A Randomized Trial Examining Preoperative Sedative Medication and Post-operative Sleep in Children

Study Objective Midazolam has been found to have beneficial effects on anxiety in children in the preoperative setting. Prior studies have examined various postoperative behaviors of children, but little research has examined the effects of preoperative use of midazolam with postoperative sleep. The purpose of this investigation was to compare postoperative sleep in children as a function of preoperative sedative medication use. Design This study was a 2-group randomized controlled trial. Setting Participants were recruited from Yale-New Haven Children\u27s Hospital. Patients Participants included a convenience sample of 70 children between the ages of 3 to 12 years undergoing ambulatory tonsillectomy and adenoidectomy. Interventions Children were randomly assigned to 1 of 2 groups: a control group who received preoperative acetaminophen only (n = 32) and an experimental group who received both acetaminophen and midazolam preoperatively (n = 38). Measurements Parents completed measures of postoperative behavioral recovery and a subset of children wore actigraphs to examine objective sleep data. Main Results Children who received midazolam experienced similar sleep changes compared to children in the control group. The actigraph data revealed that children who received midazolam were awake significantly less during the night compared to the control group (P= .01). Conclusion Children who received midazolam before surgery had similar postoperative sleep changes compared to children who did not receive midazolam. Further understanding of the postoperative behavioral effects of midazolam on children will help guide healthcare providers in their practice

Luminous Infrared Galaxies with the Submillimeter Array: I. Survey Overview and the Central Gas to Dust Ratio

We present new data obtained with the Submillimeter Array for a sample of fourteen nearby luminous and ultraluminous infrared galaxies. The galaxies were selected to have luminosity distances D < 200 Mpc and far-infrared luminosities log(L_FIR) > 11.4. The galaxies were observed with spatial resolutions of order 1 kpc in the CO J=3-2, CO J=2-1, 13CO J=2-1, and HCO+ J=4-3 lines as well as the continuum at 880 microns and 1.3 mm. We have combined our CO and continuum data to measure an average gas-to-dust mass ratio of 120 +/- 28 (rms deviation 109) in the central regions of these galaxies, very similar to the value of 150 determined for the Milky Way. This similarity is interesting given the more intense heating from the starburst and possibly accretion activity in the luminous infrared galaxies compared to the Milky Way. We find that the peak H_2 surface density correlates with the far-infrared luminosity, which suggests that galaxies with higher gas surface densities inside the central kiloparsec have a higher star formation rate. The lack of a significant correlation between total H_2 mass and far-infrared luminosity in our sample suggests that the increased star formation rate is due to the increased availability of molecular gas as fuel for star formation in the central regions. In contrast to previous analyses by other authors, we do not find a significant correlation between central gas surface density and the star formation efficiency, as trace by the ratio of far-infrared luminosity to nuclear gas mass. Our data show that it is the star formation rate, not the star formation efficiency, that increases with increasing central gas surface density in these galaxies.Comment: 66 pages, 39 figures, aastex preprint format; to be published in ApJ Supplements. Version of paper with full resolution figures available at http://www.physics.mcmaster.ca/~wilson/www_xfer/ULIRGS_publi

Hindlimb suspension in Wistar rats: Sex-based differences in muscle response

Ground-based animal models have been used extensively to understand the effects of microgravity on various physiological systems. Among them, hindlimb suspension (HLS), developed in 1979 in rats, remains the gold-standard and allows researchers to study the consequences of total unloading of the hind limbs while inducing a cephalic fluid shift. While this model has already brought valuable insights to space biology, few studies have directly compared functional decrements in the muscles of males and females during HLS. We exposed 28 adult Wistar rats (14 males and 14 females) to 14 days of HLS or normal loading (NL) to better assess how sex impacts disuse-induced muscle deconditioning. Females better maintained muscle function during HLS than males, as shown by a more moderate reduction in grip strength at 7 days (males: −37.5 ± 3.1%, females: −22.4 ± 6.5%, compared to baseline), that remains stable during the second week of unloading (males: −53.3 ± 5.7%, females: −22.4 ± 5.5%, compared to day 0) while the males exhibit a steady decrease over time (effect of sex × loading p = 0.0002, effect of sex × time × loading p = 0.0099). This was further supported by analyzing the force production in response to a tetanic stimulus. Further functional analyses using force production were also shown to correspond to sex differences in relative loss of muscle mass and CSA. Moreover, our functional data were supported by histomorphometric analyzes, and we highlighted differences in relative muscle loss and CSA. Specifically, female rats seem to experience a lesser muscle deconditioning during disuse than males thus emphasizing the need for more studies that will assess male and female animals concomitantly to develop tailored, effective countermeasures for all astronauts

Probing ISM Structure in Trumpler 14 & Carina I Using The Stratospheric Terahertz Observatory 2

