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Modern disease-modifying therapies (DMTs) in multiple sclerosis (MS) have variable modes of action and selectively suppress or modulate the immune system. In this review, we summarize the predicted and intended as well as unwanted adverse effects on leukocytes in peripheral blood as a result of treatment with DMTs for MS. We link changes in laboratory tests to the possible therapeutic risks that include secondary autoimmunity, infections, and impaired response to vaccinations. Profound knowledge of the intended effects on leukocyte counts, in particular lymphocytes, explained by the mode of action, and adverse effects which may require additional laboratory and clinical vigilance or even drug discontinuation, is needed when prescribing DMTs to treat patients with MS. [ABSTRACT FROM AUTHOR]

Background: Suicide is a serious public health problem. The development and use of effective treatments for people hospitalized for suicide attempts remain a priority. Regarding psychosocial treatment, the evidence for treatments that effectively prevent suicide repetition of suicide attempts is extremely thin. There is some evidence that cognitive behavioural therapy may be effective for reducing suicide behaviour. The primary aim of this study is to compare Group Post-Admission Cognitive Therapy for Suicidality (GPACTS) versus Individual Supportive Therapy (IST) for preventing suicide.Methods: In total, 240 participants with a high suicide risk score according to a Mini International Neuropsychiatric Interview (MINI) will be randomized to either GPACTS or IST. This is a multicentre, parallel group, randomized (1:1 ratio), two-tailed-superiority trial with endpoint-assessor blinding. Patients meeting inclusion criteria during a screening visit will be enrolled in the study and randomized into two groups: one group will undergo 6 weeks of GPACTS, and the second group will undergo 6 weeks of IST. Following 6 weeks of interventional therapy, patients are followed up for 12 months. Follow-up for both groups is identical and includes the administration of questionnaires at baseline and then within 10 days after the end of therapy sessions and then at 3, 6 and 12 months following the end of GPACTS/IST sessions.Discussion: To our knowledge, this is the first RCT of its kind to be conducted in France, and so far, there are no studies in the literature on group psychotherapy for the treatment of individuals who have attempted suicide. The outcomes will provide clear guidance for professionals to apply psychological intervention with suicide attempts. The protocol respects ethical principles, and ethical approval was obtained from the local ethics committee. The results will be disseminated through an original research published as original research in peer-reviewed manuscript, through a therapist manual for cognitive therapy, and presentations at research conferences.Trial Registration: ClinicalTrials.gov NCT02664701 . Registered on January 27, 2017. [ABSTRACT FROM AUTHOR]

Background: The localization of objects of interest is a key initial step in most image analysis workflows. For biomedical image data, classical image-segmentation methods like thresholding or edge detection are typically used. While those methods perform well for labelled objects, they are reaching a limit when samples are poorly contrasted with the background, or when only parts of larger structures should be detected. Furthermore, the development of such pipelines requires substantial engineering of analysis workflows and often results in case-specific solutions. Therefore, we propose a new straightforward and generic approach for object-localization by template matching that utilizes multiple template images to improve the detection capacity. Results: We provide a new implementation of template matching that offers higher detection capacity than single template approach, by enabling the detection of multiple template images. To provide an easy-to-use method for the automatic localization of objects of interest in microscopy images, we implemented multi-template matching as a Fiji plugin, a KNIME workflow and a python package. We demonstrate its application for the localization of entire, partial and multiple biological objects in zebrafish and medaka high-content screening datasets. The Fiji plugin can be installed by activating the Multi-Template-Matching and IJ-OpenCV update sites. The KNIME workflow is available on nodepit and KNIME Hub. Source codes and documentations are available on GitHub (https://github.com/multi-template-matching). Conclusion: The novel multi-template matching is a simple yet powerful object-localization algorithm, that requires no data-pre-processing or annotation. Our implementation can be used out-of-the-box by non-expert users for any type of 2D-image. It is compatible with a large variety of applications including, for instance, analysis of large-scale datasets originating from automated microscopy, detection and tracking of objects in time-lapse assays, or as a general image-analysis step in any custom processing pipelines. Using different templates corresponding to distinct object categories, the tool can also be used for classification of the detected regions. [ABSTRACT FROM AUTHOR]

