High-resolution three-dimensional 3 T magnetic resonance angiography for the evaluation of experimental aneurysm in the rabbit

OBJECTIVE: The standard technique of two-dimensional intra-arterial digital subtraction angiography (2D-DSA) for the imaging of experimental rabbit aneurysms is invasive and has considerable surgical risks. Therefore, minimally invasive techniques ideally providing three-dimensional imaging for intervention planning and follow-up are needed. This study evaluates the feasibility and quality of three-dimensional 3-T magnetic resonance angiography (3D-3T-MRA) and compares 3D-3T-MRA with 2D-DSA in experimental aneurysms in the rabbit. METHOD: Three microsurgically created aneurysms in three rabbits were evaluated using 2D-DSA and 3D-3T-MRA. Imaging of the aneurysms was performed 2 weeks after creation using 2D-DSA and contrast-enhanced (CE) MRA. Measurements included aneurysm dome (length and width) and aneurysm neck. Aneurysm volumes were determined using CE-MRA. RESULTS: The measurements of the aneurysms' dimensions and the evaluation of vicinity vessels with both techniques showed a good correlation. The mean aneurysm length, aneurysm width and neck width measured with DSA (6.9, 4.1 and 2.8 mm, respectively) correlated with the measurements performed in 3D-3T-MRA (6.9, 4 and 2.5 mm, respectively). The mean aneurysm volumes measured with CE-MRA was 46.7 mm(3). CONCLUSION: 3D-3T CE-MRA is feasible and less invasive and is a safer imaging alternative to DSA for experimental aneurysm. Additionally, aneurysm technique this precise offers the possibility of repetitive 3D aneurysm volumetry for long-term follow-up studies after endovascular aneurysm occlusion.

Calibration and analysis of the 2007 data

he physics program of the NA61/SHINE (SHINE = SPS Heavy Ion and Neutrino Experiment) experiment at the CERN SPS consists of three subjects. In the first stage of data taking (2007-2009) measurements of hadron production in hadron-nucleus interactions needed for neutrino (T2K) and cosmic-ray (Pierre Auger and KASCADE) experiments will be performed. In the second stage (2009-2010) hadron production in proton-proton and proton-nucleus interactions needed as reference data for a better understanding of nucleus-nucleus reactions will be studied. In the third stage (2009-2013) energy dependence of hadron production properties will be measured in p+p, p+Pb interactions and nucleus-nucleus collisions, with the aim to identify the properties of the onset of deconfinement and find evidence for the critical point of strongly interacting matter. The NA61 experiment was approved at CERN in June 2007. The first pilot run was performed during October 2007. Calibrations of all detector components have been performed successfully and preliminary uncorrected spectra have been obtained. High quality of track reconstruction and particle identification similar to NA49 has been achieved. The data and new detailed simulations confirm that the NA61 detector acceptance and particle identification capabilities cover the phase space required by the T2K experiment. This document reports on the progress made in the calibration and analysis of the 2007 data.

A quantitative phenytoin GC-MS method and it's validation for samples from human ex situ brain microdialysis, blood and saliva using solid-phase extraction

This study describes the development and validation of a gas chromatography-mass spectrometry (GC-MS) method to identify and quantitate phenytoin in brain microdialysate, saliva and blood from human samples. A solid-phase extraction (SPE) was performed with a nonpolar C8-SCX column. The eluate was evaporated with nitrogen (50°C) and derivatized with trimethylsulfonium hydroxide before GC-MS analysis. As the internal standard, 5-(p-methylphenyl)-5-phenylhydantoin was used. The MS was run in scan mode and the identification was made with three ion fragment masses. All peaks were identified with MassLib. Spiked phenytoin samples showed recovery after SPE of ≥94%. The calibration curve (phenytoin 50 to 1,200 ng/mL, n = 6, at six concentration levels) showed good linearity and correlation (r² > 0.998). The limit of detection was 15 ng/mL; the limit of quantification was 50 ng/mL. Dried extracted samples were stable within a 15% deviation range for ≥4 weeks at room temperature. The method met International Organization for Standardization standards and was able to detect and quantify phenytoin in different biological matrices and patient samples. The GC-MS method with SPE is specific, sensitive, robust and well reproducible, and is therefore an appropriate candidate for the pharmacokinetic assessment of phenytoin concentrations in different human biological samples.

