Presence of factors that activate platelet aggregation in mitral stenotic patients' plasma

BACKGROUND: Although the association between mitral stenosis (MS) and increased coagulation activity is well recognized, it is unclear whether enhanced coagulation remains localized in the left atrium or whether this represents a systemic problem. To assess systemic coagulation parameters and changes in platelet aggregation, we measured fibrinogen levels and performed in vitro platelet function tests in plasma obtained from mitral stenotic patients' and from healthy control subjects' peripheral venous blood. METHODS: Sixteen newly diagnosed patients with rheumatic MS (Group P) and 16 healthy subjects (Group N) were enrolled in the study. Platelet-equalized plasma samples were evaluated to determine in vitro platelet function, using adenosine diphosphate (ADP), collagen and epinephrine in an automated aggregometer. In vitro platelet function tests in group N were performed twice, with and without plasma obtained from group P. RESULTS: There were no significant differences between the groups with respect to demographic variables. Peripheral venous fibrinogen levels in Group P were not significantly different from those in Group N. Adenosine diphosphate, epinephrine and collagen-induced platelet aggregation ratios were significantly higher in Group P than in Group N. When plasma obtained from Group P was added to Group N subjects' platelets, ADP and collagen-induced, but not epinephrine-induced, aggregation ratios were significantly increased compared to baseline levels in Group N. CONCLUSION: Platelet aggregation is increased in patients with MS, while fibrinogen levels remain similar to controls. We conclude that mitral stenotic patients exhibit increased systemic coagulation activity and that plasma extracted from these patients may contain some transferable factors that activate platelet aggregation

The Society for Immunotherapy of Cancer statement on best practices for multiplex immunohistochemistry (IHC) and immunofluorescence (IF) staining and validation.

OBJECTIVES: The interaction between the immune system and tumor cells is an important feature for the prognosis and treatment of cancer. Multiplex immunohistochemistry (mIHC) and multiplex immunofluorescence (mIF) analyses are emerging technologies that can be used to help quantify immune cell subsets, their functional state, and their spatial arrangement within the tumor microenvironment. METHODS: The Society for Immunotherapy of Cancer (SITC) convened a task force of pathologists and laboratory leaders from academic centers as well as experts from pharmaceutical and diagnostic companies to develop best practice guidelines for the optimization and validation of mIHC/mIF assays across platforms. RESULTS: Representative outputs and the advantages and disadvantages of mIHC/mIF approaches, such as multiplexed chromogenic IHC, multiplexed immunohistochemical consecutive staining on single slide, mIF (including multispectral approaches), tissue-based mass spectrometry, and digital spatial profiling are discussed. CONCLUSIONS: mIHC/mIF technologies are becoming standard tools for biomarker studies and are likely to enter routine clinical practice in the near future. Careful assay optimization and validation will help ensure outputs are robust and comparable across laboratories as well as potentially across mIHC/mIF platforms. Quantitative image analysis of mIHC/mIF output and data management considerations will be addressed in a complementary manuscript from this task force

Light Yield in DarkSide-10: a Prototype Two-phase Liquid Argon TPC for Dark Matter Searches

As part of the DarkSide program of direct dark matter searches using liquid argon TPCs, a prototype detector with an active volume containing 10 kg of liquid argon, DarkSide-10, was built and operated underground in the Gran Sasso National Laboratory in Italy. A critically important parameter for such devices is the scintillation light yield, as photon statistics limits the rejection of electron-recoil backgrounds by pulse shape discrimination. We have measured the light yield of DarkSide-10 using the readily-identifiable full-absorption peaks from gamma ray sources combined with single-photoelectron calibrations using low-occupancy laser pulses. For gamma lines of energies in the range 122-1275 keV, we get consistent light yields averaging 8.887+-0.003(stat)+-0.444(sys) p.e./keVee. With additional purification, the light yield measured at 511 keV increased to 9.142+-0.006(stat) p.e./keVee.Comment: 10 pages, 7 figures, Accepted for publication in Astroparticle Physic

Pitfalls in machine learning‐based assessment of tumor‐infiltrating lymphocytes in breast cancer: a report of the international immuno‐oncology biomarker working group

The clinical significance of the tumor-immune interaction in breast cancer (BC) has been well established, and tumor-infiltrating lymphocytes (TILs) have emerged as a predictive and prognostic biomarker for patients with triple-negative (estrogen receptor, progesterone receptor, and HER2 negative) breast cancer (TNBC) and HER2-positive breast cancer. How computational assessment of TILs can complement manual TIL-assessment in trial- and daily practices is currently debated and still unclear. Recent efforts to use machine learning (ML) for the automated evaluation of TILs show promising results. We review state-of-the-art approaches and identify pitfalls and challenges by studying the root cause of ML discordances in comparison to manual TILs quantification. We categorize our findings into four main topics; (i) technical slide issues, (ii) ML and image analysis aspects, (iii) data challenges, and (iv) validation issues. The main reason for discordant assessments is the inclusion of false-positive areas or cells identified by performance on certain tissue patterns, or design choices in the computational implementation. To aid the adoption of ML in TILs assessment, we provide an in-depth discussion of ML and image analysis including validation issues that need to be considered before reliable computational reporting of TILs can be incorporated into the trial- and routine clinical management of patients with TNBC

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Thermal convection in the presence of a vertical magnetic field

The interaction between thermal convection and an external uniform magnetic field in the vertical is numerically simulated within a computational domain of a horizontally periodic convective box between upper and lower rigid plates. The numerical technique is based on a spectral element method developed earlier to simulate natural thermal convection. In this work, it is extended to a magnetoconvection problem. Its main features are the use of rescaled Legendre-Lagrangian polynomial interpolants in expanding the flow variables except the pressure for which a modal expansion in terms of lower order polynomials is used to avoid the complicated staggered grid approach. The technique is validated in the steady roll and oscillatory convective regimes where various experimental and numerical results are available in the literature. The effect of a vertical magnetic field in such a way to inhibit the convective motions has been demonstrated

Individualized statistical learning from medical image databases: Application to identification of brain lesions

Rad se bavi analiziranjem uloge dobavljača u procesu proizvodnje i utvrđivanjem njihove funkcije kod uspješnosti tvrtke. Da bi poduzeća mogla biti uspješna potrebno je da odrede u kojoj su mjeri dobavljači važni za njih te koliko mogu doprinijeti zajedničkom uspjehu. Osim teorije, u radu se nalaze i primjeri koji ju nadopunjuju i približavaju nas samom procesu odabira dobavljača

Acute heart failure with accompanying chronic obstructive pulmonary disease Should we focus on beta blockers?

Background. Acute heart failure (AHF) with systolic dysfunction is associated with increased morbidity and mortality, and optimal therapy is not well established, despite the findings of evidence-based medicine. Beta blockers provide a mortality and morbidity benefit in patients with chronic systolic HF, and are currently indicated in all stages of patients with systolic HF. We evaluated therapies before discharge, in particular beta blockers, in patients hospitalized with AHF with and without accompanying chronic obstructive pulmonary disease (COPD)

Metabolic syndrome negatively impacts early patency of saphenous vein grafts

Background Coronary artery bypass grafting has been performed for a long period utilizing saphenous vein grafts, the fate of which might be crucial to prognosis following the operation. Metabolic syndrome, on the other hand, has become an increasingly important part of cardiovascular practice. We examined whether there was any negative effect of metabolic syndrome on saphenous vein graft patency in a relatively short term (<= 5 years)