748 research outputs found
Cost effectiveness analysis of different approaches of screening for familial hypercholesterolaemia
Objectives To assess the cost effectiveness of
strategies to screen for and treat familial
hypercholesterolaemia.
Design Cost effectiveness analysis. A care pathway for
each patient was delineated and the associated
probabilities, benefits, and costs were calculated.
Participants Simulated population aged 16Â54 years
in England and Wales.
Interventions Identification and treatment of patients
with familial hypercholesterolaemia by universal
screening, opportunistic screening in primary care,
screening of people admitted to hospital with
premature myocardial infarction, or tracing family
members of affected patients.
Main outcome measure Cost effectiveness calculated
as cost per life year gained (extension of life
expectancy resulting from intervention) including
estimated costs of screening and treatment.
Results Tracing of family members was the most cost
effective strategy (£3097 (&5066, $4479) per life year
gained) as 2.6 individuals need to be screened to
identify one case at a cost of £133 per case detected. If
the genetic mutation was known within the family
then the cost per life year gained (£4914) was only
slightly increased by genetic confirmation of the
diagnosis. Universal population screening was least
cost effective (£13 029 per life year gained) as 1365
individuals need to be screened at a cost of £9754 per
case detected. For each strategy it was more cost
effective to screen younger people and women.
Targeted strategies were more expensive per person
screened, but the cost per case detected was lower.
Population screening of 16 year olds only was as cost
effective as family tracing (£2777 with a clinical
confirmation).
Conclusions Screening family members of people
with familial hypercholesterolaemia is the most cost
effective option for detecting cases across the whole
population
Revisiting soliton contributions to perturbative amplitudes
Open Access funded by SCOAP3. CP is
a Royal Society Research Fellow and partly supported by the U.S. Department of Energy
under grants DOE-SC0010008, DOE-ARRA-SC0003883 and DOE-DE-SC0007897. ABR
is supported by the Mitchell Family Foundation. We would like to thank the Mitchell
Institute at Texas A&M and the NHETC at Rutgers University respectively for hospitality
during the course of this work. We would also like to acknowledge the Aspen Center for
Physics and NSF grant 1066293 for a stimulating research environment
The Influence of Performance Level, Age and Gender on Pacing Strategy During a 100-km Ultramarathon
The aim of this study is to analyse the influence of performance level, age and gender on pacing during a 100-km ultramarathon. Results of a 100-km race incorporating the World Masters Championships were used to identify differences in relative speeds in each 10-km segment between participants finishing in the first, second, third and fourth quartiles of overall positions (Groups 1, 2, 3 and 4, respectively). Similar analyses were performed between the top and bottom 50% of finishers in each age category, as well as within male and female categories. Pacing varied between athletes achieving different absolute performance levels. Group 1 ran at significantly lower relative speeds than all other groups in the first three 10-km segments (all P < 0.01), and significantly higher relative speeds than Group 4 in the 6th and 10th (both P < 0.01), and Group 2 in the 8th (P = 0.04). Group 4 displayed significantly higher relative speeds than Group 2 and 3 in the first three segments (all P < 0.01). Overall strategies remained consistent across age categories, although a similar phenomenon was observed within each category whereby ‘top’ competitors displayed lower relative speeds than ‘bottom’ competitors in the early stages, but higher relative speeds in the later stages. Females showed lower relative starting speeds and higher finishing speeds than males. ‘Top’ and ‘bottom’ finishing males displayed differing strategies, but this was not the case within females. Although pacing remained consistent across age categories, it differed with level of performance within each, possibly suggesting strategies are anchored on direct competitors. Strategy differs between genders and differs depending on performance level achieved in males but not females
Asymmetric switching behavior in perpendicularly magnetized spin-valve nanopillars due to the polarizer dipole field
We report the free layer switching field distributions of spin-valve
nanopillars with perpendicular magnetization. While the distributions are
consistent with a thermal activation model, they show a strong asymmetry
between the parallel to antiparallel and the reverse transition, with energy
barriers more than 50% higher for the parallel to antiparallel transitions. The
inhomogeneous dipolar field from the polarizer is demonstrated to be at the
origin of this symmetry breaking. Interestingly, the symmetry is restored for
devices with a lithographically defined notch pair removed from the midpoint of
the pillar cross-section along the ellipse long axis. These results have
important implications for the thermal stability of perpendicular magnetized
MRAM bit cells.Comment: Submitted to Applied Physics Letters on November 4, 2011. Consists of
4 pages, 3 figure
Predicting Dementia in Cerebral Small Vessel Disease Using an Automatic Diffusion Tensor Image Segmentation Technique.
