Patient-derived iPSCs show premature neural differentiation and neuron type-specific phenotypes relevant to neurodevelopment.

Ras/MAPK pathway signaling is a major participant in neurodevelopment, and evidence suggests that BRAF, a key Ras signal mediator, influences human behavior. We studied the role of the mutation BRAFQ257R, the most common cause of cardiofaciocutaneous syndrome (CFC), in an induced pluripotent stem cell (iPSC)-derived model of human neurodevelopment. In iPSC-derived neuronal cultures from CFC subjects, we observed decreased p-AKT and p-ERK1/2 compared to controls, as well as a depleted neural progenitor pool and rapid neuronal maturation. Pharmacological PI3K/AKT pathway manipulation recapitulated cellular phenotypes in control cells and attenuated them in CFC cells. CFC cultures displayed altered cellular subtype ratios and increased intrinsic excitability. Moreover, in CFC cells, Ras/MAPK pathway activation and morphological abnormalities exhibited cell subtype-specific differences. Our results highlight the importance of exploring specific cellular subtypes and of using iPSC models to reveal relevant human-specific neurodevelopmental events

Photon Propagation in Space-Time with a Compactified Spatial Dimension

The one-loop effects of vacuum polarization induced by untwisted fermions in QED in a nonsimply connected space-time with topology $S^{1}\times R^{3}$ are investigated. It is found that photon propagation in this system is anisotropic, appearing several massive photon modes and a superluminal transverse mode. For small compactification radius $a$, the superluminal velocity increases logarithmically with $a$. At low energies the photon masses lead to an effective confinement of the gauge fields into a (2+1)-dimensional manifold transverse to the compactified direction. The system shows a topologically induced directional superconductivity.Comment: 5 pages, to appear in PL

Attenuation of acoustic waves in glacial ice and salt domes

Two classes of natural solid media (glacial ice and salt domes) are under consideration as media in which to deploy instruments for detection of neutrinos with energy >1e18 eV. Though insensitive to 1e11 to 1e16 eV neutrinos for which observatories (e.g., AMANDA and IceCube) that utilize optical Cherenkov radiation detectors are designed, radio and acoustic methods are suited for searches for the very low fluxes of neutrinos with energies >1017 eV. This is because, due to the very long attenuation lengths of radio and acoustic waves in ice and salt, detection modules can be spaced very far apart. In this paper, I calculate the absorption and scattering coefficients as a function of frequency and grain size for acoustic waves in glacial ice and salt domes and show that experimental measurements on laboratory samples and in glacial ice and salt domes are consistent with theory. For South Pole ice with grain size 0.2 cm at -51 degrees C, scattering lengths are calculated to be 2000 km and 25 km at 10 kHz and 30 kHz, respectively, and the absorption length is calculated to be 9 km at frequencies above 100 Hz. For NaCl (rock salt) with grain size 0.75 cm, scattering lengths are calculated to be 120 km and 1.4 km at 10 kHz and 30 kHz, and absorption lengths are calculated to be 30,000 km and 3300 km at 10 kHz and 30 kHz. Existing measurements are consistent with theory. For ice, absorption is the limiting factor; for salt, scattering is the limiting factor.Comment: 16 pages, 7 figures, submitted to Journal of Geophysical Research - Solid Eart

Functional and morphological evolution in gymnosperms : a portrait of implicated gene families

Gymnosperms diverged from their sister plant clade of flowering plants 300 Mya. Morphological and functional divergence between the two major seed plant clades involved significant changes in their reproductive biology, water‐conducting systems, secondary metabolism, stress defense mechanisms, and small RNA‐mediated epigenetic silencing. The relatively recent sequencing of several gymnosperm genomes and the development of new genomic resources have enabled whole‐genome comparisons within gymnosperms, and between angiosperms and gymnosperms. In this paper, we aim to understand how genes and gene families have contributed to the major functional and morphological differences in gymnosperms, and how this information can be used for applied breeding and biotechnology. In addition, we have analyzed the angiosperm versus gymnosperm evolution of the pleiotropic drug resistance (PDR) gene family with a wide range of functionalities in plants' interaction with their environment including defense mechanisms. Some of the genes reviewed here are newly studied members of gene families that hold potential for biotechnological applications related to commercial and pharmacological value. Some members of conifer gene families can also be exploited for their potential in phytoremediation applications

