Interpretation of serological assays in Lyme borreliosis requires an understanding of the clinical indications and the limitations of the currently available tests. We therefore systematically ...reviewed the accuracy of serological tests for the diagnosis of Lyme borreliosis in Europe.
We searched EMBASE en MEDLINE and contacted experts. Studies evaluating the diagnostic accuracy of serological assays for Lyme borreliosis in Europe were eligible. Study selection and data-extraction were done by two authors independently. We assessed study quality using the QUADAS-2 checklist. We used a hierarchical summary ROC meta-regression method for the meta-analyses. Potential sources of heterogeneity were test-type, commercial or in-house, Ig-type, antigen type and study quality. These were added as covariates to the model, to assess their effect on test accuracy.
Seventy-eight studies evaluating an Enzyme-Linked ImmunoSorbent assay (ELISA) or an immunoblot assay against a reference standard of clinical criteria were included. None of the studies had low risk of bias for all QUADAS-2 domains. Sensitivity was highly heterogeneous, with summary estimates: erythema migrans 50% (95% CI 40% to 61%); neuroborreliosis 77% (95% CI 67% to 85%); acrodermatitis chronica atrophicans 97% (95% CI 94% to 99%); unspecified Lyme borreliosis 73% (95% CI 53% to 87%). Specificity was around 95% in studies with healthy controls, but around 80% in cross-sectional studies. Two-tiered algorithms or antibody indices did not outperform single test approaches.
The observed heterogeneity and risk of bias complicate the extrapolation of our results to clinical practice. The usefulness of the serological tests for Lyme disease depends on the pre-test probability and subsequent predictive values in the setting where the tests are being used. Future diagnostic accuracy studies should be prospectively planned cross-sectional studies, done in settings where the test will be used in practice.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Current flu vaccines provide only limited coverage against seasonal strains of influenza viruses. The identification of V H 1-69 antibodies that broadly neutralize almost all influenza A group 1 ...viruses constituted a breakthrough in the influenza field. Here, we report the isolation and characterization of a human monoclonal antibody CR8020 with broad neutralizing activity against most group 2 viruses, including H3N2 and H7N7, which cause severe human infection. The crystal structure of Fab CR8020 with the 1968 pandemic H3 hemagglutinin (HA) reveals a highly conserved epitope in the HA stalk distinct from the epitope recognized by the V H 1-69 group 1 antibodies. Thus, a cocktail of two antibodies may be sufficient to neutralize most influenza A subtypes and, hence, enable development of a universal flu vaccine and broad-spectrum antibody therapies.
Modified two-tier testing (MTTT) for Lyme borreliosis (i.e. confirmation with an EIA instead of an immunoblot) has been shown to have improved sensitivity compared with standard two-tier testing ...(STTT) in samples from American patients, without losing specificity. The current study assesses the sensitivity and specificity of various algorithms of MTTT in European patients with erythema migrans (EM) as a model disease for early Lyme borreliosis, and in appropriate controls. Four different immunoassays were used in the first tier, followed by either an immunoblot or the C6-EIA, or were used as standalone single-tier test. These tests were performed on consecutively collected sera of 228 Dutch patients with physician-diagnosed EM in the setting of general practice, 231 controls from the general population, and 50 controls with potentially cross-reactive antibodies. All the variants of MTTT that were studied had significantly higher sensitivity compared with their equivalent STTT, while retaining comparable specificity. Within the MTTT algorithms, classifying equivocal results as positive yielded better diagnostic parameters than classifying equivocal results as negative. The best diagnostic parameters were found using the Enzygnost-2 assay in the first tier, followed by a C6-ELISA in the second tier (sensitivity 77.6%, 95% CI 71.7–82.9; specificity 96.1%, 95% CI 92.7–98.2). This algorithm performed significantly better than the equivalent STTT algorithm in terms of sensitivity (
p
< 0.001), while maintaining comparable specificity (population controls
p
= 0.617). Our results show that MTTT can be a useful tool for the serodiagnosis of European patients with early Lyme borreliosis.
Abstract Numerous tests for the detection of antibodies against Borrelia burgdorferi are commercially available. Manufacturer-derived data invariably report a high sensitivity and specificity, but ...comparative studies demonstrate large differences in clinical practice, especially with regard to specificity. We retrospectively collected data from validation studies for B. burgdorferi antibody assays from 8 laboratories in the Netherlands. The total number of samples was 809. Samples were selected based on clinical and laboratory parameters. We included samples from patients with erythema migrans, acrodermatitis chronicum atrophicans, and neuroborreliosis; cross-reactivity controls; and healthy controls. Data are presented from 10 enzyme-linked immunosorbent assays and 5 immunoblots. For manifestations of B. burgdorferi infection with short disease duration, the positivity rate of the assays varied significantly. In patients with long disease duration, the positivity rate differed only marginally. In cross-reactivity controls, there was significant variation in the reactivity rate. The majority of false-positive reactions are of the IgM isotype.