The δ 18 O of ostracod valves is widely used to infer water δ 18 O and temperature. However, ostracod δ 18 O appears sensitive to other environmental variables. In addition, there is species-dependent ostracod calcite 18 O enrichment, relative to slowly precipitated inorganic calcite under the same conditions. Together these uncertainties complicate ostracod paleoclimate reconstructions. This study presents a new understanding of the causes of ostracod δ 18 O variations based on a global database of published ostracod δ 18 O values in lake, marine and coastal environments, and from culture experiments. The database includes associated field/experiment host water parameters including temperature (−1 to 32 °C), water δ 18 O (−13.2‰ to 4.3‰ VSMOW), pH (6.9–10.4), salinity (0–72 g/kg), calcite saturation states (0.6–26), and dissolved inorganic carbon concentration [DIC] (0.9–54.3 mmol/kg). The data show that: (1) the δ 18 O of marine and non-marine ostracods reflects the 18 O/ 16 O of the sum of host water CO 3 2− and HCO 3 − ions. For example, at a given temperature, the δ 18 O of non-marine ostracods decreases by 4‰ to 6‰ as [CO 3 2− ]/[DIC] reaches 70%, depending on the ostracod species. In low [CO 3 2− ]/[DIC] settings (i.e. high HCO 3 − /CO 3 2− ), ostracod 18 O/ 16 O is close to the 18 O/ 16 O of HCO 3 − ions, which explains why on average ostracod δ 18 O is higher than the δ 18 O of inorganic calcite precipitated slowly under the same conditions. (2) Taxonomic offsets in ostracod δ 18 O vary with the host water [CO 3 2− ]/[DIC]. In environments where HCO 3 − ≫ CO 3 2− (i.e. most freshwater lakes), the 18 O/ 16 O of Candonids is indistinguishable from the 18 O/ 16 O of HCO 3 − ions (difference of 0.10 ± 0.16‰) while the 18 O/ 16 O of Cyprids is lower than the 18 O/ 16 O of HCO 3 − ions by −0.77‰ to −0.32‰, Cytherids by −0.88 ± 0.29‰, and Limnocytherids by −1.12 ± 0.05‰. (3) The sensitivity of ostracod δ 18 O to [CO 3 2− ]/[DIC] also varies with taxonomy. For each percent increase in [CO 3 2− ]/[DIC], Candonids δ 18 O decreases by −0.098 ± 0.024‰, Cyprids by −0.075 ± 0.004‰, Cytherids by −0.057 ± 0.012‰, and Limnocytherids by −0.058 ± 0.005‰. (4) The similarity in 18 O/ 16 O between ostracod calcite and the sum of host water ‘HCO 3 − and CO 3 2− ’ (despite species-specific offsets) suggests rapid precipitation of a finite DIC pool in the ostracod calcifying fluid. We propose an ostracod δ 18 O model whereby the more negative the 18 O/ 16 O of a given species relative to the sum of CO 3 2− and HCO 3 − , the greater the isotopic equilibrium between the DIC pool and H 2 O in the ostracod calcifying fluid. (5) Higher host water salinities and pH induce higher [CO 3 2− ]/[DIC], resulting in lower ostracod δ 18 O, which explains the variable salinity and pH effects on ostracod δ 18 O. Our database and ostracod δ 18 O model shows that ostracod δ 18 O records from closed basin environments likely reflect high or variable [CO 3 2− ]/[DIC], rather than water temperature and δ 18 O alone. Our study reconciles contradictory observations of controls on ostracod δ 18 O and paves the way for improved paleo-environmental interpretations and reconstructions of past water [CO 3 2− ]/[DIC]. [ABSTRACT FROM AUTHOR]

The oxygen isotope ratio (δ 18 O) of inorganic and biogenic carbonates is widely used to reconstruct past environments. However, the oxygen isotope exchange between CaCO 3 and H 2 O rarely reaches equilibrium and kinetic isotope effects (KIE) commonly complicate paleoclimate reconstructions. We present a comprehensive model of kinetic and equilibrium oxygen isotope fractionation between CaCO 3 and water ( α c / w ) that accounts for fractionation between both (a) CaCO 3 and the CO 3 2− pool ( α c / CO 3 2 - ) , and (b) CO 3 2− and water ( α CO 3 2 - / w ) , as a function of temperature, pH, salinity, calcite saturation state (Ω), the residence time of the dissolved inorganic carbon (DIC) in solution, and the activity of the enzyme carbonic anhydrase. The model results suggest that: (1) The equilibrium α c / w is only approached in solutions with low Ω (i.e. close to 1) and low ionic strength such as in the cave system of Devils Hole, Nevada. (2) The sensitivity of α c / w to the solution pH and/or the mineral growth rate depends on the level of isotopic equilibration between the CO 3 2− pool and water. When the CO 3 2− pool approaches isotopic equilibrium with water, small negative pH and/or growth rate effects on α c / w of about 1–2‰ occur where these parameters covary with Ω. In contrast, isotopic disequilibrium between CO 3 2− and water leads to strong (>2‰) positive or negative pH and growth rate effects on α CO 3 2 - / w (and α c / w ) due to the isotopic imprint of oxygen atoms derived from HCO 3 − , CO 2 , H 2 O and/or OH − . (3) The temperature sensitivity of α c / w originates from the negative effect of temperature on α CO 3 2 - / w and is expected to deviate from the commonly accepted value (−0.22 ± 0.02‰/°C between 0 and 30 °C; Kim and O’Neil, 1997) when the CO 3 2− pool is not in isotopic equilibrium with water. (4) The model suggests that the δ 18 O of planktic and benthic foraminifers reflects a quantitative precipitation of DIC in isotopic equilibrium with a high-pH calcifying fluid, leading to a relatively constant foraminifer calcite δ 18 O-temperature relationship (−0.21 ± 0.01‰/°C). The lower average coral δ 18 O data relative to foraminifers and other calcifiers is best explained by the precipitation of internal DIC derived from hydrated CO 2 in a high-pH calcifying fluid and minimal subsequent DIC-H 2 O isotopic equilibration. This leads to a reduced and variable coral aragonite δ 18 O-temperature relationship (−0.11 to −0.22‰/°C). Together, the model presented here reconciles observations of oxygen isotope fractionation over a range of CaCO 3 -DIC-H 2 O systems. [ABSTRACT FROM AUTHOR]

The benefit of using individual head-related transfer functions (HRTFs) in binaural audio is well documented with regards to improving localization precision. However, with the increased use of binaural audio in more complex scene renderings, cognitive studies, and virtual and augmented reality simulations, the perceptual impact of HRTF selection may go beyond simple localization. In this study, the authors develop a list of attributes which qualify the perceived differences between HRTFs, providing a qualitative understanding of the perceptual variance of non-individual binaural renderings. The list of attributes was designed using a Consensus Vocabulary Protocol elicitation method. Participants followed an Individual Vocabulary Protocol elicitation procedure, describing the perceived differences between binaural stimuli based on binauralized extracts of multichannel productions. This was followed by an automated lexical reduction and a series of consensus group meetings during which participants agreed on a list of relevant attributes. Finally, the proposed list of attributes was then evaluated through a listening test, leading to eight valid perceptual attributes for describing the perceptual dimensions affected by HRTF set variations. [ABSTRACT FROM AUTHOR]

This paper reports an advanced time-domain methodology to investigate the device reliability and determine its safe operating area of AlGaN/GaN HEMTs. The presented technique is based on the continued monitoring of the RF waveforms and DC parameters in order to assess the degradation of transistor characteristics in RF power amplifiers. The reliability study is carried out in class AB operation, under RF operating excitation at high drain voltages and overdrive conditions (12 dB compression). The analysis is carried out with two different output load impedances: optimum of PAE and mismatched impedance. The results show a drift of RF performances due to a variation of electrical parameters. In particular, the operation with optimum PAE load impedance induces slight positive threshold voltage shift. The operation with mismatched load shows a stronger degradation, with a positive threshold voltage shift and a drop in saturation drain current, due principally to the high temperature reached by the devices during RF stress. [ABSTRACT FROM AUTHOR]

