Effects of Parkinson’s disease on optic flow perception for heading direction during navigation

Visuoperceptual disorders have been identified in individuals with Parkinson’s disease (PD) and may affect the perception of optic flow for heading direction during navigation. Studies in healthy subjects have confirmed that heading direction can be determined by equalizing the optic flow speed (OS) between visual fields. The present study investigated the effects of PD on the use of optic flow for heading direction, walking parameters, and interlimb coordination during navigation, examining the contributions of OS and spatial frequency (dot density). Twelve individuals with PD without dementia, 18 age-matched normal control adults (NC), and 23 young control adults (YC) walked through a virtual hallway at about 0.8 m/s. The hallway was created by random dots on side walls. Three levels of OS (0.8, 1.2, and 1.8 m/s) and dot density (1, 2, and 3 dots/m2) were presented on one wall while on the other wall, OS and dot density were fixed at 0.8 m/s and 3 dots/m2, respectively. Three-dimensional kinematic data were collected, and lateral drift, walking speed, stride frequency and length, and frequency, and phase relations between arms and legs were calculated. A significant linear effect was observed on lateral drift to the wall with lower OS for YC and NC, but not for PD. Compared to YC and NC, PD veered more to the left under OS and dot density conditions. The results suggest that healthy adults perceive optic flow for heading direction. Heading direction in PD may be more affected by the asymmetry of dopamine levels between the hemispheres and by motor lateralization as indexed by handedness.Published versio

Ixekizumab Efficacy and Safety with and without Concomitant Conventional Disease-modifying Antirheumatic Drugs (cDMARDs) in Biologic DMARD (bDMARD)-naive Patients with Active Psoriatic Arthritis (PsA): Results from SPIRIT-P1

Objective: To evaluate the efficacy and safety of ixekizumab alone or with concomitant conventional disease-modifying antirheumatic drugs (cDMARDs) versus placebo in patients with active psoriatic arthritis (PsA) as part of a SPIRIT-P1 subgroup analysis (NCT01695239). Methods: Patients were stratified by cDMARD use (concomitant cDMARDs use (including methotrexate) or none (past or naive use)) and randomly assigned to treatment groups (ixekizumab 80 mg every 4 weeks (IXEQ4W) or every 2 weeks (IXEQ2W) or placebo). Efficacy was evaluated versus placebo at week 24 by the American College of Rheumatology criteria (ACR20/50/70), modified total Sharp score and Health Assessment Questionnaire-Disability Index (HAQ-DI). Safety was assessed according to cDMARD status. Results: Regardless of concomitant cDMARD usage, ACR20, ACR50 and ACR70 response rates were significantly higher versus placebo with IXEQ4W and IXEQ2W. The proportion of patients achieving HAQ-DI minimal clinically important difference was significantly higher versus placebo with IXEQ4W with concomitant cDMARD use and IXEQ2W, regardless of concomitant cDMARD use. Treatment-emergent adverse events (AE) were more frequent versus placebo for either ixekizumab-dosing regimen, regardless of concomitant cDMARD use. Serious AEs were not higher versus placebo, regardless of concomitant cDMARD use. Conclusion: Ixekizumab treatment improved measures of disease activity and physical function in patients with active PsA relative to placebo, when used with or without concomitant cDMARD therapy

On the Planet and the Disk of CoKuTau/4

Spitzer observations of the young star CoKuTau/4 reveal a disk with a 10 AU hole that is most likely caused by a newly formed planet. Assuming that the planet opened a gap in the viscous disk, we estimate that the planet mass is greater than 0.1 Jupiter masses. This estimate depends on a lower limit to the disk viscosity derived from the time scale needed to accrete the inner disk, creating the now detectable hole. The planet migration time scale must at least modestly exceed the time for the spectrally inferred hole to clear. The proximity of the planet to the disk edge implied by our limits suggests that the latter is perturbed by the nearby planet and may exhibit a spiral pattern rotating with the planet. This pattern might be resolved with current ground based mid-infrared cameras and optical cameras on the Hubble Space Telescope. The required sub-Myr planet formation may challenge core accretion formation models. However, we find that only if the planet mass is larger than about 10 Jupiter masses, allowing for a high enough surface density without inducing migration, would formation by direct gravitational instability be possible.Comment: Submitted to ApJ

American Geriatrics Society and National Institute on Aging Bench-to-Bedside conference: sensory impairment and cognitive decline in older adults

