Lunar formation. Dating the Moon-forming impact event with asteroidal meteorites.

The inner solar system's biggest and most recent known collision was the Moon-forming giant impact between a large protoplanet and proto-Earth. Not only did it create a disk near Earth that formed the Moon, it also ejected several percent of an Earth mass out of the Earth-Moon system. Here, we argue that numerous kilometer-sized ejecta fragments from that event struck main-belt asteroids at velocities exceeding 10 kilometers per second, enough to heat and degas target rock. Such impacts produce ~1000 times more highly heated material by volume than do typical main belt collisions at ~5 kilometers per second. By modeling their temporal evolution, and fitting the results to ancient impact heating signatures in stony meteorites, we infer that the Moon formed ~4.47 billion years ago, which is in agreement with previous estimates.

Origin of the orbital architecture of the giant planets of the Solar System.

Planetary formation theories suggest that the giant planets formed on circular and coplanar orbits. The eccentricities of Jupiter, Saturn and Uranus, however, reach values of 6 per cent, 9 per cent and 8 per cent, respectively. In addition, the inclinations of the orbital planes of Saturn, Uranus and Neptune take maximum values of approximately 2 degrees with respect to the mean orbital plane of Jupiter. Existing models for the excitation of the eccentricity of extrasolar giant planets have not been successfully applied to the Solar System. Here we show that a planetary system with initial quasi-circular, coplanar orbits would have evolved to the current orbital configuration, provided that Jupiter and Saturn crossed their 1:2 orbital resonance. We show that this resonance crossing could have occurred as the giant planets migrated owing to their interaction with a disk of planetesimals. Our model reproduces all the important characteristics of the giant planets' orbits, namely their final semimajor axes, eccentricities and mutual inclinations.

Chaotic capture of Jupiter's Trojan asteroids in the early Solar System.

Jupiter's Trojans are asteroids that follow essentially the same orbit as Jupiter, but lead or trail the planet by an angular distance of approximately 60 degrees (co-orbital motion). They are hypothesized to be planetesimals that formed near Jupiter and were captured onto their current orbits while Jupiter was growing, possibly with the help of gas drag and/or collisions. This idea, however, cannot explain some basic properties of the Trojan population, in particular its broad orbital inclination distribution, which ranges up to approximately 40 degrees (ref. 8). Here we show that the Trojans could have formed in more distant regions and been subsequently captured into co-orbital motion with Jupiter during the time when the giant planets migrated by removing neighbouring planetesimals. The capture was possible during a short period of time, just after Jupiter and Saturn crossed their mutual 1:2 resonance, when the dynamics of the Trojan region were completely chaotic. Our simulations of this process satisfactorily reproduce the orbital distribution of the Trojans and their total mass.

Origin of the cataclysmic Late Heavy Bombardment period of the terrestrial planets.

The petrology record on the Moon suggests that a cataclysmic spike in the cratering rate occurred approximately 700 million years after the planets formed; this event is known as the Late Heavy Bombardment (LHB). Planetary formation theories cannot naturally account for an intense period of planetesimal bombardment so late in Solar System history. Several models have been proposed to explain a late impact spike, but none of them has been set within a self-consistent framework of Solar System evolution. Here we propose that the LHB was triggered by the rapid migration of the giant planets, which occurred after a long quiescent period. During this burst of migration, the planetesimal disk outside the orbits of the planets was destabilized, causing a sudden massive delivery of planetesimals to the inner Solar System. The asteroid belt was also strongly perturbed, with these objects supplying a significant fraction of the LHB impactors in accordance with recent geochemical evidence. Our model not only naturally explains the LHB, but also reproduces the observational constraints of the outer Solar System.

The formation of Uranus and Neptune in the Jupiter-Saturn region of the Solar System.

Planets are believed to have formed through the accumulation of a large number of small bodies. In the case of the gas-giant planets Jupiter and Saturn, they accreted a significant amount of gas directly from the protosolar nebula after accumulating solid cores of about 5-15 Earth masses. Such models, however, have been unable to produce the smaller ice giants Uranus and Neptune at their present locations, because in that region of the Solar System the small planetary bodies will have been more widely spaced, and less tightly bound gravitationally to the Sun. When applied to the current Jupiter-Saturn zone, a recent theory predicts that, in addition to the solid cores of Jupiter and Saturn, two or three other solid bodies of comparable mass are likely to have formed. Here we report the results of model calculations that demonstrate that such cores will have been gravitationally scattered outwards as Jupiter, and perhaps Saturn, accreted nebular gas. The orbits of these cores then evolve into orbits that resemble those of Uranus and Neptune, as a result of gravitational interactions with the small bodies in the outer disk of the protosolar nebula.

