Impact of expanded FDA indication for icosapent ethyl on enhanced cardiovascular residual risk reduction

Hypertriglyceridemia is associated with increased cardiovascular disease (CVD) risk. The Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) demonstrated that the purified, stable ethyl ester of eicosapentaenoic acid, icosapent ethyl (IPE), added to statins reduced CVD events by 25% (p \u3c 0.001), leading to an expanded indication in the USA. IPE is now approved as an adjunct to maximally tolerated statins to reduce CVD event risk in adults with triglyceride (TG) levels ≥150 mg/dl and either established CVD or diabetes mellitus plus ≥2 additional CVD risk factors. The new indication allows co-administration of IPE for elevated TG levels with statin treatment, enabling effective residual risk reduction in a broader at-risk population beyond what can be achieved with intensive low-density lipoprotein cholesterol control alone. Keywords: cardiovascular disease; eicosapentaenoic acid; heart diseases; hypertriglyceridemia; icosapent ethyl; triglycerides

Evaluating Future Nanotechnology: The Net Societal Impacts of Atomically Precise Manufacturing

Atomically precise manufacturing (APM) is the assembly of materials with atomic precision. APM does not currently exist, and may not be feasible, but if it is feasible, then the societal impacts could be dramatic. This paper assesses the net societal impacts of APM across the full range of important APM sectors: general material wealth, environmental issues, military affairs, surveillance, artificial intelligence, and space travel. Positive effects were found for material wealth, the environment, military affairs (specifically nuclear disarmament), and space travel. Negative effects were found for military affairs (specifically rogue actor violence and AI. The net effect for surveillance was ambiguous. The effects for the environment, military affairs, and AI appear to be the largest, with the environment perhaps being the largest of these, suggesting that APM would be net beneficial to society. However, these factors are not well quantified and no definitive conclusion can be made. One conclusion that can be reached is that if APM R&D is pursued, it should go hand-in-hand with effective governance strategies to increase the benefits and reduce the harms

Alternative Foods as a Solution to Global Food Supply Catastrophes

International audienceAnalysis of future food security typically focuses on managing gradual trends such as population growth, natural resource depletion, and environmental degradation. However, several risks threaten to cause large and abrupt declines in food security. For example, nuclear war, volcanic eruptions, and asteroid impact events can block sunlight, causing abrupt global cooling. In extreme but entirely possible cases, these events could make agriculture infeasible worldwide for several years, creating a food supply catastrophe of historic proportions. This paper describes alternative foods that use non-solar energy inputs as a solution for these catastrophes. For example, trees can be used to grow mushrooms; natural gas can feed certain edible bacteria. Alternative foods are already in production today, but would need to be dramatically scaled up to become the primary food source during a global food supply catastrophe. Scale-up would require extensive depletion of natural resources and difficult social coordination. For these reasons, large-scale use of alternative foods should be considered only for desperate circumstances of food supply catastrophes. During a catastrophe, alternative foods may be the only solution capable of preventing massive famine and maintaining human civilization. Furthermore, elements of alternative foods may be applicable to non-catastrophe times, such growing mushrooms on logging residues. Society should include alternative foods as part of its contingency planning for food supply catastrophes and possibly during normal times as well

PCSK9 inhibitor valuation: A science‐based review of the two recent models

Low‐density lipoprotein cholesterol (LDL‐C) has been extensively evaluated. Prospective cohort studies, randomized controlled trials, biology, pathophysiology, genetics, and Mendelian randomization studies, have clearly taught us that LDL‐C causes atherosclerotic cardiovascular disease. The newest class of drugs to lower LDL‐C, the proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies, have been found to safely reduce LDL‐C approximately 60% when added to high‐intensity statin therapy. Because their cost is much greater than that of the currently available agents, their value has been questioned. In late August, 2017, two groups assessed the value of this class of drugs looking at cost‐effectiveness; however, the Institute for Clinical and Economic Review and Fonarow and colleagues found disparate results when assessing PCSK9 valuation. Herein, we review the evolution of LDL‐C from hypothesis to fact, and then attempt to adjudicate the 2 models, shedding light on the complex modeling process. We find that models of cost‐effectiveness are helpful adjuncts to decision making, but that their conclusions depend on many assumptions. Ultimately, clinician judgment regarding their clinical benefit, balanced by some estimation of cost, may be more productive to target the right patients for whom the benefits can be well‐justified

The Benefits and Harms of Transmitting Into Space

Deliberate and unintentional radio transmissions from Earth propagate into space. These transmissions could be detected by extraterrestrial watchers over interstellar distances. Here, we analyze the harms and benefits of deliberate and unintentional transmissions relevant to Earth and humanity. Comparing the magnitude of deliberate radio broadcasts intended for messaging to extraterrestrial intelligence (METI) with the background radio spectrum of Earth, we find that METI attempts to date have much lower detectability than emissions from current radio communication technologies on Earth. METI broadcasts are usually transient and several orders of magnitude less powerful than other terrestrial sources such as astronomical and military radars, which provide the strongest detectable signals. The benefits of radio communication on Earth likely outweigh the potential harms of detection by extraterrestrial watchers; however, the uncertainty regarding the outcome of contact with extraterrestrial beings creates difficulty in assessing whether or not to engage in long-term and large-scale METI.Comment: Published in Space Polic

