411 research outputs found
Hormonal circadian rhythms in patients with congenital adrenal hyperplasia: identifying optimal monitoring times and novel disease biomarkers
Objectives: The treatment goal in congenital adrenal hyperplasia (CAH) is to replace glucocorticoids while avoiding androgen excess and iatrogenic Cushing's syndrome. However, there is no consensus on how to monitor disease control. Our main objectives were to evaluate hormonal circadian rhythms and use these profiles to identify optimal monitoring times and novel disease biomarkers in CAH adults on intermediate- and long-acting glucocorticoids.
Design: This was an observational, cross-sectional study at the National Institutes of Health Clinical Center in 16 patients with classic CAH.
Methods: Twenty-four-hour serum sampling for ACTH, 17-hydroxyprogesterone (17OHP), androstenedione (A4), androsterone, DHEA, testosterone, progesterone and 24-h urinary pdiol and 5β-pdiol was carried out. Bayesian spectral analysis and cosinor analysis were performed to detect circadian rhythmicity. The number of hours to minimal (TminAC) and maximal (TmaxAC) adrenocortical hormone levels after dose administration was calculated.
Results: A significant rhythm was confirmed for ACTH (r2, 0.95; P<0.001), 17OHP (r2, 0.70; P=0.003), androstenedione (r2, 0.47; P=0.043), androsterone (r2, 0.80; P<0.001), testosterone (r2, 0.47; P=0.042) and progesterone (r2, 0.64; P=0.006). The mean (S.D.) TminAC and TmaxAC for 17OHP and A4 were: morning prednisone (4.3 (2.3) and 9.7 (3.5) h), evening prednisone (4.5 (2.0) and 10.3 (2.4) h), and daily dexamethasone (9.2 (3.5) and 16.4 (7.2) h). AUC0–24 h progesterone, androsterone and 24-h urine pdiol were significantly related to 17OHP.
Conclusion: In CAH patients, adrenal androgens exhibit circadian rhythms influenced by glucocorticoid replacement. Measurement of adrenocortical hormones and interpretation of results should take into account the type of glucocorticoid and time of dose administration. Progesterone and backdoor metabolites may provide alternative disease biomarkers
A bayesian multilevel modeling approach for data query in wireless sensor networks
In power-limited Wireless Sensor Network (WSN), it is important to reduce the communication load in order to achieve energy savings. This paper applies a novel statistic method to estimate the parameters based on the realtime data measured by local sensors. Instead of transmitting large real-time data, we proposed to transmit the small amount of dynamic parameters by exploiting both temporal and spatial correlation within and between sensor clusters. The temporal correlation is built on the level-1 Bayesian model at each sensor to predict local readings. Each local sensor transmits their local parameters learned from historical measurement data to their cluster heads which account for the spatial correlation and summarize the regional parameters based on level-2 Bayesian model. Finally, the cluster heads transmit the regional parameters to the sink node. By utilizing this statistical method, the sink node can predict the sensor measurements within a specified period without directly communicating with local sensors. We show that this approach can dramatically reduce the amount of communication load in data query applications and achieve significant energy savings
Salivary cortisone to estimate cortisol exposure and sampling frequency required based on serum cortisol measurements
Context: Population studies frequently measure cortisol as a marker of stress and excess cortisol is associated with increased mortality. Cortisol has a circadian rhythm and frequent blood sampling is impractical to assess exposure. We investigated measuring salivary cortisone and examined sampling frequency required to determine cortisol exposure. Methods: Serum and saliva with cortisol and cortisone measured by LC-MS/MS in independent cohorts. The relationship between serum cortisol and salivary cortisone was analysed in cohort 1 using a linear mixed effects model and resulting fixed effects component was applied to cohort 2. Saliva cannot easily be collected when sleeping so we determined minimum