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BackgroundCervical cancers are mainly caused by an oncogenic HPV. For locally advanced stages, the standard treatment is radio-chemotherapy (RTCT) followed by brachytherapy. Nevertheless, the prognosis remains highly heterogeneous between patients.ObjectiveWe investigated the prognostic value of HPV circulating tumor DNA (ctDNA) in locally advanced cervical cancers alongside that of Squamous Cell Carcinoma Antigen (SCC-A).MethodsThis single-center retrospective study included patients treated in curative intent for an IB3 to IVA squamous cell cervical cancer. Quantification of HPV ctDNA in serum collected at diagnosis was performed using a multiplex digital PCR assay for the simultaneous detection of 8 HPV genotypes.ResultsAmong the 97 patients included, 76 patients (78.4%) were treated by RTCT, followed by brachytherapy for 57 patients (60%). HPV ctDNA was detected in 59/97 patients at diagnosis (60.8%). This detection was associated with lymph node invasion (p=0.04) but not with tumor stage. A high level of SCC-A at diagnosis was associated with tumor stage (p=0.008) and lymph node invasion (p=0.012). In univariate analysis, better disease-free survival (DFS) was associated with optimal RTCT regimen (p=0.002), exposure to brachytherapy (p=0.0001) and a low SCC-A at diagnosis (continuous analysis, p=0.002). Exploratory analysis revealed that 3/3 patients (100%) whose HPV ctDNA was still detectable at the end of treatment relapsed, while 6/22 patients (27.3%) whose HPV ctDNA was negative at the end of treatment relapsed.ConclusionHPV ctDNA detection at diagnosis of locally advanced cervical squamous cell carcinomas is frequent and related to node invasion, but not to DFS. The prognostic value of HPV ctDNA detection after treatment warrants specific studies.

The ZX-calculus is a powerful framework for reasoning in quantum computing. It provides in particular a compact representation of matrices of interests. A peculiar property of the ZX-calculus is the absence of a formal sum allowing the linear combinations of arbitrary ZX-diagrams. The universality of the formalism guarantees however that for any two ZX-diagrams, the sum of their interpretations can be represented by a ZX-diagram. We introduce a general, inductive definition of the addition of ZX-diagrams, relying on the construction of controlled diagrams. Based on this addition technique, we provide an inductive differentiation of ZX-diagrams. Indeed, given a ZX-diagram with variables in the description of its angles, one can differentiate the diagram according to one of these variables. Differentiation is ubiquitous in quantum mechanics and quantum computing (e.g. for solving optimization problems). Technically, differentiation of ZX-diagrams is strongly related to summation as witnessed by the product rules. We also introduce an alternative, non inductive, differentiation technique rather based on the isolation of the variables. Finally, we apply our results to deduce a diagram for an Ising Hamiltonian.

Abstract Objective Endocrine therapy is frequently administered in patients with hormone dependent (HR+) metastatic endometrial cancer. ESR1 mutations have emerged as a key mechanism of aromatase inhibitor (AI) resistance in HR + metastatic breast cancer and can be monitored using circulating tumor DNA (ctDNA). The aim of this study was to explore the incidence and clinical relevance of circulating ESR1 mutations in patients treated by AI or megestrol acetate (M) for advanced endometrial carcinoma. Methodology This single-center retrospective study was performed at the Henri Becquerel Center (Rouen) and looked for circulating ESR1 gene mutations by droplet digital PCR (E380Q, L536R, Y537S, Y537N, Y537C, D538G, S463P) in patients with advanced HR + endometrial carcinoma treated between 2008 and 2020 for at least 30 days by AI or M. Analyses were performed before exposure and at progression/during endocrine therapy. Results Twenty-two patients were included: 13 were treated with AI, 12 of whom progressed; 9 patients were treated with M, 8 of whom progressed. 68.1% of the patients had low-grade endometrial carcinoma and 54.5% had received chemotherapy in the metastatic setting. The median duration of treatment was 152 days (min 47 – max 629) with AI and 155 days (min 91-max 1297) with M. Under AI, there was no ESR1 mutation at baseline, and one Y537C mutation at progression with a variant allele frequency (VAF) of 0.14%. Under M, one patient had a Y537C (VAF 0.2%) at baseline that disappeared during treatment. Another patient had a Y537S mutation emergence at progression after 91 days of treatment (VAF 1.83%). There was no significant difference between the circulating DNA concentration before and after hormone therapy (p = 0.16). Conclusion ESR1 mutations do not seem to be involved in the mechanisms of resistance to AI or M in HR+ endometrial cancer. The clinical relevance of their detection is not demonstrated.

