Energetic Oxygen and Sulfur Charge States in the Outer Jovian Magnetosphere: Insights From the Cassini Jupiter Flyby.

On 10 January 2001, Cassini briefly entered into the magnetosphere of Jupiter, en route to Saturn. During this excursion into the Jovian magnetosphere, the Cassini Magnetosphere Imaging Instrument/Charge-Energy-Mass Spectrometer detected oxygen and sulfur ions. While Charge-Energy-Mass Spectrometer can distinguish between oxygen and sulfur charge states directly, only 95.9 ± 2.9 keV/e ions were sampled during this interval, allowing for a long time integration of the tenuous outer magnetospheric (~200 RJ) plasma at one energy. For this brief interval for the 95.9 keV/e ions, 96% of oxygen ions were O+, with the other 4% as O2+, while 25% of the energetic sulfur ions were S+, 42% S2+, and 33% S3+. The S2+/O+ flux ratio was observed to be 0.35 (±0.06 Poisson error).

Dust grains fall from Saturn's D-ring into its equatorial upper atmosphere.

The sizes of Saturn's ring particles range from meters (boulders) to nanometers (dust). Determination of the rings' ages depends on loss processes, including the transport of dust into Saturn's atmosphere. During the Grand Finale orbits of the Cassini spacecraft, its instruments measured tiny dust grains that compose the innermost D-ring of Saturn. The nanometer-sized dust experiences collisions with exospheric (upper atmosphere) hydrogen and molecular hydrogen, which forces it to fall from the ring into the ionosphere and lower atmosphere. We used the Magnetospheric Imaging Instrument to detect and characterize this dust transport and also found that diffusion dominates above and near the altitude of peak ionospheric density. This mechanism results in a mass deposition into the equatorial atmosphere of ~5 kilograms per second, constraining the age of the D-ring.

Search for the exit: Voyager 1 at heliosphere's border with the galaxy.

We report measurements of energetic (>40 kiloelectron volts) charged particles on Voyager 1 from the interface region between the heliosheath, dominated by heated solar plasma, and the local interstellar medium, which is expected to contain cold nonsolar plasma and the galactic magnetic field. Particles of solar origin at Voyager 1, located at 18.5 billion kilometers (123 astronomical units) from the Sun, decreased by a factor of >10(3) on 25 August 2012, while those of galactic origin (cosmic rays) increased by 9.3% at the same time. Intensity changes appeared first for particles moving in the azimuthal direction and were followed by those moving in the radial and antiradial directions with respect to the solar radius vector. This unexpected heliospheric "depletion region" may form part of the interface between solar plasma and the galaxy.

Heterogeneous disease modeling for Hardy-Weinberg disequilibrium in case-control studies: application to renal stones and calcium-sensing receptor polymorphisms.

Renal stone formation due to hypercalciuria is a relatively common disorder with clear evidence for genetic predisposition, but cryptic phenotypic heterogeneity has hampered identification of candidate genes. The R990G single-nucleotide polymorphism (SNP) of the calcium sensing receptor (CASR) gene has been associated with hypercalciuria in stone formers and shows the appropriate functional phenotype in cell culture. In our preliminary association analysis of a case-control cohort, however, we observed significant Hardy-Weinberg disequilibrium (HWD) for the cases (n= 223), but not controls (n= 676) at the R990G locus, pointing us toward the general disease model incorporating HWD. Because there is an adjacent CASR SNP, A986S, which is in negative linkage disequilibrium with R990G, we extended the general disease model to enable testing of a two-site hypothesis. In our data set, there is no lack of fit (P= .345) for the single-locus model for the R990G genotype, and likelihood ratio testing favors a recessive effect with an eight-fold increase in risk (P < .001) for GG homozygotes, relative to wild-type, based on a population prevalence of 2%. Addition of the A986S genotype provides no additional information either by itself or when included in our two-site model.

Mediation of the solar wind termination shock by non-thermal ions.

Broad regions on both sides of the solar wind termination shock are populated by high intensities of non-thermal ions and electrons. The pre-shock particles in the solar wind have been measured by the spacecraft Voyager 1 (refs 1-5) and Voyager 2 (refs 3, 6). The post-shock particles in the heliosheath have also been measured by Voyager 1 (refs 3-5). It was not clear, however, what effect these particles might have on the physics of the shock transition until Voyager 2 crossed the shock on 31 August-1 September 2007 (refs 7-9). Unlike Voyager 1, Voyager 2 is making plasma measurements. Data from the plasma and magnetic field instruments on Voyager 2 indicate that non-thermal ion distributions probably have key roles in mediating dynamical processes at the termination shock and in the heliosheath. Here we report that intensities of low-energy ions measured by Voyager 2 produce non-thermal partial ion pressures in the heliosheath that are comparable to (or exceed) both the thermal plasma pressures and the scalar magnetic field pressures. We conclude that these ions are the >0.028 MeV portion of the non-thermal ion distribution that determines the termination shock structure and the acceleration of which extracts a large fraction of bulk-flow kinetic energy from the incident solar wind.

