Could antiretrovirals be treating EBV in MS? A case report

We present the case of an HIV-negative patient clinically diagnosed with relapsing-remitting MS who achieved significant disease improvement on Combivir (zidovudine/lamivudine). Within months of treatment, the patient reported complete resolution of previously unremitting fatigue and paresthesiae, with simultaneous improvements in lesion burden detected by MRI. All improvements have been sustained for more than three years. This response may be related to the action of zidovudine as a known inhibitor of EBV lytic DNA replication, suggesting future directions for clinical investigation. Keywords: Multiple sclerosis, Epstein-Barr viru

Supersymmetric Vacua in Random Supergravity

We determine the spectrum of scalar masses in a supersymmetric vacuum of a general N=1 supergravity theory, with the Kahler potential and superpotential taken to be random functions of N complex scalar fields. We derive a random matrix model for the Hessian matrix and compute the eigenvalue spectrum. Tachyons consistent with the Breitenlohner-Freedman bound are generically present, and although these tachyons cannot destabilize the supersymmetric vacuum, they do influence the likelihood of the existence of an `uplift' to a metastable vacuum with positive cosmological constant. We show that the probability that a supersymmetric AdS vacuum has no tachyons is formally equivalent to the probability of a large fluctuation of the smallest eigenvalue of a certain real Wishart matrix. For normally-distributed matrix entries and any N, this probability is given exactly by P = exp(-2N^2|W|^2/m_{susy}^2), with W denoting the superpotential and m_{susy} the supersymmetric mass scale; for more general distributions of the entries, our result is accurate when N >> 1. We conclude that for |W| \gtrsim m_{susy}/N, tachyonic instabilities are ubiquitous in configurations obtained by uplifting supersymmetric vacua.Comment: 26 pages, 6 figure

The fundamental cycle of concept construction underlying various theoretical frameworks

In this paper, the development of mathematical concepts over time is considered. Particular reference is given to the shifting of attention from step-by-step procedures that are performed in time, to symbolism that can be manipulated as mental entities on paper and in the mind. The development is analysed using different theoretical perspectives, including the SOLO model and various theories of concept construction to reveal a fundamental cycle underlying the building of concepts that features widely in different ways of thinking that occurs throughout mathematical learning

The dynamics of animal social networks: Analytical, conceptual, and theoretical advances

Social network analysis provides a broad and complex perspective on animal sociality that is widely applicable to almost any species. Recent applications demonstrate the utility of network analysis for advancing our understanding of the dynamics, selection pressures, development, and evolution of complex social systems. However, most studies of animal social networks rely primarily on a descriptive approach. To propel the field of animal social networks beyond exploratory analyses and to facilitate the integration of quantitative methods that allow for the testing of ecologically and evolutionarily relevant hypotheses, we review methodological and conceptual advances in network science, which are underutilized in studies of animal sociality. First, we highlight how the use of statistical model- ing and triadic motifs analysis can advance our understanding of the processes that structure networks. Second, we discuss how the consideration of temporal changes and spatial constraints can shed light on the dynamics of social networks. Third, we consider how the study of variation at multiple scales can potentially transform our understanding of the structure and function of animal networks. We direct readers to analytical tools that facilitate the adoption of these new concepts and methods. Our goal is to provide behavioral ecologists with a toolbox of current methods that can stimulate novel insights into the ecological influences and evolutionary pressures structuring networks and advance our understanding of the proximate and ultimate processes that drive animal sociality

The Wasteland of Random Supergravities

We show that in a general \cal{N} = 1 supergravity with N \gg 1 scalar fields, an exponentially small fraction of the de Sitter critical points are metastable vacua. Taking the superpotential and Kahler potential to be random functions, we construct a random matrix model for the Hessian matrix, which is well-approximated by the sum of a Wigner matrix and two Wishart matrices. We compute the eigenvalue spectrum analytically from the free convolution of the constituent spectra and find that in typical configurations, a significant fraction of the eigenvalues are negative. Building on the Tracy-Widom law governing fluctuations of extreme eigenvalues, we determine the probability P of a large fluctuation in which all the eigenvalues become positive. Strong eigenvalue repulsion makes this extremely unlikely: we find P \propto exp(-c N^p), with c, p being constants. For generic critical points we find p \approx 1.5, while for approximately-supersymmetric critical points, p \approx 1.3. Our results have significant implications for the counting of de Sitter vacua in string theory, but the number of vacua remains vast.Comment: 39 pages, 9 figures; v2: fixed typos, added refs and clarification

The dynamics of animal social networks: Analytical, conceptual, and theoretical advances

Social network analysis provides a broad and complex perspective on animal sociality that is widely applicable to almost any species. Recent applications demonstrate the utility of network analysis for advancing our understanding of the dynamics, selection pressures, development, and evolution of complex social systems. However, most studies of animal social networks rely primarily on a descriptive approach. To propel the field of animal social networks beyond exploratory analyses and to facilitate the integration of quantitative methods that allow for the testing of ecologically and evolutionarily relevant hypotheses, we review methodological and conceptual advances in network science, which are underutilized in studies of animal sociality. First, we highlight how the use of statistical model- ing and triadic motifs analysis can advance our understanding of the processes that structure networks. Second, we discuss how the consideration of temporal changes and spatial constraints can shed light on the dynamics of social networks. Third, we consider how the study of variation at multiple scales can potentially transform our understanding of the structure and function of animal networks. We direct readers to analytical tools that facilitate the adoption of these new concepts and methods. Our goal is to provide behavioral ecologists with a toolbox of current methods that can stimulate novel insights into the ecological influences and evolutionary pressures structuring networks and advance our understanding of the proximate and ultimate processes that drive animal sociality

Implementation facilitation to introduce and support emergency department-initiated buprenorphine for opioid use disorder in high need, low resource settings: protocol for multi-site implementation-feasibility study

Background: For many reasons, the emergency department (ED) is a critical venue to initiate OUD interventions. The prevailing culture of the ED has been that substance use disorders are non-emergent conditions better addressed outside the ED where resources are less constrained. This study, its rapid funding mechanism, and accelerated timeline originated out of the urgent need to learn whether ED-initiated buprenorphine (BUP) with referral for treatment of OUD is generalizable, as well as to develop strategies to facilitate its adoption across a variety of ED settings and under real-world conditions. It both complements and uses methods adapted from Project ED Health (CTN-0069), a Hybrid Type 3 implementation-effectiveness study of using Implementation Facilitation (IF) to integrate ED-initiated BUP and referral programs. Methods: ED-CONNECT (CTN 0079) was a three-site implementation study exploring the feasibility, acceptability, and impact of introducing ED-initiated BUP in rural and urban settings with high-need, limited resources, and different staffing structures. We used a multi-faceted approach to develop, introduce and iteratively refine site-specific ED clinical protocols and implementation plans for opioid use disorder (OUD) screening, ED-initiated BUP, and referral for treatment. We employed a participatory action research approach and use mixed methods incorporating data derived from abstraction of medical records and administrative data, assessments of recruited ED patient-participants, and both qualitative and quantitative inquiry involving staff from the ED and community, patients, and other stakeholders. Discussion: This study was designed to provide the necessary, time-sensitive understanding of how to identify OUD and initiate treatment with BUP in the EDs previously not providing ED-initiated BUP, in communities in which this intervention is most needed: high need, low resource settings. Trial registration: The study was prospectively registered on ClinicalTrials.gov (NCT03544112) on June 01, 2018: https://clinicaltrials.gov/ct2/show/NCT03544112