More than 7 million early deaths/year are attributable to air pollution. Current health concerns are especially focused on air pollution-derived particulate matter (PM). Although oxidative stress-induced airway inflammation is one of the main adverse outcome pathways triggered by air pollution-derived PM, the persistence of both these underlying mechanisms, even after exposure cessation, remained poorly studied. In this study, A/JOlaHsd mice were also exposed acutely (24 h) or sub-chronically (4 weeks), with or without a recovery period (12 weeks), to two urban PM2.5 samples collected during contrasting seasons (i.e., autumn/winter, AW or spring/summer, SS). The distinct intrinsic oxidative potentials (OPs) of AW and SS PM2.5, as evaluated in acellular conditions, were closely related to their respective physicochemical characteristics and their respective ability to really generate ROS over-production in the mouse lungs. Despite the early activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) cell signaling pathway by AW and, in a lesser degree, SS PM2.5, in the murine lungs after acute and sub-chronic exposures, the critical redox homeostasis was not restored, even after the exposure cessation. Accordingly, an inflammatory response was reported through the activation of the nuclear factor-kappa B (NF-κB) cell signaling pathway activation, the secretion of cytokines, and the recruitment of inflammatory cells, in the murine lungs after the acute and sub-chronic exposures to AW and, in a lesser extent, to SS PM2.5, which persisted after the recovery period. Taken together, these original results provided, for the first time, new relevant insights that air pollution-derived PM2.5, with relatively high intrinsic OPs, induced oxidative stress and inflammation, which persisted admittedly at a lower level in the lungs after the exposure cessation, thereby contributing to the occurrence of molecular and cellular adverse events leading to the development and/or exacerbation of future chronic inflammatory lung diseases and even cancers.

This study aimed to estimate the diagnostic performance of patient symptoms and to describe the clinical course of RT-PCR-positive compared with RT-PCR-negative patients in primary care. Symptomatic COVID-19 suspects were assessed clinically at the initial consultation in primary care between March and May 2020, followed by phone consultations over a span of at least 28 days. Sensitivity and specificity were estimated for each symptom using the initial RT-PCR result as a reference standard. The proportions of symptomatic patients according to the RT-PCR test results were compared over time, and time to recovery was estimated. Out of 883 patients, 13.9% had a positive RT-PCR test, and 17.4% were not tested. Most sensitive symptoms were cough, myalgia, and a history of fever, while most specific symptoms were fever for ≥4 days, hypo/anosmia, and hypo/ageusia. At the final follow up (median time 55 days, range 28–105 days), 44.7% of patients still reported symptoms in the RT-PCR-positive group, compared with 18.3% in the negative group (p < 0.001), mostly with hypo/anosmia (16.3%), dyspnea (12.2%), and fatigue (10.6%). The discriminative value of individual symptoms for diagnosing COVID-19 was limited. Almost half of the SARS-CoV-2-positive patients still reported symptoms at least 28 days after the initial consultation.

Precision edge preparation techniques for cemented carbides enable optimization of the geometry of tools’ cutting edges. These techniques are frequently used in high-stress environments, resulting in substantial improvements in tools’ cutting performance. This investigation examined the impact and evolution of cutting edge parameters and resulting surface finishes as a function of dry-electropolishing time on an end-mill. Findings demonstrate enlargement of the cutting edge radius, a decrease in surface roughness, and the mitigation of defects induced during previous manufacturing stages (i.e., smashed ceramic particles, burrs, chipping, etc.). Additionally, a direct correlation between dry-electropolishing time and primary cutting edges’ micro-geometry parameters has been established.

Investigation of four different surface-shaping and finishing sequences is carried out on the surface integrity of a WC-10Co hardmetal grade. The surface conditions include grinding, electrical discharge machining and grinding, followed by mechanical and dry-electrochemical polishing using the DryLyte® technology. The evaluation includes the measurement of roughness, residual stresses, the Vickers hardness, indentation fracture toughness determination and the damage induced by conical contact response. By scanning electron microscopy, a systematic and detailed examination of the residual imprints is carried out to determine the critical loads for damage initiation and development across the different surface conditions. The results indicate that the use of dry-electrochemical polishing enables the attainment of polished surfaces without any corrosive damage to the metallic binder. Moreover, it retains the mechanical attributes reminiscent of the core material, comprising 85% that were initially induced via grinding.

