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Background: Smoking cessation reduces the risk of developing smoking-related diseases. Although smoking prevalence has declined, many smokers continue smoking cigarettes. Switching to less harmful smoke-free alternatives such as the Tobacco Heating System (THS), a non-combustible tobacco-based product, is an approach to reduce the harm caused by cigarettes. Methods: We conducted a 12-month clinical study with 984 adult smokers randomized to either continue smoking or to use THS. We assessed the trajectories of biomarkers of potential harm (BoPH) known to be reversible upon smoking cessation, as one measure of different pathways involved in the pathogenesis of cardiovascular or respiratory diseases, and carcinogenicity. Beneficial impact on 8 key BoPHs was used as a proxy to evaluate harm reduction.Results: At 12 months, comparison of the 8 BoPH levels between the predominant THS use and cigarette smoking groups showed differences in favor of THS switching when contextualized to the changes reported for smoking cessation. Conclusions: Our results likely indicate a further decrease in carcinogenicity and relative risk of developing cardiovascular or respiratory diseases for smokers switching to THS compared to those who would continue smoking. These results provide additional evidence of the harm reduction potential of predominant THS use. Trial Registration clinicaltrials.gov Identifier: NCT02649556 Date of registration: 07/01/2016 (dd/mm/yyyy)(https://clinicaltrials.gov/ct2/show/NCT02649556)

Le phénomène constitutionnel est en transition, du positivisme au pluralisme juridique : il peut être construit selon une pluralité de perspectives, de paradigmes. Ces images constitutionnelles sont en concurrence : le discours constitutionnel est cadré, selon les choix plus ou moins explicites du comparatiste de droit constitutionnel. Si rien n’indique en quoi un paradigme est meilleur qu’un autre, cette question relève de la théorie de l’argumentation. Constitutional law is facing an epistemological transition : from legal positivism to legal pluralism. It may therefore be constructed through a plurality of paradigms. Those constitutional images are standing up against one another : constitutional law is hence framed, by more or less explicit choices made by constitutional legal scholars. Nothing is less certain than which paradigm is better than the other ; the question falls into the scope of argumentative theory.

Background Cigarette smoking induces cytochrome P450 1A2 (CYP1A2) expression and activity, while smoking cessation normalizes the levels of this enzyme. The aim of this publication is to summarize the data on CYP1A2 gene expression and activity in preclinical and clinical studies on the Tobacco Heating System (THS), currently marketed as IQOS® with HEETs®, and to summarize the potential effects on CYP1A2 to be expected upon switching to reduced-risk products (RRPs). Methods We summarized PMI’s preclinical and clinical data on the effects of switching from cigarette smoking to THS. Results Data from four preclinical mouse and rat studies showed that, upon either cessation of cigarette smoke exposure or switching to THS exposure, the upregulation of CYP1A2 observed with exposure to cigarette smoke reverted close to fresh-air levels. Data from four clinical studies yielded similar results on CYP1A2 activity within a time frame of five days. Furthermore, the effects of switching to THS were similar to those seen after smoking cessation. Conclusions Because smoking cessation and switching to either electronic cigarettes or THS seem to have similar effects on CYP1A2 activity, the same measures taken for patients treated with narrow therapeutic index drugs that are metabolized by CYP1A2 and who quit smoking should be recommended for those switching to RRPs.

Background: Cigarette smoking increases the risk of chronic diseases; heating instead of burning tobacco can lower these risks, contributing to tobacco harm reduction. This study (with 984 adult American smokers) examined whether favorable changes occur in 8 co-primary endpoints (HDL-C, WBC, FEV1%pred, COHb, Total NNAL, sICAM-1, 11-DTX-B2, 8-epi-PGF2α) indicative of biological and functional effects when cigarette smokers switch to the heat-not-burn Tobacco Heating System 2.2 (THS). Additionally, these biomarkers of exposure (BoExp) were quantified: MHBMA, 3-HPMA, Total NNN, CEMA, 3-OH-B[a]P, HMPMA, Total 1-OHP, NEQ, and CO exhaled. Methods: Participants were randomized to continued smoking of their preferred cigarette brand (n = 496) or to using THS (IQOS brand; n = 488) for 6 months. THS has a maximum heating temperature of 350°C, delivering 1.21 mg nicotine/stick and 3.94 mg glycerin/stick under the Health Canada Intense smoking regimen. Results: The main outcome was a favorable change 6 months after baseline, with statistically significant improvements in 5 of 8 biomarkers of effect (HDL-C, WBC, FEV1%pred, COHb, Total NNAL) when smokers switched to THS compared with those who continued to smoke cigarettes. Likewise, BoExp were markedly reduced. Conclusions: All endpoints showed favorable changes in the same direction as with smoking cessation and improved biological effects were observed in smokers who predominantly used THS compared with continued cigarette smoking, with similar nicotine levels in both groups. Impact: Improvements in 5 of 8 biomarkers of effect are supportive of the research hypothesis, suggestive of disease risk reduction potential for smokers switching to THS instead of continuing to smoke cigarettes.

