Two New Candidate Planets in Eccentric Orbits

Doppler measurements of two G-type main-sequence stars, HD210277 and HD168443, reveal Keplerian variations that imply the presence of companions with masses (M sin i) of 1.28 and 5.04 M_Jup and orbital periods of 437 d and 58 d, respectively. The orbits have large eccentricities of e=0.45 and e=0.54, respectively. All 9 known extrasolar planet candidates with a=0.2-2.5 AU have orbital eccentricities greater than 0.1, higher than that of Jupiter (e=0.05). Eccentric orbits may result from gravitational perturbations imposed by other orbiting planets or stars, by passing stars in the dense star-forming cluster, or by the protoplanetary disk. Based on published studies and our near-IR adaptive optics images, HD210277 appears to be a single star. However, HD168443 exhibits a long-term velocity trend consistent with a close stellar companion, as yet undetected directly.Comment: AASTeX, 31 pages including 10 Postscript figures, to appear in the Astrophysical Journal (July 1999

Laser frequency comb techniques for precise astronomical spectroscopy

Precise astronomical spectroscopic analyses routinely assume that individual pixels in charge-coupled devices (CCDs) have uniform sensitivity to photons. Intra-pixel sensitivity (IPS) variations may already cause small systematic errors in, for example, studies of extra-solar planets via stellar radial velocities and cosmological variability in fundamental constants via quasar spectroscopy, but future experiments requiring velocity precisions approaching ~1 cm/s will be more strongly affected. Laser frequency combs have been shown to provide highly precise wavelength calibration for astronomical spectrographs, but here we show that they can also be used to measure IPS variations in astronomical CCDs in situ. We successfully tested a laser frequency comb system on the Ultra-High Resolution Facility spectrograph at the Anglo-Australian Telescope. By modelling the 2-dimensional comb signal recorded in a single CCD exposure, we find that the average IPS deviates by <8 per cent if it is assumed to vary symmetrically about the pixel centre. We also demonstrate that series of comb exposures with absolutely known offsets between them can yield tighter constraints on symmetric IPS variations from ~100 pixels. We discuss measurement of asymmetric IPS variations and absolute wavelength calibration of astronomical spectrographs and CCDs using frequency combs.Comment: 11 pages, 7 figures. Accepted for publication in MNRA

Guillain-Barré Syndrome, Influenza Vaccination, and Antecedent Respiratory and Gastrointestinal Infections: A Case-Centered Analysis in the Vaccine Safety Datalink, 2009–2011

Background: Guillain-Barré Syndrome (GBS) can be triggered by gastrointestinal or respiratory infections, including influenza. During the 2009 influenza A (H1N1) pandemic in the United States, monovalent inactivated influenza vaccine (MIV) availability coincided with high rates of wildtype influenza infections. Several prior studies suggested an elevated GBS risk following MIV, but adjustment for antecedent infection was limited. Methods: We identified patients enrolled in health plans participating in the Vaccine Safety Datalink and diagnosed with GBS from July 2009 through June 2011. Medical records of GBS cases with 2009–10 MIV, 2010–11 trivalent inactivated influenza vaccine (TIV), and/or a medically-attended respiratory or gastrointestinal infection in the 1 through 141 days prior to GBS diagnosis were reviewed and classified according to Brighton Collaboration criteria for diagnostic certainty. Using a case-centered design, logistic regression models adjusted for patient-level time-varying sources of confounding, including seasonal vaccinations and infections in GBS cases and population-level controls. Results: Eighteen confirmed GBS cases received vaccination in the 6 weeks preceding onset, among 1.27 million 2009–10 MIV recipients and 2.80 million 2010–11 TIV recipients. Forty-four confirmed GBS cases had infection in the 6 weeks preceding onset, among 3.77 million patients diagnosed with medically-attended infection. The observed-versus-expected odds that 2009–10 MIV/2010–11 TIV was received in the 6 weeks preceding GBS onset was odds ratio = 1.54, 95% confidence interval (CI), 0.59–3.99; risk difference = 0.93 per million doses, 95% CI, −0.71–5.16. The association between GBS and medically-attended infection was: odds ratio = 7.73, 95% CI, 3.60–16.61; risk difference = 11.62 per million infected patients, 95% CI, 4.49–26.94. These findings were consistent in sensitivity analyses using alternative infection definitions and risk intervals for prior vaccination shorter than 6 weeks. Conclusions: After adjusting for antecedent infections, we found no evidence for an elevated GBS risk following 2009–10 MIV/2010–11 TIV influenza vaccines. However, the association between GBS and antecedent infection was strongly elevated

