A comprehensive resource for induced pluripotent stem cells from patients with primary tauopathies

Primary tauopathies are characterized neuropathologically by inclusions containing abnormal forms of the microtubule-associated protein tau (MAPT) and clinically by diverse neuropsychiatric, cognitive, and motor impairments. Autosomal dominant mutations in the MAPT gene cause heterogeneous forms of frontotemporal lobar degeneration with tauopathy (FTLD-Tau). Common and rare variants in the MAPT gene increase the risk for sporadic FTLD-Tau, including progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). We generated a collection of fibroblasts from 140 MAPT mutation/risk variant carriers, PSP, CBD, and cognitively normal controls; 31 induced pluripotent stem cell (iPSC) lines from MAPT mutation carriers, non-carrier family members, and autopsy-confirmed PSP patients; 33 genome engineered iPSCs that were corrected or mutagenized; and forebrain neural progenitor cells (NPCs). Here, we present a resource of fibroblasts, iPSCs, and NPCs with comprehensive clinical histories that can be accessed by the scientific community for disease modeling and development of novel therapeutics for tauopathies

Spectral averaging techniques for Jacobi matrices

Spectral averaging techniques for one-dimensional discrete Schroedinger operators are revisited and extended. In particular, simultaneous averaging over several parameters is discussed. Special focus is put on proving lower bounds on the density of the averaged spectral measures. These Wegner type estimates are used to analyze stability properties for the spectral types of Jacobi matrices under local perturbations

Analysis of variation in pre-procedural fasting duration for common inpatient gastrointestinal procedures

BACKGROUND: Gastrointestinal procedures generally require pre-procedural fasting to optimize sedation safety. While the American Society of Anesthesiologists (ASA) recommends no intake of clear liquids and solid food 2-4 and 6-8 hours respectively prior to endoscopic procedures, the actual nil per os (NPO) duration for these procedures in practice is unknown. Our objective was to analyze NPO duration for patients undergoing these procedures and to determine its association with clinical and administrative variables. METHODS: Inpatient data from 2016-2018 for the three procedures was extracted from electronic medical records and administrative data at a single-center tertiary academic medical center. Various statistical tests (Kruskal-Wallis, Wilcoxon, Pearson) were employed depending on the outcome type and data distribution. RESULTS: One thousand three hundred and twenty-five esophagogastroduodenoscopies (EGDs), 753 colonoscopies, and 550 endoscopic retrograde cholangiopancreatographies (ERCPs) were included. The median NPO time for all procedures was 12.6 hours (IQR, 9.6-16.1 hours). The median NPO times were 12.6, 11.9, and 13.1 hours for EGD, colonoscopy, and ERCP respectively. NPO duration was greater for Hispanic than non-Hispanic patients (median 13.9 CONCLUSIONS: NPO times for common inpatient gastroenterology (GI) procedures generally exceeded 12 hours, suggesting there is an opportunity to adopt changes to decrease NPO duration for low-risk patients while maintaining adherence to guidelines and best practice

Charge and Current in the Quantum Hall Matrix Model

We extend the quantum Hall matrix model to include couplings to external electric and magnetic fields. The associated current suffers from matrix ordering ambiguities even at the classical level. We calculate the linear response at low momenta -- this is unambigously defined. In particular, we obtain the correct fractional quantum Hall conductivity, and the expected density modulations in response to a weak and slowly varying magnetic field. These results show that the classical quantum Hall matrix models describe important aspects of the dynamics of electrons in the lowest Landau level. In the quantum theory the ordering ambiguities are more severe; we discuss possible strategies, but we have not been able to construct a good density operator, satisfying the pertinent lowest Landau level commutator algebra.Comment: 12 pages, no figures; a logical error below the proposed density operator (46) in version 1 is corrected, and the claim that this density operator satisfy the magnetic algebra (2) is withdrawn. Some formulations have been changed and a few misprints correcte

Evaluation of a portable retinal imaging device: towards a comparative quantitative analysis for morphological measurements of retinal blood vessels

This study investigated the possibility of using low-cost, handheld, retinal imaging devices for the automatic extraction of quantifiable measures of retinal blood vessels. Initially, the available handheld devices were compared using a Zeiss model eye incorporating a USAF resolution test chart to assess their optical properties. The only suitable camera of the five evaluated was the Horus DEC 200. This device was then subjected to a detailed evaluation in which images in human eyes taken from the handheld camera were compared in a quantitative analysis with those of the same eye from a Canon CR-DGi retinal desktop camera. We found that the Horus DEC 200 exhibited shortcomings in capturing images of human eyes by comparison with the Canon. More images were rejected as being unevaluable or suffering failures in automatic segmentation than with the Canon, and even after exclusion of affected images, the Horus yielded lower measurements of vessel density than the Canon. A number of issues affecting handheld cameras in general and some features of the Horus in particular have been identified that might contribute to the observed differences in performance. Some potential mitigations are discussed which might yield improvements in performance, thus potentially facilitating use of handheld retinal imaging devices for quantitative retinal microvascular measurements