L isteria monocytogenes is a bacterial pathogen classified into distinct serovars ( SVs) based on somatic and flagellar antigens. To correlate phenotype with genetic variation, we analyzed the wall teichoic acid ( WTA) glycosylation genes of SV 1/2, 3 and 7 strains, which differ in decoration of the ribitol-phosphate backbone with N-acetylglucosamine ( GlcNAc) and/or rhamnose. Inactivation of lmo1080 or the dTDP- l-rhamnose biosynthesis genes rml ACBD ( lmo1081-1084) resulted in loss of rhamnose, whereas disruption of lmo1079 led to GlcNAc deficiency. We found that all SV 3 and 7 strains actually originate from a SV 1/2 background, as a result of small mutations in WTA rhamnosylation and/or Glc NAcylation genes. Genetic complementation of different SV 3 and 7 isolates using intact alleles fully restored a characteristic SV 1/2 WTA carbohydrate pattern, including antisera reactions and phage adsorption. Intriguingly, phage-resistant L . monocytogenes EGDe ( SV 1/2a) isolates featured the same glycosylation gene mutations and were serotyped as SV 3 or 7 respectively. Again, genetic complementation restored both carbohydrate antigens and phage susceptibility. Taken together, our data demonstrate that L . monocytogenes SV 3 and 7 originate from point mutations in glycosylation genes, and we show that phage predation represents a major driving force for serovar diversification and evolution of L . monocytogenes. [ABSTRACT FROM AUTHOR]

We propose to acquire large sets of room impulse responses (RIRs) by simultaneously playing known source signals on multiple loudspeakers. We then estimate the RIRs via a convex optimization algorithm using convex penalties promoting sparsity and/or exponential amplitude envelope. We validate this approach on real-world recordings. The proposed algorithm makes it possible to estimate the RIRs to a reasonable accuracy even when the number of recorded samples is smaller than the number of RIR samples to be estimated, thereby leading to a speedup of the recording process compared to state-of-the-art RIR acquisition techniques. Moreover, the penalty promoting both sparsity and exponential amplitude envelope provides the best results in terms of robustness to the choice of its parameters, thereby consolidating the evidence in favor of sparse regularization for RIR estimation. Finally, the impact of the choice of the emitted signals is analyzed and evaluated. [ABSTRACT FROM AUTHOR]

Blood pressure (BP) is conventionally measured by cuff at the brachial artery as an indication of pressure experienced by the organs. However, individual variation in pulse pressure amplification means that brachial cuff BP may be a poor representation of true central BP. Estimation of central BP is now possible using non-invasive methods that are amenable for widespread use. This paper reviews the evidence regarding the potential value of central BP in hypertension management. The major lines of evidence that support the use of central BP as a clinical tool include the: (1) major discrepancies in central BP among people with similar brachial BP; (2) independent relationship of central BP with end-organ damage; (3) independent relationship of central BP with cardiovascular (CV) events and mortality; (4) differential central and brachial BP responses to antihypertensive medications and; (5) improvements in end-organ damage after therapy more strongly relate to central than brachial BP. Despite all this, important evidence gaps relating to clinical use of central BP need fulfilling. These include the lack of central BP reference values and randomized, controlled studies to determine if: (1) central BP can help with diagnostic/therapeutic decisions and; (2) CV outcome is improved by targeting therapy towards lowering central BP levels. Additional challenges such as standardization of central BP methods, and understanding which patients are most likely to benefit from central BP monitoring also need to be determined. Overall, the future for central BP as a worthwhile clinical instrument appears positive, but there is much to be done. [ABSTRACT FROM AUTHOR]

When the solid phase of a porous medium is a hydrate, bound water is chemically linked to the anhydrous solid molecule instead of being physically adsorbed. Consequently, its elimination does not consist of a continuous desorption but of a discontinuous succession of chemical heterogeneous dehydration reactions. It results in the appearance of successive plateaus in desorption isotherm curves but also in water content and temperature-drying kinetics and profiles of a hydrate. The writing of boundary conditions between the porous medium and its surroundings explains the origin of the dehydration plateau observed in convective-drying-temperature kinetics. [ABSTRACT FROM PUBLISHER]

This paper presents the design of an MMIC oscillator operating at a 38GHz frequency. This circuit was fabricated by the III-V Lab with the new InP/GaAsSb Double Heterojunction Bipolar Transistor (DHBT) submicronic technology (We = 700 nm). The transistor used in the circuit has a 15 µm long two-finger emitter. This paper describes the complete nonlinear modeling of this DHBT, including the cyclostationary modeling of its low frequency (LF) noise sources. The specific interest of the methodology used to design this oscillator resides in being able to choose a nonlinear operating condition of the transistor from an analysis in amplifier mode. The oscillator simulation and measurement results are compared. A 38GHz oscillation frequency with 8.6 dBm output power and a phase noise of -80 dBc/Hz at 100 KHz offset from carrier have been measured. [ABSTRACT FROM AUTHOR]

Abstract: A versatile method for the introduction of cyano groups onto the surface of iron oxide nanoparticles has been developed. This protocol is based on the hydrolysis and the condensation of cyanoethyltrimethoxysilane (CES) on the magnetite surface. The optimal concentration of silane coupling agent was determined ([Fe]/[CN] ratio=0.4) in order to obtain an appropriate surface density of activating groups on the nanoparticles. The size distribution of the particles was also optimized by a magnetic size sorting procedure. An adequate surface with cyano groups could facilitates their use in biomedical applications by improving the cellular labeling and the cell targeting. [ABSTRACT FROM AUTHOR]

