Improved Constraints on Primordial Gravitational Waves using Planck, WMAP, and BICEP/Keck Observations through the 2018 Observing Season.

We present results from an analysis of all data taken by the BICEP2, Keck Array, and BICEP3 CMB polarization experiments up to and including the 2018 observing season. We add additional Keck Array observations at 220 GHz and BICEP3 observations at 95 GHz to the previous 95/150/220 GHz dataset. The Q/U maps now reach depths of 2.8, 2.8, and 8.8 µK_{CMB} arcmin at 95, 150, and 220 GHz, respectively, over an effective area of ≈600 square degrees at 95 GHz and ≈400 square degrees at 150 and 220 GHz. The 220 GHz maps now achieve a signal-to-noise ratio on polarized dust emission exceeding that of Planck at 353 GHz. We take auto- and cross-spectra between these maps and publicly available WMAP and Planck maps at frequencies from 23 to 353 GHz and evaluate the joint likelihood of the spectra versus a multicomponent model of lensed ΛCDM+r+dust+synchrotron+noise. The foreground model has seven parameters, and no longer requires a prior on the frequency spectral index of the dust emission taken from measurements on other regions of the sky. This model is an adequate description of the data at the current noise levels. The likelihood analysis yields the constraint r_{0.05}<0.036 at 95% confidence. Running maximum likelihood search on simulations we obtain unbiased results and find that σ(r)=0.009. These are the strongest constraints to date on primordial gravitational waves.

In vitro anthelmintic activity assessment of six medicinal plant aqueous extracts against donkey strongyles.

The lack of anthelmintic products licensed for donkeys and the rising number of small donkey milk farms in the countries of Western Europe and Italy have led to an increased interest in the study of reliable and safe plant-derived treatment alternatives. In this study, the aqueous extracts of Achillea millefolium L. (flowers), Artemisia absinthium L. (aerial parts), Centaurium erythraea Rafn. (flowers), Gentiana asclepiadea L. (rhizomes and roots), Inula helenium L. (rhizomes and roots) and Tanacetum vulgare L. (aerial parts), have been tested in vitro for their potential ovicidal and larvicidal activity against donkey nematodes. An egg-hatching assay (EHA) and larval development assay (LDA) were performed for the in vitro study, and median lethal concentration (LC-50) values for both EHA and LDA were calculated using probit analysis. All tested plant extracts showed strong anthelmintic activity against strongyle eggs and larvae at concentrations ranging between 125 and 1.95 mg/ml, except for C. erythraea, which exhibited very little or no effect at all at the tested concentrations. A strong ovicidal effect was observed in A. absinthium, with an LC-50 value of 0.486 mg/ml (95% confidence interval (CI) 0.21-1.09). Gentiana asclepiadea showed high efficacy against strongyle larvae, with an LC-50 value of 0.041 mg/ml (95% CI 0.01-0.16). The most significant (P < 0.01) anthelmintic activity was exhibited by I. helenium, with an LC-50 value of 0.041 mg/ml (95% CI 0.01-0.16) for EHA and 0.41 mg/ml (95% CI 0.27-0.62) for LDA. The results proved the anthelmintic efficacy of the tested plant extracts, highlighting the need for further research into plant bioactive molecules both in vitro and in vivo.

Constraints on Primordial Gravitational Waves Using Planck, WMAP, and New BICEP2/Keck Observations through the 2015 Season.

We present results from an analysis of all data taken by the bicep2/Keck CMB polarization experiments up to and including the 2015 observing season. This includes the first Keck Array observations at 220 GHz and additional observations at 95 and 150 GHz. The Q and U maps reach depths of 5.2, 2.9, and 26 µK_{CMB} arcmin at 95, 150, and 220 GHz, respectively, over an effective area of ≈400 square degrees. The 220 GHz maps achieve a signal to noise on polarized dust emission approximately equal to that of Planck at 353 GHz. We take auto and cross spectra between these maps and publicly available WMAP and Planck maps at frequencies from 23 to 353 GHz. We evaluate the joint likelihood of the spectra versus a multicomponent model of lensed-ΛCDM+r+dust+synchrotron+noise. The foreground model has seven parameters, and we impose priors on some of these using external information from Planck and WMAP derived from larger regions of sky. The model is shown to be an adequate description of the data at the current noise levels. The likelihood analysis yields the constraint r_{0.05}<0.07 at 95% confidence, which tightens to r_{0.05}<0.06 in conjunction with Planck temperature measurements and other data. The lensing signal is detected at 8.8σ significance. Running a maximum likelihood search on simulations we obtain unbiased results and find that σ(r)=0.020. These are the strongest constraints to date on primordial gravitational waves.

