891 research outputs found
Efficacy and safety of recruitment maneuvers in acute respiratory distress syndrome
Recruitment maneuvers (RM) consist of a ventilatory strategy that increases the transpulmonary pressure transiently to reopen the recruitable lung units in acute respiratory distress syndrome (ARDS). The rationales to use RM in ARDS are that there is a massive loss of aerated lung and that once the end-inspiratory pressure surpasses the regional critical opening pressure of the lung units, those units are likely to reopen. There are different methods to perform RM when using the conventional ICU ventilator. The three RM methods that are mostly used and investigated are sighs, sustained inflation, and extended sigh. There is no standardization of any of the above RM. Meta-analysis recommended not to use RM in routine in stable ARDS patients but to run them in case of life-threatening hypoxemia. There are some concerns regarding the safety of RM in terms of hemodynamics preservation and lung injury as well. The rapid rising in pressure can be a factor that explains the potential harmful effects of the RM. In this review, we describe the balance between the beneficial effects and the harmful consequences of RM. Recent animal studies are discussed
Quasinormal modes of massive charged flavor branes
We present an analysis and classification of vector and scalar fluctuations
in a D3/D7 brane setup at finite termperature and baryon density. The system is
dual to an N=2 supersymmetric Yang-Mills theory with SU(N_c) gauge group and
N_f hypermultiplets in the fundamental representation in the quenched
approximation. We improve significantly over previous results on the
quasinormal mode spectrum of D7 branes and stress their novel physical
interpretation. Amongst our findings is a new purely imaginary scalar mode that
becomes tachyonic at sufficiently low temperature and baryon density. We
establish the existence of a critical density above which the scalar mode stays
in the stable regime for all temperatures. In the vector sector we study the
crossover from the hydrodynamic to the quasiparticle regime and find that it
moves to shorter wavelengths for lower temperatures. At zero baryon density the
quasinormal modes move toward distinct discrete attractor frequencies that
depend on the momentum as we increase the temperature. At finite baryon
density, however, the trajectories show a turning behavior such that for low
temperature the quasinormal mode spectrum approaches the spectrum of the
supersymmetric zero temperature normal modes. We interpret this as resolution
of the singular quasinormal mode spectrum that appears at the limiting D7 brane
embedding at vanishing baryon density.Comment: 56 pages, 40 figure
N=1 extension of minimal model holography
The CFT dual of the higher spin theory with minimal N = 1 spectrum is
determined. Unlike previous examples of minimal model holography, there is no
free parameter beyond the central charge, and the CFT can be described in terms
of a non-diagonal modular invariant of the bosonic theory at the special value
of the 't Hooft parameter lambda=1/2. As evidence in favour of the duality we
show that the symmetry algebras as well as the partition functions agree
between the two descriptions.Comment: 28 page
Transgenic Rescue of the LARGEmyd Mouse: A LARGE Therapeutic Window?
LARGE is a glycosyltransferase involved in glycosylation of α-dystroglycan (α-DG). Absence of this protein in the LARGEmyd mouse results in α-DG hypoglycosylation, and is associated with central nervous system abnormalities and progressive muscular dystrophy. Up-regulation of LARGE has previously been proposed as a therapy for the secondary dystroglycanopathies: overexpression in cells compensates for defects in multiple dystroglycanopathy genes. Counterintuitively, LARGE overexpression in an FKRP-deficient mouse exacerbates pathology, suggesting that modulation of α-DG glycosylation requires further investigation. Here we demonstrate that transgenic expression of human LARGE (LARGE-LV5) in the LARGEmyd mouse restores α-DG glycosylation (with marked hyperglycosylation in muscle) and that this corrects both the muscle pathology and brain architecture. By quantitative analyses of LARGE transcripts we also here show that levels of transgenic and endogenous LARGE in the brains of transgenic animals are comparable, but that the transgene is markedly overexpressed in heart and particularly skeletal muscle (20–100 fold over endogenous). Our data suggest LARGE overexpression may only be deleterious under a forced regenerative context, such as that resulting from a reduction in FKRP: in the absence of such a defect we show that systemic expression of LARGE can indeed act therapeutically, and that even dramatic LARGE overexpression is well-tolerated in heart and skeletal muscle. Moreover, correction of LARGEmyd brain pathology with only moderate, near-physiological LARGE expression suggests a generous therapeutic window
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Beam Energy and Centrality Dependence of Direct-Photon Emission from Ultrarelativistic Heavy-Ion Collisions.
