Forgotten fatalities: British military, mining and maritime accidents since 1900.

BACKGROUND: Comparative long-term trends in fatal accident rates in the UK's most hazardous occupations have not been reported. AIMS: To compare trends in fatal accident rates in six of the most hazardous occupations (the three armed forces, merchant shipping, sea fishing and coal mining) and the general British workforce during peacetime years since 1900. METHODS: Examinations of annual mortality reports, returns, inquiry files and statistics. The main outcome measure was the fatal accident rate per 100 000 population employed. RESULTS: These six occupations accounted for ~40% of all fatal accidents in the British workforce. Fatal accident rates were highest in merchant shipping to 1914 (400-600 per 100 000) and in the Royal Air Force and sea fishing by the early 1920s (around 300 per 100 000). Since the 1950s sea fishing has remained the most hazardous occupation (50-200). Widespread reductions in fatal accident rates for each occupation have been greatest in recent years in the three armed forces and merchant shipping. Compared with the general workforce, relative risks of fatalities have increased in recent decades in all these occupations except shipping. CONCLUSIONS: All six occupations still have high fatal accident rates. The greatly increased fatalities in sea fishing generally and in the Royal Air Force during its early years reflect, for different reasons, cultures of extreme risk-taking in these two sectors. Reductions in fatality rates in the armed forces over the last 20 years are due largely to decreases in land transport accidents.

Mars Extant Life: What's Next? Conference Report.

On November 5-8, 2019, the "Mars Extant Life: What's Next?" conference was convened in Carlsbad, New Mexico. The conference gathered a community of actively publishing experts in disciplines related to habitability and astrobiology. Primary conclusions are as follows: A significant subset of conference attendees concluded that there is a realistic possibility that Mars hosts indigenous microbial life. A powerful theme that permeated the conference is that the key to the search for martian extant life lies in identifying and exploring refugia ("oases"), where conditions are either permanently or episodically significantly more hospitable than average. Based on our existing knowledge of Mars, conference participants highlighted four potential martian refugium (not listed in priority order): Caves, Deep Subsurface, Ices, and Salts. The conference group did not attempt to reach a consensus prioritization of these candidate environments, but instead felt that a defensible prioritization would require a future competitive process. Within the context of these candidate environments, we identified a variety of geological search strategies that could narrow the search space. Additionally, we summarized a number of measurement techniques that could be used to detect evidence of extant life (if present). Again, it was not within the scope of the conference to prioritize these measurement techniques-that is best left for the competitive process. We specifically note that the number and sensitivity of detection methods that could be implemented if samples were returned to Earth greatly exceed the methodologies that could be used at Mars. Finally, important lessons to guide extant life search processes can be derived both from experiments carried out in terrestrial laboratories and analog field sites and from theoretical modeling.

4-(Heteroarylthio)-2-biphenylyltetrazoles as nonpeptide angiotensin II antagonists.

A series of 4-(heteroarylthio)-2-biphenylyltetrazoles was prepared, and the compounds were examined for their ability to displace [3H]AII from angiotensin II receptors. Analogues that exhibited significant receptor binding affinities at less than 10 microM were investigated further for potential antagonism of angiotensin II-mediated contraction of rabbit isolated aortic rings. Three 4-(heteroarylthio)-2-biphenylyltetrazoles were identified that exhibited sub-micromolar angiotensin II receptor binding affinities. These compounds and two reference agents, saralasin and losartan (DUP-753), exhibited concentration-dependent reversal of angiotensin II contraction in isolated aortic rings parallel to their receptor binding affinities. Molecular modeling studies were conducted to examine the conformational effects of the novel sulfide bridging unit contained in these 4-(heteroarylthio)-2-biphenylyltetrazoles. The biological effects of the sulfide bridge as well as alterations in the heteroaromatic moiety were investigated, and the resulting structure--activity relationships are discussed.

In situ microbial detection in Mojave Desert soil using native fluorescence.