The Timepix3 hybrid-pixel readout chip consists of a matrix made of $256\times256$ square-shaped pixels with a 55- $\mu \text{m}$ pitch, which can be hybridized to several semiconductors, such as silicon (Si) or cadmium telluride (CdTe) with thicknesses up to 5 mm. Working as an event-based readout chip, it simultaneously records the time-over-threshold (ToT) in each pixel, measuring the deposited energy, as well as the time-of-arrival (ToA), with a time resolution of 1.5 ns. In this article, we present the energy calibration of two Timepix3 chips: the first one was bump-bonded with a 300- $\mu \text{m}$ -thick silicon sensor and the second one with a 1-mm-thick CdTe sensor. Both detectors were calibrated with per pixel calibration, using the monochromatic SOurce of Low-Energy X-rays [SOLEX from Henri Becquerel National Laboratory (LNHB) at CEA Saclay] and a set of calibration-grade sealed radioactive sources. Evaluations were carried out over the energy range 6–122 keV for Timepix3 Si and 20 keV–1.332 MeV for Timepix3 CdTe. Based on this experimental procedure, an energy resolution of 2.6 keV (3.4%) at 59.5 keV was observed for Timepix3 Si. For Timepix3 CdTe, this parameter was 5.6 keV (9.4%) at 59.5 keV, 27.24 keV (4.1%) at 661.7 keV, and 47.4 keV (3.5%) at 1.332 MeV. It is the first time that CdTe bump-bonded Timepix3 spectral performances were evaluated for gamma rays above 1 MeV. The reconstruction of the full-energy peak for such high energies is possible due to the ToA information, which allows the identification of all interactions caused by a given gamma ray within the detector.

International audience; In this paper, we use a 2D bond-based peridynamic model to investigate the strength of disk-shaped particles including pre-cracks. We use a diametral (or Brazilian) test to break the particles. For the flawless particles, we find that the stress distribution compares well with an analytical model accounting for the size of the contact zone, and the particle stiffness tends linearly to a well-defined value for increasingly resolved meshing. We then introduce cracks, which are numerically defined by reducing the Young modulus of the bonds crossing linear segments. We consider in detail the effect of a single vertical crack on the yield stress as a function of its position. We also consider a randomly distributed population of cracks with sizes generated from a Gaussian size distribution. For a parametric study with a hundred particles, we found a probability of failure that is well fit by a Weibull law. Finally, using an image analysis algorithm, we investigate the statistics of cracks and the resulting fragments.

In leathers, formaldehyde is currently analyzed according to EN ISO 17226-1 standard, by reversed phase liquid chromatography after off-line precolumn derivatization with 2,4 dinitrophenylhydrazine (DNPH) in strong acidic conditions. We first demonstrate that this standard is not adapted to leather retanned with resins likely to release formaldehyde by hydrolysis. Indeed, formaldehyde content may be largely overestimated due to concomitant resin hydrolysis (in harsh acidic conditions) that releases formaldehyde during the derivatization step and during the waiting time on autosampler before analysis. Therefore, we thoroughly studied the derivatization step in order to propose new derivatization conditions. Replacing orthophosphoric acid by less acidic buffer solutions is not enough to avoid hydrolysis. A derivatization without adding acid is realized by solubilizing DNPH in acetonitrile instead of orthophosphoric acid. These conditions lead to a complete derivatization of formaldehyde in 3 h at 50 &deg, C (in a water bath) while avoiding the hydrolysis of co-extracted dicyandiamide and melamine resins. The as-obtained leather extracts are stable over time. Formaldehyde contents found with this method agree with the formaldehyde content measured immediately at the end of derivatization reaction in standard conditions or with formaldehyde content measured by a home-designed flow injection analysis with acetylacetone online derivatization and UV detection.

