304 research outputs found
Regional White Matter Integrity Differentiates Between Vascular Dementia and Alzheimer Disease
BACKGROUND AND PURPOSE: Considerable clinical and radiological overlap between vascular dementia (VaD) and Alzheimer disease (AD) often makes the diagnosis difficult. Diffusion-tensor imaging studies showed that fractional anisotropy (FA) could be a useful marker for white matter changes. This study aimed to identify regional FA changes to identify a biomarker that could be used to differentiate VaD from AD. METHODS: T1-weighted and diffusion-tensor imaging scans were obtained in 13 VaD patients, 16 AD patients, and 22 healthy elderly controls. We used tract-based spatial statistics to study regional changes in fractional anisotropy in AD, VaD, and elderly controls. We then used probabilistic tractography to parcel the corpus callosum in 7 regions according to its connectivity with major cerebral cortices using diffusion-tensor imaging data set. We compared the volume and mean FA in each set of transcallosal fibers between groups using ANOVA and then applied a discriminant analysis based on FA and T2-weighted imaging measures. RESULTS: FA reduction in forceps minor was the most significant area of difference between AD and VaD. Segmentation of the corpus callosum using tractography and comparison of FA changes of each segment confirmed the FA changes in transcallosal prefrontal tracts of patients with VaD when compared to AD. The best discriminant model was the combination of transcallosal prefrontal FA and Fazekas score with 87.5% accuracy, 100% specificity, and 93% sensitivity (P<0.0001). CONCLUSIONS: Integrating mean FA in the forceps minor to the Fazekas score provides a useful quantitative marker for differentiating AD from VaD
Evaluating the impact of the community-based health planning and services initiative on uptake of skilled birth care in Ghana
Background: the Community-based Health Planning and Services (CHPS) initiative is a major government policy to improve maternal and child health and accelerate progress in the reduction of maternal mortality in Ghana. However, strategic intelligence on the impact of the initiative is lacking, given the persistent ?problems of patchy geographical access to care for rural women. This study investigates the impact of proximity to CHPS on facilitating uptake of skilled ?birth care in rural areas.Methods and findings: data from the ?2003 and 2008 Demographic and Health Survey, ? on 4,349 births from 463 rural communities were linked to georeferenced data on health facilities, CHPS and topographic data on national road-networks. Distance to nearest health facility and CHPS was computed using the closest facility functionality in ArcGIS 10.1. Multilevel logistic regression was used to examine the effect of proximity to health facilities and CHPS on use of skilled care at birth, adjusting for relevant predictors and clustering within ?communities.? The results show that a substantial proportion of births continue to occur in communities more than 8 km from both ?health facilities and CHPS. Increases in uptake of skilled birth care are more pronounced where both health ?facilities and CHPS compounds are within 8 km, but not in communities within 8 km of CHPS but lack access to health facilities. Where both health facilities and CHPS are within 8 km, the odds of skilled ?birth care is 16% higher than ?where there is only a health facility within 8km. Conclusion: where CHPS compounds are set up near health facilities, there is improved access to care, demonstrating the facilitatory role of CHPS in stimulating access to better care at birth, in areas where health facilities are accessible. <br/
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Compulsory licensing and access to drugs
Compulsory licensing allows the use of a patented invention without the owner's consent, with the aim of improving access to essential drugs. The pharmaceutical sector argues that, if broadly used, it can be detrimental to innovation. We model the interaction between a company in the North that holds the patent for a certain drug and a government in the South that needs to purchase it. We show that both access to drugs and pharmaceutical innovation depend largely on the Southern country's ability to manufacture a generic version. If the manufacturing cost is too high, compulsory licensing is not exercised. As the cost decreases, it becomes a credible threat forcing prices down, but reducing both access and innovation. When the cost is low enough, the South produces its own generic version and access reaches its highest value, despite a reduction in innovation. The global welfare analysis shows that the overall impact of compulsory licensing can be positive, even when accounting for its impact on innovation. We also consider the interaction between compulsory licensing and the strength of intellectual property rights, which can have global repercussions in other markets beyond the South
Metabolome-wide association study on ABCA7 indicates a role of ceramide metabolism in Alzheimer’s disease
Genome-wide association studies (GWASs) have identified genetic loci associated with the risk of Alzheimer’s disease (AD), but the molecular mechanisms by which they confer risk are largely unknown. We conducted a metabolome-wide association study (MWAS) of AD-associated loci from GWASs using untargeted metabolic profiling (metabolomics) by ultraperformance liquid chromatography–mass spectrometry (UPLC-MS). We identified an association of lactosylceramides (LacCer) with AD-related single-nucleotide polymorphisms (SNPs) in ABCA7 (P = 5.0 × 10−5 to 1.3 × 10−44). We showed that plasma LacCer concentrations are associated with cognitive performance and genetically modified levels of LacCer are associated with AD risk. We then showed that concentrations of sphingomyelins, ceramides, and hexosylceramides were altered in brain tissue from Abca7 knockout mice, compared with wild type (WT) (P = 0.049–1.4 × 10−5), but not in a mouse model of amyloidosis. Furthermore, activation of microglia increases intracellular concentrations of hexosylceramides in part through induction in the expression of sphingosine kinase, an enzyme with a high control coefficient for sphingolipid and ceramide synthesis. Our work suggests that the risk for AD arising from functional variations in ABCA7 is mediated at least in part through ceramides. Modulation of their metabolism or downstream signaling may offer new therapeutic opportunities for AD
