234 research outputs found
Trends in the Measurement of Health Utilities in Published Cost-Utility Analyses
Objective:â The Panel on Cost-Effectiveness in Health and Medicine recommended the compilation of a catalog of health state utility weights for use in cost-utility analyses (CUAs), and has given methodological recommendations. This study presents an update, through 2001, to our current registry of utility weights (available at http://www.tufts-nemc.org/cearegistry ; previously at http://www.hsph.harvard.edu/cearegistry ), and documents recent changes in methods used for utility weight elicitation. Methods:â We searched the English-language medical literature for original CUAs reporting outcomes as cost per quality-adjusted life-year (QALY). Two trained readers independently audited each article, abstracting data on the health state descriptions, corresponding utility weights, methods of elicitation, and sources of the estimates. The utility elicitation methods from 1998 to 2001 were compared with the methods used to obtain utilities before 1998. Results:â We identified 306 CUAs published after 1998, reporting 1210 separate health-related utility estimates, bringing the total in our catalog to 2159 weights. Most frequently, health states pertained to the circulatory system and oncology. Methods varied substantially: 36% of authors used direct elicitation (standard gamble, time trade-off or rating scale), 23% used generic health status instruments (EQ-5D, Health Utilities Index, etc.), and 25% estimated weights based on clinical judgment. Community preferences were used in 27% of the values. Compared with pre-1998, utilities published from 1998 to 2001 were more likely to be elicited using a generic instrument, more likely elicited from community samples, and less likely derived from expert opinion, with no formally employed methodology. Conclusions:â Increasingly, analysts conducting CUAs are using generic, preference-weighted instruments, and relying on community-based preferences. Our catalog of utility weights provides a useful reference tool for producers and consumers of CUAs, but also highlights the continued need for improvement in methods and transparency.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72131/1/j.1524-4733.2006.00116.x.pd
Parametric study of EEG sensitivity to phase noise during face processing
<b>Background: </b>
The present paper examines the visual processing speed of complex objects, here faces, by mapping the relationship between object physical properties and single-trial brain responses. Measuring visual processing speed is challenging because uncontrolled physical differences that co-vary with object categories might affect brain measurements, thus biasing our speed estimates. Recently, we demonstrated that early event-related potential (ERP) differences between faces and objects are preserved even when images differ only in phase information, and amplitude spectra are equated across image categories. Here, we use a parametric design to study how early ERP to faces are shaped by phase information. Subjects performed a two-alternative force choice discrimination between two faces (Experiment 1) or textures (two control experiments). All stimuli had the same amplitude spectrum and were presented at 11 phase noise levels, varying from 0% to 100% in 10% increments, using a linear phase interpolation technique. Single-trial ERP data from each subject were analysed using a multiple linear regression model.
<b>Results: </b>
Our results show that sensitivity to phase noise in faces emerges progressively in a short time window between the P1 and the N170 ERP visual components. The sensitivity to phase noise starts at about 120â130 ms after stimulus onset and continues for another 25â40 ms. This result was robust both within and across subjects. A control experiment using pink noise textures, which had the same second-order statistics as the faces used in Experiment 1, demonstrated that the sensitivity to phase noise observed for faces cannot be explained by the presence of global image structure alone. A second control experiment used wavelet textures that were matched to the face stimuli in terms of second- and higher-order image statistics. Results from this experiment suggest that higher-order statistics of faces are necessary but not sufficient to obtain the sensitivity to phase noise function observed in response to faces.
<b>Conclusion: </b>
Our results constitute the first quantitative assessment of the time course of phase information processing by the human visual brain. We interpret our results in a framework that focuses on image statistics and single-trial analyses
Age-related delay in information accrual for faces: Evidence from a parametric, single-trial EEG approach
Background: In this study, we quantified age-related changes in the time-course of face processing
by means of an innovative single-trial ERP approach. Unlike analyses used in previous studies, our
approach does not rely on peak measurements and can provide a more sensitive measure of
processing delays. Young and old adults (mean ages 22 and 70 years) performed a non-speeded
discrimination task between two faces. The phase spectrum of these faces was manipulated
parametrically to create pictures that ranged between pure noise (0% phase information) and the
undistorted signal (100% phase information), with five intermediate steps.
Results: Behavioural 75% correct thresholds were on average lower, and maximum accuracy was
higher, in younger than older observers. ERPs from each subject were entered into a single-trial
general linear regression model to identify variations in neural activity statistically associated with
changes in image structure. The earliest age-related ERP differences occurred in the time window
of the N170. Older observers had a significantly stronger N170 in response to noise, but this age
difference decreased with increasing phase information. Overall, manipulating image phase
information had a greater effect on ERPs from younger observers, which was quantified using a
hierarchical modelling approach. Importantly, visual activity was modulated by the same stimulus
parameters in younger and older subjects. The fit of the model, indexed by R2, was computed at
multiple post-stimulus time points. The time-course of the R2 function showed a significantly slower
processing in older observers starting around 120 ms after stimulus onset. This age-related delay
increased over time to reach a maximum around 190 ms, at which latency younger observers had
around 50 ms time lead over older observers.
