Papers and patents are becoming less disruptive over time.

Theories of scientific and technological change view discovery and invention as endogenous processes, wherein previous accumulated knowledge enables future progress by allowing researchers to, in Newton's words, 'stand on the shoulders of giants'. Recent decades have witnessed exponential growth in the volume of new scientific and technological knowledge, thereby creating conditions that should be ripe for major advances. Yet contrary to this view, studies suggest that progress is slowing in several major fields.

Do synthesis centers synthesize? A semantic analysis of topical diversity in research.

Synthesis centers are a form of scientific organization that catalyzes and supports research that integrates diverse theories, methods and data across spatial or temporal scales to increase the generality, parsimony, applicability, or empirical soundness of scientific explanations. Synthesis working groups are a distinctive form of scientific collaboration that produce consequential, high-impact publications. But no one has asked if synthesis working groups synthesize: are their publications substantially more diverse than others, and if so, in what ways and with what effect? We investigate these questions by using Latent Dirichlet Analysis to compare the topical diversity of papers published by synthesis center collaborations with that of papers in a reference corpus.

A help or a hindrance? The impact of job training on the employment status of disadvantaged women.

The objective of this study is to evaluate whether welfare-sponsored, government-funded job training helps participants improve their employment status. The negligible effects found in prior studies may be due to design limitations or inherent flaws in job training programs and therefore do not necessarily contradict human capital theory. The present study uses longitudinal and representative data, dynamic modeling techniques, an appropriate counterfactual, and important contextual variables to assess the likelihood of obtaining employment for job training participants and nonparticipants.

Myocardial monovalent cation transport during the quinidine-digoxin interaction in dogs.

To study the relationship of the serum digoxin concentration to the digoxin effect on monovalent cation transport during the quinidine-digoxin interaction, we used radiolabeled rubidium to measure monovalent cation active transport in myocardial biopsy samples from dogs. In a preliminary study, we showed that quinidine did not affect rubidium uptake by myocardial samples from intact dogs. Then, we studied four groups, each consisting of 13 dogs, which received either saline, low dose digoxin, high dose digoxin, or low dose digoxin plus quinidine treatment.

Quinidine and digoxin. An important interaction.

An increase in serum digoxin concentration occurs in 90% of patients given quinidine. On average, the serum digoxin doubles during treatment with therapeutic doses of quinidine. Almost every patient treated with quinidine will have a decrease in the renal clearance of digoxin and many will have a decrease in the volume of distribution of digoxin.

Quinidine-digoxin interaction: time course and pharmacokinetics.

The time course of the rise in serum digoxin concentration was followed in 18 patients treated with digoxin as quinidine treatment was started with a loading dose. The mean serum digoxin levels rose significantly during the first 24 hours after administration of quinidine was begun, and reached a new steady state concentration after about 48 hours. Digoxin kinetics were studied in two groups of normal volunteers: Group 1 (n = 7) received a small dose of quinidine, 800 mg/day, and group II (n = 8) received 1,600 mg/day.

The effect of quinidine and other oral antiarrhythmic drugs on serum digoxin. A prospective study.

We compared the effects of quinidine and three alternate antiarrhythmic drugs on serum digoxin concentration in 63 patients before and during administration of quinidine, procainamide, disopyramide, or mexiletine. Quinidine increased digoxin concentration by at least 0.5 nmol/L in 21 of 22 patients: Mean serum digoxin rose from 1.

Enhanced cardiac effect of digoxin during quinidine treatment.

Quinidine causes an increase in the serum digoxin concentration. Three patients were studied to determine if the increase in serum concentration is paralleled by an increase in the cardiac effect of digoxin. Each patient's clinical condition and serum digoxin concentration were stable when quinidine administration was begun.

A previously unrecognized drug interaction between quinidine and digoxin.

Following the development of digoxin radioimmunoassay, we noted that serum digoxin concentrations appeared to rise in patients given quinidine. To further evaluate this important possible interaction between digoxin and quinidine, charts from 863 cardiology patients were reviewed. Ninety two patients received both drugs after having been on digoxin alone; 38 were ineligible for the study because of insufficient data and 27 were excluded because of changing renal function and/or concomitant antiarrhythmic drug therapy, leaving 27.

Interaction between quinidine and digoxin.

The serum digoxin concentration increased in 25 of 27 study patients (93%), and the mean serum digoxin concentration rose from 1.4 ng/ml to 3.2 ng/ml during quinidine therapy.

Direct current cardioversion. Effect on creatine kinase, lactic dehydrogenase and myocardial isoenzymes.

Creatine kinase (CK), lactic dehydrogenase (LDH), and more recently their isoenzyme determinations (CK-MB and LDH1) have been useful adjuncts in verification of myocardial injury. To determine whether DC cardioversion affects these serum enzyme levels, we recorded total CK, total LDH, CK-MB, and LDH1 levels serially during 24 hours following elective DC cardioversion in 18 patients without cardiac ischemia. New postcardioversion elevations in total CK and total LDH levels were small and occasional: CK (one of 18 patients), LDH (four of 18 patients).

Elderly patients with lower extremity amputations: three-year study in a rehabilitation setting.

Of the 112 mostly elderly patients with lower extremity amputations who were initially evaluated for this study, 86 were discharged as independent prosthetic ambulators after completion of both phases of a two-phase prosthetic rehabilitation program with a team approach. In four years of outpatient follow-up of the 86 patients who completed phase II, 14 died and contact was lost with 6. Sixty-six remain prosthetic ambulators.

Below-knee amputations.

Below-knee amputations are commonly performed for peripheral vascular disease. To be successful, the technic must be exacting, and it is crucial to bevel carefully the anterior and medial tibial surfaces to permit successful prosthetic rehabilitation.