Searching the ideal inhaled vasodilator: From nitric oxide to prostacyclin

Today, the technique to directly administer vasodilators via the airway to treat pulmonary hypertension and to improve pulmonary gas exchange is widely accepted among clinicians. The flood of scientific work focussing on this new therapeutic concept had been initiated by a fundamental new observation by Pepke-Zaba {[}1] and Frostell in 1991 {[}2]: Both scientists reported, that inhalation of exogenous nitric oxide (NO) gas selectively dilates pulmonary vessels without a concomittant systemic vasodilation. No more than another decade ago NO was identified as an important endogenous vasodilator {[}3] while having merely been regarded an environmental pollutant before that time. Although inhaled NO proved to be efficacious, alternatives were sought-after due to NO's potential side-effects. In search for the ideal inhaled vasodilator another group of endogenous mediators - the prostanoids - came into the focus of interest. The evidence for safety and efficacy of inhaled prostanoids is - among a lot of other valuable work - based on a series of experimental and clinical investigations that have been performed or designed at the Institute for Surgical Research under the guidance and mentorship of Prof. Dr. med. Dr. h.c. mult. K. Messmer {[}4-19]. In the following, the current and newly emerging clinical applications of inhaled prostanoids and the experimental data which they are based on, will be reviewed. Copyright (C) 2002 S. Karger AG, Basel

Variation in Protein Quality of Forage Legumes During Spring Growth

The utilisation of forage legumes in combination with reduced N inputs as fertilisers is an alternative for the production of high quality forage. Although white clover (WC) is widely used in grassland and has a high content of crude protein (CP), a combination of this high CP content with a high proportion of rapidly-available proteins and fast degradation rate in the rumen may reduce the efficiency of N use by ruminants in comparison with other forage legumes. The objective of the present study was to investigate the variation in content of CP fractions A, B and C in different forage legume during the spring growth in comparison with WC

Comparison of regional blood flow values measured by radioactive and fluorescent microspheres

Fluorescent microspheres (FM) have become an attractive alternative to radioactive microspheres (RM) for the measurement of regional blood flow (RBF). The aim of the present study was to investigate the comparability of both methods by measuring RBF with FM and RM. Eight anaesthetised pigs received simultaneous, left atrial injections of FM and RM with a diameter of 15 mum at six different time points. Blood reference samples were collected from the descending aorta. RBF was determined in tissue samples of the myocardium, spleen and kidneys of all 8 animals. After radioactivity of the tissue samples was determined, the samples were processed automatically for measuring fluorescence using a recently developed filter device (SPU). RBF was calculated with both the isotope and spectrometric data of both methods for each sample resulting in a total of 10,512 blood flow values. The comparison of the RBF values yielded high linear correlation (mean r(2) = 0.95 +/- 0.03 to 0.97 +/- 0.02) and excellent agreement (bias 5.4-6.7%, precision 9.9-16.5%) of both methods. Our results indicate the validity of MS and of the automated tissue processing technique by means of the SPU. Copyright (C) 2002 S. Karger AG, Basel

Exploiting asynchrony from exact forward recovery for DUE in iterative solvers

This paper presents a method to protect iterative solvers from Detected and Uncorrected Errors (DUE) relying on error detection techniques already available in commodity hardware. Detection operates at the memory page level, which enables the use of simple algorithmic redundancies to correct errors. Such redundancies would be inapplicable under coarse grain error detection, but become very powerful when the hardware is able to precisely detect errors. Relations straightforwardly extracted from the solver allow to recover lost data exactly. This method is free of the overheads of backwards recoveries like checkpointing, and does not compromise mathematical convergence properties of the solver as restarting would do. We apply this recovery to three widely used Krylov subspace methods, CG, GMRES and BiCGStab, and their preconditioned versions. We implement our resilience techniques on CG considering scenarios from small (8 cores) to large (1024 cores) scales, and demonstrate very low overheads compared to state-of-the-art solutions. We deploy our recovery techniques either by overlapping them with algorithmic computations or by forcing them to be in the critical path of the application. A trade-off exists between both approaches depending on the error rate the solver is suffering. Under realistic error rates, overlapping decreases overheads from 5.37% down to 3.59% for a non-preconditioned CG on 8 cores.This work has been partially supported by the European Research Council under the European Union's 7th FP, ERC Advanced Grant 321253, and by the Spanish Ministry of Science and Innovation under grant TIN2012-34557. L. Jaulmes has been partially supported by the Spanish Ministry of Education, Culture and Sports under grant FPU2013/06982. M. Moreto has been partially supported by the Spanish Ministry of Economy and Competitiveness under Juan de la Cierva postdoctoral fellowship JCI-2012-15047. M. Casas has been partially supported by the Secretary for Universities and Research of the Ministry of Economy and Knowledge of the Government of Catalonia and the Co-fund programme of the Marie Curie Actions of the European Union's 7th FP (contract 2013 BP B 00243).Peer ReviewedPostprint (author's final draft