Improved Constraints on Cosmology and Foregrounds from BICEP2 and Keck Array Cosmic Microwave Background Data with Inclusion of 95 GHz Band.

We present results from an analysis of all data taken by the BICEP2 and Keck Array cosmic microwave background (CMB) polarization experiments up to and including the 2014 observing season. This includes the first Keck Array observations at 95 GHz. The maps reach a depth of 50 nK deg in Stokes Q and U in the 150 GHz band and 127 nK deg in the 95 GHz band. We take auto- and cross-spectra between these maps and publicly available maps from WMAP and Planck at frequencies from 23 to 353 GHz. An excess over lensed ΛCDM is detected at modest significance in the 95×150 BB spectrum, and is consistent with the dust contribution expected from our previous work. No significant evidence for synchrotron emission is found in spectra such as 23×95, or for correlation between the dust and synchrotron sky patterns in spectra such as 23×353. We take the likelihood of all the spectra for a multicomponent model including lensed ΛCDM, dust, synchrotron, and a possible contribution from inflationary gravitational waves (as parametrized by the tensor-to-scalar ratio r) using priors on the frequency spectral behaviors of dust and synchrotron emission from previous analyses of WMAP and Planck data in other regions of the sky. This analysis yields an upper limit r_{0.05}<0.09 at 95% confidence, which is robust to variations explored in analysis and priors. Combining these B-mode results with the (more model-dependent) constraints from Planck analysis of CMB temperature plus baryon acoustic oscillations and other data yields a combined limit r_{0.05}<0.07 at 95% confidence. These are the strongest constraints to date on inflationary gravitational waves.

Joint analysis of BICEP2/keck array and Planck Data.

We report the results of a joint analysis of data from BICEP2/Keck Array and Planck. BICEP2 and Keck Array have observed the same approximately 400 deg^{2} patch of sky centered on RA 0 h, Dec. -57.5°. The combined maps reach a depth of 57 nK deg in Stokes Q and U in a band centered at 150 GHz. Planck has observed the full sky in polarization at seven frequencies from 30 to 353 GHz, but much less deeply in any given region (1.2 µK deg in Q and U at 143 GHz). We detect 150×353 cross-correlation in B modes at high significance. We fit the single- and cross-frequency power spectra at frequencies ≥150 GHz to a lensed-ΛCDM model that includes dust and a possible contribution from inflationary gravitational waves (as parametrized by the tensor-to-scalar ratio r), using a prior on the frequency spectral behavior of polarized dust emission from previous Planck analysis of other regions of the sky. We find strong evidence for dust and no statistically significant evidence for tensor modes. We probe various model variations and extensions, including adding a synchrotron component in combination with lower frequency data, and find that these make little difference to the r constraint. Finally, we present an alternative analysis which is similar to a map-based cleaning of the dust contribution, and show that this gives similar constraints. The final result is expressed as a likelihood curve for r, and yields an upper limit r_{0.05}<0.12 at 95% confidence. Marginalizing over dust and r, lensing B modes are detected at 7.0σ significance.

[Inflammatory Markers and Their RoIe in Assessing Prognosis of patients With Stable Coronary Artery Disease After Coronary Stenting].

In recent years, expanded data have demonstrated the association between increased inflammatory markers and risk of adverse cardiovascular events in patients undergoing percutaneous coronary intervention (PCI) with stent implantation. Particularly, several studies have demonstrated association between increased C-reactive protein (CRP) level and various risk factors of cardiovascular diseases and their complications. The role of CRP in predicting restenosis after implantation of bare metal stents has been proven, but its role in predicting drug-eluting stents restenosis is still unproved. Significant association between increased white blood cells count and risk of development and severity of coronary artery disease and as well as poor prognosis after PCI has also been demonstrated. But erythrocyte sedimentation rate has been studied insufficiently in this regard. According to some studies, including those conducted in our institute, one can suggest an association between eosinophilic inflammatory response, progression of coronary atherosclerosis, and drug-eluting stents restenosis. Identification of factors affecting prognosis of patients with coronary heart disease after PCI will allow determining further strategy of patient management.

[Inflammatory Markers and Their Role in Assessing Prognosis of Patients With Stable Coronary Artery Disease After Coronary Stenting].

