Knowledge of anticoagulation status during dabigatran therapy may be desirable in certain clinical situations.
To determine the coagulation tests that are most useful for assessing dabigatran's ...anticoagulant effect.
Peak and trough blood samples from 35 patients taking dabigatran 150 mg twice daily, and one sample each from 30 non-anticoagulated individuals, were collected. Mass spectrometry and various coagulation assays were performed. 'Therapeutic range' was defined as the range of plasma dabigatran concentrations determined by mass spectrometry between the 2.5th and 97.5th percentiles of all values.
The therapeutic range was 27-411 ng mL(-1) . The prothrombin time (PT) and activated partial thromboplastin time (APTT), determined with multiple reagents, and activated clotting time (ACT) were insensitive to therapeutic dabigatran: 29%, 18% and 40% of samples had a normal PT, APTT, and ACT, respectively. However, normal PT, ACT and APTT ruled out dabigatran levels above the 75th percentile. The thrombin clotting time (TCT) correlated well and linearly with dabigatran levels below the 50th percentile, but was unmeasurable above it. The dilute thrombin time, ecarin clotting time and ecarin chromogenic assay showed linear correlations with dabigatran levels over a broad range, and identified therapeutic and supratherapeutic levels.
The prothrombin time, APTT and ACT are often normal in spite of therapeutic dabigatran plasma levels. The TCT is useful for detecting minimal dabigatran levels. The dilute thrombin time and chromogenic and clotting ecarin assays accurately identify therapeutic and supratherapeutic dabigatran levels. This trial is registered at www.clinicaltrials.gov (#NCT01588327).
We present a meta-analysis of star formation rate (SFR) indicators in the Galaxy And Mass Assembly (GAMA) survey, producing 12 different SFR metrics and determining the SFR-M... relation for each. We ...compare and contrast published methods to extract the SFR from each indicator, using a well-defined local sample of morphologically selected spiral galaxies, which excludes sources which potentially have large recent changes to their SFR. The different methods are found to yield SFR-M... relations with inconsistent slopes and normalizations, suggesting differences between calibration methods. The recovered SFR-M... relations also have a large range in scatter which, as SFRs of the targets may be considered constant over the different time-scales, suggests differences in the accuracy by which methods correct for attenuation in individual targets. We then recalibrate all SFR indicators to provide new, robust and consistent luminosity-to-SFR calibrations, finding that the most consistent slopes and normalizations of the SFR-M... relations are obtained when recalibrated using the radiation transfer method of Popescu et al. These new calibrations can be used to directly compare SFRs across different observations, epochs and galaxy populations. We then apply our calibrations to the GAMA II equatorial data set and explore the evolution of star formation in the local Universe. We determine the evolution of the normalization to the SFR-M... relation from 0 < z < 0.35 -- finding consistent trends with previous estimates at 0.3 < z < 1.2. We then provide the definitive z < 0.35 cosmic star formation history, SFR-M... relation and its evolution over the last 3 billion years. (ProQuest: ... denotes formulae/symbols omitted.)
We use a highly complete subset of the Galaxy And Mass Assembly II (GAMA-II) redshift sample to fully describe the stellar mass dependence of close pairs and mergers between 108 and 1012 M⊙. Using ...the analytic form of this fit we investigate the total stellar mass accreting on to more massive galaxies across all mass ratios. Depending on how conservatively we select our robust merging systems, the fraction of mass merging on to more massive companions is 2.0–5.6 per cent. Using the GAMA-II data we see no significant evidence for a change in the close pair fraction between redshift z = 0.05 and 0.2. However, we find a systematically higher fraction of galaxies in similar mass close pairs compared to published results over a similar redshift baseline. Using a compendium of data and the function γ
M
= A(1 + z)
m
to predict the major close pair fraction, we find fitting parameters of A = 0.021 ± 0.001 and m = 1.53 ± 0.08, which represents a higher low-redshift normalization and shallower power-law slope than recent literature values. We find that the relative importance of in situ star formation versus galaxy merging is inversely correlated, with star formation dominating the addition of stellar material below
$\mathcal {M}^*$
and merger accretion events dominating beyond
$\mathcal {M}^*$
. We find mergers have a measurable impact on the whole extent of the galaxy stellar mass function (GSMF), manifest as a deepening of the ‘dip’ in the GSMF over the next ∼Gyr and an increase in
$\mathcal {M}^*$
by as much as 0.01–0.05 dex.
