Multi-epoch radial velocity measurements of stars can be used to identify stellar, substellar, and planetary-mass companions. Even a small number of observation epochs can be informative about ...companions, though there can be multiple qualitatively different orbital solutions that fit the data. We have custom-built a Monte Carlo sampler (The Joker) that delivers reliable (and often highly multimodal) posterior samplings for companion orbital parameters given sparse radial velocity data. Here we use The Joker to perform a search for companions to 96,231 red giant stars observed in the APOGEE survey (DR14) with ≥3 spectroscopic epochs. We select stars with probable companions by making a cut on our posterior belief about the amplitude of the variation in stellar radial velocity induced by the orbit. We provide (1) a catalog of 320 companions for which the stellar companion's properties can be confidently determined, (2) a catalog of 4898 stars that likely have companions, but would require more observations to uniquely determine the orbital properties, and (3) posterior samplings for the full orbital parameters for all stars in the parent sample. We show the characteristics of systems with confidently determined companion properties and highlight interesting systems with candidate compact object companions.
ABSTRACT
Studies of the ages, abundances, and motions of individual stars in the Milky Way provide one of the best ways to study the evolution of disc galaxies over cosmic time. The formation of the ...Milky Way’s barred inner region in particular is a crucial piece of the puzzle of disc galaxy evolution. Using data from APOGEE and Gaia, we present maps of the kinematics, elemental abundances, and age of the Milky Way bulge and disc that show the barred structure of the inner Milky Way in unprecedented detail. The kinematic maps allow a direct, purely kinematic determination of the bar’s pattern speed of $41\pm 3\, \mathrm{km\, s}^{-1}\, \mathrm{kpc}^{-1}$ and of its shape and radial profile. We find the bar’s age, metallicity, and abundance ratios to be the same as those of the oldest stars in the disc that are formed in its turbulent beginnings, while stars in the bulge outside of the bar are younger and more metal-rich. This implies that the bar likely formed ${\approx}8\, \mathrm{Gyr}$ ago, when the decrease in turbulence in the gas disc allowed a thin disc to form that quickly became bar-unstable. The bar’s formation therefore stands as a crucial epoch in the evolution of the Milky Way, a picture that is in line with the evolutionary path that emerges from observations of the gas kinematics in external disc galaxies over the last ${\approx}10\, \mathrm{Gyr}$.
ST2 is a member of the interleukin 1 receptor family with 2 main isoforms: transmembrane or cellular (ST2L) and soluble or circulating (sST2) forms. ST2 is the receptor of the IL-33, which is an ...IL-1–like cytokine that can be secreted by living cells in response to cell damage. IL-33 exerts its cellular functions by binding a receptor complex composed of ST2L and IL-1R accessory protein. The IL-33/ST2 system is upregulated in cardiomyocytes and fibroblasts as response to mechanical stimulation or injury. The interaction between IL33 and ST2L has been demonstrated to be cardioprotective: in experimental models, this interaction reduces myocardial fibrosis, prevents cardiomyocyte hypertrophy, reduces apoptosis, and improves myocardial function. The beneficial effects of IL-33 are specifically through the ST2L receptor. sST2 avidly binds IL-33 which results in interruption of the interaction between IL-33/ST2L and consequently eliminates the antiremodeling effects; thus, sST2 is viewed as a decoy receptor. In recent years, knowledge about ST2 role in the pathophysiology of cardiovascular diseases has broadly expanded, with strong links to myocardial dysfunction, fibrosis, and remodeling. Beyond its myocardial role, the IL-33/ST2 system could have an additional role in the development and progression of atherosclerosis. In conclusion, IL-33/ST2L signaling is a mechanically activated, cardioprotective fibroblast–cardiomyocyte paracrine system, which may have therapeutic potential for beneficially regulating the myocardial response to overload and injury. In contrast, sST2 acts as a decoy receptor and, by sequestering IL-33, antagonizes the cardioprotective effects of IL-33/ST2L interaction.
Alcoholic cardiomyopathy (ACM) is defined by a dilated and impaired left ventricle due to chronic excess alcohol consumption. It is largely unknown which factors determine cardiac toxicity on ...exposure to alcohol.
This study sought to evaluate the role of variation in cardiomyopathy-associated genes in the pathophysiology of ACM, and to examine the effects of alcohol intake and genotype on dilated cardiomyopathy (DCM) severity.
The authors characterized 141 ACM cases, 716 DCM cases, and 445 healthy volunteers. The authors compared the prevalence of rare, protein-altering variants in 9 genes associated with inherited DCM. They evaluated the effect of genotype and alcohol consumption on phenotype in DCM.
