644 research outputs found
Disability weights for comorbidity and their influence on Health-adjusted Life Expectancy
BACKGROUND: Comorbidity complicates estimations of health-adjusted life expectancy (HALE) using disease prevalences and disability weights from Burden of Disease studies. Usually, the exact amount of comorbidity is unknown and no disability weights are defined for comorbidity. METHODS: Using data of the Dutch national burden of disease study, the effects of different methods to adjust for comorbidity on HALE calculations are estimated. The default multiplicative adjustment method to define disability weights for comorbidity is compared to HALE estimates without adjustment for comorbidity and to HALE estimates in which the amount of disability in patients with multiple diseases is solely determined by the disease that leads to most disability (the maximum adjustment method). To estimate the amount of comorbidity, independence between diseases is assumed. RESULTS: Compared to the multiplicative adjustment method, the maximum adjustment method lowers HALE estimates by 1.2 years for males and 1.9 years for females. Compared to no adjustment, a multiplicative adjustment lowers HALE estimates by 1.0 years for males and 1.4 years for females. CONCLUSION: The differences in HALE caused by the different adjustment methods demonstrate that adjusting for comorbidity in HALE calculations is an important topic that needs more attention. More empirical research is needed to develop a more general theory as to how comorbidity influences disability
Key factors in determining surgical timing of total knee arthroplasty in osteoarthritic patients: age, radiographic severity, and symptomatic severity
HIV Envelope gp120 Activates LFA-1 on CD4 T-Lymphocytes and Increases Cell Susceptibility to LFA-1-Targeting Leukotoxin (LtxA)
The cellular adhesion molecule LFA-1 and its ICAM-1 ligand play an important role in promoting HIV-1 infectivity and transmission. These molecules are present on the envelope of HIV-1 virions and are integral components of the HIV virological synapse. However, cellular activation is required to convert LFA-1 to the active conformation that has high affinity binding for ICAM-1. This study evaluates whether such activation can be induced by HIV itself. The data show that HIV-1 gp120 was sufficient to trigger LFA-1 activation in fully quiescent naĂŻve CD4 T cells in a CD4-dependent manner, and these CD4 T cells became more susceptible to killing by LtxA, a bacterial leukotoxin that preferentially targets leukocytes expressing high levels of the active LFA-1. Moreover, virus p24-expressing CD4 T cells in the peripheral blood of HIV-infected subjects were found to have higher levels of surface LFA-1, and LtxA treatment led to significant reduction of the viral DNA burden. These results demonstrate for the first time the ability of HIV to directly induce LFA-1 activation on CD4 T cells. Although LFA-1 activation may enhance HIV infectivity and transmission, it also renders the cells more susceptible to an LFA-1-targeting bacterial toxin, which may be harnessed as a novel therapeutic strategy to deplete virus reservoir in HIV-infected individuals
Fermi Gamma-ray Imaging of a Radio Galaxy
The Fermi Gamma-ray Space Telescope has detected the gamma-ray glow emanating
from the giant radio lobes of the radio galaxy Centaurus A. The resolved
gamma-ray image shows the lobes clearly separated from the central active
source. In contrast to all other active galaxies detected so far in high-energy
gamma-rays, the lobe flux constitutes a considerable portion (>1/2) of the
total source emission. The gamma-ray emission from the lobes is interpreted as
inverse Compton scattered relic radiation from the cosmic microwave background
(CMB), with additional contribution at higher energies from the
infrared-to-optical extragalactic background light (EBL). These measurements
provide gamma-ray constraints on the magnetic field and particle energy content
in radio galaxy lobes, and a promising method to probe the cosmic relic photon
fields.Comment: 27 pages, includes Supplementary Online Material; corresponding
authors: C.C. Cheung, Y. Fukazawa, J. Knodlseder, L. Stawar
F-Actin-Dependent Regulation of NESH Dynamics in Rat Hippocampal Neurons
Synaptic plasticity is an important feature of neurons essential for learning and memory. Postsynaptic organization and composition are dynamically remodeled in response to diverse synaptic inputs during synaptic plasticity. During this process, the dynamics and localization of postsynaptic proteins are also precisely regulated. NESH/Abi-3 is a member of the Abl interactor (Abi) protein family. Overexpression of NESH is associated with reduced cell motility and tumor metastasis. Strong evidence of a close relationship between NESH and the actin cytoskeleton has been documented. Although earlier studies have shown that NESH is prominently expressed in the brain, its function and characteristics are yet to be established. Data from the present investigation suggest that synaptic localization of NESH in hippocampal neurons is regulated in an F-actin-dependent manner. The dynamic fraction of NESH in the dendritic spine was analyzed using FRAP (fluorescence recovery after photobleaching). Interestingly, F-actin stabilization and disruption significantly affected the mobile fraction of NESH, possibly through altered interactions of NESH with the F-actin. In addition, NESH was synaptically targeted from the dendritic shaft to spine after induction of chemical LTP (long-term potentiation) and the translocation was dependent on F-actin. Our data collectively support the significance of the F-actin cytoskeleton in synaptic targeting of NESH as well as its dynamics
A change in the optical polarization associated with a gamma-ray flare in the blazar 3C 279
