A monolithic collapse origin for the thin/thick disc structure of ESO 243-49

ESO 243-49 is a high-mass (circular velocity $v_{\rm c}\approx200\,{\rm km\,s^{-1}}$) edge-on S0 galaxy in the Abell 2877 cluster at a distance of $\sim95\,{\rm Mpc}$. To elucidate the origin of its thick disc, we use MUSE science verification data to study its kinematics and stellar populations. The thick disc emits $\sim80\%$ of the light at heights in excess of $3.5^{\prime\prime}$ ($1.6\,{\rm kpc}$). The rotation velocities of its stars lag by $30-40\,{\rm km\,s^{-1}}$ compared to those in the thin disc, which is compatible with the asymmetric drift. The thick disc is found to be more metal-poor than the thin disc, but both discs have old ages. We suggest an internal origin for the thick disc stars in high-mass galaxies. We propose that the thick disc formed either ${\rm a)}$ first in a turbulent phase with a high star formation rate and that a thin disc formed shortly afterwards, or ${\rm b)}$ because of the dynamical heating of a thin pre-existing component. Either way, the star formation in ESO 243-49 was quenched just a few Gyrs after the galaxy was born and the formation of a thin and a thick disc must have occurred before the galaxy stopped forming stars. The formation of the discs was so fast that it could be described as a monolithic collapse where several generations of stars formed in a rapid succession.Comment: Accepted for publication in A&A. The reduced data-cube as well as the data necessary to build the kinematic and stellar population maps are available at https://etsin.avointiede.fi/dataset/urn-nbn-fi-csc-kata2016092414291163237

RNA-protein correlation of liver toxicity markers in HepaRG cells

The liver is a main target organ for the toxicity of many different compounds. While in general, in vivo testing is still routinely used for assessing the hepatotoxic potential of test chemicals, the use of in vitro models offers advantages with regard to throughput, consumption of resources, and animal welfare aspects. Using the human hepatoma cell line HepaRG, we performed a comparative evaluation of a panel of hepatotoxicity marker mRNAs and proteins after exposure of the cells to 30 different pesticidal active compounds comprising herbizides, fungicides, insecticides, and others. The panel of hepatotoxicity markers included nuclear receptor target genes, key players of fatty acid and bile acid metabolism-related pathways, as well as recently identified biomarkers of drug-induced liver injury. Moreover, marker genes and proteins were identified, for example, S100P, ANXA10, CYP1A1, and CYP7A1. These markers respond with high sensitivity to stimulation with chemically diverse test compounds already at non-cytotoxic concentrations. The potency of the test compounds, determined as an overall parameter of their ability to deregulate marker expression in vitro, was very similar between the mRNA and protein levels. Thus, this study does not only characterize the response of human liver cells to 30 different pesticides but also demonstrates that hepatotoxicity testing in human HepaRG cells yields well comparable results at the mRNA and protein levels. Furthermore, robust hepatotoxicity marker genes and proteins were identified in HepaRG cells

Biomarker profiles of acute heart failure patients with a mid-range ejection fraction

OBJECTIVES: In this study, the authors used biomarker profiles to characterize differences between patients with acute heart failure with a midrange ejection fraction (HFmrEF) and compare them with patients with a reduced (heart failure with a reduced ejection fraction [HFrEF]) and preserved (heart failure with a preserved ejection fraction [HFpEF]) ejection fraction. BACKGROUND: Limited data are available on biomarker profiles in acute HFmrEF. METHODS: A panel of 37 biomarkers from different pathophysiological domains (e.g., myocardial stretch, inflammation, angiogenesis, oxidative stress, hematopoiesis) were measured at admission and after 24 h in 843 acute heart failure patients from the PROTECT trial. HFpEF was defined as left ventricular ejection fraction (LVEF) of ≥50% (n = 108), HFrEF as LVEF of <40% (n = 607), and HFmrEF as LVEF of 40% to 49% (n = 128). RESULTS: Hemoglobin and brain natriuretic peptide levels (300 pg/ml [HFpEF]; 397 pg/ml [HFmrEF]; 521 pg/ml [HFrEF]; ptrend <0.001) showed an upward trend with decreasing LVEF. Network analysis showed that in HFrEF interactions between biomarkers were mostly related to cardiac stretch, whereas in HFpEF, biomarker interactions were mostly related to inflammation. In HFmrEF, biomarker interactions were both related to inflammation and cardiac stretch. In HFpEF and HFmrEF (but not in HFrEF), remodeling markers at admission and changes in levels of inflammatory markers across the first 24 h were predictive for all-cause mortality and rehospitalization at 60 days (pinteraction <0.05). CONCLUSIONS: Biomarker profiles in patients with acute HFrEF were mainly related to cardiac stretch and in HFpEF related to inflammation. Patients with HFmrEF showed an intermediate biomarker profile with biomarker interactions between both cardiac stretch and inflammation markers. (PROTECT-1: A Study of the Selective A1 Adenosine Receptor Antagonist KW-3902 for Patients Hospitalized With Acute HF and Volume Overload to Assess Treatment Effect on Congestion and Renal Function; NCT00328692)

