Characterizing Coxian Distributions of Algebraic Degree q and Triangular Order p

In this research note we present a procedure to characterize the set of all Coxian distributions of algebraic degree q that have Coxian representations of order p where p > q

Extension of PRISM by Synthesis of Optimal Timeouts in Fixed-Delay CTMC

We present a practically appealing extension of the probabilistic model checker PRISM rendering it to handle fixed-delay continuous-time Markov chains (fdCTMCs) with rewards, the equivalent formalism to the deterministic and stochastic Petri nets (DSPNs). fdCTMCs allow transitions with fixed-delays (or timeouts) on top of the traditional transitions with exponential rates. Our extension supports an evaluation of expected reward until reaching a given set of target states. The main contribution is that, considering the fixed-delays as parameters, we implemented a synthesis algorithm that computes the epsilon-optimal values of the fixed-delays minimizing the expected reward. We provide a performance evaluation of the synthesis on practical examples

Modelling extreme concentration from a source in a turbulent flow over rough wall

The concentration fluctuations in passive plumes from an elevated and a groundlevel source in a turbulent boundary layer over a rough wall were studied using large eddy simulation and wind tunnel experiment. The predictions of statistics up to second order moments were thereby validated. In addition, the trend of relative fluctuations far downstream for a ground level source was estimated using dimensional analysis. The techniques of extreme value theory were then applied to predict extreme concentrations by modelling the upper tail of the probability density function of the concentration time series by the Generalised Pareto Distribution. Data obtained from both the simulations and experiments were analysed in this manner. The predicted maximum concentration (?0) normalized by the local mean concentration (Cm) or by the local r.m.s of concentration fluctuation (crms), was extensively investigated. Values for ?0/Cm and ?0/crms as large as 50 and 20 respectively were found for the elevated source and 10 and 15 respectively for the ground-level source

Modelling modal gating of ion channels with hierarchical Markov models

Many ion channels spontaneously switch between different levels of activity. Although this behaviour known as modal gating has been observed for a long time it is currently not well understood. Despite the fact that appropriately representing activity changes is essential for accurately capturing time course data from ion channels, systematic approaches for modelling modal gating are currently not available. In this paper, we develop a modular approach for building such a model in an iterative process. First, stochastic switching between modes and stochastic opening and closing within modes are represented in separate aggregated Markov models. Second, the continuous-time hierarchical Markov model, a new modelling framework proposed here, then enables us to combine these components so that in the integrated model both mode switching as well as the kinetics within modes are appropriately represented. A mathematical analysis reveals that the behaviour of the hierarchical Markov model naturally depends on the properties of its components. We also demonstrate how a hierarchical Markov model can be parametrized using experimental data and show that it provides a better representation than a previous model of the same dataset. Because evidence is increasing that modal gating reflects underlying molecular properties of the channel protein, it is likely that biophysical processes are better captured by our new approach than in earlier models

Measuring Rural Revolutionary Mobilization: The Militiamen, Soldiers, and Minutemen of Fauquier County, Virginia 1775 - 1782

The story of the rural soldiers and militiamen of Virginia that served in the American Revolution remains open to historical research and exploration. Recent scholarship of Virginia’s military contribution to the Revolution focuses heavily on relationships of power among social groups that operated within the colony’s hierarchy, concluding that a lack of white, lower-class political and economic representation disabled mobilization among the Old Dominion’s more settled regions. My study emphasizes the revolutionary backcountry’s story by using Fauquier County, Virginia as a case study. A study of Rural Virginia during the Revolution presents scholars with significant challenges. Literacy rates among the general population were meager, meaning that Virginians in the backcountry left few letters and diaries for historians to interpret. Further complicating the reconstruction of Virginia’s rural revolutionary past were the destructive events of the nineteenth century. The tumults of the Civil War destroyed many Revolutionary War records of several Virginia counties, erasing much of what the Old Dominion’s revolutionary generation documented. For these reasons, Fauquier County represents an ideal subject of study. Court minutes, tax records, property records, and even a few letters and diary entries survived history’s fires to provide enough data from which to synthesize a social history to explore rural Virginia’s revolutionary story and mobilization patterns. The revolutionaries in Fauquier County were not always in concert with those throughout the rest of the colony. In contrast to most of Virginia, the county rallied enthusiastically to pre-Declaration calls for companies of minutemen. Hundreds of rural farmers from Fauquier across the socioeconomic spectrum served in the most successful of Virginia’s fleeting minute battalions known as the Culpeper Minutemen. These men defined themselves as backcountry Virginians against their more cosmopolitan peers from the longer-established eastern settlements. As the war matured and exacted its toll, however, fault lines between the local gentry and local yeomen widened, and the county settled into a recruiting pattern like most other Revolutionary Virginian counties. Understanding the issue of representation and its effect on how communities respond to a crisis remains a highly relevant topic that continues to challenge the public and its elected representatives to this day

the COMIT’ID study protocol for using a Delphi process and face-to-face meetings to establish consensus

