Three Wide-Separation L dwarf Companions from the Two Micron All Sky Survey: Gl 337C, Gl 618.1B, and HD 89744B

We present two confirmed wide separation L-dwarf common proper motion companions to nearby stars and one candidate identified from the Two Micron All Sky Survey. Spectral types from optical spectroscopy are L0 V, L2.5 V, and L8 V. Near-infrared low resolution spectra of the companions are provided as well as a grid of known objects spanning M6 V -- T dwarfs to support spectral type assignment for these and future L-dwarfs in the z'JHK bands. Using published measurements, we estimate ages of the companions from physical properties of the primaries. These crude ages allow us to estimate companion masses using theoretical low-mass star and brown dwarf evolutionary models. The new L-dwarfs in this paper bring the number of known wide-binary (Separation >= 100 AU) L-dwarf companions of nearby stars to nine. One of the L-dwarfs is a wide separation companion to the F7 IV-V + extrasolar planet system HD89744Ab.Comment: 20 pages including 6 tables and 4 figures, AJ, in pres

Magnetotactic bacteria for cancer therapy

Magnetotactic bacteria (MTB) are aquatic microorganisms that are able to biomineralize membrane-enclosed magnetic nanoparticles called magnetosomes. Inside the MTB, magnetosomes are arranged in a chain that allows MTB to align and navigate along the Earth's magnetic field. When isolated from the MTB, magnetosomes display a number of potential applications for targeted cancer therapies, such as magnetic hyperthermia, localized drug delivery, or tumor monitoring. The characteristics and properties of magnetosomes for these applications exceed in several aspects those of synthetic magnetic nanoparticles. Likewise, the whole MTB can also be considered as promising agents for cancer treatment, taking advantage of their self-propulsion capability provided by their flagella and the guidance capabilities ensured by their magnetosome chain. Indeed, MTB are envisaged as nanobiots that can be guided and manipulated by external magnetic fields and are naturally attracted toward hypoxic areas, such as the tumor regions, while retaining the therapeutic and imaging capacities of the isolated magnetosomes. Moreover, unlike most of the bacteria currently tested in clinical trials for cancer therapy, MTB are not pathogenic but could be engineered to deliver and/or express specific cytotoxic molecules. In this article, we will review the progress and perspectives of this emerging research field and will discuss the main challenges to overcome before the use of MTB can be successfully applied in the clinic.The Spanish and Basque Governments are acknowledged for funding under Project Nos. MAT2017-83631-C3-R and IT-1245-19, respectively

A Planet at 5 AU Around 55 Cancri

We report precise Doppler shift measurements of 55 Cancri (G8V) obtained from 1989 to 2002 at Lick Observatory. The velocities reveal evidence for an outer planetary companion to 55 Cancri orbiting at 5.5 AU. The velocities also confirm a second, inner planet at 0.11 AU. The outer planet is the first extrasolar planet found that orbits near or beyond the orbit of Jupiter. It was drawn from a sample of ~50 stars observed with sufficient duration and quality to detect a giant planet at 5 AU, implying that such planets are not rare. The properties of this jupiter analog may be compared directly to those of the Jovian planets in our Solar System. Its eccentricity is modest, e=0.16, compared with e=0.05 for both Jupiter and Saturn. Its mass is at least 4.0 jupiter masses (M sin i). The two planets do not perturb each other significantly. Moreover, a third planet of sub-Jupiter mass could easily survive in between these two known planets. Indeed a third periodicity remains in the velocity measurements with P = 44.3 d and a semi-amplitude of 13 m/s. This periodicity is caused either by a third planet at a=0.24 AU or by inhomogeneities on the stellar surface that rotates with period 42 d. The planet interpretation is more likely, as the stellar surface is quiet, exhibiting log(R'_{HK}) = -5.0 and brightness variations less than 1 millimag, and any hypothetical surface inhomogeneity would have to persist in longitude for 14 yr. Even with all three planets, an additional planet of terrestrial--mass could orbit stably at ~1 AU. The star 55 Cancri is apparently a normal, middle-aged main sequence star with a mass of 0.95 solar masses, rich in heavy elements ([Fe/H] = +0.27). This high metallicity raises the issue of the relationship between its age, rotation, and chromosphere.Comment: 47 pages, 4 tables, 12 figures, uses AASTE

