162 research outputs found
Diagnosing Latent Tuberculosis Infection in the HIV Era
Tuberculin skin testing (TST) and Interferon-gamma (IFNγ)release assays (IGRAs) are presently the only available assays for the detection of Mycobacterium tuberculosis infected individuals. IGRAs might progressively replace TST, as numerous published reports establish their higher specificity and similar sensitivity when tested in BCG vaccinated, immunocompetent individuals or in populations who may have been in contact with atypical mycobacteria. However, few published reports have commented on their role in TB diagnosis in immunocompromised individuals (HIV, immunosuppressive therapy, cancer…). It is the purpose of this report to review IGRAs published studies in HIV individuals in endemic and non endemic area for tuberculosis (TB). IGRAs were tested in the presence or absence of active TB but correlated to duration of exposure. In newly diagnosed active TB, IGRAs demonstrated a similar sensitivity to TST. In TB non infected individuals, TST and IGRAs also gave similar values when categorization of individuals was correlated to the risk of infection. A higher number of positive IGRAs was observed in individuals from TB endemic areas, in similar proportions to immunocompetent individuals. Comparison between the two IGRAs: QuantiFERON-TB Gold® (QF-TB, Cellestis, Australia) and T-SPOT-TB® (Oxford Immunotec, UK), and against TST, in the same HIV population demonstrates a higher sensitivity of T-SPOT-TB and TST than QF-TB. Indeterminate results, which correspond to the absence of a positive T-cell IFNγ response towards phytohemaglutinin (PHA), is a key point when comparing both IGRAs. This PHA control is indicative of the level of immunosuppression observed in the tested individual. QF-TB seems to present, in HIV populations, more indeterminate results than T-SPOT-TB. The calibration and/or concentration of PBMC on nitrocellulose membrane for the T-SPOT-TB, as compared to a whole blood assay, might explain this difference, with less indeterminate results with the T-SPOT-TB assay. Neither assay is able to differentiate active TB from latent TB infection (LTBI). Several laboratories have tried new antigenic epitopes to solve this issue. It is of importance that these studies need to be repeated on a larger scale by others to validate their results. Two blood assays might add information characterising the evolution from LTBI to active TB: either by losing protective immunity, as demonstrated by the whole blood killing assay, or by evaluating the kinetics of the antibodies synthesized against M. tuberculosis specific antigens. In conclusion, longitudinal studies are still needed to validate IGRAs and other assays and to define their respective predictive values
An independent determination of Fomalhaut b's orbit and the dynamical effects on the outer dust belt
The nearby star Fomalhaut harbours a cold, moderately eccentric dust belt
with a sharp inner edge near 133 au. A low-mass, common proper motion companion
(Fom b), was discovered near the inner edge and was identified as a planet
candidate that could account for the belt morphology. However, the most recent
orbit determination based on four epochs of astrometry over eight years reveals
a highly eccentric orbit that appears to cross the belt in the sky plane
projection. We perform here a full orbital determination based on the available
astrometric data to independently validate the orbit estimates previously
presented. Adopting our values for the orbital elements and their associated
uncertainties, we then study the dynamical interaction between the planet and
the dust ring, to check whether the proposed disk sculpting scenario by Fom b
is plausible. We used a dedicated MCMC code to derive the statistical
distributions of the orbital elements of Fom b. Then we used symplectic N-body
integration to investigate the dynamics of the dust belt, as perturbed by a
single planet. Different attempts were made assuming different masses for Fom
b. We also performed a semi-analytical study to explain our results. Our
results are in good agreement with others regarding the orbit of Fom b. We find
that the orbit is highly eccentric, is close to apsidally aligned with the
belt, and has a moderate mutual inclination relative to the belt plane of. If
coplanar, this orbit crosses the disk. Our dynamical study then reveals that
the observed planet could sculpt a transient belt configuration with a similar
