The Current States, Challenges, Ongoing Efforts, and Future Perspectives of Pharmaceutical Excipients in Pediatric Patients in Each Country and Region

A major hurdle in pediatric formulation development is the lack of safety and toxicity data on some of the commonly used excipients. While the maximum oral safe dose for several kinds of excipients is known in the adult population, the doses in pediatric patients, including preterm neonates, are not established yet due to the lack of evidence-based data. This paper consists of four parts: (1) country-specific perspectives in different parts of the world (current state, challenges in excipients, and ongoing efforts) for ensuring the use of safe excipients, (2) comparing and contrasting the country-specific perspectives, (3) past and ongoing collaborative efforts, and (4) future perspectives on excipients for pediatric formulation. The regulatory process for pharmaceutical excipients has been developed. However, there are gaps between each region where a lack of information and an insufficient regulation process was found. Ongoing efforts include raising issues on excipient exposure, building a region-specific database, and improving excipient regulation; however, there is a lack of evidence-based information on safety for the pediatric population. More progress on clear safety limits, quantitative information on excipients of concern in the pediatric population, and international harmonization of excipients’ regulatory processes for the pediatric population are required

Tectonic inheritance and continental rift architecture: Numerical and analogue models of the East African Rift System.

The western branch of the East African Rift is composed of an arcuate succession of elongate asymmetric basins, which differ in terms of interaction geometry, fault architecture and kinematics, and patterns of uplift/subsidence and erosion/sedimentation. The basins are located within Proterozoic mobile belts at the edge of the strong Tanzanian craton; surface geology suggests that the geometry of these weak zones is an important parameter in controlling rift development and architecture, although other processes have been proposed. In this study, we use lithosphere-scale numerical models and crustal-scale analogue experiments to shed light on the relations between preexisting structures and rift architecture. Results illustrate that on a regional scale, rift localization within the mobile belts at the curved craton's western border results in an arcuate rift system, which implies that under a constant extensional stress field, part of the western branch experienced orthogonal extension and part oblique extension. Largest depocenters are predicted to form mostly orthogonal to the extension direction, and smaller depocenters will form along the oblique parts of the rift. The varying extension direction along the rift zone furthermore results in lengthwise varying rift asymmetry, segmentation characteristics, and border fault architecture (trend, length, and kinematics). Analogue models predict that discrete upper crustal fabrics may influence the location of accommodation zones and control the architecture of extension-related faults at a local scale. Models support that fabric reactivation is responsible for the oblique-slip kinematics on faults and for the development of Z-shaped or arcuate normal faults typically documented in nature. Copyright 2007 by the American Geophysical Union

The early impact histories of meteorite parent bodies

We have developed a statistical framework that uses collisional evolution models, shock physics modeling and scaling laws to determine the range of plausible collisional histories for individual meteorite parent bodies. It is likely that those parent bodies that were not catastrophically disrupted sustained hundreds of impacts on their surfaces - compacting, heating, and mixing the outer layers; it is highly unlikely that many parent bodies escaped without any impacts processing the outer few kilometers. The first 10 - 20 Myr were the most important time for impacts, both in terms of the number of impacts and the increase of specific internal energy due to impacts. The model has been applied to evaluate the proposed impact histories of several meteorite parent bodies: up to 10 parent bodies that were not disrupted in the first 100 Myr experienced a vaporizing collision of the type necessary to produce the metal inclusions and chondrules on the CB chondrite parent; around 1 - 5% of bodies that were catastrophically disrupted after 12 Myr sustained impacts at times that match the heating events recorded on the IAB/winonaite parent body; more than 75% of 100 km radius parent bodies which survived past 100 Myr without being disrupted sustained an impact that excavates to the depth required for mixing in the outer layers of the H chondrite parent body; and to protect the magnetic field on the CV chondrite parent body, the crust would have had to have been thick (~ 20 km) in order to prevent it being punctured by impacts.Comment: 30 pages, 11 figures, 3 tables. Accepted for publication in Meteoritics & Planetary Scienc