We report on the use of a portable instrument for microbial detection in the Mojave Desert soil and the potential for its use on Mars. The instrument is based on native fluorescence and employs four excitation wavelengths combined with four emission wavelengths. A soil dilution series in which known numbers of Bacillus subtilis spores were added to soil was used to determine the sensitivity of the instrument. We found that the fluorescence of the biological and organic components of the desert soil samples studied can be as strong as the fluorescence of the mineral component of these soils. Using the calibration derived from B. subtilis spores, we estimated that microbial content at our primary sampling site was 10(7) bacteria per gram of soil, a level confirmed by phospholipid fatty acid analysis. At a nearby site, but in a slightly different geological setting, we tested the instrument's ability to map out microbial concentrations in situ. Over a ∼50 m diameter circle, soil microbial concentrations determined with the B. subtilis calibration indicate that the concentrations of microorganisms detected varies from 10(4) to 10(7) cells per gram of soil. We conclude that fluorescence is a promising method for detecting soil microbes in noncontact applications in extreme environments on Earth and may have applications on future missions to Mars.

Detection thresholds for 60 Hz electric fields by nonhuman primates.

Because responses of animals to detection of the presence of an electric field (EF) are a possible mechanism for production of biological effects, it is important to know what EF intensities are detectable. Operant methods were used to train six baboons (Papio cynocephalus) to perform a psychophysical task involving detection of EF presence. During the response phase of a trial, a subject responded on one push button to report the presence of the EF and on a different push button to report the absence of the EF. Correct reports of EF presence of absence produced delivery of food rewards. The subjects became proficient at performing this psychophysical detection task; during 35 days of testing, false alarm rates averaged 9%. The average EF detection threshold was 12 kV/m; the range of means among subjects was 5-15 kV/m. Two special test procedures confirmed that the subjects were responding directly to EF presence of absence and not to artifacts that might be associated with EF generation. The EF detection threshold of nonhuman primates is similar to thresholds reported for rats and humans.

Initial exposure to 30 kV/m or 60 kV/m 60 Hz electric fields produces temporary cessation of operant behavior of nonhuman primates.

In two separate experiments, we examined the effects of a 60 Hz electric field (EF) on performance of an operant schedule consisting of two signaled components: fixed-ratio (FR30) and differential reinforcement of low-rate (DRL20). In each experiment, 12 naive baboons (Papio cynocephalus) were assigned randomly to either an EF-exposed experimental group or a sham-exposed control group. A homogeneous vertical EF of 30 kV/m was used in one experiment; 60 kV/m was used in the other. The experimental design for both experiments included 6 week preexposure, exposure, and postexposure periods. The planned analyses indicated no evidence of statistically significant (P < .05) effects of EF exposure. However, exploratory analyses comparing performance during the last week of preexposure and the first week of exposure revealed statistically significant acute effects (work stoppage): The mean response rates of the EF-exposed groups were greatly reduced on day 1 of exposure but were normal by the end of day 2 of EF exposure. We hypothesize that introduction of a highly unusual stimulus, the EF, temporarily interfered with normal operant behavior to produce a primary work stoppage. Supplementary cross-over experiments added at the end of each main experiment indicated that work stoppage occurred again when formerly EF-exposed subjects served as sham-exposed controls, while other subjects received their first EF exposure. Presumably, reoccurrence of other stimuli correlated with initial exposure to the EF became sufficient to subsequently cause secondary work stoppage in the absence of direct EF exposure. The primary and secondary work-stoppage effects were reproducible.

Nonhuman primates will not respond to turn off strong 60 Hz electric fields.