Cognitive dysfunction in naturally occurring canine idiopathic epilepsy

Globally, epilepsy is a common serious brain disorder. In addition to seizure activity, epilepsy is associated with cognitive impairments including static cognitive impairments present at onset, progressive seizure-induced impairments and co-morbid dementia. Epilepsy occurs naturally in domestic dogs but its impact on canine cognition has yet to be studied, despite canine cognitive dysfunction (CCD) recognised as a spontaneous model of dementia. Here we use data from a psychometrically validated tool, the canine cognitive dysfunction rating (CCDR) scale, to compare cognitive dysfunction in dogs diagnosed with idiopathic epilepsy (IE) with controls while accounting for age. An online cross-sectional study resulted in a sample of 4051 dogs, of which n = 286 had been diagnosed with IE. Four factors were significantly associated with a diagnosis of CCD (above the diagnostic cut-off of CCDR ≥50): (i) epilepsy diagnosis: dogs with epilepsy were at higher risk; (ii) age: older dogs were at higher risk; (iii) weight: lighter dogs (kg) were at higher risk; (iv) training history: dogs with more exposure to training activities were at lower risk. Impairments in memory were most common in dogs with IE, but progression of impairments was not observed compared to controls. A significant interaction between epilepsy and age was identified, with IE dogs exhibiting a higher risk of CCD at a young age, while control dogs followed the expected pattern of low-risk throughout middle age, with risk increasing exponentially in geriatric years. Within the IE sub-population, dogs with a history of cluster seizures and high seizure frequency had higher CCDR scores. The age of onset, nature and progression of cognitive impairment in the current IE dogs appear divergent from those classically seen in CCD. Longitudinal monitoring of cognitive function from seizure onset is required to further characterise these impairments

Evaluation of reticuloruminal pH measurements from individual cattle: sampling strategies for the assessment of herd status

The application of pH observations to clinical practice in dairy cattle is based on criteria derived primarily from single time-point observations more than 20 years ago. The aims of this study were to evaluate these criteria using data collected using continuous recording methods; to make recommendations that might improve their interpretation; and to determine the relationship between the number of devices deployed in a herd and the accuracy of the resulting estimate of the herd-mean reticuloruminal pH. The study made use of 815,475 observations of reticuloruminal pH values obtained from 75 cattle in three herds (one beef and two twice-daily milking herds) to assess sampling strategies for the diagnosis of sub-acute rumen acidosis (SARA), and to evaluate the ability of different numbers of bolus devices to accurately estimate the true herd-mean reticuloruminal pH value at any time. The traditional criteria for SARA provide low diagnostic utility, the probability of detection of animals with pH values below specified thresholds being affected by a strong effect of time of day and herd. The analysis suggests that regardless of time of feeding, sampling should be carried out in the late afternoon or evening to obtain a reasonable probability of detection of animals with pH values below the threshold level. The among-cow variation varied strongly between herds, but for a typical herd, if using reticuloruminal pH boluses to detect a predisposition to fermentation disorders while feeding a diet that is high in rapidly fermentable carbohydrates, it is recommended to use a minimum of nine boluses

A multifractal approach to space-filling recovery for PET quantification.

Purpose: A new image-based methodology is developed for estimating the apparent space-filling properties of an object of interest in PET imaging without need for a robust segmentation step and used to recover accurate estimates of total lesion activity (TLA). Methods: A multifractal approach and the fractal dimension are proposed to recover the apparent space-filling index of a lesion (tumor volume, TV) embedded in nonzero background. A practical implementation is proposed, and the index is subsequently used with mean standardized uptake value (SUVmean) to correct TLA estimates obtained from approximate lesion contours. The methodology is illustrated on fractal and synthetic objects contaminated by partial volume effects (PVEs), validated on realistic 18F-fluorodeoxyglucose PET simulations and tested for its robustness using a clinical 18F-fluorothymidine PET test-retest dataset. Results: TLA estimates were stable for a range of resolutions typical in PET oncology (4-6 mm). By contrast, the space-filling index and intensity estimates were resolution dependent. TLA was generally recovered within 15% of ground truth on postfiltered PET images affected by PVEs. Volumes were recovered within 15% variability in the repeatability study. Results indicated that TLA is a more robust index than other traditional metrics such as SUVmean or TV measurements across imaging protocols. Conclusions: The fractal procedure reported here is proposed as a simple and effective computational alternative to existing methodologies which require the incorporation of image preprocessing steps (i.e., partial volume correction and automatic segmentation) prior to quantification