Impacts of urbanization on insect herbivory and plant defences in oak trees

Systematic comparisons of species interactions in urban versus rural environments can improve our understanding of shifts in ecological processes due to urbanization. However, such studies are relatively uncommon and the mechanisms driving urbanization effects on species interactions (e.g. between plants and insect herbivores) remain elusive. Here we investigated the effects of urbanization on leaf herbivory by insect chewers and miners associated with the English oak Quercus robur by sampling trees in rural and urban areas throughout most of the latitudinal distribution of this species. In performing these comparisons, we also controlled for the size of the urban areas (18 cities) and gathered data on CO 2 emissions. In addition, we assessed whether urbanization affected leaf chemical defences (phenolic compounds) and nutritional traits (phosphorus and nitrogen), and whether such changes correlated with herbivory levels. Urbanization significantly reduced leaf chewer damage but did not affect leaf miners. In addition, we found that leaves from urban locations had lower levels of chemical defences (condensed and hydrolysable tannins) and higher levels of nutrients (nitrogen and phosphorus) compared to leaves in rural locations. The magnitude of urbanization effects on herbivory and leaf defences was not contingent upon city size. Importantly, while the effects of urbanization on chemical defences were associated with CO 2 emissions, changes in leaf chewer damage were not associated with either leaf traits or CO 2 levels. These results suggest that effects of urbanization on herbivory occur through mechanisms other than changes in the plant traits measured here. Overall, our simultaneous assessment of insect herbivory, plant traits and abiotic correlates advances our understanding of the main drivers of urbanization effects on plant–herbivore interactions.info:eu-repo/semantics/acceptedVersio

Evaluation of Fermi Read-out of the ATLAS Tilecal Prototype

Prototypes of the \fermi{} system have been used to read out a prototype of the \atlas{} hadron calorimeter in a beam test at the CERN SPS. The \fermi{} read-out system, using a compressor and a 40 MHz sampling ADC, is compared to a standard charge integrating read-out by measuring the energy resolution of the calorimeter separately with the two systems on the same events. Signal processing techniques have been designed to optimize the treatment of \fermi{} data. The resulting energy resolution is better than the one obtained with the standard read-out

Numerical modelling study on the flexural uplift of the Transantarctic Mountains

In this study, based on a 2-D thermomechanical finite element model, the uplift of the Transantarctic Mountains (TAM) is discussed in relation to the flexural uplift of a rheologically layered lithosphere, which is described by Vening-Meinesz's cantilever kinematics. The general model behaviour shows that the thickness of the crust and the geothermal gradient in the lithosphere are the principal factors in controlling the effective elastic thickness (

Fundamental properties of a selected sample of Ap stars: Inferences from interferometric and asteroseismic constraints

Magnetic fields influence the formation and evolution of stars and impact the observed stellar properties. Ap stars (magnetic A-type stars) are a prime example of this. Access to precise and accurate determinations of their stellar fundamental properties, such as masses and ages, is crucial to understand the origin and evolution of fossil magnetic fields. We propose using the radii and luminosities determined from interferometric measurements, in addition to seismic constraints when available, to infer fundamental properties of 14 Ap stars préviously characterised. We used a grid-based modelling approach, employing stellar models computed with the \textsc{cestam} stellar evolution code, and the parameter search performed with the \textsc{aims} optimisation method. The stellar model grid was built using a wide range of initial helium abundances and metallicities in order to avoid any bias originating from the initial chemical composition. The large frequency separations ( Δν ) of HR\,1217 (HD\,24712) and α~Cir (HD\,128898), two rapidly oscillating Ap stars of the sample, were used as seismic constraints. We inferred the fundamental properties of the 14 stars in the sample. The overall results are consistent within 1σ with previous studies, however, the stellar masses inferred in this study are higher. This trend likely originates from the broader range of chemical compositions considered in this work. We show that the use of Δν in the modelling significantly improves our inferences, allowing us to set reasonable constraints on the initial metallicity which is, otherwise, unconstrained. This gives an indication of the efficiency of atomic diffusion in the atmospheres of roAp stars and opens the possibility of characterising the transport of chemical elements in their interiors

An evaluation of the Canadian global meteorological ensemble prediction system for short-term hydrological forecasting

Hydrological forecasting consists in the assessment of future streamflow. Current deterministic forecasts do not give any information concerning the uncertainty, which might be limiting in a decision-making process. Ensemble forecasts are expected to fill this gap. <br><br> In July 2007, the Meteorological Service of Canada has improved its ensemble prediction system, which has been operational since 1998. It uses the GEM model to generate a 20-member ensemble on a 100 km grid, at mid-latitudes. This improved system is used for the first time for hydrological ensemble predictions. Five watersheds in Quebec (Canada) are studied: Chaudière, Châteauguay, Du Nord, Kénogami and Du Lièvre. An interesting 17-day rainfall event has been selected in October 2007. Forecasts are produced in a 3 h time step for a 3-day forecast horizon. The deterministic forecast is also available and it is compared with the ensemble ones. In order to correct the bias of the ensemble, an updating procedure has been applied to the output data. Results showed that ensemble forecasts are more skilful than the deterministic ones, as measured by the Continuous Ranked Probability Score (CRPS), especially for 72 h forecasts. However, the hydrological ensemble forecasts are under dispersed: a situation that improves with the increasing length of the prediction horizons. We conjecture that this is due in part to the fact that uncertainty in the initial conditions of the hydrological model is not taken into account