Accident causation and pre-accidental driving situations: Part 1. Overview and general statistics

WP2 of the European Project TRACE is concerned with “Types of Situations” to analyse the causation of road traffic accidents from the pre-accidental driving situation point of view. Four complementary situations were defined: stabilized situations, intersection, specific manoeuvre and degradation scenario. To reach this objective, the analysis is based on a common methodology composed on 3 steps: the “descriptive analysis” which from general statistics will allow to identify among the studied situations those them relevant and to give their characteristics, the “in-depth analysis” allowing to obtain accident causes from the generic description of the problems identified in the previous step and the risk analysis identifying the risk of being involved in an accident taking into account the results obtained from the ‘in–depth’ level. This report is dedicated to the descriptive analysis with the identification of the most relevant scenario regarding the situation in which the driver is involved just prior the accident. The results are based on the literature review, general statistics and the analysis of the national databases available in TRACE via WP8. Because the information level differ from databases to another, the available scenario presented here for the 4 predefined types of situations are generics and some specific situations could not have be distinguished. For each situation some key indicators are given, such as prevalence, severity, KSI (killed x severely injured), etc. When it is possible, these indicators are estimated at the EU27 level

Tailored second line therapy in asthmatic children with the arginine-16 genotype

The arginine-16 beta-2 receptor genotype confers increased susceptibility to exacerbations in asthmatic children taking regular long acting beta-2 agonists. We therefore evaluated using montelukast as an alternative to salmeterol as tailored second line asthma controller therapy in children expressing this susceptible genotype. 62 persistent asthmatic children with the homozygous arginine-16 genotype were randomized to receive salmeterol 50ug bid or montelukast 5/10mg od as add on to inhaled fluticasone for 1 year. School absences (the primary outcome) were reduced with montelukast arm compared to salmeterol: difference in score = 0.40 (95%CI 0.07-0.87) p=0.005. Albuterol use was also reduced with montelukast compared with salmeterol: difference in score = 0.47 (95%CI 0.16-0.79) p<0.0001. Greater improvements occurred in both symptom and quality of life scores with montelukast vs salmeterol, while there was no difference in FEV1. Montelukast may be suitable as tailored second line controller therapy instead of salmeterol in asthmatic children expressing the susceptible arginine-16 genotype - moving towards a personalised medicine approach to management

2,3,8-trisubstituted quinolines with antimalarial activity

FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCombination therapy drugs are considered a fundamental way to control malaria as it mimimizes the risk of emergence of resistance to the individual partner drugs. Consequently, this type of therapy constitutes a driving force for the discovery of new drug901212151231FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQSEM INFORMAÇÃOSEM INFORMAÇÃOWe especially thank Prof. Marcos Eberlin (Thomsom Laboratory) for HRMS analyses. We are grateful to Sergio Wittlin, Sibylle Sax and the Swiss Tropical and Public Health Institute (Basel, Switzerland) for conducting the resistance assays. We thank Mark We

Unveiling a Rich System of Faint Dwarf Galaxies in the Next Generation Fornax Survey

We report the discovery of 158 previously undetected dwarf galaxies in the Fornax cluster central regions using a deep coadded $u, g$ and $i$-band image obtained with the DECam wide-field camera mounted on the 4-meter Blanco telescope at the Cerro Tololo Interamerican Observatory as part of the {\it Next Generation Fornax Survey} (NGFS). The new dwarf galaxies have quasi-exponential light profiles, effective radii $0.1\!<\!r_e\!<\!2.8$ kpc and average effective surface brightness values $22.0\!<\!\mu_i\!<\!28.0$ mag arcsec$^{-2}$. We confirm the existence of ultra-diffuse galaxies (UDGs) in the Fornax core regions that resemble counterparts recently discovered in the Virgo and Coma galaxy clusters.~We also find extremely low surface brightness NGFS dwarfs, which are several magnitudes fainter than the classical UDGs. The faintest dwarf candidate in our NGFS sample has an absolute magnitude of $M_i\!=\!-8.0$\,mag. The nucleation fraction of the NGFS dwarf galaxy sample appears to decrease as a function of their total luminosity, reaching from a nucleation fraction of $>\!75\%$ at luminosities brighter than $M_i\!\simeq\!-15.0$ mag to $0\%$ at luminosities fainter than $M_i\!\simeq\!-10.0$ mag. The two-point correlation function analysis of the NGFS dwarf sample shows an excess on length scales below $\sim\!100$ kpc, pointing to the clustering of dwarf galaxies in the Fornax cluster core.Comment: 6 pages, 3 figures. Accepted for publication in The Astrophysical Journal Letters. Download the high-resolution version of the paper from the following link: https://www.dropbox.com/s/xb9vz8s29wlzjgf/ms.pdf?dl=