Components of heart rate variability have attracted considerable attention in psychology and medicine and have become important dependent measures in psychophysiology and behavioral medicine. Quantification and interpretation of heart rate variability, however, remain complex issues and are fraught with pitfalls. The present report (a) examines the physiological origins and mechanisms of heart rate variability, (b) considers quantitative approaches to measurement, and (c) highlights important caveats in the interpretation of heart rate variability. Summary guidelines for research in this area are outlined, and suggestions and prospects for future developments are considered.

[1] We use a global climate model to compare the effectiveness of many climate forcing agents for producing climate change. We find a substantial range in the ''efficacy'' of different forcings, where the efficacy is the global temperature response per unit forcing relative to the response to CO 2 forcing. Anthropogenic CH 4 has efficacy $110%, which increases to $145% when its indirect effects on stratospheric H 2 O and tropospheric O 3 are included, yielding an effective climate forcing of $0.8 W/m 2 for the period 1750-2000 and making CH 4 the largest anthropogenic climate forcing other than CO 2 . Black carbon (BC) aerosols from biomass burning have a calculated efficacy $58%, while fossil fuel BC has an efficacy $78%. Accounting for forcing efficacies and for indirect effects via snow albedo and cloud changes, we find that fossil fuel soot, defined as BC + OC (organic carbon), has a net positive forcing while biomass burning BC + OC has a negative forcing. We show that replacement of the traditional instantaneous and adjusted forcings, Fi and Fa, with an easily computed alternative, Fs, yields a better predictor of climate change, i.e., its efficacies are closer to unity. Fs is inferred from flux and temperature changes in a fixed-ocean model run. There is remarkable congruence in the spatial distribution of climate change, normalized to the same forcing Fs, for most climate forcing agents, suggesting that the global forcing has more relevance to regional climate change than may have been anticipated. Increasing greenhouse gases intensify the Hadley circulation in our model, increasing rainfall in the Intertropical Convergence Zone (ITCZ), Eastern United States, and East Asia, while intensifying dry conditions in the subtropics including the Southwest United States, the Mediterranean region, the Middle East, and an expanding Sahel. These features survive in model simulations that use all estimated forcings for the period 1880-2000. Responses to localized forcings, such as land use change and heavy regional concentrations of BC aerosols, include more specific regional characteristics. We suggest that anthropogenic tropospheric O 3 and the BC snow albedo effect contribute substantially to rapid warming and sea ice loss in the Arctic. As a complement to a priori forcings, such as Fi, Fa, and Fs, we tabulate the a posteriori effective forcing, Fe, which is the product of the forcing and its efficacy. Fe requires calculation of the climate response and introduces greater model dependence, but once it is calculated for a given amount of a forcing agent it provides a good prediction of the response to other forcing amounts.

Interns made substantially more serious medical errors when they worked frequent shifts of 24 hours or more than when they worked shorter shifts. Eliminating extended work shifts and reducing the number of hours interns work per week can reduce serious medical errors in the intensive care unit.

Although the entire coronary tree is exposed to the atherogenic effect of the systemic risk factors, atherosclerotic lesions form at specific arterial regions, where low and oscillatory endothelial shear stress (ESS) occur. Low ESS modulates endothelial gene expression through complex mechanoreception and mechanotransduction processes, inducing an atherogenic endothelial phenotype and formation of an early atherosclerotic plaque. Each early plaque exhibits an individual natural history of progression, regression, or stabilization, which is dependent not only on the formation and progression of atherosclerosis but also on the vascular remodeling response. Although the pathophysiologic mechanisms involved in the remodeling of the atherosclerotic wall are incompletely understood, the dynamic interplay between local hemodynamic milieu, low ESS in particular, and the biology of the wall is likely to be important. In this review, we explore the molecular, cellular, and vascular processes supporting the role of low ESS in the natural history of coronary atherosclerosis and vascular remodeling and indicate likely mechanisms concerning the different natural history trajectories of individual coronary lesions. Atherosclerotic plaques associated with excessive expansive remodeling evolve to high-risk plaques, because low ESS conditions persist, thereby promoting continued local lipid accumulation, inflammation, oxidative stress, matrix breakdown, and eventually further plaque progression and excessive expansive remodeling. An enhanced understanding of the pathobiologic processes responsible for atherosclerosis and vascular remodeling might allow for early identification of a high-risk coronary plaque and thereby provide a rationale for innovative diagnostic and/or therapeutic strategies for the management of coronary patients and prevention of acute coronary syndromes.

