Endotypes of difficult-to-control asthma in inner-city African American children.

African Americans have higher rates of asthma prevalence, morbidity, and mortality in comparison with other racial groups. We sought to characterize endotypes of childhood asthma severity in African American patients in an inner-city pediatric asthma population. Baseline blood neutrophils, blood eosinophils, and 38 serum cytokine levels were measured in a sample of 235 asthmatic children (6-17 years) enrolled in the NIAID (National Institute of Allergy and Infectious Diseases)-sponsored Asthma Phenotypes in the Inner City (APIC) study (ICAC (Inner City Asthma Consortium)-19). Cytokines were quantified using a MILLIPLEX panel and analyzed on a Luminex analyzer. Patients were classified as Easy-to-Control or Difficult-to-Control based on the required dose of controller medications over one year of prospective management. A multivariate variable selection procedure was used to select cytokines associated with Difficult-to-Control versus Easy-to-Control asthma, adjusting for age, sex, blood eosinophils, and blood neutrophils. In inner-city African American children, 12 cytokines were significant predictors of Difficult-to-Control asthma (n = 235). CXCL-1, IL-5, IL-8, and IL-17A were positively associated with Difficult-to-Control asthma, while IL-4 and IL-13 were positively associated with Easy-to-Control asthma. Using likelihood ratio testing, it was observed that in addition to blood eosinophils and neutrophils, serum cytokines improved the fit of the model. In an inner-city pediatric population, serum cytokines significantly contributed to the definition of Difficult-to-Control asthma endotypes in African American children. Mixed responses characterized by TH2 (IL-5) and TH17-associated cytokines were associated with Difficult-to-Control asthma. Collectively, these data may contribute to risk stratification of Difficult-to-Control asthma in the African American population.

A strategy for reducing neonatal mortality at high altitude using oxygen conditioning.

Neonatal mortality increases with altitude. For example, in Peru the incidence of neonatal mortality in the highlands has been shown to be about double that at lower altitudes. An important factor is the low inspired PO2 of newborn babies. Typically, expectant mothers at high altitude will travel to low altitude to have their babies if possible, but often this is not feasible because of economic factors. The procedure described here raises the oxygen concentration in the air of rooms where neonates are being housed and, in effect, this means that both the mother and baby are at a much lower altitude. Oxygen conditioning is similar to air conditioning except that the oxygen concentration of the air is increased rather than the temperature being reduced. The procedure is now used at high altitude in many hotels, dormitories and telescope facilities, and has been shown to be feasible and effective.

Relationship between land use classification and grass shrimp Palaemonetes spp. population metrics in coastal watersheds.

Estuaries in the southeastern USA have experienced increased loading of contaminants from nonpoint source runoff as well as changes in habitat (e.g., loss of wetlands) due to urbanization. These changes may pose significant risks to estuarine fauna, including crustaceans. Several studies have shown relationships between land use classification and levels of stress in estuarine populations. The grass shrimp of the genus Palaemonetes is one of the dominant species found in estuarine tidal creeks, accounting for more than 50 % of all macropelagic fauna. Grass shrimp populations were sampled monthly for 3 years at six estuarine creeks on Kiawah Island, SC. Creek watersheds were estimated using National Aerial Photograph Program color infrared and low-altitude true color aerial photography combined with in situ differentially corrected global positioning system mapping of engineered features. Land classifications delineated included water, marsh, buildings, roads, and lawns. Pairwise comparisons for grass shrimp densities among sites showed significant differences on an annual and seasonal basis. Significant relationships (p < 0.05) between land class variables and grass shrimp density were identified both annually and seasonally. These findings suggest an influence of land use on Palaemonetes spp. populations.

Recent advances into understanding some aspects of the structure and function of mammalian and avian lungs.

Recent findings are reported about certain aspects of the structure and function of the mammalian and avian lungs that include (a) the architecture of the air capillaries (ACs) and the blood capillaries (BCs); (b) the pulmonary blood capillary circulatory dynamics; (c) the adaptive molecular, cellular, biochemical, compositional, and developmental characteristics of the surfactant system; (d) the mechanisms of the translocation of fine and ultrafine particles across the airway epithelial barrier; and (e) the particle-cell interactions in the pulmonary airways. In the lung of the Muscovy duck Cairina moschata, at least, the ACs are rotund structures that are interconnected by narrow cylindrical sections, while the BCs comprise segments that are almost as long as they are wide. In contrast to the mammalian pulmonary BCs, which are highly compliant, those of birds practically behave like rigid tubes. Diving pressure has been a very powerful directional selection force that has influenced phenotypic changes in surfactant composition and function in lungs of marine mammals. After nanosized particulates are deposited on the respiratory tract of healthy human subjects, some reach organs such as the brain with potentially serious health implications. Finally, in the mammalian lung, dendritic cells of the pulmonary airways are powerful agents in engulfing deposited particles, and in birds, macrophages and erythrocytes are ardent phagocytizing cellular agents. The morphology of the lung that allows it to perform different functions-including gas exchange, ventilation of the lung by being compliant, defense, and secretion of important pharmacological factors-is reflected in its "compromise design."