Effects of study precision and risk of bias in networks of interventions: a network meta-epidemiological study

BACKGROUND Empirical research has illustrated an association between study size and relative treatment effects, but conclusions have been inconsistent about the association of study size with the risk of bias items. Small studies give generally imprecisely estimated treatment effects, and study variance can serve as a surrogate for study size. METHODS We conducted a network meta-epidemiological study analyzing 32 networks including 613 randomized controlled trials, and used Bayesian network meta-analysis and meta-regression models to evaluate the impact of trial characteristics and study variance on the results of network meta-analysis. We examined changes in relative effects and between-studies variation in network meta-regression models as a function of the variance of the observed effect size and indicators for the adequacy of each risk of bias item. Adjustment was performed both within and across networks, allowing for between-networks variability. RESULTS Imprecise studies with large variances tended to exaggerate the effects of the active or new intervention in the majority of networks, with a ratio of odds ratios of 1.83 (95% CI: 1.09,3.32). Inappropriate or unclear conduct of random sequence generation and allocation concealment, as well as lack of blinding of patients and outcome assessors, did not materially impact on the summary results. Imprecise studies also appeared to be more prone to inadequate conduct. CONCLUSIONS Compared to more precise studies, studies with large variance may give substantially different answers that alter the results of network meta-analyses for dichotomous outcomes.

Grey matter volumetric changes related to recovery from hand paresis after cortical sensorimotor stroke

Preclinical studies using animal models have shown that grey matter plasticity in both perilesional and distant neural networks contributes to behavioural recovery of sensorimotor functions after ischaemic cortical stroke. Whether such morphological changes can be detected after human cortical stroke is not yet known, but this would be essential to better understand post-stroke brain architecture and its impact on recovery. Using serial behavioural and high-resolution magnetic resonance imaging (MRI) measurements, we tracked recovery of dexterous hand function in 28 patients with ischaemic stroke involving the primary sensorimotor cortices. We were able to classify three recovery subgroups (fast, slow, and poor) using response feature analysis of individual recovery curves. To detect areas with significant longitudinal grey matter volume (GMV) change, we performed tensor-based morphometry of MRI data acquired in the subacute phase, i.e. after the stage compromised by acute oedema and inflammation. We found significant GMV expansion in the perilesional premotor cortex, ipsilesional mediodorsal thalamus, and caudate nucleus, and GMV contraction in the contralesional cerebellum. According to an interaction model, patients with fast recovery had more perilesional than subcortical expansion, whereas the contrary was true for patients with impaired recovery. Also, there were significant voxel-wise correlations between motor performance and ipsilesional GMV contraction in the posterior parietal lobes and expansion in dorsolateral prefrontal cortex. In sum, perilesional GMV expansion is associated with successful recovery after cortical stroke, possibly reflecting the restructuring of local cortical networks. Distant changes within the prefrontal-striato-thalamic network are related to impaired recovery, probably indicating higher demands on cognitive control of motor behaviour.

Palaeoenvironmental changes in Central Europe (NE Poland) during the last 6200 years reconstructed from a high-resolution multi-proxy peat archive

Peat deposits from an ombrotrophic bog (north-eastern Poland) were analysed to reconstruct peatland development and environmental changes. This paper presents reconstructions of hydrological changes and plant succession over the last 6000 years. The methods included the high-resolution analysis of plant macrofossils, pollen and testate amoebae, supported by radiocarbon dating. Three main phases were identified in the history of the bog and surrounding woodland vegetation: 4000–400 BC, 400 BC–AD 1700 and AD 1700–2011. Except for terrestrialisation and the fen-to-bog transition phase, the development of bog vegetation was mainly dependent on the climate until approximately AD 1700. The dominant taxon in Gązwa bog was Sphagnum fuscum/rubellum. Woodland development was significantly affected by human activity at several time periods. The most visible human activity, manifested by the decline of deciduous species, occurred ca. 350 BC, ca. AD 250, ca. AD 1350 and after AD 1700. These events correspond to phases of human settlement in the area. During 400–300 BC, the decline of deciduous trees, primarily Carpinus, coincided with an increase in indicators of human activity and fire frequency. At ca. AD 200, Carpinus and Tilia abundance decreased, corresponding to an increased importance of cereals (Secale and Triticum). Since ca. AD 1350, the impact of Teutonic settlement is apparent, and after AD 1700, deciduous forests largely disappeared.

Trajectory mapping of middle atmospheric water vapor by a mini network of NDACC instruments