Testing for equality of standardized composite measures of linkage disequilibrium.

We described the approximate variance for a composite measure of linkage disequilibrium (LD), which depends only on genotype frequencies and allows for departure from Hardy-Weinberg disequilibrium (Hamilton et al. 2006). Here we extend this work to allow for inferences about differences in composite LD coefficients, as we illustrate with two examples. Simulations demonstrate consistency of type I error rates under most conditions. Calculations for power and sample size are also given.

A dynamic, rotating ring current around Saturn.

The concept of an electrical current encircling the Earth at high altitudes was first proposed in 1917 to explain the depression of the horizontal component of the Earth's magnetic field during geomagnetic storms. In situ measurements of the extent and composition of this current were made some 50 years later and an image was obtained in 2001 (ref. 6). Ring currents of a different nature were observed at Jupiter and their presence inferred at Saturn. Here we report images of the ring current at Saturn, together with a day-night pressure asymmetry and tilt of the planet's plasma sheet, based on measurements using the magnetospheric imaging instrument (MIMI) on board Cassini. The ring current can be highly variable with strong longitudinal asymmetries that corotate nearly rigidly with the planet. This contrasts with the Earth's ring current, where there is no rotational modulation and initial asymmetries are organized by local time effects.

Approximate variance for a standardized composite measure of linkage disequilibrium.

The approximate variance for the standardized measure of gametic linkage disequilibrium has been described. However, this approach assumes knowledge of the phase of double heterozygotes or Hardy-Weinberg equilibrium. Here we give the approximate variance for a composite measure of linkage disequilibrium which depends only on genotype frequencies. We show by simulation that this variance approximation is valid over a range of allele probabilities and departures from Hardy-Weinberg equilibrium.

Voyager 1 in the foreshock, termination shock, and heliosheath.

Voyager 1 (V1) began measuring precursor energetic ions and electrons from the heliospheric termination shock (TS) in July 2002. During the ensuing 2.5 years, average particle intensities rose as V1 penetrated deeper into the energetic particle foreshock of the TS. Throughout 2004, V1 observed even larger, fluctuating intensities of ions from 40 kiloelectron volts (keV) to >/=50 megaelectron volts per nucleon and of electrons from >26 keV to >/=350 keV. On day 350 of 2004 (2004/350), V1 observed an intensity spike of ions and electrons that was followed by a sustained factor of 10 increase at the lowest energies and lesser increases at higher energies, larger than any intensities since V1 was at 15 astronomical units in 1982. The estimated solar wind radial flow speed was positive (outward) at approximately +100 kilometers per second (km s(-1)) from 2004/352 until 2005/018, when the radial flows became predominantly negative (sunward) and fluctuated between approximately -50 and 0 km s(-1) until about 2005/110; they then became more positive, with recent values (2005/179) of approximately +50 km s(-1). The energetic proton spectrum averaged over the postshock period is apparently dominated by strongly heated interstellar pickup ions. We interpret these observations as evidence that V1 was crossed by the TS on 2004/351 (during a tracking gap) at 94.0 astronomical units, evidently as the shock was moving radially inward in response to decreasing solar wind ram pressure, and that V1 has remained in the heliosheath until at least mid-2005.

Dynamics of Saturn's magnetosphere from MIMI during Cassini's orbital insertion.

The Magnetospheric Imaging Instrument (MIMI) onboard the Cassini spacecraft observed the saturnian magnetosphere from January 2004 until Saturn orbit insertion (SOI) on 1 July 2004. The MIMI sensors observed frequent energetic particle activity in interplanetary space for several months before SOI. When the imaging sensor was switched to its energetic neutral atom (ENA) operating mode on 20 February 2004, at approximately 10(3) times Saturn's radius RS (0.43 astronomical units), a weak but persistent signal was observed from the magnetosphere. About 10 days before SOI, the magnetosphere exhibited a day-night asymmetry that varied with an approximately 11-hour periodicity. Once Cassini entered the magnetosphere, in situ measurements showed high concentrations of H+, H2+, O+, OH+, and H2O+ and low concentrations of N+. The radial dependence of ion intensity profiles implies neutral gas densities sufficient to produce high loss rates of trapped ions from the middle and inner magnetosphere. ENA imaging has revealed a radiation belt that resides inward of the D ring and is probably the result of double charge exchange between the main radiation belt and the upper layers of Saturn's exosphere.