BackgroundNasopharyngeal antigen Rapid Diagnostic Tests (RDTs), saliva RT-PCR and nasopharyngeal (NP) RT-PCR have shown different performance characteristics to detect patients infected by SARS-CoV-2, according to the viral load (VL)-and thus transmissibility.MethodsIn October 2020, we conducted a prospective trial involving patients presenting at testing centres with symptoms of COVID-19. We compared detection rates and performance of RDT, saliva PCR and nasopharyngeal (NP) PCR, according to VL and symptoms duration.ResultsOut of 949 patients enrolled, 928 patients had all three tests performed. Detection rates were 35.2% (95%CI 32.2-38.4%) by RDT, 39.8% (36.6-43.0%) by saliva PCR, 40.1% (36.9-43.3%) by NP PCR, and 41.5% (38.3-44.7%) by any test. For those with viral loads (VL) ≥106 copies/ml, detection rates were 30.3% (27.3-33.3), 31.4% (28.4-34.5), 31.5% (28.5-34.6), and 31.6% (28.6-34.7%) respectively. Sensitivity of RDT compared to NP PCR was 87.4% (83.6-90.6%) for all positive patients, 94.5% (91.5-96.7%) for those with VL≥105 and 96.5% (93.6-98.3%) for those with VL≥106. Sensitivity of STANDARD-Q®, Panbio™ and COVID-VIRO® Ag tests were 92.9% (86.4-96.9%), 86.1% (78.6-91.7%) and 84.1% (76.9-89.7%), respectively. For those with VL≥106, sensitivity was 96.6% (90.5-99.3%), 97.8% (92.1-99.7%) and 95.3% (89.4-98.5%) respectively. No patient with VLConclusionsRDT results allow rapid identification of COVID cases with immediate isolation of most contagious individuals. RDT can thus be a game changer both in ambulatory care and community testing aimed at stopping transmission chains, and even more so in resource-constrained settings thanks to its very low price. When PCR is performed, saliva could replace NP swabbing.Trial registrationClinicalTrial.gov Identifier: NCT04613310 (03/11/2020).

Abstract Inflammatory breast cancer (IBC) is an aggressive BC subtype with poor outcomes. A targetable somatic PIK3CA mutation is reported in 30% of IBC, allowing for treatment by PI3Kα-specific inhibitors, such as alpelisib. The aim of this study was to evaluate the detection rate of circulating PIK3CA mutation in locally-advanced IBC (LAIBC) patients harbouring a PIK3CA mutation on initial biopsy. This monocentric retrospective study was based on available stored plasma samples and tumour biopsies at diagnosis from all LAIBC patients treated with neo-adjuvant chemotherapy (NCT) between 2008 and 2018 at the Centre Henri Becquerel. PIK3CA mutations (E542K, E545K, H1047R/L) were assessed by droplet digital PCR (ddPCR) in plasma samples and tumoral tissue at diagnosis. A total of 55 patients were included. Overall, 14/55 patients (25%) had a PIK3CA mutation identified on baseline biopsy (H1047R = 8; H1047L = 3; E545K = 2; E542K = 1). Among them, 11 (79%) patients had enough DNA for circulating DNA analyses, and corresponding circulating PIK3CA mutations were found in 6/11 (55%). Among the 41 patients without PIK3CA mutations on biopsy, 32 (78%) had enough DNA for circulating DNA analysis, and no circulating PIK3CA mutation was identified. Our results revealed no prognostic or predictive value of PIK3CA mutations at the diagnosis of non-metastatic IBC but highlighted the prognostic value of the cfDNA rate at diagnosis. Our study showed that a corresponding circulating PIK3CA mutation was identified in 55% of LAIBC patients with PIK3CA-mutated tumours, while no circulating mutation was found among patients with PI3KCA wild-type tumours.

The growing process of a spinel-like oxide film can be obtained through different atmospheres; in this sense Air, O2, steam, and nitrogen atmospheres were used in different steps during the aging heat treatment at 490ºC of maraging 300 and 350 alloys. The oxidation layer produced under different atmospheres was chemically, microstructurally and mechanically characterized by means of advanced techniques. The results showed (in both alloys) a non-homogeneous mix oxide formed by magnetite, nickel and cobalt ferrites and MoO3 heterogeneously distributed along the oxide thickness. It was also founded TiO2 in the innermost areas and a particularly important quantify of hematite on the external surface. A nickel-rich austenite phase was produced at the interphase due to the combination of nickel stability and the preference of cobalt, molybdenum, and iron diffuses through the film as ions. The highest thickness values were found in the oxides produced in maraging 300 steels which could indicate greater susceptibility to oxidation comparing with grade 350 maraging steel. The oxide films produced in both maraging alloys using air atmosphere presents excellent adherence, and the results show the capability for being used for tribological applications under sliding contact tests.

