More advanced Alzheimer's disease may be associated with a decrease in cerebrospinal fluid pressure

In a recent article, elevated cerebrospinal fluid pressure (CSFP) consistent with very early normal pressure hydrocephalus (NPH), was found in a small subset of Alzheimer's disease (AD) patients (possible AD-NPH hybrids) enrolled in a clinical trial for chronic low-flow cerebrospinal fluid drainage. Also in the same study, was another interesting finding that merits further discussion: a substantial proportion of AD patients had very low CSFP. Based on the characteristics of these subjects, we hypothesize that more advanced AD may be associated with a decrease in CSFP. Reduced CSFP among a group of AD patients could provide a clue towards a better understanding of the high rate of comorbidity reported between AD and glaucoma since it has been shown that mean CSFP is lower in subjects with primary open-angle glaucoma. This could result in an abnormally high trans-lamina cribrosa pressure difference and lead to glaucomatous damage

Submillimeter wavelength survey of the galactic plane from l = -5 deg to l = +62 deg: Structure and energetics of the inner disk

Results from a large scale survey of the first quadrant of the Milky Way galactic plane at wavelengths of 150, 250, and 300 microns with a 10x10 arcmin beam are presented. The emission detected in the survey arises from compact sources, most of which are identified with known peaks of 5 GHz and/or CO emission, and from an underlying diffuse background with a typical angular width of approximately 0.9 deg (FWHM) which accounts for most of the emission. A total of 80 prominent discrete sources were identified and characterized, of which about half were not previously reported at far infrared wavelengths. The total infrared luminosity within the solar circle is approximately 1 to 2x10 to the 10th power L sub 0, and is probably emitted by dust that resides in molecular clouds

The Spectrum of Integrated Millimeter Flux of the Magellanic Clouds and 30-Doradus from TopHat and DIRBE Data

We present measurements of the integrated flux relative to the local background of the Large and Small Magellanic Clouds and the region 30-Doradus (the Tarantula Nebula) in the LMC in four frequency bands centered at 245, 400, 460, and 630 GHz, based on observations made with the TopHat telescope. We combine these observations with the corresponding measurements for the DIRBE bands 8, 9, and 10 to cover the frequency range 245 - 3000 GHz (100 - 1220 micrometers) for these objects. We present spectra for all three objects and fit these spectra to a single-component greybody emission model and report best-fit dust temperatures, optical depths, and emissivity power-law indices, and we compare these results with other measurements in these regions and elsewhere. Using published dust grain opacities, we estimate the mass of the measured dust component in the three regions.Comment: 41 pages, 4 figures. Accepted for publication in Astrophysical Journa

p53 suppresses type II endometrial carcinomas in mice and governs endometrial tumour aggressiveness in humans

Type II endometrial carcinomas are a highly aggressive group of tumour subtypes that are frequently associated with inactivation of the TP53 tumour suppressor gene. We show that mice with endometrium-specific deletion of Trp53 initially exhibited histological changes that are identical to known precursor lesions of type II endometrial carcinomas in humans and later developed carcinomas representing all type II subtypes. The mTORC1 signalling pathway was frequently activated in these precursor lesions and tumours, suggesting a genetic cooperation between this pathway and Trp53 deficiency in tumour initiation. Consistent with this idea, analyses of 521 human endometrial carcinomas identified frequent mTORC1 pathway activation in type I as well as type II endometrial carcinoma subtypes. mTORC1 pathway activation and p53 expression or mutation status each independently predicted poor patient survival. We suggest that molecular alterations in p53 and the mTORC1 pathway play different roles in the initiation of the different endometrial cancer subtypes, but that combined p53 inactivation and mTORC1 pathway activation are unifying pathogenic features among histologically diverse subtypes of late stage aggressive endometrial tumours

A characteristic lengthscale causes anomalous size effects and boundary programmability in mechanical metamaterials

The architecture of mechanical metamaterialsis designed to harness geometry, non-linearity and topology to obtain advanced functionalities such as shape morphing, programmability and one-way propagation. While a purely geometric framework successfully captures the physics of small systems under idealized conditions, large systems or heterogeneous driving conditions remain essentially unexplored. Here we uncover strong anomalies in the mechanics of a broad class of metamaterials, such as auxetics, shape-changers or topological insulators: a non-monotonic variation of their stiffness with system size, and the ability of textured boundaries to completely alter their properties. These striking features stem from the competition between rotation-based deformations---relevant for small systems---and ordinary elasticity, and are controlled by a characteristic length scale which is entirely tunable by the architectural details. Our study provides new vistas for designing, controlling and programming the mechanics of metamaterials in the thermodynamic limit.Comment: Main text has 4 pages, 4 figures + Methods and Supplementary Informatio

The COBE Diffuse Infrared Background Experiment Search for the Cosmic Infrared Background: I. Limits and Detections