Standardizing a composite measure of linkage disequilibrium.

The maximum and minimum are obtained for a composite measure of linkage disequilibrium used with genotypic data when the phase of double heterozygotes cannot be determined. These bounds are used to standardize the composite measure in the same way used for D', the standardized gametic measure of linkage disequilibrium. Standardization produces a measure which lies between -1 and 1, and allows comparison of linkage disequilibrium between populations. The method is illustrated using two loci in the CASR gene.

Voyager 1 exited the solar wind at a distance of approximately 85 Au from the Sun.

The outer limit of the Solar System is often considered to be at the distance from the Sun where the solar wind changes from supersonic to subsonic flow. Theory predicts that a termination shock marks this boundary, with locations ranging from a few to over 100 au (1 Au approximately 1.5 x 10(8) km, the distance from Earth to the Sun). 'Pick-up ions' that originate as interstellar neutral atoms should be accelerated to tens of MeV at the termination shock, generating anomalous cosmic rays. Here we report a large increase in the intensity of energetic particles in the outer heliosphere, as measured by an instrument on the Voyager 1 spacecraft. We argue that the spacecraft exited the supersonic solar wind and passed into the subsonic region (possibly beyond the termination shock) on about 1 August 2002 at a distance of approximately 85 Au (heliolatitude approximately 34 degrees N), then re-entered the supersonic solar wind about 200 days later at approximately 87 au from the Sun. We show that the composition of the ions accelerated at the putative termination shock is that of anomalous cosmic rays and of interstellar pick-up ions.

New anti-Gram-positive agents.

As the prevalence of resistant Gram-positive organisms in the critical care unit has increased, so have the associated morbidity and mortality and the cost of their treatment. As a result, more toxic and less active second-line agents and combinations of agents are used, often with limited evidence of clinical benefit. Although widely used, the role of glycopeptides is limited by increasing resistance and poor pharmacokinetics. New agents now in use, such as quinupristin/dalfopristin and Linezolid (Zyvox; Pharmacia & Upjohn, Kalamazoo, MI), show promise, as do diverse agents in development. The future is likely to bring greater therapeutic choice but, inevitably, further resistance.

Rates and risk factors for recurrence of gestational diabetes.

OBJECTIVE: To determine the recurrence rate of gestational diabetes (GDM) during a subsequent pregnancy among women who had GDM during an index pregnancy and to identify factors associated with the probability of recurrence RESEARCH DESIGN AND METHODS: A retrospective longitudinal study was performed in Nova Scotia, Canada, of women who were diagnosed as having GDM during a pregnancy between the years of 1980 and 1996 and who had at least one subsequent pregnancy during this time period. When only the index and first subsequent pregnancy were analyzed, the cohort included 651 women. The recurrence rate of GDM in the pregnancy after the pregnancy with the initial diagnosis of GDM was determined. Multivariate regression models were constructed to model the recurrence of GDM in a subsequent pregnancy as functions of potential predictors to estimate RRs and CIs. RESULTS: The rate of recurrence of GDM in the pregnancy subsequent to the index pregnancy was found to the 35.6% (95% CI = 31.9-39.3%). Multivariate regression models showed that infant birth weight in the index pregnancy and maternal prepregnancy weight before the subsequent pregnancy were predictive of recurrent GDM. CONCLUSIONS: In this large cohort of women, slightly more than one-third of the subjects had diabetes in a subsequent pregnancy, which is consistent with recurrence rates in other predominately white populations. Strategies to reduce the occurrence of neonatal macrosomia and maternal prepregnancy obesity may help lower the rate of recurrence of GDM.

Technique for detecting serial topographic changes in the optic disc and peripapillary retina using scanning laser tomography.

PURPOSE: To describe and evaluate a new statistical technique for detecting topographic changes in the optic disc and peripapillary retina measured with confocal scanning laser tomography. METHODS: The 256x256-pixel array of topographic height values obtained with each image from the Heidelberg Retina Tomograph (Heidelberg Engineering, Heidelberg, Germany) was divided into an array of 64x64 superpixels, where each superpixel contained 16 (i.e., 4x4) pixels. An analysis of variance technique was developed to analyze each superpixel with three baseline and three follow-up images. The performance of the technique was tested with and without adjustment for spatial correlation of topographic values using computer simulations and with real data from a normal control subject and a patient with progressive glaucomatous disc change. RESULTS: Computer simulation with fixed population means and variance, and varying spatial correlation showed a monotonically increasing number of superpixels with significant test results (false positives), with 20% false-positives when the spatial correlation was 0.8 (the approximate median value in real patient data). The number of false-positive results was similar (17%) in serial images of a normal subject. When corrected for spatial correlation, the number of false-positives was independent of the level of spatial correlation and remained at the expected value of less than 5% in both simulations and real data. Although the number of significant test results in the patient with progressive glaucoma decreased after correction for spatial correlation, the change was readily apparent. Statistical power to detect mean differences in topographic values ranging from 0.5 to 4.0 SDs in computer simulation showed low power for changes of 1 SD or less, but increased dramatically with larger changes. CONCLUSIONS: This technique has a high level of sensitivity to detect changes in the optic disc while maintaining a high level of specificity.