eccentricity to what is observed, but it would not be simultaneously apsidally
aligned with the planet. This transient configuration only occurs a short time
after the planet is placed on such an orbit (assuming an initially circular
disk), a time that is inversely proportional to the planet's mass, and that is
in any case much less than the 440 Myr age of the star. We constrain how long
the observed dust belt could have survived with Fom b on its current orbit, as
a function of its possible mass. This analysis leads us to conclude that Fom b
is likely to have low mass, that it is unlikely to be responsible for the
sculpting of the belt, and that it supports the hypothesis of a more massive,
less eccentric planet companion Fom c.Comment: 17 pages, 15 figures, accepted for publication in Astronomy \&
Astrophysic
DC-SIGN Is the Major Mycobacterium tuberculosis Receptor on Human Dendritic Cells
Early interactions between lung dendritic cells (LDCs) and Mycobacterium tuberculosis, the etiological agent of tuberculosis, are thought to be critical for mounting a protective anti-mycobacterial immune response and for determining the outcome of infection. However, these interactions are poorly understood, at least at the molecular level. Here we show that M. tuberculosis enters human monocyte-derived DCs after binding to the recently identified lectin DC-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN). By contrast, complement receptor (CR)3 and mannose receptor (MR), which are the main M. tuberculosis receptors on macrophages (Mφs), appeared to play a minor role, if any, in mycobacterial binding to DCs. The mycobacteria-specific lipoglycan lipoarabinomannan (LAM) was identified as a key ligand of DC-SIGN. Freshly isolated human LDCs were found to express DC-SIGN, and M. tuberculosis–derived material was detected in CD14−HLA-DR+DC-SIGN+ cells in lymph nodes (LNs) from patients with tuberculosis. Thus, as for human immunodeficiency virus (HIV), which is captured by the same receptor, DC-SIGN–mediated entry of M. tuberculosis in DCs in vivo is likely to influence bacterial persistence and host immunity
Superconductivity in Li3Ca2C6 intercalated graphite
In this letter, we report the discovery of superconductivity in Li3Ca2C6.
Several graphite intercalation compounds (GICs) with electron donors, are well
known as superconductors. It is probably not astonishing, since it is generally
admitted that low dimensionality promotes high superconducting transition
temperatures. Superconductivity is lacking in pristine graphite, but after
charging the graphene planes by intercalation, its electronic properties change
considerably and superconducting behaviour can appear. Li3Ca2C6 is a ternary
GIC, for which the intercalated sheets are very thick and poly-layered (five
lithium layers and two calcium ones). It contains a great amount of metal (five
metallic atoms for six carbon ones). Its critical temperature of 11.15 K is
very close to that of CaC6 GIC (11.5 K). Both CaC6 and Li3Ca2C6 GICs possess
currently the highest transition temperatures among all the GICs.Comment: 5 pages, 3 figure
SPHERE IRDIS and IFS astrometric strategy and calibration
We present the current results of the astrometric characterization of the VLT
planet finder SPHERE over 2 years of on-sky operations. We first describe the
criteria for the selection of the astrometric fields used for calibrating the
science data: binaries, multiple systems, and stellar clusters. The analysis
includes measurements of the pixel scale and the position angle with respect to
the North for both near-infrared subsystems, the camera IRDIS and the integral
field spectrometer IFS, as well as the distortion for the IRDIS camera. The
IRDIS distortion is shown to be dominated by an anamorphism of 0.60+/-0.02%
between the horizontal and vertical directions of the detector, i.e. 6 mas at
1". The anamorphism is produced by the cylindrical mirrors in the common path
structure hence common to all three SPHERE science subsystems (IRDIS, IFS, and
ZIMPOL), except for the relative orientation of their field of view. The
current estimates of the pixel scale and North angle for IRDIS are
12.255+/-0.009 milliarcseconds/pixel for H2 coronagraphic images and
-1.75+/-0.08 deg. Analyses of the IFS data indicate a pixel scale of
7.46+/-0.02 milliarcseconds/pixel and a North angle of -102.18+/-0.13 deg. We
