Antimicrobial susceptibility of recent Australian isolates of Brachyspira hyodysenteriae

Swine dysentery (SD) is an important disease in Australia, causing considerable economic loss through reduced growth rates in grower/ finisher pigs and control costs. Swine dysentery is characterized by mucohaemorrhagic colitis, resulting from infection with the anaerobic intestinal spirochaete Brachyspira hyodysenteriae. The diseases can be controlled, but worldwide there is concern about reduced susceptibility of many strains to the commonly available antimicrobials. Furthermore, antimicrobials are being withdrawn due to fears of transmission of resistance to human pathogenic microorganisms, or the presence of potentially toxic residues. The aim of this study was to examine the susceptibility of recent Australian B. hyodysenteriae isolates to commonly available antimicrobial agents

Exposure–response modelling approaches for determining optimal dosing rules in children

Within paediatric populations, there may be distinct age groups characterised by different exposure–response relationships. Several regulatory guidance documents have suggested general age groupings. However, it is not clear whether these categorisations will be suitable for all new medicines and in all disease areas. We consider two model-based approaches to quantify how exposure–response model parameters vary over a continuum of ages: Bayesian penalised B-splines and model-based recursive partitioning. We propose an approach for deriving an optimal dosing rule given an estimate of how exposure–response model parameters vary with age. Methods are initially developed for a linear exposure–response model. We perform a simulation study to systematically evaluate how well the various approaches estimate linear exposure–response model parameters and the accuracy of recommended dosing rules. Simulation scenarios are motivated by an application to epilepsy drug development. Results suggest that both bootstrapped model-based recursive partitioning and Bayesian penalised B-splines can estimate underlying changes in linear exposure–response model parameters as well as (and in many scenarios, better than) a comparator linear model adjusting for a categorical age covariate with levels following International Conference on Harmonisation E11 groupings. Furthermore, the Bayesian penalised B-splines approach consistently estimates the intercept and slope more accurately than the bootstrapped model-based recursive partitioning. Finally, approaches are extended to estimate Emax exposure–response models and are illustrated with an example motivated by an in vitro study of cyclosporine

Chemical kinetics and photochemical data for use in stratospheric modeling. Evaluation number 6

Evaluated sets of rate constants and photochemical cross sections are presented. The primary application of the data is in the modeling of stratospheric processes, with particular emphasis on the ozone layer and its possible perturbation by anthropogenic and natural phenomena

Chemical kinetics and photochemical data for use in stratospheric modeling evaluation Number 8

This is the eighth in a series of evaluated sets of rate constants and photochemical cross sections compiled by the NASA Panel for Data Evaluation. The primary application of the data is in the modeling of stratospheric processes, with particular emphasis on the ozone layer and its possible perturbation by anthropogenic and natural phenomena. Copies of this evaluation are available from the Jet Propulsion Laboratory, Documentation Section, 111-116B, California Institute of Technology, Pasadena, California, 91109

Effective flow properties of heterolithic, cross-bedded tidal sandstones: Part 1. Surface-based modeling

Tidal heterolithic sandstones are commonly characterized by millimeter- to centimeter-scale intercalations of mudstone and sandstone. Consequently, their effective flow properties are poorly predicted by (1) data that do not sample a representative volume or (2) models that fail to capture the complex three-dimensional architecture of sandstone and mudstone layers. We present a modeling approach in which surfaces are used to represent all geologic heterogeneities that control the spatial distribution of reservoir rock properties (surface-based modeling). The workflow uses template surfaces to represent heterogeneities classified by geometry instead of length scale. The topology of the template surfaces is described mathematically by a small number of geometric input parameters, and models are constructed stochastically. The methodology has been applied to generate generic, three-dimensional minimodels (9 m3 volume) of cross-bedded heterolithic sandstones representing trough and tabular cross-bedding with differing proportions of sandstone and mudstone, using conditioning data from two outcrop analogs from a tide-dominated deltaic deposit. The minimodels capture the cross-stratified architectures observed in outcrop and are suitable for flow simulation, allowing computation of effective permeability values for use in larger-scale models. We show that mudstone drapes in cross-bedded heterolithic sandstones significantly reduce effective permeability and also impart permeability anisotropy in the horizontal as well as vertical flow directions. The workflow can be used with subsurface data, supplemented by outcrop analog observations, to generate effective permeability values to be derived for use in larger-scale reservoir models. The methodology could be applied to the characterization and modeling of heterogeneities in other types of sandstone reservoirs

Chemical kinetics and photochemical data for use in stratospheric modeling

Rate constants and photochemical cross sections are presented. The primary application of the data is for modeling of the stratospheric processes, with particular emphasis on the ozone layer and its possible perturbation by anthropogenic and natural phenomena

Chemical kinetics and photochemical data for use in stratospheric modeling

As part of a series of evaluated sets, rate constants and photochemical cross sections compiled by the NASA Panel for Data Evaluation are provided. The primary application of the data is in the modeling of stratospheric processes, with particular emphasis on the ozone layer and its possible perturbation by anthropogenic and natural phenomena. Copies of this evaluation are available from the Jet Propulsion Laboratory

Advanced therapy medicinal products and health technology assessment principles and practices for value-based and sustainable healthcare

Background Advanced therapy medicinal products (ATMPs) are beginning to reach European markets, and questions are being asked about their value for patients and how healthcare systems should pay for them. Objectives To identify and discuss potential challenges of ATMPs in view of current health technology assessment (HTA) methodology—specifically economic evaluation methods—in Europe as it relates to ATMPs, and to suggest potential solutions to these challenges. Methods An Expert Panel reviewed current HTA principles and practices in relation to the specific characteristics of ATMPs. Results Three key topics were identified and prioritised for discussion—uncertainty, discounting, and health outcomes and value. The panel discussed that evidence challenges linked to increased uncertainty may be mitigated by collection of follow-on data, use of value of information analysis, and/or outcomes-based contracts. For discount rates, an international, multi-disciplinary forum should be established to consider the economic, social and ethical implications of the choice of rate. Finally, consideration of the feasibility of assessing the value of ATMPs beyond health gain may also be key for decision-making. Conclusions ATMPs face a challenge in demonstrating their value within current HTA frameworks. Consideration of current HTA principles and practices with regards to the specific characteristics of ATMPs and continued dialogue will be key to ensuring appropriate market access. Classification code I