Christ University

Full list of authors: Price-Whelan, Adrian M.; Lim, Pey Lian; Earl, Nicholas; Starkman, Nathaniel; Bradley, Larry; Shupe, David L.; Patil, Aarya A.; Corrales, Lia; Brasseur, C. E.; Noethe, Maximilian; Donath, Axel; Tollerud, Erik; Morris, Brett M.; Ginsburg, Adam; Vaher, Eero; Weaver, Benjamin A.; Tocknell, James; Jamieson, William; van Kerkwijk, Marten H.; Robitaille, Thomas P.; Merry, Bruce; Bachetti, Matteo; Gunther, H. Moritz; Aldcroft, Thomas L.; Alvarado-Montes, Jaime A.; Archibald, Anne M.; Bodi, Attila; Bapat, Shreyas; Barentsen, Geert; Bazan, Juanjo; Biswas, Manish; Boquien, Mederic; Burke, D. J.; Cara, Daria; Cara, Mihai; Conroy, Kyle E.; Conseil, Simon; Craig, Matthew W.; Cross, Robert M.; Cruz, Kelle L.; D'Eugenio, Francesco; Dencheva, Nadia; Devillepoix, Hadrien A. R.; Dietrich, Jorg P.; Eigenbrot, Arthur Davis; Erben, Thomas; Ferreira, Leonardo; Foreman-Mackey, Daniel; Fox, Ryan; Freij, Nabil; Garg, Suyog; Geda, Robel; Glattly, Lauren; Gondhalekar, Yash; Gordon, Karl D.; Grant, David; Greenfield, Perry; Groener, Austen M.; Guest, Steve; Gurovich, Sebastian; Handberg, Rasmus; Hart, Akeem; Hatfield-Dodds, Zac; Homeier, Derek; Hosseinzadeh, Griffin; Jenness, Tim; Jones, Craig K.; Joseph, Prajwel; Kalmbach, J. Bryce; Karamehmetoglu, Emir; Kaluszynski, Mikolaj; Kelley, Michael S. P.; Kern, Nicholas; Kerzendorf, Wolfgang E.; Koch, Eric W.; Kulumani, Shankar; Lee, Antony; Ly, Chun; Ma, Zhiyuan; MacBride, Conor; Maljaars, Jakob M.; Muna, Demitri; Murphy, N. A.; Norman, Henrik; O'Steen, Richard; Oman, Kyle A.; Pacifici, Camilla; Pascual, Sergio; Pascual-Granado, J.; Patil, Rohit R.; Perren, Gabriel, I; Pickering, Timothy E.; Rastogi, Tanuj; Roulston, Benjamin R.; Ryan, Daniel F.; Rykoff, Eli S.; Sabater, Jose; Sakurikar, Parikshit; Salgado, Jesus; Sanghi, Aniket; Saunders, Nicholas; Savchenko, Volodymyr; Schwardt, Ludwig; Seifert-Eckert, Michael; Shih, Albert Y.; Jain, Anany Shrey; Shukla, Gyanendra; Sick, Jonathan; Simpson, Chris; Singanamalla, Sudheesh; Singer, Leo P.; Singhal, Jaladh; Sinha, Manodeep; Sipocz, Brigitta M.; Spitler, Lee R.; Stansby, David; Streicher, Ole; Sumak, Jani; Swinbank, John D.; Taranu, Dan S.; Tewary, Nikita; Tremblay, Grant R.; De Val-Borro, Miguel; Vasovic, Zlatan; Van Kooten, Samuel J.; Verma, Shresth; Cardoso, Jose Vinicius de Miranda; Williams, Peter K. G.; Wilson, Tom J.; Winkel, Benjamin; Wood-Vasey, W. M.; Xue, Rui; Yoachim, Peter; Zhang, Chen; Zonca, Andrea; Astropy Project Contributors; TARDIS Collaboration; Astropy Coordination Comm.--This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