The PHENIX collaboration presents first measurements of low-momentum (0.41 GeV/c) direct-photon yield dN_{γ}^{dir}/dη is a smooth function of dN_{ch}/dη and can be well described as proportional to (dN_{ch}/dη)^{α} with α≈1.25. This scaling behavior holds for a wide range of beam energies at the Relativistic Heavy Ion Collider and the Large Hadron Collider, for centrality selected samples, as well as for different A+A collision systems. At a given beam energy, the scaling also holds for high p_{T} (>5 GeV/c), but when results from different collision energies are compared, an additional sqrt[s_{NN}]-dependent multiplicative factor is needed to describe the integrated-direct-photon yield
Production of phi mesons at mid-rapidity in sqrt(s_NN) = 200 GeV Au+Au collisions at RHIC
We present the first results of meson production in the K^+K^- decay channel
from Au+Au collisions at sqrt(s_NN) = 200 GeV as measured at mid-rapidity by
the PHENIX detector at RHIC. Precision resonance centroid and width values are
extracted as a function of collision centrality. No significant variation from
the PDG accepted values is observed. The transverse mass spectra are fitted
with a linear exponential function for which the derived inverse slope
parameter is seen to be constant as a function of centrality. These data are
also fitted by a hydrodynamic model with the result that the freeze-out
temperature and the expansion velocity values are consistent with the values
previously derived from fitting single hadron inclusive data. As a function of
transverse momentum the collisions scaled peripheral.to.central yield ratio RCP
for the is comparable to that of pions rather than that of protons. This result
lends support to theoretical models which distinguish between baryons and
mesons instead of particle mass for explaining the anomalous proton yield.Comment: 326 authors, 24 pages text, 23 figures, 6 tables, RevTeX 4. To be
submitted to Physical Review C as a regular article. Plain text data tables
for the points plotted in figures for this and previous PHENIX publications
are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm
Chemokines in cerebrospinal fluid correlate with cerebral metabolite patterns in HIV-infected individuals
Chemokines influence HIV neuropathogenesis by affecting the HIV life cycle, trafficking of macrophages into the nervous system, glial activation, and neuronal signaling and repair processes; however, knowledge of their relationship to in vivo measures of cerebral injury is limited. The primary objective of this study was to determine the relationship between a panel of chemokines in cerebrospinal fluid (CSF) and cerebral metabolites measured by proton magnetic resonance spectroscopy (MRS) in a cohort of HIV-infected individuals. One hundred seventy-one stored CSF specimens were assayed from HIV-infected individuals who were enrolled in two ACTG studies that evaluated the relationship between neuropsychological performance and cerebral metabolites. Concentrations of six chemokines (fractalkine, IL-8, IP-10, MCP-1, MIP-1β, and SDF-1) were measured and compared with cerebral metabolites individually and as composite neuronal, basal ganglia, and inflammatory patterns. IP-10 and MCP-1 were the chemokines most strongly associated with individual cerebral metabolites. Specifically, (1) higher IP-10 levels correlated with lower N-acetyl aspartate (NAA)/creatine (Cr) ratios in the frontal white matter and higher MI/Cr ratios in all three brain regions considered and (2) higher MCP-1 levels correlated with lower NAA/Cr ratios in frontal white matter and the parietal cortex. IP-10, MCP-1, and IL-8 had the strongest associations with patterns of cerebral metabolites. In particular, higher levels of IP-10 correlated with lower neuronal pattern scores and higher basal ganglia and inflammatory pattern scores, the same pattern which has been associated with HIV-associated neurocognitive disorders (HAND). Subgroup analysis indicated that the effects of IP-10 and IL-8 were influenced by effective antiretroviral therapy and that memantine treatment may mitigate the neuronal effects of IP-10. This study supports the role of chemokines in HAND and the validity of MRS as an assessment tool. In particular, the findings identify relationships between the immune response—particularly an interferon-inducible chemokine, IP-10—and cerebral metabolites and suggest that antiretroviral therapy and memantine modify the impact of the immune response on neurons
