Azimuthal Anisotropy in U+U and Au+Au Collisions at RHIC.

Collisions between prolate uranium nuclei are used to study how particle production and azimuthal anisotropies depend on initial geometry in heavy-ion collisions. We report the two- and four-particle cumulants, v_{2}{2} and v_{2}{4}, for charged hadrons from U+U collisions at sqrt[s_{NN}]=193  GeV and Au+Au collisions at sqrt[s_{NN}]=200  GeV. Nearly fully overlapping collisions are selected based on the energy deposited by spectators in zero degree calorimeters (ZDCs).

SOAP-V: Introducing a method to empower medical students to be change agents in bending the cost curve.

Medical students must learn how to practice high-value, cost-conscious care. By modifying the traditional SOAP (Subjective-Objective-Assessment-Plan) presentation to include a discussion of value (SOAP-V), we developed a cognitive forcing function designed to promote discussion of high-value, cost-conscious care during patient delivery. The SOAP-V model prompts the student to consider (1) the evidence that supports a test or treatment, (2) the patient's preferences and values, and (3) the financial cost of a test or treatment compared to alternatives.

Precision Measurement of the Longitudinal Double-Spin Asymmetry for Inclusive Jet Production in Polarized Proton Collisions at sqrt[s]=200 GeV.

We report a new measurement of the midrapidity inclusive jet longitudinal double-spin asymmetry, A_{LL}, in polarized pp collisions at center-of-mass energy sqrt[s]=200  GeV. The STAR data place stringent constraints on polarized parton distribution functions extracted at next-to-leading order from global analyses of inclusive deep-inelastic scattering (DIS), semi-inclusive DIS, and RHIC pp data. The measured asymmetries provide evidence at the 3σ level for positive gluon polarization in the Bjorken-x region x>0.

Local effects of human PCSK9 on the atherosclerotic lesion.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes atherosclerosis by increasing low-density lipoprotein (LDL) cholesterol levels through degradation of hepatic LDL receptor (LDLR). Studies have described the systemic effects of PCSK9 on atherosclerosis, but whether PCSK9 has local and direct effects on the plaque is unknown. To study the local effect of human PCSK9 (hPCSK9) on atherosclerotic lesion composition, independently of changes in serum cholesterol levels, we generated chimeric mice expressing hPCSK9 exclusively from macrophages, using marrow from hPCSK9 transgenic (hPCSK9tg) mice transplanted into apoE(-/-) and LDLR(-/-) mice, which were then placed on a high-fat diet (HFD) for 8 weeks.

Uric acid correlates to oxidation and inflammation in opposite directions in women.

Objective: To evaluate the association of uric acid (UA) levels with a panel of markers of oxidative stress and inflammation.

Methods: Plasma UA levels, along with a panel of oxidative stress and inflammatory markers, were measured in 755 Chinese women.

Results: Plasma UA levels were inversely associated with urinary levels of the oxidative stress marker F2-isoprostanes and positively correlated to levels of inflammatory markers, such as C-reactive protein and some proinflammatory cytokines (tumor necrosis factor-α and interleukin-6) in blood as well as prostaglandin E2 metabolites in urine.

Intake of polyunsaturated fat in relation to mortality among statin users and non-users in the Southern Community Cohort Study.

Background And Aims: Consumption of polyunsaturated fatty acids (PUFA), especially the n3-series, may protect against cardiovascular disease (CVD), but recent randomized studies have failed to demonstrate these benefits. One of the prevailing hypotheses is that PUFA intake may not confer benefits beyond those provided by statins, but studies comparing statin users to non-users with regard to effects of PUFA are lacking.

Methods And Results: Black and white men and women (n = 69,559) in the Southern Community Cohort Study were studied.

Observation of Charge Asymmetry Dependence of Pion Elliptic Flow and the Possible Chiral Magnetic Wave in Heavy-Ion Collisions.

