Advances in neonatal care have resulted in increased survival of children born extremely pre-term (EP). Nevertheless the incidence of bronchopulmonary dysplasia and long-term respiratory morbidity ...remains high. We investigated the nature of pathophysiological changes at 11 yrs of age to ascertain whether respiratory morbidity in EP children primarily reflects alterations in the lung periphery or more centralised airway function in this population. Spirometry, plethysmography, diffusing capacity, exhaled nitric oxide, multiple-breath washout, skin tests and methacholine challenge were used during laboratory-based assessments in a subgroup of the 1995 EPICure cohort and in controls. Results were obtained in 49 EP and 52 control children. Lung function abnormalities were found in 78% of EP children, with evidence of airway obstruction, ventilation inhomogeneity, gas trapping and airway hyperresponsiveness. Levels of atopy and exhaled nitric oxide were similar between the groups. Prior wheeze was associated with significant reductions in forced flows and volumes. By contrast, abnormalities of the lung periphery appear to be mediated primarily through EP birth per se. The prevalence of lung function abnormalities, which is largely obstructive in nature and likely to have long-term implications, remains high among 11-yr-old children born EP. Spirometry proved an effective means of detecting these persistent abnormalities.
Gold nanoparticles (GNPs) have been shown to sensitize cancer cells to x-ray radiation, particularly at kV energies where photoelectric interactions dominate and the high atomic number of gold makes ...a large difference to x-ray absorption. Protons have a high cross-section for gold at a large range of relevant clinical energies, and so potentially could be used with GNPs for increased therapeutic effect. Here, we investigate the contribution of secondary electron emission to cancer cell radiosensitization and investigate how this parameter is affected by proton energy and a free radical scavenger. We simulate the emission from a realistic cell phantom containing GNPs after traversal by protons and x-rays with different energies. We find that with a range of proton energies (1-250 MeV) there is a small increase in secondaries compared to a much larger increase with x-rays. Secondary electrons are known to produce toxic free radicals. Using a cancer cell line in vitro we find that a free radical scavenger has no protective effect on cells containing GNPs irradiated with 3 MeV protons, while it does protect against cells irradiated with x-rays. We conclude that GNP generated free radicals are a major cause of radiosensitization and that there is likely to be much less dose enhancement effect with clinical proton beams compared to x-rays.
Summary
The principles and theoretical background are presented for a new process‐based model (PESERA) that is designed to estimate long‐term average erosion rates at 1 km resolution and has, to ...date, been applied to most of Europe. The model is built around a partition of precipitation into components for overland flow (infiltration excess, saturation excess and snowmelt), evapo‐transpiration and changes in soil moisture storage. Transpiration is used to drive a generic plant growth model for biomass, constrained as necessary by land use decisions, primarily on a monthly time step. Leaf fall, with corrections for cropping, grazing, etc., also drives a simple model for soil organic matter. The runoff threshold for infiltration excess overland flow depends dynamically on vegetation cover, organic matter and soil properties, varying over the year. The distribution of daily rainfall totals has been fitted to a Gamma distribution for each month, and drives overland flow and sediment transport (proportional to the sum of overland flow squared) by summing over this distribution. Total erosion is driven by erodibility, derived from soil properties, squared overland flow discharge and gradient; it is assessed at the slope base to estimate total loss from the land, and delivered to stream channels.
Preclinical radiation research lacks standardized dosimetry procedures that provide traceability to a primary standard. Consequently, ensuring accuracy and reproducibility between studies is ...challenging. Using 3D printed murine phantoms we undertook a dosimetry audit of Xstrahl Small Animal Radiation Research Platforms (SARRPs) installed at 7 UK centres. The geometrically realistic phantom accommodated alanine pellets and Gafchromic EBT3 film for simultaneous measurement of the dose delivered and the dose distribution within a 2D plane, respectively. Two irradiation scenarios were developed: (1) a 10 × 10 mm
static field targeting the pelvis, and (2) a 5 × 5 mm
90° arc targeting the brain. For static fields, the absolute difference between the planned dose and alanine measurement across all centres was 4.1 ± 4.3% (mean ± standard deviation), with an overall range of - 2.3 to 10.5%. For arc fields, the difference was - 1.2% ± 6.1%, with a range of - 13.1 to 7.7%. EBT3 dose measurements were greater than alanine by 2.0 ± 2.5% and 3.5 ± 6.0% (mean ± standard deviation) for the static and arc fields, respectively. 2D dose distributions showed discrepancies to the planned dose at the field edges. The audit demonstrates that further work on preclinical radiotherapy quality assurance processes is merited.
In this paper, we develop a subsampling Newton’s method to efficiently approximate the maximum likelihood estimate in logistic regression, which is especially useful for large-sample problems. One ...distinct feature of our algorithm is that matrix inversion is not explicitly performed. We propose two algorithms which are used to construct iteratively a sequence of matrices which converge to the Hessian of the maximum likelihood function on the subsample. We provide numerical examples to show that the proposed method is efficient and robust.