We present observations of the Trumpler 14/Carina I region carried out using the Stratospheric Terahertz Observatory 2 (STO2). The Trumpler 14/Carina I region is in the west part of the Carina Nebula Complex, which is one of the most extreme star-forming regions in the Milky Way. We observed Trumpler 14/Carina I in the 158 $\mu$m transition of [C\,{\sc ii}] with a spatial resolution of 48$''$ and a velocity resolution of 0.17 km s$^{-1}$. The observations cover a 0.25$^\circ$ by 0.28$^\circ$ area with central position {\it l} = 297.34$^\circ$, {\it b} = -0.60$^\circ$. The kinematics show that bright [C\,{\sc ii}] structures are spatially and spectrally correlated with the surfaces of CO clouds, tracing the photodissociation region and ionization front of each molecular cloud. Along 7 lines of sight that traverse Tr 14 into the dark ridge to the southwest, we find that the [C\,{\sc ii}] luminosity from the HII region is 3.7 times that from the PDR. In same los we find in the PDRs an average ratio of 1:4.1:5.6 for the mass in atomic gas:dark-CO gas: molecular gas traced by CO. Comparing multiple gas tracers including HI 21cm, [C\,{\sc ii}], CO, and radio recombination lines, we find that the HII regions of the Carina Nebula Complex are well-described as HII regions with one-side freely expanding towards us, consistent with the champagne model of ionized gas evolution. The dispersal of the GMC in this region is dominated by EUV photoevaporation; the dispersal timescale is 20-30 Myr.Comment: ApJ accepte

Mechanisms of CFTR Functional Variants That Impair Regulated Bicarbonate Permeation and Increase Risk for Pancreatitis but Not for Cystic Fibrosis

CFTR is a dynamically regulated anion channel. Intracellular WNK1-SPAK activation causes CFTR to change permeability and conductance characteristics from a chloride-preferring to bicarbonate-preferring channel through unknown mechanisms. Two severe CFTR mutations (CFTRsev) cause complete loss of CFTR function and result in cystic fibrosis (CF), a severe genetic disorder affecting sweat glands, nasal sinuses, lungs, pancreas, liver, intestines, and male reproductive system. We hypothesize that those CFTR mutations that disrupt the WNK1-SPAK activation mechanisms cause a selective, bicarbonate defect in channel function (CFTRBD) affecting organs that utilize CFTR for bicarbonate secretion (e.g. the pancreas, nasal sinus, vas deferens) but do not cause typical CF. To understand the structural and functional requirements of the CFTR bicarbonate-preferring channel, we (a) screened 984 well-phenotyped pancreatitis cases for candidate CFTRBD mutations from among 81 previously described CFTR variants; (b) conducted electrophysiology studies on clones of variants found in pancreatitis but not CF; (c) computationally constructed a new, complete structural model of CFTR for molecular dynamics simulation of wild-type and mutant variants; and (d) tested the newly defined CFTRBD variants for disease in non-pancreas organs utilizing CFTR for bicarbonate secretion. Nine variants (CFTR R74Q, R75Q, R117H, R170H, L967S, L997F, D1152H, S1235R, and D1270N) not associated with typical CF were associated with pancreatitis (OR 1.5, p = 0.002). Clones expressed in HEK 293T cells had normal chloride but not bicarbonate permeability and conductance with WNK1-SPAK activation. Molecular dynamics simulations suggest physical restriction of the CFTR channel and altered dynamic channel regulation. Comparing pancreatitis patients and controls, CFTRBD increased risk for rhinosinusitis (OR 2.3, p<0.005) and male infertility (OR 395, p<<0.0001). WNK1-SPAK pathway-activated increases in CFTR bicarbonate permeability are altered by CFTRBD variants through multiple mechanisms. CFTRBD variants are associated with clinically significant disorders of the pancreas, sinuses, and male reproductive system.Fil: LaRusch, Jessica. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: Jung, Jinsei. Yonsei University College of Medicine; Corea del SurFil: General, Ignacio. University of Pittsburgh; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lewis, Michele D.. Mayo Clinic. Division of Gastroenterology and Hepatology; Estados UnidosFil: Park, Hyun Woo. Yonsei University College of Medicine; Corea del SurFil: Brand, Randall E.. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: Gelrud, Andres. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: Anderson, Michelle A.. University of Michigan; Estados UnidosFil: Banks, Peter A.. Brigham and Women’s Hospital. Division of Gastroenterology; Estados UnidosFil: Conwell, Darwin. Brigham and Women’s Hospital. Division of Gastroenterology; Estados UnidosFil: Lawrence, Christopher. Medical University of South Carolina; Estados UnidosFil: Romagnuolo, Joseph. Medical University of South Carolina; Estados UnidosFil: Baillie, John. University of Duke; Estados UnidosFil: Alkaade, Samer. St. Louis University. School of Medicine; Estados UnidosFil: Cote, Gregory. Indiana University; Estados UnidosFil: Gardner, Timothy B.. Dartmouth-Hitchcock Medical Center; Estados UnidosFil: Amann, Stephen T.. North Mississippi Medical Center; Estados UnidosFil: Slivka, Adam. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: Sandhu, Bimaljit. Virginia Commonwealth University Medical Center; Estados UnidosFil: Aloe, Amy. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: Kienholz, Michelle L.. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: Yadav, Dhiraj. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: Barmada, M. Michael. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: Bahar, Ivet. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: Lee, Min Goo. Yonsei University College of Medicine; Corea del SurFil: Whitcomb, David C.. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: North American Pancreatitis Study Group. No especifica

