Limitation of Trypanosoma brucei parasitaemia results from a combination of density-dependent parasite differentiation and parasite killing by the host immune response

In the bloodstream of its mammalian host, the "slender" form of Trypanosoma brucei replicates extracellularly, producing a parasitaemia. At high density, the level of parasitaemia is limited at a sublethal level by differentiation to the non-replicative "stumpy" form and by the host immune response. Here, we derive continuous time equations to model the time-course, cell types and level of trypanosome parasitaemia, and compare the best fits with experimental data. The best fits that were obtained favour a model in which both density-dependent trypanosome differentiation and host immune response have a role in limiting the increase of parasites, much poorer fits being obtained when differentiation and immune response are considered independently of one another. Best fits also favour a model in which the slender-to-stumpy differentiation progresses in a manner that is essentially independent of the cell cycle. Finally, these models also make the prediction that the density-dependent trypanosome differentiation mechanism can give rise to oscillations in parasitaemia level. These oscillations are independent of the immune system and are not due to antigenic variation

Status Quo Analysis of the Flathead River Conflict

Status quo analysis algorithms developed within the paradigm of the graph model for conflict resolution are applied to an international river basin conflict involving the United States and Canada to assess the likeliness of various compromise resolutions. The conflict arose because the state of Montana feared that further expansion of the Sage Creek Coal Company facilities in Canada would pollute the Flathead River, which flows from British Columbia into Montana. Significant insights not generally available from a static stability analysis are obtained about potential resolutions of the conflict under study and about how decision makers’ interactions may direct the conflict to distinct resolutions. Analyses also show how political considerations may affect a particular decision maker’s choice, thereby influencing the evolution of the conflict

Role of a plausible nuisance contributor in the declining obesity-mortality risks over time.

CONTEXT: Recent analyses of epidemiological data including the National Health and Nutrition Examination Survey (NHANES) have suggested that the harmful effects of obesity may have decreased over calendar time. The shifting BMI distribution over time coupled with the application of fixed broad BMI categories in these analyses could be a plausible nuisance contributor to this observed change in the obesity-associated mortality over calendar time. OBJECTIVE: To evaluate the extent to which observed temporal changes in the obesity-mortality association may be due to a shifting population distribution for body mass index (BMI), coupled with analyses based on static, broad BMI categories. DESIGN, SETTING, AND PARTICIPANTS: Simulations were conducted using data from NHANES I and III linked with mortality data. Data from NHANES I were used to fit a true model treating BMI as a continuous variable. Coefficients estimated from this model were used to simulate mortality for participants in NHANES III. Hence, the population-level association between BMI and mortality in NHANES III was fixed to be identical to the association estimated in NHANES I. Hazard ratios (HRs) for obesity categories based on BMI for NHANES III with simulated mortality data were compared to the corresponding estimated HRs from NHANES I. MAIN OUTCOME MEASURES: Change in hazard ratios for simulated data in NHANES III compared to observed estimates from NHANES I. RESULTS: On average, hazard ratios for NHANES III based on simulated mortality data were 29.3% lower than the estimates from NHANES I using observed mortality follow-up. This reduction accounted for roughly three-fourths of the apparent decrease in the obesity-mortality association observed in a previous analysis of these data. CONCLUSIONS: Some of the apparent diminution of the association between obesity and mortality may be an artifact of treating BMI as a categorical variable

Trispectrum versus Bispectrum in Single-Field Inflation

In the standard slow-roll inflationary cosmology, quantum fluctuations in a single field, the inflaton, generate approximately Gaussian primordial density perturbations. At present, the bispectrum and trispectrum of the density perturbations have not been observed and the probability distribution for these perturbations is consistent with Gaussianity. However, Planck satellite data will bring a new level of precision to bear on this issue, and it is possible that evidence for non-Gaussian effects in the primordial distribution will be discovered. One possibility is that a trispectrum will be observed without evidence for a non-zero bispectrum. It is not difficult for this to occur in inflationary models where quantum fluctuations in a field other than the inflaton contribute to the density perturbations. A natural question to ask is whether such an observation would rule out the standard scenarios. We explore this issue and find that it is possible to construct single-field models in which inflaton-generated primordial density perturbations have an observable trispectrum, but a bispectrum that is too small to be observed by the Planck satellite. However, an awkward fine tuning seems to be unavoidable.Comment: 15 pages, 3 figures; journal versio

Respiratory challenge MRI: practical aspects

Respiratory challenge MRI is the modification of arterial oxygen (PaO2) and/or carbon dioxide (PaCO2) concentration to induce a change in cerebral function or metabolism which is then measured by MRI. Alterations in arterial gas concentrations can lead to profound changes in cerebral haemodynamics which can be studied using a variety of MRI sequences. Whilst such experiments may provide a wealth of information, conducting them can be complex and challenging. In this paper we review the rationale for respiratory challenge MRI including the effects of oxygen and carbon dioxide on the cerebral circulation. We also discuss the planning, equipment, monitoring and techniques that have been used to undertake these experiments. We finally propose some recommendations in this evolving area for conducting these experiments to enhance data quality and comparison between techniques