Power-law distributions and Levy-stable intermittent fluctuations in stochastic systems of many autocatalytic elements

A generic model of stochastic autocatalytic dynamics with many degrees of freedom $w_i$ $i=1,...,N$ is studied using computer simulations. The time evolution of the $w_i$'s combines a random multiplicative dynamics $w_i(t+1) = \lambda w_i(t)$ at the individual level with a global coupling through a constraint which does not allow the $w_i$'s to fall below a lower cutoff given by $c \cdot \bar w$, where $\bar w$ is their momentary average and $0<c<1$ is a constant. The dynamic variables $w_i$ are found to exhibit a power-law distribution of the form $p(w) \sim w^{-1-\alpha}$. The exponent $\alpha (c,N)$ is quite insensitive to the distribution $\Pi(\lambda)$ of the random factor $\lambda$, but it is non-universal, and increases monotonically as a function of $c$. The "thermodynamic" limit, N goes to infty and the limit of decoupled free multiplicative random walks c goes to 0, do not commute: $\alpha(0,N) = 0$ for any finite $N$ while $\alpha(c,\infty) \ge 1$ (which is the common range in empirical systems) for any positive $c$. The time evolution of ${\bar w (t)}$ exhibits intermittent fluctuations parametrized by a (truncated) L\'evy-stable distribution $L_{\alpha}(r)$ with the same index $\alpha$. This non-trivial relation between the distribution of the $w_i$'s at a given time and the temporal fluctuations of their average is examined and its relevance to empirical systems is discussed.Comment: 7 pages, 4 figure

Bounds on the heat kernel of the Schroedinger operator in a random electromagnetic field

We obtain lower and upper bounds on the heat kernel and Green functions of the Schroedinger operator in a random Gaussian magnetic field and a fixed scalar potential. We apply stochastic Feynman-Kac representation, diamagnetic upper bounds and the Jensen inequality for the lower bound. We show that if the covariance of the electromagnetic (vector) potential is increasing at large distances then the lower bound is decreasing exponentially fast for large distances and a large time.Comment: some technical improvements, new references, to appear in Journ.Phys.

RACE-IT - Rapid Acute Coronary Syndrome Exclusion using the Beckman Coulter Access high-sensitivity cardiac troponin I: A stepped-wedge cluster randomized trial

Background: Protocols utilizing high-sensitivity cardiac troponin (hs-cTn) assays for the evaluation of suspected acute coronary syndrome (ACS) in the emergency department (ED) have been gaining popularity across the US and the world. These protocols more rapidly rule-out ACS and more accurately identify the presence of acute myocardial injury. At this time, few randomized trials have evaluated the safety and operational impact of these assays, resulting in limited evidence to guide the use and implementation of hs-cTn in the ED. Objective: The main study objective is to test the effectiveness of a rapid ACS rule-out pathway using hs-cTnI in safely discharging patients from the ED for whom clinical suspicion for ACS exists. Design: This prospective, implementation trial (n = 11,070) will utilize a stepped wedge cluster randomized trial design. The design will allow for all participating sites to capture benefit from the implementation of the hs-cTnI pathway while providing data evaluating the effectiveness in providing safe and rapid evaluation of patients with clinical suspicion for ACS. Summary: Demonstrating that clinical pathways using hs-cTnI can be effectively implemented to rapidly rule-out ACS while conserving costly hospital resources has significant implications for the care of patients with possible acute cardiac conditions in EDs across the US. Clinicaltrialsgov identifier: NCT04488913

Floquet scattering theory of quantum pumps

We develop the Floquet scattering theory for quantum mechanical pumping in mesoscopic conductors. The nonequilibrium distribution function, the dc charge and heat currents are investigated at arbitrary pumping amplitude and frequency. For mesoscopic samples with discrete spectrum we predict a sign reversal of the pumped current when the pump frequency is equal to the level spacing in the sample. This effect allows to measure the phase of the transmission coefficient through the mesoscopic sample. We discuss the necessary symmetry conditions (both spatial and temporal) for pumping.Comment: 11 pages, 5 figure

Impacts of Climate Change on indirect human exposure to pathogens and chemicals from agriculture