Aim: To investigate the evolution of the incretin‐like peptide 26RFa in a prospective cohort of women living with obesity with or without type 2 diabetes (T2D) before and after sleeve gastrectomy (SG). Methods: In this study, a total of 61 women were divided into three groups: women living with severe obesity without T2D (WlwOB group), women living with severe obesity and T2D (WlwOB‐T2D group) and lean healthy volunteers (control group). Serum 26RFa concentrations were measured using a 26RFa enzyme‐linked immunosorbent assay developed specifically for this study during meal tests before SG, and 30 and 180 days after SG. Results: At baseline, serum 26RFa levels were reduced in the WlwOB (P <.05) and WlwOB‐T2D (P <.01) groups compared with controls. In the WlwOB‐T2D group, fasting 26RFa levels were found to increase throughout the entire follow‐up period up to 6 months after the SG (P <.001). During the meal tests, serum 26RFa levels increased, especially in the WlwOB‐T2D group at baseline. At the end of the follow‐up, the profile of 26RFa concentrations obtained during the meal test in patients with severe obesity and T2D was similar to that of the controls. Conclusions: This prospective clinical study provides the first evidence that circulating 26RFa is altered mainly in WlwOB‐T2D, and that these defects are partially reversed after SG. [ABSTRACT FROM AUTHOR]

Background: Cervical cancers are mainly caused by an oncogenic HPV. For locally advanced stages, the standard treatment is radio-chemotherapy (RTCT) followed by brachytherapy. Nevertheless, the prognosis remains highly heterogeneous between patients. Objective: We investigated the prognostic value of HPV circulating tumor DNA (ctDNA) in locally advanced cervical cancers alongside that of Squamous Cell Carcinoma Antigen (SCC-A). Methods: This single-center retrospective study included patients treated in curative intent for an IB3 to IVA squamous cell cervical cancer. Quantification of HPV ctDNA in serum collected at diagnosis was performed using a multiplex digital PCR assay for the simultaneous detection of 8 HPV genotypes. Results: Among the 97 patients included, 76 patients (78.4%) were treated by RTCT, followed by brachytherapy for 57 patients (60%). HPV ctDNA was detected in 59/97 patients at diagnosis (60.8%). This detection was associated with lymph node invasion (p=0.04) but not with tumor stage. A high level of SCC-A at diagnosis was associated with tumor stage (p=0.008) and lymph node invasion (p=0.012). In univariate analysis, better disease-free survival (DFS) was associated with optimal RTCT regimen (p=0.002), exposure to brachytherapy (p=0.0001) and a low SCC-A at diagnosis (continuous analysis, p=0.002). Exploratory analysis revealed that 3/3 patients (100%) whose HPV ctDNA was still detectable at the end of treatment relapsed, while 6/22 patients (27.3%) whose HPV ctDNA was negative at the end of treatment relapsed. Conclusion: HPV ctDNA detection at diagnosis of locally advanced cervical squamous cell carcinomas is frequent and related to node invasion, but not to DFS. The prognostic value of HPV ctDNA detection after treatment warrants specific studies. [ABSTRACT FROM AUTHOR]

Amoeboid cells are associated with melanoma invasive capacity. Here, the authors show that the WNT11-FZD7-DAAM1 pathway regulates tumour-initiating potential, invasion and metastasis lead by amoeboid cells in the invasive front of melanoma tumours.