Structure and Evolution of Nearby Stars with Planets II. Physical Properties of ~1000 Cool Stars from the SPOCS Catalog

We derive detailed theoretical models for 1074 nearby stars from the SPOCS (Spectroscopic Properties of Cool Stars) Catalog. The California and Carnegie Planet Search has obtained high-quality echelle spectra of over 1000 nearby stars taken with the Hamilton spectrograph at Lick Observatory, the HIRES spectrograph at Keck, and UCLES at the Anglo Australian Observatory. A uniform analysis of the high-resolution spectra has yielded precise stellar parameters, enabling systematic error analyses and accurate theoretical stellar modeling. We have created a large database of theoretical stellar evolution tracks using the Yale Stellar Evolution Code (YREC) to match the observed parameters of the SPOCS stars. Our very dense grids of evolutionary tracks eliminate the need for interpolation between stellar evolutionary tracks and allow precise determinations of physical stellar parameters (mass, age, radius, size and mass of the convective zone, etc.). Combining our stellar models with the observed stellar atmospheric parameters and uncertainties, we compute the likelihood for each set of stellar model parameters separated by uniform time steps along the stellar evolutionary tracks. The computed likelihoods are used for a Bayesian analysis to derive posterior probability distribution functions for the physical stellar parameters of interest. We provide a catalog of physical parameters for 1074 stars that are based on a uniform set of high quality spectral observations, a uniform spectral reduction procedure, and a uniform set of stellar evolutionary models. We explore this catalog for various possible correlations between stellar and planetary properties, which may help constrain the formation and dynamical histories of other planetary systems.Comment: 28 pages, 19 figures, 5 tables, Accepted for publication in ApJS; the catalog of stellar parameters is available at http://exoplanets.org/SPOCS_evol.htm

On the buildup of massive early-type galaxies at z<~1. I- Reconciling their hierarchical assembly with mass-downsizing

Several studies have tried to ascertain whether or not the increase in abundance of the early-type galaxies (E-S0a's) with time is mainly due to major mergers, reaching opposite conclusions. We have tested it directly through semi-analytical modelling, by studying how the massive early-type galaxies with log(M_*/Msun)>11 at z~0 (mETGs) would have evolved backwards-in-time, under the hypothesis that each major merger gives place to an early-type galaxy. The study was carried out just considering the major mergers strictly reported by observations at each redshift, and assuming that gas-rich major mergers experience transitory phases of dust-reddened, star-forming galaxies (DSFs). The model is able to reproduce the observed evolution of the galaxy LFs at z<~1, simultaneously for different rest-frame bands (B, I, and K) and for different selection criteria on color and morphology. It also provides a framework in which apparently-contradictory results on the recent evolution of the luminosity function (LF) of massive, red galaxies can be reconciled, just considering that observational samples of red galaxies can be significantly contaminated by DSFs. The model proves that it is feasible to build up ~50-60% of the present-day mETG population at z<~1 and to reproduce the observational excess by a factor of ~4-5 of late-type galaxies at 0.8<z<1 through the coordinated action of wet, mixed, and dry major mergers, fulfilling global trends that are in general agreement with mass-downsizing. The bulk of this assembly takes place during ~1 Gyr elapsed at 0.8<z<1. The model suggests that major mergers have been the main driver for the observational migration of mass from the massive-end of the blue galaxy cloud to that of the red sequence in the last ~8 Gyr.(Abridged)Comment: Accepted for publication in Astronomy & Astrophysics; 21 pages, 8 figures. Minor corrections included, shortened title. Results and conclusions unchange

Differential body composition effects of protease inhibitors recommended for initial treatment of HIV infection: A randomized clinical trial

