Sirolimus for pediatric cervicofacial lymphatic malformation: A systematic review and meta-analysis

Objective This study is a systematic review and meta-analysis of the efficacy and safety of sirolimus in the management of pediatric cervicofacial lymphatic malformations (LMs). Data Sources EMBASE, Medline, Scopus, and Cochrane databases were searched, along with the reference list of all included articles. Review Methods The study protocol was registered with PROSPERO and a systematic literature search strategy was designed and conducted with the aid of a medical librarian. All studies including case reports were included, with pooled analysis of raw data. A meta-analysis was conducted of magnetic resonance imaging (MRI), clinical, and airway outcomes. Results Thirteen case series and five individual case reports were included. Meta-analysis showed 78% (95% CI 57%–94%) of 62 patients had a reduction in LM volume, on MRI criteria, by 20% or more, and 32% (95% CI 11%–57%) had a reduction of 50% or more. Further meta-analysis showed 97% (95% CI 88%–100%) of 78 patients reported some clinical improvement on sirolimus. Sirolimus may be of particular value in management of airway LMs; out of 27 tracheostomy-dependent patients, meta-analysis showed 33% (95% CI 1%–78%) were decannulated after starting sirolimus. Individual patient meta-analysis on 24 individuals showed a statistically significant better response to sirolimus when initiated under the age of 2 years. Conclusion This review and meta-analysis support the efficacy of sirolimus in pediatric LMs of the head, neck, and airway. A large multi-center trial is needed to further explore its role and limitations. Laryngoscope, 134:2038–2047, 202

Limits of applicability of the advection-dispersion model in aquifers containing connected high-conductivity channels

This is the published version. Copyright American Geophysical Union[1] The macrodispersion model from stochastic transport theory is demonstrated to be of limited utility when applied to heterogeneous aquifer systems containing narrow connected pathways. This is so even when contrasts in hydraulic conductivity (K) are small and variance in ln K is less than 0.10. We evaluated how well an advection-dispersion model (ADM) could be used to represent solute plumes transported through mildly heterogeneous three-dimensional (3-D) systems characterized by a well-connected dendritic network of 10 cm wide high-K channels. Each high-K channel network was generated using an invasion percolation algorithm and consisted of ∼10% by volume high-K regions. Contrasts in K between the channels and matrix were varied systematically from 2:1 to 30:1, corresponding to ln K values ranging from 0.04 to 1.05. Simulations involved numerical models with 3-D decimeter discretization, and each model contained 2–4 million active cells. Transport through each channel network considered only the processes of advection and molecular diffusion. In every case, the temporal change in the second spatial moment of concentrations was linear, with R2 values ranging from 0.97 to 0.99. The third spatial moment, or alternatively, the skewness coefficient values, indicated significant tailing downstream of the plume center. For each case, a corresponding ADM was used to simulate transport through the system. The corresponding ADM employed the effective mean hydraulic conductivity that reproduced the total discharge through the channel network system under an identical ambient gradient. Dispersivity values used in the ADM were obtained from the temporal change in the second spatial moments of concentrations for the plumes in the channel network systems and ranged from 0.014 m to 0.85 m. The results indicate that as the conductivity contrast between the channels and matrix increased, the simulated plumes in the channel network system became more and more asymmetric, with little solute dispersed upstream of the plume center and extensive downstream spreading of low concentrations. Distinctly different spreading was found upstream versus downstream of the plume center. The ADM failed to capture this asymmetry. Comparison of each plume in the channel network system with the corresponding plume produced using the corresponding ADM showed a maximum correlation of only 0.64 and a minimum fractional error of 0.29 for cases in which the log K variance was ∼0.20 (ln K variance was ∼1.0). At early times the correlations were as low as 0.40. The greatest correlation occurred at late times and for cases in which a wide source was considered

Brief report:An evaluation of the AQ-10 as a brief screening instrument for ASD in adults

