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Radiation: behavioral implications in space.

Abstract

Since future space missions are likely to be beyond Earth's protective atmosphere, a potentially significant hazard is radiation. The following behavioral situations are addressed in this paper: (1) space radiations are more effective at disrupting behavior; (2) task demands can aggravate the radiation-disruption; (3) efforts to mitigate disruption with drugs or shielding are not satisfactory and the drugs can be behaviorally toxic; and (4) space- and radiation-induced emesis combined may be synergistic. Thus, future space travel will be a demanding, exciting time for behavioral toxicologists, and while the circumstances may seem insurmountable at first, creative application of scientific expertise should illicit solutions, similar to demanding situations confronted before.

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BibTeXRIS

V Bogo. 1988. Radiation: behavioral implications in space.. https://doi.org/10.1016/0300-483x(88)90012-1

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A sequential procedure for monitoring clinical trials against historical controls.

In this paper, we develop a sequential procedure to monitor clinical trials against historical controls. When there is a strong ethical concern about randomizing patients to existing treatment because biological and medical evidence suggests that the new treatment is potentially superior to the existing one, or when the enrollment is too limited for randomization of subjects into experimental and control groups, one can monitor the trial sequentially against historical controls if the historical data with required quality and sample size are available to form a valid reference for the trial. This design of trial is sometimes the only alternative to a randomized phase III trial design that is intended but not feasible in situations such as above. Monitoring this type of clinical trial leads to a statistical problem of comparing two population means in a situation in which data from one population are sequentially collected and compared with all data from the other population at each interim look. The proposed sequential procedures is based on the sequential conditional probability ratio test (SCPRT) by which the conclusion of the sequential test would be virtually the same as that arrived at by a non-sequential test based on all data at the planned end of the trial. We develop the sequential procedure by proposing a Brownian motion that emulates the test statistic, and then proposing an SCPRT that is adapted to the special properties of the trial.

Amifostine↗

Amifostine protects rat kidneys during peptide receptor radionuclide therapy with [177Lu-DOTA0,Tyr3]octreotate.

PURPOSE: In peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues, the kidneys are the major dose-limiting organs, because of tubular reabsorption and retention of radioactivity. Preventing renal uptake or toxicity will allow for higher tumour radiation doses. We tested the cytoprotective drug amifostine, which selectively protects healthy tissue during chemo- and radiotherapy, for its renoprotective capacities after PRRT with high-dose [(177)Lu-DOTA(0),Tyr(3)]octreotate. METHODS: Male Lewis rats were injected with 278 or 555 MBq [(177)Lu-DOTA(0),Tyr(3)]octreotate to create renal damage and were followed up for 130 days. For renoprotection, rats received either amifostine or co-injection with lysine. Kidneys, blood and urine were collected for toxicity measurements. At 130 days after PRRT, a single-photon emission computed tomography (SPECT) scan was performed to quantify tubular uptake of (99m)Tc-dimercaptosuccinic acid (DMSA), a measure of tubular function. RESULTS: Treatment with 555 MBq [(177)Lu-DOTA(0),Tyr(3)]octreotate resulted in body weight loss, elevated creatinine and proteinuria. Amifostine and lysine treatment significantly prevented this rise in creatinine and the level of proteinuria, but did not improve the histological damage. In contrast, after 278 MBq [(177)Lu-DOTA(0),Tyr(3)]octreotate, creatinine values were slightly, but not significantly, elevated compared with the control rats. Proteinuria and histological damage were different from controls and were significantly improved by amifostine treatment. Quantification of (99m)Tc-DMSA SPECT scintigrams at 130 days after [(177)Lu-DOTA(0),Tyr(3)]octreotate therapy correlated well with 1/creatinine (r(2)=0.772, p<0.001). CONCLUSION: Amifostine and lysine effectively decreased functional renal damage caused by high-dose [(177)Lu-DOTA(0),Tyr(3)]octreotate. Besides lysine, amifostine might be used in clinical PRRT as well as to maximise anti-tumour efficacy.

Amifostine↗