Guidelines on "Standards of management of idiopathic scoliosis with corrective braces in everyday clinics and in clinical research": SOSORT Consensus 2008

<p>Abstract</p> <p>Background</p> <p>Reported failure rates,(defined based on percentage of cases progressing to surgery) of corrective bracing for idiopathic scoliosis are highly variable. This may be due to the quality of the brace itself, but also of the patient care during treatment. The latter is sometimes neglected, even though it is considered a main determinant of good results among conservative experts of SOSORT. The aim of this paper was to develop and verify the Consensus on management of scoliosis patients treated with braces</p> <p>Methods</p> <p>We followed a Delphi process in four steps, distributing and gradually changing according to the results a set of recommendations: we involved the SOSORT Board twice, then all SOSORT members twice, with a Pre-Meeting Questionnaire (PMQ), and during a Consensus Session at the SOSORT Athens Meeting with a Meeting Questionnaire (MQ). We set a 90% agreement as the minimum to be reached.</p> <p>Results</p> <p>We had a 71% response rate to PMQ, and 66.7% to MQ. Since the PMQ we had a good agreement (no answers below 72% – 70.2% over 90%). With the MQ the agreement consistently increased for all the answers previously below 90% (no answers below 83%, 75% over 90%). With increasing experience in bracing all numerical criteria tended to become more strict. We finally produced a set of 14 recommendations, grouped in 6 Domains (Experience/competence, Behaviours, Prescription, Construction, Brace Check, Follow-up).</p> <p>Conclusion</p> <p>The Consensus permits establishment of recommendations concerning the standards of management of idiopathic scoliosis with bracing, with the aim to increase efficacy and compliance to treatment. The SOSORT recommends to professionals engaged in patient care to follow the guidelines of this Consensus in their clinical practice. The SOSORT criteria should also be followed in clinical research studies to achieve a minimum quality of care. If the aim is to verify the efficacy of bracing these criteria should be companions of the methodological research criteria for bracing proposed by other societies.</p

Do Interventions Designed to Support Shared Decision-Making Reduce Health Inequalities? : A Systematic Review and Meta-Analysis

Copyright: © 2014 Durand et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Increasing patient engagement in healthcare has become a health policy priority. However, there has been concern that promoting supported shared decision-making could increase health inequalities. Objective: To evaluate the impact of SDM interventions on disadvantaged groups and health inequalities. Design: Systematic review and meta-analysis of randomised controlled trials and observational studies.Peer reviewe

Characterization of Nanoparticle Batch-To-Batch Variability

A central challenge for the safe design of nanomaterials (NMs) is the inherent variability of NM properties, both as produced and as they interact with and evolve in, their surroundings. This has led to uncertainty in the literature regarding whether the biological and toxicological effects reported for NMs are related to specific NM properties themselves, or rather to the presence of impurities or physical effects such as agglomeration of particles. Thus, there is a strong need for systematic evaluation of the synthesis and processing parameters that lead to potential variability of different NM batches and the reproducible production of commonly utilized NMs. The work described here represents over three years of effort across 14 European laboratories to assess the reproducibility of nanoparticle properties produced by the same and modified synthesis routes for four of the OECD priority NMs (silica dioxide, zinc oxide, cerium dioxide and titanium dioxide) as well as amine-modified polystyrene NMs, which are frequently employed as positive controls for nanotoxicity studies. For 46 different batches of the selected NMs, all physicochemical descriptors as prioritized by the OECD have been fully characterized. The study represents the most complete assessment of NMs batch-to-batch variability performed to date and provides numerous important insights into the potential sources of variability of NMs and how these might be reduced