The human lung: did evolution get it wrong?

Some 300 million yrs ago, the ancestors of modern reptiles emerged from water and were committed to air breathing. They were exothermic and incapable of sustained levels of high physical activity. But from them evolved the two great classes of vertebrates with high levels of maximal oxygen consumption: the mammals and birds. A remarkable feature of these two divergent evolutionary lines is that, although the physiology of many organ systems shows many similarities, the lungs are radically different. A major difference is that the ventilation of the gas-exchanging tissue has a flow-through pattern in the bird but is reciprocating in the mammal. The result is that mammals have a reduced alveolar and arterial oxygen tension, a potential for uneven ventilation, and relatively large terminal air spaces. This in turn means that the pulmonary capillaries are poorly supported compared with the bird. The result is that the pulmonary capillaries in the bird have much thinner and more uniform walls, with more efficient gas exchange. Other advantages of the bird lung are that it utilises a more efficient cross-current pattern of gas-exchange, and the bird has separated the ventilatory and gas exchange functions. From a structure-function standpoint, the bird lung is superior.

Species-specific patterns of hydraulic lift in co-occurring adult trees and grasses in a sandhill community.

Plants can significantly affect ecosystem water balance by hydraulic redistribution (HR) from dry to wet soil layers via roots (also called hydraulic lift, HL, when the redistribution is from deep to shallow soil). However, the information on how co-occurring species in natural habitats differ in HL ability is insufficient. In a field study, we compared HL ability of four tree species (including three congeneric oak species) and two C4 bunch grass species that co-occur in subxeric habitats of fall-line sandhills in southeastern USA. Soil water potentials (psi(s)) were recorded hourly for 3 years both in large chambers that isolated roots for each species and outside the chambers. Outside of root chambers, soil drying occurred periodically in the top 25 cm and corresponded with lack of precipitation during the summer growing season. Soil moisture was continuously available at a 1 m depth. HL activity was observed in three of the tree species, with greater frequency for Pinus palustris than for Quercus laevis and Q. incana. The fourth tree species Q. margaretta did not exhibit HL activity even though it experienced a similar psi(s) gradient. For the C4 bunch grasses, Aristida stricta exhibited a small amount of HL activity, but Schizachyrium scoparium did not. The capacity for HL activity may be linked to the species ecological distribution. The four species that exhibited HL activity in this subxeric habitat are also dominant in adjacent xeric sandhill habitats, whereas the species that did not exhibit HL are scarcely found in the xeric areas. This is consistent with other studies that found greater fine root survival in dry soil for the four xeric species exhibiting HL activity. The differential ability of these species to redistribute water from the deep soil to the rapidly drying shallow soil likely has a strong effect on the water balance of sandhill plant communities, and is likely linked to their differential distribution across edaphic gradients.

The distribution of target registration error in rigid-body point-based registration.

Guidance systems designed for neurosurgery, hip surgery, spine surgery and for approaches to other anatomy that is relatively rigid can use rigid-body transformations to accomplish image registration. These systems often rely on point-based registration to determine the transformation and many such systems use attached fiducial markers to establish accurate fiducial points for the registration, the points being established by some fiducial localization process. Accuracy is important to these systems, as is knowledge of the level of that accuracy. An advantage of marker-based systems, particularly those in which the markers are bone-implanted, is that registration error depends only on the fiducial localization and is, thus, to a large extent independent of the particular object being registered. Thus, it should be possible to predict the clinical accuracy of marker-based systems on the basis of experimental measurements made with phantoms or previous patients. For most registration tasks, the most important error measure is target registration error (TRE), which is the distance after registration between corresponding points not used in calculating the registration transform. In this paper, we derive an approximation to the distribution of TRE; this is an extension of previous work that gave the expected squared value of TRE. We show the distribution of the squared magnitude of TRE and that of the component of TRE in an arbitrary direction. Using numerical simulations, we show that our theoretical results are a close match to the simulated ones.

Sleep, performance, circadian rhythms, and light-dark cycles during two space shuttle flights.