A full appreciation of the role played by gas metallicity (Z), star formation rate (SFR) and stellar mass (M
*) is fundamental to understanding how galaxies form and evolve. The connections between ...these three parameters at different redshifts significantly affect galaxy evolution, and thus provide important constraints for galaxy evolution models. Using data from the Sloan Digital Sky Survey-Data Release 7 (SDSS-DR7) and the Galaxy and Mass Assembly (GAMA) surveys, we study the relationships and dependences between SFR, Z and M
*, as well as the Fundamental Plane for star-forming galaxies. We combine both surveys using volume-limited samples up to a redshift of z 0.36. The GAMA and SDSS surveys complement each other when analysing the relationships between SFR, M
* and Z. We present evidence for SFR and metallicity evolution to z ∼ 0.2. We study the dependences between SFR, M
*, Z and specific SFR (SSFR) on the M
*-Z, M
*-SFR, M
*-SSFR, Z-SFR and Z-SSFR relations, finding strong correlations between all. Based on those dependences, we propose a simple model that allows us to explain the different behaviour observed between low- and high-mass galaxies. Finally, our analysis allows us to confirm the existence of a Fundamental Plane, for which M
* = f(Z, SFR) in star-forming galaxies.
The Galaxy And Mass Assembly (GAMA) survey is one of the largest contemporary spectroscopic surveys of low redshift galaxies. Covering an area of ∼286 deg2 (split among five survey regions) down to a ...limiting magnitude of r < 19.8 mag, we have collected spectra and reliable redshifts for 238 000 objects using the AAOmega spectrograph on the Anglo-Australian Telescope. In addition, we have assembled imaging data from a number of independent surveys in order to generate photometry spanning the wavelength range 1 nm–1 m. Here, we report on the recently completed spectroscopic survey and present a series of diagnostics to assess its final state and the quality of the redshift data. We also describe a number of survey aspects and procedures, or updates thereof, including changes to the input catalogue, redshifting and re-redshifting, and the derivation of ultraviolet, optical and near-infrared photometry. Finally, we present the second public release of GAMA data. In this release, we provide input catalogue and targeting information, spectra, redshifts, ultraviolet, optical and near-infrared photometry, single-component Sérsic fits, stellar masses, Hα-derived star formation rates, environment information, and group properties for all galaxies with r < 19.0 mag in two of our survey regions, and for all galaxies with r < 19.4 mag in a third region (72 225 objects in total). The data base serving these data is available at http://www.gama-survey.org/.
To describe the phenotype of adult patients with variant and classic ataxia-telangiectasia (A-T), to raise the degree of clinical suspicion for the diagnosis variant A-T, and to assess a ...genotype-phenotype relationship for mutations in the ATM gene.
Retrospective analysis of the clinical characteristics and course of disease in 13 adult patients with variant A-T of 9 families and 6 unrelated adults with classic A-T and mutation analysis of the ATM gene and measurements of ATM protein expression and kinase activity.
Patients with variant A-T were only correctly diagnosed in adulthood. They often presented with extrapyramidal symptoms in childhood, whereas cerebellar ataxia appeared later. Four patients with variant A-T developed a malignancy. Patients with classic and variant A-T had elevated serum alpha-fetoprotein levels and chromosome 7/14 rearrangements. The mildest variant A-T phenotype was associated with missense mutations in the ATM gene that resulted in expression of some residual ATM protein with kinase activity. Two splicing mutations, c.331 + 5G>A and c.496 + 5G>A, caused a more severe variant A-T phenotype. The splicing mutation c.331 + 5G>A resulted in less ATM protein and kinase activity than the missense mutations.
Ataxia-telangiectasia (A-T) should be considered in patients with unexplained extrapyramidal symptoms. Early diagnosis is important given the increased risk of malignancies and the higher risk for side effects of subsequent cancer treatment. Measurement of serum alpha-fetoprotein and chromosomal instability precipitates the correct diagnosis. There is a clear genotype-phenotype relation for A-T, since the severity of the phenotype depends on the amount of residual kinase activity as determined by the genotype.
This study presents a systematic evaluation of the homogeneity of daily surface temperature observations for the Caribbean and neighboring regions on a monthly timescale. The reference series are ...developed using adjacent sea‐surface temperatures (SSTs). This novel approach is undertaken instead of the conventional use of highly correlated nearby stations, given the sparse station network for the Caribbean and adjacent Caribbean. The temperature data are from the regional climate change workshops held for the Caribbean, and Central and Northern South America in 2001 and 2004, respectively, complemented with data from the National Climatic Data Center (NCDC), the Caribbean Institute for Meteorology and Hydrology (CIMH), and the Caribbean meteorological stations. Correlations are used to explore the degree of association between the maximum and minimum temperatures and SSTs, and homogeneity tests are performed on their individual and difference series (e.g., maximum temperature minus SSTs). The results suggest SSTs as a viable option for use in evaluating homogeneity in the data sparse region of the Caribbean. Common statistically significant change points identified across at least three stations are investigated using composite analysis to determine links to large‐scale atmospheric circulation patterns. The study identifies two homogeneous periods from the analyses, i.e., 1970–1992 and 1984–1998, with the former used to reanalyze some extreme temperature trends for the Caribbean and adjacent Caribbean. The results are found to be consistent with those obtained from the 2001 Caribbean data workshop.
