Abstract
NGC 7793 P13 is a variable (luminosity range ∼100) ultraluminous X-ray source proposed to host a stellar-mass black hole of less than 15 M⊙ in a binary system with orbital period of 64 d and ...a 18–23 M⊙ B9Ia companion. Within the EXTraS (Exploring the X-ray Transient and variable Sky) project, we discovered pulsations at a period of ∼0.42 s in two XMM–Newton observations of NGC 7793 P13, during which the source was detected at L
X ∼ 2.1 × 1039 and 5 × 1039 erg s−1 (0.3–10 keV band). These findings unambiguously demonstrate that the compact object in NGC 7793 P13 is a neutron star accreting at super-Eddington rates. While standard accretion models face difficulties accounting for the pulsar X-ray luminosity, the presence of a multipolar magnetic field with B ∼ few × 1013 G close to the base of the accretion column appears to be in agreement with the properties of the system.
We have measured the spectrum of the Cosmic X-ray Background (CXB) in the 2-8 keV range with the high throughput EPIC/MOS instrument onboard XMM-Newton. A large sample of high galactic latitude ...observations was used, covering a total solid angle of 5.5 square degrees. Our study is based on a very careful characterization and subtraction of the instrumental background, which is crucial for a robust measurement of the faintest diffuse source of the X-ray sky. The CXB spectrum is consistent with a power law having a photon index Gamma = 1.41 plus or minus 0.06 and a normalization of 2.46 plus or minus 0.09 photons cm super(-2) s super(-1) sr super(-1) keV super(-1) at 3 keV ( similar to 11.6 photons cm super(-2) s super(-1) sr super(-1) keV super(-1) at 1 keV), corresponding to a 2-10 keV flux of (2.24 plus or minus 0.16) x 10 super(-11) erg cm super(-2) s super(-1) deg super(-1) (90% confidence level, including the absolute flux calibration uncertainty). Our results are in excellent agreement with two of the most recent CXB measurements, performed with BeppoSAX LECS/MECS data (Vecchi et al. 1999) and with an independent analysis of XMM-Newton EPIC/MOS data (Lumb et al. 2002), providing a very strong constraint to the absolute sky surface brightness in this energy range, so far affected by an similar to 40% uncertainty. Our measurement implies that the fraction of CXB resolved by the recent deep X-ray observations in the 2-10 keV band is of 80 plus or minus 7% (1 sigma ), suggesting the existence of a new population of faint sources, largely undetected within the current sensitivity limits of the deepest X-ray surveys.
BACKGROUND—Elderly patients are at elevated risk of both ischemic and bleeding complications after an acute coronary syndrome (ACS), and display higher on-clopidogrel platelet reactivity as compared ...to younger patients. Prasugrel 5 mg provides more predictable platelet inhibition, as compared to clopidogrel, in the elderly, suggesting the possibility of reducing ischemic events without increasing bleeding.
METHODS—In a multicenter, randomized, open-label, blinded-endpoint trial, we compared a once daily maintenance dose of prasugrel 5 mg with the standard clopidogrel 75 mg in patients >74 years with ACS undergoing percutaneous coronary intervention (PCI). The primary endpoint was the composite of mortality, myocardial infarction, disabling stroke and re-hospitalization for cardiovascular causes or bleeding within one year. The study was designed to demonstrate superiority of prasugrel 5 mg over clopidogrel 75 mg.
RESULTS—Enrolment was interrupted, according to pre-specified criteria, after a planned interim analysis, when 1443 patients (40% women, mean age 80 years) had been enrolled, with a median follow-up of 12 months, due to futility for efficacy. The primary endpoint occurred in 121 patients (17%) with prasugrel and 121 (16.6%) with clopidogrel (HR 1.007, 95% CI, 0.78-1.30; P =0.955). Definite/probable stent thrombosis rates were 0.7% with prasugrel vs 1.9% with clopidogrel (OR 0.36, C.I. 0.13-1.00, p=0.06). Bleeding Academic Research Consortium types ≥2 were 4.1% with prasugrel vs 2.7% with clopidogrel (OR 1.52, C.I. 0.85-3.16, P= 0.18).
CONCLUSIONS—The present study in elderly ACS patients showed no difference in the primary endpoint between reduced-dose prasugrel and standard-dose clopidogrel. However, the study should be interpreted in the light of premature termination of the trial.
CLINICAL TRIAL REGISTRATION—URLhttps://clinicaltrials.gov/ Unique IdentifierNCT01777503
•A comparison among methods for calculating heating degree-days (HDD) is provided.•ASHRAE method is used for analyze the historical trends of HDD and CDD in Italy.•The HDD historical profile for Rome ...is decomposed in its characterizing components.