Particle formation rates are usually measured at sizes larger than the critical size at which nucleation occurs. Due to loss of particles during their growth to the detection threshold, the measured ...formation rate is often substantially lower than the nucleation rate. For this reason a correction needs to be applied in order to determine the nucleation rate from the measured formation rate. Analytical formulae for the correction factor are provided in the literature. However, these methods were derived for atmospheric nucleation measurements and therefore need to be adjusted in order to be applied to chamber nucleation studies. Here we propose an alternative, numerical method that allows precise nucleation rates to be determined in arbitrary experimental environments. The method requires knowledge of the particle size distribution above detection threshold, the particle growth rate, and the particle loss rates as a function of particle size. The effect of self-coagulation, i.e., cluster–cluster collisions, is taken into account in the method.
Computational simulations, such as Monte Carlo track structure simulations, offer a powerful tool for quantitatively investigating radiation interactions within cells. The modelling of the spatial ...distribution of energy deposition events as well as diffusion of chemical free radical species, within realistic biological geometries, can help provide a comprehensive understanding of the effects of radiation on cells. Track structure simulations, however, generally require advanced computing skills to implement. The TOPAS-nBio toolkit, an extension to TOPAS (TOol for PArticle Simulation), aims to provide users with a comprehensive framework for radiobiology simulations, without the need for advanced computing skills. This includes providing users with an extensive library of advanced, realistic, biological geometries ranging from the micrometer scale (e.g. cells and organelles) down to the nanometer scale (e.g. DNA molecules and proteins). Here we present the geometries available in TOPAS-nBio.
This work studies the valuation and optimal surrender of variable (equity-linked) annuities under a Lévy-driven equity market with mortality risk. We consider a practical periodic fee structure which ...can vary over time and is assessed as a proportion of the fund value. At maturity, the fund value is returned to the policyholder according to a guaranteed minimum accumulation benefit (GMAB). Mortality risk is also modeled discretely, and the contract offers a guaranteed minimum death benefit (GMBD) prior to maturity. The benefits accommodate caps on the growth of funds (in addition to the rising floor) to reduce the fee level and as a disincentive to early surrender. Interest rates are modeled via a deterministic discounting term structure, which can be calibrated (bootstrapped) to the rates market, according to market convention. An efficient and accurate valuation framework is developed, along with closed form pricing formulas in the case where policy surrender is not permitted. Numerous experiments are conducted to illustrate the interplay between contract parameters and the decision to surrender, and we provide an extensive analysis that investigates how to structure contracts to disincentivize early surrender.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Formation of new aerosol particles from trace gases is a major source of cloud condensation nuclei (CCN) in the global atmosphere, with potentially large effects on cloud optical properties and ...Earth's radiative balance. Controlled laboratory experiments have resolved, in detail, the different nucleation pathways likely responsible for atmospheric new particle formation, yet very little is known from field studies about the molecular steps and compounds involved in different regions of the atmosphere. The scarcity of primary particle sources makes secondary aerosol formation particularly important in the Antarctic atmosphere. Here, we report on the observation of ion-induced nucleation of sulfuric acid and ammonia-a process experimentally investigated by the CERN CLOUD experiment-as a major source of secondary aerosol particles over coastal Antarctica. We further show that measured high sulfuric acid concentrations, exceeding 10
molecules cm
, are sufficient to explain the observed new particle growth rates. Our findings show that ion-induced nucleation is the dominant particle formation mechanism, implying that galactic cosmic radiation plays a key role in new particle formation in the pristine Antarctic atmosphere.
Woodlands can reduce the risk of rainfall‐generated flooding through increased interception, soil infiltration and available storage. Despite growing evidence, there is still low confidence in using ...woodlands as a flood mitigation method due to limited empirical data, particularly for broadleaf woodlands. We measured soil properties and streamflow for nine small (<0.2 km2) upland catchments and compared mature semi‐natural broadleaf woodland where no stock grazing occurs to pasture with varied grazing intensity. We compared streamflow across 28 storm events including a 1 in 10‐year event, two 1 in 4‐year events and five 1 in 1.5‐year events, identified over a 13‐month period. We found that semi‐natural broadleaf woodlands reduce specific peak discharge by 23%–60% and peak runoff coefficients by 30%–60% compared with pasture. Response to storm events took 14–50% longer in woodland compared to pasture. These differences in flood response are partly explained by more permeable woodland soils, 11–20 times greater than pasture soil. The more muted response of wooded catchments to storm events is consistent across the storms investigated, including Storm Ciara, a 1 in 10‐year event. Our analysis strengthens the argument that semi‐natural woodlands can reduce rainfall‐generated flooding contributing to the evidence base for natural flood management.
We established a correlation catchment field study in Cumbria, UK. We found that semi‐natural woodlands significantly reduced peak streamflow, at both high and low flows and exhibited higher topsoil permeability. These results support woodlands as a method of natural flood management (NFM).
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