Seasonal influenza vaccines are updated almost annually to match the antigenic drift in influenza hemagglutinin (HA) surface glycoprotein. A new HA stem-based antigen, the so-called "mini-HA," was ...recently shown to induce cross-protective antibodies. However, cross-reactive antibodies targeting the HA stem can also be found in mice and humans after administration of seasonal vaccine. This has raised the question whether in similar conditions such a mini-HA would be able to show an increased breadth of protection over immunization with full length (FL) HA. We show in mice that in a direct comparison to H1 FL HA, using the same immunization regimen, dosing and adjuvant, a group 1 mini-HA has a higher protective efficacy against group 1 influenza virus challenges not homologous to the H1 FL HA. Although both antigens induce a similar breadth of HA subtype binding, mini-HA immunization induces significantly more HA stem-specific antibodies correlating with survival. In addition, both mini-HA and H1 FL HA immunization induce influenza neutralizing antibodies while mini-HA induces significantly higher levels of mFcγRIII activation, involved in Fc-mediated antibody effector functions. In agreement with previous findings, this confirms that more than one mechanism contributes to protection against influenza. Together our results further warrant the development of a universal influenza vaccine based on the HA stem region.
Purpose:
Spectral information of the output of x‐ray tubes in (dual source) computer tomography (CT) scanners can be used to improve the conversion of CT numbers to proton stopping power and can be ...used to advantage in CT scanner quality assurance. The purpose of this study is to design, validate, and apply a compact portable Compton spectrometer that was constructed to accurately measure x‐ray spectra of CT scanners.
Methods:
In the design of the Compton spectrometer, the shielding materials were carefully chosen and positioned to reduce background by x‐ray fluorescence from the materials used. The spectrum of Compton scattered x‐rays alters from the original source spectrum due to various physical processes. Reconstruction of the original x‐ray spectrum from the Compton scattered spectrum is based on Monte Carlo simulations of the processes involved. This reconstruction is validated by comparing directly and indirectly measured spectra of a mobile x‐ray tube. The Compton spectrometer is assessed in a clinical setting by measuring x‐ray spectra at various tube voltages of three different medical CT scanner x‐ray tubes.
Results:
The directly and indirectly measured spectra are in good agreement (their ratio being 0.99) thereby validating the reconstruction method. The measured spectra of the medical CT scanners are consistent with theoretical spectra and spectra obtained from the x‐ray tube manufacturer.
Conclusions:
A Compton spectrometer has been successfully designed, constructed, validated, and applied in the measurement of x‐ray spectra of CT scanners. These measurements show that our compact Compton spectrometer can be rapidly set‐up using the alignment lasers of the CT scanner, thereby enabling its use in commissioning, troubleshooting, and, e.g., annual performance check‐ups of CT scanners.
Abstract
The extraction system of the superconducting AGOR cyclotron consists of an electrostatic deflector and three electromagnetic channels. As the electrostatic deflector has only a moderate ...field strength (<100 kV/cm), the first electromagnetic channel (EMC1) has to generate a rather strong dipole component resulting in current densities up to 169 A/mm
2
in water-cooled copper coils. In the original design the coils consist of sections of hollow conductors, parallel to the beam path, vacuum-brazed to machined “bridges” over the beam aperture. Altogether there are over 200 brazed joints made in three subsequent cycles in the three coils (dipole, quadrupole and first harmonic corrector). In 25 years of operation two channels of this type have been “consumed”. The channels developed water leaks due to erosion of the copper by the high speed cooling water flow in the “bridge” regions that ultimately could not be repaired anymore. To remedy this problem the channel has been redesigned using bent conductors. A production technique for small radius bends and a new joining method to avoid vacuum brazing have been developed. The coil support taking up the 10 kN/m Lorentz forces on the windings are now made from isolating material instead of anodized aluminium to prevent grounding errors. The new channel (EMC1-U) has been in operation now for two years without any failure. A detailed comparison of the old and new design will be presented.
Soy protein isolate (SPI) and wheat gluten (WG) films can be cast from appropriate solvent systems. Such films can find use as edible or nonedible food packaging materials. The effect of pH of WG and ...SPI film-forming solutions on film formation, tensile strength TS), percentage elongation at break E), and water vapor permeability (WVP) was investigated. WG films formed within pH 2-4 and 9-13, whereas SPI films formed within pH 1-3 and 6-12. Film formation was inhibited by poor protein dispersion around the isoelectric pH region of SPI (pH 4.5) and WG (pH 7.6). SPI films prepared from pH 6 to 11 had significantly (P 0.05) higher TS, higher E, and lower WVP than films from pH 1 to 3. WG films produced under alkaline conditions had significantly P 0.05) higher TS than films processed under acidic conditions
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