Pursuing the Longevity Dividend

The aging of humanity is about to experience a radical change as the demographic transformation to an older world is approaching its final stage. In recent decades, scientists have learned enough about the biological aging processes that many believe it will become possible to slow aging in humans. We contend that the social, economic, and health benefits that would result from such advances may be thought of as “longevity dividends,” and that they should be aggressively pursued as the new approach to health promotion and disease prevention in the 21st century. The time has arrived for governments and national and international healthcare organizations to make research into healthy aging a major research priority.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75679/1/annals.1396.050.pd

REDUCE-IT USA: Results From the 3146 Patients Randomized in the United States.

BackgroundSome trials have found that patients from the United States derive less benefit than patients enrolled outside the United States. This prespecified REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl - Intervention Trial) subgroup analysis was conducted to determine the degree of benefit of icosapent ethyl in the United States.MethodsREDUCE-IT randomized 8179 statin-treated patients with qualifying triglycerides ≥135 and <500 mg/dL and low-density lipoprotein cholesterol >40 and ≤100 mg/dL and a history of atherosclerosis or diabetes mellitus to icosapent ethyl 4 g/d or placebo. The primary composite end point was cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or hospitalization for unstable angina. The key secondary composite end point was cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. A hierarchy was prespecified for examination of individual and composite end points.ResultsA total of 3146 US patients (38.5% of the trial) were randomized and followed for a median of 4.9 years; 32.3% were women and 9.7% were Hispanic. The primary composite end point occurred in 24.7% of placebo-treated patients versus 18.2% of icosapent ethyl-treated patients (hazard ratio [HR], 0.69 [95% CI, 0.59-0.80]; P=0.000001); the key secondary composite end point occurred in 16.6% versus 12.1% (HR, 0.69 [95% CI, 0.57-0.83]; P=0.00008). All prespecified hierarchical end points were meaningfully and significantly reduced, including cardiovascular death (6.7% to 4.7%; HR, 0.66 [95% CI, 0.49-0.90]; P=0.007), myocardial infarction (8.8% to 6.7%; HR, 0.72 [95% CI, 0.56-0.93]; P=0.01), stroke (4.1% to 2.6%; HR, 0.63 [95% CI, 0.43-0.93]; P=0.02), and all-cause mortality (9.8% to 7.2%; HR, 0.70 [95% CI, 0.55-0.90]; P=0.004); for all-cause mortality in the US versus non-US patients, Pinteraction=0.02. Safety and tolerability findings were consistent with the full study cohort.ConclusionsWhereas the non-US subgroup showed significant reductions in the primary and key secondary end points, the US subgroup demonstrated particularly robust risk reductions across a variety of individual and composite end points, including all-cause mortality.Clinical trial registrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT01492361

Lifespan extension and the doctrine of double effect

Recent developments in biogerontology—the study of the biology of ageing—suggest that it may eventually be possible to intervene in the human ageing process. This, in turn, offers the prospect of significantly postponing the onset of age-related diseases. The biogerontological project, however, has met with strong resistance, especially by deontologists. They consider the act of intervening in the ageing process impermissible on the grounds that it would (most probably) bring about an extended maximum lifespan—a state of affairs that they deem intrinsically bad. In a bid to convince their deontological opponents of the permissibility of this act, proponents of biogerontology invoke an argument which is grounded in the doctrine of double effect. Surprisingly, their argument, which we refer to as the ‘double effect argument’, has gone unnoticed. This article exposes and critically evaluates this ‘double effect argument’. To this end, we first review a series of excerpts from the ethical debate on biogerontology in order to substantiate the presence of double effect reasoning. Next, we attempt to determine the role that the ‘double effect argument’ is meant to fulfil within this debate. Finally, we assess whether the act of intervening in ageing actually can be justified using double effect reasoning

