41 Pharmacokinetics of nasally administered tobramycin, colistin sulphomethate sodium and a combination of tobramycin and colistin sulphomethate sodium

The paranasal sinuses can constitute a niche for bacteria which can migrate to the lungs. Nasal administration of antibiotics may be effective, but safety of this treatment has to be established first. Objectives: Investigation of the pharmacokinetics (PK) of nasally administered tobramycin (T), colistin sulphomethate sodium (CSS) and a combination of both drugs using systemic absorption, expressed as % absorbed, as surrogate for safety. In addition, tolerability of the nasal irrigations was examined. Methods: Ten adult CF patients performed three different nasal irrigations: 300 mg of T, 2 million IU of CSS and 300 mg of T combined with 2 million IU of CSS. Serum concentrations T and CSS were analysed using a validated assay. Individual PK parameters were calculated and assimilated with T and colistin serum values using a computerized CF-based population model. Maximum serum level (Cmax), trough serum level (Ctrough ) and bioavailability (F) were calculated. T Cmax >30 mg/L and Ctrough >0.5 mg/L were considered to be toxic. For colistin toxic levels are not known. Tolerability was measured using a Visual Analog Scale (VAS). Results: Following the T and the combined irrigation only 2 patients had detectable tobramycin serum levels with a Cma

Glides and laryngeals as a structural class

Theoretical and Experimental Linguistic

Spatial and temporal patterns of snowmelt refreezing in a Himalayan catchment

Recent progress has been made in quantifying snowmelt in the Himalaya. Although the conditions are favorable for refreezing, little is known about the spatial variability of meltwater refreezing, hindering a complete understanding of seasonal snowmelt dynamics. This study aims to improve our understanding about how refreezing varies in space and time. We simulated refreezing with the seNorge (v2.0) snow model for the Langtang catchment, Nepalese Himalaya, covering a 5-year period. Meteorological forcing data were derived from a unique elaborate network of meteorological stations and high-resolution meteorological simulations. The results show that the annual catchment average refreezing amounts to 122 mm w.e. (21% of the melt), and varies strongly in space depending on elevation and aspect. In addition, there is a seasonal altitudinal variability related to air temperature and snow depth, with most refreezing during the early melt season. Substantial intra-annual variability resulted from fluctuations in snowfall. Daily refreezing simulations decreased by 84% (annual catchment average of 19 mm w.e.) compared to hourly simulations, emphasizing the importance of using sub-daily time steps to capture melt-refreeze cycles. Climate sensitivity experiments revealed that refreezing is highly sensitive to changes in air temperature as a 2°C increase leads to a refreezing decrease of 35%

Applicability and reproducibility of the CPAT-grading system for pancreas allograft thrombosis

Purpose: : Although pancreas allograft thrombosis (PAT) incidence has progressively decreased, it remains the most common cause of early graft failure. Currently, there is no consensus on documentation of PAT, which has resulted in a great variability in reporting. The Cambridge Pancreas Allograft Thrombosis (CPAT) grading system has recently been developed for classification of PAT. In this study we aimed to assess the applicability and validate the reproducibility of the CPAT grading system.Methods: : This study is a retrospective cohort study. Selected for this study were all 177 pancreas transplantations performed at our center between January 1 st, 2008 and September 1 st, 2018 were included.Results: : A total of 318 Computed Tomography (CT) images was reevaluated according the CPAT system by two local radiologists. Inter-rater agreement expressed in Cohen's kappa was 0.403 for arterial and 0.537 for venous thrombosis. Inter-rater agreement, expressed in the Fleiss' kappa, within clinically relevant thrombosis categories was 0.626 for Grade 2 and 0.781 for Grade 3 venous thrombosis.Conclusions: : Although not perfect, we believe that implementation of the CPAT system would improve current documentation on PAT. However, it is questionable whether identification of a small Grade 1 thrombosis would be relevant in clinical practice.Furthermore, a good quality CT scan, including adequate phasing, is essential to accurately identify potential thrombus and extend after pancreas transplantation.Cardiovascular Aspects of Radiolog

Correlation of the tumour-stroma ratio with diffusion weighted MRI in rectal cancer

Objective: This study evaluated the correlation between intratumoural stmma proportion, expressed as tumour-stroma ratio (TSR), and apparent diffusion coefficient (ADC) values in patients with rectal cancer.Methods: This multicentre retrospective study included all consecutive patients with rectal cancer, diagnostically confirmed by biopsy and MRI. The training cohort (LUMC, Netherlands) included 33 patients and the validation cohort (VHIO, Spain) 69 patients. Two observers measured the mean and minimum ADCs based on single-slice and whole-volume segmentations. The TSR was determined on diagnostic haematoxylin & eosin stained slides of rectal tumour biopsies. The correlation between TSR and ADC was assessed by Spearman correlation (r(s)).Results: The ADC values between stroma-low and stroma-high tumours were not significantly different. Intraclass correlation (ICC) demonstrated a good level of agreement for the ADC measurements, ranging from 0.84-0.86 for single slice and 0.86-0.90 for the whole-volume protocol. No correlation was observed between the TSR and ADC values, with ADC(mean), r(s) = -0.162 (p= 0.38) and ADC(m)(in), r(s) = 0.041 (p= 0.82) for the single-slice and r(s) = -0.108 (p= 0.55) and r(s) = 0.019 (p= 0.92) for the whole-volume measurements in the training cohort, respectively. Results from the validation cohort were consistent; ADC(mean )r(s) = -0.022 (p= 0.86) and ADC(min), r(s) = 0.049 (p= 0.69) for the single-slice and r(s) = -0.064 (p= 0.59) and r(s) = -0.063 (p= 0.61) for the whole-volume measurements.Conclusions: Reproducibility of ADC values is good. Despite positive reports on the correlation between TSR and ADC values in other tumours, this could not be confirmed for rectal cancer.Surgical oncolog