There is a need for brief screening instruments for autistic spectrum disorders (ASD) that can be used by frontline healthcare professionals to aid in the decision as to whether an individual should be referred for a full diagnostic assessment. In this study we evaluated the ability of a short form of the autism spectrum quotient (AQ) questionnaire, the 10 item AQ-10, to correctly classify individuals as having or not having ASD. In a sample of 149 individuals with ASD and 134 controls without an ASD diagnosis, we found that the full AQ (AQ-50) abridged AQ (AQ-S) and AQ-10 all performed well as a screen for ASD. ROC analysis indicated that sensitivity, specificity and area under the curve were very similar at suggested cut-off's for ASD across measures, with little difference in performance between the AQ-10 and full AQ-50. Results indicate the potential usefulness of the AQ-10 as a brief screen for ASD

Thick disk kinematics from RAVE and the solar motion

Radial velocity surveys such as the Radial Velocity Experiment (RAVE) provide us with measurements of hundreds of thousands of nearby stars most of which belong to the Galactic thin, thick disk or halo. Ideally, to study the Galactic disks (both thin and thick) one should make use of the multi-dimensional phase-space and the whole pattern of chemical abundances of their stellar populations. In this paper, with the aid of the RAVE Survey, we study the thin and thick disks of the Milky Way, focusing on the latter. We present a technique to disentangle the stellar content of the two disks based on the kinematics and other stellar parameters such as the surface gravity of the stars. Using the Padova Galaxy Model, we checked the ability of our method to correctly isolate the thick disk component from the Galaxy mixture of stellar populations. We introduce selection criteria in order to clean the observed radial velocities from the Galactic differential rotation and to take into account the partial sky coverage of RAVE. We developed a numerical technique to statistically disentangle thin and thick disks from their mixture. We deduce the components of the solar motion relative to the Local Standard of Rest (LSR) in the radial and vertical direction, the rotational lag of the thick disk component relative to the LSR, and the square root of the absolute value of the velocity dispersion tensor for the thick disk alone. The analysis of the thin disk is presented in another paper. We find good agreement with previous independent parameter determinations. In our analysis we used photometrically determined distances. In the Appendix we show that similar values can be found for the thick disk alone as derived in the main sections of our paper even without the knowledge of photometric distances.Comment: accepted on A&A, please see companion paper "THIN disk kinem...

Cognitive facilitation following intentional odor exposure

This paper reviews evidence that, in addition to incidental olfactory pollutants, intentional odor delivery can impact cognitive operations both positively and negatively. Evidence for cognitive facilitation/interference is reviewed alongside four potential explanations for odor-induced effects. It is concluded that the pharmacological properties of odors can induce changes in cognition. However, these effects can be accentuated/attenuated by the shift in mood following odor exposure, expectancy of cognitive effects, and cues to behavior via the contextual association with the odor. It is proposed that greater consideration is required in the intentional utilization of odors within both industrial and private locations, since differential effects are observed for odors with positive hedonic qualities

Constraints on the Galactic bar from the Hercules stream as traced with RAVE across the Galaxy

Non-axisymmetries in the Galactic potential (spiral arms and bar) induce kinematic groups such as the Hercules stream. Assuming that Hercules is caused by the effects of the outer Lindblad resonance of the Galactic bar, we model analytically its properties as a function of position in the Galaxy and its dependence on the bar's pattern speed and orientation. Using data from the RAVE survey we find that the azimuthal velocity of the Hercules structure decreases as a function of Galactocentric radius, in a manner consistent with our analytical model. This allows us to obtain new estimates of the parameters of the Milky Way's bar. The combined likelihood function of the bar's pattern speed and angle has its maximum for a pattern speed of Omega(b) = (1.89 +/- 0.08) x Omega(0), where Omega(0) is the local circular frequency. Assuming a solar radius of 8.05 kpc and a local circular velocity of 238 km s(-1), this corresponds to Omega(b) = 56 +/- 2km s(-1) kpc(-1). On the other hand, the bar's orientation phi(b) cannot be constrained with the available data. In fact, the likelihood function shows that a tight correlation exists between the pattern speed and the orientation, implying that a better description of our best fit results is given by the linear relation Omega(b)/Omega(0) = 1.91+0.0044 (phi(b)(deg) - 48), with standard deviation of 0.02. For example, for an angle of phi(b) = 30 deg the pattern speed is 54.0 +/- 0.5 km s(-1) kpc(-1). These results are not very sensitive to the other Galactic parameters such as the circular velocity curve or the peculiar motion of the Sun, and are robust to biases in distance

