diffuse non-thermal sources detected in galaxy clusters: halos, relics and mini-halos. We discuss their classification and properties. We report published results up to date and obtain and discuss statistical properties. We present the properties of large-scale magnetic fields in clusters and in even larger structures: filaments connecting galaxy clusters. We summarize the current models of the origin of these cluster components, and outline the improvements that are expected in this area from future developments thanks to the new generation of radio telescopes.Comment: Accepted for the publication in The Astronomy and Astrophysics Review. 58 pages, 26 figure

Metabolism within the tumor microenvironment and its implication on cancer progression: an ongoing therapeutic target

Since reprogramming energy metabolism is considered a new hallmark of cancer, tumor metabolism is again in the spotlight of cancer research. Many studies have been carried out and many possible therapies have been developed in the last years. However, tumor cells are not alone. A series of extracellular components and stromal cells, such as endothelial cells, cancer-associated fibroblasts, tumor-associated macrophages and tumor-infiltrating T cells, surround tumor cells in the so-called tumor microenvironment. Metabolic features of these cells are being studied in deep in order to find relationships between metabolism within the tumor microenvironment and tumor progression. Moreover, it cannot be forgotten that tumor growth is able to modulate host metabolism and homeostasis, so that tumor microenvironment is not the whole story. Importantly, the metabolic switch in cancer is just a consequence of the flexibility and adaptability of metabolism and should not be surprising. Treatments of cancer patients with combined therapies including anti-tumor agents with those targeting stromal cell metabolism, anti-angiogenic drugs and/or immunotherapy are being developed as promising therapeutics.Mª Carmen Ocaña is recipient of a predoctoral FPU grant from the Spanish Ministry of Education, Culture and Sport. Supported by grants BIO2014-56092-R (MINECO and FEDER), P12-CTS-1507 (Andalusian Government and FEDER) and funds from group BIO-267 (Andalusian Government). The "CIBER de Enfermedades Raras" is an initiative from the ISCIII (Spain). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript