248 research outputs found
Identification of PKD1L1 Gene Variants in Children with the Biliary Atresia Splenic Malformation Syndrome
Biliary atresia (BA) is the most common cause of endâstage liver disease in children and the primary indication for pediatric liver transplantation, yet underlying etiologies remain unknown. Approximately 10% of infants affected by BA exhibit various laterality defects (heterotaxy) including splenic abnormalities and complex cardiac malformations â a distinctive subgroup commonly referred to as the biliary atresia splenic malformation (BASM) syndrome. We hypothesized that genetic factors linking laterality features with the etiopathogenesis of BA in BASM patients could be identified through whole exome sequencing (WES) of an affected cohort. DNA specimens from 67 BASM subjects, including 58 patientâparent trios, from the NIDDKâsupported Childhood Liver Disease Research Network (ChiLDReN) underwent WES. Candidate gene variants derived from a preâspecified set of 2,016 genes associated with ciliary dysgenesis and/or dysfunction or cholestasis were prioritized according to pathogenicity, population frequency, and mode of inheritance. Five BASM subjects harbored rare and potentially deleterious biâallelic variants in polycystin 1âlike 1, PKD1L1, a gene associated with ciliary calcium signaling and embryonic laterality determination in fish, mice and humans. Heterozygous PKD1L1 variants were found in 3 additional subjects. Immunohistochemical analysis of liver from the one BASM subject available revealed decreased PKD1L1 expression in bile duct epithelium when compared to normal livers and livers affected by other nonâcholestatic diseases. Conclusion WES identified biâallelic and heterozygous PKD1L1 variants of interest in 8 BASM subjects from the ChiLDReN dataset. The dual roles for PKD1L1 in laterality determination and ciliary function suggest that PKD1L1 is a new, biologically plausible, cholangiocyteâexpressed candidate gene for the BASM syndrome
Error-analysis and comparison to analytical models of numerical waveforms produced by the NRAR Collaboration
The Numerical-Relativity-Analytical-Relativity (NRAR) collaboration is a
joint effort between members of the numerical relativity, analytical relativity
and gravitational-wave data analysis communities. The goal of the NRAR
collaboration is to produce numerical-relativity simulations of compact
binaries and use them to develop accurate analytical templates for the
LIGO/Virgo Collaboration to use in detecting gravitational-wave signals and
extracting astrophysical information from them. We describe the results of the
first stage of the NRAR project, which focused on producing an initial set of
numerical waveforms from binary black holes with moderate mass ratios and
spins, as well as one non-spinning binary configuration which has a mass ratio
of 10. All of the numerical waveforms are analysed in a uniform and consistent
manner, with numerical errors evaluated using an analysis code created by
members of the NRAR collaboration. We compare previously-calibrated,
non-precessing analytical waveforms, notably the effective-one-body (EOB) and
phenomenological template families, to the newly-produced numerical waveforms.
We find that when the binary's total mass is ~100-200 solar masses, current EOB
and phenomenological models of spinning, non-precessing binary waveforms have
overlaps above 99% (for advanced LIGO) with all of the non-precessing-binary
numerical waveforms with mass ratios <= 4, when maximizing over binary
parameters. This implies that the loss of event rate due to modelling error is
below 3%. Moreover, the non-spinning EOB waveforms previously calibrated to
five non-spinning waveforms with mass ratio smaller than 6 have overlaps above
99.7% with the numerical waveform with a mass ratio of 10, without even
maximizing on the binary parameters.Comment: 51 pages, 10 figures; published versio
The Accuracy of the Electrocardiogram during Exercise Stress Test Based on Heart Size
BACKGROUND: Multiple studies have shown that the exercise electrocardiogram (ECG) is less accurate for predicting ischemia, especially in women, and there is additional evidence to suggest that heart size may affect its diagnostic accuracy. HYPOTHESIS: The purpose of this investigation was to assess the diagnostic accuracy of the exercise ECG based on heart size. METHODS: We evaluated 1,011 consecutive patients who were referred for an exercise nuclear stress test. Patients were divided into two groups: small heart size defined as left ventricular end diastolic volume (LVEDV) <65 mL (Group A) and normal heart size defined as LVEDV âĽ65 mL (Group B) and associations between ECG outcome (false positive vs. no false positive) and heart size (small vs. normal) were analyzed using the Chi square test for independence, with a Yates continuity correction. LVEDV calculations were performed via a computer-processing algorithm. SPECT myocardial perfusion imaging was used as the gold standard for the presence of coronary artery disease (CAD). RESULTS: Small heart size was found in 142 patients, 123 female and 19 male patients. There was a significant association between ECG outcome and heart size (Ď(2)â=â4.7, pâ=â0.03), where smaller hearts were associated with a significantly greater number of false positives. CONCLUSIONS: This study suggests a possible explanation for the poor diagnostic accuracy of exercise stress testing, especially in women, as the overwhelming majority of patients with small heart size were women
Pennsylvania Folklife Vol. 39, No. 4
⢠Our Church ⢠Pig Roast ⢠Wooden Jointed Dolls ⢠Coal Jewelry ⢠The Pennsylvania Long Rifle ⢠The Mennonites ⢠Festival Focus ⢠Festival Programs ⢠Blockprinting ⢠Dried Flowers, Wreaths and Baskets ⢠Broom Making ⢠Wood-Turning ⢠Moravian and German Stars ⢠A Plain Costume Primer ⢠Farewell to the Folk Festival Magazinehttps://digitalcommons.ursinus.edu/pafolklifemag/1128/thumbnail.jp
TIC 168789840: A Sextuply-Eclipsing Sextuple Star System
We report the discovery of a sextuply-eclipsing sextuple star system from
TESS data, TIC 168789840, also known as TYC 7037-89-1, the first known sextuple
system consisting of three eclipsing binaries. The target was observed in
Sectors 4 and 5 during Cycle 1, with lightcurves extracted from TESS Full Frame
Image data. It was also previously observed by the WASP survey and ASAS-SN. The
system consists of three gravitationally-bound eclipsing binaries in a
hierarchical structure of an inner quadruple system with an outer binary
subsystem. Follow-up observations from several different observatories were
conducted as a means of determining additional parameters. The system was
resolved by speckle interferometry with a 0."42 separation between the inner
quadruple and outer binary, inferring an estimated outer period of ~2 kyr. It
was determined that the fainter of the two resolved components is an 8.217 day
eclipsing binary, which orbits the inner quadruple that contains two eclipsing
binaries with periods of 1.570 days and 1.306 days. MCMC analysis of the
stellar parameters has shown that the three binaries of TIC 168789840 are
"triplets", as each binary is quite similar to the others in terms of mass,
radius, and Teff. As a consequence of its rare composition, structure, and
orientation, this object can provide important new insight into the formation,
dynamics, and evolution of multiple star systems. Future observations could
reveal if the intermediate and outer orbital planes are all aligned with the
planes of the three inner eclipsing binaries
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