Nd doped fluoroapatites Sr
x
Ca
5−
x
(PO
4)
3F(S
x
C
5−
x
PF,
x = 0, 1, 2, 3, 4, and 5) single crystals have been grown by the Czochralski technique. Their polarized absorption and emission spectra ...have been recorded at room temperature and used to calculate the absorption and stimulated emission cross sections. Broadening of the absorption and emission bands is observed for Nd
3+ in the solid solutions SPF-CPF compared to Nd
3+ in CPF or SPF. 1% Nd:S
x
C
5−
x
PF,
x = 0, 2, 3, 4, and 5, laser rods have been tested in a cavity longitudinally pumped by a 1 W AlGaAs laser diode and compared to Nd:YAG and Nd:YVO
4 rods. All fluoroapatites exhibit very good laser performance with low thresholds and high slope efficiencies, higher than in the case of YAG and equal to the YVO
4 samples. The dependance of the laser output power versus the diode temperature has also been measured for all materials. The laser output was found to be as sensitive to the diode temperature fluctuations for fluoroapatites as for YAG.
Bloodstream bacterial infections are life-threatening conditions necessitating prompt medical care. Rapid pathogen identification is essential for early setting of the best anti-infectious therapy. ...However, the bacterial load in blood samples from patients with bacteremia is too low and under the limit of detection of most methods for direct identification of bacteria. Therefore, a preliminary step enabling the bacterial multiplication is required. To do so, blood cultures still remain the gold standard before bacteremia diagnosis. Bacterial identification is then usually obtained within 24 to 48 hours -at least- after blood sampling. In the present work, the fast and direct identification of bacteria present in blood cultures is completed in less than 12 hours, during bacterial growth, using an antibody microarray coupled to a Surface Plasmon Resonance imager (SPRi). Less than one bacterium (Salmonella enterica serovar Enteritidis) per milliliter of blood sample is successfully detected and identified in blood volumes similar to blood tests collected in clinics (i.e. several milliliters). This proof of concept demonstrates the workability of our method for human samples, despite the highly complex intrinsic nature of unprocessed blood. Our label-free method then opens new perspectives for direct and faster bacterial identification in a larger range of clinical samples.
Summary
Background
Primary cutaneous lymphomas (PCLs) are a heterogeneous group of T‐cell (CTCL) and B‐cell (CBCL) malignancies. Little is known about their epidemiology at initial presentation in ...Europe and about potential changes over time.
Objectives
The aim of this retrospective study was to analyse the frequency of PCLs in the French Cutaneous Lymphoma Registry (GFELC) and to describe the demography of patients.
Methods
Patients with a centrally validated diagnosis of primary PCL, diagnosed between 2005 and 2019, were included.
Results
The calculated incidence was unprecedently high at 1·06 per 100 000 person‐years. The number of included patients increased yearly. Most PCL subtypes were more frequent in male patients, diagnosed at a median age of 60 years. The relative frequency of rare CTCL remained stable, the proportion of classical mycosis fungoides (MF) decreased, and the frequency of its variants (e.g. folliculotropic MF) increased. Similar patterns were observed for CBCL; for example, the proportion of marginal‐zone CBCL increased over time.
Conclusions
Changes in PCL frequencies may be explained by the emergence of new diagnostic criteria and better description of the entities in the most recent PCL classification. Moreover, we propose that an algorithm should be developed to confirm the diagnosis of PCL by central validation of the cases.
What is already known about this topic?
Primary cutaneous lymphomas (PCLs) are a heterogeneous group of diseases.
Little is known about changes over time in their epidemiology and about patients’ characteristics and disease stages at the initial presentation.
What does this study add?
In this population‐based study we present changes over time in PCL epidemiology over a 15‐year period and show an unprecedentedly high incidence in Europe.
The relative frequency of rare PCL remained stable over time, while other PCL subtypes were better stratified.
This study suggests that the diagnosis of PCL should be evoked more frequently, and delivers up‐to‐date information on patients’ characteristics at initial diagnosis in a European population.
Linked Comment: Vermeer. Br J Dermatol 2021; 184:993–994.
