White matter lesions in watershed territories studied with MRI and parenchymography: a comparative study

Brain aging affects an increasing segment of the population and the role of chronic cerebrovascular disease is considered to be one of the main parameters involved. For this purpose we compared retrospectively MRI data with digitized subtraction angiography (DSA) data in a group of 50 patients focusing onto the watershed area of the carotid artery vascular territories. In order to evaluate the presence of white matter lesions (WML) in the hemispheric watershed areas, coronal fluid-attenuated inversion-recovery or axial T2 weighted MRI images of patients with symptomatic cerebrovascular insufficiency areas were compared with the capillary phase of DSA studies in anterior-posterior projection. Presence of cerebrovascular occlusive disease was evaluated on DSA using North American symptomatic carotid endarterectomy trial criteria and including evaluation of collateral vascular supply. Pathological MRI findings in the region of the watershed territories correlated overall in 66% of cases with a defect or delayed filling on DSA. In the case of asymmetrical MRI findings, there was a pathological finding of the capillary phase in the watershed area in 92% of DSA studies. Hypoperfusion in the capillary phase of the watershed area as seen on DSA correlated with the stenosis degree of the concerned carotid artery. Our findings suggest that asymmetrical findings of WML in the watershed areas as seen on MRI are caused by hemodynamic effect and a differentiation between small vessel disease and a consequence of distant stenosis may be possible under such condition

MRI-guided, transrectal, intraprostatic steam application as potential focal therapeutic modality for prostatic diseases in a large animal translational model: A feasibility follow-up study

Parallel to establishment of diagnostic surveillance protocols for detection of prostatic diseases, novel treatment strategies should be developed. The aim of the present study is to evaluate the feasibility and possible side effects of transrectal, MRI-targeted intraprostatic steam application in dogs as an established large animal translational model for prostatic diseases in humans. Twelve healthy experimental, intact, male beagle dogs without evidence of prostatic pathology were recruited. An initial MRI examination was performed, and MRI-targeted steam was applied intraprostatically immediately thereafter. Serum levels of C-reactive protein (CRP), clinical and ultrasonographic examinations were performed periodically following the procedure to assess treatment effect. Four weeks after treatment, all dogs underwent follow-up MRI examinations and three needle-core biopsies were obtained from each prostatic lobe. Descriptive statistics were performed. MRI-guided intraprostatic steam application was successfully performed in the study population. The first day after steam application, 7/12 dogs had minimal signs of discomfort (grade 1/24 evaluated with the short-form Glasgow Composite Measure Pain Scale) and no dogs showed any sign of discomfort by day 6. CRP elevations were detected in 9/12 dogs during the first week post steam application. Mild to moderate T2 hyperintense intraparenchymal lesions were identified during follow-up MRI in 11/12 dogs four weeks post procedure. Ten of these lesions enhanced mild to moderately after contrast administration. Coagulative necrosis or associated chronic inflammatory response was detected in 80.6% (58/72) of the samples obtained. MRI-targeted intraprostatic steam application is a feasible technique and displays minimal side effects in healthy dogs as translational model for human prostatic diseases. This opens the possibility of minimally invasive novel treatment strategies for intraprostatic lesions

WIRA-C: a compact 142-GHz-radiometer for continuous middle-atmospheric wind measurements