We prove that the equivalence between Vershik's standardness criterion and the I- cosiness criterion for a filtration in discrete, negative time holds separately for each random variable. This gives a strengthening and a more direct proof of the global equivalence between these two criteria. We also provide more elementary original propositions on Vershik's standardness criterion, while emphasizing that similar statements for I-cosiness are sometimes not so obvious. [ABSTRACT FROM AUTHOR]

With the availability of whole-genome sequence data biologists are able to test hypotheses regarding the demography of populations. Furthermore, the advancement of the Approximate Bayesian Computation (ABC) methodology allows the demographic inference to be performed in a simple framework using summary statistics. We present here msABC, a coalescent-based software that facilitates the simulation of multi-locus data, suitable for an ABC analysis. msABC is based on Hudson’s ms algorithm, which is used extensively for simulating neutral demographic histories of populations. The flexibility of the original algorithm has been extended so that sample size may vary among loci, missing data can be incorporated in simulations and calculations, and a multitude of summary statistics for single or multiple populations is generated. The source code of msABC is available at or upon request from the authors. [ABSTRACT FROM AUTHOR]

Reference 1 Thomas LSV, Gehrig J. Multi-template matching: a versatile tool for object-localization in microscopy images. Correction to: BMC Bioinformatics (2020) 21:44 https://doi.org/10.1186/s12859-020-3363-7 Following the publication of the original article [[1]], the authors would like to update Additional file 3 in the supplementary information. [Extracted from the article]

Reference 1 Thomas LSV, Gehrig J. Multi-template matching: a versatile tool for object-localization in microscopy images. Correction to: BMC Bioinformatics (2020) 21:44 https://doi.org/10.1186/s12859-020-3363-7 Following the publication of the original article [[1]], the authors would like to update Additional file 3 in the supplementary information. [Extracted from the article]

Abstract: Pulverisation phenomena occurring during the charge/discharge cycling of metal hydride materials were studied by acoustic emission coupled to electrochemical measurements. Two kinds of materials were studied: a commercial LaNi5-based alloy and a ball-milled MgNi alloy. In both alloys, two populations of acoustic signals were detected during charging steps: P1, showing peak frequencies between 230 and 260kHz, high energy and low rise time, and P2 with peak frequencies between 150 and 180kHz, lower energy and longer rise time. Population P2 is related to the hydrogen evolution reaction whereas P1 is associated with pulverisation phenomena. No acoustic activity was detected during discharge. We also investigated pulverisation phenomena through cycles by monitoring the P1 population. It appears that pulverisation occurs mainly during the five first cycles for LaNi5 with a maximum at the second cycle, while pulverisation takes place all along the cycling for MgNi, but at a decreasing rate. By comparing the P1 activities, it appears that the pulverization phenomenon is less intensive on the MgNi electrode than on the LaNi5-based electrode. [Copyright &y& Elsevier]

Abstract: Background: Since patients with diabetes mellitus have increased rates of cardiovascular morbidity and mortality, it is critical to evaluate cardiovascular risk perioperatively. Although several preoperative risk indices have been developed, including the Goldman and Detsky indices, none have been designed specifically for diabetic patients. In this study, we attempted to identify predictors of postoperative cardiac and noncardiac complications in diabetic patients undergoing elective general surgery. Study Design: A cohort of 107 diabetic patients undergoing elective surgery was assembled. Basic demographic and clinical data were recorded perioperatively, and all patients were followed up prospectively daily for 7 days postoperatively. Patients were interviewed at 5 years postoperatively. Univariate and multivariate analyses were performed to identify predictors of postoperative complications and long-term cardiac and vascular morbidity and mortality. Results: Total cardiac complications and myocardial infarction were predicted by the Goldman index. Wound complications were not predicted by any of the variables studied. At 5 years postoperatively, cardiac and vascular deaths and events were predicted by age, history of myocardial infarction or stroke, presence of vascular disease, Goldman index, duration of diabetes or hypertension, Charlson comorbidity score, and postoperative myocardial infarction or cardiac arrest. Blood sugar control during surgery was not predictive of any short- or long-term cardiovascular complications. Conclusions: Total cardiac complications had a significant preoperative predictor: the Goldman index. Both preoperative and postoperative variables and indices predicted long-term cardiac and vascular complications. Further study is necessary to investigate these relationships to better assess and manage the diabetic patient in the perioperative setting. [Copyright &y& Elsevier]

Abstract: Gd and Eu complexes of PMN-tetraacetic acid show interesting properties either for MRI or for optical imaging; that is, for the Gd-complex, a high proton relaxivity with favorable water residence time; for the Eu-complex, a luminescence lifetime of 400μs at room temperature compatible with the use of time-resolved luminescence technique. Both complexes have a good stability in physiological medium. [Copyright &y& Elsevier]

Objective: Previous studies have related poor glycemic control and/or some diabetes complications to low socioeconomic status. Some aspects of socioeconomic status have not been assessed in these studies. In the present study, we used an individual index of deprivation, the Evaluation de la Précarité et des Inégalités de santé dans les Centres d'Examens de Santé (Evaluation of Precarity and Inequalities in Health Examination Centers [EPICES]) score, to determine the relationship among glycemic control, diabetes complications, and individual conditions of deprivation.Research Design and Methods: We conducted a cross-sectional prevalence study in 135 consecutive diabetic patients (age 59.41 +/- 13.2 years [mean +/- SD]) admitted in the hospitalization unit of a French endocrine department. Individual deprivation was assessed by the EPICES score, calculated from 11 socioeconomic questions. Glycemic control, lipid levels, blood pressure, retinopathy, neuropathy, and nephropathy were assessed.Results: HbA(1c) level was significantly correlated with the EPICES score (r = 0.366, P < 0.001). The more deprived patients were more likely than the less deprived patients to have poor glycemic control (beta = 1.984 [SE 0.477], P < 0.001), neuropathy (odds ratio 2.39 [95% CI 1.05-5.43], P = 0.037), retinopathy (3.66 [1.39-9.64], P = 0.009), and being less often admitted for 1-day hospitalization (0.32 [0.14-0.74], P = 0.008). No significant relationship was observed with either nephropathy or cardiovascular risk factors.Conclusions: Deprivation status is associated with poor metabolic control and more frequent microvascular complications, i.e., retinopathy and neuropathy. The medical and economic burden of deprived patients is high. [ABSTRACT FROM AUTHOR]

