Cryptococcal Meningoencephalitis Presenting as Cerebell itis - A case report -

, , We herein report an elderly patient with cryptococcosis in the nervous system who presented with cerebellar dysfunction and showed cerebellar parenchymal lesion with adjacent focal meningeal enhancement on the brain CT and the serial brain MRls. The cerebellar lesion suggests cryptococcal inflammatory reaction or a cerebellar infarction from the arteritis of a branch of the left superior cerebellar artery. This clinical and neuroimaging finding of cerebellitis has not been reported in cryptococcosis. We think cryptococcosis would be included in the differential diagnosis of cerebellitis

Topological quantization and degeneracy in Josephson-junction arrays

We consider the conductivity quantization in two-dimensional arrays of mesoscopic Josephson junctions, and examine the associated degeneracy in various regimes of the system. The filling factor of the system may be controlled by the gate voltage as well as the magnetic field, and its appropriate values for quantization is obtained by employing the Jain hierarchy scheme both in the charge description and in the vortex description. The duality between the two descriptions then suggests the possibility that the system undergoes a change in degeneracy while the quantized conductivity remains fixed.Comment: To appear in Phys. Rev.

Performance of the CREAM calorimeter in accelerator beam test

The CREAM calorimeter, designed to measure the spectra of cosmic-ray nuclei from under 1 TeV to 1000 TeV, is a 20 radiation length (X0) deep sampling calorimeter. The calorimeter is comprised of 20 layers of tungsten interleaved with 20 layers of scintillating fiber ribbons, and is preceded by a pair of graphite interaction targets providing about 0.42 proton interaction lengths (\lambda int). The calorimeter was placed in one of CERN's SPS accelerator beams for calibration and testing. Beams of 150 GeV electrons were used for calibration, and a variety of electron, proton, and nuclear fragment beams were used to test the simulation model of the detector. In this paper we discuss the performance of the calorimeter in the electron beam and compare electron beam data with simulation results.The CREAM calorimeter, designed to measure the spectra of cosmic-ray nuclei from under 1 TeV to 1000 TeV, is a 20 radiation length (X0) deep sampling calorimeter. The calorimeter is comprised of 20 layers of tungsten interleaved with 20 layers of scintillating fiber ribbons, and is preceded by a pair of graphite interaction targets providing about 0.42 proton interaction lengths (\lambda int). The calorimeter was placed in one of CERN's SPS accelerator beams for calibration and testing. Beams of 150 GeV electrons were used for calibration, and a variety of electron, proton, and nuclear fragment beams were used to test the simulation model of the detector. In this paper we discuss the performance of the calorimeter in the electron beam and compare electron beam data with simulation results

Flexible Near-Field Wireless Optoelectronics as Subdermal Implants for Broad Applications in Optogenetics

In vivo optogenetics provides unique, powerful capabilities in the dissection of neural circuits implicated in neuropsychiatric disorders. Conventional hardware for such studies, however, physically tethers the experimental animal to an external light source, limiting the range of possible experiments. Emerging wireless options offer important capabilities that avoid some of these limitations, but the current size, bulk, weight, and wireless area of coverage is often disadvantageous. Here, we present a simple but powerful setup based on wireless, near-field power transfer and miniaturized, thin, flexible optoelectronic implants, for complete optical control in a variety of behavioral paradigms. The devices combine subdermal magnetic coil antennas connected to microscale, injectable light-emitting diodes (LEDs), with the ability to operate at wavelengths ranging from UV to blue, green-yellow, and red. An external loop antenna allows robust, straightforward application in a multitude of behavioral apparatuses. The result is a readily mass-producible, user-friendly technology with broad potential for optogenetics applications.114419Ysciescopu

Enhanced understanding of non-axisymmetric intrinsic and controlled field impacts in tokamaks