Journal Article The Calculus of Consent: Logical Foundations of Constitutional Democracy Get access The Calculus of Consent: Logical Foundations of Constitutional Democracy. By J. M. Buchanan and G. Tuxlock. (Ann Arbor, Michigan: University of Michigan Press, 1962. Pp. x + 361. $6.95.) J. E. Meade J. E. Meade Christ's College, Cambridge Search for other works by this author on: Oxford Academic Google Scholar The Economic Journal, Volume 73, Issue 289, 1 March 1963, Pages 101–104, https://doi.org/10.2307/2228407 Published: 01 March 1963

OBJECTIVE: To develop an objective scale to measure the severity of the multiple organ dysfunction syndrome as an outcome in critical illness. DESIGN: Systematic literature review; prospective cohort study. SETTING: Surgical intensive care unit (ICU) of a tertiary-level teaching hospital. PATIENTS: All patients (n = 692) admitted for > 24 hrs between May 1988 and March 1990. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Computerized database review of MEDLINE identified clinical studies of multiple organ failure that were published between 1969 and 1993. Variables from these studies were evaluated for construct and content validity to identify optimal descriptors of organ dysfunction. Clinical and laboratory data were collected daily to evaluate the performance of these variables individually and in aggregate as an organ dysfunction score. Seven systems defined the multiple organ dysfunction syndrome in more than half of the 30 published reports reviewed. Descriptors meeting criteria for construct and content validity could be identified for five of these seven systems: a) the respiratory system (Po2/FIO2 ratio); b) the renal system (serum creatinine concentration); c) the hepatic system (serum bilirubin concentration); d) the hematologic system (platelet count); and e) the central nervous system (Glasgow Coma Scale). In the absence of an adequate descriptor of cardiovascular dysfunction, we developed a new variable, the pressure-adjusted heart rate, which is calculated as the product of the heart rate and the ratio of central venous pressure to mean arterial pressure. These candidate descriptors of organ dysfunction were then evaluated for criterion validity (ICU mortality rate) using the clinical database. From the first half of the database (the development set), intervals for the most abnormal value of each variable were constructed on a scale from 0 to 4 so that a value of 0 represented essentially normal function and was associated with an ICU mortality rate of < 5%, whereas a value of 4 represented marked functional derangement and an ICU mortality rate of > or = 50%. These intervals were then tested on the second half of the data set (the validation set). Maximal scores for each variable were summed to yield a Multiple Organ Dysfunction Score (maximum of 24). This score correlated in a graded fashion with the ICU mortality rate, both when applied on the first day of ICU admission as a prognostic indicator and when calculated over the ICU stay as an outcome measure. For the latter, ICU mortality was approximately 25% at 9 to 12 points, 50% at 13 to 16 points, 75% at 17 to 20 points, and 100% at levels of > 20 points. The score showed excellent discrimination, as reflected in areas under the receiver operating characteristic curve of 0.936 in the development set and 0.928 in the validation set. The incremental increase in scores over the course of the ICU stay (calculated as the difference between maximal scores and those scores obtained on the first day [i.e., the delta Multiple Organ Dysfunction Score]) also demonstrated a strong correlation with the ICU mortality rate. In a logistic regression model, this incremental increase in scores accounted for more of the explanatory power than admission severity indices. CONCLUSIONS: This multiple organ dysfunction score, constructed using simple physiologic measures of dysfunction in six organ systems, mirrors organ dysfunction as the intensivist sees it and correlates strongly with the ultimate risk of ICU mortality and hospital mortality. The variable, delta Multiple Organ Dysfunction Score, reflects organ dysfunction developing during the ICU stay, which therefore is potentially amenable to therapeutic manipulation. (ABSTRACT TRUNCATED)

AIM: The "2022 ACC/AHA Guideline for the Diagnosis and Management of Aortic Disease" provides recommendations to guide clinicians in the diagnosis, genetic evaluation and family screening, medical therapy, endovascular and surgical treatment, and long-term surveillance of patients with aortic disease across its multiple clinical presentation subsets (ie, asymptomatic, stable symptomatic, and acute aortic syndromes). METHODS: A comprehensive literature search was conducted from January 2021 to April 2021, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, CINHL Complete, and other selected databases relevant to this guideline. Additional relevant studies, published through June 2022 during the guideline writing process, were also considered by the writing committee, where appropriate. Structure: Recommendations from previously published AHA/ACC guidelines on thoracic aortic disease, peripheral artery disease, and bicuspid aortic valve disease have been updated with new evidence to guide clinicians. In addition, new recommendations addressing comprehensive care for patients with aortic disease have been developed. There is added emphasis on the role of shared decision making, especially in the management of patients with aortic disease both before and during pregnancy. The is also an increased emphasis on the importance of institutional interventional volume and multidisciplinary aortic team expertise in the care of patients with aortic disease.

