Oral anticoagulants (OACs) are first-line drugs for stroke prevention in patients with atrial fibrillation (AF). The introduction of new lines of therapy with direct oral anticoagulants (DOACs) has ...led to a decreased use of vitamin K antagonists (VKAs). Comparative analyses of DOACs in clinical trials are scarce and the comparator has mostly been warfarin. Their impact on health outcomes in observational studies has not always been consistent. The aim of this study is to evaluate the effectiveness and safety of DOACs and VKAs in patients with AF using Real-World Data (RWD).
Abstract Objectives 1) To assess the association of NETosis and NETosis-derived products with the activity of the disease and the development of cardiovascular disease in RA; 2) To evaluate the ...involvement of NETosis on the effects of biologic therapies such as anti-TNF alpha (Infliximab) and anti-IL6R drugs (Tocilizumab). Methods One hundred and six RA patients and 40 healthy donors were evaluated for the occurrence of NETosis. Carotid-intimae media thickness was analyzed as early atherosclerosis marker. Inflammatory and oxidative stress mediators were quantified in plasma and neutrophils. Two additional cohorts of 75 RA patients, treated either with Infliximab (n = 55) or Tocilizumab (n = 20) for six months, were evaluated. Results NETosis was found increased in RA patients, beside myeloperoxidase and neutrophil elastase protein levels. Cell-free nucleosomes plasma levels were elevated, and strongly correlated with the activity of the disease and the positivity for autoantibodies, alongside inflammatory and oxidative profiles in plasma and neutrophils. Moreover, ROC analyses showed that cell-free nucleosomes levels could identify RA patients showing early atherosclerosis with high specificity. RA patients treated either with IFX or TCZ for six months exhibited decreased generation of NETs. Concomitantly, clinical parameters and serum markers of inflammation were found reduced. Mechanistic in vitro analyses showed that inhibition of NETs extrusion by either DNase, IFX or TCZ, further abridged the endothelial dysfunction and the activation of immune cells, thus influencing the global activity of the vascular system. Conclusions NETosis-derived products may have diagnostic potential for disease activity and atherosclerosis, as well as for the assessment of therapeutic effectiveness in RA.
We were able to accurately predict the shadow path and successfully observe an occultation of a bright star by Chiron on December 15, 2022. The Kottamia Astronomical Observatory in Egypt did not ...detect the occultation by the solid body, but we found three extinction features in the light curve that had symmetrical counterparts with respect to the central time of the occultation. One of the features is broad and shallow, whereas the other two features are sharper, with a maximum extinction of ∼25% at the achieved spatial resolution of 19 km per data point. From the Wise Observatory in Israel, we detected the occultation caused by the main body and several extinction features surrounding the body. When all the secondary features are plotted in the sky plane, we find that they can be caused by a broad ∼580 km disk with concentrations at radii of 325 ± 16 km and 423 ± 11 km surrounding Chiron. At least one of these structures appears to be outside the Roche limit. The ecliptic coordinates of the pole of the disk are
λ
= 151° ±8° and
β
= 18° ±11°, in agreement with previous results. We also reveal our long-term photometry results, indicating that Chiron had suffered a brightness outburst of at least 0.6 mag between March and September 2021 and that Chiron was still somewhat brighter at the occultation date than at its nominal pre-outburst phase. The outermost extinction features might be consistent with a bound or temporarily bound structure associated with the brightness increase. However, the nature of the brightness outburst is unclear, and it is also unclear whether the dust or ice released in the outburst could be feeding a putative ring structure or whether it is emanating from it.
In this paper, the non-linear optical response of photodeposited zinc nanoparticles onto an etched optical fiber is reported. Through chemical etching, 20 mm of the cladding of a standard single-mode ...optical fiber was removed to expose its core and subsequently, photodeposit zinc nanoparticles on it at different times (1, 5 and 10 min) by using a continuous wave laser at 1550 nm. The non-linear optical response was obtained by the P-scan technique using a high-gain pulsed amplifier with a pulse duration of 10 ns at a wavelength of 1550 nm. The experimental results showed that it is possible to get the effects of reverse saturable absorption (RSA) at irradiances less than 380 MW/cm 2 and saturable absorption (SA) for higher values. Consequently, the analysis of the results obtained shows that the third-order non-linear susceptibility x3 of the RSA is 2.2130 × 10−06 (esu) for 10 min of photodeposition, which decreases for shorter photodeposition times; On the other hand, the third-order non-linear susceptibility x3 of the SA is −5.8955 × 10−07 (esu) for 10 min of photodeposition, which increases for shorter exposure times. Finally, the experimental results obtained show that it is possible to make a photonic device with desired non-linear absorption properties by the photodeposition of metallic nanoparticles onto etched fibers, which makes it ideal for applications in optical communications.