Antithrombotic therapy in atrial fibrillation associated with valvular heart disease: A joint consensus document from the European Heart Rhythm Association (EHRA) and European Society of Cardiology Working Group on Thrombosis, endorsed by the ESC Working Group on Valvular Heart Disease, Cardiac Arrhythmia Society of Southern Africa (CASSA), Heart Rhythm Society (HRS), Asia Pacific Heart Rhythm Society (APHRS), South African Heart (SA Heart) Association and Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología (SOLEACE)

Atrial fibrillation (AF) is a major public health problem1 with global prevalence rates (per 1000000 population) in 2010 being 596.2 (95% uncertainty interval (UI), 558.4-636.7) in men and 373.1 (95% UI, 347.9-402.2) in women; the incidence rates increased to 77.5 (95% UI, 65.2-95.4) in men and 59.5 (95% UI, 49.9-74.9) in women.2 Worldwide, AF in association with valvular heart disease (VHD) is also common, and management strategies for this group of patients have been less addressed by randomized trials. The latter have largely focused on 'non-valvular AF' patients leading to major uncertainties over how to define (and treat) such patients. There is also an important heterogeneity in the definition of valvular and non-valvular AF.3 Some physicians assume that any valve disease should be considered as 'valvular' AF. Others consider that only mechanical valve prosthesis and rheumatic mitral stenosis should be defined as 'valvular' AF. The term valvular AF has been arbitrarily applied and the 2016 ESC guidelines have avoided the term 'valvular AF' and refer simply to 'AF related to hemodynamically significant mitral stenosis or prosthetic mechanical heart valves'.4 AF clearly leads to an incremental risk for thromboembolism in patients with mitral valve stenosis, but there are limited data for other valvular diseases. Another proposal is to use the acronym MARM-AF as a simple acronym to designate 'Mechanical and Rheumatic Mitral AF' as an alternative to term 'valvular AF' to designate the clinical scenarios for which at the non-vitamin K antagonist oral anticoagulants (NOACs) are not indicated.5 For this document we recognize the uncertainty in terminology, and our scope largely relates to AF related to 'hemodynamically significant' rheumatic VHD (ie. severe enough to impact on patient's survival or necessitates an intervention or surgery) or prosthetic mechanical heart valves. Nonetheless, thrombo-embolic (TE) risk varies according to valve lesion and may be associated with CHA2DS2VASc score risk factor components, rather than the valve disease per se being causal.6,7 TE risk may also be influenced not only by type but also the severity of the lesion. For example, the degree of mitral regurgitation may matter when it comes to risk of TE as some studies suggest that mild (Grade 1) mitral regurgitation is associated with a 2.7-fold increased risk of stroke/TE, while severe forms may possibly have a 'protective' effect (HR = 0.45 for stroke and 0.27 for LA stasis.8 An appropriate definition of 'valvular AF' would need to identify a subgroup of patients with similar pathophysiology of thrombo-embolism, TE risk, and treatment strategies6,9; however, this would be challenging given the major heterogeneity of the condition. This consensus document proposes that the term 'valvular AF' is outdated and given that any definition ultimately relates to the evaluated practical use of oral anticoagulation (OAC) type, we propose a functional EHRA (EvaluatedHeartvalves, Rheumatic orArtificial) categorization in relation to the type of OAC use in patients with AF, as follows:Evaluated Heartvalves, Rheumatic or Artificial (EHRA) Type 1,which refers to AF patients with 'VHD needing therapy with a Vitamin K antagonist (VKA)

An Analysis of the Myocardial Transcriptome in a Mouse Model of Cardiac Dysfunction with Decreased Cholinergic Neurotransmission

Autonomic dysfunction is observed in many cardiovascular diseases and contributes to cardiac remodeling and heart disease. We previously reported that a decrease in the expression levels of the vesicular acetylcholine transporter (VAChT) in genetically-modified homozygous mice (VAChT KDHOM) leads to decreased cholinergic tone, autonomic imbalance and a phenotype resembling cardiac dysfunction. In order to further understand the molecular changes resulting from chronic long-term decrease in parasympathetic tone, we undertook a transcriptome-based, microarray-driven approach to analyze gene expression changes in ventricular tissue from VAChT KDHOM mice. We demonstrate that a decrease in cholinergic tone is associated with alterations in gene expression in mutant hearts, which might contribute to increased ROS levels observed in these cardiomyocytes. In contrast, in another model of cardiac remodeling and autonomic imbalance, induced through chronic isoproterenol treatment to increase sympathetic drive, these genes did not appear to be altered in a pattern similar to that observed in VAChT KDHOM hearts. These data suggest the importance of maintaining a fine balance between the two branches of the autonomic nervous system and the significance of absolute levels of cholinergic tone in proper cardiac function

