654 research outputs found
Cold atom gas at very high densities in an optical surface microtrap
An optical microtrap is realized on a dielectric surface by crossing a
tightly focused laser beam with an horizontal evanescent-wave atom mirror. The
nondissipative trap is loaded with cesium atoms through elastic
collisions from a cold reservoir provided by a large-volume optical surface
trap. With an observed 300-fold local increase of the atomic number density
approaching , unprecedented conditions of cold atoms
close to a surface are realized
EQ-5D-5L versus 3L: the impact on cost-effectiveness
Objectives To model the relationship between EQ-5D-3L and EQ-5D-5L and examine how differences impact on cost-effectiveness in case studies. Methods We used two datasets that included both EQ-5D-3L and EQ-5D-3L from the same respondents. The EuroQoL dataset (n=3551) included patients with different diseases and a healthy cohort. The National Databank (NDB) dataset included patients with rheumatoid disease (n=5205). We estimated a system of ordinal regressions in each dataset using copula models, to link responses to the 3L instrument to 5L and its tariff, and vice versa. Results were applied to nine cost-effectiveness studies. Results Best-fitting models differed between EuroQoL and NDB datasets in terms of the explanatory variables, copulas and coefficients. In both cases the coefficients of the covariates and latent factor between -3L and -5L were significantly different, indicating that the two instruments are not a uniform realignment of the response levels for most dimensions. In the case studies, moving from 3L to 5L caused a decrease of up to 87% in incremental QALYs gained from effective technologies in almost all cases. ICERs increased, often substantially. Conversely, one technology with a significant mortality gain saw increased incremental QALYs. Conclusion 5L shifts mean utility scores up the utility scale towards full health and compresses them into a smaller range, compared to -3L. Improvements in quality of life are valued less using 5L than with 3L. 3L and 5L can produce substantially different estimates of cost effectiveness. There is no simple proportional adjustment that can be made to reconcile these differences
Positron Emission Tomography/Computed Tomography with Gallium-68-labeled Prostate-specific Membrane Antigen Detects Relapse After Vascular-targeted Photodynamic Therapy in a Prostate Cancer Model
BACKGROUND: Evaluating the efficacy of focal therapy for prostate cancer is limited by current approaches and may be improved with biological imaging techniques.
OBJECTIVE: We assessed whether positron emission tomography/computed tomography with gallium-68-labeled prostate-specific membrane antigen (Ga-PSMA PET/CT) can be used to predict relapse after vascular-targeted photodynamic therapy (VTP).
DESIGN, SETTING, AND PARTICIPANTS: A total of 1Ă10 LNCaP cells were grafted subcutaneously in the flanks of 6-8-wk-old SCID mice. Of 24 mice with measurable tumors 6 wk after tumor implantation, 20 were treated with VTP (150mW/cm) to ablate the tumors. Blood prostate-specific antigen (PSA) levels were assessed, and â¶âžGa-PSMA PET/CT images were performed 1 d before VTP and 1 and 4 wk after.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Local tumor relapse was evaluated by histology, and tumors were analyzed by prostate-specific membrane antigen (PSMA) and PSA immunohistochemistry. T tests and Kruskal-Wallis tests were used to determine significance.
RESULTS AND LIMITATIONS: Four weeks after VTP, 11 (65%) mice had complete responses and six (35%) had tumor relapses confirmed by histology (hematoxylin and eosin, and PSMA immunohistochemistry). All mice with local relapse had positive Ga-PSMA PET/CT findings 4 wk after VTP; all complete responders did not. One week after VTP, the relapse detection sensitivity of Ga-PSMA PET/CT was 75%, whereas the sensitivity of PSA was only 33%. Compared with controls, relapsed tumors had a three-fold reduction in the number of cells with strong PSA staining by immunohistochemistry (1.5% vs 4.5%; p=0.01).
CONCLUSIONS: In a preclinical prostate cancer model, we show that Ga-PSMA PET/CT can identify and predict relapse earlier than blood PSA level. These findings support further testing in clinical trials.
PATIENT SUMMARY: Positron emission tomography/computed tomography with gallium-68-labeled prostate-specific membrane antigen may be used to follow and evaluate treatment outcomes in men who receive focal therapy for prostate cancer
PGE2 inhibits TIL expansion by disrupting IL-2 signalling and mitochondrial function.
