Longitudinal Tracking of Human Fetal Cells Labeled with Super Paramagnetic Iron Oxide Nanoparticles in the Brain of Mice with Motor Neuron Disease

Stem Cell (SC) therapy is one of the most promising approaches for the treatment of Amyotrophic Lateral Sclerosis (ALS). Here we employed Super Paramagnetic Iron Oxide nanoparticles (SPIOn) and Hoechst 33258 to track human Amniotic Fluid Cells (hAFCs) after transplantation in the lateral ventricles of wobbler (a murine model of ALS) and healthy mice. By in vitro, in vivo and ex vivo approaches we found that: 1) the main physical parameters of SPIOn were maintained over time; 2) hAFCs efficiently internalized SPIOn into the cytoplasm while Hoechst 33258 labeled nuclei; 3) SPIOn internalization did not alter survival, cell cycle, proliferation, metabolism and phenotype of hAFCs; 4) after transplantation hAFCs rapidly spread to the whole ventricular system, but did not migrate into the brain parenchyma; 5) hAFCs survived for a long time in the ventricles of both wobbler and healthy mice; 6) the transplantation of double-labeled hAFCs did not influence mice survival

The Zwicky Transient Facility: Science Objectives

The Zwicky Transient Facility (ZTF), a public–private enterprise, is a new time-domain survey employing a dedicated camera on the Palomar 48-inch Schmidt telescope with a 47 deg2 field of view and an 8 second readout time. It is well positioned in the development of time-domain astronomy, offering operations at 10% of the scale and style of the Large Synoptic Survey Telescope (LSST) with a single 1-m class survey telescope. The public surveys will cover the observable northern sky every three nights in g and r filters and the visible Galactic plane every night in g and r. Alerts generated by these surveys are sent in real time to brokers. A consortium of universities that provided funding (“partnership”) are undertaking several boutique surveys. The combination of these surveys producing one million alerts per night allows for exploration of transient and variable astrophysical phenomena brighter than r∼20.5 on timescales of minutes to years. We describe the primary science objectives driving ZTF, including the physics of supernovae and relativistic explosions, multi-messenger astrophysics, supernova cosmology, active galactic nuclei, and tidal disruption events, stellar variability, and solar system objects. © 2019. The Astronomical Society of the Pacific

GROWTH on S190425z: Searching Thousands of Square Degrees to Identify an Optical or Infrared Counterpart to a Binary Neutron Star Merger with the Zwicky Transient Facility and Palomar Gattini-IR

The third observing run by LVC has brought the discovery of many compact binary coalescences. Following the detection of the first binary neutron star merger in this run (LIGO/Virgo S190425z), we performed a dedicated follow-up campaign with the Zwicky Transient Facility (ZTF) and Palomar Gattini-IR telescopes. The initial skymap of this single-detector gravitational wave (GW) trigger spanned most of the sky observable from Palomar Observatory. Covering 8000 deg2 of the initial skymap over the next two nights, corresponding to 46% integrated probability, ZTF system achieved a depth of ≈21 m AB in g- and r-bands. Palomar Gattini-IR covered 2200 square degrees in J-band to a depth of 15.5 mag, including 32% integrated probability based on the initial skymap. The revised skymap issued the following day reduced these numbers to 21% for the ZTF and 19% for Palomar Gattini-IR. We narrowed 338,646 ZTF transient "alerts" over the first two nights of observations to 15 candidate counterparts. Two candidates, ZTF19aarykkb and ZTF19aarzaod, were particularly compelling given that their location, distance, and age were consistent with the GW event, and their early optical light curves were photometrically consistent with that of kilonovae. These two candidates were spectroscopically classified as young core-collapse supernovae. The remaining candidates were ruled out as supernovae. Palomar Gattini-IR did not identify any viable candidates with multiple detections only after merger time. We demonstrate that even with single-detector GW events localized to thousands of square degrees, systematic kilonova discovery is feasible

GROWTH on GW190425: Searching thousands of square degrees to identify an optical or infrared counterpart to a binary neutron star merger with the Zwicky Transient Facility and Palomar Gattini IR

The beginning of the third observing run by the network of gravitational-wave detectors has brought the discovery of many compact binary coalescences. Prompted by the detection of the first binary neutron star merger in this run (GW190425 / LIGO/Virgo S190425z), we performed a dedicated follow-up campaign with the Zwicky Transient Facility (ZTF) and Palomar Gattini-IR telescopes. As it was a single gravitational-wave detector discovery, the initial skymap spanned most of the sky observable from Palomar Observatory, the site of both instruments. Covering 8000 deg$^2$ of the inner 99\% of the initial skymap over the next two nights, corresponding to an integrated probability of 46\%, the ZTF system achieved a depth of $\approx$\,21 $m_\textrm{AB}$ in $g$- and $r$-bands. Palomar Gattini-IR covered a total of 2200 square degrees in $J$-band to a depth of 15.5\,mag, including 32\% of the integrated probability based on the initial sky map. However, the revised skymap issued the following day reduced these numbers to 21\% for the Zwicky Transient Facility and 19\% for Palomar Gattini-IR. Out of the 338,646 ZTF transient "alerts" over the first two nights of observations, we narrowed this list to 15 candidate counterparts. Two candidates, ZTF19aarykkb and ZTF19aarzaod were particularly compelling given that their location, distance, and age were consistent with the gravitational-wave event, and their early optical lightcurves were photometrically consistent with that of kilonovae. These two candidates were spectroscopically classified as young core-collapse supernovae. The remaining candidates were photometrically or spectroscopically ruled-out as supernovae. Palomar Gattini-IR identified one fast evolving infrared transient after the merger, PGIR19bn, which was later spectroscopically classified as an M-dwarf flare. [abridged