This article summarizes the presentations and recommendations of the tenth annual American Geriatrics Society and National Institute on Aging Bench‐to‐Bedside research conference, “Sensory Impairment and Cognitive Decline,” on October 2–3, 2017, in Bethesda, Maryland. The risk of impairment in hearing, vision, and other senses increases with age, and almost 15% of individuals aged 70 and older have dementia. As the number of older adults increases, sensory and cognitive impairments will affect a growing proportion of the population. To limit its scope, this conference focused on sensory impairments affecting vision and hearing. Comorbid vision, hearing, and cognitive impairments in older adults are more common than would be expected by chance alone, suggesting that some common mechanisms might affect these neurological systems. This workshop explored the mechanisms and consequences of comorbid vision, hearing, and cognitive impairment in older adults; effects of sensory loss on the aging brain; and bench‐to‐bedside innovations and research opportunities. Presenters and participants identified many research gaps and questions; the top priorities fell into 3 themes: mechanisms, measurement, and interventions. The workshop delineated specific research questions that provide opportunities to improve outcomes in this growing population.Funding was provided by National Institutes of Health (NIH) Grant U13 AG054139-01. Dr. Whitson's efforts and contributions were supported by R01AG043438, R24AG045050, UH2AG056925, and 5P30AG028716. Dr. Lin's effort and contributions were also supported by R01AG055426, R01HL096812, and R33DC015062. (U13 AG054139-01 - National Institutes of Health (NIH); R01AG043438; R24AG045050; UH2AG056925; 5P30AG028716; R01AG055426; R01HL096812; R33DC015062)Accepted manuscrip

GPER-induced signaling is essential for the survival of breast cancer stem cells.

G protein-coupled estrogen receptor-1 (GPER), a member of the G protein-coupled receptor (GPCR) superfamily, mediates estrogen-induced proliferation of normal and malignant breast epithelial cells. However, its role in breast cancer stem cells (BCSCs) remains unclear. Here we showed greater expression of GPER in BCSCs than non-BCSCs of three patient-derived xenografts of ER- /PR+ breast cancers. GPER silencing reduced stemness features of BCSCs as reflected by reduced mammosphere forming capacity in vitro, and tumor growth in vivo with decreased BCSC populations. Comparative phosphoproteomics revealed greater GPER-mediated PKA/BAD signaling in BCSCs. Activation of GPER by its ligands, including tamoxifen (TMX), induced phosphorylation of PKA and BAD-Ser118 to sustain BCSC characteristics. Transfection with a dominant-negative mutant BAD (Ser118Ala) led to reduced cell survival. Taken together, GPER and its downstream signaling play a key role in maintaining the stemness of BCSCs, suggesting that GPER is a potential therapeutic target for eradicating BCSCs

Suomi NPP VIIRS Prelaunch and On-orbit Geometric Calibration and Characterization

The Visible Infrared Imager Radiometer Suite (VIIRS) sensor was launched 28 October 2011 on the Suomi National Polarorbiting Partnership (SNPP) satellite. VIIRS has 22 spectral bands covering the spectrum between 0.412 m and 12.01 m, including 16 moderate resolution bands (M-bands) with a spatial resolution of 750 m at nadir, 5 imaging resolution bands (I-bands) with a spatial resolution of 375 m at nadir, and 1 day-night band (DNB) with a near-constant 750 m spatial resolution throughout the scan. These bands are located in a visible and near infrared (VisNIR) focal plane assembly (FPA), a short- and mid-wave infrared (SWMWIR) FPA and a long-wave infrared (LWIR) FPA. All bands, except the DNB, are co-registered for proper environmental data records (EDRs) retrievals. Observations from VIIRS instrument provide long-term measurements of biogeophysical variables for climate research and polar satellite data stream for the operational communitys use in weather forecasting and disaster relief and other applications. Well Earth-located (geolocated) instrument data is important to retrieving accurate biogeophysical variables. This paper describes prelaunch pointing and alignment measurements, and the two sets of on-orbit correction of geolocation errors, the first of which corrected error from 1,300 m to within 75 m (20 I-band pixel size), and the second of which fine tuned scan angle dependent errors, bringing VIIRS geolocation products to high maturity in one and a half years of the SNPP VIIRS on-orbit operations. Prelaunch calibration and the on-orbit characterization of sensor spatial impulse responses and band-to-band co-registration (BBR) are also described

Lack of uniform diagnostic criteria for cervical radiculopathy in conservative intervention studies: A systematic review

Purpose: Cervical radiculopathy (CR) is a common diagnosis. It is unclear if intervention studies use uniform definitions and criteria for patient selection. Our objective was to assess the uniformity of diagnostic criteria and definitions used in intervention studies to select patients with CR. Methods: We electronically searched the Cochrane Controlled Trials Register, MEDLINE, EMBASE and CINAHL. Studies were included when evaluating conservative interventions in randomised clinical trials (RCTs) in patients with CR. Selection criteria and definitions for patients with CR were extracted and evaluated on their uniformity. Results: Thirteen RCTs were included. Pain was used as an inclusion criterion in 11 studies. Inclusion based on the duration and location of pain varied between studies. Five studies used sensory symptoms in the arm as inclusion crite