When a sham operation is performed 6 h before partial hepatectomy (PH), the regenerative response is accelerated suggesting that sham operation itself contributes to cellular events leading to proliferation.In order to examine the mechanisms implicated in this acceleration, we compared the activation of several factors associated with the progression through the cell cycle at various times after PH and after PH preceded by sham operation (S6 h + PH). The effect of a single sham (S) and two combined sham operations (S6 h + S) was also examined. Nonoperated rats were used as controls (C).The early factors NF-κB and Stat3 were activated after S6 h + PH and S6 h + S. C-junexpression was increased 0·5 h and 2 h after PH and 6 h after sham. There was no further increase in S6 h + PH and S6 h + S. In contrast, c-mycexpression returned to baseline levels after S6 h and a new increase was observed 2 h after S6 h + PH but not after S6 h + S. P53 mRNA was significantly expressed 6 h after S6 h + PH, but at a level similar than that observed 6 and 12 h after PH alone. An earlier increase in c-Ha-rasmRNA and cyclin E protein was found in S6 h + PH, in comparison with PH alone.The first divergent response between the two combined models involved c-mycexpression. However, major differences related to the accelerated liver regenerative response observed after S6 h + PH were found at late time points associating an earlier expression of c-Ha-rasand nuclear cyclin E. [ABSTRACT FROM AUTHOR]

A simple, rapid method for the simultaneous determination of cardiovascular drugs: celiprolol, bisoprolol and irbesartan in human plasma is described. The two main features of the proposed method deal first, with a simultaneous solid phase extraction of weakly basic beta-blockers derivatives and irbesartan which exhibit weak acidic properties; second with an absorbance monitoring using diode array detection in order to insure an improved selectivity. The separation is performed on a C18 Kromasil® 4.6 mm×150 mm column using a linear gradient to achieve an entire separation of the four species in less than 20 min. The full analytical validation is performed according to guidance for industry for bioanalytical method validation. Linearity of the response was demonstrated for each drug for a range fulfilling the reported plasma levels, that is 10–500, 5–250 and 20–1000 ng l−1 for celiprolol, bisoprolol and irbesartan respectively. Intra- and inter-day relative standard deviations for all compounds were, in any case, lower than 11% and the method exhibits a convenient accuracy (percentage of relative error lower than 6% for each drug). In each case, the LOD were sufficient to detect post dose trough concentrations for checking patient’s observance. Moreover, selectivity towards either endogenous species or co-administered drugs was demonstrated by combination of the use of the solid phase extraction process, gradient elution and diode array detection facilities, making thus, the proposed technique especially suitable for routine drug monitoring of resistant hypertensive patients. [Copyright &y& Elsevier]

The coding region of the preproinsulin gene has been cloned and partly sequenced in a variety of marine and terrestrial birds (28 species). All genes showed the “ancestral” structure with a large intron-2. The size of intron-2 changed considerably during the evolution of birds (2.4–4.2 kb). The hydrophobicity of signal peptides was conserved. Bird C-peptides were predicted to be 28 amino acids long, but circulating C-peptides would be only 26 amino acids long, with Passer as a possible exception. Bird C-peptides were found to lack the sequences identified in mammals as responsible for peptide bioactivity and the structure of the central part. In contrast, predicted insulin sequences were highly conserved. Only two types of analog were identified: the hypoactive form (GluA8), present only in Anseriformes and the hyperactive form (His A8), present in all other species. Based on 3′-nucleotide sequence analysis (extending into intron-2), birds appeared to be monophyletic. Five groups were clearly identified: Paleognathae, Galliformes, Anseriformes, Passeriformes, and Charadriiformes. Paleognathae were suggested as the basal group, supporting the traditional view of avian evolution. Subsequent branching identified a gallo-anserae group and a group containing all other Neognathae. Surprisingly, Columba livia (Columbiforme order) clustered with Galliformes. With represented species, Procellariiformes and possibly Ciconiiformes, and Pelicaniformes were suggested as paraphyletic, in agreement with conclusions from some studies based on mitochondrial DNA sequences. [Copyright &y& Elsevier]

We report on optical orientation of electrons in n-doped InAs/GaAs quantum dots. Under non-resonant cw optical pumping, we measure a negative circular polarization of the luminescence of charged excitons (or trions) at low temperature (T=10 K). The dynamics of the recombination and of the circular polarization is studied by time-resolved spectroscopy. We discuss a simple theoretical model for the trion relaxation, that accounts for this remarkable polarization reversal. The interpretation relies on the bypass of Pauli blocking allowed by the anisotropic electron–hole exchange. Eventually, the spin relaxation time of doping electrons trapped in quantum dots is measured by a non-resonant pump–probe experiment. [Copyright &y& Elsevier]

Aim: The enzymatic defect in Fabry disease results in the slow systemic deposition of uncleaved glycosphingolipids in the lysosomes of vascular endothelium and smooth muscle cells, leading to ischaemic strokes, cardiomyopathy and renal failure. Whereas it is known that Fabry disease affects small blood vessels, little is known about its effects on peripheral large arteries. We therefore set out to compare parameters of arterial wall structure and function in a cohort of patients with Fabry disease and an age-matched control group. Methods: Large artery phenotype was non-invasively investigated in 21 hemizygous patients with Fabry disease and 24 age-matched male controls. Common carotid and radial artery diameter, intima-media thickness (IMT) and distensibility were determined with high-definition echotracking systems and aplanation tonometry. Results: Patients with Fabry disease had a significant twofold increase in radial artery IMT and distensibility, independent of body surface area, age and mean blood pressure. In both groups, older age at the time of examination was significantly associated with larger radial artery IMT. The relationship between age and radial IMT was 2.3-fold higher in patients with Fabry disease than in controls (p < 0.01). Carotid IMT was mildly but significantly increased in patients with Fabry disease (+18%), whereas distensibility was unchanged. Conclusion: This study presents evidence of a major increase in arterial wall thickness and distensibility, measurable at the site of a medium-sized artery, in a cohort of patients with classic Fabry disease. [ABSTRACT FROM AUTHOR]