Pseudomonas aeruginosa and Burkholderia cepacia infection in cystic fibrosis patients treated in Toronto and Copenhagen.

Differences in the course of pulmonary disease in cystic fibrosis (CF) may be altered by different treatment strategies in different CF centers. The Copenhagen clinic uses scheduled, regular and very aggressive treatment of lung infection. The Toronto clinic treats pulmonary infection with oral, inhaled, or intravenous antibiotics, and has emphasized aggressive nutritional therapy. This study compared the clinical status of CF patients treated in the two centers (Toronto, Canada, n=302, and Copenhagen, Denmark, n=214) using a cross-sectional design in terms of Pseudomonas aeruginosa (PA) and Burkholderia cepacia (BC) lung infections, pulmonary function, and levels of PA and BC precipitating antibodies (precipitins). Median ages were similar, but the age distribution was significantly different, with a higher proportion of patients under 10 and > or = 25 years in Toronto, and higher proportion of patients 11-24 years of age in Copenhagen. A higher number of female patients was observed in Copenhagen than in Toronto. Seventy-nine percent of Copenhagen patients, and 52% of Toronto patients were deltaF508 homozygous. Of all the patients, 20.1% of Copenhagen patients and 38% of Toronto patients were deltaF508 heterozygous. Ten percent of Toronto patients had two uncommon mutations. Pulmonary function and nutritional status in both groups were similar despite varying treatment strategies. The prevalence of PA was lower in Danish children and higher in Danish adults than in Canada. These differences are probably due to cohort isolation, which was introduced in Copenhagen in 1981. The prevalence of BC was higher in Toronto than in Copenhagen patients at all ages. In both centers, the number of PA and BC precipitins increased with age in patients chronically infected with PA and BC, respectively, and the number of both PA and BC precipitins rose with declining lung function. This study suggests that the clinic populations had similar pulmonary and nutritional statuses despite differing clinic antibiotic treatment strategies. Microbial colonization seemed to differ, at least in part, because of differences in cohort isolation strategies. Early, aggressive anti-pseudomonal chemotherapy may have reduced pseudomonal colonization among younger patients in Copenhagen. Future studies will be required to assess the impact of this on this cohort's outcome.

Cratering rates on the Galilean satellites.

We exploit recent theoretical advances toward the origin and orbital evolution of comets and asteroids to obtain revised estimates for cratering rates in the jovian system. We find that most, probably more than 90%, of the craters on the Galilean satellites are caused by the impact of Jupiter-family comets (JFCs). These are comets with short periods, in generally low-inclination orbits, whose dynamics are dominated by Jupiter. Nearly isotropic comets (long period and Halley-type) contribute at the 1-10% level. Trojan asteroids might also be important at the 1-10% level; if they are important, they would be especially important for smaller craters. Main belt asteroids are currently unimportant, as each 20-km crater made on Ganymede implies the disruption of a 200-km diameter parental asteroid, a destruction rate far beyond the resources of today's asteroid belt. Twenty-kilometer diameter craters are made by kilometer-size impactors; such events occur on a Galilean satellite about once in a million years. The paucity of 20-km craters on Europa indicates that its surface is of order 10 Ma. Lightly cratered surfaces on Ganymede are nominally of order 0.5-1.0 Ga. The uncertainty in these estimates is about a factor of five. Callisto is old, probably more than 4 Ga. It is too heavily cratered to be accounted for by the current flux of JFCs. The lack of pronounced apex-antapex asymmetries on Ganymede may be compatible with crater equilibrium, but it is more easily understood as evidence for nonsynchronous rotation of an icy carapace.

A disk of scattered icy objects and the origin of Jupiter-family comets.

