Evaluation of changes in sleep breathing patterns after primary palatoplasty in cleft children

Introduction: There is a need to more clearly understand the characteristics of breathing patterns in children with cleft palate in the first year of life, as there is little data available to guide current practice. Pierre Robin patients are known to have a higher incidence, however we hypothesised sleep breathing disturbance is not confined to this sub-group of cleft patient. Methods: We conducted a prospective observational study of sleep disordered breathing patterns in a cohort of infants with oro-nasal clefts (cleft palate with or without cleft lip) to describe the spectrum of sleep breathing patterns both pre and post palate repair. Sleep breathing studies were performed pre- and post-operatively in sequential infants referred to a regional cleft lip and palate unit. Results of sleep breathing studies were analysed according to American Academy of Sleep Medicine scoring guidelines and correlated with clinical history and details of peri-operative respiratory compromise. The degree of sleep disordered breathing was characterised using desaturation indices (number of desaturations from baseline SpO2 of >=4%, per hour). Results: Thirty-nine infants were included in this study, twenty-five female and fourteen male. Twelve had isolated Cleft Palate as part of an associated syndrome. Patients were categorised into Isolated Cleft Palate, Isolated Cleft Palate in the context of Pierre Robin Sequence, and those with Cleft Lip and Palate. All groups demonstrated some degree of sleep breathing abnormality. Not unsurprisingly the eight infants with Pierre Robin Sequence had a significantly higher desaturation index before surgical intervention (p=0.043), and were more likely to require a pre-operative airway intervention (p=0.009). Palate repair in this group did not alter the relative distribution of patients in each severity category of sleep disorder breathing. Surgical repair of the secondary palate in the remaining children was associated with some improvement but by no means complete resolution of their sleep disordered breathing patterns. Conclusions: We conclude that sleep breathing disturbance is not confined to Pierre Robin patients alone and all cleft palate patients should undergo pre-operative and post-operative sleep breathing analysis

Herschel and ALMA observations of the ISM in massive high-redshift galaxy clusters

The Sunyaev-Zel'dovich effect (SZE) can be used to select samples of galaxy clusters that are essentially mass-limited out to arbitrarily high redshifts. I will present results from an investigation of the star formation properties of galaxies in four massive clusters, extending to z~1, which were selected on the basis of their SZE decrements in the Atacama Cosmology Telescope (ACT) survey. All four clusters have been imaged with Herschel/PACS (tracing star formation rate) and two with ALMA (tracing dust and cold gas mass); newly discovered ALMA CO(4-3) and [CI] line detections expand an already large sample of spectroscopically confirmed cluster members. Star formation rate appears to anti-correlate with environmental density, but this trend vanishes after controlling for stellar mass. Elevated star formation and higher CO excitation are seen in "El Gordo," a violent cluster merger, relative to a virialized cluster at a similar high (z~1) redshift. Also exploiting ATCA 2.1 GHz observations to identify radio-loud active galactic nuclei (AGN) in our sample, I will use these data to develop a coherent picture of how environment influences galaxies' ISM properties and evolution in the most massive clusters at early cosmic times

Detection of the Power Spectrum of Cosmic Microwave Background Lensing by the Atacama Cosmology Telescope

We report the first detection of the gravitational lensing of the cosmic microwave background through a measurement of the four-point correlation function in the temperature maps made by the Atacama Cosmology Telescope. We verify our detection by calculating the levels of potential contaminants and performing a number of null tests. The resulting convergence power spectrum at 2-degree angular scales measures the amplitude of matter density fluctuations on comoving length scales of around 100 Mpc at redshifts around 0.5 to 3. The measured amplitude of the signal agrees with Lambda Cold Dark Matter cosmology predictions. Since the amplitude of the convergence power spectrum scales as the square of the amplitude of the density fluctuations, the 4-sigma detection of the lensing signal measures the amplitude of density fluctuations to 12%.Comment: 4 pages, 4 figures, replaced title and author list with version accepted by Physical Review Letters. Likelihood code can be downloaded from http://bccp.lbl.gov/~sudeep/ACTLensLike.htm

Introducing the composite time trade-off: a test of feasibility and face validity

__Abstract__ __Introduction__ This study was designed to test the feasibility and face validity of the composite time trade-off (composite TTO), a new approach to TTO allowing for a more consistent elicitation of negative health state values. __Methods__ The new instrument combines a conventional TTO to elicit values for states regarded better than dead and a lead-time TTO for states worse than dead. __Results__ A total of 121 participants completed the composite TTO for ten EQ-5D-5L health states. Mean values ranged from −0.104 for health state 53555 to 0.946 for 21111. The instructions were clear to 98 % of the respondents, and 95 % found the task easy to understand, indicating feasibility. Further, the average number of steps taken in the iteration procedure to achieve the point of indifference in the TTO and the average duration of each task were indicative of a deliberate cognitive process. __Conclusion__ Face validity was confirmed by the high mean values for the mild health states (>0.90) and low mean values for the severe states (<0.42). In conclusion, this study demonstrates the feasibility and face validity of the composite TTO in a face-to-face standardized computer-assisted interview setting