To determine whether the onset of myocardial infarction occurs randomly throughout the day, we analyzed the time of onset of pain in 2999 patients admitted with myocardial infarction. A marked circadian rhythm in the frequency of onset was detected, with a peak from 6 a.m. to noon (P less than 0.01). In 703 of the patients, the time of the first elevation in the plasma creatine kinase MB (CK-MB) level could be used to time the onset of myocardial infarction objectively. CK-MB-estimated timing confirmed the existence of a circadian rhythm, with a three-fold increase in the frequency of onset of myocardial infarction at peak (9 a.m.) as compared with trough (11 p.m.) periods. The circadian rhythm was not detected in patients receiving beta-adrenergic blocking agents before myocardial infarction but was present in those not receiving such therapy. If coronary arteries become vulnerable to occlusion when the intima covering an atherosclerotic plaque is disrupted, the circadian timing of myocardial infarction may result from a variation in the tendency to thrombosis. If the rhythmic processes that drive the circadian rhythm of myocardial-infarction onset can be identified, their modification may delay or prevent the occurrence of infarction.

Abstract-Atherosclerotic cardiovascular disease results in Ͼ19 million deaths annually, and coronary heart disease accounts for the majority of this toll. Despite major advances in treatment of coronary heart disease patients, a large number of victims of the disease who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs. The recognition of the role of the vulnerable plaque has opened new avenues of

We study climate sensitivity and feedback processes in three independent ways: (1) by using a three dimensional (3-D) global climate model for experiments in which solar irradiance S o is increased 2 percent or CO 2 is doubled, (2) by using the CLIMAP climate boundary conditions to analyze the contributions of different physical processes to the cooling of the last ice age (18K years ago), and (3) by using estimated changes in global temperature and the abundance of atmospheric greenhouse gases to deduce an empirical climate sensitivity for the period 1850-1980. Our 3-D global climate model yields a warming of ~4°C for either a 2 percent increase of S o or doubled CO 2. This indicates a net feedback factor of f = 3-4, because either of these forcings would cause the earth's surface temperature to warm 1.2-1.3°C to restore radiative balance with space, if other factors remained unchanged. Principal positive feedback processes in the model are changes in atmospheric water vapor, clouds and snow/ice cover. Feedback factors calculated for these processes, with atmospheric dynamical feedbacks implicitly incorporated, are respectively f water vapor ~ 1.6, f clouds ~ 1.3 and f snow/ice ~ 1.1, with the latter mainly caused by sea ice changes. A number of potential feedbacks, such as land ice cover, vegetation cover and ocean heat transport were held fixed in these experiments. We calculate land ice, sea ice and vegetation feedbacks for the 18K climate to be f land ice ~ 1.2-1.3, f sea ice ~ 1.2, and f vegetation ~ 1.05-1.1 from their effect on the radiation budget at the top of the atmosphere. This sea ice feedback at 18K is consistent with the smaller f snow/ice ~ 1.1 in the S o and CO 2 experiments, which applied to a warmer earth with less sea ice. We also obtain an empirical estimate of f = 2-4 for the fast feedback processes (water vapor, clouds, sea ice) operating on 10-100 year time scales by comparing the cooling due to slow or specified changes (land ice, CO 2 , vegetation) to the total cooling at 18K. The temperature increase believed to have occurred in the past 130 years (approximately 0.5°C) is also found to imply a climate sensitivity of 2.5-5°C for doubled CO 2 (f = 2-4), if (1) the temperature increase is due to the added greenhouse gases, (2) the 1850 CO 2 abundance was 270 ± 10 ppm, and (3) the heat perturbation is mixed like a passive tracer in the ocean with vertical mixing coefficient k ~ 1 cm 2 s −1. These analyses indicate that f is substantially greater than unity on all time scales. Our best estimate for the current climate due to processes operating on the 10-100 year time scale is f = 2-4, corresponding to a climate sensitivity of 2.5-5°C for doubled CO 2. The physical process contributing the greatest uncertainty to f on this time scale appears to be the cloud feedback.

Information obtained during the past decade suggests the need to reexamine the possibility that the onset of myocardial infarction and sudden cardiac death is frequently triggered by daily activities. The importance of physical or mental stress in triggering onset of coronary thrombosis is supported by the findings that 1) the frequencies of onset of myocardial infarction, sudden cardiac death, and stroke show marked circadian variations with parallel increases in the period from 6:00 AM to noon, 2) transient myocardial ischemia shows a similar morning increase, and episodes are often preceded by mental or physical triggers, 3) a ruptured atherosclerotic plaque, often nonobstructive by itself, lies at the base of most coronary thrombi, 4) a number of physiologic processes that could lead to plaque rupture, a hypercoagulable state or coronary vasoconstriction, are accentuated in the morning, and 5) aspirin and beta-adrenergic blocking agents, which block certain of these processes, have been shown to prevent disease onset. The hypothesis is presented that occlusive coronary thrombosis occurs when 1) an atherosclerotic plaque becomes vulnerable to rupture, 2) mental or physical stress causes the plaque to rupture, and 3) increases in coagulability or vasoconstriction, triggered by daily activities, contribute to complete occlusion of the coronary artery lumen. Recognition of the circadian variation--and the possibility of frequent triggering--of onset of acute disease suggests the need for pharmacologic protection of patients during vulnerable periods, and provides clues to mechanism, the investigations of which may lead to improved methods of prevention.