It is widely accepted that strong and variable radiation detected over all
accessible energy bands in a number of active galaxies arises from a
relativistic, Doppler-boosted jet pointing close to our line of sight. The size
of the emitting zone and the location of this region relative to the central
supermassive black hole are, however, poorly known, with estimates ranging from
light-hours to a light-year or more. Here we report the coincidence of a
gamma-ray flare with a dramatic change of optical polarization angle. This
provides evidence for co-spatiality of optical and gamma-ray emission regions
and indicates a highly ordered jet magnetic field. The results also require a
non-axisymmetric structure of the emission zone, implying a curved trajectory
for the emitting material within the jet, with the dissipation region located
at a considerable distance from the black hole, at about 10^5 gravitational
radii.Comment: Published in Nature issued on 18 February 2010. Corresponding
authors: Masaaki Hayashida and Greg Madejsk
Variations in the pre-operative status of patients coming to primary hip replacement for osteoarthritis in European orthopaedic centres.
addresses: Nuffield Department of Orthopaedic Surgery, University of Oxford, Nuffield Orthopaedic Centre, Headington, Oxford, UK. [email protected]: PMCID: PMC2654855types: Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't© 2009 Dieppe et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Total hip joint replacement (THR) is a high volume, effective intervention for hip osteoarthritis (OA). However, indications and determinants of outcome remain unclear. The 'EUROHIP consortium' has undertaken a cohort study to investigate these questions. This paper describes the variations in disease severity in this cohort and the relationships between clinical and radiographic severity, and explores some of the determinants of variation
Analysis of ecological thresholds in a temperate forest undergoing dieback.
Positive feedbacks in drivers of degradation can cause threshold responses in natural ecosystems. Though threshold responses have received much attention in studies of aquatic ecosystems, they have been neglected in terrestrial systems, such as forests, where the long time-scales required for monitoring have impeded research. In this study we explored the role of positive feedbacks in a temperate forest that has been monitored for 50 years and is undergoing dieback, largely as a result of death of the canopy dominant species (Fagus sylvatica, beech). Statistical analyses showed strong non-linear losses in basal area for some plots, while others showed relatively gradual change. Beech seedling density was positively related to canopy openness, but a similar relationship was not observed for saplings, suggesting a feedback whereby mortality in areas with high canopy openness was elevated. We combined this observation with empirical data on size- and growth-mediated mortality of trees to produce an individual-based model of forest dynamics. We used this model to simulate changes in the structure of the forest over 100 years under scenarios with different juvenile and mature mortality probabilities, as well as a positive feedback between seedling and mature tree mortality. This model produced declines in forest basal area when critical juvenile and mature mortality probabilities were exceeded. Feedbacks in juvenile mortality caused a greater reduction in basal area relative to scenarios with no feedback. Non-linear, concave declines of basal area occurred only when mature tree mortality was 3-5 times higher than rates observed in the field. Our results indicate that the longevity of trees may help to buffer forests against environmental change and that the maintenance of old, large trees may aid the resilience of forest stands. In addition, our work suggests that dieback of forests may be avoidable providing pressures on mature and juvenile trees do not pass critical thresholds
Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV
The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of âs = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pTâ„20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60â€pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2â€{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration
Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector
The inclusive and dijet production cross-sections have been measured for jets
containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass
energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The
measurements use data corresponding to an integrated luminosity of 34 pb^-1.
The b-jets are identified using either a lifetime-based method, where secondary
decay vertices of b-hadrons in jets are reconstructed using information from
the tracking detectors, or a muon-based method where the presence of a muon is
used to identify semileptonic decays of b-hadrons inside jets. The inclusive
b-jet cross-section is measured as a function of transverse momentum in the
range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet
cross-section is measured as a function of the dijet invariant mass in the
range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets
and the angular variable chi in two dijet mass regions. The results are
compared with next-to-leading-order QCD predictions. Good agreement is observed
between the measured cross-sections and the predictions obtained using POWHEG +
Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet
cross-section. However, it does not reproduce the measured inclusive
cross-section well, particularly for central b-jets with large transverse
momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final
version published in European Physical Journal
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