A multispecies model for the transmission and control of mastitis in dairy cows

Mastitis in dairy cows is a significant economic and animal welfare issue in the dairy industry. The bacterial pathogens responsible for infection of the mammary gland may be split into two main categories: major and minor pathogens. Infection with major pathogens generally results in clinical illness or strong inflammatory responses and reduced milk yields, whereas minor pathogen infection is usually subclinical. Previous investigations have considered the transmission of these pathogens independently. Experimental evidence has shown cross-protection between species of pathogens. In this study a mathematical model for the coupled transmission of major and minor pathogens along with their interaction via the host was developed in order to consider various methods for controlling the incidence of major pathogen infection. A stability analysis of the model equilibria provides explanations for observed phenomena and previous decoupled modelling results. This multispecies model structure has provided a basis for quantifying the extent of cross-protection between species and assessing possible control strategies against the disease

The reinfection threshold

Thresholds in transmission are responsible for critical changes in infectious disease epidemiology. The epidemic threshold indicates whether infection invades a totally susceptible population. The reinfection threshold indicates whether self-sustained transmission occurs in a population that has developed a degree of partial immunity to the pathogen (by previous infection or vaccination). In models that combine susceptible and partially immune individuals, the reinfection threshold is technically not a bifurcation of equilibria as correctly pointed out by Breban and Blower. However, we show that a branch of equilibria to a reinfection submodel bifurcates from the disease-free equilibrium as transmission crosses this threshold. Consequently, the full model indicates that levels of infection increase by two orders of magnitude and the effect of mass vaccination becomes negligible as transmission increases across the reinfection threshold. (c) 2005 Elsevier Ltd. All rights reserve

Infection, reinfection, and vaccination under suboptimal immune protection: epidemiological perspectives

The SIR (susceptible-infectious-resistant) and SIS (susceptible-infectious-susceptible) frameworks for infectious disease have been extensively studied and successfully applied. They implicitly assume the upper and lower limits of the range of possibilities for host immune response. However, the majority of infections do not fall into either of these extreme categories. We combine two general avenues that straddle this range: temporary immune protection (immunity wanes over time since infection), and partial immune protection (immunity is not fully protective but reduces the risk of reinfection). We present a systematic analysis of the dynamics and equilibrium properties of these models in comparison to SIR and SIS, and analyse the outcome of vaccination programmes. We describe how the waning of immunity shortens inter-epidemic periods, and poses major difficulties to disease eradication. We identify a "reinfection threshold" in transmission when partial immunity is included. Below the reinfection threshold primary infection dominates, levels of infection are low, and vaccination is highly effective (approximately an SIR model). Above the reinfection threshold reinfection dominates, levels of infection are high, and vaccination fails to protect (approximately an SIS situation). This association between high prevalence of infection and vaccine failure emphasizes the problems of controlling recurrent infections in high-burden regions. However, vaccines that induce a better protection than natural infection have the potential to increase the reinfection threshold, and therefore constitute interventions with a surprisingly high capacity to reduce infection where reduction is most neede

Modelling the dynamics of intramammary E. coli infections in dairy cows: understanding mechanisms that distinguish transient from persistent infections

The majority of intramammary infections with Escherichia coli in dairy cows result in transient infections with duration of about 10 days or less, although more persistent infections (2 months or longer) have been identified. We apply a mathematical model to explore the role of an intracellular mammary epithelial cell reservoir in the dynamics of infection. We included biological knowledge of the bovine immune response and known characteristics of the bacterial population in both transient and persistent infections. The results indicate that varying the survival duration of the intracellular reservoir reproduces the data for both transient and persistent infections. Survival in an intracellular reservoir is the most likely mechanism that ensures persistence of E. coli infections in mammary glands. Knowledge of the pathogenesis of persistent infections is essential to develop preventive and treatment programmes for these important infections in dairy cows

The development and validation of an age-structured model for the evaluation of disease control strategies for intestinal helminths