The Reproductive Revolution

Este texto fue publicado en 2009 por The Sociological Review. Rogamos que, a efectos de divulgación, docencia y cita bibliográfica se acuda a la publicación impresa (u online de la propia revista) y la cita sea esta: MacInnes, J., Pérez Díaz, J. (2009), "The reproductive revolution" The Sociological Review 57 (2): 262-284. Su versión html puede encontrarse en esta dirección:http://www3.interscience.wiley.com/cgi-bin/fulltext/122368561/HTMLSTART Quienes estén interesados en ampliar la información sobre nuestra Teoría de la Revolución Reproductiva pueden visitar la página web siguiente: http://www.ieg.csic.es/jperez/pags/RRweb/RRweb.htm También encontrarán en este mismo repositorio otra publicación con unaexposición en castellano de las mismas ideas y publicada en la REIS bajo el título “La tercera revolución de la modernidad: la reproductiva”.We suggest that a third revolution alongside the better known economic and political ones has been vital to the rise of modernity: the reproductive revolution, comprising a historically unrepeatable shift in the efficiency of human reproduction which for the first time brought demographic security.As well as highlighting the contribution of demographic change to the rise of modernity and addressing the limitations of orthodox theories of the demographic transition, the concept of the reproductive revolution offers a better way to integrate sociology and demography. The former has tended to pay insufficient heed to sexual reproduction, individual mortality and the generational replacement of population, while the latter has undervalued its own distinctive theoretical contribution, portraying demographic change as the effect of causes lying elsewhere. We outline a theory of the reproductive revolution, review some relevant supporting empirical evidence and briefly discuss its implications both for demographic transition theory itself, and for a range of key social changes that we suggest it made possible: the decline of patriarchy and feminisation of the public sphere, the deregulation and privatisation of sexuality, family change, the rise of identity, ‘low’ fertility and ‘population ageing’.Peer reviewe

Inventory of Essential Facilities in Mid-America

The earthquake hazard in mid-America is characterized by large, but infrequent events. As a result, the level of seismic building design and retrofit is generally thought to be lower than in many other seismically active regions, however the exact nature of the building stock is not known. In developing its research agenda the Mid-America Earthquake Center determined that an inventory of essential facilities in the region was part of the foundation needed to support its research efforts. Rather than focus on the entire building stock, we selected essential facilities as the most critical target for this initial investigation. Essential facilities are those facilities that must play an important role in the recovery period following an earthquake. They include hospitals, police and fire stations and schools, which often serve as emergency shelters. This report summarizes the analysis of 1306 essential facilities for which key structural characteristics were collected through telephone survey contacts. The essential facility inventory was found to be relatively fragile with a large number of unreinforced masonry structures. Schools appear to be the most vulnerable type of facility due to their age, construction types and location with respect to the hazard. The data described here is available to state and local emergency managers over the Internet: http://mae.ce.uiuc.edu/ResearchPrograms/CRP/BodyEFP.htm or http://cgis.gatech.edu/Projects/projects.html.National Science Foundation EEC-970178

Evaluating Earthquake Risk in Mid-American Communities

The goal of this research project was to provide earthquake loss estimates for two test communities, Carbondale, IL, and Sikeston, MO, using readily available methods. The results must be in a form usable by each community, and the methods must be feasible for use by other similar communities. This project fits into a larger MAE Center program to evaluate and improve earthquake safety of essential facilities (hospitals, schools, fire stations, police stations) in Mid- America.NSF EEC-9701785unpublishednot peer reviewe