We present the first measurements of the eover -->p-->epgamma cross section in the deeply virtual Compton scattering (DVCS) regime and the valence quark region. The Q(2) dependence (from 1.5 to 2.3 ...GeV(2)) of the helicity-dependent cross section indicates the twist-2 dominance of DVCS, proving that generalized parton distributions (GPDs) are accessible to experiment at moderate Q(2). The helicity-independent cross section is also measured at Q(2)=2.3 GeV(2). We present the first model-independent measurement of linear combinations of GPDs and GPD integrals up to the twist-3 approximation.
Sixteen CGD cases were clinically, functionally and genetically characterized and classified as suffering from different variant forms (X910, X91− or X91+) according to NOX2 expression and NADPH ...oxidase activity in their neutrophils. The pathological impact of each mutation of the new and extremely rare double missense mutation Thr208Arg‐Thr503Ile in CYBB was investigated using stable transfection in the NOX2 knock‐out PLB‐985 cell line. Low NADPH oxidase activity found in X91−‐CGD patients correlates with mild clinical forms, whereas X910‐CGD and X91+‐CGD cases remain the most clinically severes.
Summary
Chronic granulomatous disease (CGD) is a rare inherited disorder in which phagocytes lack nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. The most common form is the X‐linked CGD (X91‐CGD), caused by mutations in the CYBB gene. Clinical, functional and genetic characterizations of 16 CGD cases of male patients and their relatives were performed. We classified them as suffering from different variants of CGD (X910, X91− or X91+), according to NADPH oxidase 2 (NOX2) expression and NADPH oxidase activity in neutrophils. Eleven mutations were novel (nine X910‐CGD and two X91−‐CGD). One X910‐CGD was due to a new and extremely rare double missense mutation Thr208Arg‐Thr503Ile. We investigated the pathological impact of each single mutation using stable transfection of each mutated cDNA in the NOX2 knock‐out PLB‐985 cell line. Both mutations leading to X91−‐CGD were also novel; one deletion, c.‐67delT, was localized in the promoter region of CYBB; the second c.253‐1879A>G mutation activates a splicing donor site, which unveils a cryptic acceptor site leading to the inclusion of a 124‐nucleotide pseudo‐exon between exons 3 and 4 and responsible for the partial loss of NOX2 expression. Both X91−‐CGD mutations were characterized by a low cytochrome b558 expression and a faint NADPH oxidase activity. The functional impact of new missense mutations is discussed in the context of a new three‐dimensional model of the dehydrogenase domain of NOX2. Our study demonstrates that low NADPH oxidase activity found in both X91−‐CGD patients correlates with mild clinical forms of CGD, whereas X910‐CGD and X91+‐CGD cases remain the most clinically severe forms.
The present experiment exploits the interference between the deeply virtual Compton scattering (DVCS) and the Bethe-Heitler processes to extract the imaginary part of DVCS amplitudes on the neutron ...and on the deuteron from the helicity-dependent D(e,e'gamma)X cross section measured at Q2=1.9 GeV2 and xB=0.36. We extract a linear combination of generalized parton distributions (GPDs) particularly sensitive to E_{q}, the least constrained GPD. A model dependent constraint on the contribution of the up and down quarks to the nucleon spin is deduced.
We present final results on the photon electroproduction ($\vec{e}p\rightarrow ep\gamma$) cross section in the deeply virtual Compton scattering (DVCS) regime and the valence quark region from ...Jefferson Lab experiment E00-110. Results from an analysis of a subset of these data were published before, but the analysis has been improved which is described here at length, together with details on the experimental setup. Furthermore, additional data have been analyzed resulting in photon electroproduction cross sections at new kinematic settings, for a total of 588 experimental bins. Results of the $Q^2$- and $x_B$-dependences of both the helicity-dependent and helicity-independent cross sections are discussed. The $Q^2$-dependence illustrates the dominance of the twist-2 handbag amplitude in the kinematics of the experiment, as previously noted. Thanks to the excellent accuracy of this high luminosity experiment, it becomes clear that the unpolarized cross section shows a significant deviation from the Bethe-Heitler process in our kinematics, compatible with a large contribution from the leading twist-2 DVCS$^2$ term to the photon electroproduction cross section. The necessity to include higher-twist corrections in order to fully reproduce the shape of the data is also discussed. The DVCS cross sections in this study represent the final set of experimental results from E00-110, superseding the previous publication.
We present measurements of the ep->ep pi^0 cross section extracted at two values of four-momentum transfer Q^2=1.9 GeV^2 and Q^2=2.3 GeV^2 at Jefferson Lab Hall A. The kinematic range allows to study ...the evolution of the extracted hadronic tensor as a function of Q^2 and W. Results will be confronted with Regge inspired calculations and GPD predictions. An intepretation of our data within the framework of semi-inclusive deep inelastic scattering has also been attempted.