Degree days (DD) represent a versatile climatic indicator which is commonly used in the analysis of building energy performance, as e.g. (i) to perform energetic assessment of existent and new buildings, (ii) to analyze the territory energy consumption, (iii) to develop scenario analyses in terms of energy consumption forecasting, and so on.
Different methods can be used for determining the DD values, depending on the available climatic data of each location. In the present paper, the simplified methods based on reduced climatic data set have been compared assuming the mean daily degree-hours method (MDDH) as reference. Hourly temperature profiles recorded by the meteorological station located at the University of Genoa have been used for these analyses.
In the second part of the present work, the ASHRAE method has been selected to calculate heating (HDD) and cooling (CDD) degree days for several Italian cities. In particular, daily meteorological data of several Italian cities (covering the whole climatic conditions which occur in Italy) have been used to calculate heating and cooling degree days in the period 1978–2013, in order to analyze their trends in the last years. Finally, the historical profiles of Rome and Milan have been treated as time-series and analyzed in the frequency domain, performing a decomposition of the original data set into different characterizing components. This simplified approach permits to deeply analyze the historical profile of DD and represents a simple starting point method for future analyses with forecasting perspectives.
Purpose
We investigated the autophagic response of rat Müller rMC-1 cells during a short-term high glucose challenge.
Methods
rMC-1 cells were maintained in 5 mM glucose (LG) or exposed to 25 mM ...glucose (HG). Western blot analysis was used to evaluate the expression levels of markers of autophagy (LC3-II, p62) and glial activation (AQP4), as well as the activation of TRAF2/JNK, ERK and AKT pathways. Autophagic flux assessment was performed using the autophagy inhibitor chloroquine. ROS levels were measured by flow cytometry using dichlorofluorescein diacetate. ERK involvement in autophagy induction was addressed using the ERK inhibitor FR180204. The effect of autophagy inhibition on cell viability was evaluated by SRB assay.
Results
Activation of autophagy was observed in the first 2–6 h of HG exposure. This early autophagic response was transient, not accompanied by an increase in AQP4 or in the phospho-activation of JNK, a key mediator of cellular response to oxidative stress, and required ERK activity. Cells exposed to HG had a lower viability upon autophagy inhibition by chloroquine, as compared to those maintained in LG.
Conclusion
A short-term HG challenge triggers in rMC-1 cells a process improving the ability to cope with stressful conditions, which involves ERK and an early and transient autophagy activation.
The dopamine D2 and D3 receptors are implicated in schizophrenia and its pharmacological treatments. These receptors undergo intracellular trafficking processes that are modulated by dysbindin-1 ...(Dys). Indeed, Dys variants alter cognitive responses to antipsychotic drugs through D2-mediated mechanisms. However, the mechanism by which Dys might selectively interfere with the D3 receptor subtype is unknown. Here, we revealed an interaction between functional genetic variants altering Dys and D3. Specifically, both in patients with schizophrenia and in genetically modified mice, concomitant reduction in D3 and Dys functionality was associated with improved executive and working memory abilities. This D3/Dys interaction produced a D2/D3 imbalance favoring increased D2 signaling in the prefrontal cortex (PFC) but not in the striatum. No epistatic effects on the clinical positive and negative syndrome scale (PANSS) scores were evident, while only marginal effects on sensorimotor gating, locomotor functions, and social behavior were observed in mice. This genetic interaction between D3 and Dys suggests the D2/D3 imbalance in the PFC as a target for patient stratification and procognitive treatments in schizophrenia.
Background Lower muscle mass is a known predictor of unfavorable outcome, but its prognostic impact on COVID-19 patients is unknown. Purpose To investigate the contribution of CT-derived muscle ...status in predicting clinical outcomes in COVID-19 patients. Materials and Methods Clinical/laboratory data and outcomes (intensive care unit ICU admission and death) were retrospectively retrieved for patients with reverse transcriptase polymerase chain reaction-confirmed COVID-19, who underwent chest CT on admission in four hospitals in Northern Italy from February 21 to April 30, 2020. Extent and type of pulmonary involvement, mediastinal lymphadenopathy, and pleural effusion were assessed. Cross-sectional areas and attenuation of paravertebral muscles were measured on axial CT images at T5 and T12 vertebral level. Multivariable linear and binary logistic regression, including calculation odds ratios (OR) with 95% confidence intervals (CIs), were used to build four models to predict ICU admission and death, tested and compared using receiver operating characteristic curve (ROC) analysis. Results A total 552 patients (364 men; median age 65 years, interquartile range 54-75) were included. In a CT-based model, lower-than-median T5 paravertebral muscle area showed the highest ORs for ICU admission (OR 4.8, 95% CI 2.7-8.5;
<.001) and death (OR 2.3, 95% CI 1.0-2.9;
=.027). When clinical variables were included in the model, lower-than-median T5 paravertebral muscle area still showed the highest ORs both for ICU admission (OR 4.3; 95% CI 2.5-7.7;
<.001) and death (OR 2.3, 95% CI 1.3-3.7;
=.001). At ROC analysis, the CT-based model and the model including clinical variables showed the same area under the curve (AUC) for ICU admission prediction (AUC 0.83,
=.380) and were not different in predicting death (AUC 0.86 versus AUC 0.87, respectively,
=.282). Conclusion In hospitalized patients with COVID-19, lower muscle mass on CT was independently associated with ICU admission and hospital mortality.
