Targeting cardiovascular inflammation: next steps in clinical translation

2020 ◽  
Author(s):  
Patrick R Lawler ◽  
Deepak L Bhatt ◽  
Lucas C Godoy ◽  
Thomas F Lüscher ◽  
Robert O Bonow ◽  
...  
Keyword(s):  
Vascular Inflammation ◽  
Large Body ◽  
High Sensitivity ◽  
Clinical Translation ◽  
Stable Phase ◽  
Atherosclerotic Cardiovascular Disease ◽  
The Road ◽  
Reactive Protein ◽  
On The Road ◽  
The Right

Abstract Systemic vascular inflammation plays multiple maladaptive roles which contribute to the progression and destabilization of atherosclerotic cardiovascular disease (ASCVD). These roles include: (i) driving atheroprogression in the clinically stable phase of disease; (ii) inciting atheroma destabilization and precipitating acute coronary syndromes (ACS); and (iii) responding to cardiomyocyte necrosis in myocardial infarction (MI). Despite an evolving understanding of these biologic processes, successful clinical translation into effective therapies has proven challenging. Realizing the promise of targeting inflammation in the prevention and treatment of ASCVD will likely require more individualized approaches, as the degree of inflammation differs among cardiovascular patients. A large body of evidence has accumulated supporting the use of high-sensitivity C-reactive protein (hsCRP) as a clinical measure of inflammation. Appreciating the mechanistic diversity of ACS triggers and the kinetics of hsCRP in MI may resolve purported inconsistencies from prior observational studies. Future clinical trial designs incorporating hsCRP may hold promise to enable individualized approaches. The aim of this Clinical Review is to summarize the current understanding of how inflammation contributes to ASCVD progression, destabilization, and adverse clinical outcomes. We offer forward-looking perspective on what next steps may enable successful clinical translation into effective therapeutic approaches—enabling targeting the right patients with the right therapy at the right time—on the road to more individualized ASCVD care.

Determination of Resistance to Abrasive Wear. VIII. Influence of Softeners in Tests with the Akron-Croydon and Du Pont Machines

1949 ◽  
Vol 22 (1) ◽  
pp. 259-262
Author(s):  
J. F. Morley
Keyword(s):  
Unit Area ◽  
Published Data ◽  
The Road ◽  
Abrasive Surface ◽  
Abrasive Power ◽  
The Difference ◽  
On The Road ◽  
The Right ◽  
Abrasion Testing

Abstract These experiments indicate that softeners can influence abrasion resistance, as measured by laboratory machines, in some manner other than by altering the stress-strain properties of the rubber. One possible explanation is that the softener acts as a lubricant to the abrasive surface. Since this surface, in laboratory abrasion-testing machines, is relatively small, and comes repeatedly into contact with the rubber under test, it seems possible that it may become coated with a thin layer of softener that reduces its abrasive power. It would be interesting in this connection to try an abrasive machine in which a long continuous strip of abrasive material was used, no part of it being used more than once, so as to eliminate or minimize this lubricating effect. The fact that the effect of the softener is more pronounced on the du Pont than on the Akron-Croydon machine lends support to the lubrication hypothesis, because on the former machine the rate of wear per unit area of abrasive is much greater. Thus in the present tests the volume of rubber abraded per hr. per sq. cm. of abrasive surface ranges from 0.03 to 0.11 cc. on the du Pont machine and from 0.0035 to 0.0045 cc. on the Akron-Croydon machine. On the other hand, if the softener acts as a lubricant, it would be expected to reduce considerably the friction between the abrasive and the rubber and hence the energy used in dragging the rubber over the abrasive surface. The energy figures given in the right-hand columns of Tables 1 and 3, however, show that there is relatively little variation between the different rubbers. As a test of the lubrication hypothesis, it would be of interest to vary the conditions of test so that approximately the same amount of rubber per unit area of abrasive is abraded in a given time on both machines; this should show whether the phenomena observed under the present test conditions are due solely to the difference in rate of wear or to an inherent difference in the type of wear on the two machines. This could most conveniently be done by considerably reducing the load on the du Pont machine. In the original work on this machine the load was standardized at 8 pounds, but no figures are quoted to show how abrasion loss varies with the load. As an addition to the present investigation, it is proposed to examine the effect of this variation with special reference to rubbers containing various amounts and types of softener. Published data on the influence of softeners on the road wear of tire rubbers do not indicate anything like such large effects as are shown by the du Pont machine. This throws some doubt on the value of this machine for testing tire tread rubbers, a conclusion which is confirmed by information obtained from other workers.

