4,122 research outputs found
Consanguinity and rare mutations outside of MCCC genes underlie nonspecific phenotypes of MCCD.
Purpose3-Methylcrotonyl-CoA carboxylase deficiency (MCCD) is an autosomal recessive disorder of leucine catabolism that has a highly variable clinical phenotype, ranging from acute metabolic acidosis to nonspecific symptoms such as developmental delay, failure to thrive, hemiparesis, muscular hypotonia, and multiple sclerosis. Implementation of newborn screening for MCCD has resulted in broadening the range of phenotypic expression to include asymptomatic adults. The purpose of this study was to identify factors underlying the varying phenotypes of MCCD.MethodsWe performed exome sequencing on DNA from 33 cases and 108 healthy controls. We examined these data for associations between either MCC mutational status, genetic ancestry, or consanguinity and the absence or presence/specificity of clinical symptoms in MCCD cases.ResultsWe determined that individuals with nonspecific clinical phenotypes are highly inbred compared with cases that are asymptomatic and healthy controls. For 5 of these 10 individuals, we discovered a homozygous damaging mutation in a disease gene that is likely to underlie their nonspecific clinical phenotypes previously attributed to MCCD.ConclusionOur study shows that nonspecific phenotypes attributed to MCCD are associated with consanguinity and are likely not due to mutations in the MCC enzyme but result from rare homozygous mutations in other disease genes.Genet Med 17 8, 660-667
Accessibility and allocation of public parks and gardens in England and Wales: a COVID-19 social distancing perspective
Visiting parks and gardens supports physical and mental health. We quantified access to public parks and gardens in urban areas of England and Wales, and the potential for park crowdedness 22during periods of high use. We combined data from the Office for National Statistics and Ordnance Survey to quantify(i) the number of parks within 500and 1,000metresof urban postcodes (i.e., availability), (ii) the distance of postcodes to the nearest park (i.e., accessibility), and (iii) per-capita space in each park for people living within 1,000m.We26examined variability by city and share of flats. Around 25.4 million people(~87%) can access public parks or gardens within a ten-minute walk, while 3.8 million residents (~13%) live farther away; of these 21% are children and 13% are elderly. Areas with a higher share of flats on average are closer to a park but people living in these areas visit parks that are potentially overcrowded during periods of high use. Such disparity in urban areas of England and Wales becomes particularly evident during COVID-19 pandemic and lockdown when local parks, the only available out-of-home space option, hinder social distancing requirements. Cities aiming to facilitate social distancing while keeping public green spaces safe might require implementing measures such as dedicated park times for different age groups or entry allocation systems that, combined with smartphone apps or drones, can monitor and manage the total number of people using the park
Ambiguity, multiple streams, and EU policy
The multiple streams framework draws insight from interactions between agency and institutions to explore the impact of context, time, and meaning on policy change and to assess the institutional and issue complexities permeating the European Union (EU) policy process. The authors specify the assumptions and structure of the framework and review studies that have adapted it to reflect more fully EU decision-making processes. The nature of policy entrepreneurship and policy windows are assessed to identify areas of improvement. Finally, the authors sketch out a research agenda that refines the logic of political manipulation which permeates the lens and the institutional complexity which frames the EU policy process
Intermediate Element Abundances in Galaxy Clusters
We present the average abundances of the intermediate elements obtained by
performing a stacked analysis of all the galaxy clusters in the archive of the
X-ray telescope ASCA. We determine the abundances of Fe, Si, S, and Ni as a
function of cluster temperature (mass) from 1--10 keV, and place strong upper
limits on the abundances of Ca and Ar. In general, Si and Ni are overabundant
with respect to Fe, while Ar and Ca are very underabundant. The discrepancy
