"We are the world (of anaesthesia)": reflections on (and lessons learned at) the World Congress of Anaesthesiologists 2004.
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Membrane receptors and proteins involved in signal transduction display numerous binding domains and operate as molecular scaffolds generating a variety of parallel reactions and protein complexes. The resulting combinatorial explosion of the number of feasible chemical species and, hence, different states of a network greatly impedes mechanistic modeling of signaling systems. Here we present novel general principles and identify kinetic requirements that allow us to replace a mechanistic picture of all possible micro-states and transitions by a macro-description of states of separate binding sites of network proteins. This domain-oriented approach dramatically reduces computational models of cellular signaling networks by dissecting mechanistic trajectories into the dynamics of macro- and meso-variables. We specify the conditions when the temporal dynamics of micro-states can be exactly or approximately expressed in terms of the product of the relative concentrations of separate domains. We prove that our macro-modeling approach equally applies to signaling systems with low population levels, analyzed by stochastic rather than deterministic equations. Thus, our results greatly facilitate quantitative analysis and computational modeling of multi-protein signaling networks.
New experimental evidence shows that policing behaviour by dominant monkeys stabilizes and integrates macaque societies.
OBJECTIVE: To describe and compare the duration of lochia in seven groups of women; to investigate the occurrence of a possible "end-of-puerperium" bleeding episode; and to determine the frequency of bleeding episodes before postpartum day 56, which applies to the practice of the lactational amenorrhea method of contraception. DESIGN: Prospective longitudinal study with fortnightly follow-up, beginning within 7 days of delivery. SETTING: Five developing and two developed countries. PATIENT(S): Four thousand one hundred eighteen breast-feeding women. INTERVENTION(S): Postpartum lochia and all days of bleeding per vaginam were recorded. MAIN OUTCOME MEASURE(S): Duration of lochia, frequency of an end-of-puerperium bleeding episode, and frequency of postlochia bleeding episodes within 56 days of delivery. RESULT(S): The median duration of lochia was 27 days; it varied significantly among the centers (range, 22-34 days). In 11% of the women, lochia lasted >40 days. An end-of-puerperium bleeding episode around the 40th day postpartum was reported by 20.3% of the women. Bleeding within 56 days of delivery (separated from lochia by at least 14 days) occurred in 11.3% of the women and usually was followed by a confirmatory bleeding episode 21-70 days later. CONCLUSION(S): The duration of lochia varied significantly among the study populations, and long durations were not unusual. The significance of the end-of-puerperium bleeding episode is unknown. Most users of the lactational amenorrhea method will not experience a postlochia bleeding episode before postpartum day 56.
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Patterns of terminals labeled after WGA-HRP injections in the superior colliculus (SC) in squirrel monkeys and macaque monkeys, and after DiI application in marmosets, were related to the architecture of the pulvinar and dorsal lateral geniculate nucleus (LGN). In all studied species, the SC projects densely to two architectonic subdivisions of the inferior pulvinar, the posterior inferior pulvinar nucleus (PIp) and central medial inferior pulvinar nucleus (PIcM). These projection zones expressed substance P. Thus, sections processed for substance P reveal SC termination zones in the inferior pulvinar. The medial subdivision of the inferior pulvinar, PIm, which is known to project to visual area MT, does not receive a significant collicular input. Injections in MT of a squirrel monkey revealed no overlap between SC terminals and neurons projecting to area MT. Thus, PIm is not the significant relay station of visual input from the SC to MT. The SC also sends an input to the LGN, however, this projection is sparser than the input directed to pulvinar.
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