The important task to observe the global coverage of middle atmospheric trace gases like water vapor or ozone usually is accomplished by satellites. Climate and atmospheric studies rely upon the knowledge of trace gas distributions throughout the stratosphere and mesosphere. Many of these gases are currently measured from satellites, but it is not clear whether this capability will be maintained in the future. This could lead to a significant knowledge gap of the state of the atmosphere. We explore the possibilities of mapping middle atmospheric water vapor in the Northern Hemisphere by using Lagrangian trajectory calculations and water vapor profile data from a small network of five ground-based microwave radiometers. Four of them are operated within the frame of NDACC (Network for the Detection of Atmospheric Composition Change). Keeping in mind that the instruments are based on different hardware and calibration setups, a height-dependent bias of the retrieved water vapor profiles has to be expected among the microwave radiometers. In order to correct and harmonize the different data sets, the Microwave Limb Sounder (MLS) on the Aura satellite is used to serve as a kind of traveling standard. A domain-averaging TM (trajectory mapping) method is applied which simplifies the subsequent validation of the quality of the trajectory-mapped water vapor distribution towards direct satellite observations. Trajectories are calculated forwards and backwards in time for up to 10 days using 6 hourly meteorological wind analysis fields. Overall, a total of four case studies of trajectory mapping in different meteorological regimes are discussed. One of the case studies takes place during a major sudden stratospheric warming (SSW) accompanied by the polar vortex breakdown; a second takes place after the reformation of stable circulation system. TM cases close to the fall equinox and June solstice event from the year 2012 complete the study, showing the high potential of a network of ground-based remote sensing instruments to synthesize hemispheric maps of water vapor.

A Thalamic-Fronto-Parietal Structural Covariance Network Emerging in the Course of Recovery from Hand Paresis after Ischemic Stroke.

AIM To describe structural covariance networks of gray matter volume (GMV) change in 28 patients with first-ever stroke to the primary sensorimotor cortices, and to investigate their relationship to hand function recovery and local GMV change. METHODS Tensor-based morphometry maps derived from high-resolution structural images were subject to principal component analyses to identify the networks. We calculated correlations between network expression and local GMV change, sensorimotor hand function and lesion volume. To verify which of the structural covariance networks of GMV change have a significant relationship to hand function, we performed an additional multivariate regression approach. RESULTS Expression of the second network, explaining 9.1% of variance, correlated with GMV increase in the medio-dorsal (md) thalamus and hand motor skill. Patients with positive expression coefficients were distinguished by significantly higher GMV increase of this structure during stroke recovery. Significant nodes of this network were located in md thalamus, dorsolateral prefrontal cortex, and higher order sensorimotor cortices. Parameter of hand function had a unique relationship to the network and depended on an interaction between network expression and lesion volume. Inversely, network expression is limited in patients with large lesion volumes. CONCLUSION Chronic phase of sensorimotor cortical stroke has been characterized by a large scale co-varying structural network in the ipsilesional hemisphere associated specifically with sensorimotor hand skill. Its expression is related to GMV increase of md thalamus, one constituent of the network, and correlated with the cortico-striato-thalamic loop involved in control of motor execution and higher order sensorimotor cortices. A close relation between expression of this network with degree of recovery might indicate reduced compensatory resources in the impaired subgroup.

Trajectory mapping of middle atmospheric water vapor by a mini network of NDACC instruments

The important task to observe the global coverage of middle atmospheric trace gases like water vapor or ozone usually is accomplished by satellites. Climate and atmospheric studies rely upon the knowledge of trace gas distributions throughout the stratosphere and mesosphere. Many of these gases are currently measured from satellites, but it is not clear whether this capability will be maintained in the future. This could lead to a significant knowledge gap of the state of the atmosphere. We explore the possibilities of mapping middle atmospheric water vapor in the Northern Hemisphere by using Lagrangian trajectory calculations and water vapor profile data from a small network of five ground-based microwave radiometers. Four of them are operated within the frame of NDACC (Network for the Detection of Atmospheric Composition Change). Keeping in mind that the instruments are based on different hardware and calibration setups, a height-dependent bias of the retrieved water vapor profiles has to be expected among the microwave radiometers. In order to correct and harmonize the different data sets, the Microwave Limb Sounder (MLS) on the Aura satellite is used to serve as a kind of traveling standard. A domain-averaging TM (trajectory mapping) method is applied which simplifies the subsequent validation of the quality of the trajectory-mapped water vapor distribution towards direct satellite observations. Trajectories are calculated forwards and backwards in time for up to 10 days using 6 hourly meteorological wind analysis fields. Overall, a total of four case studies of trajectory mapping in different meteorological regimes are discussed. One of the case studies takes place during a major sudden stratospheric warming (SSW) accompanied by the polar vortex breakdown; a second takes place after the reformation of stable circulation system. TM cases close to the fall equinox and June solstice event from the year 2012 complete the study, showing the high potential of a network of ground-based remote sensing instruments to synthesize hemispheric maps of water vapor.

Psychological therapies for panic disorder with or without agoraphobia in adults: a network meta-analysis.