Haplotype-based stratification of Huntington's disease

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease caused by expansion of a CAG trinucleotide repeat in HTT, resulting in an extended polyglutamine tract in huntingtin. We and others have previously determined that the HD-causing expansion occurs on multiple different haplotype backbones, reflecting more than one ancestral origin of the same type of mutation. In view of the therapeutic potential of mutant allele-specific gene silencing, we have compared and integrated two major systems of HTT haplotype definition, combining data from 74 sequence variants to identify the most frequent disease-associated and control chromosome backbones and revealing that there is potential for additional resolution of HD haplotypes. We have used the large collection of 4078 heterozygous HD subjects analyzed in our recent genome-wide association study of HD age at onset to estimate the frequency of these haplotypes in European subjects, finding that common genetic variation at HTT can distinguish the normal and CAG-expanded chromosomes for more than 95% of European HD individuals. As a resource for the HD research community, we have also determined the haplotypes present in a series of publicly available HD subject-derived fibroblasts, induced pluripotent cells, and embryonic stem cells in order to facilitate efforts to develop inclusive methods of allele-specific HTT silencing applicable to most HD patients. Our data providing genetic guidance for therapeutic gene-based targeting will significantly contribute to the developments of rational treatments and implementation of precision medicine in HD

Haplotype-based stratification of Huntington's disease

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease caused by expansion of a CAG trinucleotide repeat in HTT, resulting in an extended polyglutamine tract in huntingtin. We and others have previously determined that the HD-causing expansion occurs on multiple different haplotype backbones, reflecting more than one ancestral origin of the same type of mutation. In view of the therapeutic potential of mutant allele-specific gene silencing, we have compared and integrated two major systems of HTT haplotype definition, combining data from 74 sequence variants to identify the most frequent disease-associated and control chromosome backbones and revealing that there is potential for additional resolution of HD haplotypes. We have used the large collection of 4078 heterozygous HD subjects analyzed in our recent genome-wide association study of HD age at onset to estimate the frequency of these haplotypes in European subjects, finding that common genetic variation at HTT can distinguish the normal and CAG-expanded chromosomes for more than 95% of European HD individuals. As a resource for the HD research community, we have also determined the haplotypes present in a series of publicly available HD subject-derived fibroblasts, induced pluripotent cells, and embryonic stem cells in order to facilitate efforts to develop inclusive methods of allele-specific HTT silencing applicable to most HD patients. Our data providing genetic guidance for therapeutic gene-based targeting will significantly contribute to the developments of rational treatments and implementation of precision medicine in HD

Population-specific genetic modification of Huntington\u27s disease in Venezuela.

Modifiers of Mendelian disorders can provide insights into disease mechanisms and guide therapeutic strategies. A recent genome-wide association (GWA) study discovered genetic modifiers of Huntington\u27s disease (HD) onset in Europeans. Here, we performed whole genome sequencing and GWA analysis of a Venezuelan HD cluster whose families were crucial for the original mapping of the HD gene defect. The Venezuelan HD subjects develop motor symptoms earlier than their European counterparts, implying the potential for population-specific modifiers. The main Venezuelan HD family inherits HTT haplotype hap.03, which differs subtly at the sequence level from European HD hap.03, suggesting a different ancestral origin but not explaining the earlier age at onset in these Venezuelans. GWA analysis of the Venezuelan HD cluster suggests both population-specific and population-shared genetic modifiers. Genome-wide significant signals at 7p21.2-21.1 and suggestive association signals at 4p14 and 17q21.2 are evident only in Venezuelan HD, but genome-wide significant association signals at the established European chromosome 15 modifier locus are improved when Venezuelan HD data are included in the meta-analysis. Venezuelan-specific association signals on chromosome 7 center on SOSTDC1, which encodes a bone morphogenetic protein antagonist. The corresponding SNPs are associated with reduced expression of SOSTDC1 in non-Venezuelan tissue samples, suggesting that interaction of reduced SOSTDC1 expression with a population-specific genetic or environmental factor may be responsible for modification of HD onset in Venezuela. Detection of population-specific modification in Venezuelan HD supports the value of distinct disease populations in revealing novel aspects of a disease and population-relevant therapeutic strategies

Kepler-68: Three Planets, One With a Density Between That of Earth and Ice Giants