Sleep, circadian rhythm, and neurobehavioral performance measures were obtained in five astronauts before, during, and after 16-day or 10-day space missions. In space, scheduled rest-activity cycles were 20-35 min shorter than 24 h. Light-dark cycles were highly variable on the flight deck, and daytime illuminances in other compartments of the spacecraft were very low (5.0-79.4 lx). In space, the amplitude of the body temperature rhythm was reduced and the circadian rhythm of urinary cortisol appeared misaligned relative to the imposed non-24-h sleep-wake schedule. Neurobehavioral performance decrements were observed. Sleep duration, assessed by questionnaires and actigraphy, was only approximately 6.5 h/day. Subjective sleep quality diminished. Polysomnography revealed more wakefulness and less slow-wave sleep during the final third of sleep episodes. Administration of melatonin (0.3 mg) on alternate nights did not improve sleep. After return to earth, rapid eye movement (REM) sleep was markedly increased. Crewmembers on these flights experienced circadian rhythm disturbances, sleep loss, decrements in neurobehavioral performance, and postflight changes in REM sleep.

Historical aspects of the early Soviet/Russian manned space program.

Human spaceflight was one of the great physiological and engineering triumphs of the 20th century. Although the history of the United States manned space program is well known, the Soviet program was shrouded in secrecy until recently. Konstantin Edvardovich Tsiolkovsky (1857-1935) was an extraordinary Russian visionary who made remarkable predictions about space travel in the late 19th century. Sergei Pavlovich Korolev (1907-1966) was the brilliant "Chief Designer" who was responsible for many of the Soviet firsts, including the first artificial satellite and the first human being in space. The dramatic flight of Sputnik 1 was followed within a month by the launch of the dog Laika, the first living creature in space. Remarkably, the engineering work for this payload was all done in less than 4 wk. Korolev's greatest triumph was the flight of Yuri Alekseyevich Gagarin (1934-1968) on April 12, 1961. Another extraordinary feat was the first extravehicular activity by Aleksei Arkhipovich Leonov (1934-) using a flexible airlock that emphasized the entrepreneurial attitude of the Soviet engineers. By the mid-1960s, the Soviet program was overtaken by the United States program and attempts to launch a manned mission to the Moon failed. However, the early Soviet manned space program has a preeminent place in the history of space physiology.

Microgravity reduces sleep-disordered breathing in humans.

To understand the factors that alter sleep quality in space, we studied the effect of spaceflight on sleep-disordered breathing. We analyzed 77 8-h, full polysomnographic recordings (PSGs) from five healthy subjects before spaceflight, on four occasions per subject during either a 16- or 9-d space shuttle mission and shortly after return to earth. Microgravity was associated with a 55% reduction in the apnea-hypopnea index (AHI), which decreased from a preflight value of 8.3 +/- 1.6 to 3.4 +/- 0.8 events/h inflight. This reduction in AHI was accompanied by a virtual elimination of snoring, which fell from 16.5 +/- 3.0% of total sleep time preflight to 0.7 +/- 0.5% inflight. Electroencephalogram (EEG) arousals also decreased in microgravity (by 19%), and this decrease was almost entirely a consequence of the reduction in respiratory-related arousals, which fell from 5.5 +/- 1.2 arousals/h preflight to 1.8 +/- 0.6 inflight. Postflight there was a return to near or slightly above preflight levels in these variables. We conclude that sleep quality during spaceflight is not degraded by sleep-disordered breathing. This is the first direct demonstration that gravity plays a dominant role in the generation of apneas, hypopneas, and snoring in healthy subjects.

Fiducial point placement and the accuracy of point-based, rigid body registration.

OBJECTIVE: To demonstrate that the shape of the configuration of fiducial points is an important factor governing target registration error (TRE) in point-based, rigid registration. METHODS: We consider two clinical situations: cranial neurosurgery and pedicle screw placement. For cranial neurosurgery, we apply theoretical results concerning TRE prediction, which we have previously derived and validated, to three hypothetical fiducial marker configurations. We illustrate the profile of expected TRE for each configuration. For pedicle screw placement, we apply the same theory to a common anatomic landmark configuration (tips of spinous and transverse processes) used for pedicle screw placement, and we estimate the error rate expected in placement of the screw. RESULTS: In the cranial neurosurgery example, we demonstrate that relatively small values of TRE may be achieved by using widely spread fiducial markers and/or placing the centroid of the markers near the target. We also demonstrate that near-collinear marker configurations far from the target may result in large TRE values. In the pedicle screw placement example, we demonstrate that the screw must be approximately 4 mm narrower than the pedicle in which it is implanted to minimize the chance of pedicle violation during placement. CONCLUSION: The placement of fiducial points is an important factor in minimizing the error rate for point-based, rigid registration. By using as many points as possible, avoiding near-collinear configurations, and ensuring that the centroid of the fiducial points is as near as possible to the target, TREs can be minimized.

