Virus-specific T-helper cells are considered critical for the control of
chronic viral infections. Successful treatment of acute
HIV-1 infection leads to augmentation of these responses,
but whether ...this enhances immune control has not been determined. We administered
one or two supervised treatment interruptions to eight subjects with treated
acute infection, with the plan to restart therapy if viral load exceeded 5,000
copies of HIV-1 RNA per millilitre of plasma (the level at which therapy has
been typically recommended) for three consecutive weeks, or 50,000 RNA copies
per ml at one time. Here we show that, despite rebound in viraemia, all subjects
were able to achieve at least a transient steady state off therapy with viral
load below 5,000 RNA copies per ml. At present, five out of eight subjects
remain off therapy with viral loads of less than 500 RNA copies per ml plasma
after a median 6.5 months (range 5-8.7 months). We observed
increased virus-specific cytotoxic T lymphocytes and maintained T-helper-cell
responses in all. Our data indicate that functional immune responses can be
augmented in a chronic viral infection, and provide rationale for immunotherapy
in HIV-1 infection.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The T2K experiment has observed electron neutrino appearance in a muon neutrino beam produced 295 km from the Super-Kamiokande detector with a peak energy of 0.6 GeV. A total of 28 electron neutrino ...events were detected with an energy distribution consistent with an appearance signal, corresponding to a significance of 7.3σ when compared to 4.92±0.55 expected background events. In the Pontecorvo-Maki-Nakagawa-Sakata mixing model, the electron neutrino appearance signal depends on several parameters including three mixing angles θ12, θ23, θ13, a mass difference Δm(32)(2) and a CP violating phase δ(CP). In this neutrino oscillation scenario, assuming |Δm(32)(2)|=2.4×10(-3) eV(2), sin(2)θ(23)=0.5, and Δm322>0 (Δm(32)(2)<0), a best-fit value of sin(2)2θ(13)=0.140(-0.032)(+0.038) (0.170(-0.037)(+0.045)) is obtained at δ(CP)=0. When combining the result with the current best knowledge of oscillation parameters including the world average value of θ(13) from reactor experiments, some values of δ(CP) are disfavored at the 90% C.L.
Primary graft dysfunction (PGD) is a major cause of early mortality after lung transplant. We aimed to define objective estimates of PGD risk based on readily available clinical variables, using a ...prospective study of 11 centers in the Lung Transplant Outcomes Group (LTOG). Derivation included 1255 subjects from 2002 to 2010; with separate validation in 382 subjects accrued from 2011 to 2012. We used logistic regression to identify predictors of grade 3 PGD at 48/72 h, and decision curve methods to assess impact on clinical decisions. 211/1255 subjects in the derivation and 56/382 subjects in the validation developed PGD. We developed three prediction models, where low‐risk recipients had a normal BMI (18.5–25 kg/m2), chronic obstructive pulmonary disease/cystic fibrosis, and absent or mild pulmonary hypertension (mPAP<40 mmHg). All others were considered higher‐risk. Low‐risk recipients had a predicted PGD risk of 4–7%, and high‐risk a predicted PGD risk of 15–18%. Adding a donor‐smoking lung to a higher‐risk recipient significantly increased PGD risk, although risk did not change in low‐risk recipients. Validation demonstrated that probability estimates were generally accurate and that models worked best at baseline PGD incidences between 5% and 25%. We conclude that valid estimates of PGD risk can be produced using readily available clinical variables.
Using three clinical prediction models based on recipient and donor factors for the development of primary graft dysfunction (PGD) after lung transplantation, the authors demonstrate that elevated mean pulmonary arterial pressures, a diagnosis other than cystic fibrosis or chronic obstructive pulmonary disease, and obesity define high‐risk recipients, and addition of a lung from a smoking donor significantly increases PGD risk in the high‐risk group.
T2K reports its first results in the search for CP violation in neutrino oscillations using appearance and disappearance channels for neutrino- and antineutrino-mode beams. The data include all runs ...from January 2010 to May 2016 and comprise 7.482×10^{20} protons on target in neutrino mode, which yielded in the far detector 32 e-like and 135 μ-like events, and 7.471×10^{20} protons on target in antineutrino mode, which yielded 4 e-like and 66 μ-like events. Reactor measurements of sin^{2}2θ_{13} have been used as an additional constraint. The one-dimensional confidence interval at 90% for the phase δ_{CP} spans the range (-3.13, -0.39) for normal mass ordering. The CP conservation hypothesis (δ_{CP}=0, π) is excluded at 90% C.L.
The K2K experiment observes indications of neutrino oscillation: a reduction of nu(mu) flux together with a distortion of the energy spectrum. Fifty-six beam neutrino events are observed in ...Super-Kamiokande (SK), 250 km from the neutrino production point, with an expectation of 80.1(+6.2)(-5.4). Twenty-nine one ring mu-like events are used to reconstruct the neutrino energy spectrum, which is better matched to the expected spectrum with neutrino oscillation than without. The probability that the observed flux at SK is explained by statistical fluctuation without neutrino oscillation is less than 1%.