Ground-based microwave wind radiometry provides a method to measure horizontal wind speeds at altitudes between 35 and 75&thinsp;km as has been shown by various previous studies. No other method is capable of continuously delivering wind measurements in this altitude region. As opposed to lidar systems, microwave radiometers operate autonomously and independent of daylight and clouds.In this paper, we present the WIRA-C (Wind Radiometer for Campaigns) instrument that observes the 142.17504&thinsp;GHz rotational transition line of ozone with a high spectral resolution using a low noise single side band heterodyne receiver. Because the emitting molecules are drifting with the wind, the line is Doppler shifted. Together with the pressure broadening effect, this allows the retrieval of altitude resolved wind profiles.The novel WIRA-C instrument represents the newest development in microwave wind radiometry and implements many improvements over its predecessor, the WIRA instrument. The main improvements include the compact structure, lower noise and an advanced retrieval setup. This paper describes the instrument and the data processing with a focus on the retrieval that takes into account a three-dimensional atmosphere and has never been used in ground-based radiometry before. The retrieval yields profiles of horizontal wind speeds with a 12&thinsp;h time resolution and a vertical resolution of 10&thinsp;km for zonal and 10 to 15&thinsp;km for meridional wind speeds. We give an error estimate that accounts for the thermal noise on the measured spectra and additionally estimate systematic errors using Monte Carlo methods.WIRA-C has been continuously measuring horizontal wind speeds for 1 year at the Maïdo observatory on Réunion (21.4°&thinsp;S, 55.9°&thinsp;E). We present the time series of this campaign and compare our measurements to model data from the European Centre for Medium-range Weather Forecasts (ECMWF) and coincident measurements of the co-located Rayleigh–Mie Doppler wind lidar. We find a good agreement between our measurements and the ECMWF operational analysis for the time series, where many features are present in both datasets. The wind profiles of the coincident WIRA-C and lidar observations are consistent and agree within their respective uncertainties for the lidar measurements with long integration times.</p

Comparison of co-located independent ground-based middle atmospheric wind and temperature measurements with numerical weather prediction models

High-resolution, ground-based and independent observations including co-located windradiometer, lidar stations, and infrasound instruments are used to evaluate the accuracy of general circulationmodels and data-constrained assimilation systems in the middle atmosphere at northern hemispheremidlatitudes. Systematic comparisons between observations, the European Centre for Medium-Range WeatherForecasts (ECMWF) operational analyses including the recent Integrated Forecast System cycles 38r1 and 38r2,the NASA’s Modern-Era Retrospective Analysis for Research and Applications (MERRA) reanalyses, and thefree-running climate Max Planck Institute–Earth System Model–Low Resolution (MPI-ESM-LR) are carried out inboth temporal and spectral dom ains. We find that ECMWF and MERRA are broadly consistent with lidar and windradiometer measurements up to ~40 km. For both temperature and horizontal wind components, deviationsincrease with altitude as the assimilated observations become sparser. Between 40 and 60 km altitude, thestandard deviation of the mean difference exceeds 5 K for the temperature and 20 m/s for the zonal wind. Thelargest deviations are observed in winter when the variability from large-scale planetary waves dominates.Between lidar data and MPI-ESM-LR, there is an overall agreement in spectral amplitude down to 15–20 days. Atshorter time scales, the variability is lacking in the model by ~10 dB. Infrasound observations indicate a generalgood agreement with ECWMF wind and temperature products. As such, this study demonstrates the potentialof the infrastructure of the Atmospheric Dynamics Research Infrastructure in Europe project that integratesvarious measurements and provides a quantitative understanding of stratosphere-troposphere dynamicalcoupling for numerical weather prediction applications

O-GlcNAcylation enhances CPS1 catalytic efficiency for ammonia and promotes ureagenesis

Life-threatening hyperammonemia occurs in both inherited and acquired liver diseases affecting ureagenesis, the main pathway for detoxification of neurotoxic ammonia&nbsp;in mammals. Protein O-GlcNAcylation is a reversible and nutrient-sensitive post-translational modification using as substrate UDP-GlcNAc, the end-product of hexosamine biosynthesis pathway. Here we show that increased liver UDP-GlcNAc during hyperammonemia increases protein O-GlcNAcylation and enhances ureagenesis. Mechanistically, O-GlcNAcylation on specific threonine residues increased the catalytic efficiency for ammonia of carbamoyl phosphate synthetase 1 (CPS1), the rate-limiting enzyme in ureagenesis. Pharmacological inhibition of O-GlcNAcase, the enzyme removing O-GlcNAc&nbsp;from proteins, resulted in clinically relevant reductions of systemic ammonia in both genetic (hypomorphic mouse model of propionic acidemia) and acquired (thioacetamide-induced acute liver failure) mouse models of liver diseases. In conclusion, by fine-tuned control of ammonia entry into ureagenesis, hepatic O-GlcNAcylation of CPS1 increases ammonia detoxification and is a novel target for therapy of hyperammonemia in both genetic and acquired diseases