An extensive study of intrinsic and controlled non-axisymmetric field (dB) impacts in KSTAR has enhanced the understanding about non-axisymmetric field physics and its implications, in particular, on resonant magnetic perturbation (RMP) physics and power threshold (Pth) for L-H transition. The n = 1 intrinsic non-axisymmetric field in KSTAR was measured to remain as low as delta B/ B0 x 4 x 10(-5) even at high-beta plasmas (beta(N) similar to 2), which corresponds to approximately 20% below the targeted ITER tolerance level. As for the RMP edge-localized-modes (ELM) control, robust n = 1 RMP ELM-crash-suppression has been not only sustained for more than similar to 90 iota(E), but also confirmed to be compatible with rotating RMP. An optimal window of radial position of lower X-point (i. e. R-x = 1.44 +/- 0.02 m) proved to be quite critical to reach full n = 1 RMP-driven ELM-crash-suppression, while a constraint of the safety factor could be relaxed (q(95) = 5 +/- 0.25). A more encouraging finding was that even when Rx cannot be positioned in the optimal window, another systematic scan in the vicinity of the previously optimal Rx allows for a new optimal window with relatively small variations of plasma parameters. Also, we have addressed the importance of optimal phasing (i. e. toroidal phase difference between adjacent rows) for n = 1 RMP-driven ELM control, consistent with an ideal plasma response modeling which could predict phasing-dependent ELM suppression windows. In support of ITER RMP study, intentionally misaligned RMPs have been found to be quite effective during ELMmitigation stage in lowering the peaks of divertor heat flux, as well as in broadening the ` wet' areas. Besides, a systematic survey of Pth dependence on non-axisymmetric field has revealed the potential limit of the merit of low intrinsic non-axisymmetry. Considering that the ITER RMP coils are composed of 3-rows, just like in KSTAR, further 3D physics study in KSTAR is expected to help us minimize the uncertainties of the ITER RMP coils, as well as establish an optimal 3D configuration for ITER and future reactors

On the constraints violation in forward dynamics of multibody systems

It is known that the dynamic equations of motion for constrained mechanical multibody systems are frequently formulated using the Newton-Euler’s approach, which is augmented with the acceleration constraint equations. This formulation results in the establishment of a mixed set of partial differential and algebraic equations, which are solved in order to predict the dynamic behavior of general multibody systems. The classical resolution of the equations of motion is highly prone to constraints violation because the position and velocity constraint equations are not fulfilled. In this work, a general and comprehensive methodology to eliminate the constraints violation at the position and velocity levels is offered. The basic idea of the described approach is to add corrective terms to the position and velocity vectors with the intent to satisfy the corresponding kinematic constraint equations. These corrective terms are evaluated as function of the Moore-Penrose generalized inverse of the Jacobian matrix and of the kinematic constraint equations. The described methodology is embedded in the standard method to solve the equations of motion based on the technique of Lagrange multipliers. Finally, the effectiveness of the described methodology is demonstrated through the dynamic modeling and simulation of different planar and spatial multibody systems. The outcomes in terms of constraints violation at the position and velocity levels, conservation of the total energy and computational efficiency are analyzed and compared with those obtained with the standard Lagrange multipliers method, the Baumgarte stabilization method, the augmented Lagrangian formulation, the index-1 augmented Lagrangian and the coordinate partitioning method.The first author expresses his gratitude to the Portuguese Foundation for Science and Technology through the PhD grant (PD/BD/114154/2016). This work has been supported by the Portuguese Foundation for Science and Technology with the reference project UID/EEA/04436/2013, by FEDER funds through the COMPETE 2020 – Programa Operacional Competitividade e Internacionalização (POCI) with the reference project POCI-01-0145-FEDER-006941.info:eu-repo/semantics/publishedVersio

Genotype-Phenotype Correlation in NF1: Evidence for a More Severe Phenotype Associated with Missense Mutations Affecting NF1 Codons 844–848

Neurofibromatosis type 1 (NF1), a common genetic disorder with a birth incidence of 1:2,000–3,000, is characterized by a highly variable clinical presentation. To date, only two clinically relevant intragenic genotype-phenotype correlations have been reported for NF1 missense mutations affecting p.Arg1809 and a single amino acid deletion p.Met922del. Both variants predispose to a distinct mild NF1 phenotype with neither externally visible cutaneous/plexiform neurofibromas nor other tumors. Here, we report 162 individuals (129 unrelated probands and 33 affected relatives) heterozygous for a constitutional missense mutation affecting one of five neighboring NF1 codons—Leu844, Cys845, Ala846, Leu847, and Gly848—located in the cysteine-serine-rich domain (CSRD). Collectively, these recurrent missense mutations affect ∼0.8% of unrelated NF1 mutation-positive probands in the University of Alabama at Birmingham (UAB) cohort. Major superficial plexiform neurofibromas and symptomatic spinal neurofibromas were more prevalent in these individuals compared with classic NF1-affected cohorts (both p < 0.0001). Nearly half of the individuals had symptomatic or asymptomatic optic pathway gliomas and/or skeletal abnormalities. Additionally, variants in this region seem to confer a high predisposition to develop malignancies compared with the general NF1-affected population (p = 0.0061). Our results demonstrate that these NF1 missense mutations, although located outside the GAP-related domain, may be an important risk factor for a severe presentation. A genotype-phenotype correlation at the NF1 region 844–848 exists and will be valuable in the management and genetic counseling of a significant number of individuals

Integrating sequence and array data to create an improved 1000 Genomes Project haplotype reference panel