Abstract Background Endocrine therapy is recommended as a first-line treatment for hormone receptor-positive metastatic breast cancer (HR+MBC) patients. No biomarker has been validated to predict tumor progression in that setting. We aimed to prospectively compare the risk of early progression according to circulating ESR1 mutations, CA-15.3, and circulating cell-free DNA in MBC patients treated with a first-line aromatase inhibitor (AI). Methods Patients with MBC treated with a first-line AI were prospectively included. Circulating biomarker assessment was performed every 3 months. The primary objective was to determine the risk of progression or death at the next follow-up visit (after 3 months) in case of circulating ESR1 mutation detection among patients treated with a first-line AI for HR+MBC. Results Overall, 103 patients were included, and 70 (68%) had progressive disease (PD). Circulating ESR1 mutations were detected in 22/70 patients with PD and in 0/33 patients without progression (p

Here we report results of a detailed analysis of the urban and non-urban contributions to particulate matter (PM) concentrations and source contributions in five European cities, namely Schiedam (the Netherlands, NL), Lens (France, FR), Leipzig (Germany, DE), Zurich (Switzerland, CH) and Barcelona (Spain, ES). PM chemically speciated data from 12 European paired monitoring sites (one traffic, five urban, five regional and one continental background) were analysed by positive matrix factorisation (PMF) and Lenschow's approach to assign measured PM and source contributions to the different spatial levels. Five common sources were obtained at the 12 sites: sulfate-rich (SSA) and nitrate-rich (NSA) aerosols, road traffic (RT), mineral matter (MM), and aged sea salt (SS). These sources explained from 55 % to 88 % of PM mass at urban low-traffic-impact sites (UB) depending on the country. Three additional common sources were identified at a subset of sites/countries, namely biomass burning (BB) (FR, CH and DE), explaining an additional 9 %–13 % of PM mass, and residual oil combustion (V–Ni) and primary industrial (IND) (NL and ES), together explaining an additional 11 %–15 % of PM mass. In all countries, the majority of PM measured at UB sites was of a regional+continental (R+C) nature (64 %–74 %). The R+C PM increments due to anthropogenic emissions in DE, NL, CH, ES and FR represented around 66 %, 62 %, 52 %, 32 % and 23 %, respectively, of UB PM mass. Overall, the R+C PM increments due to natural and anthropogenic sources showed opposite seasonal profiles with the former increasing in summer and the latter increasing in winter, even if exceptions were observed. In ES, the anthropogenic R+C PM increment was higher in summer due to high contributions from regional SSA and V–Ni sources, both being mostly related to maritime shipping emissions at the Spanish sites. Conversely, in the other countries, higher anthropogenic R+C PM increments in winter were mostly due to high contributions from NSA and BB regional sources during the cold season. On annual average, the sources showing higher R+C increments were SSA (77 %–91 % of SSA source contribution at the urban level), NSA (51 %–94 %), MM (58 %–80 %), BB (42 %–78 %) and IND (91 % in NL). Other sources showing high R+C increments were photochemistry and coal combustion (97 %–99 %; identified only in DE). The highest regional SSA increment was observed in ES, especially in summer, and was related to ship emissions, enhanced photochemistry and peculiar meteorological patterns of the Western Mediterranean. The highest R+C and urban NSA increments were observed in NL and associated with high availability of precursors such as NOx and NH3. Conversely, on average, the sources showing higher local increments were RT (62 %–90 % at all sites) and V–Ni (65 %–80 % in ES and NL). The relationship between SSA and V–Ni indicated that the contribution of ship emissions to the local sulfate concentrations in NL has strongly decreased since 2007 thanks to the shift from high-sulfur- to low-sulfur-content fuel used by ships. An improvement of air quality in the five cities included here could be achieved by further reducing local (urban) emissions of PM, NOx and NH3 (from both traffic and non-traffic sources) but also SO2 and PM (from maritime ships and ports) and giving high relevance to non-urban contributions by further reducing emissions of SO2 (maritime shipping) and NH3 (agriculture) and those from industry, regional BB sources and coal combustion.

Spontaneous coronary artery dissection (SCAD) is a rare cause of acute myocardial infarction (ACS). We report a case of acute coronary syndrome due to SCAD of the right coronary artery. Diagnosis was based on clinical presentation and coronary angiography, and confirmed by optical coherence tomography which guided our treatment strategy. (Level of Difficulty: Beginner.)