The Zwicky Transient Facility: System Overview, Performance, and First Results

The Zwicky Transient Facility (ZTF) is a new optical time-domain survey that uses the Palomar 48 inch Schmidt telescope. A custom-built wide-field camera provides a 47 deg^2 field of view and 8 s readout time, yielding more than an order of magnitude improvement in survey speed relative to its predecessor survey, the Palomar Transient Factory. We describe the design and implementation of the camera and observing system. The ZTF data system at the Infrared Processing and Analysis Center provides near-real-time reduction to identify moving and varying objects. We outline the analysis pipelines, data products, and associated archive. Finally, we present on-sky performance analysis and first scientific results from commissioning and the early survey. ZTF's public alert stream will serve as a useful precursor for that of the Large Synoptic Survey Telescope

Does the effect of lifestyle intervention for individuals with diabetes vary by food insecurity status? A preplanned subgroup analysis of the REAL HEALTH randomized clinical trial

Introduction We aimed to test the effectiveness of a lifestyle intervention (LI) for individuals with food insecurity and type 2 diabetes.Research design and methods Adults with type 2 diabetes, body mass index ≥25 kg/m2 (or ≥23 kg/m2 if Asian), hemoglobin A1c of 6.5%–11.5% (48–97 mmol/mol) and who were willing to lose 5%–7% bodyweight were enrolled in REAL HEALTH-Diabetes. This practice-based randomized clinical trial compared LI (delivered inperson or by telephone) with medical nutrition therapy (MNT) on weight loss at 6 and 12 months. Two or more affirmative responses on the six-item US Department of Agriculture Food Security Survey Module indicated food insecurity. In this prespecified subgroup analysis, we tested using linear mixed effects models whether the intervention effect varied by food security status.Results Of 208 participants, 13% were food insecure. Those with food insecurity were more likely to be racial/ethnic minorities (p<0.001) and have lower education (p<0.001). LI, versus MNT, led to greater weight loss at 6 months (5.1% lost vs 1.1% lost; p<0.0001) and 12 months (4.7% lost vs 2.0% lost; p=0.0005). The intervention effect was similar regardless of food security status (5.1% bodyweight lost vs 1.1% in food secure participants and 5.1% bodyweight lost vs 1.3% in food insecure participants at 6 months; 4.7% bodyweight lost vs 2.1% in food secure participants and 4.5% bodyweight lost vs 0.9% in food insecure participants at 12 months; p for interaction=0.99).Conclusions The REAL HEALTH-Diabetes lifestyle intervention led to meaningful weight loss for individuals with food insecurity and type 2 diabetes.Trial registration number NCT02320253

Deficits and Disparities in Early Uptake of GLP-1 Receptor Agonists and SGLT2 Inhibitors among Medicare-insured Adults Following a New Diagnosis of Cardiovascular Disease or Heart Failure

   Objective: To examine the association of race/ethnicity and socioeconomic deprivation with initiation of guideline-recommended diabetes medications with cardiovascular benefit (glucagon-like peptide-1 receptor agonists (GLP1-RA) and sodium-glucose co-transporter-2 inhibitors (SGLT2i)) among older adults with type 2 diabetes (T2D) and either incident atherosclerotic cardiovascular disease (ASCVD) or congestive heart failure (CHF). Research Design and Methods: Using Medicare data (2016-2019), we identified 4,057,725 individuals over age 65 with T2D and either incident ASCVD or CHF. We estimated incidence rates (IR) and hazard ratios (HR) of GLP1-RA or SGLT2i initiation within 180 days by race/ethnicity and zip code-level Social Deprivation Index (SDI) using adjusted Cox proportional hazards models.  Results: IRs of GLP1-RA or SGLT2i initiation increased over time but remained low ( Conclusions: Among older adults with T2D and either ASCVD or CHF, initiation of GLP1-RA or SGLT2i was low, suggesting a substantial deficit in delivery of guideline-recommended care or treatment barriers. Individuals of Black and Other race/ethnicity and those with higher area-level socioeconomic deprivation were less likely to initiate these medications.</p

Algorithmic identification of atypical diabetes in electronic health record (EHR) systems.

AimsUnderstanding atypical forms of diabetes (AD) may advance precision medicine, but methods to identify such patients are needed. We propose an electronic health record (EHR)-based algorithmic approach to identify patients who may have AD, specifically those with insulin-sufficient, non-metabolic diabetes, in order to improve feasibility of identifying these patients through detailed chart review.MethodsPatients with likely T2D were selected using a validated machine-learning (ML) algorithm applied to EHR data. "Typical" T2D cases were removed by excluding individuals with obesity, evidence of dyslipidemia, antibody-positive diabetes, or cystic fibrosis. To filter out likely type 1 diabetes (T1D) cases, we applied six additional "branch algorithms," relying on various clinical characteristics, which resulted in six overlapping cohorts. Diabetes type was classified by manual chart review as atypical, not atypical, or indeterminate due to missing information.ResultsOf 114,975 biobank participants, the algorithms collectively identified 119 (0.1%) potential AD cases, of which 16 (0.014%) were confirmed after expert review. The branch algorithm that excluded T1D based on outpatient insulin use had the highest percentage yield of AD (13 of 27; 48.2% yield). Together, the 16 AD cases had significantly lower BMI and higher HDL than either unselected T1D or T2D cases identified by ML algorithms (PConclusionOur EHR-based algorithms followed by manual chart review identified collectively 16 individuals with AD, representing 0.22% of biobank enrollees with T2D. With a maximum yield of 48% cases after manual chart review, our algorithms have the potential to drastically improve efficiency of AD identification. Recognizing patients with AD may inform on the heterogeneity of T2D and facilitate enrollment in studies like the Rare and Atypical Diabetes Network (RADIANT)