BACKGROUND Panic disorder is characterised by the presence of recurrent unexpected panic attacks, discrete periods of fear or anxiety that have a rapid onset and include symptoms such as racing heart, chest pain, sweating and shaking. Panic disorder is common in the general population, with a lifetime prevalence of 1% to 4%. A previous Cochrane meta-analysis suggested that psychological therapy (either alone or combined with pharmacotherapy) can be chosen as a first-line treatment for panic disorder with or without agoraphobia. However, it is not yet clear whether certain psychological therapies can be considered superior to others. In order to answer this question, in this review we performed a network meta-analysis (NMA), in which we compared eight different forms of psychological therapy and three forms of a control condition. OBJECTIVES To assess the comparative efficacy and acceptability of different psychological therapies and different control conditions for panic disorder, with or without agoraphobia, in adults. SEARCH METHODS We conducted the main searches in the CCDANCTR electronic databases (studies and references registers), all years to 16 March 2015. We conducted complementary searches in PubMed and trials registries. Supplementary searches included reference lists of included studies, citation indexes, personal communication to the authors of all included studies and grey literature searches in OpenSIGLE. We applied no restrictions on date, language or publication status. SELECTION CRITERIA We included all relevant randomised controlled trials (RCTs) focusing on adults with a formal diagnosis of panic disorder with or without agoraphobia. We considered the following psychological therapies: psychoeducation (PE), supportive psychotherapy (SP), physiological therapies (PT), behaviour therapy (BT), cognitive therapy (CT), cognitive behaviour therapy (CBT), third-wave CBT (3W) and psychodynamic therapies (PD). We included both individual and group formats. Therapies had to be administered face-to-face. The comparator interventions considered for this review were: no treatment (NT), wait list (WL) and attention/psychological placebo (APP). For this review we considered four short-term (ST) outcomes (ST-remission, ST-response, ST-dropouts, ST-improvement on a continuous scale) and one long-term (LT) outcome (LT-remission/response). DATA COLLECTION AND ANALYSIS As a first step, we conducted a systematic search of all relevant papers according to the inclusion criteria. For each outcome, we then constructed a treatment network in order to clarify the extent to which each type of therapy and each comparison had been investigated in the available literature. Then, for each available comparison, we conducted a random-effects meta-analysis. Subsequently, we performed a network meta-analysis in order to synthesise the available direct evidence with indirect evidence, and to obtain an overall effect size estimate for each possible pair of therapies in the network. Finally, we calculated a probabilistic ranking of the different psychological therapies and control conditions for each outcome. MAIN RESULTS We identified 1432 references; after screening, we included 60 studies in the final qualitative analyses. Among these, 54 (including 3021 patients) were also included in the quantitative analyses. With respect to the analyses for the first of our primary outcomes, (short-term remission), the most studied of the included psychological therapies was CBT (32 studies), followed by BT (12 studies), PT (10 studies), CT (three studies), SP (three studies) and PD (two studies).The quality of the evidence for the entire network was found to be low for all outcomes. The quality of the evidence for CBT vs NT, CBT vs SP and CBT vs PD was low to very low, depending on the outcome. The majority of the included studies were at unclear risk of bias with regard to the randomisation process. We found almost half of the included studies to be at high risk of attrition bias and detection bias. We also found selective outcome reporting bias to be present and we strongly suspected publication bias. Finally, we found almost half of the included studies to be at high risk of researcher allegiance bias.Overall the networks appeared to be well connected, but were generally underpowered to detect any important disagreement between direct and indirect evidence. The results showed the superiority of psychological therapies over the WL condition, although this finding was amplified by evident small study effects (SSE). The NMAs for ST-remission, ST-response and ST-improvement on a continuous scale showed well-replicated evidence in favour of CBT, as well as some sparse but relevant evidence in favour of PD and SP, over other therapies. In terms of ST-dropouts, PD and 3W showed better tolerability over other psychological therapies in the short term. In the long term, CBT and PD showed the highest level of remission/response, suggesting that the effects of these two treatments may be more stable with respect to other psychological therapies. However, all the mentioned differences among active treatments must be interpreted while taking into account that in most cases the effect sizes were small and/or results were imprecise. AUTHORS' CONCLUSIONS There is no high-quality, unequivocal evidence to support one psychological therapy over the others for the treatment of panic disorder with or without agoraphobia in adults. However, the results show that CBT - the most extensively studied among the included psychological therapies - was often superior to other therapies, although the effect size was small and the level of precision was often insufficient or clinically irrelevant. In the only two studies available that explored PD, this treatment showed promising results, although further research is needed in order to better explore the relative efficacy of PD with respect to CBT. Furthermore, PD appeared to be the best tolerated (in terms of ST-dropouts) among psychological treatments. Unexpectedly, we found some evidence in support of the possible viability of non-specific supportive psychotherapy for the treatment of panic disorder; however, the results concerning SP should be interpreted cautiously because of the sparsity of evidence regarding this treatment and, as in the case of PD, further research is needed to explore this issue. Behaviour therapy did not appear to be a valid alternative to CBT as a first-line treatment for patients with panic disorder with or without agoraphobia.