Expansion of antigen-experienced CD8+ T cells is critical for the success of tumour-infiltrating lymphocyte (TIL)-adoptive cell therapy (ACT) in patients with cancer1. Interleukin-2 (IL-2) acts as a key regulator of CD8+ cytotoxic T lymphocyte functions by promoting expansion and cytotoxic capability2,3. Therefore, it is essential to comprehend mechanistic barriers to IL-2 sensing in the tumour microenvironment to implement strategies to reinvigorate IL-2 responsiveness and T cell antitumour responses. Here we report that prostaglandin E2 (PGE2), a known negative regulator of immune response in the tumour microenvironment4,5, is present at high concentrations in tumour tissue from patients and leads to impaired IL-2 sensing in human CD8+ TILs via the PGE2 receptors EP2 and EP4. Mechanistically, PGE2 inhibits IL-2 sensing in TILs by downregulating the IL-2RÎłc chain, resulting in defective assembly of IL-2RÎČ-IL2RÎłc membrane dimers. This results in impaired IL-2-mTOR adaptation and PGC1α transcriptional repression, causing oxidative stress and ferroptotic cell death in tumour-reactive TILs. Inhibition of PGE2 signalling to EP2 and EP4 during TIL expansion for ACT resulted in increased IL-2 sensing, leading to enhanced proliferation of tumour-reactive TILs and enhanced tumour control once the cells were transferred in vivo. Our study reveals fundamental features that underlie impairment of human TILs mediated by PGE2 in the tumour microenvironment. These findings have therapeutic implications for cancer immunotherapy and cell therapy, and enable the development of targeted strategies to enhance IL-2 sensing and amplify the IL-2 response in TILs, thereby promoting the expansion of effector T cells with enhanced therapeutic potential
Search for composite and exotic fermions at LEP 2
A search for unstable heavy fermions with the DELPHI detector at LEP is
reported. Sequential and non-canonical leptons, as well as excited leptons and
quarks, are considered. The data analysed correspond to an integrated
luminosity of about 48 pb^{-1} at an e^+e^- centre-of-mass energy of 183 GeV
and about 20 pb^{-1} equally shared between the centre-of-mass energies of 172
GeV and 161 GeV. The search for pair-produced new leptons establishes 95%
confidence level mass limits in the region between 70 GeV/c^2 and 90 GeV/c^2,
depending on the channel. The search for singly produced excited leptons and
quarks establishes upper limits on the ratio of the coupling of the excited
fermio
Search for displaced vertices arising from decays of new heavy particles in 7 TeV pp collisions at ATLAS
We present the results of a search for new, heavy particles that decay at a
significant distance from their production point into a final state containing
charged hadrons in association with a high-momentum muon. The search is
conducted in a pp-collision data sample with a center-of-mass energy of 7 TeV
and an integrated luminosity of 33 pb^-1 collected in 2010 by the ATLAS
detector operating at the Large Hadron Collider. Production of such particles
is expected in various scenarios of physics beyond the standard model. We
observe no signal and place limits on the production cross-section of
supersymmetric particles in an R-parity-violating scenario as a function of the
neutralino lifetime. Limits are presented for different squark and neutralino
masses, enabling extension of the limits to a variety of other models.Comment: 8 pages plus author list (20 pages total), 8 figures, 1 table, final
version to appear in Physics Letters
Search for lightest neutralino and stau pair production in light gravitino scenarios with stau NLSP
Promptly decaying lightest neutralinos and long-lived staus are searched for
in the context of light gravitino scenarios. It is assumed that the stau is the
next to lightest supersymmetric particle (NLSP) and that the lightest
neutralino is the next to NLSP (NNLSP). Data collected with the Delphi detector
at centre-of-mass energies from 161 to 183 \GeV are analysed. No evidence of
the production of these particles is found. Hence, lower mass limits for both
kinds of particles are set at 95% C.L.. The mass of gaugino-like neutralinos is
found to be greater than 71.5 GeV/c^2. In the search for long-lived stau,
masses less than 70.0 to 77.5 \GeVcc are excluded for gravitino masses from 10
to 150 \eVcc . Combining this search with the searches for stable heavy leptons
and Minimal Supersymmetric Standard Model staus a lower limit of 68.5 \GeVcc
may be set for the stau mas
Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment
This paper describes an analysis of the angular distribution of W->enu and
W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with
the ATLAS detector at the LHC in 2010, corresponding to an integrated
luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and
the missing transverse energy, the W decay angular distribution projected onto
the transverse plane is obtained and analysed in terms of helicity fractions
f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV
and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw
> 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour,
are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017
+/- 0.030, where the first uncertainties are statistical, and the second
include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables,
revised author list, matches European Journal of Physics C versio
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