Sex Differences in the Management and Outcomes of Heart Failure with Preserved Ejection Fraction in Patients Presenting to the Emergency Department with Acute Heart Failure

Background Heart failure (HF) with preserved ejection fraction (HFpEF) is more common in women than in men; data characterizing sex differences in the management and outcomes of HFpEF patients presenting to the emergency department (ED) are limited. Methods and Results Using Acute Decompensated Heart Failure National Registry Emergency Module data linked to Medicare claims, we conducted a retrospective analysis of acute HF patients in the ED, identifying HFpEF (ejection fraction [EF] ≥40%) patients and stratifying by sex to compare baseline characteristics, ED therapies, hospital length of stay (LOS), in-hospital mortality, and post-discharge outcomes. Of 4161 HFpEF patients, 2808 (67%) were women, who were more likely to be older and hypertensive, but less likely to be diabetic or smokers (all P 140 mm Hg (62.5% vs 56.4%; P = .0001) and higher EF. There were no sex differences in ED therapies, adjusted 30- and 180-day all-cause mortality, in-hospital mortality, or 30- and 180-day readmissions. After adjustment, women had longer LOS (0.40 days, 95% confidence interval [CI] 0.10–0.70; P = .008). Conclusions Women with HFpEF presenting to the ED were more likely to have elevated systolic blood pressure, but overall ED management strategies were similar to those in men. We observed adjusted differences in hospital LOS, but no differences in 30- and 180-day outcomes

RNA-protein correlation of liver toxicity markers in HepaRG cells

The liver is a main target organ for the toxicity of many different compounds. While in general, in vivo testing is still routinely used for assessing the hepatotoxic potential of test chemicals, the use of in vitro models offers advantages with regard to throughput, consumption of resources, and animal welfare aspects. Using the human hepatoma cell line HepaRG, we performed a comparative evaluation of a panel of hepatotoxicity marker mRNAs and proteins after exposure of the cells to 30 different pesticidal active compounds comprising herbizides, fungicides, insecticides, and others. The panel of hepatotoxicity markers included nuclear receptor target genes, key players of fatty acid and bile acid metabolism-related pathways, as well as recently identified biomarkers of drug-induced liver injury. Moreover, marker genes and proteins were identified, for example, S100P, ANXA10, CYP1A1, and CYP7A1. These markers respond with high sensitivity to stimulation with chemically diverse test compounds already at non-cytotoxic concentrations. The potency of the test compounds, determined as an overall parameter of their ability to deregulate marker expression in vitro, was very similar between the mRNA and protein levels. Thus, this study does not only characterize the response of human liver cells to 30 different pesticides but also demonstrates that hepatotoxicity testing in human HepaRG cells yields well comparable results at the mRNA and protein levels. Furthermore, robust hepatotoxicity marker genes and proteins were identified in HepaRG cells

Differences in health care use and outcomes by the timing of in-hospital worsening heart failure

BACKGROUND: Patients hospitalized with acute heart failure may experience worsening symptoms requiring escalation of therapy. In-hospital worsening heart failure is associated with worse in-hospital and postdischarge outcomes, but associations between the timing of worsening heart failure and outcomes are unknown. METHODS: Using data from a large clinical registry linked to Medicare claims, we examined characteristics, outcomes, and costs of patients hospitalized for acute heart failure. We defined in-hospital worsening heart failure by the use of inotropes or intravenous vasodilators or initiation of mechanical circulatory support, hemodialysis, or ventilation. The study groups were early worsening heart failure (n = 1,990), late worsening heart failure (n = 4,223), complicated presentation (n = 15,361), and uncomplicated hospital course (n = 41,334). RESULTS: Among 62,908 patients, those with late in-hospital worsening heart failure had higher in-hospital and postdischarge mortality than patients with early worsening heart failure or complicated presentation. Those with early or late worsening heart failure had more frequent all-cause and heart failure readmissions at 30 days and 1 year, with resultant higher costs, compared with patients with an uncomplicated hospital course. CONCLUSION: Although late worsening heart failure was associated with the highest mortality, both early and late worsening heart failures were associated with more frequent readmissions and higher health care costs compared to uncomplicated hospital course. Prevention of worsening heart failure may be an important focus in the care of hospitalized patients with acute heart failure

Association between potassium level and outcomes in heart failure with reduced ejection fraction: a cohort study from the Swedish Heart Failure Registry