Does congenital deafness affect the structural and functional architecture of primary visual cortex?

Deafness results in greater reliance on the remaining senses. It is unknown whether the cortical architecture of the intact senses is optimized to compensate for lost input. Here we performed widefield population receptive field (pRF) mapping of primary visual cortex (V1) with functional magnetic resonance imaging (fMRI) in hearing and congenitally deaf participants, all of whom had learnt sign language after the age of 10 years. We found larger pRFs encoding the peripheral visual field of deaf compared to hearing participants. This was likely driven by larger facilitatory center zones of the pRF profile concentrated in the near and far periphery in the deaf group. pRF density was comparable between groups, indicating pRFs overlapped more in the deaf group. This could suggest that a coarse coding strategy underlies enhanced peripheral visual skills in deaf people. Cortical thickness was also decreased in V1 in the deaf group. These findings suggest deafness causes structural and functional plasticity at the earliest stages of visual cortex

Investigations of the Mars Upper Atmosphere with ExoMars Trace Gas Orbiter

The Martian mesosphere and thermosphere, the region above about 60 km, is not the primary target of the ExoMars 2016 mission but its Trace Gas Orbiter (TGO) can explore it and address many interesting issues, either in-situ during the aerobraking period or remotely during the regular mission. In the aerobraking phase TGO peeks into thermospheric densities and temperatures, in a broad range of latitudes and during a long continuous period. TGO carries two instruments designed for the detection of trace species, NOMAD and ACS, which will use the solar occultation technique. Their regular sounding at the terminator up to very high altitudes in many different molecular bands will represent the first time that an extensive and precise dataset of densities and hopefully temperatures are obtained at those altitudes and local times on Mars. But there are additional capabilities in TGO for studying the upper atmosphere of Mars, and we review them briefly. Our simulations suggest that airglow emissions from the UV to the IR might be observed outside the terminator. If eventually confirmed from orbit, they would supply new information about atmospheric dynamics and variability. However, their optimal exploitation requires a special spacecraft pointing, currently not considered in the regular operations but feasible in our opinion. We discuss the synergy between the TGO instruments, specially the wide spectral range achieved by combining them. We also encourage coordinated operations with other Mars-observing missions capable of supplying simultaneous measurements of its upper atmosphere

Clinical added value of MRI to CT in patients scheduled for local therapy of colorectal liver metastases (CAMINO): study protocol for an international multicentre prospective diagnostic accuracy study

Background: Abdominal computed tomography (CT) is the standard imaging method for patients with suspected colorectal liver metastases (CRLM) in the diagnostic workup for surgery or thermal ablation. Diffusion-weighted and gadoxetic-acid-enhanced magnetic resonance imaging (MRI) of the liver is increasingly used to improve the detection rate and characterization of liver lesions. MRI is superior in detection and characterization of CRLM as compared to CT. However, it is unknown how MRI actually impacts patient management. The primary aim of the CAMINO study is to evaluate whether MRI has sufficient clinical added value to be routinely added to CT in the staging of CRLM. The secondary objective is to identify subgroups who benefit the most from additional MRI.Methods: In this international multicentre prospective incremental diagnostic accuracy study, 298 patients with primary or recurrent CRLM scheduled for curative liver resection or thermal ablation based on CT staging will be enrolled from 17 centres across the Netherlands, Belgium, Norway, and Italy. All study participants will undergo CT and diffusion-weighted and gadoxetic-acid enhanced MRI prior to local therapy. The local multidisciplinary team will provide two local therapy plans: first, based on CT-staging and second, based on both CT and MRI. The primary outcome measure is the proportion of clinically significant CRLM (CS-CRLM) detected by MRI not visible on CT. CS-CRLM are defined as liver lesions leading to a change in local therapeutical management. If MRI detects new CRLM in segments which would have been resected in the original operative plan, these are not considered CS-CRLM. It is hypothesized that MRI will lead to the detection of CS-CRLM in >= 10% of patients which is considered the minimal clinically important difference. Furthermore, a prediction model will be developed using multivariable logistic regression modelling to evaluate the predictive value of patient, tumor and procedural variables on finding CS-CRLM on MRI.Discussion: The CAMINO study will clarify the clinical added value of MRI to CT in patients with CRLM scheduled for local therapy. This study will provide the evidence required for the implementation of additional MRI in the routine work-up of patients with primary and recurrent CRLM for local therapy.Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas