Drug allergies are heterogeneous and multifactorial diseases and are always the consequence of an exaggerated immune-mediated reaction. Previously described models of immunologic mechanisms (mainly ...based on Gell and Combs' classification) cannot fully explain the physiopathology of these diseases; it seems therefore important to identify risk factors. Clinical and biologic tests are helpful diagnostic tools but are limited in their sensitivity and reliability and are certainly not predictive. Epidemiologic data supply information concerning the prevalence of drug hypersensitivity: female gender, concomitant infections (HIV, herpes) and concurrent illnesses (systemic lupus erythematosus) are all significant risk factors. Another host-related factor is the genetic predisposition of patients and is currently under investigation in our laboratory. Most genetic studies concern HLA haplotype association or polymorphism in genes encoding drug-metabolising enzymes. A current study by our group seems to implicate polymorphisms within the promoter of IL-10, a cytokine with anti-inflammatory properties. The chemical properties of the drug and the treatment regimen also influence the development of drug allergies.
Neuroblastoma is an embryonic tumour of the sympathetic nervous system and is one of the most common cancers in childhood. A high differentiation stage has been associated with a favourable outcome; ...however, the mechanisms governing neuroblastoma cell differentiation are not completely understood. The MYCN gene is considered the hallmark of neuroblastoma. Even though it has been reported that MYCN has a role during embryonic development, it is needed its decrease so that differentiation can be completed. We aimed to better define the role of MYCN in the differentiation processes, particularly during the early stages. Considering the ability of MYCN to regulate non-coding RNAs, our hypothesis was that N-Myc protein might be necessary to activate differentiation (mimicking embryonic development events) by regulating miRNAs critical for this process. We show that MYCN expression increased in embryonic cortical neural precursor cells at an early stage after differentiation induction. To investigate our hypothesis, we used human neuroblastoma cell lines. In LAN-5 neuroblastoma cells, MYCN was upregulated after 2 days of differentiation induction before its expected downregulation. Positive modulation of various differentiation markers was associated with the increased MYCN expression. Similarly, MYCN silencing inhibited such differentiation, leading to negative modulation of various differentiation markers. Furthermore, MYCN gene overexpression in the poorly differentiating neuroblastoma cell line SK-N-AS restored the ability of such cells to differentiate. We identified three key miRNAs, which could regulate the onset of differentiation programme in the neuroblastoma cells in which we modulated MYCN. Interestingly, these effects were accompanied by changes in the apoptotic compartment evaluated both as expression of apoptosis-related genes and as fraction of apoptotic cells. Therefore, our idea is that MYCN is necessary during the activation of neuroblastoma differentiation to induce apoptosis in cells that are not committed to differentiate.
Background: Allergic reactions to β‐lactam antibiotics represent the most frequent cause of immunological drug reactions.
Objective: This study evaluates the involvement of genetic susceptibility ...factors in patients with immediate allergic reactions to β‐lactams. We examined 15 single nucleotide polymorphisms (SNP) of genes coding proteins implicated in immunoglobulin (Ig)E synthesis regulation.
Methods: We performed a case–control study involving 44 patients with immediate β‐lactam allergy and 44 control subjects, all matched for sex and atopy. Interleukin (IL)‐4, IL‐13, IL‐4Rα, signal transducer and activator of transcription 6 (STAT6), interferon (IFN)‐γR1, IFN‐γR2 and FcɛRIβ gene polymorphisms were determined using polymerase chain reaction (PCR) restriction fragment length polymorphism, and IL‐21R gene and IL‐10 promoter polymorphisms by direct sequencing.
Results: Our analysis did not reveal differences in the distribution of the 15 SNPs between allergic patients and controls. However, among atopic subjects, we found two distinct significant associations between immediate β‐lactam allergy in women and the Ile75Val variant of IL‐4Rα gene (P = 0.012, OR = 5.4, CI: 1.16–27.7), and two linked IL‐10 promoter gene polymorphisms, −819C>T and −592 C>A (P = 0.023, OR = 17.5, CI: 1.26–533.07). In contrast, we observed no association in allergic male subjects in the atopic population. Interestingly, the IL‐4Rα Ile75Val variant could have a paradoxal protective effect in atopic male patients (P = 0.004, OR = 0.07, CI: 0.01–0.66).