Using a set of six baboons (Papio cynocephalus), we conducted a series of seven experiments designed to evaluate the potentially aversive character of a 60 Hz electric field (EF). Initially, the subjects were trained, using food rewards as the reinforcer, to respond only when a cue light was illuminated. Next, an EF was presented along with the cue light; responses produced delivery of a food pellet and turned off both the cue light and the EF. Then, stimulus and reward conditions were varied. We determined that 1) presence of a strong EF does not affect operant responding for food rewards, 2) subjects will not respond at normal rates when the only reinforcer is termination of a strong EF, 3) presence of a strong EF can serve as a discriminative stimulus, 4) presence of a strong EF does not affect extinction of an appetite-motivated task, and 5) presentation of an EF can become a secondary reinforcer. The pattern of results was consistent across all experiments, suggesting that an EF of as much 65 kV/m is not aversive to nonhuman primates. Separately, we demonstrated that the average EF detection threshold for baboons in 12 kV/m. Thus, EF exposure at intensities well above the detection threshold and at species-scaled EF strengths greater than those found environmentally does not appear to be aversive.

Exposure of baboons to combined 60 Hz electric and magnetic fields does not produce work stoppage or affect operant performance on a match-to-sample task.

We examined the effects of combined 60 Hz electric and magnetic field (EMF) exposure on performance of delayed match-to-sample (MTS) procedure involving the flash rate of a light as the stimulus. Six baboons (Papio cynocephalus) fully acquired the task; four others functioned accurately only when cued. All ten subjects were assigned to EMF-exposed or sham-exposed groups of five and were used to test for a work-stoppage effect that was previously observed with initial exposure to electric fields (EF) of 30 or 60 kV/m. Here, we report the results of two experiments, each consisting of 6 week preexposure, exposure, and postexposure periods. We found no evidence of work stoppage with fields of 6 kV/m and 50 microT (0.5 G) or with 30 kV/m and 100 microT (1.0 G). In neither experiment was there evidence of an adverse effect of 60 Hz EMF exposure on MTS performance.

Initial studies on the effects of combined 60 Hz electric and magnetic field exposure on the immune system of nonhuman primates.

In a pilot immunology experiment, peripheral blood samples from six baboons (Papio cynocephalus) housed as a social group were collected during week 5 of preexposure, exposure, and postexposure periods that were each 6 weeks in duration. The subjects were exposed to vertical 6 kV/m and horizontal 50 microT (0.5 G) fields for 12 h per day. Lymphocytes collected during the exposure period displayed statistically significant (p < .05) reductions in CD3+ and CD4+ counts, interleukin 2 receptor expression, and proliferative response to pokeweed mitogen. A second experiment was conducted using samples from seven subjects exposed to 30 kV/m and 100 microT (1.0 G) and eight sham-exposed subjects. Statistically significant Period x Group interactions occurred for total white blood cell count and CD4+ to CD8+ ratio, but the pattern of results was not suggestive of an exposure-related effect. Although components of the nonhuman primate immune system appear to be affected by 60 Hz electric and magnetic field exposure in one of two experiments, additional experiments are required to evaluate this possibility.

Kinetics of a cellular response to interleukin 6.

The stimulation of the production of haptoglobin from the human hepatoma HepG2 was used as a model to examine the kinetics of a cellular response to interleukin 6 (IL-6). It was demonstrated that IL-6 upregulated the production of haptoglobin in a time-dependent manner: using a sensitive radioimmunoassay for haptoglobin, increases were already detectable 2 hr after IL-6 treatment began. The haptoglobin level continued to rise in a linear fashion to at least 16 hr. The stimulation of haptoglobin by IL-6 was abolished in the presence of 5 micrograms/ml actinomycin D and was thus likely pretranslational. It was further demonstrated that the upregulation of haptoglobin continued well after the removal of IL-6 from the system. An 8-hr "pulse" of IL-6 gave rise to haptoglobin secretion which was above control levels for the following 4 days. The effects of IL-6 in vivo can therefore be predicted to be long-lived despite its own short half-life, especially since the products of IL-6 stimulation, e.g., immunoglobulin and acute-phase proteins, are themselves long-lived in the circulation.