Patients with inherited deficiency of the interleukin (IL)-12/IL-23-interferon (IFN)-γ axis show increased susceptibility to invasive disease caused by the intramacrophage pathogens salmonellae and ...mycobacteria. We analyzed data on 154 patients with such deficiency. Significantly more patients with IL-12/IL-23-component deficiency had a history of salmonella disease than did those with IFN-γ-component deficiency. Salmonella disease was typically severe, extraintestinal, and caused by nontyphoidal serovars. These findings strongly suggest that IL-12/IL-23 is a key cytokine for immunity against salmonella in humans and that IL-12/IL-23 mediates this protective effect partly through IFN-γ-independent pathways. Investigation of the IL-12/IL-23-IFN-γ axis should be considered in patients with invasive salmonella disease.
There has been recent interest in the possible role of reperfusion-induced inflammation with neuronal injury after stroke. Enlimomab, a murine intercellular adhesion molecule-1 (ICAM-1) antibody, ...reduces leukocyte adhesion and infarct size in experimental stroke studies. The purpose of the current clinical trial was to evaluate the use of enlimomab after ischemic stroke.
A total of 625 patients with ischemic stroke were randomized to receive either enlimomab (n = 317) or placebo (n = 308) within 6 hours of stroke onset. Treatment was given over 5 days. Patients were evaluated at baseline and on days 5 and 90 after initiation of treatment; long-term assessments were carried out after 6 and 12 months. The primary efficacy endpoint was the response to therapy at 90 days on the Modified Rankin Scale; other endpoints included Barthel Index (BI) and NIH Stroke Scale and survival.
At day 90, the Modified Rankin Scale score was worse in patients treated with enlimomab than with placebo (p = 0.004). Fewer patients had symptom-free recovery on enlimomab than placebo (p = 0.004), and more died (22.2 versus 16.2%). The negative effect of enlimomab was apparent on days 5, 30, and 90 of treatment (p = 0.005). There were significantly more adverse events with enlimomab treatment than placebo, primarily infections and fever. Patients experiencing fever were more likely to have a poor outcome or die.
The authors conclude that anti-ICAM therapy with enlimomab is not an effective treatment for ischemic stroke in the model studied and, indeed, may significantly worsen stroke outcome.
Electronic medical records (EMR) are currently being implemented in psychiatric hospitals throughout Europe. The perceptions of health care professionals can contribute important information that may ...predict their acceptance of and desired mode of use for EMR, thus guiding EMR implementation.
To develop a self-administered instrument designed to assess health care professionals' satisfaction regarding EMR in a psychiatric hospital, based only on the professional point of view, according to the psychometric standards.
The development was supervised by a steering committee and undertaken by three standard steps. Item generation was derived from 115 face-to-face interviews with health care professionals in a French, public, psychiatric hospital. The item-reduction process resulted in a 25-item questionnaire. The validation process was based on construct validity, reliability and some aspects of external validity.
The final version of the questionnaire contained 25 items that described five dimensions, leading to a global score. The factor structure accounted for 72% of the total variance. Internal consistency was satisfactory (item-internal consistency over 0.40 and Cronbach's alpha coefficients ranged from 0.86 to 0.95). The scalability was satisfactory with INFIT statistics inside an acceptable range. Scores of dimensions were strongly positively correlated with visual analogue scale scores (all p < 0.001). External validity showed statistical associations between scores and age, gender, seniority in psychiatry and ward type. Participation rate was 66%.
The availability of a reliable and valid questionnaire (professionals' satisfaction questionnaire with electronic medical records PSQ-EMR) concerning health care professionals' satisfaction regarding EMR in psychiatry, exclusively generated from interviews with health care professionals, enables legitimate feedback to be incorporated into EMR implementation in order to formulate a high-quality health care.
Accumulation of human CD21
B cells in peripheral blood is a hallmark of chronic activation of the adaptive immune system in certain infections and autoimmune disorders. The molecular pathways ...underpinning the development, function, and fate of these CD21
B cells remain incompletely characterized. Here, combined transcriptomic and chromatin accessibility analyses supported a prominent role for the transcription factor T-bet in the transcriptional regulation of these T-bet
CD21
B cells. Investigating essential signals for generating these cells in vitro established that B cell receptor (BCR)/interferon-γ receptor (IFNγR) costimulation induced the highest levels of T-bet expression and enabled their differentiation during cell cultures with Toll-like receptor (TLR) ligand or CD40L/interleukin-21 (IL-21) stimulation. Low proportions of CD21
B cells in peripheral blood from patients with defined inborn errors of immunity (IEI), because of mutations affecting canonical NF-κB, CD40, and IL-21 receptor or IL-12/IFNγ/IFNγ receptor/signal transducer and activator of transcription 1 (STAT1) signaling, substantiated the essential roles of BCR- and certain T cell–derived signals in the in vivo expansion of T-bet
CD21
B cells. Disturbed TLR signaling due to MyD88 or IRAK4 deficiency was not associated with reduced CD21
B cell proportions. The expansion of human T-bet
CD21
B cells correlated with an expansion of circulating T follicular helper 1 (cTfh1) and T peripheral helper (Tph) cells, identifying potential sources of CD40L, IL-21, and IFNγ signals. Thus, we identified important pathways to target autoreactive T-bet
CD21
B cells in human autoimmune conditions, where these cells are linked to pathogenesis and disease progression.
PDF
