450 research outputs found
Design of vaccine efficacy trials during public health emergencies
Public Health Emergencies (PHEs) provide a complex and challenging environment for vaccine evaluation. Under the R&D Blueprint Plan of Action, the World Health Organization (WHO) has convened a group of experts to agree on standard procedures to rapidly evaluate experimental vaccines during PHEs while maintaining the highest scientific and ethical standards. The Blueprint priority diseases, selected for their likelihood to cause PHEs and the lack of adequate medical countermeasures,were used to frame our methodological discussions. Here, we outline major vaccine study designs to be used in PHEs and summarize high-level recommendations for their use in this setting. We recognize that the epidemiology and transmission dynamics of the Blueprint priority diseasesmay be highly uncertain and that the unique characteristics of the vaccines and outbreak settings may affect our study design. To address these challenges, our group underscores the need for novel, flexible,and responsive trial designs. We conclude that assignment to study groups using randomization is a key principle underlying rigorous study design and should be utilized except in exceptional circumstances. Advance planning for vaccine trial designs is critical for rapid and effective response to a PHE and to advance knowledge to address and mitigate future PHEs
Interpreting ambiguous ‘trace’ results in Schistosoma mansoni CCA Tests: Estimating sensitivity and specificity of ambiguous results with no gold standard
Background The development of new diagnostics is an important tool in the fight against disease. Latent Class Analysis (LCA) is used to estimate the sensitivity and specificity of tests in the absence of a gold standard. The main field diagnostic for Schistosoma mansoni infection, Kato-Katz (KK), is not very sensitive at low infection intensities. A point-of-care circulating cathodic antigen (CCA) test has been shown to be more sensitive than KK. However, CCA can return an ambiguous ‘trace’ result between ‘positive’ and ‘negative’, and much debate has focused on interpretation of traces results. Methodology/Principle findings We show how LCA can be extended to include ambiguous trace results and analyse S. mansoni studies from both Côte d’Ivoire (CdI) and Uganda. We compare the diagnostic performance of KK and CCA and the observed results by each test to the estimated infection prevalence in the population. Prevalence by KK was higher in CdI (13.4%) than in Uganda (6.1%), but prevalence by CCA was similar between countries, both when trace was assumed to be negative (CCAtn: 11.7% in CdI and 9.7% in Uganda) and positive (CCAtp: 20.1% in CdI and 22.5% in Uganda). The estimated sensitivity of CCA was more consistent between countries than the estimated sensitivity of KK, and estimated infection prevalence did not significantly differ between CdI (20.5%) and Uganda (19.1%). The prevalence by CCA with trace as positive did not differ significantly from estimates of infection prevalence in either country, whereas both KK and CCA with trace as negative significantly underestimated infection prevalence in both countries. Conclusions Incorporation of ambiguous results into an LCA enables the effect of different treatment thresholds to be directly assessed and is applicable in many fields. Our results showed that CCA with trace as positive most accurately estimated infection prevalence
Hurricanes and climate in the Caribbean during the past 3700 years BP
International audienceA multiproxy analysis of lacustrine sediments cored in Grand-Case Pond at Saint-Martin, north of the Lesser Antilles archipelago, reveals three distinct climatic periods for the last 3700 years. From 3700 to ~2500 yr cal. BP and from 1150 yr cal. BP to the present, carbonate mud deposition occurred in connection with pond lowstands. These periods were also punctuated by severe drought events, marked by gypsum laminae, and hurricane landfalls, leading to marine sand inputs into the pond. The intermediate time interval, from 2500 to 1150 yr cal. BP, is typified by black organic mud deposition, suggesting that hypoxic to anoxic conditions prevailed at the pond bottom. These were probably linked with a perennial pond highstand and reflect more uniform and wetter climatic conditions than today. The carbon isotopic composition of the ostracod Perissocytheridea bisulcata shows that the lowest δ13C values are recorded during the hypoxic periods, as a consequence of bacterial recycling of isotopically depleted organic matter. Such a climatic history agrees closely with that documented from other records in the Caribbean area, such as the Cariaco Basin, central coast of Belize or Barbados. By constrast, discrepancies seem to emerge from the comparison between hurricane activity recorded at Saint-Martin on the one hand and Vieques (Puerto Rico) on the other hand. We explain this apparent contradiction by a balance between two distinct storm paths in response to latitudinal shifts of the Intertropical Convergence Zone (ITCZ). Stronger storm activity over the Gulf coast and the inner Caribbean Sea is favoured by a southern position of the ITCZ in connection with dry climatic conditions. Plausible links with the North Atlantic Oscillation (NAO) are also suggested
Photo- and Electroproduction of Eta Mesons
Eta photo- and electroproduction off the nucleon is investigated in an
effective lagrangian approach that contains Born terms and both vector meson
and nucleon resonance contributions. In particular, we review and develop the
formalism for coincidence experiments with polarization degrees of freedom. The
different response functions appearing in single and double polarization
experiments have been studied. We will present calculations for structure
functions and kinematical conditions that are most sensitive to details of the
lagrangian, in particular with regard to contributions of nucleon resonances
beyond the dominant (1535) resonance.Comment: 24 pages RevTeX/LaTeX2.09, NFSS1, 13 figures (in separate file
(tar,gzip and uue)), accepted for publication in Z. Phys.