Inhalation of welding fumes (WFs) containing high levels of transition metals (Cr, Cu, Fe, Mn, Ni...) is associated with numerous health effects including oxidative stress. However, the measurements of the oxidative potential (OP) and bioaccessibility of WF transition metals depend on several physicochemical parameters and may be subject to several experimental artifacts. In this work, we investigated the influence of the experimental conditions that may affect the bioaccessibility of transition metals and their OP on stainless-steel WF extracts. WFs were produced using a generation bench and sampled on filters. The soluble fraction of the metals was analysed. Two different extraction fluids mimicking physiological pulmonary conditions were studied: phosphate buffer and Hatch's solution. Three extraction times were tested to determine the optimal time for a significant OPDTT using the dithiothreitol (DTT) method. The storage conditions of WFs after filter sampling such as duration, temperature and atmospheric conditions were investigated. The results indicate that experimental conditions can significantly affect the OPDTT and metal bioaccessibility analyses. Cr, Cu and Ni show higher solubility in Hatch's solution than in the phosphate buffer. Mn is highly sensitive to DTT and shows close solubility in the two fluids. An extraction time of 0.5 h in phosphate buffer allows a better sensitivity to OPDTT, probably by limiting complexations, interactions between metals and precipitation. Storage time and temperature can influence the physical or chemical evolution of the WFs, which can affect their OPDTT and Mn solubility. However, storage under N2(g) limits these changes. On-line measurements of OPDTT could provide an alternative to filter sampling to overcome these artifacts. [ABSTRACT FROM AUTHOR]

The ZX-calculus is a powerful framework for reasoning in quantum computing. It provides in particular a compact representation of matrices of interest. A peculiar property of the ZX-calculus is the absence of a formal sum allowing the linear combinations of arbitrary ZX-diagrams. The universality of the formalism guarantees however that for any two ZX-diagrams, the sum of their interpretations can be represented by a ZX-diagram. We introduce a general, inductive definition of the addition of ZX-diagrams, relying on the construction of controlled diagrams. Based on this addition technique, we provide an inductive differentiation of ZX-diagrams. Indeed, given a ZX-diagram with variables in the description of its angles, one can differentiate the diagram according to one of these variables. Differentiation is ubiquitous in quantum mechanics and quantum computing (e.g. for solving optimization problems). Technically, the differentiation of ZX-diagrams is strongly related to summation as witnessed by the product rules. We also introduce an alternative, non-inductive, differentiation technique rather based on the isolation of the variables. Finally, we apply our results to deduce a diagram for an Ising Hamiltonian. [ABSTRACT FROM AUTHOR]

The primary sugar compounds (SCs, defined as glucose, arabitol, and mannitol) are widely recognized as suitable molecular markers to characterize and apportion primary biogenic organic aerosol emission sources. This work improves our understanding of the spatial behavior and distribution of these chemical species and evidences their major effective environmental drivers. We conducted a large study focusing on the daily (24 h) PM10 SC concentrations for 16 increasing space scale sites (local to nationwide), over at least 1 complete year. These sites are distributed in several French geographic areas of different environmental conditions. Our analyses, mainly based on the examination of the short-term evolutions of SC concentrations, clearly show distance-dependent correlations. SC concentration evolutions are highly synchronous at an urban city scale and remain well correlated throughout the same geographic regions, even if the sites are situated in different cities. However, sampling sites located in two distinct geographic areas are poorly correlated. Such a pattern indicates that the processes responsible for the evolution of the atmospheric SC concentrations present a spatial homogeneity over typical areas of at least tens of kilometers. Local phenomena, such as the resuspension of topsoil and associated microbiota, do no account for the major emissions processes of SC in urban areas not directly influenced by agricultural activities. The concentrations of SC and cellulose display remarkably synchronous temporal evolution cycles at an urban site in Grenoble, indicating a common source ascribed to vegetation. Additionally, higher concentrations of SC at another site located in a crop field region occur during each harvest periods, indicating resuspension processes of plant materials (crop detritus, leaf debris) and associated microbiota for agricultural and nearby urbanized areas. Finally, ambient air temperature, relative humidity, and vegetation density constitute the main effective drivers of SC atmospheric concentrations.