AimsHyperkalaemia and hypokalaemia are common in heart failure and associated with worse outcomes. However, the optimal potassium range is unknown. We sought to determine the optimal range of potassium in patients with heart failure and reduced ejection fraction (5.0- mmol/L. Potassium 5.0- mmol/L were more common with lower estimated glomerular filtration rate and heart failure of longer duration and greater severity. The potassium level associated with the lowest hazard risk for mortality at 30- days, 12 months, and maximal follow- up was 4.2- mmol/L, and there was a steep increase in risk with both higher and lower potassium levels. In adjusted strata analyses, lower potassium was independently associated with all- cause mortality at 12 months and maximal follow- up, while higher potassium levels only increased risk at 30- days.ConclusionIn this nationwide registry, the relationship between potassium and mortality was U- shaped, with an optimal potassium value of 4.2- mmol/L. After multivariable adjustment, hypokalaemia was associated with increased long- term mortality but hyperkalaemia was associated with increased short- term mortality.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162724/3/EJHF1757-sup-0001-APPS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162724/2/ejhf1757_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162724/1/ejhf1757.pd

Urban fuelwood demand and markets in a small town in South Africa: Livelihood vulnerability and alien plant control

Fuelwood is the primary energy for most households throughout the developing world. With increasing urbanization and declining local availability of fuelwood, a growing proportion of households obtain their fuelwood by purchasing it. These fuelwood markets are the key nexus in supply and demand scenarios and can be potentially significant points for intervention to address energy security amongst the urban poor. This paper reports on the fuelwood demand and marketing in a small town in South Africa. Despite the availability of more modern fuels and state subsidization of electricity, fuelwood was still used by half the households. Annual demand was 1.2 t per household. Over half of the households bought their fuelwood requirements because local stocks were limited. Those households that did collect their own fuelwood were significantly poorer than households that purchased fuelwood, as well as households that did not use fuelwood at all. Fuelwood markets operated through 45-60 vendors who transported fuelwood from further afield. Income from the fuelwood trade was low, but was strongly linked to hours worked. Thus, vendors working a full week did earn a meaningful income, especially in the context of high unemployment in the area. Fuelwood vendors also provided casual employment opportunities for unskilled labour. Most vendors harvested fuelwood from commonage lands, with most of the wood being from alien species. Local stocks of wood are declining in the face of constant transformation of commonage to residential areas, and a national water and biodiversity conservation programme to eradicate alien plants. This decline poses a threat to the financial viability of fuelwood markets. Yet, an opportunity exists to incorporate the vendors into the alien plant clearing programme, since they already perform such a function

Effects of exenatide and open-label SGLT2 inhibitor treatment, given in parallel or sequentially, on mortality and cardiovascular and renal outcomes in type 2 diabetes:insights from the EXSCEL trial

Background Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) improve cardiovascular and renal outcomes in patients with type 2 diabetes through distinct mechanisms. However, evidence on clinical outcomes in patients treated with both GLP-1 RA and SGLT2i is lacking. We aim to provide insight into the effects of open-label SGLT2i use in parallel with or shortly after once-weekly GLP-1 RA exenatide (EQW) on cardiorenal outcomes. Methods In the EXSCEL cardiovascular outcomes trial EQW arm, SGLT2i drop-in occurred in 8.7% of participants. These EQW+SGLT2i users were propensity-matched to: (1) placebo-arm participants not taking SGLT2i (n = 572 per group); and to (2) EQW-arm participants not taking SGLT2i (n = 575), based on their last measured characteristics before SGLT2i initiation, and equivalent study visit in comparator groups. Time-to-first major adverse cardiovascular event (MACE) and all-cause mortality (ACM) were compared using Cox regression analyses. eGFR slopes were quantified using mixed model repeated measurement analyses. Results In adjusted analyses, the risk for MACE with combination EQW+SGLT2i use was numerically lower compared with both placebo (adjusted hazard ratio 0.68, 95% CI 0.39-1.17) and EQW alone (0.85, 0.48-1.49). Risk of ACM was nominally significantly reduced compared with placebo (0.38, 0.16-0.90) and compared with EQW (0.41, 0.17-0.95). Combination EQW+SGLT2i use also nominally significantly improved estimated eGFR slope compared with placebo (+ 1.94, 95% CI 0.94-2.94 mL/min/1.73 m(2)/year) and EQW alone (+ 2.38, 1.40-3.35 mL/min/1.73 m(2)/year). Conclusions This post hoc analysis supports the hypothesis that combinatorial EQW and SGLT2i therapy may provide benefit on cardiovascular outcomes and mortality. Trial registration Clinicaltrials.gov, Identifying number: NCT01144338, Date of registration: June 15, 2010