Orbital integrations carried out for 4 billion years produced a disk of scattered objects beyond the orbit of Neptune. Objects in this disk can be distinguished from Kuiper belt objects by a greater range of eccentricities and inclinations. This disk was formed in the simulations by encounters with Neptune during the early evolution of the outer solar system. After particles first encountered Neptune, the simulations show that about 1 percent of the particles survive in this disk for the age of the solar system. A disk currently containing as few as approximately 6 x 10(8) objects could supply all of the observed Jupiter-family comets. Two recently discovered objects, 1996 RQ20 and 1996 TL66, have orbital elements similar to those predicted for objects in this disk, suggesting that they are thus far the only members of this disk to be identified.

Does ketotifen have a steroid-sparing effect in childhood asthma?

In view of the possible systemic side-effects of inhaled corticosteroids (ICS), a study was performed to determine whether ketotifen (versus placebo) can replace or allow a reduction in the dose of ICS required for the maintenance treatment of childhood asthma. Sixty six children (aged 6-13 yrs) with asthma (confirmed by methacholine challenge), who were maintained on ICS, at a dose of < or = 1 mg.day-1, were selected, and 52 subjects completed the trial. Children on long-term oral steroids or cromoglycate were excluded. After a 4 week baseline period, the children were randomized to receive ketotifen, 2 mg.day-1, or placebo for 32 Weeks. Between weeks 13-20 of the study, the daily dose of steroid was tapered by 25% every second week to the minimum dose tolerated by the patients. For the remainder of the study (Weeks 21-32) the patients continued on this dose (if tolerated). Beta 2-agonists were allowed, as necessary, for symptom relief. During the baseline period, the mean daily ICS dosage was 432 micrograms in the ketotifen group versus 408 micrograms in the placebo group (NS). Among the-patients who completed the study, the average ICS dosage during the final phase of the study (Weeks 21-32) was only 18% of baseline in the ketotifen group versus 35% in the placebo group (NS). Lung function, diurnal variability in peak flow rates and methacholine sensitivity (provocative concentration producing a 20% fall in forced expiratory volume in one second (PC20)) remained unchanged in both groups throughout the study. During the last 12 weeks of the study, the ketotifen-treated patients were symptomatically better controlled. In the present study, ketotifen did not have a greater steroid-sparing effect than placebo.

Longitudinal analysis of pulmonary function decline in patients with cystic fibrosis.

BACKGROUND: Chronic progressive lung disease is the most prominent cause of morbidity and death in patients with cystic fibrosis (CF), but severity of lung disease and rate of lung function decline are widely variable. Accurate estimates of decline have been difficult to define and compare because the timing of measurements and duration of follow-up differ in various patient groups. PATIENTS: Three hundred sixty-six patients with CF, born from 1960 to 1974, were selected from a CF database birth cohort if they had two or more measurements of pulmonary function, at least one of which was performed before the age of 10 years. METHODS: Mixed model regression analysis provided estimates of the average rate of decline of spirometry measurements in subgroups on the basis of survival age, sex, pancreatic status, and genotype. RESULTS: Patients who died before the age of 15 years had significantly poorer pulmonary function when first tested and a more rapid decline in pulmonary function thereafter than patients who survived beyond the age of 15 years. In the latter, functional levels at the age of 5 years were normal, but average rates of decline were significantly related to survival age. Female patients had significantly steeper decline than male patients, and those with pancreatic insufficiency had much steeper decline than those with pancreatic sufficiency. In the subset of 197 who survived to 1990 and were subsequently genotyped, rate of decline was greater in those homozygous for the delta F508 mutation, compared with those who were heterozygous for delta F508 or those, who had two other mutations. DISCUSSION: All but the most severely affected patients, who died before age 15, appear to have had normal pulmonary function when first tested in early childhood. Pancreatic sufficiency, male gender, and some non-delta F508 mutations are associated with a slower rate of pulmonary function decline. Mixed model analysis is a valuable tool for describing and comparing pulmonary function decline in groups of patients with CF.

The role of corticosteroids in respiratory diseases of children.

Glucocorticosteroids are potent anti-inflammatory agents and have an important role in a variety of respiratory diseases. Although their exact mode of action is unknown, it is thought that they exert their effects by binding to cytoplasmic glucocorticoid receptors. In certain conditions, such as asthma, the value of steroids cannot be questioned, and inhaled steroids have revolutionized management. In other situations, such as interstitial lung disease, the true role of steroids is still to be defined. In the management of diseases such as tuberculosis, the use of steroids is solely based on anecdotal experience.