The goal of this study was to determine the predictive value of cardiac T2* magnetic resonance for heart failure and arrhythmia in thalassemia major.
We analyzed cardiac and liver T2* magnetic ...resonance and serum ferritin in 652 thalassemia major patients from 21 UK centers with 1442 magnetic resonance scans. The relative risk for heart failure with cardiac T2* values <10 ms (compared with >10 ms) was 160 (95% confidence interval, 39 to 653). Heart failure occurred in 47% of patients within 1 year of a cardiac T2* <6 ms with a relative risk of 270 (95% confidence interval, 64 to 1129). The area under the receiver-operating characteristic curve for predicting heart failure was significantly greater for cardiac T2* (0.948) than for liver T2* (0.589; P<0.001) or serum ferritin (0.629; P<0.001). Cardiac T2* was <10 ms in 98% of scans in patients who developed heart failure. The relative risk for arrhythmia with cardiac T2* values <20 ms (compared with >20 ms) was 4.6 (95% confidence interval, 2.66 to 7.95). Arrhythmia occurred in 14% of patients within 1 year of a cardiac T2* of <6 ms. The area under the receiver-operating characteristic curve for predicting arrhythmia was significantly greater for cardiac T2* (0.747) than for liver T2* (0.514; P<0.001) or serum ferritin (0.518; P<0.001). The cardiac T2* was <20 ms in 83% of scans in patients who developed arrhythmia.
Cardiac T2* magnetic resonance identifies patients at high risk of heart failure and arrhythmia from myocardial siderosis in thalassemia major and is superior to serum ferritin and liver iron. Using cardiac T2* for the early identification and treatment of patients at risk is a logical means of reducing the high burden of cardiac mortality in myocardial siderosis. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00520559.
Implementation of wildfire- and climate-adaptation strategies in seasonally dry forests of western North America is impeded by numerous constraints and uncertainties. After more than a century of ...resource and land use change, some question the need for proactive management, particularly given novel social, ecological, and climatic conditions. To address this question, we first provide a framework for assessing changes in landscape conditions and fire regimes. Using this framework, we then evaluate evidence of change in contemporary conditions relative to those maintained by active fire regimes, i.e., those uninterrupted by a century or more of human-induced fire exclusion. The cumulative results of more than a century of research document a persistent and substantial fire deficit and widespread alterations to ecological structures and functions. These changes are not necessarily apparent at all spatial scales or in all dimensions of fire regimes and forest and nonforest conditions. Nonetheless, loss of the once abundant influence of low- and moderate-severity fires suggests that even the least fire-prone ecosystems may be affected by alteration of the surrounding landscape and, consequently, ecosystem functions. Vegetation spatial patterns in fire-excluded forested landscapes no longer reflect the heterogeneity maintained by interacting fires of active fire regimes. Live and dead vegetation (surface and canopy fuels) is generally more abundant and continuous than before European colonization. As a result, current conditions are more vulnerable to the direct and indirect effects of seasonal and episodic increases in drought and fire, especially under a rapidly warming climate. Long-term fire exclusion and contemporaneous social-ecological influences continue to extensively modify seasonally dry forested landscapes. Management that realigns or adapts fire-excluded conditions to seasonal and episodic increases in drought and fire can moderate ecosystem transitions as forests and human communities adapt to changing climatic and disturbance regimes. As adaptation strategies are developed, evaluated, and implemented, objective scientific evaluation of ongoing research and monitoring can aid differentiation of warranted and unwarranted uncertainties.
Different brain regions can be grouped together, based on cross-sectional correlations among their cortical characteristics; this patterning has been used to make inferences about ageing processes. ...However, cross-sectional brain data conflate information on ageing with patterns that are present throughout life. We characterised brain cortical ageing across the eighth decade of life in a longitudinal ageing cohort, at ages ~73, ~76, and ~79 years, with a total of 1376 MRI scans. Volumetric changes among cortical regions of interest (ROIs) were more strongly correlated (average r = 0.805, SD = 0.252) than were cross-sectional volumes of the same ROIs (average r = 0.350, SD = 0.178). We identified a broad, cortex-wide, dimension of atrophy that explained 66% of the variance in longitudinal changes across the cortex. Our modelling also discovered more specific fronto-temporal and occipito-parietal dimensions that were orthogonal to the general factor and together explained an additional 20% of the variance. The general factor was associated with declines in general cognitive ability (r = 0.431, p < 0.001) and in the domains of visuospatial ability (r = 0.415, p = 0.002), processing speed (r = 0.383, p < 0.001) and memory (r = 0.372, p < 0.001). Individual differences in brain cortical atrophy with ageing are manifest across three broad dimensions of the cerebral cortex, the most general of which is linked with cognitive declines across domains. Longitudinal approaches are invaluable for distinguishing lifelong patterns of brain-behaviour associations from patterns that are specific to aging.
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