The T2K experiment observes indications of ν(μ) → ν(e) appearance in data accumulated with 1.43×10(20) protons on target. Six events pass all selection criteria at the far detector. In a three-flavor ...neutrino oscillation scenario with |Δm(23)(2)| = 2.4×10(-3) eV(2), sin(2)2θ(23) = 1 and sin(2)2θ(13) = 0, the expected number of such events is 1.5±0.3(syst). Under this hypothesis, the probability to observe six or more candidate events is 7×10(-3), equivalent to 2.5σ significance. At 90% C.L., the data are consistent with 0.03(0.04) < sin(2)2θ(13) < 0.28(0.34) for δ(CP) = 0 and a normal (inverted) hierarchy.
New data from the T2K neutrino oscillation experiment produce the most precise measurement of the neutrino mixing parameter θ23. Using an off-axis neutrino beam with a peak energy of 0.6 GeV and a ...data set corresponding to 6.57×10(20) protons on target, T2K has fit the energy-dependent νμ oscillation probability to determine oscillation parameters. The 68% confidence limit on sin(2)(θ23) is 0.514(-0.056)(+0.055) (0.511±0.055), assuming normal (inverted) mass hierarchy. The best-fit mass-squared splitting for normal hierarchy is Δm32(2)=(2.51±0.10)×10(-3) eV(2)/c(4) (inverted hierarchy: Δm13(2)=(2.48±0.10)×10(-3) eV(2)/c(4)). Adding a model of multinucleon interactions that affect neutrino energy reconstruction is found to produce only small biases in neutrino oscillation parameter extraction at current levels of statistical uncertainty.
Cosmic-ray-muon spallation-induced radioactive isotopes with beta decays are one of the major backgrounds for solar, reactor, and supernova relic neutrino experiments. Unlike in scintillator, ...production yields for cosmogenic backgrounds in water have not been exclusively measured before, yet they are becoming more and more important in next generation neutrino experiments designed to search for rare signals. We have analyzed the low-energy trigger data collected at Super-Kamiokande IV in order to determine the production rates of B super(12), N super(12), N super(16), Be super(11), Li super(9), He super(8), C super(9), Li super(8), B super(8), and C super(15). These rates were extracted from fits to time differences between parent muons and subsequent daughter beta 's by fixing the known isotope lifetimes. Since Li super(9) can fake an inverse-beta-decay reaction chain via a beta +n cascade decay, producing an irreducible background with detected energy up to a dozen MeV, a dedicated study is needed for evaluating its impact on future measurements; the application of a neutron tagging technique using correlated triggers was found to improve this Li super(9) measurement. The measured yields were generally found to be comparable with theoretical calculations, except the cases of the isotopes Li super(8)/B super(8) and Li super(9).
We report the first measurement of the flux-averaged cross section for charged current coherent π^{+} production on carbon for neutrino energies less than 1.5 GeV, and with a restriction on the final ...state phase space volume in the T2K near detector, ND280. Comparisons are made with predictions from the Rein-Sehgal coherent production model and the model by Alvarez-Ruso et al., the latter representing the first implementation of an instance of the new class of microscopic coherent models in a neutrino interaction Monte Carlo event generator. We observe a clear event excess above background, disagreeing with the null results reported by K2K and SciBooNE in a similar neutrino energy region. The measured flux-averaged cross sections are below those predicted by both the Rein-Sehgal and Alvarez-Ruso et al.
See also Iorio A, Marcucci M, Makris M. Concentrate‐related inhibitor risk: is a difference always real? This issue, pp 2176–9.
Summary. Background: As a result of the infrequency of inhibitors in ...previously treated patients (PTPs) with hemophilia A and the small size of available clinical studies, the immunogenicity of factor (F)VIII products has been difficult to assess. Objectives: A meta‐analysis of prospective clinical studies was conducted to test the hypothesis that de novo inhibitor incidence differs between PTPs receiving full‐length recombinant FVIII (FL‐rFVIII) and B‐domain deleted recombinant FVIII (BDD‐rFVIII). Methods: Prospective studies with data on inhibitors in PTPs receiving FL‐rFVIII or BDD‐rFVIII were sought using systematic methods including bibliographic database searches. Data were secured from published study reports and inquiries to investigators. Between‐group differences in inhibitor incidence rates were evaluated using mixed effects Cox regression. Results: Twenty‐nine studies with 3012 total PTPs were included. Patients were at risk of de novo inhibitor development for a median of 79 exposure days. A total of 35 de novo inhibitors were observed. The cumulative hazard for all de novo inhibitors was 1.25% with a 95% confidence interval (CI) of 0.63–1.88%. The corresponding rate for high‐titer de novo inhibitors > 5 Bethesda units (BU) was 0.29% (CI, 0.01–0.57%). Exposure to BDD‐rFVIII was associated with an increased risk of all de novo inhibitors (hazard ratio, 7.26; CI, 2.12–24.9; P = 0.0016) and of high‐titer de novo inhibitors (hazard ratio, 10.8; CI, 2.17–53.7; P = 0.0037), compared with FL‐rFVIII. Conclusions: This meta‐analysis of prospective clinical studies suggests that recombinant FVIII products may differ in immunogenicity.
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