76 research outputs found
MOST detects variability on tau Bootis possibly induced by its planetary companion
(abridged) There is considerable interest in the possible interaction between
parent stars and giant planetary companions in 51 Peg-type systems. We
demonstrate from MOST satellite photometry and Ca II K line emission that there
has been a persistent, variable region on the surface of tau Boo A which
tracked its giant planetary companion for some 440 planetary revolutions and
lies ~68deg (phi=0.8) in advance of the sub-planetary point. The light curves
are folded on a range of periods centered on the planetary orbital period and
phase dependent variability is quantified by Fourier methods and by the mean
absolute deviation (MAD) of the folded data for both the photometry and the Ca
II K line reversals. The region varies in brightness on the time scale of a
rotation by ~1 mmag. In 2004 it resembled a dark spot of variable depth, while
in 2005 it varied between bright and dark. Over the 123 planetary orbits
spanned by the photometry the variable region detected in 2004 and in 2005 are
synchronised to the planetary orbital period within 0.0015 d. The Ca II K line
in 2001, 2002 and 2003 also shows enhanced K-line variability centered on
phi=0.8, extending coverage to some 440 planetary revolutions. The apparently
constant rotation period of the variable region and its rapid variation make an
explanation in terms of conventional star spots unlikely. The lack of
complementary variability at phi=0.3 and the detection of the variable region
so far in advance of the sub-planetary point excludes tidal excitation, but the
combined photometric and Ca II K line reversal results make a good case for an
active region induced magnetically on the surface of tau Boo A by its planetary
companion.Comment: 7 pages, 7 figures; accepted for publication in A&
The First High-Precision Radial Velocity Search for Extra-Solar Planets
In the late 1970s and early 1980s, the introduction of solid-state,
signal-generating detectors and absorption cells to impose wavelength fiducials
directly on the starlight, the errors in stellar radial velocity (RV)
measurements were reduced to the point where Doppler searches for planets
became feasible. In 1980 we began to use a hydrogen fluoride gas cell with the
CFHT coud\'{e} spectrograph and, for 12 years, monitored RVs of some 29
solar-type stars. Since extra-solar planets were expected to resemble Jupiter
in both mass and orbit, we were awarded only three or four two-night observing
runs each year. In 1988 we highlighted a potential planetary companion to
Cep (K1 IV), in 1993 one to Gem (K0 III), and another to
Eri (K2 V) in 1992. The putative planets all resembled Jovian
systems with periods and masses of 2.5 yr and 1.4 , 1.6 yr and 2.6
, and 6.9 yr and 0.9 , respectively. All three were subsequently
confirmed from more extensive data by the Texas group led by Cochran and Hatzes
who derived the currently accepted orbital elements. None of the systems is
simple and some still question Eri b.Comment: 23 pages, 7 figure
The distribution of exoplanet masses
The present study derives the distribution of secondary masses M2 for the 67
exoplanets and very low-mass brown dwarf companions of solar-type stars, known
as of April 4, 2001. This distribution is related to the distribution of M2 sin
i through an integral equation of Abel's type. Although a formal solution
exists for this equation, it is known to be ill-behaved, and thus very
sensitive to the statistical noise present in the input M2 sin i distribution.
To overcome that difficulty, we present two robust, independent approaches: (i)
the formal solution of the integral equation is numerically computed after
performing an optimal smoothing of the input distribution, (ii) the
Lucy-Richardson algorithm is used to invert the integral equation. Both
approaches give consistent results. The resulting statistical distribution of
exoplanet true masses reveals that there is no reason to ascribe the transition
between giant planets and brown dwarfs to the threshold mass for deuterium
ignition (about 13 MJ). The M2 distribution shows instead that all the objects
have M2 < 10 MJ, except the heavier candidates which cluster around 15 MJ.Comment: Accepted by Astronomy & Astrophysics (7 pages, 4 figures
Protocol for a systematic review and thematic synthesis of patient experiences of central venous access devices in anti-cancer treatment
Background:
Three types of central venous access devices (CVADs)—peripherally inserted central catheters (PICCs), skin-tunnelled central catheters (Hickman-type devices), and implantable chest wall Ports (Ports)—are routinely used in the intravenous administration of anti-cancer treatment. These devices avoid the need for peripheral cannulation and allow for home delivery of treatment. Assessments of these devices have tended to focus on medical and economic factors, but there is increased interest in the importance of patient experiences and perspectives in this area. The aim of this systematic review is to synthesise existing research regarding patient experiences of these CVADs to help clinicians guide, prepare, and support patients receiving CVADs for the administration of anti-cancer treatment.