A growing number of studies are using specific primary sugar species, such as sugar alcohols or primary saccharides, as marker compounds to characterize and apportion primary biogenic organic aerosols (PBOAs) in the atmosphere. To better understand their annual cycles, as well as their spatiotemporal abundance in terms of concentrations and sources, we conducted a large study focusing on three major atmospheric primary sugar compounds (i.e., arabitol, mannitol, and glucose) measured in various environmental conditions for about 5300 filter samples collected at 28 sites in France. Our results show significant atmospheric concentrations of polyols (defined here as the sum of arabitol and mannitol) and glucose at each sampling location, highlighting their ubiquity. Results also confirm that polyols and glucose are mainly associated with the coarse rather than the fine aerosol mode. At nearly all sites, atmospheric concentrations of polyols and glucose display a well-marked seasonal pattern, with maximum concentrations from late spring to early autumn, followed by an abrupt decrease in late autumn, and a minimum concentration during wintertime. Such seasonal patterns support biogenic emissions associated with higher biological metabolic activities (sporulation, growth, etc.) during warmer periods. Results from a previous comprehensive study using positive matrix factorization (PMF) based on an extended aerosol chemical composition dataset of up to 130 species for 16 of the same sample series have also been used in the present work. The polyols-to-PMPBOA ratio is 0.024±0.010 on average for all sites, with no clear distinction between traffic, urban, or rural typology. Overall, even if the exact origin of the PBOA source is still under investigation, it appears to be an important source of particulate matter (PM), especially during summertime. Results also show that PBOAs are significant sources of total organic matter (OM) in PM10 (13±4 % on a yearly average, and up to 40 % in some environments in summer) at most of the investigated sites. The mean PBOA chemical profile is clearly dominated by contribution from OM (78±9 % of the mass of the PBOA PMF on average), and only a minor contribution from the dust class (3±4 %), suggesting that ambient polyols are most likely associated with biological particle emissions (e.g., active spore discharge) rather than soil dust resuspension.

The stabilizer ZX-calculus is a rigorous graphical language for reasoning about quantum mechanics. The language is sound and complete: one can transform a stabilizer ZX-diagram into another one using the graphical rewrite rules if and only if these two diagrams represent the same quantum evolution or quantum state. We previously showed that the stabilizer ZX-calculus can be simplified by reducing the number of rewrite rules, without losing the property of completeness [Backens, Perdrix & Wang, EPTCS 236:1--20, 2017]. Here, we show that most of the remaining rules of the language are indeed necessary. We do however leave as an open question the necessity of two rules. These include, surprisingly, the bialgebra rule, which is an axiomatisation of complementarity, the cornerstone of the ZX-calculus. Furthermore, we show that a weaker ambient category -- a braided autonomous category instead of the usual compact closed category -- is sufficient to recover the meta rule 'only connectivity matters', even without assuming any symmetries of the generators.

BackgroundA better understanding of the influenza epidemiology among primary care workers could guide future recommendations to prevent transmission in primary care practices. Therefore, we designed a pilot study to assess the feasibility of using a work-based online influenza surveillance system among primary care workers. Such an approach is of particular relevance in the context of the coronavirus disease (COVID-19) pandemic, as its findings could apply to other infectious diseases with similar mechanisms of transmission. ObjectiveThis study aims to determine the feasibility of using a work-based online influenza surveillance system for primary care workers in Switzerland. MethodsPhysicians and staff of one walk-in clinic and two selected primary care practices were enrolled in this observational prospective pilot study during the 2017-2018 influenza season. They were invited to record symptoms of influenza-like illness in a weekly online survey sent by email and to self-collect a nasopharyngeal swab in case any symptoms were recorded. Samples were tested by real-time polymerase chain reaction for influenza A, influenza B, and a panel of respiratory pathogens. ResultsAmong 67 eligible staff members, 58% (n=39) consented to the study and 53% (n=36) provided data. From the time all participants were included, the weekly survey response rate stayed close to 100% until the end of the study. Of 79 symptomatic episodes (mean 2.2 episodes per participant), 10 episodes in 7 participants fitted the definition of an influenza-like illness case (attack rate: 7/36, 19%). One swab tested positive for influenza A H1N1 (attack rate: 3%, 95% CI 0%-18%). Swabbing was considered relatively easy. ConclusionsA work-based online influenza surveillance system is feasible for use among primary care workers. This promising methodology could be broadly used in future studies to improve the understanding of influenza epidemiology and other diseases such as COVID-19. This could prove to be highly useful in primary care settings and guide future recommendations to prevent transmission. A larger study will also help to assess asymptomatic infections.