A High Statistics Search for Ultra-High Energy Gamma-Ray Emission from Cygnus X-3 and Hercules X-1
We have carried out a high statistics (2 Billion events) search for
ultra-high energy gamma-ray emission from the X-ray binary sources Cygnus X-3
and Hercules X-1. Using data taken with the CASA-MIA detector over a five year
period (1990-1995), we find no evidence for steady emission from either source
at energies above 115 TeV. The derived upper limits on such emission are more
than two orders of magnitude lower than earlier claimed detections. We also
find no evidence for neutral particle or gamma-ray emission from either source
on time scales of one day and 0.5 hr. For Cygnus X-3, there is no evidence for
emission correlated with the 4.8 hr X-ray periodicity or with the occurrence of
large radio flares. Unless one postulates that these sources were very active
earlier and are now dormant, the limits presented here put into question the
earlier results, and highlight the difficulties that possible future
experiments will have in detecting gamma-ray signals at ultra-high energies.Comment: 26 LaTeX pages, 16 PostScript figures, uses psfig.sty to be published
in Physical Review
Centrality dependence of charged particle production at large transverse momentum in Pb-Pb collisions at TeV
The inclusive transverse momentum () distributions of primary
charged particles are measured in the pseudo-rapidity range as a
function of event centrality in Pb-Pb collisions at
TeV with ALICE at the LHC. The data are presented in the range
GeV/ for nine centrality intervals from 70-80% to 0-5%.
The Pb-Pb spectra are presented in terms of the nuclear modification factor
using a pp reference spectrum measured at the same collision
energy. We observe that the suppression of high- particles strongly
depends on event centrality. In central collisions (0-5%) the yield is most
suppressed with at -7 GeV/. Above
GeV/, there is a significant rise in the nuclear modification
factor, which reaches for GeV/. In
peripheral collisions (70-80%), the suppression is weaker with almost independently of . The measured nuclear
modification factors are compared to other measurements and model calculations.Comment: 17 pages, 4 captioned figures, 2 tables, authors from page 12,
published version, figures at
http://aliceinfo.cern.ch/ArtSubmission/node/284
Anisotropic flow of charged hadrons, pions and (anti-)protons measured at high transverse momentum in Pb-Pb collisions at TeV
The elliptic, , triangular, , and quadrangular, , azimuthal
anisotropic flow coefficients are measured for unidentified charged particles,
pions and (anti-)protons in Pb-Pb collisions at TeV
with the ALICE detector at the Large Hadron Collider. Results obtained with the
event plane and four-particle cumulant methods are reported for the
pseudo-rapidity range at different collision centralities and as a
function of transverse momentum, , out to GeV/.
The observed non-zero elliptic and triangular flow depends only weakly on
transverse momentum for GeV/. The small dependence
of the difference between elliptic flow results obtained from the event plane
and four-particle cumulant methods suggests a common origin of flow
fluctuations up to GeV/. The magnitude of the (anti-)proton
elliptic and triangular flow is larger than that of pions out to at least
GeV/ indicating that the particle type dependence persists out
to high .Comment: 16 pages, 5 captioned figures, authors from page 11, published
version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/186
Two-pion Bose-Einstein correlations in central Pb-Pb collisions at = 2.76 TeV
The first measurement of two-pion Bose-Einstein correlations in central Pb-Pb
collisions at TeV at the Large Hadron Collider is
presented. We observe a growing trend with energy now not only for the
longitudinal and the outward but also for the sideward pion source radius. The
pion homogeneity volume and the decoupling time are significantly larger than
those measured at RHIC.Comment: 17 pages, 5 captioned figures, 1 table, authors from page 12,
published version, figures at
http://aliceinfo.cern.ch/ArtSubmission/node/388
Suppression of charged particle production at large transverse momentum in central Pb-Pb collisions at TeV
Inclusive transverse momentum spectra of primary charged particles in Pb-Pb
collisions at = 2.76 TeV have been measured by the ALICE
Collaboration at the LHC. The data are presented for central and peripheral
collisions, corresponding to 0-5% and 70-80% of the hadronic Pb-Pb cross
section. The measured charged particle spectra in and GeV/ are compared to the expectation in pp collisions at the same
, scaled by the number of underlying nucleon-nucleon
collisions. The comparison is expressed in terms of the nuclear modification
factor . The result indicates only weak medium effects ( 0.7) in peripheral collisions. In central collisions,
reaches a minimum of about 0.14 at -7GeV/ and increases
significantly at larger . The measured suppression of high- particles is stronger than that observed at lower collision energies,
indicating that a very dense medium is formed in central Pb-Pb collisions at
the LHC.Comment: 15 pages, 5 captioned figures, 3 tables, authors from page 10,
published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/98
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