In recent years, expanded data have demonstrated the association between increased inflammatory markers and risk of adverse cardiovascular events in patients undergoing percutaneous coronary intervention (PCI) with stent implantation. Particularly, several studies have demonstrated association between increased C-reactive protein (CRP) level and various risk factors of cardiovascular diseases and their complications. The role of CRP in predicting restenosis after implantation of bare metal stents has been proven, but its role in predicting drug-eluting stents restenosis is still unproved. Significant association between increased white blood cells count and risk of development and severity of coronary artery disease and as well as poor prognosis after PCI has also been demonstrated. But erythrocyte sedimentation rate has been studied insufficiently in this regard. According to some studies, including those conducted in our institute, one can suggest an association between eosinophilic inflammatory response, progression of coronary atherosclerosis, and drug-eluting stents restenosis.

[Prognostic value of markers of inflammation in patients with stable ischemic heart disease after implantation of stents with drug covering at the background of long-term therapy with statins (inhospital period)].

The objective of this study was to examine the prognostic value of C-reactive protein, erythrocyte sedimentation rate (ESR), white blood count, phospholipase A2 in patients with stable ischemic disease on long-term statin therapy undergoing percutaneous coronary intervention (PCI) with drug-eluting stent implantation. In the interim analysis in- hospital outcomes were assessed a total of 602 patients from December 2009 through December 2010 underwent successful PCI with at least one DES implanted. They were prospectively followed before discharge. MACE (death, myocardial infarction [MI], stroke, stent thrombosis [ST] which did not lead to MI) occurred in 10,6% of the patients. There was no death or stroke before discharge. MI (including 0,3% of Q-MI) occurred in 10,3% of the patients. 6 patients had verified ST. Multivariate logistic regression identified ESR level before PCI and total length of stents implanted as independent predictors of MACE.

[Assessment of the course of ischemic heart disease after placement of stents with drug covering and uncovered metal stents: data of 3 years follow-up].

The placement of sirolimus-eluting stents decreases the frequency of repeat revascularization procedures in patients undergoing percutaneous coronary intervention (PCI) in randomized clinical trials. However, there is uncertainty about the effectiveness of sirolimus-eluting stents, and increasing concern about their safety in routine clinical practice. From the prof. Samko PCI laboratory in Moscow, Russia, we identified 426 patients, who received either bare-metal stents alone or sirolimus-eluting stents alone during an index PCI procedure between March 1, 2002, and September 31, 2004.The primary outcomes of the study were the rates of target-lesion revascularization, myocardial infarction, death, late stent thrombosis. The 3-year rate of target-lesion revascularization was significantly lower among patients who received sirolimus-eluting stents than among those who received bare-metal stents (3.1% vs. 19 %, p=0.001). The 3-year mortality rate was not different between the bare-metal stent group and the sirolimus eluting stent group (5.9% vs. 7.2%, p=0.68), the 3-year rate of all ARC late stent thrombosis was similar in the two groups (5.9% and 7.2%, respectively; p=0.95). Sirolimus-eluting stents are effective in reducing the need for target-vessel revascularization without significantly increased rates of death, late stent thrombosis, myocardial infarction.

[Comparative transcriptome analysis of human aorta atherosclerotic lesions and peripheral blood leukocytes from essential hypertension patients].

One of the major cardiovascular risk factor which predisposes to and accelerates atherosclerosis is arterial hypertension (AH). To determine the molecular basis of the crosslink between AH and atherosclerosis for the development of new treatment strategies large-scale transcriptome analysis of the cells implicated in atherogenesis is needed. We used cDNA microarray technique for simultaneous analysis of gene expression in human abdominal aorta normal sites and atherosclerotic lesions of different histological types, as well as in peripheral blood leukocytes from patients with essential hypertension (EH) and donors. The microarray data were verified by quantitative RT-PCR (reverse transcription coupled with polymerase chain reaction) and immunohistochemical analysis. Differential expression of 40 genes has been found, among which twenty two genes demonstrated up-regulation and 18 genes demonstrated down-regulation in atherosclerotic aorta compared with normal vessel. New gene-candidates, implicated in atherogenesis, have been identified - FPRL2, CD37, CD53, RGS1, LCP1, SPI1, CTSA, EPAS1, FHL1, GEM, RHOB, SPARCL1, ITGA8, PLN, and COL14A1. These genes participate in cell migration and adhesion, phenotypic changes of smooth muscle cells, immune and inflammatory reactions, oxidative processes and extracellular matrix remodeling. We have found increased expression levels of CD53, SPI1, FPRL2, SPP1, CTSD, ACP5, LCP1, CTSA and LIPA genes in peripheral blood leukocytes from EH patients and in atherosclerotic lesions of human aorta. The majority of these genes significantly (p<0.005) positively (r>0.5) correlated with AH stage as well as with histological grading of atherosclerotic lesions.