scholarly journals Characterisation of cyclists’ willingness to pay for green initiatives at Africa’s largest cycle tour

2016 ◽  
Vol 19 (3) ◽  
pp. 432-439
Author(s):  
Melville Saayman ◽  
Waldo Krugell ◽  
Andrea Saayman
Keyword(s):  
Willingness To Pay ◽  
Carbon Footprint ◽  
Climate Change Mitigation ◽  
Demographic Variables ◽  
The Road ◽  
Road Cycling ◽  
Different Types ◽  
On The Road ◽  
The Right ◽  
Change Mitigation

The Cape Argus Pick n Pay Cycle Tour is a major event on the road cycling calendar. The majority of cyclists travel significant distances and participation produces a substantial carbon footprint. This paper examines participants’ willingness to pay to offset their carbon footprint. The purpose of this paper is to make a contribution to the literature by linking willingness to pay to attitudes towards or beliefs (green views) about the initiatives in place, to ensure a greener cycle tour. Factor analysis is used to identify different types of cyclists, based on their green views: those with green money, those who prefer green products and the “re-cyclers”. The results of the regression analysis reveal that socio-demographic variables and the right attitude towards the environment are significant predictors of stated willingness to pay for climate change mitigation.

Abstract 14093: High-Sensitivity C-reactive Protein Modifies the Effect of Lipoprotein (a) on Cardiovascular Risk: The Multi-Ethnic Study of Atherosclerosis (MESA)

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Wei Zhang ◽  
Jaime L Speiser ◽  
Miguel Cainzos Achirica ◽  
Khurram Nasir ◽  
Michael Tsai ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Reference Group ◽  
High Sensitivity ◽  
Chinese Americans ◽  
Cox Proportional Hazards ◽  
Atherosclerotic Cardiovascular Disease ◽  
C Reactive Protein ◽  
Lipoprotein A ◽  
Reactive Protein ◽  
Ascvd Risk

Introduction: Lipoprotein (a) (Lp(a)) and inflammation, as represented by elevated high-sensitivity C-reactive protein (hsCRP) concentration, are both considered as risk-enhancers in the 2018 AHA/ACC Cholesterol guidelines. However, little is known as to whether the association of Lp(a) with atherosclerotic cardiovascular disease (ASCVD) risk is modified by inflammation. Objective: We assessed whether hsCRP modifies the association of Lp(a) with ASCVD risk. Methods: MESA participants with baseline hsCRP and Lp(a) levels were included. Incident ASCVD events were ascertained from baseline through 2017. Time to incident ASCVD was analyzed using Kaplan Meir curves. Cox proportional hazards models were used to assess the association between Lp(a), hsCRP, and time to ASCVD events adjusting for covariates. Results: The study included 4,654 participants with mean age of 62 and 52.5% females (1,702 Caucasians, 557 Chinese Americans, 1,336 African Americans and 1,059 Hispanics). With a mean 13.6-year follow-up, 676 ASCVD events occurred among 4,609 participants (Figure 1). In participants with hsCRP <2mg/L, the association of Lp(a) (per 1 Log unit increase) and risk for ASCVD as represented by hazard ratio (HR) and 95%CI was 1.01 (0.79, 1.28). In subjects with hsCRP ≥2mg/L, the risk increased to 1.26 (1.01, 1.58). When compared to the reference group with Lp(a) <50mg/dL and hsCRP <2mg/L, the risk for ASCVD in participants with Lp(a) ≥50mg/dL and hsCRP <2mg/L was 1.13 (0.85, 1.50) and in those with Lp(a) <50mg/dL and hsCRP ≥2mg/L was 1.09 (0.92, 1.31). The risk increased significantly to 1.62 (1.26, 2.07) in participants with Lp(a) ≥50mg/dL and hsCRP ≥2mg/L. Conclusions: Lp(a)-related ASCVD risk is modified by hsCRP levels. The findings of this analysis suggest that Lp(a) may serve as a risk enhancing factor in individuals with hsCRP level ≥2mg/L. Future studies are needed to determine whether Lp(a) is associated with risk of ASCVD in the absence of subclinical inflammation.