The prevalence of overweight among children and adolescents has dramatically increased. There may be vulnerable periods for weight gain during childhood and adolescence that also offer opportunities for prevention of overweight. Overweight in children and adolescents can result in a variety of adverse health outcomes, including type 2 diabetes, obstructive sleep apnea, hypertension, dyslipidemia, and the metabolic syndrome. The best approach to this problem is prevention of abnormal weight gain. Several strategies for prevention are presented. In addition, treatment approaches are presented, including behavioral, pharmacological, and surgical treatment. Childhood and adolescent overweight is one of the most important current public health concerns.

PURPOSE: The aim of this statement is to present current and comprehensive recommendations for the diagnosis and treatment of acute spontaneous intracerebral hemorrhage. METHODS: A formal literature search of Medline was performed through the end date of August 2006. The results of this search were complemented by additional articles on related issues known to the writing committee. Data were synthesized with the use of evidence tables. The American Heart Association Stroke Council's Levels of Evidence grading algorithm was used to grade each recommendation. Prerelease review of the draft guideline was performed by 5 expert peer reviewers and by the members of the Stroke Council Leadership Committee. It is intended that this guideline be fully updated in 3 years' time. RESULTS: Evidence-based guidelines are presented for the diagnosis of intracerebral hemorrhage, the management of increased arterial blood pressure and intracranial pressure, the treatment of medical complications of intracerebral hemorrhage, and the prevention of recurrent intracerebral hemorrhage. Recent trials of recombinant factor VII to slow initial bleeding are discussed. Recommendations for various surgical approaches for treatment of spontaneous intracerebral hemorrhage are presented. Finally, withdrawal-of-care and end-of-life issues in patients with intracerebral hemorrhage are examined.

The "2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care" increased the focus on methods to ensure that high-quality cardiopulmonary resuscitation (CPR) is performed in all resuscitation attempts. There are 5 critical components of high-quality CPR: minimize interruptions in chest compressions, provide compressions of adequate rate and depth, avoid leaning between compressions, and avoid excessive ventilation. Although it is clear that high-quality CPR is the primary component in influencing survival from cardiac arrest, there is considerable variation in monitoring, implementation, and quality improvement. As such, CPR quality varies widely between systems and locations. Victims often do not receive high-quality CPR because of provider ambiguity in prioritization of resuscitative efforts during an arrest. This ambiguity also impedes the development of optimal systems of care to increase survival from cardiac arrest. This consensus statement addresses the following key areas of CPR quality for the trained rescuer: metrics of CPR performance; monitoring, feedback, and integration of the patient's response to CPR; team-level logistics to ensure performance of high-quality CPR; and continuous quality improvement on provider, team, and systems levels. Clear definitions of metrics and methods to consistently deliver and improve the quality of CPR will narrow the gap between resuscitation science and the victims, both in and out of the hospital, and lay the foundation for further improvements in the future.

PURPOSE: The aim of this updated statement is to provide comprehensive and evidence-based recommendations for management of patients with unruptured intracranial aneurysms. METHODS: Writing group members used systematic literature reviews from January 1977 up to June 2014. They also reviewed contemporary published evidence-based guidelines, personal files, and published expert opinion to summarize existing evidence, indicate gaps in current knowledge, and when appropriate, formulated recommendations using standard American Heart Association criteria. The guideline underwent extensive peer review, including review by the Stroke Council Leadership and Stroke Scientific Statement Oversight Committees, before consideration and approval by the American Heart Association Science Advisory and Coordinating Committee. RESULTS: Evidence-based guidelines are presented for the care of patients presenting with unruptured intracranial aneurysms. The guidelines address presentation, natural history, epidemiology, risk factors, screening, diagnosis, imaging and outcomes from surgical and endovascular treatment.

