55 research outputs found
Light meson form factors at high from lattice QCD
Measurements and theoretical calculations of meson form factors are essential
for our understanding of internal hadron structure and QCD, the dynamics that
bind the quarks in hadrons. The pion electromagnetic form factor has been
measured at small space-like momentum transfer ~GeV by pion
scattering from atomic electrons and at values up to ~GeV by
scattering electrons from the pion cloud around a proton. On the other hand, in
the limit of very large (or infinite) , perturbation theory is
applicable. This leaves a gap in the intermediate where the form factors
are not known.
As a part of their 12 GeV upgrade Jefferson Lab will measure pion and kaon
form factors in this intermediate region, up to of ~GeV. This is
then an ideal opportunity for lattice QCD to make an accurate prediction ahead
of the experimental results. Lattice QCD provides a from-first-principles
approach to calculate form factors, and the challenge here is to control the
statistical and systematic uncertainties as errors grow when going to higher
values.
Here we report on a calculation that tests the method using an
meson, a 'heavy pion' made of strange quarks, and also present preliminary
results for kaon and pion form factors. We use the ensembles made
by the MILC collaboration and Highly Improved Staggered Quarks, which allows us
to obtain high statistics. The HISQ action is also designed to have small
discretisation errors. Using several light quark masses and lattice spacings
allows us to control the chiral and continuum extrapolation and keep systematic
errors in check.Comment: Presented at Lattice 2017, the 35th International Symposium on
Lattice Field Theory at Granada, Spain (18-24 June 2017
Lymph node but not intradermal injection site macrophages are critical for germinal center formation and antibody responses to rabies vaccination.
UNLABELLED: Replication-deficient rabies virus (RABV)-based vaccines induce rapid and potent antibody responses via T cell-independent and T cell-dependent mechanisms. To further investigate early events in vaccine-induced antibody responses against RABV infections, we studied the role of macrophages as mediators of RABV-based vaccine immunogenicity. In this report, we show that a recombinant matrix gene-deleted RABV-based vaccine (rRABV-ΔM) infects and activates primary murine macrophages in vitro. Immunization of mice with live RABV-based vaccines results in accumulation of macrophages at the site of immunization, which suggests that macrophages in tissues support the development of effective anti-RABV B cell responses. However, we show that draining lymph node macrophages, but not macrophages at the site of immunization, are essential for the generation of germinal center B cells, follicular T helper cells, and RABV-specific antibodies. Our findings have implications for the design of new RABV-based vaccines for which early immunological events are important for the protection against RABV in postexposure settings.
IMPORTANCE: More than two-thirds of the world\u27s population live in regions where rabies is endemic. Postexposure prophylaxis is the primary means of treating humans. Identifying immunological principles that guide the development of rapid and potent antibody responses against rabies infections will greatly increase our ability to produce more-effective rabies vaccines. Here we report that macrophages in the draining lymph node, but not in the tissue at the site of immunization are important for vaccine-induced antibody responses to rabies. Information gleaned from this study may help guide the development of a single-dose vaccine against rabies infections
APRIL:TACI axis is dispensable for the immune response to rabies vaccination.
There is significant need to develop a single-dose rabies vaccine to replace the current multi-dose rabies vaccine regimen and eliminate the requirement for rabies immune globulin in post-exposure settings. To accomplish this goal, rabies virus (RABV)-based vaccines must rapidly activate B cells to secrete antibodies which neutralize pathogenic RABV before it enters the CNS. Increased understanding of how B cells effectively respond to RABV-based vaccines may improve efforts to simplify post-exposure prophylaxis (PEP) regimens. Several studies have successfully employed the TNF family cytokine a proliferation-inducing ligand (APRIL) as a vaccine adjuvant. APRIL binds to the receptors TACI and B cell maturation antigen (BCMA)-expressed by B cells in various stages of maturation-with high affinity. We discovered that RABV-infected primary murine B cells upregulate APRIL ex vivo. Cytokines present at the time of antigen exposure affect the outcome of vaccination by influencing T and B cell activation and GC formation. Therefore, we hypothesized that the presence of APRIL at the time of RABV-based vaccine antigen exposure would support the generation of protective antibodies against RABV glycoprotein (G). In an effort to improve the response to RABV vaccination, we constructed and characterized a live recombinant RABV-based vaccine vector which expresses murine APRIL (rRABV-APRIL). Immunogenicity testing in mice demonstrated that expressing APRIL from the RABV genome does not impact the primary antibody response against RABV G compared to RABV alone. In order to evaluate the necessity of APRIL for the response to rabies vaccination, we compared the responses of APRIL-deficient and wild-type mice to immunization with rRABV. APRIL deficiency does not affect the primary antibody response to vaccination. Furthermore, APRIL expression by the vaccine did not improve the generation of long-lived antibody-secreting plasma cells (PCs) as serum antibody levels were equivalent in response to rRABV-APRIL and the vector eight weeks after immunization. Moreover, APRIL is dispensable for the long-lived antibody-secreting PC response to rRABV vaccination as anti-RABV G IgG levels were similar in APRIL-deficient and wild-type mice six months after vaccination. Mice lacking the APRIL receptor TACI demonstrated primary anti-RABV G antibody responses similar to wild-type mice following immunization with the vaccine vector indicating that this response is independent of TACI-mediated signals. Collectively, our findings demonstrate that APRIL and associated TACI signaling is dispensable for the immune response to RABV-based vaccination