The New Conservatives

2017 ◽  
pp. 106-139
Author(s):  
Peter Kolozi
Keyword(s):  
World War Ii ◽  
Cold War ◽  
The State ◽  
Economic Systems ◽  
World War ◽  
Post World War Ii ◽  
The Road ◽  
On The Road ◽  
The Right

Post World War II conservative thinking witnessed a marked shift in criticism away from capitalism itself and to the state. Cold War conservatives’ anti-communism led many on the right to perceive economic systems in stark terms as either purely capitalistic or on the road to communism.

A Tryst with Reality: Child Labor in the Heart of India, New Delhi

2012 ◽  
Vol 3 (1) ◽  
Author(s):  
Rewa Singh
Keyword(s):  
Child Labor ◽  
Life Histories ◽  
Ground Level ◽  
New Delhi ◽  
Social Evil ◽  
The Road ◽  
The People ◽  
The Government ◽  
On The Road ◽  
The Right

“Why do we have to pay the price of poverty? We didn’t create poverty, adults did.” This might be the sentiment of every child who is forced to work at an age when he or she deserves to go to school unlike the fellow kids who are born in a family that can afford to give them a decent childhood. Child Labor is the single most damaging impediment on the road to achieving the goal of development and the purpose of this paper is to show the obstacles that this social evil poses in the path to development. The study used Exploratory, rather unstructured research design and instruments such as case studies and life histories. The study indicates that the government of India has taken some strict measures to eradicate this evil such as the passing of the Right to Education Bill, illegalization of employment of children under the age of 14 years, schemes like “Sarva Siksha Abhiyan” (Education for all campaign), free afternoon meal and so on. But on the ground level their implementation is shoddy due to (as bureaucrats would put it) practical problems. The problem is of course, in the system but it has more to do with the mindsets of the people too. There are people who speak against child labor in India and back at their own house or office, many of them will have at least one child working for them. People need to realize that what a waste of talent and a major obstacle to a country’s development, Child Labor is.   Keywords - Children. Child labor India. Social evil. Illegal employment.

Endothelial dysfunction in adult survivors of childhood cancer: A report from the St. Jude Lifetime Cohort study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 10564-10564
Author(s):  
Daniel A. Mulrooney ◽  
Kirsten K. Ness ◽  
Sujuan Huang ◽  
Aimee Santucci ◽  
Robert P. Hebbel ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Vascular Inflammation ◽  
High Sensitivity ◽  
Adult Survivors ◽  
Childhood Cancer Survivors ◽  
Reactive Protein ◽  
Inflammatory Processes ◽  
Cardiovascular Medications

10564 Background: Endothelial dysfunction, as an indicator of vascular disease in childhood cancer survivors (CCS) has not been widely studied. Methods: Markers of vascular inflammation (high sensitivity C-reactive protein [hsCRP]), hemostasis (fibrinogen), activation (endothelial cell expression of vascular cell adhesion molecule [VCAM-1]) and functional testing (large/small artery elasticity [L/SAE], pulse wave velocity [PWV]) were assessed in 200 CCS, ≥10 years from diagnosis, and 192 age/gender matched healthy controls. Exclusion criteria included: inflammatory processes, use of anti-inflammatory or cardiovascular medications, or pregnancy. Differences were assessed by adjusted multivariable linear regression. Results: CCS (53% male) of leukemia/lymphoma (59%), central nervous system tumors (6%), sarcomas (11.5%), embryonal tumors (22.5%), and other (1%) had a mean age at diagnosis 7.3 years (SD ±5.7). CCS and controls did not differ in current age (mean 34.1 ±9.2 vs. 33.5 years ±9.8), body mass index, smoking, mean systolic (124 mm Hg ±11.7 vs. 123 ±11.9) or diastolic blood pressure (73 ±9.5 vs. 71 ±9.5). Fasting low- (110 mg/dl ±31 vs. 102 ±30) and high-density (52 ±16 vs. 56 ±18) cholesterol levels differed between survivors and controls (p<0.01). Endothelial expression of VCAM-1 and PWV were statistically significantly increased in CCS; arterial elasticity was significantly reduced (table). Therapeutic exposures (anthracyclines and radiation) were not significantly associated with endothelial dysfunction. Conclusions: Childhood cancer survivors have greater endothelial dysfunction, a sign of atherosclerosis, and preventive measures should be investigated. [Table: see text]