Nowadays ambient particulate matter (PM) levels still regularly exceed the guideline values established by World Health Organization in most urban areas. Numerous experimental studies have already demonstrated the airway toxicity of the fine fraction of PM (FP), mainly triggered by oxidative stress-induced airway inflammation. However, only few studies have actually paid close attention to the ultrafine fraction of PM (UFP), which is likely to be more easily internalized in cells and more biologically reactive. Mitochondria are major endogenous sources of reactive oxygen species (ROS) through oxidative metabolism, and coordinate many critical cellular signaling processes. Mitochondria have been often studied in the context of PM toxicity and generally associated with apoptosis activation. However, little is known about the underlying adaptation mechanisms that could occur following exposure at sub-apoptotic doses of ambient PM. Here, normal human bronchial epithelial BEAS-2B cells were acutely or repeatedly exposed to relatively low doses (5 µg.cm−2) of FP (PM2.5-0.18) or quasi-UFP (Q-UFP; PM0.18) to better access the critical changes in mitochondrial morphology, functions, and dynamics. No significant cytotoxicity nor increase of apoptotic events were reported for any exposure. Mitochondrial membrane potential (ΔΨm) and intracellular ATP content were also not significantly impaired. After cell exposure to sub-apoptotic doses of FP and notably Q-UFP, oxidative phosphorylation was increased as well as mitochondrial mass, resulting in increased production of mitochondrial superoxide anion. Given this oxidative boost, the NRF2-ARE signaling pathway was significantly activated. However, mitochondrial dynamic alterations in favor of accentuated fission process were observed, in particular after Q-UFP vs FP, and repeated vs acute exposure. Taken together, these results supported mitochondrial quality control and metabolism dysfunction as an early lung underlying mechanism of toxicity, thereby leading to accumulation of defective mitochondria and enhanced endogenous ROS generation. Therefore, these features might play a key role in maintaining PM-induced oxidative stress and inflammation within lung cells, which could dramatically contribute to the exacerbation of inflammatory chronic lung diseases. The prospective findings of this work could also offer new insights into the physiopathology of lung toxicity, arguably initiate and/or exacerbate by acutely and rather repeated exposure to ambient FP and mostly Q-UFP.

The ZX-Calculus is a graphical language for diagrammatic reasoning in quantum mechanics and quantum information theory. It comes equipped with an equational presentation. We focus here on a very important property of the language: completeness, which roughly ensures the equational theory captures all of quantum mechanics. We first improve on the known-to-be-complete presentation for the so-called Clifford fragment of the language - a restriction that is not universal - by adding some axioms. Thanks to a system of back-and-forth translation between the ZX-Calculus and a third-party complete graphical language, we prove that the provided axiomatisation is complete for the first approximately universal fragment of the language, namely Clifford+T. We then prove that the expressive power of this presentation, though aimed at achieving completeness for the aforementioned restriction, extends beyond Clifford+T, to a class of diagrams that we call linear with Clifford+T constants. We use another version of the third-party language - and an adapted system of back-and-forth translation - to complete the language for the ZX-Calculus as a whole, that is, with no restriction. We briefly discuss the added axioms, and finally, we provide a complete axiomatisation for an altered version of the language which involves an additional generator, making the presentation simpler.

Abstract Background Detection of circulating ESR1 mutations is associated with acquired resistance to aromatase inhibitor (AI) in metastatic breast cancer. Until now, the presence of circulating ESR1 mutations at the end of adjuvant treatment by AI in early breast cancer had never been clearly established. In this context, the aim of the present study was to evaluate the circulating ESR1 mutation frequency at the end of adjuvant treatment and after relapse. Methods This monocentric retrospective study was based on available stored plasmas and included all early breast cancer patients who completed at least 2 years of AI adjuvant treatment and experienced a documented relapse after the end of their treatment. Circulating ESR1 mutations (D538G, Y537S/N/C) were assessed by droplet digital PCR in plasma samples taken at the end of adjuvant treatment, at time of relapse and at time of progression under first line metastatic treatment. Results A total of 42 patients were included, with a median adjuvant AI exposure of 60 months (range 41–85). No circulating ESR1 mutation was detectable at the end of AI adjuvant therapy. At first relapse, 5.3% of the patients (2/38) had a detectable circulating ESR1 mutation. At time of progression on first-line metastatic treatment, 33% of the patients (7/21) under AI had a detectable circulating ESR1 mutation compared to none of the patients under chemotherapy (0/10). The two patients with a detectable ESR1 mutation at relapse were treated by AI and had an increase of their variant allele fraction at time of progression on first-line metastatic treatment. Conclusions Circulating ESR1 mutation detection at the end of AI-based adjuvant treatment is not clinically useful. Circulating ESR1 mutation could be assessed as soon as first relapse to guide interventional studies.

We introduce a ZX-like diagrammatic language devoted to manipulating real matrices – and rebits –, with its own set of axioms. We prove the necessity of some non trivial axioms of these. We show that some restriction of the language is complete. We exhibit two interpretations to and from the ZX-Calculus, thus showing the consistency between the two languages. Finally, we derive from our work a way to extract the real or imaginary part of a ZX-diagram, and prove that a restriction of our language is complete if the equivalent restriction of the ZX-calculus is complete.