•We report the non-linear optical response of photodeposited zinc nanoparticles (ZnNPs) onto an etched optical fiber.•An optical fiber was chemically etched, and then ZnNPs were photodeposited onto its core at different times.•Our results showed that it is possible to get the effects of reverse saturable absorption (RSA) at irradiances less than 380 MW/cm2 and saturable absorption (SA) for higher values.•The third-order non-linear susceptibility x(3) of the RSA is 2.2130 × 10-6 (esu) and to SA is −5.8955 × 10-07 (esu) for 10 min of photodeposition.•The results reported in this work can be used as optical switching devices.
To develop and validate a nomogram and web-based calculator to predict overall survival (OS) in Caucasian-advanced oesophagogastric adenocarcinoma (AOA) patients undergoing first-line combination ...chemotherapy.
Nine hundred twenty-four AOA patients treated at 28 Spanish teaching hospitals from January 2008 to September 2014 were used as derivation cohort. The result of an adjusted-Cox proportional hazards regression was represented as a nomogram and web-based calculator. The model was validated in 502 prospectively recruited patients treated between October 2014 and December 2016. Harrell's c-index was used to evaluate discrimination.
The nomogram includes seven predictors associated with OS: HER2-positive tumours treated with trastuzumab, Eastern Cooperative Oncology Group performance status, number of metastatic sites, bone metastases, ascites, histological grade, and neutrophil-to-lymphocyte ratio. Median OS was 5.8 (95% confidence interval (CI), 4.5-6.6), 9.4 (95% CI, 8.5-10.6), and 14 months (95% CI, 11.8-16) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the derivation set and 4.6 (95% CI, 3.3-8.1), 12.7 (95% CI, 11.3-14.3), and 18.3 months (95% CI, 14.6-24.2) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the validation set. The nomogram is well-calibrated and reveals acceptable discriminatory capacity, with optimism-corrected c-indices of 0.618 (95% CI, 0.591-0.631) and 0.673 (95% CI, 0.636-0.709) in derivation and validation groups, respectively. The AGAMENON nomogram outperformed the Royal Marsden Hospital (c-index=0.583; P=0.00046) and Japan Clinical Oncology Group prognostic indices (c-index=0.611; P=0.03351).
We developed and validated a straightforward model to predict survival in Caucasian AOA patients initiating first-line polychemotherapy. This model can contribute to inform clinical decision-making and optimise clinical trial design.
MicroRNAs markedly affect the immune system, and have a relevant role in CVD and autoimmune diseases. Yet, no study has analyzed their involvement in atherothrombosis related to APS and SLE patients. ...This study intended to: 1) identify and characterize microRNAs linked to CVD in APS and SLE; 2) assess the effects of specific autoantibodies. Six microRNAs, involved in atherothrombosis development, were quantified in purified leukocytes from 23 APS and 64 SLE patients, and 56 healthy donors. Levels of microRNAs in neutrophils were lower in APS and SLE than in healthy donors. Gene and protein expression of miRNA biogenesis-related molecules were also reduced. Accordingly, more than 75% of identified miRNAs by miRNA profiling were underexpressed. In monocytes, miR124a and -125a were low, while miR-146a and miR-155 appeared elevated. Altered microRNAs' expression was linked to autoimmunity, thrombosis, early atherosclerosis, and oxidative stress in both pathologies. In vitro treatment of neutrophils, monocytes, and ECs with aPL-IgG or anti-dsDNA-IgG antibodies deregulated microRNAs expression, and decreased miRNA biogenesis-related proteins. Monocyte transfections with pre-miR-124a and/or -125a caused reduction in atherothrombosis-related target molecules. In conclusion, microRNA biogenesis, significantly altered in neutrophils of APS and SLE patients, is associated to their atherothrombotic status, further modulated by specific autoantibodies.
