A new Bihari inequality and initial value problems of first order fractional differential equations.

We prove existence of solutions, and particularly positive solutions, of initial value problems (IVPs) for nonlinear fractional differential equations involving the Caputo differential operator of order α∈(0,1). One novelty in this paper is that it is not assumed that f is continuous but that it satisfies an Lp-Carathéodory condition for some p>1α (detailed definitions are given in the paper). We prove existence on an interval [0, T] in cases where T can be arbitrarily large, called global solutions. The necessary a priori bounds are found using a new version of the Bihari inequality that we prove here. We show that global solutions exist when f(t, u) grows at most linearly in u, and also in some cases when the growth is faster than linear. We give examples of the new results for some fractional differential equations with nonlinearities related to some that occur in combustion theory. We also discuss in detail the often used alternative definition of Caputo fractional derivative and we show that it has severe disadvantages which restricts its use. In particular we prove that there is a necessary condition in order that solutions of the IVP can exist with this definition, which has often been overlooked in the literature.

Benefits and unintended consequences of antimicrobial de-escalation: Implications for stewardship programs.

Sequential antimicrobial de-escalation aims to minimize resistance to high-value broad-spectrum empiric antimicrobials by switching to alternative drugs when testing confirms susceptibility. Though widely practiced, the effects de-escalation are not well understood. Definitions of interventions and outcomes differ among studies. We use mathematical models of the transmission and evolution of Pseudomonas aeruginosa in an intensive care unit to assess the effect of de-escalation on a broad range of outcomes, and clarify expectations. In these models, de-escalation reduces the use of high-value drugs and preserves the effectiveness of empiric therapy, while also selecting for multidrug-resistant strains and leaving patients vulnerable to colonization and superinfection. The net effect of de-escalation in our models is to increase infection prevalence while also increasing the probability of effective treatment. Changes in mortality are small, and can be either positive or negative. The clinical significance of small changes in outcomes such as infection prevalence and death may exceed more easily detectable changes in drug use and resistance. Integrating harms and benefits into ranked outcomes for each patient may provide a way forward in the analysis of these tradeoffs. Our models provide a conceptual framework for the collection and interpretation of evidence needed to inform antimicrobial stewardship.

Population models with quasi-constant-yield harvest rates.

One-dimensional logistic population models with quasi-constant-yield harvest rates are studied under the assumptions that a population inhabits a patch of dimensionless width and no members of the population can survive outside of the patch. The essential problem is to determine the size of the patch and the ranges of the harvesting rate functions under which the population survives or becomes extinct. This is the first paper which discusses such models with the Dirichlet boundary conditions and can tell the exact quantity of harvest rates of the species without having the population die out. The methodology is to establish new results on the existence of positive solutions of semi-positone Hammerstein integral equations using the fixed point index theory for compact maps defined on cones, and apply the new results to tackle the essential problem. It is expected that the established analytical results have broad applications in management of sustainable ecological systems.

Treatment-donation-stockpile dynamics in ebola convalescent blood transfusion therapy.

The interim guidance issued by the World Health Organization during the West Africa 2014 Ebola outbreak provides guidelines on the use of convalescent blood from Ebola survivors for transfusion therapy. Here we develop a novel mathematical model, based on the interim guidance, to examine the nonlinear transmission-treatment-donation-stockpile dynamics during an Ebola outbreak and with a large scale use of the transfusion therapy in the population. We estimate the reduction of case fatality ratio by introducing convalescent blood transfusion as a therapy, and inform optimal treatment-donation-stockpile strategies to balance the treatment need for case fatality ratio reduction and the strategic need of maintaining a minimal blood bank stockpile for other control priorities.