The synthesis and inhibitory activity against MraY of a series of simplified analogues of liposidomycins are described. These compounds were mainly obtained by performing parallel synthesis in the 6′-position of a scaffold that gathers key features found necessary for the binding to MraY. Thus, inhibitory activity was improved from 5300 to 140 nM. This improvement was correlated with the length and lipophilicity of substituents, but was found to be independent of the nature of the chemical bond generated. In addition, some of these inhibitors presented encouraging antibacterial activities. [Copyright &y& Elsevier]

Focuses on the failure of Diprifuser anesthetic infusion pumps manufactured by Graseby PLC. Possible reasons for the failure of the medical device; Presentation of clinical cases of product failure; Recommended guidelines to prevent the occurrence of similar product failures in the future.

Key Clinical Message: Gliosarcoma, a rare cerebral neoplasm, has not been linked to hippocampal changes in cats. We report a case of complex partial seizures with orofacial involvement, revealing gliosarcoma concurrent with bilateral hippocampal sclerosis. A 16‐year‐old neutered female domestic shorthair cat presented with acute inappetence, ataxia, disorientation, and vacant staring. Brain MRI revealed an ill‐defined, round, intra‐axial mass in the right piriform lobe, showing hyperintensity on T2W, T2‐FLAIR, and T2*W, and hypointensity on T1W images. The lesion exhibited mass effect and contrast enhancement in its center. Bilateral hyperintensity on T2‐FLAIR images and contrast enhancement were observed in the hippocampus. Brain histologic and immunohistochemical analysis revealed cerebral gliosarcoma with concurrent hippocampal sclerosis. Feline LGI1‐antibody testing on the serum and/or CSF was not performed due to insufficient biomaterial. Although retrospective testing on brain tissue was considered, it ultimately proved unfeasible, preventing us from ruling out antibody‐associated limbic encephalitis. In conclusion, cerebral gliosarcoma should be included in feline intracranial tumor differentials, warranting brain MRI and feline LGI1‐antibody testing in cats showing complex partial seizures with orofacial involvement. In our case, the prognosis remained poor due to the presence of a high‐grade glioma. [ABSTRACT FROM AUTHOR]

Presents a study which examined the issue of dominating control and warmth in fathers and mothers as perceived by adult Chinese sons and daughters. Separate analyses for fathers and mothers; Greater perceived parental dominating related to less perceived parental warmth; Subjects; Measures; Discussion.

CTLA-4 is the major negative regulator of T cell responses. We have analyzed the expression of CTLA-4 in human monocytes and monocyte-derived DCs and the effects of its engagement on cytokine production and T cell stimulatory activity by mature DCs (mDCs). We found that CTLA-4 was highly expressed on freshly isolated monocytes, then down-modulated on the immature DCs (iDCs) and upregulated on mDCs. Treatment of mDCs with an agonistic anti-CTLA-4 mAb enhanced secretion of IL-10 but reduced secretion of IL-8 and IL-12, as well as autologous CD4+ T-cell proliferation in response to stimulation with PPD recall antigen-loaded-DCs. Neutralization of IL-10 with an anti-IL-10 antibody partially restored the ability of anti-CTLA-4-treated mDCs to stimulate T cell proliferation in response to PPD. Our data provide the first evidence that CTLA-4 receptor is expressed by human mDCs and exerts immune modulatory effects in these cells. [ABSTRACT FROM AUTHOR]

We demonstrated an integrated three terminal device able to modulate the cavity losses of quantum cascade lasers. By growing asymmetric doped quantum wells coupled to the laser’s mode an absorption peak can be electrically shifted in and out the laser transition. The use of three terminals allows one to drive the laser independently from the wells and therefore to modulate the laser’s amplitude with an electrical power of only a few milliwatts. This is far less than the power needed for a direct modulation of the laser light. [ABSTRACT FROM AUTHOR]

We present an optimized technique for the measurement of gain and losses of semiconductor lasers. We optically inject the beam of a distributed feedback laser (DFB) inside the cavity of the lasers under study. The DFB laser operates in a pulsed mode and shifts its emission wavelength as a function of time. This frequency chirp creates the Fabry–Pérot fringes of the transmitted intensity that contains all the information on the cavity losses. The setup has been validated by a quantitative study of the losses as a function of the injected current, for a quantum cascade laser emitting at 7.6 μm. [ABSTRACT FROM AUTHOR]

We propose a technique based on Fabry-Pérot fringes to analyze, in a broad wavelength range, the waveguide properties of semiconductor lasers in the midinfrared spectrum. This technique has been applied to strain-balanced Ga0.32In0.68As/Al0.64In0.36As quantum cascade lasers, with a double phonon active region, in order to determine propagation losses and the effective index between 2.5 and 8 μm wavelength. These results are in good agreement with the values obtained using another method. [ABSTRACT FROM AUTHOR]

Photon correlation measurements are performed on single GaAs quantum dots with various excitonic radiative lifetimes. A continuous increase of the probability that the quantum dot emits more than one photon per excitation pulse is observed when decreasing the exciton radiative lifetime. The authors show that this increase is due to recapture processes into the quantum dot. A model for the second-order autocorrelation function including relaxation processes is developed and gives good description of the experimental observations. [ABSTRACT FROM AUTHOR]