The Sloan Digital Sky Survey Quasar Lens Search. II. Statistical lens sample from the third data release

We report the first results of our systematic search for strongly lensed quasars using the spectroscopically confirmed quasars in the Sloan Digital Sky Survey (SDSS). Among 46,420 quasars from the SDSS Data Release 3 (~4188 deg^2), we select a subsample of 22,683 quasars that are located at redshifts between 0.6 and 2.2 and are brighter than the Galactic extinction-corrected i-band magnitude of 19.1. We identify 220 lens candidates from the quasar subsample, for which we conduct extensive and systematic follow-up observations in optical and near-infrared wavebands, in order to construct a complete lensed quasar sample at image separations between 1" and 20" and flux ratios of faint to bright lensed images larger than 10^(−0.5). We construct a statistical sample of 11 lensed quasars. Ten of these are galaxy-scale lenses with small image separations (~ 1"-2") and one is a large separation (15") system which is produced by a massive cluster of galaxies, representing the first statistical sample of lensed quasars including both galaxy- and cluster-scale lenses. The Data Release 3 spectroscopic quasars contain an additional 11 lensed quasars outside the statistical sample

The Metabochip, a Custom Genotyping Array for Genetic Studies of Metabolic, Cardiovascular, and Anthropometric Traits

PMCID: PMC3410907This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Symbiotic Nitrogen Fixation and the Challenges to Its Extension to Nonlegumes

Access to fixed or available forms of nitrogen limits the productivity of crop plants and thus food production. Nitrogenous fertilizer production currently represents a significant expense for the efficient growth of various crops in the developed world. There are significant potential gains to be had from reducing dependence on nitrogenous fertilizers in agriculture in the developed world and in developing countries, and there is significant interest in research on biological nitrogen fixation and prospects for increasing its importance in an agricultural setting. Biological nitrogen fixation is the conversion of atmospheric N2 to NH3, a form that can be used by plants. However, the process is restricted to bacteria and archaea and does not occur in eukaryotes. Symbiotic nitrogen fixation is part of a mutualistic relationship in which plants provide a niche and fixed carbon to bacteria in exchange for fixed nitrogen. This process is restricted mainly to legumes in agricultural systems, and there is considerable interest in exploring whether similar symbioses can be developed in nonlegumes, which produce the bulk of human food. We are at a juncture at which the fundamental understanding of biological nitrogen fixation has matured to a level that we can think about engineering symbiotic relationships using synthetic biology approaches. This minireview highlights the fundamental advances in our understanding of biological nitrogen fixation in the context of a blueprint for expanding symbiotic nitrogen fixation to a greater diversity of crop plants through synthetic biology.Biotechnology and Biological Sciences Research Council (Great Britain) (Grants BB/L011484/1 and BB/L011476/1)National Science Foundation (U.S.) (Grant 1331098

Mismatch Repair Genes Mlh1 and Mlh3 Modify CAG Instability in Huntington's Disease Mice: Genome-Wide and Candidate Approaches

The Huntington's disease gene (HTT) CAG repeat mutation undergoes somatic expansion that correlates with pathogenesis. Modifiers of somatic expansion may therefore provide routes for therapies targeting the underlying mutation, an approach that is likely applicable to other trinucleotide repeat diseases. Huntington's disease HdhQ111 mice exhibit higher levels of somatic HTT CAG expansion on a C57BL/6 genetic background (B6.HdhQ111) than on a 129 background (129.HdhQ111). Linkage mapping in (B6x129).HdhQ111 F2 intercross animals identified a single quantitative trait locus underlying the strain-specific difference in expansion in the striatum, implicating mismatch repair (MMR) gene Mlh1 as the most likely candidate modifier. Crossing B6.HdhQ111 mice onto an Mlh1 null background demonstrated that Mlh1 is essential for somatic CAG expansions and that it is an enhancer of nuclear huntingtin accumulation in striatal neurons. HdhQ111 somatic expansion was also abolished in mice deficient in the Mlh3 gene, implicating MutLγ (MLH1–MLH3) complex as a key driver of somatic expansion. Strikingly, Mlh1 and Mlh3 genes encoding MMR effector proteins were as critical to somatic expansion as Msh2 and Msh3 genes encoding DNA mismatch recognition complex MutSβ (MSH2–MSH3). The Mlh1 locus is highly polymorphic between B6 and 129 strains. While we were unable to detect any difference in base-base mismatch or short slipped-repeat repair activity between B6 and 129 MLH1 variants, repair efficiency was MLH1 dose-dependent. MLH1 mRNA and protein levels were significantly decreased in 129 mice compared to B6 mice, consistent with a dose-sensitive MLH1-dependent DNA repair mechanism underlying the somatic expansion difference between these strains. Together, these data identify Mlh1 and Mlh3 as novel critical genetic modifiers of HTT CAG instability, point to Mlh1 genetic variation as the likely source of the instability difference in B6 and 129 strains and suggest that MLH1 protein levels play an important role in driving of the efficiency of somatic expansions