Method:
A systematic search of MEDLINE, Embase, and CINAHL research databases will be carried out along with a supplementary reference list search. This review will include quantitative, qualitative, and mixed methods studies published in peer-review journals, reporting some aspect(s) of patient experiences or perspectives regarding the use of PICC, Hickman, or Port CVADs for the administration of anti-cancer drugs. The methodological quality and risk of bias of included papers will be assessed using the Mixed Methods Appraisal Tool (MMAT). Relevant outcome data will be extracted from included studies and analysed using a thematic synthesis approach.
Discussion:
The results section of the review will comprise thematic synthesis of quantitative studies, thematic synthesis of qualitative studies, and the aggregation of the two. Results will aim to offer an account of current understandings of patient experiences and perspective regarding PICC, Hickman-type, and Port devices in the context of anti-cancer treatment. Confidence in cumulative evidence will be assessed using the Confidence in the Evidence from Reviews of Qualitative research (CERQual) approach
Nanoliter Reactors Improve Multiple Displacement Amplification of Genomes from Single Cells
Since only a small fraction of environmental bacteria are amenable to laboratory culture, there is great interest in genomic sequencing directly from single cells. Sufficient DNA for sequencing can be obtained from one cell by the Multiple Displacement Amplification (MDA) method, thereby eliminating the need to develop culture methods. Here we used a microfluidic device to isolate individual Escherichia coli and amplify genomic DNA by MDA in 60-nl reactions. Our results confirm a report that reduced MDA reaction volume lowers nonspecific synthesis that can result from contaminant DNA templates and unfavourable interaction between primers. The quality of the genome amplification was assessed by qPCR and compared favourably to single-cell amplifications performed in standard 50-μl volumes. Amplification bias was greatly reduced in nanoliter volumes, thereby providing a more even representation of all sequences. Single-cell amplicons from both microliter and nanoliter volumes provided high-quality sequence data by high-throughput pyrosequencing, thereby demonstrating a straightforward route to sequencing genomes from single cells
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Targeted DNA Demethylation and Endogenous Gene Activation Using Programmable TALE-TET1 Fusions
Gene-specific ACMG/AMP classification criteria for germline APC variants: recommendations from the ClinGen InSIGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel
Purpose
The Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel (VCEP) was established by the International Society for Gastrointestinal Hereditary Tumours and the Clinical Genome Resource, who set out to develop recommendations for the interpretation of germline APC variants underlying Familial Adenomatous Polyposis, the most frequent hereditary polyposis syndrome.
Methods
Through a rigorous process of database analysis, literature review, and expert elicitation, the APC VCEP derived gene-specific modifications to the ACMG/AMP (American College of Medical Genetics and Genomics and Association for Molecular Pathology) variant classification guidelines and validated such criteria through the pilot classification of 58 variants.
Results
The APC-specific criteria represented gene- and disease-informed specifications, including a quantitative approach to allele frequency thresholds, a stepwise decision tool for truncating variants, and semiquantitative evaluations of experimental and clinical data. Using the APC-specific criteria, 47% (27/58) of pilot variants were reclassified including 14 previous variants of uncertain significance (VUS).
Conclusion
The APC-specific ACMG/AMP criteria preserved the classification of well-characterized variants on ClinVar while substantially reducing the number of VUS by 56% (14/25). Moving forward, the APC VCEP will continue to interpret prioritized lists of VUS, the results of which will represent the most authoritative variant classification for widespread clinical use
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Warm spring reduced carbon cycle impact of the 2012 US summer drought
The global terrestrial carbon sink offsets one-third of the world’s fossil fuel emissions, but the strength of this sink is highly sensitive to large-scale extreme events. In 2012, the contiguous United States experienced exceptionally warm temperatures and the most severe drought since the Dust Bowl era of the 1930s, resulting in substantial economic damage. It is crucial to understand the dynamics of such events because warmer temperatures and a higher prevalence of drought are projected in a changing climate. Here, we combine an extensive network of direct ecosystem flux measurements with satellite remote sensing and atmospheric inverse modeling to quantify the impact of the warmer spring and summer drought on biosphere-atmosphere carbon and water exchange in 2012. We consistently find that earlier vegetation activity increased spring carbon uptake and compensated for the reduced uptake during the summer drought, which mitigated the impact on net annual carbon uptake. The early phenological