Conclusion: Our findings suggest that polymorphisms in the IL‐10 promoter and IL‐4Rα genes are genetic factors that favour β‐lactam immediate allergies in female patients with atopy.
One of the major challenges of modern cosmology is the detection of B-mode polarization anisotropies in the Cosmic Microwave Background. These originate from tensor fluctuations of the metric ...produced during the inflationary phase. Their detection would therefore constitute a major step towards understanding the primordial Universe. The expected level of these anisotropies is however so small that it requires a new generation of instruments with high sensitivity and extremely good control of systematic effects.
We propose the QUBIC instrument based on the novel concept of bolometric interferometry, bringing together the sensitivity advantages of bolometric detectors with the systematics effects advantages of interferometry.
The instrument will directly observe the sky through an array of entry horns whose signals will be combined together using an optical combiner. The whole set-up is located inside a cryostat. Polarization modulation will be achieved using a rotating half-wave plate and the images of the interference fringes will be formed on two focal planes (separated by a polarizing grid) tiled with bolometers.
We show that QUBIC can be considered as a synthetic imager, exactly similar to a usual imager but with a synthesized beam formed by the array of entry horns. Scanning the sky provides an additional modulation of the signal and improve the sky coverage shape. The usual techniques of map-making and power spectrum estimation can then be applied. We show that the sensitivity of such an instrument is comparable with that of an imager with the same number of horns. We anticipate a low level of beam-related systematics thanks to the fact that the synthesized beam is determined by the location of the primary horns. Other systematics should be under good control thanks to an autocalibration technique, specific to our concept, that will permit the accurate determination of most of the instrumental parameters that would otherwise lead to systematics.
Patient Safety First series. Projected impact of the US nursing shortage on patient care in the future. Rationale for the shortage, the long-term effects of the current and past economy on these ...shortages and national trends are outlined. Recommendations by regulatory bodies (Institute of Medicine and Robert Wood Foundation) to address this problem are considered and AORN's fully integrated curriculum for new perioperative nurses is presented. 24 references
Cosmological constraints from Archeops Benoît, A.; Ade, P.; Amblard, A. ...
Astronomy and astrophysics (Berlin),
03/2003, Volume:
399, Issue:
3
Journal Article
Peer reviewed
Open access
We analyze the cosmological constraints that Archeops (Benoît et al. 2003) places on adiabatic cold dark matter models with passive power-law initial fluctuations. Because its angular power spectrum ...has small bins in $\ell$ and large $\ell$ coverage down to COBE scales, Archeops provides a precise determination of the first acoustic peak in terms of position at multipole $l_{\rm peak}=220\pm 6$, height and width. An analysis of Archeops data in combination with other CMB datasets constrains the baryon content of the Universe, $\Omega_{\rm b}h^2= 0.022^{+0.003}_{-0.004}$, compatible with Big-Bang nucleosynthesis and with a similar accuracy. Using cosmological priors obtained from recent non–CMB data leads to yet tighter constraints on the total density, e.g. $\Omega_{\rm tot}=1.00^{+0.03}_{-0.02}$ using the HST determination of the Hubble constant. An excellent absolute calibration consistency is found between Archeops and other CMB experiments, as well as with the previously quoted best fit model. The spectral index n is measured to be $1.04^{+0.10}_{-0.12}$ when the optical depth to reionization, τ, is allowed to vary as a free parameter, and $0.96^{+0.03}_{-0.04}$ when τ is fixed to zero, both in good agreement with inflation.