A major use of the 1000 Genomes Project (1000GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or 'scaffold') of haplotypes across each chromosome. We then phase the sequence data 'onto' this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000GP haplotype reference set for use by the human genetic community. Using a set of validation genotypes at SNP and bi-allelic indels we show that these haplotypes have lower genotype discordance and improved imputation performance into downstream GWAS samples, especially at low-frequency variants. © 2014 Macmillan Publishers Limited. All rights reserved

Measuring progress and projecting attainment on the basis of past trends of the health-related Sustainable Development Goals in 188 countries: an analysis from the Global Burden of Disease Study 2016

The UN’s Sustainable Development Goals (SDGs) are grounded in the global ambition of “leaving no one behind”. Understanding today’s gains and gaps for the health-related SDGs is essential for decision makers as they aim to improve the health of populations. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016), we measured 37 of the 50 health-related SDG indicators over the period 1990–2016 for 188 countries, and then on the basis of these past trends, we projected indicators to 2030

Global, regional, and national under-5 mortality, adult mortality, age-specific mortality, and life expectancy, 1970–2016: a systematic analysis for the Global Burden of Disease Study 2016

BACKGROUND: Detailed assessments of mortality patterns, particularly age-specific mortality, represent a crucial input that enables health systems to target interventions to specific populations. Understanding how all-cause mortality has changed with respect to development status can identify exemplars for best practice. To accomplish this, the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) estimated age-specific and sex-specific all-cause mortality between 1970 and 2016 for 195 countries and territories and at the subnational level for the five countries with a population greater than 200 million in 2016. METHODS: We have evaluated how well civil registration systems captured deaths using a set of demographic methods called death distribution methods for adults and from consideration of survey and census data for children younger than 5 years. We generated an overall assessment of completeness of registration of deaths by dividing registered deaths in each location-year by our estimate of all-age deaths generated from our overall estimation process. For 163 locations, including subnational units in countries with a population greater than 200 million with complete vital registration (VR) systems, our estimates were largely driven by the observed data, with corrections for small fluctuations in numbers and estimation for recent years where there were lags in data reporting (lags were variable by location, generally between 1 year and 6 years). For other locations, we took advantage of different data sources available to measure under-5 mortality rates (U5MR) using complete birth histories, summary birth histories, and incomplete VR with adjustments; we measured adult mortality rate (the probability of death in individuals aged 15-60 years) using adjusted incomplete VR, sibling histories, and household death recall. We used the U5MR and adult mortality rate, together with crude death rate due to HIV in the GBD model life table system, to estimate age-specific and sex-specific death rates for each location-year. Using various international databases, we identified fatal discontinuities, which we defined as increases in the death rate of more than one death per million, resulting from conflict and terrorism, natural disasters, major transport or technological accidents, and a subset of epidemic infectious diseases; these were added to estimates in the relevant years. In 47 countries with an identified peak adult prevalence for HIV/AIDS of more than 0·5% and where VR systems were less than 65% complete, we informed our estimates of age-sex-specific mortality using the Estimation and Projection Package (EPP)-Spectrum model fitted to national HIV/AIDS prevalence surveys and antenatal clinic serosurveillance systems. We estimated stillbirths, early neonatal, late neonatal, and childhood mortality using both survey and VR data in spatiotemporal Gaussian process regression models. We estimated abridged life tables for all location-years using age-specific death rates. We grouped locations into development quintiles based on the Socio-demographic Index (SDI) and analysed mortality trends by quintile. Using spline regression, we estimated the expected mortality rate for each age-sex group as a function of SDI. We identified countries with higher life expectancy than expected by comparing observed life expectancy to anticipated life expectancy on the basis of development status alone. FINDINGS: Completeness in the registration of deaths increased from 28% in 1970 to a peak of 45% in 2013; completeness was lower after 2013 because of lags in reporting. Total deaths in children younger than 5 years decreased from 1970 to 2016, and slower decreases occurred at ages 5-24 years. By contrast, numbers of adult deaths increased in each 5-year age bracket above the age of 25 years. The distribution of annualised rates of change in age-specific mortality rate differed over the period 2000 to 2016 compared with earlier decades: increasing annualised rates of change were less frequent, although rising annualised rates of change still occurred in some locations, particularly for adolescent and younger adult age groups. Rates of stillbirths and under-5 mortality both decreased globally from 1970. Evidence for global convergence of death rates was mixed; although the absolute difference between age-standardised death rates narrowed between countries at the lowest and highest levels of SDI, the ratio of these death rates-a measure of relative inequality-increased slightly. There was a strong shift between 1970 and 2016 toward higher life expectancy, most noticeably at higher levels of SDI. Among countries with populations greater than 1 million in 2016, life expectancy at birth was highest for women in Japan, at 86·9 years (95% UI 86·7-87·2), and for men in Singapore, at 81·3 years (78·8-83·7) in 2016. Male life expectancy was generally lower than female life expectancy between 1970 and 2016, an