G-estimation of causal effects: isolated systolic hypertension and cardiovascular death in the Framingham Heart Study.

Time-dependent covariates are often both confounders and intermediate variables. In the presence of such covariates, standard approaches for adjustment for confounding are biased. The method of G-estimation allows for appropriate adjustment. Previous studies applying the G-estimation method have addressed effects on all-cause mortality rather than on specific causes of death. In the present study, a method to adjust for censoring by competing risks is presented. The authors used the approach to estimate the causal effect of isolated systolic hypertension on cardiovascular mortality in the Framingham Heart Study, with a 10-year follow-up using data from 1956 to 1970. Arterial rigidity is a major determinant of isolated systolic hypertension and may be a confounder of the relation between isolated systolic hypertension and cardiovascular death. Conversely, isolated systolic hypertension may by itself contribute to stiffening of the vessel wall, and arterial rigidity may therefore also be an intermediate variable in the causal pathway from isolated systolic hypertension to cardiovascular death. While controlling for arterial rigidity and other baseline and time-dependent covariates, isolated systolic hypertension decreased the time to cardiovascular death by 45% (95% confidence interval 3-69).

Active compliance in robotic surgery--the use of force control as a dynamic constraint.

Robotic surgery can be carried out automatically by using a robot to move the cutting tool under position control. However, although the surgeon can observe the procedure on a visual display and has the ability to stop the operation in an emergency, he has little direct contact with the task. An alternative approach is to involve the surgeon more directly, by his moving a robot using active force control. The robot is then used to allow motion in preprogrammed regions, by the surgeon back-driving the robot motors, while preventing motion in prohibited areas. This active constraint robot (or ACROBOT) is described in this paper applied to knee surgery, in which the knee bones are accurately machined to allow the fitting of prosthetic knee implants. The ACROBOT is, however, ideally suited to a range of surgical procedure, because it allows the surgeon to feel the forces exerted during cutting and take appropriate action. This ability to be in direct control, while being constrained to cut within a permitted region, enhances safety and makes the system more acceptable to the medical community. The system of programmable constraint also allows the ACROBOT to provide the traditional benefits of robot surgery, namely the ability to machine complex geometrical surfaces very accurately and to make repetitive motions tirelessly. The system also has a potential for minimally invasive procedures. In knee surgery, for example, the robot could operate through a small incision in the skin and excise a volume into which a small, specially designed, unicompartmental prosthesis could fit.

Aortic calcified plaques and cardiovascular disease (the Framingham Study).

The relation between the presence of calcified plaques in the thoracic aorta, as detected on chest x-rays, and the development of cardiovascular disease is examined during 12 years of follow-up of the Framingham cohort (n = 5,209). The prevalence of aortic calcified plaques approximately doubled with each decade of age, with only a trivial male predominance. Its presence was associated with a twofold increase in risk of cardiovascular death in men and women younger than age 65, even after other risk factors were taken into account. Similar increases in risk were found for coronary artery disease, stroke and intermittent claudication among middle-aged women. In middle-aged men these risks were less marked. The predictive value of aortic calcified plaques generally diminished with age. Risk of sudden coronary death in men with calcified plaques in the thoracic aorta ranged from a sevenfold increase at age 35 to no excess risk at age 70 years. These results support the view that atherosclerosis is a generalized process. The finding of aortic calcified plaques in a relatively young subject on a routine chest x-ray should be regarded as a sign for potential development of clinically manifest atherosclerotic disease in the cardiac, cerebral and peripheral arterial circulation.

An evaluation of adenosine 3',5'-cyclic monophospate-dependent protein kinase activity in atopic dermatitis.

Activity of adenosine 3',5'-cyclic monophosphate-dependent protein kinase has been measured in the skin of normal controls, patients with non-atopic skin disorders, and those with atopic dermatitis. All samples analyzed displayed the presence of this enzymatic activity. However, the enzyme from the atopic skin did not seem to be dependent on cyclic AMP for activity. Whether this is due to an artifact of isolation of protein kinase or is indeed the true in vivo nature of the enzyme remains to be established.

Iron meteorites with low cosmic ray exposure ages.

Analysis of argon-38 and argon-39 produced by cosmic rays in four iron meteorites gives normal amounts of the radioactive product argon-39 and abnormally low amounts of stable argon-38. This indicates that these meteorites were exposed to cosmic rays for unusually short periods of time. These exposure times are one or two orders of magnitude shorter than those for the average iron meteorite, and they overlap the periods found for chondrites. It is suggested that perhaps 20 percent of the iron meteorites have similarly short exposure periods.