Heart failure (HF) is a syndromic condition with a high incidence in current medicine. When the symptoms of HF progress, and become refractory, cardiac transplant is the best therapeutic option. ...However, due to the shortage of donors and the long waiting lists, many of those patients are candidates for implantation of ventricular assist devices as a bridge to the cardiac transplant, or when this is not an option, as a definitive therapy. A series of four clinical cases of patients with ventricular assist devices that required surgical intervention, is presented. Three of them were assisted with long-term care: two EXCOR (pulsatile and para-corporeal) and one HEARTWARE (non-pulsatile and intra-corporeal), and the last one with short-term assistance; CentriMag biventricular Levitronix. There is no significant literature on the peri-operative implications of these patients when they undergo urgent or scheduled surgery. The experience in our centre leads us to raise the need to determine a series of aspects: operation of each device, emphasising the correct placement of the cannulas during the surgery; the proper management of any medication, emphasising the importance of anticoagulant and anti-platelet therapies; the Pathophysiological changes at cardiopulmonary level due to the implantation of these devices; and the importance of the administration of a correct antibiotic therapy. Given the complexity of these cases, the limited experience in this field, and the few cases that exist in these situations, it is recommended to create protocols to ensure their proper management.
A Monte Carlo dust tail model has been applied to extract the dust environment parameters of the comet C/2012 S1 (ISON) from both Earth-based and SOHO LASCO C3 observations, performed from about six ...astronomical units (AU) inbound, to just after perihelion passage, when only a small portion of the original comet nucleus has survived in the form of a cloud of tiny particles. The early Afrho and image data are consistent with particle ejection from an extended active area located at latitudes 35degreesN to 90degreesN (for a prograde rotating nucleus), with the spin axis having a large obliquity (I ~ 70degrees). This configuration nicely fits the early images and Afrho data until 3.9 AU inbound, when the emission should become isotropic in order to fit the data. The analysis of LASCO images reveals that, assuming an original nucleus of R sub(N) = 500 m with rho = 1000 kg m super(-3), at least half of its mass was vaporized when the comet was at about 17 R sub(middot in circle) inbound. We conclude that at that time the nucleus suffered a cataclysmic fragmentation releasing a huge amount of material of 2.3 x10 super(11) kg, equivalent to a sphere of 380 m in radius with density 1000 kg m super(-3). The surviving material after perihelion passage consists of very small dust particles of 0.1-50 mu m in radius with a total mass of just 6.7x10 super(8) kg.
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•Thermal analysis of exoskeletons: Antipathes caribbeana and Limulus polyphemus.•DMTA revealed Limulus has a stronger structure with a stepper glass transition.•DSC measurements ...exhibited a much larger water holding capacity in Antipathes.•X-ray diffraction analysis shows a higher crystallinity index in Limulus•FTIR showed α-chitin structures and high temperature C–N groups prevalence.
Thermomechanical and structural properties of two marine species exoskeletons, Antipathes caribbeana (black coral) and Limulus polyphemus (xiphosure), were studied using dynamic mechanical thermal analysis (DMTA), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). DMTA curves indicate the viscoelastic behavior and glass transition around 255°C, black coral presented a second transition (175°C) associated to the acetamide group attached to the α-chitin chain. DSC measurements showed a endothermic peak around 100°C, with enthalpies of 4.02 and 118.04J/g, indicating strong differences between exoskeletons respect to their water holding capacity and strength water–polymer interaction. A comparative analysis involving DSC and X-ray diffraction showed that lower values ΔH in xiphosure correspond to a material with a higher crystallinity (30), in contrast black coral exhibits higher values ΔH and a lower crystallinity (19). FTIR confirmed α-chitin based structure, at higher temperature diminishes the amide bands and a new one appears, related to C–N groups.
Aims. This paper is a continuation of the first paper in this series, where we presented an extended study of the dust environment of a sample of short-period comets and their dynamical history. On ...this occasion, we focus on comets 81P/Wild 2 and 103P/Hartley 2, which are of special interest as targets of the spacecraft missions Stardust and EPOXI. Methods. As in the previous study, we used two sets of observational data: a set of images, acquired at Sierra Nevada and Lulin observatories, and the Afρ data as a function of the heliocentric distance provided by the amateur astronomical association Cometas-Obs. The dust environment of comets (dust loss rate, ejection velocities, and size distribution of the particles) was derived from our Monte Carlo dust tail code. To determine their dynamical history we used the numerical integrator Mercury 6.2 to ascertain the time spent by these objects in the Jupiter family Comet region. Results. From the dust analysis, we conclude that both 81P/Wild 2 and 103P/Hartley 2 are dusty comets, with an annual dust production rate of 2.8 × 109 kg yr-1 and (0.4-1.5) × 109 kg yr-1, respectively. From the dynamical analysis, we determined their time spent in the Jupiter family Comet region as ~40 yr in the case of 81P/Wild 2 and ~1000 yr for comet 103P/Hartley 2. These results imply that 81P/Wild 2 is the youngest and the most active comet of the eleven short-period comets studied so far, which tends to favor the correlation between the time spent in JFCs region and the comet activity previously discussed.
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