Chemical gradients in the Milky Way from the RAVE data

Aims. We aim at measuring the chemical gradients of the elements Mg, Al, Si, and Fe along the Galactic radius to provide new constraints on the chemical evolution models of the Galaxy and Galaxy models such as the Besancon model. Thanks to the large number of stars of our RAVE sample we can study how the gradients vary as function of the distance from the Galactic plane. Methods. We analysed three different samples selected from three independent datasets: a sample of 19 962 dwarf stars selected from the RAVE database, a sample of 10 616 dwarf stars selected from the Geneva-Copenhagen Survey (GCS) dataset, and a mock sample (equivalent to the RAVE sample) created by using the GALAXIA code, which is based on the Besancon model. The three samples were analysed by using the very same method for comparison purposes. We integrated the Galactic orbits and obtained the guiding radii (R-g) and the maximum distances from the Galactic plane reached by the stars along their orbits (Z(max)). We measured the chemical gradients as functions of R-g at different Z(max). Results. We found that the chemical gradients of the RAVE and GCS samples are negative and show consistent trends, although they are not equal: at Z(max) < 0.4 kpc and 4.5 < R-g(kpc) < 9.5, the iron gradient for the RAVE sample is d[Fe/H]/dR(g) = -0.065 dex kpc(-1), whereas for the GCS sample it is d[Fe/H]/dR(g) = -0.043 dex kpc(-1) with internal errors of +/-0.002 and +/-0.004 dex kpc(-1), respectively. The gradients of the RAVE and GCS samples become flatter at larger Z(max). Conversely, the mock sample has a positive iron gradient of d[Fe/H]/dR(g) = +0.053 +/- 0.003 dex kpc(-1) at Z(max) < 0.4 kpc and remains positive at any Z(max). These positive and unrealistic values originate from the lack of correlation between metallicity and tangential velocity in the Besancon model. In addition, the low metallicity and asymmetric drift of the thick disc causes a shift of the stars towards lower R-g and metallicity which, together with the thin-disc stars with a higher metallicity and R-g, generates a fictitious positive gradient of the full sample. The flatter gradient at larger Z(max) found in the RAVE and the GCS samples may therefore be due to the superposition of thin-and thick-disc stars, which mimicks a flatter or positive gradient. This does not exclude the possibility that the thick disc has no chemical gradient. The discrepancies between the observational samples and the mock sample can be reduced by i) decreasing the density; ii) decreasing the vertical velocity; and iii) increasing the metallicity of the thick disc in the Besancon model

In Search of a Trade Mark: Search Practices and Bureaucratic Poetics

Trade marks have been understood as quintessential ‘bureaucratic properties’. This article suggests that the making of trade marks has been historically influenced by bureaucratic practices of search and classification, which in turn were affected by the possibilities and limits of spatial organisation and technological means of access and storage. It shows how the organisation of access and retrieval did not only condition the possibility of conceiving new trade marks, but also served to delineate their intangible proprietary boundaries. Thereby they framed the very meaning of a trade mark. By advancing a historical analysis that is sensitive to shifts, both in actual materiality and in the administrative routines of trade mark law, the article highlights the legal form of trade mark as inherently social and materially shaped. We propose a historical understanding of trade mark law that regards legal practice and bureaucratic routines as being co-constitutive of the very legal object itself