development in the Eastern Temperate Forests played a major role for the continental-scale carbon balance in 2012. The warm spring also depleted soil water resources earlier, and thus exacerbated water limitations during summer. Our results show that the detrimental effects of severe summer drought on ecosystem carbon storage can be mitigated by warming-induced increases in spring carbon uptake. However, the results also suggest that the positive carbon cycle effect of warm spring enhances water limitations and can increase summer heating through biosphere–atmosphere feedbacks.Data deposition: The eddy-covariance data are available in the AmeriFlux data archive at the Carbon Dioxide Information Analysis Center at the Oak Ridge National Laboratory (cdiac.ornl.gov/ftp/ameriflux/data). This is the publisher’s final pdf. The article is published by National Academy of Sciences and can be found at: http://www.pnas.org/Keywords: ecosystem fluxes, eddy covariance, carbon uptake, biosphere, seasonal climate anomalies, atmosphere feedback
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Evidence-based recommendations for gene-specific ACMG/AMP variant classification from the ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel
The ENIGMA research consortium develops and applies methods to determine clinical significance of variants in hereditary breast and ovarian cancer genes. An ENIGMA BRCA1/2 classification sub-group, formed in 2015 as a ClinGen external expert panel, evolved into a ClinGen internal Variant Curation Expert Panel (VCEP) to align with Food and Drug Administration recognized processes for ClinVar contributions. The VCEP reviewed American College of Medical Genetics and Genomics/Association of Molecular Pathology (ACMG/AMP) classification criteria for relevance to interpreting BRCA1 and BRCA2 variants. Statistical methods were used to calibrate evidence strength for different data types. Pilot specifications were tested on 40 variants and documentation revised for clarity and ease of use. The original criterion descriptions for 13 evidence codes were considered non-applicable or overlapping with other criteria. Scenario of use was extended or re-purposed for eight codes. Extensive analysis and/or data review informed specification descriptions and weights for all codes. Specifications were applied to pilot variants with pre-existing ClinVar classification as follows: 13 uncertain significance or conflicting, 14 pathogenic and/or likely pathogenic, and 13 benign and/or likely benign. Review resolved classification for 11/13 uncertain significance or conflicting variants and retained or improved confidence in classification for the remaining variants. Alignment of pre-existing ENIGMA research classification processes with ACMG/AMP classification guidelines highlighted several gaps in the research processes and the baseline ACMG/AMP criteria. Calibration of evidence strength was key to justify utility and strength of different data types for gene-specific application. The gene-specific criteria demonstrated value for improving ACMG/AMP-aligned classification of BRCA1 and BRCA2 variants
ENIGMA CHEK2gether Project: A Comprehensive Study Identifies Functionally Impaired CHEK2 Germline Missense Variants Associated with Increased Breast Cancer Risk
PURPOSE: Germline pathogenic variants in CHEK2 confer moderately elevated breast cancer risk (odds ratio, OR ∼ 2.5), qualifying carriers for enhanced breast cancer screening. Besides pathogenic variants, dozens of missense CHEK2 variants of uncertain significance (VUS) have been identified, hampering the clinical utility of germline genetic testing (GGT).
EXPERIMENTAL DESIGN: We collected 460 CHEK2 missense VUS identified by the ENIGMA consortium in 15 countries. Their functional characterization was performed using CHEK2-complementation assays quantifying KAP1 phosphorylation and CHK2 autophosphorylation in human RPE1-CHEK2-knockout cells. Concordant results in both functional assays were used to categorize CHEK2 VUS from 12 ENIGMA case-control datasets, including 73,048 female patients with breast cancer and 88,658 ethnicity-matched controls.
RESULTS: A total of 430/460 VUS were successfully analyzed, of which 340 (79.1%) were concordant in both functional assays and categorized as functionally impaired (N = 102), functionally intermediate (N = 12), or functionally wild-type (WT)-like (N = 226). We then examined their association with breast cancer risk in the case-control analysis. The OR and 95% CI (confidence intervals) for carriers of functionally impaired, intermediate, and WT-like variants were 2.83 (95% CI, 2.35-3.41), 1.57 (95% CI, 1.41-1.75), and 1.19 (95% CI, 1.08-1.31), respectively. The meta-analysis of population-specific datasets showed similar results.
CONCLUSIONS: We determined the functional consequences for the majority of CHEK2 missense VUS found in patients with breast cancer (3,660/4,436; 82.5%). Carriers of functionally impaired missense variants accounted for 0.5% of patients with breast cancer and were associated with a moderate risk similar to that of truncating CHEK2 variants. In contrast, 2.2% of all patients with breast cancer carried functionally wild-type/intermediate missense variants with no clinically relevant breast cancer risk in heterozygous carriers
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