This article has been accepted for publication in Clinical Infectious Diseases ©2014 The Authors .Published by Oxford University Press on Clinical Infectious Disease 60.5. DOI: 10.1093/cid/ciu898Background. It is unclear whether metabolic or body composition effects may differ between protease inhibitor-based regimens recommended for initial treatment of HIV infection. Methods. ATADAR is a phase IV, open-label, multicenter randomized clinical trial. Stable antiretroviral-naive HIV-infected adults were randomly assigned to atazanavir/ritonavir 300/100 mg or darunavir/ritonavir 800/100 mg in combination with tenofovir/emtricitabine daily. Pre-defined end-points were treatment or virological failure, drug discontinuation due to adverse effects, and laboratory and body composition changes at 96 weeks. Results. At 96 weeks, 56 (62%) atazanavir/ritonavir and 62 (71%) darunavir/ritonavir patients remained free of treatment failure (estimated difference 8.2%; 95%CI -0.6 to 21.6); and 71 (79%) atazanavir/ritonavir and 75 (85%) darunavir/ritonavir patients remained free of virological failure (estimated difference 6.3%; 95%CI -0.5 to 17.6). Seven vs. five patients discontinued atazanavir/ritonavir or darunavir/ritonavir due to adverse effects. Total and HDL cholesterol similarly increased in both arms, but triglycerides increased more in atazanavir/ritonavir arm. At 96 weeks, body fat (estimated difference 2862.2 gr; 95%CI 726.7 to 4997.7; P=0.0090), limb fat (estimated difference 1403.3 gr; 95%CI 388.4 to 2418.2; P=0.0071), and subcutaneous abdominal adipose tissue (estimated difference 28.4 cm2; 95%CI 1.9 to 55.0; P=0.0362) increased more in atazanavir/ritonavir than in darunavir/ritonavir arm. Body fat changes in atazanavir/ritonavir arm were associated with higher insulin resistance. Conclusions. We found no major differences between atazanavir/ritonavir and darunavir/ritonavir in efficacy, clinically-relevant side effects, or plasma cholesterol fractions. However, atazanavir/ritonavir led to higher triglycerides and total and subcutaneous fat than darunavir/ritonavir and fat gains with atazanavir/ritonavir were associated with insulin resistanceThis is an Investigator Sponsored Research study. It was supported in part by research grants from Bristol‐Myers Squibb and Janssen‐Cilag; Instituto de Salud Carlos III (PI12/01217) and Red Temática Cooperativa de Investigación en SIDA G03/173 (RIS‐EST11), Ministerio de Ciencia e Innovación, Spain. (Registration number: NCT01274780; registry name: ATADAR; EUDRACT; 2010‐021002‐38)

Translational Stroke Research Using a Rabbit Embolic Stroke Model: A Correlative Analysis Hypothesis for Novel Therapy Development

Alteplase (tissue plasminogen activator, tPA) is currently the only FDA-approved treatment that can be given to acute ischemic stroke (AIS) patients if patients present within 3 h of an ischemic stroke. After 14 years of alteplase clinical research, evidence now suggests that the therapeutic treatment window can be expanded 4.5 h, but this is not formally approved by the FDA. Even though there remains a significant risk of intracerebral hemorrhage associated with alteplase administration, there is an increased chance of favorable outcome with tPA treatment. Over the last 30 years, the use of preclinical models has assisted with the search for new effective treatments for stroke, but there has been difficulty with the translation of efficacy from animals to humans. Current research focuses on the development of new and potentially useful thrombolytics, neuroprotective agents, and devices which are also being tested for efficacy in preclinical and clinical trials. One model in particular, the rabbit small clot embolic stroke model (RSCEM) which was developed to test tPA for efficacy, remains the only preclinical model used to gain FDA approval of a therapeutic for stroke. Correlative analyses from existing preclinical translational studies and clinical trials indicate that there is a therapeutic window ratio (ARR) of 2.43-3 between the RSCEM and AIS patients. In conclusion, the RSCEM can be used as an effective translational tool to gauge the clinical potential of new treatments

Sarilumab in patients admitted to hospital with severe or critical COVID-19: a randomised, double-blind, placebo-controlled, phase 3 trial