Background and Purpose- Cerebral small vessel disease (SVD) is the most common cause of vascular cognitive impairment, with a significant proportion of cases going on to develop dementia. We explore the extent to which diffusion tensor image segmentation technique (DSEG; which characterizes microstructural damage across the cerebrum) predicts both degree of cognitive decline and conversion to dementia, and hence may provide a useful prognostic procedure. Methods- Ninety-nine SVD patients (aged 43-89 years) underwent annual magnetic resonance imaging scanning (for 3 years) and cognitive assessment (for 5 years). DSEG-θ was used as a whole-cerebrum measure of SVD severity. Dementia diagnosis was based Diagnostic and Statistical Manual of Mental Disorders V criteria. Cox regression identified which DSEG measures and vascular risk factors were related to increased risk of dementia. Linear discriminant analysis was used to classify groups of stable versus subsequent dementia diagnosis individuals. Results- DSEG-θ was significantly related to decline in executive function and global cognition (P<0.001). Eighteen (18.2%) patients converted to dementia. Baseline DSEG-θ predicted dementia with a balanced classification rate=75.95% and area under the receiver operating characteristic curve=0.839. The best classification model included baseline DSEG-θ, change in DSEG-θ, age, sex, and premorbid intelligence quotient (balanced classification rate of 79.65%; area under the receiver operating characteristic curve=0.903). Conclusions- DSEG is a fully automatic technique that provides an accurate method for assessing brain microstructural damage in SVD from a single imaging modality (diffusion tensor imaging). DSEG-θ is an important tool in identifying SVD patients at increased risk of developing dementia and has potential as a clinical marker of SVD severity
Change in multimodal MRI markers predicts dementia risk in cerebral small vessel disease.
OBJECTIVE: To determine whether MRI markers, including diffusion tensor imaging (DTI), can predict cognitive decline and dementia in patients with cerebral small vessel disease (SVD). METHODS: In the prospective St George's Cognition and Neuroimaging in Stroke study, multimodal MRI was performed annually for 3 years and cognitive assessments annually for 5 years in a cohort of 99 patients with SVD, defined as symptomatic lacunar stroke and confluent white matter hyperintensities (WMH). Progression to dementia was determined in all patients. Progression of WMH, brain volume, lacunes, cerebral microbleeds, and a DTI measure (the normalized peak height of the mean diffusivity histogram distribution) as a marker of white matter microstructural damage were determined. RESULTS: Over 5 years of follow-up, 18 patients (18.2%) progressed to dementia. A significant change in all MRI markers, representing deterioration, was observed. The presence of new lacunes, and rate of increase in white matter microstructural damage on DTI, correlated with both decline in executive function and global functioning. Growth of WMH and deterioration of white matter microstructure on DTI predicted progression to dementia. A model including change in MRI variables together with their baseline values correctly classified progression to dementia with a C statistic of 0.85. CONCLUSIONS: This longitudinal prospective study provides evidence that change in MRI measures including DTI, over time durations during which cognitive change is not detectable, predicts cognitive decline and progression to dementia. It supports the use of MRI measures, including DTI, as useful surrogate biomarkers to monitor disease and assess therapeutic interventions
Progression of MRI markers in cerebral small vessel disease: sample size considerations for clinical trials.
Detecting treatment efficacy using cognitive change in trials of cerebral small vessel disease (SVD) has been challenging, making the use of surrogate markers such as magnetic resonance imaging (MRI) attractive. We determined the sensitivity of MRI to change in SVD and used this information to calculate sample size estimates for a clinical trial. Data from the prospective SCANS (St George's Cognition and Neuroimaging in Stroke) study of patients with symptomatic lacunar stroke and confluent leukoaraiosis was used (n=121). Ninety-nine subjects returned at one or more time points. Multimodal MRI and neuropsychologic testing was performed annually over 3 years. We evaluated the change in brain volume, T2 white matter hyperintensity (WMH) volume, lacunes, and white matter damage on diffusion tensor imaging (DTI). Over 3 years, change was detectable in all MRI markers but not in cognitive measures. WMH volume and DTI parameters were most sensitive to change and therefore had the smallest sample size estimates. MRI markers, particularly WMH volume and DTI parameters, are more sensitive to SVD progression over short time periods than cognition. These markers could significantly reduce the size of trials to screen treatments for efficacy in SVD, although further validation from longitudinal and intervention studies is required.Journal of Cerebral Blood Flow & Metabolism advance online publication, 3 June 2015; doi:10.1038/jcbfm.2015.113
Clues to the Metallicity Distribution in the Galactic Bulge: Abundances in OGLE-2007_BLG-349S
We present an abundance analysis based on high dispersion and high
signal-to-noise ratio Keck spectra of a very highly microlensed Galactic bulge
dwarf, OGLE-2007-BLG-349S, with Teff ~ 5400 K. The amplification at the time
the spectra were taken ranged from 350 to 450. This bulge star is highly
enhanced in metallicity with [Fe/H] = +0.51 \pm 0.09 dex. The abundance ratios
for the 28 species of 26 elements for which features could be detected in the
spectra are solar. In particular, there is no evidence for enhancement of any
of the alpha-elements including O and Mg. We conclude that the high [Fe/H] seen
in this star, when combined with the equally high [Fe/H] derived in previous
detailed abundance analysis of two other Galactic bulge dwarfs, both also
microlensed, implies that the median metallicity in the Galactic bulge is very
high. We thus infer that many previous estimates of the metallicity
distribution in the Galactic bulge have substantially underestimated the mean
Fe-metallicity there due to sample bias, and suggest a candidate mechanism for
such. If our conjecture proves valid, it may be necessary to update the
calibrations for the algorithms used by many groups to interpret spectra and
broad band photometry of the integrated light of very metal-rich old stellar
populations, including luminous elliptical galaxies.Comment: version accepted by the ApJ, minor changes from originl submission,
38 pages with 6 figures (2 in color
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