between the abundances of Si, S, Ar, and Ca indicate that the alpha-elements do
not behave homogeneously as a single group. We show that the abundances of the
most well-determined elements Fe, Si, and S in conjunction with recent
theoretical supernovae yields do not give a consistent solution for the
fraction of material produced by Type Ia and Type II supernovae at any
temperature or mass. The general trend is for higher temperature clusters to
have more of their metals produced in Type II supernovae than in Type Ias. The
inconsistency of our results with abundances in the Milky Way indicate that
spiral galaxies are not the dominant metal contributors to the intracluster
medium (ICM). The pattern of elemental abundances requires an additional source
of metals beyond standard SNIa and SNII enrichment. The properties of this new
source are well matched to those of Type II supernovae with very massive,
metal-poor progenitor stars. These results are consistent with a significant
fraction of the ICM metals produced by an early generation of population III
stars.Comment: 18 pages, 11 figures, 7 tables. Submitted to Ap
Demonstration of Cross-Reactive Antibodies to Smooth Gram-Negative Bacteria in Antiserum to Escherichia coli J5
We investigated the discrepancy between the broad cross-protection against gram-negative infections afforded by antiserum to Escherichia coli J5 and its apparently narrow cross-reactivity in vitro. Rabbits immunized with J5 bacteria produced antibodies to both the J5 lipopolysaccharide (LPS; titer by ELISA, 1:60,000) and LPS from the Re mutant of Salmonella minnesota (i.e., to the ketodeoxyoctonate [KDO] and lipid A determinants; titer, 1:3,200). In highly diluted antiserum, titers of antibody to J5 LPS were reduced by 28%-41% after adsorption with seven strains of smooth gram-negative bacteria and by only 4% after adsorption with the Re mutant. Smooth gram-negative bacteria adsorbed virtually all antibody to Re LPS. Therefore, rabbit antiserum to J5 contains type-specific antibodies to core determinants distal to KDO that can obscure highly cross-reactive antibodies to lipid A-KDO in vitro. Cross-reactive antibodies are demonstrable by adsorption with whole bacteria at limiting concentrations of antibod
GefĂ€Ămedizin heute: Die Berner Sicht
Zusammenfassung: Die moderne Behandlung von GefĂ€Ăpatienten stellt eine reizvolle und anspruchsvolle Aufgabe dar, welche aufgrund der KomplexitĂ€t und der Breite des Spektrums heute in interdisziplinĂ€ren GefĂ€Ăzentren durchgefĂŒhrt werden sollte. Die enge Zusammenarbeit zwischen GefĂ€Ăchirurgen und Angiologen hat an der UniversitĂ€t Bern eine lange Tradition. Der vorliegende Artikel legt die grundlegende Philosophie unserer gefĂ€Ăchirurgisch-angiologischen Freundschaft und Zusammenarbeit dar und schildert deren Umsetzung im klinischen Allta
A 23 GHz Survey of GRB Error Boxes
The Haystack 37-meter telescope was used in a pilot project in May 1995 to
observe GRB error boxes at 23~GHz. Seven BATSE error boxes and two IPN arcs
were scanned by driving the beam of the telescope rapidly across their area.
For the BATSE error boxes, the radio observations took place two to eighteen
days after the BATSE detection, and several boxes were observed more than once.
Total power data were recorded continuously as the telescope was driven at a
rate of 0.2~degrees/second, yielding Nyquist sampling of the beam with an
integration time of 50~milliseconds, corresponding to a theoretical rms
sensitivity of 0.5~Jy. Under conditions of good weather, this sensitivity was
achieved. In a preliminary analysis of the data we detect only two sources,
3C273 and 0552+398, both catalogued sources that are known to be variable at
23~GHz. Neither had a flux density that was unusally high or low at the time of
our observations.Comment: 5 pages, 1 postscript figure. To appear in Proceedings of the Third
Huntsville Symposium on Gamma-Ray Bursts (eds. C. Kouveliotou, M. S. Briggs,
and G. J. Fishman
General-Relativistic Thomas-Fermi model
A system of self-gravitating massive fermions is studied in the framework of
the general-relativistic Thomas-Fermi model. We study the properties of the
free energy functional and its relation to Einstein's field equations. A
self-gravitating fermion gas we then describe by a set of Thomas-Fermi type
self-consistency equations.Comment: 7 pages, LaTex, to appear in Gen. Rel. Gra
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