Human genetic studies have recently suggested that the postsynaptic activity-regulated cytoskeleton-associated protein (Arc) complex is a convergence signal for several genes implicated in ...schizophrenia. However, the functional significance of Arc in schizophrenia-related neurobehavioral phenotypes and brain circuits is unclear. Here, we find that, consistent with schizophrenia-related phenotypes, disruption of Arc in mice produces deficits in sensorimotor gating, cognitive functions, social behaviors, and amphetamine-induced psychomotor responses. Furthermore, genetic disruption of Arc leads to concomitant hypoactive mesocortical and hyperactive mesostriatal dopamine pathways. Application of a D1 agonist to the prefrontal cortex or a D2 antagonist in the ventral striatum rescues Arc-dependent cognitive or psychomotor abnormalities, respectively. Our findings demonstrate a role for Arc in the regulation of dopaminergic neurotransmission and related behaviors. The results also provide initial biological support implicating Arc in dopaminergic and behavioral abnormalities related to schizophrenia.
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•Arc genetic disruption recapitulates schizophrenia-relevant behavioral abnormalities•Arc disruption leads to hypoactive PFC dopamine (DA) and hyperactive striatal DA system•Hypo-PFC and hyper-striatal DA mediates cognitive and motor changes, respectively•Arc is a convergence point for genes implicated in schizophrenia risk
Managò et al. find that, consistent with schizophrenia-related phenotypes, disruption of Arc in mice produces deficits in sensorimotor gating, cognitive functions, social behaviors, and amphetamine-induced psychomotor responses. Furthermore, genetic disruption of Arc leads to concomitant hypoactive mesocortical and hyperactive mesostriatal dopamine pathways.
Abstract Recently, the interest in the Helmet interface during non-invasive respiratory support (NIRS) has increased due to the COVID-19 pandemic. During NIRS, positive end-expiratory pressure (PEEP) ...can be given as continuous positive airway pressure (CPAP), which maintains a positive airway pressure throughout the whole respiratory cycle with Helmet as an interface (H-CPAP). The main disadvantage of the H-CPAP is the inability to measure tidal volume (V T ). Opto-electronic plethysmography (OEP) is a non-invasive technique that is not sensitive to gas compression/expansion inside the helmet. OEP acquisitions were performed on 28 healthy volunteers (14 females and 14 males) at baseline and during Helmet CPAP. The effect of posture (semi-recumbent vs. prone), flow (50 vs. 60 L/min), and PEEP (0 vs. 5 vs. 10 cmH 2 O) on the ventilatory and thoracic-abdominal pattern and the operational volumes were investigated. Prone position limited vital capacity, abdominal expansion and chest wall recruitment. A constant flow of 60 L/min reduced the need for the subject to ventilate while having a slight recruitment effect (100 mL) in the semi-recumbent position. A progressive increasing recruitment was found with higher PEEP but limited by the prone position. It is possible to accurately measure tidal volume during H-CPAP to deliver non-invasive ventilatory support using opto-electronic plethysmography during different clinical settings.
We discovered 2.8 s pulsations in the X-ray emission of the ultraluminous X-ray source (ULX) M51 ULX-7 within the UNSEeN project, which was designed to hunt for new pulsating ULXs (PULXs) with ...XMM-Newton. The pulse shape is sinusoidal, and large variations of its amplitude were observed even within single exposures (pulsed fraction from less than 5% to 20%). Source M51 ULX-7 is variable, generally observed at an X-ray luminosity between 1039 and 1040 erg s−1, located in the outskirts of the spiral galaxy M51a at a distance of 8.6 Mpc. According to our analysis, the X-ray pulsar orbits in a 2 day binary with a projected semimajor axis 28 lt-s. For a neutron star (NS) of 1.4 M , this implies a lower limit on the companion mass of 8 M , placing the system hosting M51 ULX-7 in the high-mass X-ray binary class. The barycentric pulse period decreased by 0.4 ms in the 31 days spanned by our 2018 May-June observations, corresponding to a spin-up rate . In an archival 2005 XMM-Newton exposure, we measured a spin period of ∼3.3 s, indicating a secular spin-up of , a value in the range of other known PULXs. Our findings suggest that the system consists of a massive donor, possibly an OB giant or supergiant, and a moderately magnetic (dipole field component in the range 1012 G G) accreting NS with weakly beamed emission ( ).
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