Background: Elevated proinflammatory cytokines are associated with greater COVID-19 severity. We aimed to assess safety and efficacy of sarilumab, an interleukin-6 receptor inhibitor, in patients with severe (requiring supplemental oxygen by nasal cannula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or extracorporeal support) COVID-19. Methods: We did a 60-day, randomised, double-blind, placebo-controlled, multinational phase 3 trial at 45 hospitals in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia, and Spain. We included adults (≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and pneumonia, who required oxygen supplementation or intensive care. Patients were randomly assigned (2:2:1 with permuted blocks of five) to receive intravenous sarilumab 400 mg, sarilumab 200 mg, or placebo. Patients, care providers, outcome assessors, and investigators remained masked to assigned intervention throughout the course of the study. The primary endpoint was time to clinical improvement of two or more points (seven point scale ranging from 1 [death] to 7 [discharged from hospital]) in the modified intention-to-treat population. The key secondary endpoint was proportion of patients alive at day 29. Safety outcomes included adverse events and laboratory assessments. This study is registered with ClinicalTrials.gov, NCT04327388; EudraCT, 2020-001162-12; and WHO, U1111-1249-6021. Findings: Between March 28 and July 3, 2020, of 431 patients who were screened, 420 patients were randomly assigned and 416 received placebo (n=84 [20%]), sarilumab 200 mg (n=159 [38%]), or sarilumab 400 mg (n=173 [42%]). At day 29, no significant differences were seen in median time to an improvement of two or more points between placebo (12·0 days [95% CI 9·0 to 15·0]) and sarilumab 200 mg (10·0 days [9·0 to 12·0]; hazard ratio [HR] 1·03 [95% CI 0·75 to 1·40]; log-rank p=0·96) or sarilumab 400 mg (10·0 days [9·0 to 13·0]; HR 1·14 [95% CI 0·84 to 1·54]; log-rank p=0·34), or in proportions of patients alive (77 [92%] of 84 patients in the placebo group; 143 [90%] of 159 patients in the sarilumab 200 mg group; difference −1·7 [−9·3 to 5·8]; p=0·63 vs placebo; and 159 [92%] of 173 patients in the sarilumab 400 mg group; difference 0·2 [−6·9 to 7·4]; p=0·85 vs placebo). At day 29, there were numerical, non-significant survival differences between sarilumab 400 mg (88%) and placebo (79%; difference +8·9% [95% CI −7·7 to 25·5]; p=0·25) for patients who had critical disease. No unexpected safety signals were seen. The rates of treatment-emergent adverse events were 65% (55 of 84) in the placebo group, 65% (103 of 159) in the sarilumab 200 mg group, and 70% (121 of 173) in the sarilumab 400 mg group, and of those leading to death 11% (nine of 84) were in the placebo group, 11% (17 of 159) were in the sarilumab 200 mg group, and 10% (18 of 173) were in the sarilumab 400 mg group. Interpretation: This trial did not show efficacy of sarilumab in patients admitted to hospital with COVID-19 and receiving supplemental oxygen. Adequately powered trials of targeted immunomodulatory therapies assessing survival as a primary endpoint are suggested in patients with critical COVID-19. Funding: Sanofi and Regeneron Pharmaceuticals

Non-motor symptom burden in patients with Parkinson's disease with impulse control disorders and compulsive behaviours : results from the COPPADIS cohort

The study was aimed at analysing the frequency of impulse control disorders (ICDs) and compulsive behaviours (CBs) in patients with Parkinson's disease (PD) and in control subjects (CS) as well as the relationship between ICDs/CBs and motor, nonmotor features and dopaminergic treatment in PD patients. Data came from COPPADIS-2015, an observational, descriptive, nationwide (Spain) study. We used the validated Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) for ICD/CB screening. The association between demographic data and ICDs/CBs was analyzed in both groups. In PD, this relationship was evaluated using clinical features and treatment-related data. As result, 613 PD patients (mean age 62.47 ± 9.09 years, 59.87% men) and 179 CS (mean age 60.84 ± 8.33 years, 47.48% men) were included. ICDs and CBs were more frequent in PD (ICDs 12.7% vs. 1.6%, p < 0.001; CBs 7.18% vs. 1.67%, p = 0.01). PD patients had more frequent previous ICDs history, premorbid impulsive personality and antidepressant treatment (p < 0.05) compared with CS. In PD, patients with ICDs/CBs presented younger age at disease onset, more frequent history of previous ICDs and premorbid personality (p < 0.05), as well as higher comorbidity with nonmotor symptoms, including depression and poor quality of life. Treatment with dopamine agonists increased the risk of ICDs/CBs, being dose dependent (p < 0.05). As conclusions, ICDs and CBs were more frequent in patients with PD than in CS. More nonmotor symptoms were present in patients with PD who had ICDs/CBs compared with those without. Dopamine agonists have a prominent effect on ICDs/CBs, which could be influenced by dose