Intracranial Aneurysm Classifier Using Phenotypic Factors: An International Pooled Analysis

Intracranial aneurysms (IAs) are usually asymptomatic with a low risk of rupture, but consequences of aneurysmal subarachnoid hemorrhage (aSAH) are severe. Identifying IAs at risk of rupture has important clinical and socio-economic consequences. The goal of this study was to assess the effect of patient and IA characteristics on the likelihood of IA being diagnosed incidentally versus ruptured. Patients were recruited at 21 international centers. Seven phenotypic patient characteristics and three IA characteristics were recorded. The analyzed cohort included 7992 patients. Multivariate analysis demonstrated that: (1) IA location is the strongest factor associated with IA rupture status at diagnosis; (2) Risk factor awareness (hypertension, smoking) increases the likelihood of being diagnosed with unruptured IA; (3) Patients with ruptured IAs in high-risk locations tend to be older, and their IAs are smaller; (4) Smokers with ruptured IAs tend to be younger, and their IAs are larger; (5) Female patients with ruptured IAs tend to be older, and their IAs are smaller; (6) IA size and age at rupture correlate. The assessment of associations regarding patient and IA characteristics with IA rupture allows us to refine IA disease models and provide data to develop risk instruments for clinicians to support personalized decision-making

Toward an improved representation of middle atmospheric dynamics thanks to the ARISE project

This paper reviews recent progress toward understanding the dynamics of the middle atmosphere in the framework of the Atmospheric Dynamics Research InfraStructure in Europe (ARISE) initiative. The middle atmosphere, integrating the stratosphere and mesosphere, is a crucial region which influences tropospheric weather and climate. Enhancing the understanding of middle atmosphere dynamics requires improved measurement of the propagation and breaking of planetary and gravity waves originating in the lowest levels of the atmosphere. Inter-comparison studies have shown large discrepancies between observations and models, especially during unresolved disturbances such as sudden stratospheric warmings for which model accuracy is poorer due to a lack of observational constraints. Correctly predicting the variability of the middle atmosphere can lead to improvements in tropospheric weather forecasts on timescales of weeks to season. The ARISE project integrates different station networks providing observations from ground to the lower thermosphere, including the infrasound system developed for the Comprehensive Nuclear-Test-Ban Treaty verification, the Lidar Network for the Detection of Atmospheric Composition Change, complementary meteor radars, wind radiometers, ionospheric sounders and satellites. This paper presents several examples which show how multi-instrument observations can provide a better description of the vertical dynamics structure of the middle atmosphere, especially during large disturbances such as gravity waves activity and stratospheric warming events. The paper then demonstrates the interest of ARISE data in data assimilation for weather forecasting and re-analyzes the determination of dynamics evolution with climate change and the monitoring of atmospheric extreme events which have an atmospheric signature, such as thunderstorms or volcanic eruptions

Suboptimal herd performance amplifies the spread of infectious disease in the cattle industry

Farms that purchase replacement breeding cattle are at increased risk of introducing many economically important diseases. The objectives of this analysis were to determine whether the total number of replacement breeding cattle purchased by individual farms could be reduced by improving herd performance and to quantify the effects of such reductions on the industry-level transmission dynamics of infectious cattle diseases. Detailed information on the performance and contact patterns of British cattle herds was extracted from the national cattle movement database as a case example. Approximately 69% of beef herds and 59% of dairy herds with an average of at least 20 recorded calvings per year purchased at least one replacement breeding animal. Results from zero-inflated negative binomial regression models revealed that herds with high average ages at first calving, prolonged calving intervals, abnormally high or low culling rates, and high calf mortality rates were generally more likely to be open herds and to purchase greater numbers of replacement breeding cattle. If all herds achieved the same level of performance as the top 20% of herds, the total number of replacement beef and dairy cattle purchased could be reduced by an estimated 34% and 51%, respectively. Although these purchases accounted for only 13% of between-herd contacts in the industry trade network, they were found to have a disproportionately strong influence on disease transmission dynamics. These findings suggest that targeting extension services at herds with suboptimal performance may be an effective strategy for controlling endemic cattle diseases while simultaneously improving industry productivity