Retrospective estimation of the birth prevalence for delayed onset disorders: application to cystic fibrosis in Nova Scotia.

Maximum likelihood methods are used to estimate the birth prevalence, the age-at-diagnosis distribution, and the number of infants born with CF in Nova Scotia over a 20 year period. The data were taken from a registry of CF cases, and, because of the delayed onset of symptoms, some CF affected individuals were not diagnosed by the end of the study period. A goodness-of-fit test for assessing whether the age-at-diagnosis distribution is stable over the 20 years is provided. These methods could be applied equally well to data on any genetic disorder with delayed onset.

Molecular diagnosis of cystic fibrosis in Maritime Canada.

Many of the people in Maritime Canada can trace their ancestry to some of the oldest settlements in North America. Consequently, both founder effect and genetic drift can be shown to account for the high frequency of some genetic disorders and virtual absence of others. The birth prevalence rate for cystic fibrosis (CF) in Maritime Canada is similar to other North American regions, but we recognized that similar factors might apply to CF genotypes and thereby impair the accuracy of counselling based on molecular markers. We therefore screened the majority (53%) of our CF population for the commonest mutation (delta F508) and for frequency of haplotypes based on 4 linked RFLPs: XV2C, KM19, J3.11, and MP6d9. The proportion with the delta F508 mutation--100 (76%) of 131 CF chromosomes--was similar to that found in other centres. In comparing frequencies of XV2C and KM19 haplotypes on non-delta F508 CF chromosomes with those from a more heterogeneous Canadian population (Kerem et al.) and a Swiss population (Liechti-Gallati et al.), no statistically significant differences were identified. Extended haplotyping to include MP6d9 and J3.11 alleles revealed 3 new haplotypes, but the overall frequency distribution was not statistically different. We can therefore exclude substantial founder effects in our population. Genotype frequencies and recurrence risks for non-delta F508 CF genotypes can be used in counselling most Maritime Canadian families with cystic fibrosis. Further mutational analysis should focus on chromosomes bearing unique haplotypes and individuals from specific subpopulations.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma Composition in Jupiter's Magnetosphere: Initial Results from the Solar Wind Ion Composition Spectrometer.

The ion composition in the Jovian environment was investigated with the Solar Wind Ion Composition Spectrometer on board Ulysses. A hot tenuous plasma was observed throughout the outer and middle magnetosphere. In some regions two thermally different components were identified. Oxygen and sulfur ions with several different charge states, from the volcanic satellite lo, make the largest contribution to the mass density of the hot plasma, even at high latitude. Solar wind particles were observed in all regions investigated. Ions from Jupiter's ionosphere were abundant in the middle magnetosphere, particularly in the highlatitude region on the dusk side, which was traversed for the first time.

Inorganic sulfate metabolism in the very low birthweight infant.

The effect of vitamin D supplementation on inorganic sulfate metabolism was examined in very low birth weight (less than 1,500 g) infants at biweekly intervals after birth until 6 weeks of postnatal age. Baseline serum sulfate concentrations were significantly higher in all infants (471 +/- 24 mumol/l, n = 80) than in adults (299 +/- 25 mumol/l, n = 17). In controls, the levels did not change significantly over the ensuing 6 weeks, although serum creatinine declined. Urinary sulfate excretion rose significantly to near adult levels by 2 weeks. Both urine and serum sulfate were correlated with weight gain but not with estimated glomerular filtration rate, suggesting that factors other than renal clearance have a preponderant influence on serum sulfate in these infants. At 6 weeks, the mean serum sulfate in the high-dose group (receiving 2,170 +/- 23 U/day of vitamin D, n = 41) was significantly higher than in controls (receiving 360 +/- 22 U/day, n = 40). In all infants, there was a significant correlation (r = 0.36, p less than 0.001) between serum sulfate and 25(OH)-vitamin D concentrations, but not other analytes or clinical variables, suggesting that vitamin D may be one of the factors modulating sulfate metabolism in the newborn period.