The DIRBE on the COBE spacecraft was designed primarily to conduct systematic search for an isotropic CIB in ten photometric bands from 1.25 to 240 microns. The results of that search are presented here. Conservative limits on the CIB are obtained from the minimum observed brightness in all-sky maps at each wavelength, with the faintest limits in the DIRBE spectral range being at 3.5 microns (\nu I_\nu < 64 nW/m^2/sr, 95% CL) and at 240 microns (\nu I_\nu < 28 nW/m^2/sr, 95% CL). The bright foregrounds from interplanetary dust scattering and emission, stars, and interstellar dust emission are the principal impediments to the DIRBE measurements of the CIB. These foregrounds have been modeled and removed from the sky maps. Assessment of the random and systematic uncertainties in the residuals and tests for isotropy show that only the 140 and 240 microns data provide candidate detections of the CIB. The residuals and their uncertainties provide CIB upper limits more restrictive than the dark sky limits at wavelengths from 1.25 to 100 microns. No plausible solar system or Galactic source of the observed 140 and 240 microns residuals can be identified, leading to the conclusion that the CIB has been detected at levels of \nu I_\nu = 25+-7 and 14+-3 nW/m^2/sr at 140 and 240 microns respectively. The integrated energy from 140 to 240 microns, 10.3 nW/m^2/sr, is about twice the integrated optical light from the galaxies in the Hubble Deep Field, suggesting that star formation might have been heavily enshrouded by dust at high redshift. The detections and upper limits reported here provide new constraints on models of the history of energy-releasing processes and dust production since the decoupling of the cosmic microwave background from matter.Comment: 26 pages and 5 figures, accepted for publication in the Astrophyical Journa

Smoking Enhances Risk for New External Genital Warts in Men

Repeat episodes of HPV-related external genital warts reflect recurring or new infections. No study before has been sufficiently powered to delineate how tobacco use, prior history of EGWs and HIV infection affect the risk for new EGWs. Behavioral, laboratory and examination data for 2,835 Multicenter AIDS Cohort Study participants examined at 21,519 semi-annual visits were evaluated. Fourteen percent (391/2835) of men reported or were diagnosed with EGWs at 3% (675/21,519) of study visits. Multivariate analyses showed smoking, prior episodes of EGWs, HIV infection and CD4+ T-lymphocyte count among the infected, each differentially influenced the risk for new EGWs

287 Effects of ruxolitinib cream on pruritus in black patients with atopic dermatitis

Atopic dermatitis (AD) is an inflammatory skin disease that has phenotypic differences across race and can be more severe in Black patients. In two phase 3 identical design studies (TRuE-AD1/TRuE-AD2), patients (≥12 years old with AD for ≥2 years, Investigator’s Global Assessment [IGA] score 2/3, 3%–20% affected body surface area) were randomized (2:2:1) to twice-daily 0.75% or 1.5% ruxolitinib (Janus kinase [JAK]1/JAK 2 inhibitor) cream or vehicle for 8 weeks. Here we describe the effect of ruxolitinib cream on itch in Black patients using pooled data from the 2 studies (n=292). Mean itch numerical rating scale (NRS) score at baseline was 5.3/5.4 for ruxolitinib cream (0.75%/1.5%) and 5.7 for vehicle. Reductions in mean itch NRS score with ruxolitinib cream (0.75%/1.5%) were evident within approximately 12 hours of first application (–0.6/–0.7 vs −0.2 for vehicle), with statistically significant reductions by Day 4 vs vehicle (–1.4/–1.6 vs –0.6; both P\u3c0.05). For those with baseline itch NRS ≥4 (n=187; 64.0%), more patients achieved ≥4-point itch NRS improvement vs vehicle by Day 2 (6.1%/16.4% vs 0%); this increased to 15.9%/26.6% vs 3.0% on Day 7 and 30.1%/43.2% vs 17.5% at Week 8 (P=0.212/P=0.009). More patients applying 0.75%/1.5% ruxolitinib cream vs vehicle reported no days of itch per question 1 of the Patient-Oriented Eczema Measure (POEM) at Week 2 (19.0%/19.4% vs 5.3%); this increased at Week 8 (34.0%/30.8% vs 12.2%). In summary, ruxolitinib cream monotherapy over 8 weeks was associated with rapid and considerable itch relief in Black patients with AD

275 Effects of ruxolitinib cream on sleep and quality of life over 52 weeks in black patients with atopic dermatitis

Atopic dermatitis (AD) is an inflammatory skin disease with phenotypic differences across race and can affect sleep and quality of life (QoL). In 2 phase 3 studies of identical design (TRuE-AD1/TRuE-AD2), patients (pts; ≥12 y with AD for ≥2 y; Investigator’s Global Assessment score 2/3; 3%–20% affected body surface area) were randomized (2:2:1) to twice-daily 0.75% or 1.5% ruxolitinib (RUX; Janus kinase [JAK]1/JAK2 inhibitor) cream or vehicle for 8 wk (continuous treatment), followed by a long-term safety period (LTS; as-needed treatment) up to Wk 52. Pts randomized to RUX cream remained on their regimen during the LTS; pts on vehicle were rerandomized to either RUX cream strength. For Black pts who were initially randomized to the 0.75% RUX cream/1.5% RUX cream/vehicle to 0.75% RUX cream/vehicle to 1.5% RUX cream groups and continued in the LTS (n=91/97/25/22), sleep-related impairment and sleep disturbance scores per Patient-Reported Outcomes Measurement Information System at baseline (BL) were 16.3/16.4/15.0/17.5 and 18.9/19.7/17.9/19.8, respectively. Scores had decreased (less impairment) at LTS start in the RUX cream groups (Wk 8; 14.2/14.7/16.1/15.5 and 16.7/17.5/19.0/19.4) and were below BL at Wk 52 in all groups (14.3/14.8/13.9/14.4 and 18.0/18.0/17.4/16.3). Dermatology Life Quality Index (DLQI) scores were decreased at Wk 8 (mean change from BL, −7.4/−6.6/−3.8/−4.8); decreased scores were maintained to Wk 52 (−7.1/−6.5/−5.6/−8.8). Results were similar for children’s DLQI (Wk 8, −4.0/−6.9/−4.0/−3.0 [n=12/9/1/3]; Wk 52, −5.6/−11.6/−12.0/−7.3 [n=9/7/1/4]). In summary, sleep and QoL improved with RUX cream; improvements were maintained for 44 wk with as-needed use in Black pts