We present measurements of π(-) and π(+) elliptic flow, v(2), at midrapidity in Au+Au collisions at √[s(NN)]=200, 62.4, 39, 27, 19.6, 11.

Atherosclerosis following renal injury is ameliorated by pioglitazone and losartan via macrophage phenotype.

Objective: Chronic kidney disease (CKD) amplifies atherosclerosis, which involves renin-angiotensin system (RAS) regulation of macrophages. RAS influences peroxisome proliferator-activated receptor-γ (PPARγ), a modulator of atherogenic functions of macrophages, however, little is known about its effects in CKD. We examined the impact of combined therapy with a PPARγ agonist and angiotensin receptor blocker on atherogenesis in a murine uninephrectomy model.

Sex-Specific Parental Effects on Offspring Lipid Levels.

Background: Plasma lipid levels are highly heritable traits, but known genetic loci can only explain a small portion of their heritability.

Methods And Results: In this study, we analyzed the role of parental levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TGs) in explaining the values of the corresponding traits in adult offspring. We also evaluated the contribution of nongenetic factors that influence lipid traits (age, body mass index, smoking, medications, and menopause) alone and in combination with variability at the genetic loci known to associate with TC, LDL-C, HDL-C, and TG levels.

Macrophage SR-BI mediates efferocytosis via Src/PI3K/Rac1 signaling and reduces atherosclerotic lesion necrosis.

Macrophage apoptosis and efferocytosis are key determinants of atherosclerotic plaque inflammation and necrosis. Bone marrow transplantation studies in ApoE- and LDLR-deficient mice revealed that hematopoietic scavenger receptor class B type I (SR-BI) deficiency results in severely defective efferocytosis in mouse atherosclerotic lesions, resulting in a 17-fold higher ratio of free to macrophage-associated dead cells in lesions containing SR-BI(-/-) cells, 5-fold more necrosis, 65.2% less lesional collagen content, nearly 7-fold higher dead cell accumulation, and 2-fold larger lesion area.

Summary of the evidence on modifiable risk factors for cognitive decline and dementia: A population-based perspective.

An estimated 47 million people worldwide are living with dementia in 2015, and this number is projected to triple by 2050. In the absence of a disease-modifying treatment or cure, reducing the risk of developing dementia takes on added importance. In 2014, the World Dementia Council (WDC) requested the Alzheimer's Association evaluate and report on the state of the evidence on modifiable risk factors for cognitive decline and dementia.

Residual Cardiovascular Risk in Chronic Kidney Disease: Role of High-density Lipoprotein.

Although reducing low-density lipoprotein-cholesterol (LDL-C) levels with lipid-lowering agents (statins) decreases cardiovascular disease (CVD) risk, a substantial residual risk (up to 70% of baseline) remains after treatment in most patient populations. High-density lipoprotein (HDL) is a potential contributor to residual risk, and low HDL-cholesterol (HDL-C) is an established risk factor for CVD. However, in contrast to conventional lipid-lowering therapies, recent studies show that pharmacologic increases in HDL-C levels do not bring about clinical benefits.

Method applied to the background analysis of energy data to be considered for the European Reference Life Cycle Database (ELCD).

Under the framework of the European Platform on Life Cycle Assessment, the European Reference Life-Cycle Database (ELCD - developed by the Joint Research Centre of the European Commission), provides core Life Cycle Inventory (LCI) data from front-running EU-level business associations and other sources. The ELCD contains energy-related data on power and fuels. This study describes the methods to be used for the quality analysis of energy data for European markets (available in third-party LC databases and from authoritative sources) that are, or could be, used in the context of the ELCD.

Background qualitative analysis of the European Reference Life Cycle Database (ELCD) energy datasets - part I: fuel datasets.

Introduction: The aim of this study is to identify areas of potential improvement of the European Reference Life Cycle Database (ELCD) fuel datasets.