finally discuss plans for providing astrometric calibration to the SPHERE users
outside the instrument consortium.Comment: 12 pages, 6 figures, 3 table
High precision astrometry mission for the detection and characterization of nearby habitable planetary systems with the Nearby Earth Astrometric Telescope (NEAT)
(abridged) A complete census of planetary systems around a volume-limited
sample of solar-type stars (FGK dwarfs) in the Solar neighborhood with uniform
sensitivity down to Earth-mass planets within their Habitable Zones out to
several AUs would be a major milestone in extrasolar planets astrophysics. This
fundamental goal can be achieved with a mission concept such as NEAT - the
Nearby Earth Astrometric Telescope. NEAT is designed to carry out space-borne
extremely-high-precision astrometric measurements sufficient to detect
dynamical effects due to orbiting planets of mass even lower than Earth's
around the nearest stars. Such a survey mission would provide the actual
planetary masses and the full orbital geometry for all the components of the
detected planetary systems down to the Earth-mass limit. The NEAT performance
limits can be achieved by carrying out differential astrometry between the
targets and a set of suitable reference stars in the field. The NEAT instrument
design consists of an off-axis parabola single-mirror telescope, a detector
with a large field of view made of small movable CCDs located around a fixed
central CCD, and an interferometric calibration system originating from
metrology fibers located at the primary mirror. The proposed mission
architecture relies on the use of two satellites operating at L2 for 5 years,
flying in formation and offering a capability of more than 20,000
reconfigurations (alternative option uses deployable boom). The NEAT primary
science program will encompass an astrometric survey of our 200 closest F-, G-
and K-type stellar neighbors, with an average of 50 visits. The remaining time
might be allocated to improve the characterization of the architecture of
selected planetary systems around nearby targets of specific interest (low-mass
stars, young stars, etc.) discovered by Gaia, ground-based high-precision
radial-velocity surveys.Comment: Accepted for publication in Experimental Astronomy. The full member
list of the NEAT proposal and the news about the project are available at
http://neat.obs.ujf-grenoble.fr. The final publication is available at
http://www.springerlink.co
DC-SIGN Induction in Alveolar Macrophages Defines Privileged Target Host Cells for Mycobacteria in Patients with Tuberculosis
BACKGROUND: Interplays between Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB) in human and host professional phagocytes, namely macrophages (Mφs) and dendritic cells (DCs), are central to immune protection against TB and to TB pathogenesis. We and others have recently shown that the C-type lectin dendritic cell–specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN; CD209) mediates important interactions between mycobacteria and human monocyte-derived DCs (MoDCs) in vitro. METHODS AND FINDINGS: In order to explore the possible role of DC-SIGN in M. tuberculosis infection in vivo, we have analysed DC-SIGN expression in broncho-alveolar lavage (BAL) cells from patients with TB (n = 40) or with other non-mycobacterial lung pathologies, namely asthma (n = 14) and sarcoidosis (n = 11), as well as from control individuals (n = 9). We show that in patients with TB, up to 70% of alveolar Mφs express DC-SIGN. By contrast, the lectin is barely detected in alveolar Mφs from all other individuals. Flow cytometry, RT-PCR, and enzyme-linked immunosorbent assay analyses of BAL-derived fluids and cells indicated that M. tuberculosis infection induces DC-SIGN expression in alveolar Mφs by a mechanism that is independent of Toll-like receptor-4, interleukin (IL)-4, and IL-13. This mechanism most likely relies on the secretion of soluble host and/or mycobacterial factors that have yet to be identified, as both infected and uninfected bystander Mφs were found to express DC-SIGN in the presence of M. tuberculosis. Immunohistochemical examination of lung biopsy samples from patients with TB showed that the bacilli concentrate in pulmonary regions enriched in DC-SIGN-expressing alveolar Mφs in vivo. Ex vivo binding and inhibition of binding experiments further revealed that DC-SIGN–expressing alveolar Mφs constitute preferential target cells for M. tuberculosis, as compared to their DC-SIGN(−) counterparts. In contrast with what has been reported previously in MoDCs in vitro, ex vivo DC-SIGN ligation by mycobacterial products failed to induce IL-10 secretion by alveolar Mφs, and IL-10 was not detected in BALs from patients with TB. CONCLUSION: Altogether, our results provide further evidence for an important role of DC-SIGN during TB in humans. DC-SIGN induction in alveolar Mφs may have important consequences on lung colonization by the tubercle bacillus, and on pulmonary inflammatory and immune responses in the infected host