Objective: Climate change is likely to affect the nature of pathogens and chemicals in the environment and their fate and transport. Future risks of pathogens and chemicals could therefore be very different from those of today. In this review, we assess the implications of climate change for changes in human exposures to pathogens and chemicals in agricultural systems in the United Kingdom and discuss the subsequent effects on health impacts. Data sources: In this review, we used expert input and considered literature on climate change ; health effects resulting from exposure to pathogens and chemicals arising from agriculture ; inputs of chemicals and pathogens to agricultural systems ; and human exposure pathways for pathogens and chemicals in agricultural systems. Data synthesis: We established the current evidence base for health effects of chemicals and pathogens in the agricultural environment ; determined the potential implications of climate change on chemical and pathogen inputs in agricultural systems ; and explored the effects of climate change on environmental transport and fate of different contaminant types. We combined these data to assess the implications of climate change in terms of indirect human exposure to pathogens and chemicals in agricultural systems. We then developed recommendations on future research and policy changes to manage any adverse increases in risks. Conclusions: Overall, climate change is likely to increase human exposures to agricultural contaminants. The magnitude of the increases will be highly dependent on the contaminant type. Risks from many pathogens and particulate and particle-associated contaminants could increase significantly. These increases in exposure can, however, be managed for the most part through targeted research and policy changes

Recombination rate and selection strength in HIV intra-patient evolution

The evolutionary dynamics of HIV during the chronic phase of infection is driven by the host immune response and by selective pressures exerted through drug treatment. To understand and model the evolution of HIV quantitatively, the parameters governing genetic diversification and the strength of selection need to be known. While mutation rates can be measured in single replication cycles, the relevant effective recombination rate depends on the probability of coinfection of a cell with more than one virus and can only be inferred from population data. However, most population genetic estimators for recombination rates assume absence of selection and are hence of limited applicability to HIV, since positive and purifying selection are important in HIV evolution. Here, we estimate the rate of recombination and the distribution of selection coefficients from time-resolved sequence data tracking the evolution of HIV within single patients. By examining temporal changes in the genetic composition of the population, we estimate the effective recombination to be r=1.4e-5 recombinations per site and generation. Furthermore, we provide evidence that selection coefficients of at least 15% of the observed non-synonymous polymorphisms exceed 0.8% per generation. These results provide a basis for a more detailed understanding of the evolution of HIV. A particularly interesting case is evolution in response to drug treatment, where recombination can facilitate the rapid acquisition of multiple resistance mutations. With the methods developed here, more precise and more detailed studies will be possible, as soon as data with higher time resolution and greater sample sizes is available.Comment: to appear in PLoS Computational Biolog

Blocking TLR7- and TLR9-mediated IFN-α Production by Plasmacytoid Dendritic Cells Does Not Diminish Immune Activation in Early SIV Infection

Persistent production of type I interferon (IFN) by activated plasmacytoid dendritic cells (pDC) is a leading model to explain chronic immune activation in human immunodeficiency virus (HIV) infection but direct evidence for this is lacking. We used a dual antagonist of Toll-like receptor (TLR) 7 and TLR9 to selectively inhibit responses of pDC but not other mononuclear phagocytes to viral RNA prior to and for 8 weeks following pathogenic simian immunodeficiency virus (SIV) infection of rhesus macaques. We show that pDC are major but not exclusive producers of IFN-α that rapidly become unresponsive to virus stimulation following SIV infection, whereas myeloid DC gain the capacity to produce IFN-α, albeit at low levels. pDC mediate a marked but transient IFN-α response in lymph nodes during the acute phase that is blocked by administration of TLR7 and TLR9 antagonist without impacting pDC recruitment. TLR7 and TLR9 blockade did not impact virus load or the acute IFN-α response in plasma and had minimal effect on expression of IFN-stimulated genes in both blood and lymph node. TLR7 and TLR9 blockade did not prevent activation of memory CD4+ and CD8+ T cells in blood or lymph node but led to significant increases in proliferation of both subsets in blood following SIV infection. Our findings reveal that virus-mediated activation of pDC through TLR7 and TLR9 contributes to substantial but transient IFN-α production following pathogenic SIV infection. However, the data indicate that pDC activation and IFN-α production are unlikely to be major factors in driving immune activation in early infection. Based on these findings therapeutic strategies aimed at blocking pDC function and IFN-α production may not reduce HIV-associated immunopathology. © 2013 Kader et al