Dietary intakes of young children with cystic fibrosis: is there a difference?

Caloric intakes of preadolescent and adolescent girls and boys with cystic fibrosis (CF) were compared in order to evaluate the possibility that poor caloric intake contributes to poor nutritional status and high mortality among girls with CF. Fifty-six CF patients (26 girls and 30 boys), 10-15 years old, completed a 3-day food record, answered a short questionnaire, and underwent anthropometric and pulmonary function assessment. The mean ages of the girls and boys were similar, but the height and weight percentiles of the girls were lower than those of the boys (p = 0.02). Mean caloric intakes were no different (116% and 112% of the recommended nutrient intake in the girls and boys, respectively). Nutritional status, as determined by weight as a percentage of ideal weight for height, mean triceps skinfold thickness, and midarm muscle circumference, was normal and similar in both sexes. Most girls and boys with CF in this study had an appropriate perception of their body weight. Pulmonary function tests suggested mild lung disease with no significant difference between girls and boys (forced expiratory volume in 1 s of 82.2% and 79.8% of predicted values, respectively). The similar nutritional and pulmonary status of the girls and boys with CF in this age group is in contrast to previous reports. This finding may be the result of our policy, introduced > 15 years ago, of expecting normal growth, by paying close attention to enzyme therapy and encouraging high energy intake from the time of diagnosis. It remains to be seen whether boys and girls continue to maintain similar nutritional and pulmonary status at a later age and whether both sexes experience a similar mortality rate as they age.

Correlation of sweat chloride concentration with classes of the cystic fibrosis transmembrane conductance regulator gene mutations.

OBJECTIVE: To compare differences in epithelial chloride conductance according to class of mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. METHODS: We evaluated the relationship between the functional classes of CFTR mutations and chloride conductance using the first diagnostic sweat chloride concentration in a large cystic fibrosis (CF) population. RESULTS: There was no difference in sweat chloride value value between classes of CFTR mutations that produce no protein (class I), fail to reach the apical membrane because of defective processing (class II), or produce protein that fails to respond to cyclic adenosine monophosphate (class III). Those mutations that produce a cyclic adenosine monophosphate-responsive channel with reduced conductance (class IV) were associated with a significantly lower, intermediate sweat chloride value. However, patients with the mutations that cause reduced synthesis or partially defective processing of normal CFTR (class V) had sweat chloride concentrations similar to those in classes I to III. CONCLUSION: Studies of differences in chloride conductance between functional classes of CFTR mutations provide insight into phenotypic expression of the disease.

Comparison of airway reactivity induced by cold air and metacholine challenges in asthmatic children.

Bronchial responsiveness to isocapnic hyperventilation with cold air (CAH) and to inhaled methacholine (MCH) was compared in 17 children with bronchial asthma. The response to cold air was expressed as the percent drop in FEV1 from baseline at 4 min. after the challenge (delta % FEV1 CAH), and the response to methacholine as the provocative concentration required to reduce the FEV1 by 20% from baseline (PC20MCH). Both tests were sensitive (94%) for detecting airway hyperreactivity. There was no statistically significant relationship between delta % FEV1 CAH and the log PC20MCH (r = 0.39; P = 0.12). In clinical practice, methacholine test is easier to perform, but in the research field cold air challenge may be preferable because it avoids potential drug effects.

Efficacy of frequent nebulized ipratropium bromide added to frequent high-dose albuterol therapy in severe childhood asthma.

OBJECTIVE: The objective of this trial was to determine the efficacy of frequent nebulized ipratropium added to high-dose albuterol therapy in children with severe asthma. METHODS: One hundred twenty children (5 to 17 years) of age) with severe acute asthma (forced expiratory volume in 1 second (FEV1), < 50% of the predicted value) were enrolled into a randomized double-blind three-arm placebo-controlled trial comparing three groups: group 1, three doses of nebulized ipratropium bromide within 60 minutes (250 micrograms/dose); group 2, one dose of ipratropium; group 3, no ipratropium. All patients were also treated with three doses of nebulized albuterol within 60 minutes (0.15 mg/kg per dose). Pulmonary function and clinical measures were assessed every 20 minutes for up to 120 minutes. RESULTS: The groups were comparable at baseline. At 120 minutes, the mean percentage of predicted FEV1 improved from 33.4% to 56.7% in group 1, from 34.2% to 52.3% in group 2, and from 35.4% to 48.4% in group 3 (p = 0.0001). The differences between groups were larger in those children with a baseline FEV1 < or = 30% of the predicted value: FEV1 increased from 24.5% to 50.9% in group 1, from 25.0% to 39.8% in group 2, and from 25.9% to 36.5% in group 3 (p = 0.0001). In group 1, 38% of the patients were hospitalized after the study, 44% in group 2, and 46% in group 3 (p value not significant). However, in patients with FEV1 < or = 30%, the hospitalization rates were 27% in group 1, 56% in group 2, and 83% in group 3 (p = 0.027). There were no toxic effects attributable to ipratropium. CONCLUSION: The addition of repeated doses of nebulized ipratropium to frequent high-dose albuterol therapy in patients with acute severe asthma is both safe and more effective than albuterol alone; its use in patients with very severe asthma may reduce hospitalizations.