Thin films of perovskitelike CaCu2Mn5O12 have been grown by pulsed laser deposition. These films are ferromagnetic with a Curie temperature (TC) of 292 K which is very close to that expected for the bulk material (TC=310 K). Increasing the oxygen pressure during cooling does not markedly affect the out-of-plane lattice parameter (c) or TC of the films, but enhances the magnetization at low temperature. Transport properties of films exhibit metallic behavior in the temperature range of 10–360 K. The most important difference between these films and the bulk material was observed in their magnetotransport characteristics. The magnetoresistance effect is important at low temperatures for the bulk material, while for the thin films, this effect is large (-8%) close to TC, as expected for a regular ferromagnetic material. [ABSTRACT FROM AUTHOR]

We report on the spontaneous emission of a single-quantum dot embedded in a two-dimensional photonic crystal cavity. The resonant coupling between the dot and the strongly localized optical mode significantly shortens the spontaneous emission lifetime, so that the coherence time of the emitted photons is dominated by radiative effects: The emitted photons are indistinguishable, with a mean wave-packet overlap as high as 72%. [ABSTRACT FROM AUTHOR]

Background electrolytes affect calcite precipitation and dissolution rates and hence have the potential to impact kinetic isotope fractionation between calcite and the dissolved inorganic carbon (DIC) species. We grew inorganic calcite from NaCl-CaCl 2 solutions (T = 25 °C, pH = 8.3, and crystal growth rate = 10−6.3 ± 0.3 mol m−2 s−1) to test for potential ionic strength effects on the oxygen isotope fractionation between calcite and an isotopically equilibrated inorganic carbon pool (α c/EIC). Calcite was grown in the presence of the enzyme carbonic anhydrase from bovine erythrocytes (bCA) to promote isotopic equilibration of the DIC pool. No evidence of an ionic strength effect on α c/EIC was found for NaCl concentrations up to 0.35 M (1000lnα c/w = 28.0 ± 0.1; n = 7). For experiments conducted with [NaCl] > 0.35 M, the DIC pool could not be maintained in isotopic equilibrium with water due to the inhibitory effect of NaCl on bCA. The use of other types of CA may be required to maintain isotopic equilibration of DIC in solution with ionic strength close to or above that of seawater. The oxygen isotope results were modeled successfully with an isotopic box model for a CO 2 -fed solution that tracks the isotopic composition of each DIC species and CaCO 3. The experimental and modeling results suggest that the efficacy of bCA decreases exponentially with increasing [NaCl]. We quantify the salt effect on the quantity k cat / K M , which relates the catalyzed rate constant for CO 2 hydration to the concentration of bCA. The salt effect can be implemented in models of biomineralization with potential to extend our knowledge of oxygen isotope vital effects in marine organisms. [ABSTRACT FROM AUTHOR]

The Kepler and Transiting Exoplanet Survey Satellite (TESS) missions have generated over 100,000 potential transit signals that must be processed in order to create a catalog of planet candidates. During the past few years, there has been a growing interest in using machine learning to analyze these data in search of new exoplanets. Different from the existing machine learning works, ExoMiner , the proposed deep learning classifier in this work, mimics how domain experts examine diagnostic tests to vet a transit signal. ExoMiner is a highly accurate, explainable, and robust classifier that (1) allows us to validate 301 new exoplanets from the MAST Kepler Archive and (2) is general enough to be applied across missions such as the ongoing TESS mission. We perform an extensive experimental study to verify that ExoMiner is more reliable and accurate than the existing transit signal classifiers in terms of different classification and ranking metrics. For example, for a fixed precision value of 99%, ExoMiner retrieves 93.6% of all exoplanets in the test set (i.e., recall = 0.936), while this rate is 76.3% for the best existing classifier. Furthermore, the modular design of ExoMiner favors its explainability. We introduce a simple explainability framework that provides experts with feedback on why ExoMiner classifies a transit signal into a specific class label (e.g., planet candidate or not planet candidate). [ABSTRACT FROM AUTHOR]

The Kepler and Transiting Exoplanet Survey Satellite (TESS) missions have generated over 100,000 potential transit signals that must be processed in order to create a catalog of planet candidates. During the past few years, there has been a growing interest in using machine learning to analyze these data in search of new exoplanets. Different from the existing machine learning works, ExoMiner, the proposed deep learning classifier in this work, mimics how domain experts examine diagnostic tests to vet a transit signal. ExoMiner is a highly accurate, explainable, and robust classifier that (1) allows us to validate 301 new exoplanets from the MAST Kepler Archive and (2) is general enough to be applied across missions such as the ongoing TESS mission. We perform an extensive experimental study to verify that ExoMiner is more reliable and accurate than the existing transit signal classifiers in terms of different classification and ranking metrics. For example, for a fixed precision value of 99%, ExoMiner retrieves 93.6% of all exoplanets in the test set (i.e., recall = 0.936), while this rate is 76.3% for the best existing classifier. Furthermore, the modular design of ExoMiner favors its explainability. We introduce a simple explainability framework that provides experts with feedback on why ExoMiner classifies a transit signal into a specific class label (e.g., planet candidate or not planet candidate). [ABSTRACT FROM AUTHOR]

Contact investigations following the diagnosis of active tuberculosis (TB) are paramount for the control of the disease. Epidemiological data are very powerful for contact tracing but might be delayed and/or difficult to integrate, especially in the setting of multiple contact-tracing investigations. The aim of this study was to address the added-value of whole-genome sequencing (WGS) to routine local TB surveillance systems. From November 2016 to July 2017, the local TB surveillance system identified three clusters that could constitute a unique larger outbreak. Epidemiological and clinical information were integrated with WGS genotyping data of Mycobacterium tuberculosis strains obtained using a simple DNA extraction method coupled with sequencing using an Illumina MiSeq platform and an in-house bioinformatics pipeline for single nucleotide polymorphism (SNP) analysis. Epidemiological investigations identified three putative TB clusters potentially interrelated including eight patients with active TB. Seven M. tuberculosis isolates were available and analysed by WGS. Using a 5-SNP threshold to define recent transmission, WGS-based genotyping supported the occurrence of the three clusters as well as a link between clusters 1 and 2 (SNP ≤1), constituting a larger outbreak. This outbreak was clearly delineated by refuting a potential link with the third cluster (SNP >500). Genotyping data did not support the belonging of patient 7 to any studied cluster. This study illustrates the usefulness of WGS genotyping for routine TB surveillance systems in local communities to rapidly confirm or disprove epidemiological hypotheses and delineate TB clusters, especially in the context of multiple contact-tracing investigations. [ABSTRACT FROM AUTHOR]