Hydroxylated polyphenols, also called flavonoids, are richly present in vegetables, fruits, cereals, nuts, herbs, seeds, stems, and flowers of numerous plants. They possess numerous medicinal properties such as antioxidant, anti-cancer, anti-microbial, neuroprotective, and anti-inflammation. Studies show that flavonoids activate antioxidant pathways that render an anti-inflammatory effect. They inhibit the secretions of enzymes such as lysozymes and β-glucuronidase and inhibit the secretion of arachidonic acid, which reduces inflammatory reactions. Flavonoids such as quercetin, genistein, apigenin, kaempferol, and epigallocatechin 3-gallate modulate the expression and activation of a cytokine such as interleukin-1beta (IL-1β), Tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8); regulate the gene expression of many pro-inflammatory molecules such s nuclear factor kappa-light chain enhancer of activated B cells (NF-κB), activator protein-1 (AP-1), intercellular adhesion molecule-1 (ICAM), vascular cell adhesion molecule-1 (VCAM), and E-selectins; and also inhibits inducible nitric oxide (NO) synthase, cyclooxygenase-2, and lipoxygenase, which are pro-inflammatory enzymes. Understanding the anti-inflammatory action of flavonoids provides better treatment options, including coronavirus disease 2019 (COVID-19)-induced inflammation, inflammatory bowel disease, obstructive pulmonary disorder, arthritis, Alzheimer's disease, cardiovascular disease, atherosclerosis, and cancer. This review highlights the sources, biochemical activities, and role of flavonoids in enhancing human health.

HomeCirculationVol. 108, No. 20Case Definitions for Acute Coronary Heart Disease in Epidemiology and Clinical Research Studies

Covering: 2016. Previous review: Nat. Prod. Rep., 2017, 34, 235-294This review covers the literature published in 2016 for marine natural products (MNPs), with 757 citations (643 for the period January to December 2016) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1277 in 432 papers for 2016), together with the relevant biological activities, source organisms and country of origin. Reviews, biosynthetic studies, first syntheses, and syntheses that led to the revision of structures or stereochemistries, have been included.

OBJECTIVE: The long-term efficacy and safety of responsive direct neurostimulation was assessed in adults with medically refractory partial onset seizures. METHODS: All participants were treated with a cranially implanted responsive neurostimulator that delivers stimulation to 1 or 2 seizure foci via chronically implanted electrodes when specific electrocorticographic patterns are detected (RNS System). Participants had completed a 2-year primarily open-label safety study (n = 65) or a 2-year randomized blinded controlled safety and efficacy study (n = 191); 230 participants transitioned into an ongoing 7-year study to assess safety and efficacy. RESULTS: The average participant was 34 (±11.4) years old with epilepsy for 19.6 (±11.4) years. The median preimplant frequency of disabling partial or generalized tonic-clonic seizures was 10.2 seizures a month. The median percent seizure reduction in the randomized blinded controlled trial was 44% at 1 year and 53% at 2 years (p < 0.0001, generalized estimating equation) and ranged from 48% to 66% over postimplant years 3 through 6 in the long-term study. Improvements in quality of life were maintained (p < 0.05). The most common serious device-related adverse events over the mean 5.4 years of follow-up were implant site infection (9.0%) involving soft tissue and neurostimulator explantation (4.7%). CONCLUSIONS: The RNS System is the first direct brain responsive neurostimulator. Acute and sustained efficacy and safety were demonstrated in adults with medically refractory partial onset seizures arising from 1 or 2 foci over a mean follow-up of 5.4 years. This experience supports the RNS System as a treatment option for refractory partial seizures. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for adults with medically refractory partial onset seizures, responsive direct cortical stimulation reduces seizures and improves quality of life over a mean follow-up of 5.4 years.

Throughout this article, the reader will notice combinations of superscripted letters and numbers (eg, "Cricoid Pressure ALS-CPR&A-007B "). These callouts are hyperlinked to evidence-based worksheets, which were used in the development of this article. An appendix of worksheets, applicable to this article, is located at the end of the text. The worksheets are available in PDF format and are open access. The topics reviewed by the International Liaison Committee on Resuscitation (ILCOR) Advanced Life Support Task Force are grouped as follows: (1) airway and ventilation, (2) supporting the circulation during cardiac arrest, (3) periarrest arrhythmias, (4) cardiac arrest in special circumstances, (5) identifying reversible causes, (6) postresuscitation care, (7) prognostication, and (8) organ donation. Defibrillation topics are discussed in Part 6.