Snorkel breathing in the elephant explains the unique anatomy of its pleura.

It has been known for over 300 years that the anatomy of the elephant lung is unique among mammals in that the pleural cavity is obliterated by connective tissue. However no satisfactory explanation has been advanced. Recent studies suggest that the elephant has an aquatic ancestry and the trunk may have developed for snorkeling. In addition, the modern day elephant is the only mammal that can remain submerged far below the surface of the water while snorkeling. The resulting differences of pressures within the thorax mean that the small blood vessels of the pleura are in great danger of rupturing or causing severe edema. The same distribution of pressures occurs when the animal raises water inside its trunk prior to drinking although in this case the pressure differences are relatively short-lived. Evolution has provided a remarkable solution to this problem by replacing the normally delicate parietal and visceral pleurae by dense connective tissue, and separating the two pleurae by loose connective tissue to allow some sliding movement.

Safe upper limits for oxygen enrichment of room air at high altitude.

Oxygen enrichment of room air at high altitude has been shown to improve mental performance, sleep quality, and work capacity. Until now, the usual strategy has been to use an oxygen concentration that reduces the equivalent altitude to about 3,000 m, where the equivalent altitude is that which gives the same inspired PO2 during air breathing. However, standards adopted by the National Fire Protection Association allow considerably higher oxygen concentrations without introducing a fire hazard. For example, by raising the oxygen concentration to 31.5% at an altitude of 5,000 m, the equivalent altitude can be safely reduced to less than 2,000 m. At the extreme altitude of 8,000 m, the equivalent altitude can be reduced to less than 4,000 m without increasing the fire hazard. These increased levels of oxygen enrichment are feasible in practice using oxygen concentrators. They may be useful if lowlanders need to ascend rapidly and stay at high altitude, or for treating people with high altitude illnesses.

Effect of high transcapillary pressures on capillary ultrastructure and permeability coefficients in dog lung.

To determine the correlation between ultrastructural and physiological changes in blood-gas barrier function in lungs transiently exposed to very high vascular pressures, we increased capillary transmural pressure (Ptm) of 6 canine isolated perfused left lower lung lobe preparations (high-pressure group) to 80.3 Torr for 3.8 min and then determined the capillary filtration (K(fc)) and osmotic reflection (sigma(d)) coefficients at a Ptm of 19.1 Torr in the ventilated lung lobes. This was followed by perfusion fixation of the lobes at a Ptm of 20.5 Torr for ultrastructural analysis. These data were compared with those obtained in six lobes in which Ptm was not transiently elevated before K(fc), sigma(d), and ultrastructural evaluation. K(fc) was higher [0.249 +/- 0.042 (SE) vs. 0.054 +/- 0.009 g. min(-1). Torr(-1). 100 g(-1); P < 0.01] and sigma(d) was lower (0.52 +/- 0.07 vs. 0.85 +/- 0.08; P < 0.01) in the high-pressure group. In contrast, although endothelial and epithelial breaks were occasionally observed in some experiments, their incidence was not increased in the high-pressure group. These data suggest that the increased transvascular water and protein flux occurred through pathways of a size not resolvable by electron microscopy after vascular perfusion-fixation at a Ptm of 20.5 Torr.

Nocturnal oxygen enrichment of room air at 3800 meter altitude improves sleep architecture.

Sleep is known to be impaired at high altitude, and this may be a factor contributing to reduced work efficiency, general malaise, and the development of acute mountain sickness (AMS). Nocturnal room oxygen enrichment at 3800 m has been shown to reduce the time spent in periodic breathing and the number of apneas, to improve subjective quality of sleep, and to reduce the AMS score. The present study was designed to evaluate the effect of oxygen enrichment to 24% at 3800 m (lowering the equivalent altitude to 2800 m) on sleep architecture. Full polysomnography and actigraphy were performed on 12 subjects who ascended in 1 day to 3800 m and slept in a specially constructed room that allowed oxygen enrichment or ambient air conditions in a randomized, crossover, double-blind study. The results showed that subjects spent a significantly greater percentage of time in deep sleep (stages III and IV combined, or slow wave sleep) with oxygen enrichment versus ambient air (17.2 +/- 10.0% and 13.9 +/- 6.7%, respectively; p < 0.05 in paired analysis). No differences between treatments were seen with subjective assessments of sleep quality or with subject's assessment of the extent to which they suffered from AMS. This study provides further objective evidence of improved sleep as a result of oxygen enrichment at 3800 m and suggests that alleviating hypoxia may improve sleep quality.