sampling required to estimate cortisol exposure (eAUC) using 24-hour cortisol profiles (AUC24) and calculated the relative error (RE - a measure similar to the coefficient of variation) for the eAUC. Results: >90% of variability in salivary cortisone could be accounted for by change in serum cortisol. A single serum cortisol measurement was a poor estimate of AUC24 especially in the morning or last thing at night (RE > 68%), however 3 equally spaced samples gave a median RE of 0% (Interquartile range (IQR) between -15.6% and 15.1%). In patients with adrenal incidentalomas the eAUC based on 3 serum cortisol samples showed a difference between those with autonomous cortisol secretion and those without (p=0.03). Interpretation: Accepting that most people sleep 7-8 hours, using approximately 8-hourly salivary cortisone measurements provides a non-invasive method of estimating 24-hour cortisol exposure for population studies
Measuring Black Hole Spin using X-ray Reflection Spectroscopy
I review the current status of X-ray reflection (a.k.a. broad iron line)
based black hole spin measurements. This is a powerful technique that allows us
to measure robust black hole spins across the mass range, from the stellar-mass
black holes in X-ray binaries to the supermassive black holes in active
galactic nuclei. After describing the basic assumptions of this approach, I lay
out the detailed methodology focusing on "best practices" that have been found
necessary to obtain robust results. Reflecting my own biases, this review is
slanted towards a discussion of supermassive black hole (SMBH) spin in active
galactic nuclei (AGN). Pulling together all of the available XMM-Newton and
Suzaku results from the literature that satisfy objective quality control
criteria, it is clear that a large fraction of SMBHs are rapidly-spinning,
although there are tentative hints of a more slowly spinning population at high
(M>5*10^7Msun) and low (M<2*10^6Msun) mass. I also engage in a brief review of
the spins of stellar-mass black holes in X-ray binaries. In general,
reflection-based and continuum-fitting based spin measures are in agreement,
although there remain two objects (GROJ1655-40 and 4U1543-475) for which that
is not true. I end this review by discussing the exciting frontier of
relativistic reverberation, particularly the discovery of broad iron line
reverberation in XMM-Newton data for the Seyfert galaxies NGC4151, NGC7314 and
MCG-5-23-16. As well as confirming the basic paradigm of relativistic disk
reflection, this detection of reverberation demonstrates that future large-area
X-ray observatories such as LOFT will make tremendous progress in studies of
strong gravity using relativistic reverberation in AGN.Comment: 19 pages. To appear in proceedings of the ISSI-Bern workshop on "The
Physics of Accretion onto Black Holes" (8-12 Oct 2012). Revised version adds
a missing source to Table 1 and Fig.6 (IRAS13224-3809) and corrects the
referencing of the discovery of soft lags in 1H0707-495 (which were in fact
first reported in Fabian et al. 2009
Atomic X-ray Spectroscopy of Accreting Black Holes
Current astrophysical research suggests that the most persistently luminous
objects in the Universe are powered by the flow of matter through accretion
disks onto black holes. Accretion disk systems are observed to emit copious
radiation across the electromagnetic spectrum, each energy band providing
access to rather distinct regimes of physical conditions and geometric scale.
X-ray emission probes the innermost regions of the accretion disk, where
relativistic effects prevail. While this has been known for decades, it also
has been acknowledged that inferring physical conditions in the relativistic
regime from the behavior of the X-ray continuum is problematic and not
satisfactorily constraining. With the discovery in the 1990s of iron X-ray
lines bearing signatures of relativistic distortion came the hope that such
emission would more firmly constrain models of disk accretion near black holes,
as well as provide observational criteria by which to test general relativity
in the strong field limit. Here we provide an introduction to this phenomenon.