Pemphigus is a severe blistering condition of the skin and mucosa caused by autoantibodies directed against desmogleins, which are a type of keratinocyte adhesion protein. B cell depletion by ...rituximab has short-term efficacy against pemphigus. We aimed to assess the long-term course of pemphigus patients after B cell depletion and to understand the immunological mechanisms that mediate long-lasting remissions. We evaluated the clinical course of 22 pemphigus patients treated with rituximab after a 79-month median follow-up and compared the anti-desmoglein B cell response and B and T lymphocyte subpopulations and repertoire between patients who achieved complete remission (CR) and those who had incomplete remission (IR). Thirteen patients (59%) experienced CR during the study, including 10 patients off treatment and 3 patients with prednisone doses <10 mg/day; 9 patients had IR. A marked increase was observed in the ratio of CD19(+)CD27(-) naïve B cells to CD19(+)CD27(+) memory B cells. Indeed, patients in CR had a fourfold higher number of transitional B cells and interleukin-10-secreting regulatory B cells than those in IR. Furthermore, CR was associated with modification of the initial B cell repertoire and the disappearance of desmoglein-specific circulating immunoglobulin G-positive (IgG(+)) B lymphocytes, whereas a skewed B cell repertoire was observed in patients in IR. Thus, a blockage of B cell maturation, a prolonged repopulation with naïve B cells, and a delayed reappearance of memory B cells, which resulted in the disappearance of circulating desmoglein-specific IgG(+) B lymphocytes, contribute to the long-lasting effectiveness of rituximab for treating pemphigus.
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and highly aggressive leukemia for which knowledge on disease mechanisms and effective therapies are currently lacking. Only a handful ...of recurring genetic mutations have been identified and none is specific to BPDCN. In this study, through molecular cloning in an index case that presented a balanced t(3;5)(q21;q31) and molecular cytogenetic analyses in a further 46 cases, we identify monoallelic deletion of NR3C1 (5q31), encoding the glucocorticoid receptor (GCR), in 13 of 47 (28%) BPDCN patients. Targeted deep sequencing in 36 BPDCN cases, including 10 with NR3C1 deletion, did not reveal NR3C1 point mutations or indels. Haploinsufficiency for NR3C1 defined a subset of BPDCN with lowered GCR expression and extremely poor overall survival (P = .0006). Consistent with a role for GCR in tumor suppression, functional analyses coupled with gene expression profiling identified corticoresistance and loss-of-EZH2 function as major downstream consequences of NR3C1 deletion in BPDCN. Subsequently, more detailed analyses of the t(3;5)(q21;q31) revealed fusion of NR3C1 to a long noncoding RNA (lncRNA) gene (lincRNA-3q) that encodes a novel, nuclear, noncoding RNA involved in the regulation of leukemia stem cell programs and G1/S transition, via E2F. Overexpression of lincRNA-3q was a consistent feature of malignant cells and could be abrogated by bromodomain and extraterminal domain (BET) protein inhibition. Taken together, this work points to NR3C1 as a haploinsufficient tumor suppressor in a subset of BPDCN and identifies BET inhibition, acting at least partially via lncRNA blockade, as a novel treatment option in BPDCN.
•NR3C1 haploinsufficiency is found in patients with a plasmacytoid dendritic cell neoplasm characterized by very poor clinical outcome.•Overexpression of lincRNA-3q is a consistent feature of malignant cells in these patients and can be abrogated by BET protein inhibition.
A three-dimensional atomic characterization of AISI 304L plasma nitrided at 400 degree C has been carried out with atom probe tomography (APT). While only a single phase, usually called phase or ...expanded austenite, can be detected by the X-ray diffraction, APT reveals the formation of nanometric MN (M=Cr, Fe) precipitates. Preferential precipitation of MN at planar defects has been observed. These results suggest that even at moderate nitriding temperatures the diffusion of Cr takes place resulting in slow but nevertheless detectable precipitation kinetics.
