Psychiatry and the 'new genetics': hunting for genes for behaviour and drug response.
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We developed a high-throughput screening system that allows identification of genes prolonging life span in the budding yeast Saccharomyces cerevisiae. The method is based on isolating yeast mother cells with an extended number of cell divisions as indicated by the increased number of bud scars on their surface. Fluorescently labeled wheat germ agglutinin (WGA) was used for specific staining of bud scars. Screening of a human HepG2 cDNA expression library in yeast resulted in the isolation of several yeast transformants with a potentially prolonged life span. The budding yeast S. cerevisiae, one of the favorite models used to study aging, has been studied extensively for the better understanding of the mechanisms of human aging. Because human disease genes often have yeast counterparts, they can be studied efficiently in this organism. One interesting example is the WRN gene, the human DNA helicase, which participates in the DNA repair pathway. The mutation of the WRN gene causes Werner syndrome showing premature-aging phenotype. Budding yeast contains WRN homologue, SGS1, and its mutation results in shortening yeast life span. The knowledge gained from the studies of budding yeast will benefit studies in humans for better understanding of aging and aging-related disease.
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OBJECTIVE: To examine the relation between analgesic use at baseline and the subsequent risk of chronic pain (> or =15 days/month) and the risk of analgesic overuse. METHODS: In total, 32, 067 adults reported the use of analgesics in 1984 to 1986 and at follow-up 11 years later (1995 to 1997). The risk ratios (RR) of chronic pain and RR of analgesic overuse in the different diagnostic groups (i.e., migraine, nonmigrainous headache, neck pain, and low-back pain) were estimated in relation to analgesic consumption at baseline. RESULTS: Individuals who reported use of analgesics daily or weekly at baseline showed significant increased risk for having chronic pain at follow-up. The risk was most evident for chronic migraine (RR = 13.3, 95% CI: 9.3 to 19.1), intermediate for chronic nonmigrainous headaches (RR = 6.2, 95% CI: 5.0 to 7.7), and lowest for chronic neck (RR = 2.4, 95% CI: 2.0 to 2.8) or chronic low-back (RR = 2.3, 95% CI: 2.0 to 2.8) pain. Among subjects with chronic pain associated with analgesic overuse, the RR was 37.6 (95% CI: 21.3 to 66.4) for chronic migraine, 14.4 (95% CI: 10.4 to 19.9) for chronic nonmigrainous headaches, 7.1 for chronic neck pain (95% CI: 5.5 to 9.2), and 6.4 for chronic low-back pain (95% CI: 4.9 to 8.4). The RR for chronic headache (migraine and nonmigrainous headache combined) associated with analgesic overuse was 19.6 (95% CI: 14.8 to 25.9) compared with 3.1 (95% CI: 2.4 to 4.2) for those without overuse. CONCLUSION: Overuse of analgesics strongly predicts chronic pain and chronic pain associated with analgesic overuse 11 years later, especially among those with chronic migraine.
OBJECTIVES: To examine the association between the use of analgesics and primary headache disorders (i.e., migraine and tension-type headache) among adolescents in relation to age, gender, and headache frequency. METHODS: This cross-sectional, population-based study was conducted in Norway from 1995 to 1997. The total study population consisted of 5,471 adolescents, 13 to 18 years of age, who were interviewed about their headache complaints and completed a comprehensive questionnaire including use of analgesics. RESULTS: The prevalence of daily headache associated with analgesic use was 0.5%, with a higher rate for girls (0.8%) than for boys (0.2%). There was a significant association for both genders between analgesic use and headache, although most pronounced for migraine. There was a significant linear relationship between analgesic use and headache frequency. Analgesic use was more common among girls than boys and increased with age both for those with and those without headache. CONCLUSIONS: The use of analgesics is common among adolescents with headache, especially among girls. Although this study did not directly evaluate for medication-overuse headache, the trend of frequent analgesic use suggests this possibility. Parents and physicians should increase their awareness of potential analgesic overuse, especially among adolescents with frequent headache.
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To rationalize and restrict health care spending, policy, makers in many jurisdictions have withdrawn insurance or funding for selected health care technologies. Numerous analytic frameworks and applied exercises have emerged to guide decisions about "which" services to cut. But in their focus on choice-making processes, these efforts have paid little attention to the problem of defining and dividing the set of technologies to choose among. If technology assessment refers to methods for weighing services for their relative value, the term technology assembly might be used to refer to methods for framing the technological trade-offs to enroll in such contests. This article examines technology assemblies found in several types of theoretical and applied rationing exercises (including Oregon's Medicaid rationing process, economic evaluation literature, citizen "values" surveys, and Canadian provincial deinsurance policies). Based on this review, some key conceptual conventions and problems in technology assembly can be identified. The boundaries between health technologies are fuzzy, interlocked, layered, and continuously moving. Consequently, the defining features of technological trade-offs are inevitably socially constructed and negotiated. Trade-offs can be arranged along numerous dimensions, and the divisions typically correspond to broader political, administrative, and ethical dilemmas in health policy. Examples include equity among demographic classes, concepts of need, legitimacy of therapeutic goals, and so forth. Insights into the process of constructing technological trade-offs may help policy makers better question what technologies they are looking at and why, before moving on to the task of determining which ones to cover.