Background The reporting of outcomes in clinical trials of subjective tinnitus indicates that many different tinnitus-related complaints are of interest to investigators, from perceptual attributes of the sound (e.g. loudness) to psychosocial impacts (e.g. quality of life). Even when considering one type of intervention strategy for subjective tinnitus, there is no agreement about what is critically important for deciding whether a treatment is effective. The main purpose of this observational study is, therefore to, develop Core Outcome Domain Sets for the three different intervention strategies (sound, psychological, and pharmacological) for adults with chronic subjective tinnitus that should be measured and reported in every clinical trial of these interventions. Secondary objectives are to identify the strengths and limitations of our study design for recruiting and reducing attrition of participants, and to explore uptake of the core outcomes. Methods The ‘Core Outcome Measures in Tinnitus: International Delphi’ (COMIT’ID) study will use a mixed-methods approach that incorporates input from health care users at the pre-Delphi stage, a modified three-round Delphi survey and final consensus meetings (one for each intervention). The meetings will generate recommendations by stakeholder representatives on agreed Core Outcome Domain Sets specific to each intervention. A subsequent step will establish a common cross-cutting Core Outcome Domain Set by identifying the common outcome domains included in all three intervention-specific Core Outcome Domain Sets. To address the secondary objectives, we will gather feedback from participants about their experience of taking part in the Delphi process. We aspire to conduct an observational cohort study to evaluate uptake of the core outcomes in published studies at 7 years following Core Outcome Set publication. Discussion The COMIT’ID study aims to develop a Core Outcome Domain Set that is agreed as critically important for deciding whether a treatment for subjective tinnitus is effective. Such a recommendation would help to standardise future clinical trials worldwide and so we will determine if participation increases use of the Core Outcome Set in the long term. Trial registration This project has been registered (November 2014) in the database of the Core Outcome Measures in Effectiveness Trials (COMET) initiative

Development of a Lethal Rodent Model of Lymphocytic Choriomeningitis Virus Infection for Preclinical Antiviral Drug Testing

Lymphocyctic Choriomeningitis virus (LCMV) is an Old World arenavirus belonging to the family Arenaviridae. The natural host is the common house mouse, with about 5% of the population persistently carrying and shedding the virus. LCMV is spread to humans through the aerosolized excrements of rodents or passed from mother to fetus through the placenta. Some of these cases lead to aseptic meningitis or meningoencephalitis with permanent neurological damage possible. Studies indicate that 2-5% of people are positive for serum LCMV antibodies [1]. LCMV infection has also occurred in organ transplant recipients, with nearly all cases being fatal [2]. There are currently limited treatments for LCMV infection, including the antiviral ribavirin which has associated toxicity. This highlights the need for a suitable animal model to evaluate potential antiviral compounds. This research aims to develop a more robust and consistent lethal mouse model of LCMV infection that can be utilized to assess promising antiviral compounds. An animal disease model that is consistently lethal and produces clinical manifestations seen in the human disease will have a dramatic positive effect on identifying successful treatment. This work is especially critical for fetuses that contract the disease congenitally and immunosuppressed organ transplant recipients at the highest risk to the often fatal effects of an LCMV infection. 1. Mathur G, Yadav K, Ford B, et al. High clinical suspicion of donor-derived disease leads to timely recognition and early intervention to treat solid organ transplant-transmitted lymphocytic choriomeningitis virus. Transpl Infect Dis 2017; Aug;19(4):e12707.2. Amman BR, Pavlin BI, Albariño CG, Comer JA, Erickson BR, Oliver JB, Sealy TK, Vincent MJ, Nichol ST, Paddock CD, Tumpey AJ, Wagoner KD, Glauer RD, Smith KA, Winpisinger KA, Parsely MS, Wyrick P, Hannafin CH, Bandy U, Zaki S, Rollin PE, Ksiazek TG. Pet rodents and fatal lymphocytic choriomeningitis in transplant patients. Emerg Infect Dis. 2007 May;13(5):719-25. doi: 10.3201/eid1305.061269. PMID: 17553250; PMCID: PMC2738461. Presentation Time: Thursday, 11 a.m.-12p.m