A thorough understanding of which of the effects assessed in the in vivo Draize eye test are responsible for driving UN GHS/EU CLP classification is critical for an adequate selection of chemicals to ...be used in the development and/or evaluation of alternative methods/strategies and for properly assessing their predictive capacity and limitations. For this reason, Cosmetics Europe has compiled a database of Draize data (Draize eye test Reference Database, DRD) from external lists that were created to support past validation activities. This database contains 681 independent in vivo studies on 634 individual chemicals representing a wide range of chemical classes. A description of all the ocular effects observed in vivo, i.e. degree of severity and persistence of corneal opacity (CO), iritis, and/or conjunctiva effects, was added for each individual study in the database, and the studies were categorised according to their UN GHS/EU CLP classification and the main effect driving the classification. An evaluation of the various in vivo drivers of classification compiled in the database was performed to establish which of these are most important from a regulatory point of view. These analyses established that the most important drivers for Cat 1 Classification are (1) CO mean ≥ 3 (days 1–3) (severity) and (2) CO persistence on day 21 in the absence of severity, and those for Cat 2 classification are (3) CO mean ≥ 1 and (4) conjunctival redness mean ≥ 2. Moreover, it is shown that all classifiable effects (including persistence and CO = 4) should be present in ≥60 % of the animals to drive a classification. As a consequence, our analyses suggest the need for a critical revision of the UN GHS/EU CLP decision criteria for the Cat 1 classification of chemicals. Finally, a number of key criteria are identified that should be taken into consideration when selecting reference chemicals for the development, evaluation and/or validation of alternative methods and/or strategies for serious eye damage/eye irritation testing. Most important, the DRD is an invaluable tool for any future activity involving the selection of reference chemicals.
The nitriding behavior of AISI M2 steel was studied on samples previously submitted to two different heat treatments in order to investigate the effects of the initial microstructure on the thickness ...and hardness of nitrided layer. Prior to nitriding, one group of samples was fully annealed while the other group was quenched and tempered, thus acquiring the lowest and highest hardness respectively. Plasma nitriding was performed at 450
°C for 8
h with a mixture of N
2 and H
2 in a plasma reactor working under floating potential. Structural and mechanical properties of nitrided layers were characterized using X-ray diffraction (XRD), optical microscopy and microhardness testing. Variations in surface roughness were obtained by 3D surface profilometry analysis. The thicker nitrided layer was obtained for the fully annealed samples, in which the nitrided layer is composed of
γ′-Fe
4N and
ε-Fe
2–3N phases plus a diffusion zone. For the hardened–tempered samples, the nitrided region mainly consisted of a diffusion zone. Plasma nitriding increased the surface hardness of the fully annealed samples by 330% and that of the quenched–tempered samples by 50%. The nitrided depth was also estimated using cross-sectional microhardness profiles; giving about 140
µm and ∼
70
µm for the fully annealed and quenched–tempered samples, respectively. Due to the grain to grain nitrogen diffusion, plasma nitriding also increased the surface roughness. The largest roughness was obtained for the fully annealed samples, in accordance with the largest nitrided depth. The difference in the nitriding behavior was explained on the basis of the microstructural aspects of the substrates such as the concentration of the freely dispersed alloying elements and the level of compressive residual stresses.
•Key qualification parameters defined for HPLC/UPLC-spectrophotometry systems.•HPLC/UPLC-spectrophotometry for formazan detection is highly reproducible.•High concordance of classification using OD ...and HPLC/UPLC-spectrophotometry.•Applicable for highly coloured chemicals interfering with standard detection method.•Applicable to in vitro RhT test methods for eye/skin irritation and skin corrosion.
A number of in vitro test methods using Reconstructed human Tissues (RhT) are regulatory accepted for evaluation of skin corrosion/irritation. In such methods, test chemical corrosion/irritation potential is determined by measuring tissue viability using the photometric MTT-reduction assay. A known limitation of this assay is possible interference of strongly coloured test chemicals with measurement of formazan by absorbance (OD). To address this, Cosmetics Europe evaluated use of HPLC/UPLC-spectrophotometry as an alternative formazan measurement system. Using the approach recommended by the FDA guidance for validation of bio-analytical methods, three independent laboratories established and qualified their HPLC/UPLC-spectrophotometry systems to reproducibly measure formazan from tissue extracts. Up to 26 chemicals were then tested in RhT test systems for eye/skin irritation and skin corrosion. Results support that: (1) HPLC/UPLC-spectrophotometry formazan measurement is highly reproducible; (2) formazan measurement by HPLC/UPLC-spectrophotometry and OD gave almost identical tissue viabilities for test chemicals not exhibiting colour interference nor direct MTT reduction; (3) independent of the test system used, HPLC/UPLC-spectrophotometry can measure formazan for strongly coloured test chemicals when this is not possible by absorbance only. It is therefore recommended that HPLC/UPLC-spectrophotometry to measure formazan be included in the procedures of in vitro RhT-based test methods, irrespective of the test system used and the toxicity endpoint evaluated to extend the applicability of these test methods to strongly coloured chemicals.
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