Flux-Induced Vortex in Mesoscopic Superconducting Loops
We predict the existence of a quantum vortex for an unusual situation. We
study the order parameter in doubly connected superconducting samples embedded
in a uniform magnetic field. For samples with perfect cylindrical symmetry, the
order parameter has been known for long and no vortices are present in the
linear regime. However, if the sample is not symmetric, there exist ranges of
the field for which the order parameter vanishes along a line, parallel to the
field. In many respects, the behavior of this line is qualitatively different
from that of the vortices encountered in type II superconductivity. For samples
with mirror symmetry, this flux-induced vortex appears at the thin side for
small fluxes and at the opposite side for large fluxes. We propose direct and
indirect experimental methods which could test our predictions.Comment: 6 pages, Latex, 4 figs., uses RevTex, extended to situations far from
cylindrical symmetr
Magnetic resonance lung function – a breakthrough for lung imaging and functional assessment? A phantom study and clinical trial
BACKGROUND: Chronic lung diseases are a major issue in public health. A serial pulmonary assessment using imaging techniques free of ionizing radiation and which provides early information on local function impairment would therefore be a considerably important development. Magnetic resonance imaging (MRI) is a powerful tool for the static and dynamic imaging of many organs. Its application in lung imaging however, has been limited due to the low water content of the lung and the artefacts evident at air-tissue interfaces. Many attempts have been made to visualize local ventilation using the inhalation of hyperpolarized gases or gadolinium aerosol responding to MRI. None of these methods are applicable for broad clinical use as they require specific equipment. METHODS: We have shown previously that low-field MRI can be used for static imaging of the lung. Here we show that mathematical processing of data derived from serial MRI scans during the respiratory cycle produces good quality images of local ventilation without any contrast agent. A phantom study and investigations in 85 patients were performed. RESULTS: The phantom study proved our theoretical considerations. In 99 patient investigations good correlation (r = 0.8; p ≤ 0.001) was seen for pulmonary function tests and MR ventilation measurements. Small ventilation defects were visualized. CONCLUSION: With this method, ventilation defects can be diagnosed long before any imaging or pulmonary function test will indicate disease. This surprisingly simple approach could easily be incorporated in clinical routine and may be a breakthrough for lung imaging and functional assessment
Hard Two-Photon Contribution to Elastic Lepton-Proton Scattering: Determined by the OLYMPUS Experiment
The OLYMPUS collaboration reports on a precision measurement of the
positron-proton to electron-proton elastic cross section ratio, ,
a direct measure of the contribution of hard two-photon exchange to the elastic
cross section. In the OLYMPUS measurement, 2.01~GeV electron and positron beams
were directed through a hydrogen gas target internal to the DORIS storage ring
at DESY. A toroidal magnetic spectrometer instrumented with drift chambers and
time-of-flight scintillators detected elastically scattered leptons in
coincidence with recoiling protons over a scattering angle range of to . The relative luminosity between the two beam species
was monitored using tracking telescopes of interleaved GEM and MWPC detectors
at , as well as symmetric M{\o}ller/Bhabha calorimeters at
. A total integrated luminosity of 4.5~fb was collected. In
the extraction of , radiative effects were taken into account
using a Monte Carlo generator to simulate the convolutions of internal
bremsstrahlung with experiment-specific conditions such as detector acceptance
and reconstruction efficiency. The resulting values of , presented
here for a wide range of virtual photon polarization ,
are smaller than some hadronic two-photon exchange calculations predict, but
are in reasonable agreement with a subtracted dispersion model and a
phenomenological fit to the form factor data.Comment: 5 pages, 3 figures, 2 table
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