The transfer of unsterilized material from Mars to Phobos: Laboratory tests, modelling and statistical evaluation.

Sample return missions to Phobos are the subject of future exploration plans. Given the proximity of Phobos to Mars, Mars' potential to have supported life, and the possibility of material transfer from Mars to Phobos, careful consideration of planetary protection is required. If life exists, or ever existed, on Mars, there is a possibility that material carrying organisms could be present on Phobos and be collected by a sample return mission such as the Japanese Martian Moons eXplorer (MMX). Here we describe laboratory experiments, theoretical modelling and statistical analysis undertaken to quantify whether the likelihood of a sample from Phobos material containing unsterilized material transferred from Mars is less than 10-6, the threshold to transition between restricted and unrestricted sample return classification for planetary protection. We have created heat, impact and radiation sterilization models based on the Phobos environment, and through statistical analyses investigated the level of sterilization expected for martian material transferred to Phobos. These analyses indicate that radiation is the major sterilization factor, sterilizing the Phobos surface over timescales of millions of years. The specific events of most relevance in the Phobos sample return context are the 'young' cratering events on Mars that result in Zunil-sized craters, which can emplace a large mass of martian material on Phobos, in a short period of time, thus inhibiting the effects of radiation sterilization. Major unknowns that cannot yet be constrained accurately enough are found to drive the results - the most critical being the determination of exact crater ages to statistical certainty, and the initial biological loading on Mars prior to transfer. We find that, when taking a conservative perspective and assuming the best-case scenario for organism survival, for a 100 g sample of the Phobos regolith to be below the planetary protection requirement for unrestricted sample return, the initial biological loading on Mars must be <8.2 × 103cfu kg-1. For the planned MMX mission, a ∼10 g sample to be obtained from a 25-30 mm diameter core as planned would require an initial martian biological loading to be <1.6 × 104cfu kg-1, in order to remain compliant with the planetary protection threshold.

The subjective experience of taking antipsychotic medication: a content analysis of Internet data.

OBJECTIVE: We explored the subjective effects associated with olanzapine, risperidone and older antipsychotics. METHOD: We conducted a content analysis of an Internet database of comments about prescribed medications. RESULTS: We analysed 223 comments on risperidone, 170 on olanzapine and 46 relating to three older antipsychotics. The predominant subjective effects produced by all drugs consisted of sedation, cognitive impairment and emotional flattening or indifference. Connections appeared between these effects and Parkinsonian-like symptoms with the older drugs, sexual impairment with risperidone and metabolic effects with olanzapine. The experience of akathisia was frequently linked to suicidal thoughts. Some respondents described how the drugs' subjective effects helped to reduce symptoms of mania, psychosis and anxiety. CONCLUSION: The generalisability of Internet data is uncertain. However, the data suggest that adverse subjective effects play a central role in the experience of taking antipsychotic drugs and may be related to the drugs' desired benefits.

Pharmacokinetics of the 5-hydroxytryptamine1A agonist 8-hydroxy-2-(N,N-di-n-propylamino)tetralin (8-OHDPAT) in the rat after intravenous and oral administration.

1. Plasma levels of 3H and unchanged drug were measured in the non-anaesthetized male rat after intravenous (i.v.) or oral administration of (+/-)-(R,S)-[propyl-3H]-8-OHD-PAT, at three dose levels per route of administration. The excretion of conjugated metabolites in bile was also studied following i.v. administration. 2. For unchanged 8-OHDPAT following i.v. administration, terminal t1/2 was 1.56 +/- 0.01 h (mean +/- SD, n > or = 4), kelim 0.45 +/- 0.01 h-1, volume of distribution 0.14 +/- 0.02 litres and clearance 1.10 +/- 0.17 mlmin-1. After oral administration, terminal t1/2, kelim, apparent volume of distribution and clearance were essentially the same when bioavailability was taken into account. Neither dose size nor route of administration had any significant effect on either terminal t1/2 or kelim. Comparison of AUCs following i.v. and oral administration yielded a mean for absolute oral bioavailability of 2.60 +/- 0.24%. 3. Comparison of AUCB for total plasma 3H showed that the extent of absorption was 80.1%, indicating that the low oral bioavailability of 8-OHDPAT is due to first-pass metabolism, rather than poor absorption from the GI tract. 4. Following i.v. administration, irrespective of dose, some 10% of the 3H dose was excreted in the bile in 6 h, 8.5% as 8-OHDPAT-glucuronide and 1.5% as the glucuronide of the N-despropylated metabolite, 8-OHDPAT. The majority of the biliary excretion occurred within 3 h of dosing.

Metabolism of [propyl-3H]-8-hydroxy-2-(N,N-di-n-propylamino)tetralin in rat.