The Cedars ultramafic block hosts alkaline springs (pH > 11) in which calcium carbonate forms upon uptake of atmospheric CO 2 and at times via mixing with surface water. These processes lead to distinct carbonate morphologies with "floes" forming at the atmosphere-water interface, "snow" of fine particles accumulating at the bottom of pools and terraced constructions of travertine. Floe material is mainly composed of aragonite needles despite CaCO 3 precipitation occurring in waters with low Mg/Ca (<0.01). Precipitation of aragonite is likely promoted by the high pH (11.5–12.0) of pool waters, in agreement with published experiments illustrating the effect of pH on calcium carbonate polymorph selection. The calcium carbonates exhibit an extreme range and approximately 1:1 covariation in δ13C (−9 to −28‰ VPDB) and δ18O (0 to −20‰ VPDB) that is characteristic of travertine formed in high pH waters. The large isotopic fractionations have previously been attributed to kinetic isotope effects accompanying CO 2 hydroxylation but the controls on the δ13C-δ18O endmembers and slope have not been fully resolved, limiting the use of travertine as a paleoenvironmental archive. The limited areal extent of the springs (∼0.5 km2) and the limited range of water sources and temperatures, combined with our sampling strategy, allow us to place tight constraints on the processes involved in generating the systematic C and O isotope variations. We develop an isotopic reaction–diffusion model and an isotopic box model for a CO 2 -fed solution that tracks the isotopic composition of each dissolved inorganic carbon (DIC) species and CaCO 3. The box model includes four sources or sinks of DIC (atmospheric CO 2 , high pH spring water, fresh creek water, and CaCO 3 precipitation). Model parameters are informed by new floe Δ44Ca data (−0.75 ± 0.07‰), direct mineral growth rate measurements (4.8 to 8 × 10−7 mol/m2/s) and by previously published elemental and isotopic data of local water and DIC sources. Model results suggest two processes control the extremes of the array: (1) the isotopically light end member is controlled by the isotopic composition of atmospheric CO 2 and the kinetic isotope fractionation factor (KFF (‰) = (α − 1) × 1000) accompanying CO 2 hydroxylation, estimated here to be −17.1 ± 0.8‰ (vs. CO 2(aq)) for carbon and −7.1 ± 1.1‰ (vs. 'CO 2(aq) + H 2 O') for oxygen at 17.4 ± 1.0 °C. Combining our results with revised CO 2 hydroxylation KFF values based on previous work suggests consistent KFF values of −17.0 ± 0.3‰ (vs. CO 2(aq)) for carbon and −6.8 ± 0.8‰ for oxygen (vs. 'CO 2(aq) + H 2 O') over the 17–28 °C temperature range. (2) The isotopically heavy endmember of calcium carbonates at The Cedars reflects the composition of isotopically equilibrated DIC from creek or surface water (mostly HC O 3 - , pH = 7.8–8.7) that occasionally mixes with the high-pH spring water. The bulk carbonate δ13C and δ18O values of modern and ancient travertines therefore reflect the proportion of calcium carbonate formed by processes (1) and (2), with process (2) dominating the carbonate precipitation budget at The Cedars. These results show that recent advances in understanding kinetic isotope effects allow us to model complicated but common natural processes, and suggest ancient travertine may be used to retrieve past meteoric water δ18O and atmospheric δ13C values. There is evidence that older travertine at The Cedars recorded atmospheric δ13C that predates large-scale combustion of fossil fuels. [ABSTRACT FROM AUTHOR]

The notion of shared memory is unclear. How can we ensure that representations of the past are really identical for a group of individuals? In the first part of this text, I suggest that the blur surrounding the notion of shared memory is only a special case of the floating meaning intrinsic to holistic rhetoric used in the social sciences to designate shared or supposedly shared representations. In the second part, I present two of the three modalities of memory sharing (protomemory and memory itself) and propose 18 criteria intended to test the sharing of the second modality. The last part is devoted to collective metamemory—the third modality—defined by its narrative dimension, that is, by the storytelling of a shared or supposedly shared memory. I argue that the metamemorial narrative gives consistency to memory sharing by propagating belief in shared memory, notably through narrative illumination effects of past events. The shape of this memory intersubjectivity can be paradoxical: often, what we take for a shared memory is in reality the shared narrative of a belief in the sharing of this memory. [ABSTRACT FROM AUTHOR]

Background: Head and neck cancer is particular due to its infiltrative nature and lymphatic extension, with multidisciplinary treatment. Immunotherapy may be a brand-new therapeutic approach.Case Presentation: We report a case of patient with advanced head and neck cancer resistant to cytotoxic treatment, with astonishing response to antibodies anti Programmed Death 1 (PD1).Conclusion: Further studies are needed in order to obtained predictive index of immunotherapy responding, aiming to select appropriately patients for this treatment. [ABSTRACT FROM AUTHOR]

Trabectedin (ET-743) is a marine alkaloid isolated from the Caribbean tunicate Ecteinascidia turbinata, with a chemical structure characterized by three fused tetrahydroisoquinoline rings. In the present case report, two patients with advanced and metastatic uterine leiomyosarcomas (ULMS) with significant progression-free survival (PFS) and overall survival (OS) administered Trabectedin as second and third line treatment are reported. The first case received third line Trabectedin with a PFS of 24 months and an OS of 35 months. The second case received second line Trabectedin with a PFS of 24 months and an OS of 30 months. In addition, a good safety record was obtained in the long-term administration of Trabectedin (more so in case 1 than case 2), with a good quality of life. [ABSTRACT FROM AUTHOR]