The Real World: Rethinking Immigration

1999 ◽  
Vol 21 (2) ◽  
pp. 53-54 ◽  
Author(s):  
Rob Winthrop
Keyword(s):  
Public Policy ◽  
Task Force ◽  
Policy Issues ◽  
The Road ◽  
Noam Chomsky ◽  
Policy Debates ◽  
National Media ◽  
On The Road ◽  
The One ◽  
The Right

Many of us might aspire to become "public intellectuals," standing side-by-side with Noam Chomsky (for those on the left) or Bill Bennett (for those on the right), using the national media to scourge the politicians, guide the journalists, and correct the wayward public. Unfortunately, few are willing to do the requisite heavy lifting, mastering the details of particular policy debates and cultivating contacts with the relevant players, as first steps on the road to this intellectual Valhalla. As the American Anthropological Association's Task Force on Public Policy commented in its January 1998 report: "Cultural ambivalence within AAA is demonstrated in anthropologists' failure to engage in public policy issues on the one hand, and, on the other hand, anthropologists' indignation at not being consulted on policy issues perceived as being related to anthropology."

scholarly journals The Use of High Sensitivity C-Reactive Protein in Cardiovascular Disease Detection

2018 ◽  
Vol 21 ◽  
pp. 496-503 ◽  
Author(s):  
Ana Rita Castro ◽  
Sara Oliveira Silva ◽  
Sandra Clara Soares
Keyword(s):  
Vascular Inflammation ◽  
Life Quality ◽  
High Sensitivity ◽  
Medical Community ◽  
Concentration Limit ◽  
C Reactive Protein ◽  
High Concentration ◽  
Cvd Risk ◽  
Plaque Instability ◽  
Reactive Protein

Cardiovascular diseases (CVDs) are responsible for a high mortality rate worldwide. One of the most common causes of CVDs is vascular inflammation associated to atherosclerosis. Inflammatory biomarkers are used to assist the detection of CVDs and monitor their evaluation, prognosis and therapy implementation. C-reactive protein (CRP) is an acute phase protein produced after stimulation by pro-inflammatory cytokines. CRP is a biomarker of the inflammatory reaction and an important mediator of atherosclerosis. Given it actively contributes to the development of the atherosclerotic plaque, instability and subsequent clot formation it is also considered a CVD risk factor. Since 2010, the plasma concentration of hsCRP (high sensitivity CRP) has been used as a biomarker for disease prognosis in patients with intermediate risk for CVDs. It could be useful to establish a high concentration limit of hsCRP that can be used by clinicians for diagnosis of acute myocardial infarction, cardio embolic or ischemic stroke, and hypertrophic cardiomyopathy. The end cost/effectiveness of hsCRP screening is still an area of controversy but it is a priority to make the medical community aware of the positive relation between high hsCRP and CVDs to improve median survival and life quality of the patients.

scholarly journals Industry 4.0 Readiness Assessment

2020 ◽  
Vol 14 (2) ◽  
pp. 212-217 ◽  
Author(s):  
Bernhard Axmann ◽  
Harmoko Harmoko
Keyword(s):  
Data Storage ◽  
Industry 4.0 ◽  
Assessment Tool ◽  
Small And Medium Enterprises ◽  
Quality Data ◽  
Readiness Assessment ◽  
The Road ◽  
On The Road ◽  
The Right ◽  
Medium Enterprises

This research aims to establish an assessment tool for assessing the readiness of small and medium enterprises (SME) in industry 4.0. The assessment of the current and future status is crucial for companies to decide on the right strategy and actions on the road to a digital company. First will be compared existing tools such as: IMPULS (VDMA), PwC and Uni-Warwick. On that basis, a tool for SME will be introduce. The tool has 12 categories: data sharing, data storage, data quality, data processing, product design and development, smart material planning, smart production, smart maintenance, smart logistic, IT security, machines readiness and communication between machines. Those categories are grouped into three: data, software and hardware. Each category has five levels of readiness (from 1 to 5), with particular criteria that refer to literature studies and expert’s opinion.

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