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Archer fish can shoot down insect prey with a sharp jet of water. Fish usually fire from positions that are not directly below their target so that a dislodged insect falls ballistically with a horizontal velocity component. Only 100 ms after the insect is on its path both the shooter and other school members can initiate a rapid turn and then head straight in the direction of the later point of impact of their falling prey. The quick turn and subsequent take-off are performed ;open-loop', based on the initial values of the falling insect's motion. We report here that archer fish can not only take off in the direction of the later point of impact but also predict its distance. Distance information allows the fish to adjust their take-off speed so that they would arrive within a narrow time slot slightly (about 50 ms) after their prey's impact, despite large differences in the size of the aligning turn and in the distance to be covered. Selecting a constant speed program with matched speed and catching the insect on the move minimizes frictional losses. The initial speed of starting fish is slightly but systematically too slow and is increased later so that the fish arrive 20 ms earlier than expected and often make the catch on a higher than take-off speed. The variability of later speed changes suggests a systematic ;error' in the take-off, as if the fish underestimated distance. However, this apparent deficiency seems well adapted to the fish catching their prey at a high speed: if later the fish had no possibility to correct an initial error then it is better to start slightly too slow in order to minimize the risk of overshooting the point of catch.
We examined aspects of hearing in the red bat (Lasiurus borealis) related to its use of biosonar. Evoked potential audiograms, obtained from volume-conducted auditory brainstem responses, were obtained in two bats, and the sound pressure transformation of the pinna was measured in three specimens. Field-recorded echolocation signals were analysed for comparison. The fundamental sonar search calls sweep from 45 to 30 kHz (peak energy at 35 kHz), approach-phase calls sweep from 65 to 35 kHz (peak 40 kHz) and terminal calls sweep from 70 to 30 kHz (peak 45 kHz). The most sensitive region of the audiogram extended from 10 kHz to 45-55 kHz, with maximum sensitivity as low as 20 dB SPL occurring between 25 and 30 kHz. A relative threshold minimum occurred between 40 and 50 kHz. With increasing frequency, the acoustic axis of the pinna moves upwards and medially. The sound pressure transformation was noteworthy near 40-45 kHz; the acoustic axis was closest to the midline, the -3 dB acceptance angles showed local minima, and the pinna gain and interaural intensity difference were maximal. These results are related to the known echolocation and foraging behavior of this species and match the spectral components of approach- and final-phase calls. We conclude that co-evolution with hearing prey has put a higher selective pressure on optimizing localization and tracking of prey than on improving detection performance.
Previous experimental studies have shown that neotropical wandering spiders (Cupiennius salei) inject more venom when attacking larger crickets. It has been postulated that this is a consequence of predator-prey interactions during envenomation, which increase in intensity with the size of a given prey species. The present study was designed to test this hypothesis using anaesthetized crickets of different sizes that were moved artificially. Cupiennius salei was found (1) to inject more venom the greater the intensity of the struggling movement of the crickets (prey size kept constant); (2) to inject more venom the longer the duration of the struggling movement of the crickets (prey size and intensity of movement kept constant); and (3) to inject equal amounts into crickets of different size (duration and intensity of movement kept constant). These results indicate that C. salei alters the amount of venom it releases according to the size and motility of its prey. Venom expenditure depends mainly on the extent of the interactions with the prey during the envenomation process, whereas prey size is of minor significance. The regulation of venom injection in concert with behavioural adaptations in response to various types of prey minimizes the energetic cost of venom production, thus increasing the profitability of a given prey item.
We have demonstrated in behavioural experiments that success in capturing prey from surfaces in 'trawling Myotis' (Leuconoë-type) depends on the acoustic properties of the surface on which the prey is presented. Two types of surface structure were ensonified with artificial bat signals to probe their acoustic characteristics. We have shown that perception of prey by echolocation is easier if the prey is presented on a smooth surface (such as calm water) than if it is presented on a structured surface (such as vegetation or the ground). This is because the smooth surface reflects a much lower level of clutter echoes than the structured one if ensonified at an angle typical for bats foraging low over water. The ensonification experiments revealed that the sound pressure level of the echo was even higher for mealworms on a smooth surface than for mealworms suspended in air. This might be because waves travelling via the surface also contribute to the echo (e.g. reflection from the surface to the mealworm, back to the surface and then to the receiver). From the behavioural experiments, we conclude that 'trawling Myotis' take isolated objects on smooth (water) surfaces for prey. Those objects reflect isolated, stationary acoustic glints back to the echolocating bats. Conversely, 'trawling Myotis' will not recognise prey if prey echoes are embedded in numerous clutter echoes. We have demonstrated marked similarities between the three European 'trawling Myotis' species M. dasycneme, M. daubentonii and M. capaccinii in echolocation behaviour, search image, foraging strategy and prey perception. We propose that a combination of prey abundance and acoustic advantages could have led to repeated and convergent evolution of 'trawling' bats in different parts of the world.