Epidemiological modelling can be a useful tool for the evaluation of parasite control strategies. An age-structured epidemiological model of intestinal helminth dynamics is developed. This model includes the explicit representation of changing worm distributions between hosts as a result of treatment, and estimates the morbidity due to heavy infections. The model is used to evaluate the effectiveness of different programmes of age-targeted community chemotherapy in reducing the amount of morbidity due to helminth infection. The magnitude of age-related heterogeneities is found to be very important in determining the results of age-targeted treatment programmes. The model was verified using field data from control programmes for Ascaris lumbricoides and Trichuris trichiura, and was found to provide accurate predictions of prevalence and mean intensities of infection during and following different control regime

The development of an age structured model for schistosomiasis transmission dynamics and control and its validation for Schistosoma mansoni

Mathematical models are potentially useful tools to aid in the design of control programmes for parasitic diseases. In this paper, a fully age structured epidemiological model of human schistosomiasis is developed and parameterized, and used to predict trends in infection prevalence, intensity and prevalence of heavy infections over age and time during several rounds of mass and age targeted treatment. The model is validated against data from a Schistosoma mansoni control programme in Keny

Quantitative Analysis of Survivin Protein Expression and Its Therapeutic Depletion by an Antisense Oligonucleotide in Human Lung Tumors

RNA-directed antisense and interference therapeutics are a promising treatment option for cancer. The demonstration of depletion of target proteins within human tumors in vivo using validated methodology will be a key to the application of this technology. Here, we present a flow cytometric-based approach to quantitatively determine protein levels in solid tumor material derived by fiber optic brushing (FOB) of non-small cell lung cancer (NSCLC) patients. Focusing upon the survivin protein, and its depletion by an antisense oligonucleotide (ASO) (LY2181308), we show that we can robustly identify a subpopulation of survivin positive tumor cells in FOB samples, and, moreover, detect survivin depletion in tumor samples from a patient treated with LY2181308. Survivin depletion appears to be a result of treatment with this ASO, because a tumor treated with conventional cytotoxic chemotherapy did not exhibit a decreased percentage of survivin positive cells. Our approach is likely to be broadly applicable to, and useful for, the quantification of protein levels in tumor samples obtained as part of clinical trials and studies, facilitating the proof-of-principle testing of novel targeted therapies

AC-induced superfluidity

We argue that a system of ultracold bosonic atoms in a tilted optical lattice can become superfluid in response to resonant AC forcing. Among others, this allows one to prepare a Bose-Einstein condensate in a state associated with a negative effective mass. Our reasoning is backed by both exact numerical simulations for systems consisting of few particles, and by a theoretical approach based on Floquet-Fock states.Comment: Accepted for publication in Europhysics letters, 6 pages, 4 figures, Changes in v2: reference 7 replaced by a more recent on

Raman Spectroscopy of Mott insulator states in optical lattices

We propose and analyse a Raman spectroscopy technique for probing the properties of quantum degenerate bosons in the ground band of an optical lattice. Our formalism describes excitations to higher vibrational bands and is valid for deep lattices where a tight-binding approach can be applied to the describe the initial state of the system. In sufficiently deep lattices, localized states in higher vibrational bands play an important role in the system response, and shifts in resonant frequency of excitation are sensitive to the number of particles per site. We present numerical results of this formalism applied to the case of a uniform lattice deep in the Mott insulator regime.Comment: 10 pages, 3 figure

Towards quantum magnetism with ultracold atoms

22nd International Conference on Atomic PhysicsAt ICAP we presented the efforts and progress at MIT towards using ultracold atoms for the realization of various forms of quantum magnetism. These efforts include a study of fermions with strong repulsive interactions in which we obtained evidence for a phase transition to itinerant ferromagnetism, the characterization of cold atom systems by noise measurements, and a new adiabatic gradient demagnetization cooling scheme which has enabled us to realize temperatures of less than 350 picokelvin and spin temperatures of less than 50 picokelvin in optical lattices. These are the lowest temperatures ever measured in any physical system