[Drug-eluting stents: long-term safety].

The review concerns the problem of late thromboses of drug-eluting stents and their influence on late prognosis of the patients; presents long-term results of the trial of sirolimus-eluting stents implanted to patients with coronary heart disease; analyses mechanisms of development of late stent thrombosis, data from different meta-analyses and registers comparing long-term outcomes in patients with implanted sirolimus-eluting stents and metallic stents; suggests risk factors of late thromboses of drug-eluting stents; presents original evidence on 3.5-year follow-up of patients with implanted sirolimus-eluting stents and metallic stents.

Observational Prospective study to esTIMAte the rates of outcomes in patients undergoing PCI with drug-eluting stent implantation who take statins -follow-up (OPTIMA II).

OBJECTIVE: The OPTIMA II study sought to evaluate rates of major adverse cardiac and cerebrovascular events (MACCEs) during the long-term follow-up of chronic statin users who underwent percutaneous coronary intervention (PCI) with implantation of a drug-eluting stent (DES). RESEARCH DESIGN AND METHODS: OPTIMA II was a non-interventional, observational study conducted at a single center in the Russian Federation. Included patients were aged ≥18 years with stable angina who had received long-term (≥1 month) statin therapy prior to elective PCI with DES implantation and who had participated in the original OPTIMA study. Patients received treatment for stable angina after PCI as per routine study site clinical practice. Study data were collected from patient medical records and a routine visit 4 years after PCI. CLINICAL TRIAL REGISTRATION: NCT02099565. MAIN OUTCOME MEASURES: Rate of MACCEs 4 years after PCI. RESULTS: Overall, 543 patients agreed to participate in the study (90.2% of patients in the original OPTIMA study). The mean (± standard deviation [SD]) duration of follow-up from the date of PCI to data collection was 4.42 ± 0.58 (range: 0.28-5.56) years. The frequency of MACCEs (including data in patients who died) was 30.8% (95% confidence interval: 27.0-34.7); half of MACCEs occurred in the first year of follow-up. After PCI, the majority of patients had no clinical signs of angina. Overall, 24.3% of patients discontinued statin intake in the 4 years after PCI. Only 7.7% of patients achieved a low-density lipoprotein (LDL) cholesterol goal of <1.8 mmol/L. Key limitations of this study related to its observational nature; for example, the sample size was small, the clinical results were derived from outpatients and hospitalized medical records, only one follow-up visit was performed at the end of the study (after 4 years' follow-up), only depersonalized medical information was made available for statistical analysis, and adherence to statin treatment was evaluated on the basis of patient questionnaire. CONCLUSIONS: Long-term follow-up of patients who underwent PCI with DES implantation demonstrated MACCEs in nearly one-third of patients, which is comparable to data from other studies. PCI was associated with relief from angina or minimal angina frequency, but compliance with statin therapy and the achievement of LDL cholesterol targets 4 years after PCI were suboptimal.

Altered gene expression pattern in peripheral blood leukocytes from patients with arterial hypertension.

The role of various inflammatory mechanisms and oxidative stress in the development of atherosclerosis and arterial hypertension (AH) has been increasingly acknowledged during recent years. Hypertension per se or factors that cause hypertension along with other complications lead to infiltration of activated leukocytes in the vascular wall, where these cells contribute to the development of vascular injury by releasing cytokines, oxygen radicals, and other toxic mediators. However, molecular mechanisms underlying leukocyte activation at transcriptional level in AH are still far from being clear. To solve this problem we employed cDNA microarray technology to reveal the differences in gene expression in peripheral blood leukocytes from patients with AH compared with healthy individuals. The microarray data were verified by a semi-quantitative RT-PCR method. We found 25 genes with differential expression in leukocytes from AH patients among which 21 genes were upregulated and 4 genes were downregulated. These genes are implicated in apoptosis (CASP2, CASP4, and CASP8, p53, UBID4, NAT1, and Fte-1), inflammatory response (CAGC, CXCR4, and CX3CR1), control of MAP kinase function (PYST1, PAC1, RAF1, and RAFB1), vesicular trafficking of molecules among cellular organelles (GDI-1 and GDI-2), cell redox homeostasis (GLRX), cellular stress (HSPA8 and HSP40), and other processes. Gene expression pattern of the majority of genes was similar in AH patients independent of the disease stage and used hypotensive therapy, but was clearly different from that of normotensive subjects.