Variants in well-characterized DCM-causing genes were more prevalent in patients with ACM than control subjects (13.5% vs. 2.9%; p = 1.2 ×10−5), but similar between patients with ACM and DCM (19.4%; p = 0.12) and with a predominant burden of titin truncating variants (TTNtv) (9.9%). Separately, we identified an interaction between TTN genotype and excess alcohol consumption in a cohort of DCM patients not meeting ACM criteria. On multivariate analysis, DCM patients with a TTNtv who consumed excess alcohol had an 8.7% absolute reduction in ejection fraction (95% confidence interval: −2.3% to −15.1%; p < 0.007) compared with those without TTNtv and excess alcohol consumption. The presence of TTNtv did not predict phenotype, outcome, or functional recovery on treatment in ACM patients.
TTNtv represent a prevalent genetic predisposition for ACM, and are also associated with a worse left ventricular ejection fraction in DCM patients who consume alcohol above recommended levels. Familial evaluation and genetic testing should be considered in patients presenting with ACM.
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Background
Sparse evidence of the prognostic benefit of the anti‐inflammatory drug colchicine in chronic and acute coronary syndromes (CCS/ACS) exists.
Methods
We performed a systematic search of ...studies on CCS or ACS comparing colchicine vs. placebo and reporting data on cardiovascular outcomes (primary end points of each study) and/or changes in hs‐CRP.
Results
Ten studies were selected: three on CCS (LoDoCo, LoDoCo2 and the CCS subgroup of COLCHICINE‐PCI; total patient number = 6256), three on ACS (COLCOT, COPS, ACS subgroup of COLCHICINE‐PCI; n = 5,654) and five (n = 532) on hs‐CRP changes from 1 week to 12 months, in CCS and/or ACS. In patients with CCS, colchicine reduced by 49% risk of a composite end point (hazard ratio HR 0.51, 95% confidence interval CI 0.32 to 0.81, P = .005). The favourable effect of colchicine on the risk of cardiovascular events did not change when excluding COLCHICINE‐PCI from analysis (HR 0.51, 95% CI 0.25 to 1.03, P = .061). In patients with ACS, the use of colchicine tended to decrease the occurrence of the combined end point compared with placebo (HR = 0.77, 95% CI 0.56 to 1.05, P = .100), and colchicine became significantly protective when removing COLCHICINE‐PCI from analysis (HR = 0.72, 95% CI 0.56 to 0.92, P = .009). Furthermore, colchicine tended to reduce the hs‐CRP increase (standardized mean difference=−0.31, 95% CI −0.72 to 0.1, P = .133) compared with placebo.
Conclusions
Colchicine therapy near halves the risk of cardiovascular events in CCS compared with placebo and is associated with a nonsignificant 23% risk reduction in ACS, together with a trend towards a greater reduction of hs‐CRP.
Donation after circulatory death (DCD) represents a promising opportunity to overcome the relative shortage of donors for heart transplantation. However, the necessary period of warm ischemia is a ...concern. This study aims to determine the critical warm ischemia time based on in vivo biochemical changes. Sixteen DCD non‐cardiac donors, without cardiovascular disease, underwent serial endomyocardial biopsies immediately before withdrawal of life‐sustaining therapy (WLST), at circulatory arrest (CA) and every 2 min thereafter. Samples were processed into representative pools to assess calcium homeostasis, mitochondrial function and cellular viability. Compared to baseline, no significant deterioration was observed in any studied parameter at the time of CA (median: 9 min; IQR: 7–13 min; range: 4–19 min). Ten min after CA, phosphorylation of cAMP‐dependent protein kinase‐A on Thr197 and SERCA2 decreased markedly; and parallelly, mitochondrial complex II and IV activities decreased, and caspase 3/7 activity raised significantly. These results did not differ when donors with higher WLST to CA times (≥9 min) were analyzed separately. In human cardiomyocytes, the period from WLST to CA and the first 10 min after CA were not associated with a significant compromise in cellular function or viability. These findings may help to incorporate DCD into heart transplant programs.
In‐vivo monitoring of changes in cardiac myocytes during donation after circulatory death shows that the time period from withdrawal of life‐sustaining therapy through ten minutes after cardiac arrest is not associated with significant compromise in cellular function or viability, supporting this duration of warm ischemia as safe for heart donation.
Background:
Curcumin, quercetin, and vitamin D3 (cholecalciferol) are common natural ingredients of human nutrition and reportedly exhibit promising anti-inflammatory, immunomodulatory, ...broad-spectrum antiviral, and antioxidant activities.