Atmospheric emission is a dominant source of disturbance in ground-based astronomy at millimetric wavelengths. The Antarctic plateau is recognized as an ideal site for millimetric and submillimetric ...observations, and the French/Italian base of Dome Concordia (Dome C) is among the best sites on Earth for these observations. In this paper, we present measurements at Dome C of the atmospheric emission in intensity and polarization at a 2-mm wavelength. This is one of the best observational frequencies for cosmic microwave background (CMB) observations when considering cosmic signal intensity, atmospheric transmission, detector sensitivity and foreground removal. Using the B-mode radiation interferometer (BRAIN)-pathfinder experiment, we have performed measurements of the atmospheric emission at 150 GHz. Careful characterization of the airmass synchronous emission has been performed, acquiring more than 380 elevation scans (i.e. 'skydip') during the third BRAIN-pathfinder summer campaign in 2009 December/2010 January. The extremely high transparency of the Antarctic atmosphere over Dome C is proven by the very low measured optical depth, 〈τI〉= 0.050 ± 0.003 ± 0.011, where the first error is statistical and the second is the systematic error. Mid-term stability, over the summer campaign, of the atmosphere emission has also been studied. Adapting the radiative transfer atmosphere emission model am to the particular conditions found at Dome C, we also infer the level of the precipitable water vapor (PWV) content of the atmosphere, which is notoriously the main source of disturbance in millimetric astronomy (
mm). Upper limits on the airmass correlated polarized signal are also placed for the first time. The degree of circular polarization of atmospheric emission is found to be lower than 0.2 per cent 95 per cent confidence level (CL), while the degree of linear polarization is found to be lower than 0.1 per cent (95 per cent CL). These limits include signal-correlated instrumental spurious polarization.
Background The concept of a team-based model for delivery of care has been critical at our institution for improving efficiency and safety. Despite these measures, difficulties continue to occur ...during lengthy operating room procedures. Using a novel team-based practice model, a multidisciplinary team was organized to improve efficiency in microsurgical breast reconstruction. We describe development of an intraoperative pathway for deep inferior epigastric perforator (DIEP) flap breast reconstruction and its impact on various outcomes. Study Design We evaluated 150 patients who underwent DIEP flap breast reconstruction at Beth Israel Deaconess Medical Center from 2005 to 2008. Patient groups were subdivided into 50 unilateral and 50 bilateral procedures before the intraoperative pathway and 25 unilateral and 25 bilateral procedures after. Outcomes measured included operative time, complications, operating room and hospital costs, proper administration of prophylactic antibiotics and heparin, and staff satisfaction surveys. Results Mean operative times decreased after pathway implementation in both unilateral (8.2 hours to 6.9 hours; p < 0.001) and bilateral groups (12.8 hours to 10.6 hours; p < 0.001) and complication rates were unchanged. Mean operating room costs decreased in the unilateral group by 10.2% (p = 0.018). Prophylactic heparin administration showed substantial improvements, although antibiotic administration and redosing of antibiotics trended upward. Staff surveys showed improved interdisciplinary communication, transition guidelines, and enhanced efficiency through standardization. Conclusions Implementation of an intraoperative pathway led to improvements in operative time, cost, quality measures, and staff satisfaction. Refinement of the pathway with team resolution of variances might continue to improve outcomes. Complex, multi-team procedures can derive benefits from standardization and intraoperative pathway development.
We present a determination by the Archeops experiment of the angular power spectrum of the cosmic microwave background anisotropy in 16 bins over the multipole range $\ell=15{-}350$. Archeops was ...conceived as a precursor of the Planck HFI instrument by using the same optical design and the same technology for the detectors and their cooling. Archeops is a balloon–borne instrument consisting of a 1.5 m aperture diameter telescope and an array of 21 photometers maintained at $\sim 100$ mK that are operating in 4 frequency bands centered at 143, 217, 353 and 545 GHz. The data were taken during the Arctic night of February 7, 2002 after the instrument was launched by CNES from Esrange base (Sweden). The entire data cover ~30% of the sky. This first analysis was obtained with a small subset of the dataset using the most sensitive photometer in each CMB band (143 and 217 GHz) and 12.6% of the sky at galactic latitudes above 30 degrees where the foreground contamination is measured to be negligible. The large sky coverage and medium resolution (better than 15 arcmin) provide for the first time a high signal-to-noise ratio determination of the power spectrum over angular scales that include both the first acoustic peak and scales probed by COBE/DMR. With a binning of $\Delta \ell=7$ to 25 the error bars are dominated by sample variance for $\ell$ below 200. A companion paper details the cosmological implications.
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