Testing for an Unusual Distribution of Rare Variants

Technological advances make it possible to use high-throughput sequencing as a primary discovery tool of medical genetics, specifically for assaying rare variation. Still this approach faces the analytic challenge that the influence of very rare variants can only be evaluated effectively as a group. A further complication is that any given rare variant could have no effect, could increase risk, or could be protective. We propose here the C-alpha test statistic as a novel approach for testing for the presence of this mixture of effects across a set of rare variants. Unlike existing burden tests, C-alpha, by testing the variance rather than the mean, maintains consistent power when the target set contains both risk and protective variants. Through simulations and analysis of case/control data, we demonstrate good power relative to existing methods that assess the burden of rare variants in individuals

Observing the Evolution of the Universe

How did the universe evolve? The fine angular scale (l>1000) temperature and polarization anisotropies in the CMB are a Rosetta stone for understanding the evolution of the universe. Through detailed measurements one may address everything from the physics of the birth of the universe to the history of star formation and the process by which galaxies formed. One may in addition track the evolution of the dark energy and discover the net neutrino mass. We are at the dawn of a new era in which hundreds of square degrees of sky can be mapped with arcminute resolution and sensitivities measured in microKelvin. Acquiring these data requires the use of special purpose telescopes such as the Atacama Cosmology Telescope (ACT), located in Chile, and the South Pole Telescope (SPT). These new telescopes are outfitted with a new generation of custom mm-wave kilo-pixel arrays. Additional instruments are in the planning stages.Comment: Science White Paper submitted to the US Astro2010 Decadal Survey. Full list of 177 author available at http://cmbpol.uchicago.ed

Spitzer MIPS 24 and 70 micron Imaging near the South Ecliptic Pole: Maps and Source Catalogs

We have imaged an 11.5 sq. deg. region of sky towards the South Ecliptic Pole (RA = 04h43m, Dec = -53d40m, J2000) at 24 and 70 microns with MIPS, the Multiband Imaging Photometer for Spitzer. This region is coincident with a field mapped at longer wavelengths by AKARI and the Balloon-borne Large Aperture Submillimeter Telescope. We discuss our data reduction and source extraction procedures. The median depths of the maps are 47 microJy/beam at 24 micron and 4.3 mJy/beam at 70 micron. At 24 micron, we identify 93098 point sources with signal-to-noise ratio (SNR) >5, and an additional 63 resolved galaxies; at 70 micron, we identify 891 point sources with SNR >6. From simulations, we determine a false detection rate of 1.8% (1.1%) for the 24 micron (70 micron) catalog. The 24 and 70 micron point-source catalogs are 80% complete at 230 microJy and 11 mJy, respectively. These mosaic images and source catalogs will be available to the public through the NASA/IPAC Infrared Science Archive.Comment: 30 pages, 9 figures, 4 tables. Submitted to ApJS. Maps and catalogs can be downloaded from http://blastexperiment.info/release/SEP_MIPS/sep-mips.php, and will be soon be available through IRS

The Atacama Cosmology Telescope: Detection of mm-wave transient sources

We report on the serendipitous discovery of three transient mm-wave sources using data from the Atacama Cosmology Telescope. The first, detected at RA = 273.8138, dec = -49.4628 at ${\sim}50\sigma$ total, brightened from less than 5 mJy to at least 1100 mJy at 150 GHz with an unknown rise time shorter than thirteen days, during which the increase from 250 mJy to 1100 mJy took only 8 minutes. Maximum flux was observed on 2019-11-8. The source's spectral index in flux between 90 and 150 GHz was positive, $\alpha = 1.5\pm0.2$. The second, detected at RA = 105.1584, dec = -11.2434 at ${\sim}20\sigma$ total, brightened from less than 20 mJy to at least 300 mJy at 150 GHz with an unknown rise time shorter than eight days. Maximum flux was observed on 2019-12-15. Its spectral index was also positive, $\alpha = 1.8\pm0.2$. The third, detected at RA = 301.9952, dec = 16.1652 at ${\sim}40\sigma$ total, brightened from less than 8 mJy to at least 300 mJy at 150 GHz over a day or less but decayed over a few days. Maximum flux was observed on 2018-9-11. Its spectrum was approximately flat, with a spectral index of $\alpha = -0.2\pm0.1$. None of the sources were polarized to the limits of these measurements. The two rising-spectrum sources are coincident in position with M and K stars, while the third is coincident with a G star.Comment: 8 pages, 4 figures, 1 tabl

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.