Light-quark connected intermediate-window contributions to the muon hadronic vacuum polarization from lattice QCD
We present a lattice-QCD calculation of the light-quark connected
contribution to window observables associated with the leading-order hadronic
vacuum polarization contribution to the anomalous magnetic moment of the muon,
. We employ the MILC Collaboration's isospin-symmetric
QCD gauge-field ensembles, which contain four flavors of dynamical
highly-improved-staggered quarks with four lattice spacings between -~fm and close-to-physical quark masses. We consider several
effective-field-theory-based schemes for finite-volume and other lattice
corrections and combine the results via Bayesian model averaging to obtain
robust estimates of the associated systematic uncertainties. After unblinding,
our final results for the intermediate and ``W2'' windows are and , respectively
Changes in Cognition and Mortality in Relation to Exercise in Late Life: A Population Based Study
BACKGROUND: On average, cognition declines with age but this average hides considerable variability, including the chance of improvement. Here, we investigate how exercise is associated with cognitive change and mortality in older people and, particularly, whether exercise might paradoxically increase the risk of dementia by allowing people to live longer. METHODS AND PRINCIPAL FINDINGS: In the Canadian Study of Health and Aging (CSHA), of 8403 people who had baseline cognition measured and exercise reported at CSHA-1, 2219 had died and 5376 were re-examined at CSHA-2. We used a parametric Markov chain model to estimate the probabilities of cognitive improvement, decline, and death, adjusted for age and education, from any cognitive state as measured by the Modified Mini-Mental State Examination. High exercisers (at least three times per week, at least as intense as walking, n = 3264) had more frequent stable or improved cognition (42.3%, 95% confidence interval: 40.6-44.0) over 5 years than did low/no exercisers (all other exercisers and non exercisers, n = 4331) (27.8% (95% CI 26.4-29.2)). The difference widened as baseline cognition worsened. The proportion whose cognition declined was higher amongst the high exercisers but was more similar between exercise groups (39.4% (95% CI 37.7-41.1) for high exercisers versus 34.8% (95% CI 33.4-36.2) otherwise). People who did not exercise were also more likely to die (37.5% (95% CI 36.0-39.0) versus 18.3% (95% CI 16.9-19.7)). Even so, exercise conferred its greatest mortality benefit to people with the highest baseline cognition. CONCLUSIONS: Exercise is strongly associated with improving cognition. As the majority of mortality benefit of exercise is at the highest level of cognition, and declines as cognition declines, the net effect of exercise should be to improve cognition at the population level, even with more people living longer
Report of the Snowmass 2021 Topical Group on Lattice Gauge Theory
Lattice gauge theory continues to be a powerful theoretical and computational
approach to simulating strongly interacting quantum field theories, whose
applications permeate almost all disciplines of modern-day research in
High-Energy Physics. Whether it is to enable precision quark- and lepton-flavor
physics, to uncover signals of new physics in nucleons and nuclei, to elucidate
hadron structure and spectrum, to serve as a numerical laboratory to reach
beyond the Standard Model, or to invent and improve state-of-the-art
computational paradigms, the lattice-gauge-theory program is in a prime
position to impact the course of developments and enhance discovery potential
of a vibrant experimental program in High-Energy Physics over the coming
decade. This projection is based on abundant successful results that have
emerged using lattice gauge theory over the years: on continued improvement in
theoretical frameworks and algorithmic suits; on the forthcoming transition
into the exascale era of high-performance computing; and on a skillful,
dedicated, and organized community of lattice gauge theorists in the U.S. and
worldwide. The prospects of this effort in pushing the frontiers of research in
High-Energy Physics have recently been studied within the U.S. decadal Particle
Physics Planning Exercise (Snowmass 2021), and the conclusions are summarized
in this Topical Report.Comment: 57 pages, 1 figure. Submitted to the Proceedings of the US Community
Study on the Future of Particle Physics (Snowmass 2021). Topical Group Report
for TF05 - Lattice Gauge Theor
Imminent brain death: point of departure for potential heart-beating organ donor recognition
Contains fulltext :
88186.pdf (publisher's version ) (Closed access)PURPOSE: There is, in European countries that conduct medical chart review of intensive care unit (ICU) deaths, no consensus on uniform criteria for defining a potential organ donor. Although the term is increasingly being used in recent literature, it is seldom defined in detail. We searched for criteria for determination of imminent brain death, which can be seen as a precursor for organ donation. METHODS: We organized meetings with representatives from the field of clinical neurology, neurotraumatology, intensive care medicine, transplantation medicine, clinical intensive care ethics, and organ procurement management. During these meetings, all possible criteria were discussed to identify a patient with a reasonable probability to become brain dead (imminent brain death). We focused on the practical usefulness of two validated coma scales (Glasgow Coma Scale and the FOUR Score), brain stem reflexes and respiration to define imminent brain death. Further we discussed criteria to determine irreversibility and futility in acute neurological conditions. RESULTS: A patient who fulfills the definition of imminent brain death is a mechanically ventilated deeply comatose patient, admitted to an ICU, with irreversible catastrophic brain damage of known origin. A condition of imminent brain death requires either a Glasgow Coma Score of 3 and the progressive absence of at least three out of six brain stem reflexes or a FOUR score of E(0)M(0)B(0)R(0). CONCLUSION: The definition of imminent brain death can be used as a point of departure for potential heart-beating organ donor recognition on the intensive care unit or retrospective medical chart analysis.1 september 201
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