NASA's Kepler Mission has revealed two transiting planets orbiting Kepler-68. Follow-up Doppler measurements have established the mass of the innermost planet and revealed a third jovian-mass planet orbiting beyond the two transiting planets. Kepler-68b, in a 5.4 day orbit has mass 8.3 +/- 2.3 Earth, radius 2.31 +/- 0.07 Earth radii, and a density of 3.32 +/- 0.92 (cgs), giving Kepler-68b a density intermediate between that of the ice giants and Earth. Kepler-68c is Earth-sized with a radius of 0.953 Earth and transits on a 9.6 day orbit; validation of Kepler-68c posed unique challenges. Kepler-68d has an orbital period of 580 +/- 15 days and minimum mass of Msin(i) = 0.947 Jupiter. Power spectra of the Kepler photometry at 1-minute cadence exhibit a rich and strong set of asteroseismic pulsation modes enabling detailed analysis of the stellar interior. Spectroscopy of the star coupled with asteroseismic modeling of the multiple pulsation modes yield precise measurements of stellar properties, notably Teff = 5793 +/- 74 K, M = 1.079 +/- 0.051 Msun, R = 1.243 +/- 0.019 Rsun, and density 0.7903 +/- 0.0054 (cgs), all measured with fractional uncertainties of only a few percent. Models of Kepler-68b suggest it is likely composed of rock and water, or has a H and He envelope to yield its density of about 3 (cgs).Comment: 32 pages, 13 figures, Accepted to Ap

Fundamental Properties of Kepler Planet-Candidate Host Stars using Asteroseismology

We have used asteroseismology to determine fundamental properties for 66 Kepler planet-candidate host stars, with typical uncertainties of 3% and 7% in radius and mass, respectively. The results include new asteroseismic solutions for four host stars with confirmed planets (Kepler-4, Kepler-14, Kepler-23 and Kepler-25) and increase the total number of Kepler host stars with asteroseismic solutions to 77. A comparison with stellar properties in the planet-candidate catalog by Batalha et al. shows that radii for subgiants and giants obtained from spectroscopic follow-up are systematically too low by up to a factor of 1.5, while the properties for unevolved stars are in good agreement. We furthermore apply asteroseismology to confirm that a large majority of cool main-sequence hosts are indeed dwarfs and not misclassified giants. Using the revised stellar properties, we recalculate the radii for 107 planet candidates in our sample, and comment on candidates for which the radii change from a previously giant-planet/brown-dwarf/stellar regime to a sub-Jupiter size, or vice versa. A comparison of stellar densities from asteroseismology with densities derived from transit models in Batalha et al. assuming circular orbits shows significant disagreement for more than half of the sample due to systematics in the modeled impact parameters, or due to planet candidates which may be in eccentric orbits. Finally, we investigate tentative correlations between host-star masses and planet candidate radii, orbital periods, and multiplicity, but caution that these results may be influenced by the small sample size and detection biases.Comment: 19 pages, 10 figures, 4 tables; accepted for publication in ApJ; machine-readable versions of tables 1-3 are available as ancillary files or in the source code; v2: minor changes to match published versio

Neural Tube Defects and Folate Pathway Genes: Family-Based Association Tests of Gene–Gene and Gene–Environment Interactions

BACKGROUND: Folate metabolism pathway genes have been examined for association with neural tube defects (NTDs) because folic acid supplementation reduces the risk of this debilitating birth defect. Most studies addressed these genes individually, often with different populations providing conflicting results. OBJECTIVES: Our study evaluates several folate pathway genes for association with human NTDs, incorporating an environmental cofactor: maternal folate supplementation. METHODS: In 304 Caucasian American NTD families with myelomeningocele or anencephaly, we examined 28 polymorphisms in 11 genes: folate receptor 1, folate receptor 2, solute carrier family 19 member 1, transcobalamin II, methylenetetrahydrofolate dehydrogenase 1, serine hydroxymethyl-transferase 1, 5,10-methylenetetrahydrofolate reductase (MTHFR), 5-methyltetrahydrofolate-homo-cysteine methyltransferase, 5-methyltetrahydrofolate-homocysteine methyltransferase reductase, betaine-homocysteine methyltransferase (BHMT), and cystathionine-beta-synthase. RESULTS: Only single nucleotide polymorphisms (SNPs) in BHMT were significantly associated in the overall data set; this significance was strongest when mothers took folate-containing nutritional supplements before conception. The BHMT SNP rs3733890 was more significant when the data were stratified by preferential transmission of the MTHFR rs1801133 thermolabile T allele from parent to offspring. Other SNPs in folate pathway genes were marginally significant in some analyses when stratified by maternal supplementation, MTHFR, or BHMT allele transmission. CONCLUSIONS: BHMT rs3733890 is significantly associated in our data set, whereas MTHFR rs1801133 is not a major risk factor. Further investigation of folate and methionine cycle genes will require extensive SNP genotyping and/or resequencing to identify novel variants, inclusion of environmental factors, and investigation of gene–gene interactions in large data sets