Case Description: The revision is based on the data quality indicators described by the ILCD Handbook, applied on sectorial basis. These indicators evaluate the technological, geographical and time-related representativeness of the dataset and the appropriateness in terms of completeness, precision and methodology.

Plasma lipid levels and colorectal adenoma risk.

Purpose: Abnormalities in lipid levels have been associated with colorectal neoplasm risk; however, few studies have adjusted for use of cholesterol-lowering medications. The objective of this study was to determine the association of plasma lipid levels with adenoma risk while accounting for statin medication use.

Methods: We included 254 subjects with advanced adenoma, 246 with single small adenoma, 179 with multiple small adenoma cases, and 403 control participants in the Tennessee Colorectal Polyp Study who also had plasma lipid measurements performed.

Isolevuglandin-type lipid aldehydes induce the inflammatory response of macrophages by modifying phosphatidylethanolamines and activating the receptor for advanced glycation endproducts.

Aims: Increased lipid peroxidation occurs in many conditions associated with inflammation. Because lipid peroxidation produces lipid aldehydes that can induce inflammatory responses through unknown mechanisms, elucidating these mechanisms may lead to development of better treatments for inflammatory diseases. We recently demonstrated that exposure of cultured cells to lipid aldehydes such as isolevuglandins (IsoLG) results in the modification of phosphatidylethanolamine (PE).

Targeting PCSK9 for therapeutic gains.

Even though it is only a little over a decade from the discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9) as a plasma protein that associates with both hypercholesterolemia and low cholesterol syndromes, a rich literature has developed describing its unique physiology and the impact of antagonism of this molecule on cholesterol metabolism for therapeutic purposes. Indeed, the PCSK9 story is unfolding rapidly, with many answers and more questions. This review summarizes the most recent data from phase II/III clinical trials of PCSK9 inhibition with the three leading antibodies, highlights the clinical significance of the ongoing studies, and suggests future areas of investigation based on recent basic science discoveries on the physiology of PCSK9.

PCSK9 inhibition to reduce cardiovascular disease risk: recent findings from the biology of PCSK9.

Purpose Of Review: Review novel insights into the biology of proprotein convertase subtilisin/kexin 9 (PCSK9) that may explain the extreme efficiency of PCSK9 inhibition and the unexpected metabolic effects resulting from PCSK9 monoclonal antibody therapy, and may identify additional patients as target of therapy.

Recent Findings: For over 20 years, the practical knowledge of cholesterol metabolism has centered around cellular mechanisms, and around the idea that statin therapy is the essential step to control metabolic abnormalities for cardiovascular risk management. This view has been embraced by the recent AHA/ACC guidelines, but is being challenged by recent studies including nonstatin medications and by the development of a new class of cholesterol-lowering agents that seems destined to early US Food and Drug Administration approval.

The role of PCSK9 in intestinal lipoprotein metabolism: synergism of statin and ezetimibe.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a major role in the regulation of lipoprotein metabolism, mostly through control of low-density lipoprotein receptor degradation. Depletion of cellular cholesterol causes a compensatory increase in plasma PCSK9 levels, which can diminish the cholesterol-lowering power of statins and may lead to the overproduction of intestinal lipoproteins, mainly thorough the up regulation of microsomal triglyceride transfer protein and the Niemann-Pick C1-like 1 protein, the target of ezetimibe. Thus, ezetimibe therapy may counter this unwanted effect of statins, providing an additional theoretical rationale for combining the effect of ezetimibe on intestinal cholesterol absorption and that of statins on cholesterol synthesis.

Background qualitative analysis of the European reference life cycle database (ELCD) energy datasets - part II: electricity datasets.

The aim of this paper is to identify areas of potential improvement of the European Reference Life Cycle Database (ELCD) electricity datasets. The revision is based on the data quality indicators described by the International Life Cycle Data system (ILCD) Handbook, applied on sectorial basis. These indicators evaluate the technological, geographical and time-related representativeness of the dataset and the appropriateness in terms of completeness, precision and methodology.