The Tyrphostin Agent AG490 Prevents and Reverses Type 1 Diabetes in NOD Mice
<div><h3>Background</h3><p>Recent studies in the NOD (non-obese diabetic) mouse model of type 1 diabetes (T1D) support the notion that tyrosine kinase inhibitors have the potential for modulating disease development. However, the therapeutic effects of AG490 on the development of T1D are unknown.</p> <h3>Materials and Methods</h3><p>Female NOD mice were treated with AG490 (i.p, 1 mg/mouse) or DMSO starting at either 4 or 8 week of age, for five consecutive week, then once per week for 5 additional week. Analyses for the development and/or reversal of diabetes, insulitis, adoptive transfer, and other mechanistic studies were performed.</p> <h3>Results</h3><p>AG490 significantly inhibited the development of T1D (p = 0.02, p = 0.005; at two different time points). Monotherapy of newly diagnosed diabetic NOD mice with AG490 markedly resulted in disease remission in treated animals (n = 23) in comparision to the absolute inability (0%; 0/10, p = 0.003, Log-rank test) of DMSO and sustained eugluycemia was maintained for several months following drug withdrawal. Interestingly, adoptive transfer of splenocytes from AG490 treated NOD mice failed to transfer diabetes to recipient NOD.<em>Scid</em> mice. CD4 T-cells as well as bone marrow derived dendritic cells (BMDCs) from AG490 treated mice, showed higher expression of Foxp3 (p<0.004) and lower expression of co-stimulatory molecules, respectively. Screening of the mouse immune response gene arrary indicates that expression of costimulaotry molecule Ctla4 was upregulated in CD4+ T-cell in NOD mice treated with AG490, suggesting that AG490 is not a negative regulator of the immune system.</p> <h3>Conclusion</h3><p>The use of such agents, given their extensive safety profiles, provides a strong foundation for their translation to humans with or at increased risk for the disease.</p> </div
Retention in Care and Connection to Care among HIV-Infected Patients on Antiretroviral Therapy in Africa: Estimation via a Sampling-Based Approach
Current estimates of retention among HIV-infected patients on antiretroviral therapy (ART) in Africa consider patients who are lost to follow-up (LTF) as well as those who die shortly after their last clinic visit to be no longer in care and to represent limitations in access to care. Yet many lost patients may have "silently" transferred and deaths shortly after the last clinic visit more likely represent limitations in clinical care rather than access to care after initial linkage.We evaluated HIV-infected adults initiating ART from 1/1/2004 to 9/30/2007 at a clinic in rural Uganda. A representative sample of lost patients was tracked in the community to obtain updated information about care at other ART sites. Updated outcomes were incorporated with probability weights to obtain "corrected" estimates of retention for the entire clinic population. We used the competing risks approach to estimate "connection to care"--the percentage of patients accessing care over time (including those who died while in care).Among 3,628 patients, 829 became lost, 128 were tracked and in 111, updated information was obtained. Of 111, 79 (71%) were alive and 35/48 (73%) of patients interviewed in person were in care and on ART. Patient retention for the clinic population assuming lost patients were not in care was 82.3%, 68.9%, and 60.1% at 1, 2 and 3 years. Incorporating updated care information from the sample of lost patients increased estimates of patient retention to 85.8% to 90.9%, 78.9% to 86.2% and 75.8% to 84.7% at the same time points.Accounting for "silent transfers" and early deaths increased estimates of patient retention and connection to care substantially. Deaths soon after the last clinic visit (potentially reflecting limitations in clinical effectiveness) and disconnection from care among patient who were alive each accounted for approximately half of failures of retention
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