Pilot testing the EARS-Vet surveillance network for antibiotic resistance in bacterial pathogens from animals in the EU/EEA
IntroductionAs part of the EU Joint Action on Antimicrobial Resistance (AMR) and Healthcare-Associated Infections, an initiative has been launched to build the European AMR Surveillance network in veterinary medicine (EARS-Vet). So far, activities included mapping national systems for AMR surveillance in animal bacterial pathogens, and defining the EARS-Vet objectives, scope, and standards. Drawing on these milestones, this study aimed to pilot test EARS-Vet surveillance, namely to (i) assess available data, (ii) perform cross-country analyses, and (iii) identify potential challenges and develop recommendations to improve future data collection and analysis.MethodsEleven partners from nine EU/EEA countries participated and shared available data for the period 2016–2020, representing a total of 140,110 bacterial isolates and 1,302,389 entries (isolate-antibiotic agent combinations).ResultsCollected data were highly diverse and fragmented. Using a standardized approach and interpretation with epidemiological cut-offs, we were able to jointly analyze AMR trends of 53 combinations of animal host-bacteria–antibiotic categories of interest to EARS-Vet. This work demonstrated substantial variations of resistance levels, both among and within countries (e.g., between animal host species).DiscussionKey issues at this stage include the lack of harmonization of antimicrobial susceptibility testing methods used in European surveillance systems and veterinary diagnostic laboratories, the absence of interpretation criteria for many bacteria–antibiotic combinations of interest, and the lack of data from a lot of EU/EEA countries where little or even surveillance currently exists. Still, this pilot study provides a proof-of-concept of what EARS-Vet can achieve. Results form an important basis to shape future systematic data collection and analysis
Temporal Dynamics of Interferon Gamma Responses in Children Evaluated for Tuberculosis
BACKGROUND: Development of T-cells based-Interferon gamma (IFNgamma) assays has offered new possibilities for the diagnosis of latent tuberculosis infection (LTBI) and active disease in adults. Few studies have been performed in children, none in France. With reference to the published data on childhood TB epidemiology in the Paris and Ile de France Region, we considered it important to evaluate the performance of IGRA (QuantiFERON TB Gold In Tube(R), QF-TB-IT) in the diagnosis and the follow-up through treatment of LTBI and active TB in a cohort of French children. METHODOLOGY/PRINCIPAL FINDINGS: 131 children were recruited during a prospective and multicentre study (October 2005 and May 2007; Ethical Committee St Louis Hospital, Paris, study number 2005/32). Children were sampled at day 0, 10, 30, 60 (except Healthy Contacts, HC) and 90 for LTBI and HC, and a further day 120, and day 180 for active TB children. Median age was 7.4 years, with 91% of the children BCG vaccinated. LTBI and active TB children undergoing therapy produced significant higher IFNgamma values after 10 days of treatment (p = 0.035). In addition, IFNgamma values were significantly lower at the end of treatment compared to IFNgamma values at day 0, although the number of positive patients was not significantly different between day 0 and end of treatment. CONCLUSIONS/ SIGNIFICANCE: By following quantitative IFNgamma values in each enrolled child with LTBI or active TB and receiving treatment, we were able to detect an increase in the IFNgamma response at day 10 of treatment which might allow the confirmation of a diagnosis. In addition, a decline in IFNgamma values during treatment makes it possible for clinicians to monitor the effect of preventive or curative therapy
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