Self-care is defined as a naturalistic decision-making process addressing both the prevention and management of chronic illness, with core elements of self-care maintenance, self-care monitoring, and self-care management. In this scientific statement, we describe the importance of self-care in the American Heart Association mission and vision of building healthier lives, free of cardiovascular diseases and stroke. The evidence supporting specific self-care behaviors such as diet and exercise, barriers to self-care, and the effectiveness of self-care in improving outcomes is reviewed, as is the evidence supporting various individual, family-based, and community-based approaches to improving self-care. Although there are many nuances to the relationships between self-care and outcomes, there is strong evidence that self-care is effective in achieving the goals of the treatment plan and cannot be ignored. As such, greater emphasis should be placed on self-care in evidence-based guidelines.

This review covers the literature published in 2013 for marine natural products (MNPs), with 982 citations (644 for the period January to December 2013) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1163 for 2013), together with the relevant biological activities, source organisms and country of origin. Reviews, biosynthetic studies, first syntheses, and syntheses that lead to the revision of structures or stereochemistries, have been included.

Sunlight inactivation in fresh (river) water of fecal coliforms, enterococci, Escherichia coli, somatic coliphages, and F-RNA phages from waste stabilization pond (WSP) effluent was compared. Ten experiments were conducted outdoors in 300-liter chambers, held at 14C (mean river water temperature). Sunlight inactivation (k(S)) rates, as a function of cumulative global solar radiation (insolation), were all more than 10 times higher than the corresponding dark inactivation (k(D)) rates in enclosed (control) chambers. The overall k(S) ranking (from greatest to least inactivation) was as follows: enterococci > fecal coliforms greater-than-or-equal E. coli > somatic coliphages > F-RNA phages. In winter, fecal coliform and enterococci inactivation rates were similar but, in summer, enterococci were inactivated far more rapidly. In four experiments that included freshwater-raw sewage mixtures, enterococci survived longer than fecal coliforms (a pattern opposite to that observed with the WSP effluent), but there was little difference in phage inactivation between effluents. In two experiments which included simulated estuarine water and seawater, sunlight inactivation of all of the indicators increased with increasing salinity. Inactivation rates in freshwater, as seen under different optical filters, decreased with the increase in the spectral cutoff (50% light transmission) wavelength. The enterococci and F-RNA phages were inactivated by a wide range of wavelengths, suggesting photooxidative damage. Inactivation of fecal coliforms and somatic coliphages was mainly by shorter (UV-B) wavelengths, a result consistent with photobiological damage. Fecal coliform repair mechanisms appear to be activated in WSPs, and the surviving cells exhibit greater sunlight resistance in natural waters than those from raw sewage. In contrast, enterococci appear to suffer photooxidative damage in WSPs, rendering them susceptible to further photooxidative damage after discharge. This suggests that they are unsuitable as indicators of WSP effluent discharges to natural waters. Although somatic coliphages are more sunlight resistant than the other indicators in seawater, F-RNA phages are the most resistant in freshwater, where they may thus better represent enteric virus survival.