While the presentation is intended to be primarily tutorial in nature, we aim
also to acquaint the reader with trends in current research. To achieve these
ends, we present the basic applications of general relativity that pertain to
X-ray spectroscopic observations of black hole accretion disk systems, focusing
on the Schwarzschild and Kerr solutions to the Einstein field equations. To
this we add treatments of the fundamental concepts associated with the
theoretical and modeling aspects of accretion disks, as well as relevant topics
from observational and theoretical X-ray spectroscopy.Comment: 63 pages, 21 figures, Einstein Centennial Review Article, Canadian
Journal of Physics, in pres
Confocal microscopy analysis reveals that only a small proportion of extracellular vesicles are successfully labelled with commonly utilised staining methods
Assessing genuine extracellular vesicle (EV) uptake is crucial for understanding the functional roles of EVs. This study measured the bona fide labelling of EVs utilising two commonly used fluorescent dyes, PKH26 and C5-maleimide-Alexa633. MCF7 EVs tagged with mEmerald-CD81 were isolated from conditioned media by size exclusion chromatography (SEC) and characterised using Nanoparticle Tracking Analysis (NTA), Transmission Electron Microscopy (TEM), MACsPlex immunocapture assay and immunoblots. These fluorescently tagged EVs were subsequently stained with C5-maleimide-Alexa633 or PKH26, according to published protocols. Colocalisation of dual-labelled EVs was assessed by confocal microscopy and quantified using the Rank-Weighted Colocalisation (RWC) algorithm. We observed strikingly poor colocalisation between mEmerald-CD81-tagged EVs and C5-Maleimide-Alexa633 (5.4% ± 1.8) or PKH26 (4.6% ± 1.6), that remained low even when serum was removed from preparations. Our data confirms previous work showing that some dyes form contaminating aggregates. Furthermore, uptake studies showed that maleimide and mEmerald-CD81-tagged EVs can be often located into non-overlapping subcellular locations. By using common methods to isolate and stain EVs we observed that most EVs remained unstained and most dye signal does not appear to be EV associated. Our work shows that there is an urgent need for optimisation and standardisation in how EV researchers use these tools to assess genuine EV signals
Black Hole Spin via Continuum Fitting and the Role of Spin in Powering Transient Jets
The spins of ten stellar black holes have been measured using the
continuum-fitting method. These black holes are located in two distinct classes
of X-ray binary systems, one that is persistently X-ray bright and another that
is transient. Both the persistent and transient black holes remain for long
periods in a state where their spectra are dominated by a thermal accretion
disk component. The spin of a black hole of known mass and distance can be
measured by fitting this thermal continuum spectrum to the thin-disk model of
Novikov and Thorne; the key fit parameter is the radius of the inner edge of
the black hole's accretion disk. Strong observational and theoretical evidence
links the inner-disk radius to the radius of the innermost stable circular
orbit, which is trivially related to the dimensionless spin parameter a_* of
the black hole (|a_*| < 1). The ten spins that have so far been measured by
this continuum-fitting method range widely from a_* \approx 0 to a_* > 0.95.
The robustness of the method is demonstrated by the dozens or hundreds of
independent and consistent measurements of spin that have been obtained for
several black holes, and through careful consideration of many sources of
systematic error. Among the results discussed is a dichotomy between the
transient and persistent black holes; the latter have higher spins and larger
masses. Also discussed is recently discovered evidence in the transient sources
for a correlation between the power of ballistic jets and black hole spin.Comment: 30 pages. Accepted for publication in Space Science Reviews. Also to
appear in hard cover in the Space Sciences Series of ISSI "The Physics of
Accretion onto Black Holes" (Springer Publisher). Changes to Sections 5.2,
6.1 and 7.4. Section 7.4 responds to Russell et al. 2013 (MNRAS, 431, 405)
who find no evidence for a correlation between the power of ballistic jets
and black hole spi
Self-regulation and self-control in exercise: The strength-energy model
Self-regulation is an important component of psychosocial theories of exercise behaviour and lack of self-regulatory skills are associated with low adherence to health-related exercise. This review presents a strength-energy model of self-control as an explanation of self-regulation in exercise contexts. The review will provide impetus for original research aimed at understanding exercise behaviour and help develop recommendations for exercise promotion. In the model, self-control is conceptualized as a global but limited resource. Engaging in actions requiring self-control depletes resources leading to self-regulatory failure. Self-control resource depletion is reduced through rest and frequent training on self-control. The expectation of the need to exert self-control in future leads to a conservation of self-control resources. Proposed mechanisms for self-control resource depletion include changes in physiological markers and blood glucose levels. Based on our review, we propose an integrated model of self-regulation incorporating hypotheses from the strength-energy model with those from traditional psychosocial models of exercise behaviour. Recommendations for future research include incorporating hypotheses from the strength-energy model into theories of self-presentation and interpersonal relations in exercise. Practical recommendations aimed at minimising self-control depletion in exercise include the provision of advice on nutrition and recovery, self-control training and motivational and implementation intention strategies
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