Conclusion: Using a component-free ERP analysis that provides a precise timing of the visual
system sensitivity to image structure, the current study demonstrates that older observers
accumulate face information more slowly than younger subjects. Additionally, the N170 appears to
be less face-sensitive in older observers
Aptamer-based multiplexed proteomic technology for biomarker discovery
Interrogation of the human proteome in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology. We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 [mu]L of serum or plasma). Our current assay allows us to measure ~800 proteins with very low limits of detection (1 pM average), 7 logs of overall dynamic range, and 5% average coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding DNA aptamer concentration signature, which is then quantified with a DNA microarray. In essence, our assay takes advantage of the dual nature of aptamers as both folded binding entities with defined shapes and unique sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to discover unique protein signatures characteristic of various disease states. More generally, we describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine
The Pierre Auger Observatory III: Other Astrophysical Observations
Astrophysical observations of ultra-high-energy cosmic rays with the Pierre
Auger ObservatoryComment: Contributions to the 32nd International Cosmic Ray Conference,
Beijing, China, August 201
Anisotropy and chemical composition of ultra-high energy cosmic rays using arrival directions measured by the Pierre Auger Observatory
The Pierre Auger Collaboration has reported evidence for anisotropy in the
distribution of arrival directions of the cosmic rays with energies
eV. These show a correlation with the distribution
of nearby extragalactic objects, including an apparent excess around the
direction of Centaurus A. If the particles responsible for these excesses at
are heavy nuclei with charge , the proton component of the
sources should lead to excesses in the same regions at energies . We here
report the lack of anisotropies in these directions at energies above
(for illustrative values of ). If the anisotropies
above are due to nuclei with charge , and under reasonable
assumptions about the acceleration process, these observations imply stringent
constraints on the allowed proton fraction at the lower energies
The Fluorescence Detector of the Pierre Auger Observatory
The Pierre Auger Observatory is a hybrid detector for ultra-high energy
cosmic rays. It combines a surface array to measure secondary particles at
ground level together with a fluorescence detector to measure the development
of air showers in the atmosphere above the array. The fluorescence detector
comprises 24 large telescopes specialized for measuring the nitrogen
fluorescence caused by charged particles of cosmic ray air showers. In this
paper we describe the components of the fluorescence detector including its
optical system, the design of the camera, the electronics, and the systems for
relative and absolute calibration. We also discuss the operation and the
monitoring of the detector. Finally, we evaluate the detector performance and
precision of shower reconstructions.Comment: 53 pages. Submitted to Nuclear Instruments and Methods in Physics
Research Section
Update on the correlation of the highest energy cosmic rays with nearby extragalactic matter
Data collected by the Pierre Auger Observatory through 31 August 2007 showed
evidence for anisotropy in the arrival directions of cosmic rays above the
Greisen-Zatsepin-Kuz'min energy threshold, \nobreak{eV}. The
anisotropy was measured by the fraction of arrival directions that are less
than from the position of an active galactic nucleus within 75 Mpc
(using the V\'eron-Cetty and V\'eron catalog). An updated
measurement of this fraction is reported here using the arrival directions of
cosmic rays recorded above the same energy threshold through 31 December 2009.
The number of arrival directions has increased from 27 to 69, allowing a more
precise measurement. The correlating fraction is , compared
with expected for isotropic cosmic rays. This is down from the early
estimate of . The enlarged set of arrival directions is
examined also in relation to other populations of nearby extragalactic objects:
galaxies in the 2 Microns All Sky Survey and active galactic nuclei detected in
hard X-rays by the Swift Burst Alert Telescope. A celestial region around the
position of the radiogalaxy Cen A has the largest excess of arrival directions
relative to isotropic expectations. The 2-point autocorrelation function is
shown for the enlarged set of arrival directions and compared to the isotropic
expectation.Comment: Accepted for publication in Astroparticle Physics on 31 August 201
Atmospheric effects on extensive air showers observed with the Surface Detector of the Pierre Auger Observatory
Atmospheric parameters, such as pressure (P), temperature (T) and density,
affect the development of extensive air showers initiated by energetic cosmic
rays. We have studied the impact of atmospheric variations on extensive air
showers by means of the surface detector of the Pierre Auger Observatory. The
rate of events shows a ~10% seasonal modulation and ~2% diurnal one. We find
that the observed behaviour is explained by a model including the effects
associated with the variations of pressure and density. The former affects the
longitudinal development of air showers while the latter influences the Moliere
radius and hence the lateral distribution of the shower particles. The model is
validated with full simulations of extensive air showers using atmospheric
profiles measured at the site of the Pierre Auger Observatory.Comment: 24 pages, 9 figures, accepted for publication in Astroparticle
Physic
Search for First Harmonic Modulation in the Right Ascension Distribution of Cosmic Rays Detected at the Pierre Auger Observatory
We present the results of searches for dipolar-type anisotropies in different
energy ranges above eV with the surface detector array of
the Pierre Auger Observatory, reporting on both the phase and the amplitude
measurements of the first harmonic modulation in the right-ascension
distribution. Upper limits on the amplitudes are obtained, which provide the
most stringent bounds at present, being below 2% at 99% for EeV
energies. We also compare our results to those of previous experiments as well
as with some theoretical expectations.Comment: 28 pages, 11 figure
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