AIMS: The prediction of future trends in cardiovascular disease (CVD) mortality and their risk factors can assist policy-makers in healthcare planning. This study aims to project geospatial trends in CVDs and their underlying risk factors from 2025 to 2050. METHODS AND RESULTS: Using historical data on mortality and disability-adjusted life years (DALYs) from the Global Burden of Disease (GBD) 2019 study, encompassing the period of 1990 to 2019, Poisson regression was performed to model mortality and DALYs associated with CVD and its associated risk factors from 2025 to 2050. Subgroup analysis was based on GBD super-regions. Between 2025 and 2050, a 90.0% increase in cardiovascular prevalence, 73.4% increase in crude mortality, and 54.7% increase in crude DALYs are projected, with an expected 35.6 million cardiovascular deaths in 2050 (from 20.5 million in 2025). However, age-standardized cardiovascular prevalence will be relatively constant (-3.6%), with decreasing age-standardized mortality (-30.5%) and age-standardized DALYs (-29.6%). In 2050, ischaemic heart disease will remain the leading cause of cardiovascular deaths (20 million deaths) while high systolic blood pressure will be the main cardiovascular risk factor driving mortality (18.9 million deaths). Central Europe, Eastern Europe, and Central Asia super-region is set to incur the highest age-standardized cardiovascular mortality rate in 2050 (305 deaths per 100 000 population). CONCLUSION: In the coming decades, the relatively constant age-standardized prevalence of global CVD suggests that the net effect of summative preventative efforts will likely continue to be unchanged. The fall in age-standardized cardiovascular mortality reflects the improvement in medical care following diagnosis. However, future healthcare systems can expect a rapid rise in crude cardiovascular mortality, driven by the ageing global populace. The continued rise in CVD burden will largely be attributed to atherosclerotic diseases. REGISTRATION: Not applicable.

Approximately 10% of ischemic strokes are associated with atrial fibrillation (AF) first diagnosed at the time of stroke. Detecting asymptomatic AF would provide an opportunity to prevent these strokes by instituting appropriate anticoagulation. The AF-SCREEN international collaboration was formed in September 2015 to promote discussion and research about AF screening as a strategy to reduce stroke and death and to provide advocacy for implementation of country-specific AF screening programs. During 2016, 60 expert members of AF-SCREEN, including physicians, nurses, allied health professionals, health economists, and patient advocates, were invited to prepare sections of a draft document. In August 2016, 51 members met in Rome to discuss the draft document and consider the key points arising from it using a Delphi process. These key points emphasize that screen-detected AF found at a single timepoint or by intermittent ECG recordings over 2 weeks is not a benign condition and, with additional stroke factors, carries sufficient risk of stroke to justify consideration of anticoagulation. With regard to the methods of mass screening, handheld ECG devices have the advantage of providing a verifiable ECG trace that guidelines require for AF diagnosis and would therefore be preferred as screening tools. Certain patient groups, such as those with recent embolic stroke of uncertain source (ESUS), require more intensive monitoring for AF. Settings for screening include various venues in both the community and the clinic, but they must be linked to a pathway for appropriate diagnosis and management for screening to be effective. It is recognized that health resources vary widely between countries and health systems, so the setting for AF screening should be both country- and health system-specific. Based on current knowledge, this white paper provides a strong case for AF screening now while recognizing that large randomized outcomes studies would be helpful to strengthen the evidence base.

Journal Article Classics in the Theory of Public Finance Get access Classics in the Theory of Public Finance. Edited by Richard A. Musgrave and Alan T. Peacock for The International Economic Association. (London: Macmillan, 1958. Pp. 244 + xx. 30s.) A. R. Prest A. R. Prest Christ’s College Cambridge Search for other works by this author on: Oxford Academic Google Scholar The Economic Journal, Volume 69, Issue 273, 1 March 1959, Pages 138–139, https://doi.org/10.2307/2227831 Published: 01 March 1959

Adverse experiences in childhood and adolescence, defined as subjectively perceived threats to the safety or security of the child's bodily integrity, family, or social structures, are known to be associated with cardiometabolic outcomes over the life course into adulthood. This American Heart Association scientific statement reviews the scientific literature on the influence of childhood adversity on cardiometabolic outcomes that constitute the greatest public health burden in the United States, including obesity, hypertension, type 2 diabetes mellitus, and cardiovascular disease. This statement also conceptually outlines pathways linking adversity to cardiometabolic health, identifies evidence gaps, and provides suggestions for future research to inform practice and policy. We note that, despite a lack of objective agreement on what subjectively qualifies as exposure to childhood adversity and a dearth of prospective studies, substantial evidence documents an association between childhood adversity and cardiometabolic outcomes across the life course. Future studies that focus on mechanisms, resiliency, and vulnerability factors would further strengthen the evidence and provide much-needed information on targets for effective interventions. Given that childhood adversities affect cardiometabolic health and multiple health domains across the life course, interventions that ameliorate these initial upstream exposures may be more appropriate than interventions remediating downstream cardiovascular disease risk factor effects later in life.