After an average of four years of supplementation, the combination of beta carotene and vitamin A had no benefit and may have had an adverse effect on the incidence of lung cancer and on the risk of death from lung cancer, cardiovascular disease, and any cause in smokers and workers exposed to asbestos.

CARET participants receiving the combination of beta-carotene and vitamin A had no chemopreventive benefit and had excess lung cancer incidence and mortality. The results are highly consistent with those found for beta-carotene in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study in 29133 male smokers in Finland.

Temperature rise, measured a short distance from a line heat source, can be used to determine the volumetric specific heat of soil and other materials. Volumetric specific heat is linearly related to the inverse of the temperature rise. The purpose of this note is to describe the construction and performance of a device for measuring specific heat using the line source method. The device was constructed from two hypodermic needles, 0.813 mm in diam. and 28 mm long, and spaced 6 mm apart. One needle contained a heater and the other a thermocouple. The temperature rise from heat pulses given to the heater were measured with the thermocouple. The coefficientof variation (CV) of specific heat on replicate samples was around 1%. Since water is the main variable component of the specific heat in nonswelling soil, changes in water content might be resolved to 0.01 or better in nonswelling soils.

The previously reported adverse effects of beta-carotene and retinyl palmitate on lung cancer incidence and all-cause mortality in cigarette smokers and individuals with occupational exposure to asbestos persisted after drug administration was stopped although they are no longer statistically significant. Planned subgroup analyses suggest that the excess risks of lung cancer were restricted primarily to females, and cardiovascular disease mortality primarily to females and to former smokers.

We have combined electrophysiology and imaging to measure the release of neurotransmitter and fluorescent dye at synapses of cultured hippocampal neurons. These experiments have revealed a ''kiss and run'' mode of exocytosis in which synaptic vesicles release glutamate normally but do not permit dye to enter or escape from the vesicle. During ''kiss and run,'' the vesicle interior may be exposed very transiently (<6 ms), or a special configuration of the fusion pore may prevent dye exchange. We estimate that about 20% of the vesicles normally use this ''kiss and run'' pathway, and that the fraction of ''kiss and run'' events can be increased to over 80% by superfusing the synapses with hypertonic solution. D uring a study of synaptic vesicle trafficking in which we measured the release of the fluorescent dye FM1-43 (1) after stimulation with either action potentials or hypertonic solution, we noticed that, with hypertonic stimulation, the escape of dye from previously loaded vesicles seemed to be partly prevented even though the neurotransmitter glutamate was released normally. Hypertonic solution application produces asynchronous release of synaptic vesicles at a rate that is graded with osmolarity, and this type of stimulation draws on the same pool of vesicles as action potential-evoked release; but hypertonic stimulation circumvents the normal dependence of vesicle fusion on calcium ions, presumably through a mechanical lowering of the energy barrier for membrane fusion (2). The experiments presented here are an analysis of this dissociation between neurotransmitter and dye release.Our main observation is a simple one: when exocytosis is produced by hypertonic solution, a fraction of the vesicles that release neurotransmitter fail either to release or take up fluorescent dye, and this fraction increases to over 80% with increasing osmolarity. Synaptic vesicles participating in exocytosis normally take up (3) or release (4) the dye in less than about 20 ms, so the failure of dye exchange means that either a fusion pore exists for a very brief time (so brief that dye has insufficient time to enter or leave the vesicle), or the conformation of the fusion pore is one that permits glutamate outflow but excludes dye passage. We identify this special exocytic state of the vesicle with ''kiss and run'' and, at least under the conditions of our experiments, estimate that ''kiss and run'' constitutes about 20% of the release events during normal synaptic transmission. Experimental ProceduresCell Culture. Primary cultures of hippocampal neurons were prepared from P0-1 rat pups by using standard methods. We used both conventional and ''microdot'' cultures with single-cell islands (2, 5).Solutions. Cultures were superfused with 50 M D,L-2-amino-5-phosphonovaleric acid (Research Biochemicals) in physiological saline [132 mM NaCl͞2 mM KCl͞2.6 mM CaCl 2 ͞1.3 mM MgCl 2 ͞10 mM glucose͞10 mM Hepes, with pH Ϸ7.2 and osmolarity adjusted to Ϸ0.3 osmolar (osM) with sorbitol]. In addition, 10 M 6-cyano-7-nitroquinoxaline-2,3-dione ...