Improved Photometric Redshifts with Surface Luminosity Priors

We apply Bayesian statistics with prior probabilities of galaxy surface luminosity (SL) to improve photometric redshifts. We apply the method to a sample of 1266 galaxies with spectroscopic redshifts in the GOODS North and South fields at 0.1 < z < 2.0. We start with spectrophotometric redshifts (SPZs) based on Probing Evolution and Reionization Spectroscopically grism spectra, which cover a wavelength range of 6000-9000A, combined with (U)BViz(JHK) broadband photometry in the GOODS fields. The accuracy of SPZ redshifts is estimated to be \sigma (\Delta(z))=0.035 with an systematic offset of -0.026, where \Delta(z)=\Delta z / (1+z), for galaxies in redshift range of 0.5 < z < 1.25. The addition of the SL prior probability helps break the degeneracy of SPZ redshifts between low redshift 4000 A break galaxies and high-redshift Lyman break galaxies which are mostly catastrophic outliers. For the 1138 galaxies at z < 1.6, the fraction of galaxies with redshift deviation \Delta (z) > 0.2 is reduced from 15.0% to 10.4%, while the rms scatter of the fractional redshift error does not change much.Comment: 7 pages, 7 figures, published in A

Long-Term Trajectories of Human Civilization

Purpose This paper aims to formalize long-term trajectories of human civilization as a scientific and ethical field of study. The long-term trajectory of human civilization can be defined as the path that human civilization takes during the entire future time period in which human civilization could continue to exist. Design/methodology/approach This paper focuses on four types of trajectories: status quo trajectories, in which human civilization persists in a state broadly similar to its current state into the distant future; catastrophe trajectories, in which one or more events cause significant harm to human civilization; technological transformation trajectories, in which radical technological breakthroughs put human civilization on a fundamentally different course; and astronomical trajectories, in which human civilization expands beyond its home planet and into the accessible portions of the cosmos. Findings Status quo trajectories appear unlikely to persist into the distant future, especially in light of long-term astronomical processes. Several catastrophe, technological transformation and astronomical trajectories appear possible. Originality/value Some current actions may be able to affect the long-term trajectory. Whether these actions should be pursued depends on a mix of empirical and ethical factors. For some ethical frameworks, these actions may be especially important to pursue

Would contact with extraterrestrials benefit or harm humanity? A scenario analysis

While humanity has not yet observed any extraterrestrial intelligence (ETI), contact with ETI remains possible. Contact could occur through a broad range of scenarios that have varying consequences for humanity. However, many discussions of this question assume that contact will follow a particular scenario that derives from the hopes and fears of the author. In this paper, we analyze a broad range of contact scenarios in terms of whether contact with ETI would benefit or harm humanity. This type of broad analysis can help us prepare for actual contact with ETI even if the details of contact do not fully resemble any specific scenario.Comment: 33 Pages, 1 Figure, PDF Fil

Contemporary Homozygous Familial Hypercholesterolemia in the United States: Insights From the CASCADE FH Registry

Erratum in: J Am Heart Assoc. 2023 Jun 6;12(11):e027706. doi: 10.1161/JAHA.122.027706. Epub 2023 Jun 1.Free PMC article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10227232/Background: Homozygous familial hypercholesterolemia (HoFH) is a rare, treatment-resistant disorder characterized by earlyonset atherosclerotic and aortic valvular cardiovascular disease if left untreated. Contemporary information on HoFH in the United States is lacking, and the extent of underdiagnosis and undertreatment is uncertain. Methods and Results: Data were analyzed from 67 children and adults with clinically diagnosed HoFH from the CASCADE (Cascade Screening for Awareness and Detection) FH Registry. Genetic diagnosis was confirmed in 43 patients. We used the clinical characteristics of genetically confirmed patients with HoFH to query the Family Heart Database, a US anonymized payer health database, to estimate the number of patients with similar lipid profiles in a “real-world” setting. Untreated lowdensity lipoprotein cholesterol levels were lower in adults than children (533 versus 776mg/dL; P=0.001). At enrollment, atherosclerotic cardiovascular disease and supravalvular and aortic valve stenosis were present in 78.4% and 43.8% and 25.5% and 18.8% of adults and children, respectively. At most recent follow-up, despite multiple lipid-lowering treatment, low-density lipoprotein cholesterol goals were achieved in only a minority of adults and children. Query of the Family Heart Database identified 277 individuals with profiles similar to patients with genetically confirmed HoFH. Advanced lipid-lowering treatments were prescribed for 18%; 40% were on no lipid-lowering treatment; atherosclerotic cardiovascular disease was reported in 20%; familial hypercholesterolemia diagnosis was uncommon. Conclusions: Only patients with the most severe HoFH phenotypes are diagnosed early. HoFH remains challenging to treat. Results from the Family Heart Database indicate HoFH is systemically underdiagnosed and undertreated. Earlier screening, aggressive lipid-lowering treatments, and guideline implementation are required to reduce disease burden in HoFH.Dr Martin is supported by grants/contracts from the American Heart Association (20SFRN35380046, 20SFRN35490003, 878924, and 882415), Patient‐Centered Outcomes Research Institute (PCORI) (ME‐2019C1‐15328), National Institutes of Health (NIH) (R01AG071032 and P01 HL108800), the David and June Trone Family Foundation, Pollin Digital Health Innovation Fund, and Sandra and Larry Small; Dr Knowles is supported by the NIH through grants P30 DK116074 (to the Stanford Diabetes Research Center), R01 DK116750, R01 DK120565, and R01 DK106236; and by a grant from the Bilateral Science Foundation. Dr Linton is supported by NIH grants P01HL116263, HL148137, HL159487, and HL146134.info:eu-repo/semantics/publishedVersio