1. Male Sprague-Dawley rats given (RS)-[3H]-8-OHDPAT by intraperitoneal (i.p.) or intravenous (i.v.) injection, or orally (p.o.) by gavage, excreted the majority of the dose in the urine (> 80% in 3 days and > 70% in the first 24 h). A smaller proportion of the dose was excreted in the faeces (> 10% in 3 days), mostly in the first 24 h. Total recovery was > 90% (mean: i.p. = 94.9; i.v. = 99 and p.o. = 92.9%). 2. Urinary metabolites were separated by reversed-phase hplc before and after treatment with beta-glucuronidase or sulphatase and quantitated by liquid scintillation spectrometry. Metabolites were identified by hydrolysis by specific enzymes, comparison of hplc retention time with those of authentic standards and by LC-MS. 3. Two major metabolites were identified and quantitated in the 24-h urine, namely 8-OHDPAT-glucuronide, accounting for some 45% of dose, and its N-despropylated metabolite, 8-hydroxy-2-(N-n-propylamino)tetralin, excreted as its glucuronide, which accounted for 15% of dose. Small amounts (< 1%) of two monohydroxylated metabolites were also identified, one eluting slightly earlier than and the other co-eluting with the mono-despropylated metabolite. When analysed by LC-MS-MS, the first of these exhibited a fragmentation pattern consistent with ring hydroxylation and the other appeared to be a side chain oxidized metabolite, which may constitute an intermediate in N-despropylation. However, these metabolites were present at too low a level to allow the exact position of hydroxylation to be determined. 4. These studies suggest that the low oral activity exhibited by 8-OHDPAT is most likely the result of rapid and extensive glucuronidation rather than poor absorption from the gastrointestinal tract.

Calcium and phosphorus requirement of swine from weaning to market weight: II. Development of response curves for bone criteria and comparison of bending and shear bone testing.

Three trials involving 251 crossbred pigs were conducted to establish response surfaces for effects of Ca/P levels (70, 85, 100, 115 and 130% of NRC [1979] estimated requirements) and time (weaning to market) on bone criteria and to compare bending and shear bone testing. Nine replicates, each consisting of five pigs, were used over the three trials. One pig per replicate was slaughtered every 4 wk following the start of the trials. Third metacarpals and metatarsals (3M) and fourth metacarpals and metatarsals (4M) were collected at slaughter; the bone length, bending or shear stress, and dry, fat-free ash percentage (DFF%) were determined. Most bone criteria increased (P less than .01) at a decreasing rate (P less than .05) in response to increasing dietary Ca/P intake and increased linearly (P less than .01) with time on test, although bone length and stress increased at a decreasing rate with time on test. Asymptotic models relating continuous effects of total Ca + P intake ratio (CAP; expressed as a percentage of NRC) and number of days on test before slaughter to bone measurements were fit to least squares slaughter time by diet means. Bone length and DFF% reached 98% maximum at or near 100% the NRC estimated CAP level; however, to reach 98% of maximum bone shear and breaking stress higher CAP levels were required. Shear testing of bones was more desirable than bend testing as a method of determining bone strength due to reduced variability, better discrimination of Ca/P and time effects and ease of calculation.

A study of certain environmental factors and mineral chelation on the reproductive performance of young and yearling turkey hens.

The study presented was designed to determine the effects of laying cages and conventional litter floors, pen temperatures of 12.8 degrees, 21.1 degrees and 29.4 degrees C., and chelated (EDTA-Zn) vs. nonchelated trace mineral mixes on the reproductive performance of yearling force-molted and young Large White female turkeys. Reproductive performance, as measured by egg production, settable eggs, fertility and hatchability of fertile eggs, was not significantly different between young and yearling hens. Females fed a chelated trace mineral mix had a higher percentage of settable eggs, greater feed consumption and thicker egg shells. Females in laying cages laid at a higher rate, ate more feed, and weighed more than those on conventional floors. Significant differences were not observed between the two pen environments for hatchability of fertile eggs or egg weight. The percentages of settable eggs and of fertile eggs were lower when females were maintained in cages. A constant temperature of 29.4 degrees C. reduced egg production below that obtained from females maintained at 12.8 degrees and 21.1 degrees C. The high pen temperature also caused lower body and egg weights, more birds out of production and an increased incidence of molting. Feed consumption decreased with increasing pen temperatures. Fertility, hatchability, percentage of settable eggs and egg shell thickness were unaffected by the imposed temperature environments. Temperatures of 12.8 degrees and 21.1 degrees C. yielded comparable results for all reproductive parameters measured. Within the range of temperatures studied, results obtained suggest that optimum reproductive performance can be obtained with breeder turkeys when environmental temperatures are maintained between 12.8 degrees and 21.1 degrees C.