Maximal expiratory flows generated by rapid chest compression following end-inspiratory occlusion or expiratory clamping in young children.

Partial forced expiratory flow-volume curves obtained by the rapid chest compression technique are being widely used to assess pulmonary function in infants and young children. The aim of this study is to assess whether in this age group flow limitation is achieved with the partial forced expiratory flow-volume curve with rapid chest compression. In eight infants and young children sedated with chloral hydrate, flow-volume curves were obtained by regular rapid chest compression technique, end-inspiratory airway occlusion prior to rapid chest compression, and expiratory clamping prior to rapid chest compression. In each technique, beginning with a cuff pressure of 20 cmH2O, the cuff pressure was increased by 10 cmH2O increments until the compression pressure reached 90 cmH2O. Maximal flow-volume curves were generated by each technique. End-inspiratory occlusion prior to rapid chest compression caused higher flows over the entire phase of expiration than the regular rapid chest compression. This increase could be observed over the entire phase of expiration. Forced expiratory flow at 50% and at 75% of vital capacity (V50 and V75) with regular rapid chest compression were 207 +/- 44 ml.s-1 (mean +/- SD) and 138 +/- 59 ml.sec-1, respectively. When end-inspiratory occlusion preceded rapid chest compression, V50 and V75 increased to 283 +/- 114 and 206 +/- 61 ml.sec-1 respectively, with a mean increase in V50 of 34% and in V75 of 31%. When expiratory clamping preceded the compression, even higher expiratory flows resulted.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma carnitine levels in cystic fibrosis.

Plasma carnitine concentrations were measured in 43 children and adults with cystic fibrosis (CF), and values were compared with those from normal controls. Clinically significant abnormalities of plasma carnitine concentration were not found in CF patients. The concentration of free carnitine was slightly but significantly elevated in CF patients, and the acylcarnitine concentration and acylcarnitine/free-carnitine ratio were slightly but significantly lower. Total carnitine concentrations were similar to those of controls. The CF patients did not have abnormal urinary acylcarnitines. Altered concentrations of free and esterified carnitine were not associated with nutritional status or with liver or pulmonary function.

Passive smoking and lung function in cystic fibrosis.

The relationship between passive exposure to cigarette smoking and objective measures of health was examined in 340 patients with cystic fibrosis attending a large hospital-based clinic. Patients who came from households with smokers did not differ from those living in smoke-free households in terms of nutritional status, clinical scores, spirometry, or colonization with Pseudomonas. The number of cigarettes smoked in the household was not significantly related to nutritional status, clinical score, spirometry, or hospitalization. Similar results were found when children 6 to 11 yr of age were analyzed separately, except that height percentile was negatively related to the number of cigarettes smoked in the household. The effects of household exposure to cigarette smoke were further evaluated by analyzing changes in nutritional status, clinical score, and spirometry over a 15-yr period among patients whose families never, always, stopped, or started smoking during this time. Height percentile increased slightly during this interval among those whose households never smoked, whereas no change occurred among patients whose households always smoked, and a decline was seen among patients whose households quit. These differences were statistically significant. Patients whose households never smoked had consistently higher pulmonary function measurements than did patients whose families always smoked, although the differences were not statistically significant. The rates of decline were similar in these two groups. Patients whose households stopped smoking had significantly lower pulmonary functions at the end of the study than did subjects whose households never smoked.(ABSTRACT TRUNCATED AT 250 WORDS)