Objective:
The present study aimed to investigate the possible therapeutic benefits of a single oral formulation containing supplements curcumin, quercetin, and cholecalciferol (combinedly referred to here as CQC) as an adjuvant therapy for early-stage of symptomatic coronavirus disease 2019 (COVID-19) in a pilot open-label, randomized controlled trial conducted at Mayo Hospital, King Edward Medical University, Lahore, Pakistan.
Methods:
Reverse transcriptase polymerase chain reaction (RT-PCR) confirmed, mild to moderate symptomatic COVID-19 outpatients were randomized to receive either the standard of care (SOC) (
n
= 25) (control arm) or a daily oral co-supplementation of 168 mg curcumin, 260 mg quercetin, and 9 µg (360 IU) of cholecalciferol, as two oral soft capsules b.i.d. as an add-on to the SOC (
n
= 25) (CQC arm) for 14 days. The SOC includes paracetamol with or without antibiotic (azithromycin). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR test, acute symptoms, and biochemistry including C-reactive protein (CRP), D-dimer, lactate dehydrogenase, ferritin, and complete blood count were evaluated at baseline and follow-up day seven.
Results:
Patients who received the CQC adjuvant therapy showed expedited negativization of the SARS-CoV-2 RT-PCR test, i.e., 15 (60.0%) vs. five (20.0%) of the control arm,
p
= 0.009. COVID-19- associated acute symptoms were rapidly resolved in the CQC arm, i.e., 15 (60.0%) vs. 10 (40.0%) of the control arm,
p
= 0.154. Patients in the CQC arm experienced a greater fall in serum CRP levels, i.e., from (median (IQR) 34.0 (21.0, 45.0) to 11.0 (5.0, 16.0) mg/dl as compared to the control arm, i.e., from 36.0 (28.0, 47.0) to 22.0 (15.0, 25.0) mg/dl,
p
= 0.006. The adjuvant therapy of co-supplementation of CQC was safe and well-tolerated by all 25 patients and no treatment-emergent effects, complications, side effects, or serious adverse events were reported.
Conclusion:
The co-supplementation of CQC may possibly have a therapeutic role in the early stage of COVID-19 infection including speedy negativization of the SARS-CoV-2 RT-PCR test, resolution of acute symptoms, and modulation of the hyperinflammatory response. In combination with routine care, the adjuvant co-supplementation of CQC may possibly help in the speedy recovery from early-stage mild to moderate symptoms of COVID-19. Further research is warranted.
Clinical Trial Registration:
Clinicaltrials.gov
, identifier NCT05130671
We report the INTernational Gamma-ray Astrophysics Laboratory (INTEGRAL) detection of the short gamma-ray burst GRB 170817A (discovered by Fermi-GBM) with a signal-to-noise ratio of 4.6, and, for the ...first time, its association with the gravitational waves (GWs) from binary neutron star (BNS) merging event GW170817 detected by the LIGO and Virgo observatories. The significance of association between the gamma-ray burst observed by INTEGRAL and GW170817 is 3.2 , while the association between the Fermi-GBM and INTEGRAL detections is 4.2 . GRB 170817A was detected by the SPI-ACS instrument about 2 s after the end of the GW event. We measure a fluence of (1.4 0.4 0.6) × 10−7 erg cm−2 (75-2000 keV), where, respectively, the statistical error is given at the 1 confidence level, and the systematic error corresponds to the uncertainty in the spectral model and instrument response. We also report on the pointed follow-up observations carried out by INTEGRAL, starting 19.5 hr after the event, and lasting for 5.4 days. We provide a stringent upper limit on any electromagnetic signal in a very broad energy range, from 3 keV to 8 MeV, constraining the soft gamma-ray afterglow flux to <7.1 × 10−11 erg cm−2 s−1 (80-300 keV). Exploiting the unique capabilities of INTEGRAL, we constrained the gamma-ray line emission from radioactive decays that are expected to be the principal source of the energy behind a kilonova event following a BNS coalescence. Finally, we put a stringent upper limit on any delayed bursting activity, for example, from a newly formed magnetar.
Here, we consider a stationary inclusion in a real Hilbert space X, governed by a set of constraints K, a nonlinear operator A, and an element f∈X. Under appropriate assumptions on the data, the ...inclusion has a unique solution, denoted by u. We state and prove a covergence criterion, i.e., we provide necessary and sufficient conditions on a sequence {un}⊂X, which guarantee its convergence to the solution u. We then present several applications that provide the continuous dependence of the solution with respect to the data K, A and f on the one hand, and the convergence of an associate penalty problem on the other hand. We use these abstract results in the study of a frictional contact problem with elastic materials that, in a weak formulation, leads to a stationary inclusion for the deformation field. Finally, we apply the abstract penalty method in the analysis of two nonlinear elastic constitutive laws.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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