In addition to smoking cessation, for those who would otherwise continue to smoke, replacing cigarettes with less harmful alternatives can reduce the harms of smoking. Heating instead of burning tobacco reduces, or eliminates, the formation of harmful and potentially harmful constituents (HPHC) that are found in cigarette smoke. The Carbon-Heated Tobacco Product (CHTP), a heat-not-burn tobacco product, mimics the cigarette smoking ritual. This randomized, open-label, two-arm, parallel-group, short-term confinement study tested the hypothesis that the geometric means of the BoExp levels for subjects switching to CHTP 1.0 for 5 days are lower relative to those continuing to smoke cigarettes. Biomarkers of exposure (BoExp), including nicotine, urinary excretion of mutagenic constituents (Ames test), and cytochrome P450 (CYP) 1A2 activity, were measured in blood and/or 24-h urine samples during ad libitum product use. Nicotine exposure remained at similar levels in individuals using CHTP as in those continuing to smoke cigarettes. Switching to CHTP resulted in marked decreases in all other urinary BoExp (56–97%), carboxyhemoglobin (59%), urinary mutagenic constituents, and CYP1A2 activity compared with continued cigarette smoking. Our results provide evidence of decreased exposure to 15 selected HPHCs in smokers switching from cigarettes to exclusive CHTP use.Trial registration ClinicalTrials.gov: NCT02503254; Date of first registration: 20/07/2015 https://www.clinicaltrials.gov/ct2/show/NCT02503254.Study protocol Study protocol published at: https://www.clinicaltrials.gov/ProvidedDocs/54/NCT02503254/Prot_000.pdf.

International audience

The invention concerns a method for crushing a mineral material, which method comprises: -a step of providing said mineral material to be crushed and at least one grinding aid, said at least one grinding aid is chosen from organic plant materials in order to form a plant grinding aid, - a step of crushing said mineral material in the presence of said at least one grinding aid. And, according to the invention, said at least one grinding aid is composed of particles. And in the course of the crushing step, the at least one plant grinding aid is mixed with the mineral material in a proportion by mass less than 5% of the total mass.; L'invention concerne un procédé pour le broyage d'une matière minérale, lequel procédé comprend: -une étape de fourniture de ladite matière minérale à broyer et d'au moins un agent de mouture, lequel au moins un agent de mouture est choisi parmi les matières organiques végétales pour former un agent de mouture végétal, -une étape de broyage de ladite matière minérale, en présence dudit au moins un agent de mouture. Et, selon l'invention, ledit au moins un agent de mouture est composé de particules. Et au cours de ladite étape de broyage, ledit au moins un agent de mouture végétal est mélangé avec ladite matière minérale dans une proportion massique inférieure à 5% de la masse totale.

International audience; The energy efficiency of dry fine grinding process of powders dramatically declines with decreasing particle size, and represents a growing concern in various cutting-edge technical applications for pharmaceutical and cosmetic products, advanced-ceramics, and food industry. In this paper, we report on a detailed experimental analysis of the long-term grinding behavior of silica sand as a model material in an oscillatory ball mill for a broad range of the values of vibration frequency and amount of powder. We show that the re-agglomeration of fine particles unambiguously explains the anomalous increase of grinding power consumption. We also find that the agglomeration phenomena are correlated with the volume fraction of the class of finest particles. A nonlinear comminution model is shown to capture this effect for the prediction of the evolution of the specific surface area.

International audience

BACKGROUND Smoking is a significant risk factor for periodontal disease and tooth loss, as shown in several clinical studies comparing smokers and nonsmokers. Although only a few longitudinal studies have assessed the outcome of periodontal disease after smoking cessation, they indicated that recovery after nonsurgical treatment was more successful in those who had quit smoking. As part of tobacco harm reduction strategies, substituting cigarettes with alternative, less harmful tobacco products is an approach complementary to cessation for smokers who would otherwise continue to smoke. The Tobacco Heating System (THS), developed by Philip Morris International (commercialized as IQOS), is part of the heat-not-burn product category. The IQOS device electrically heats tobacco instead of burning it, at much lower temperatures than cigarettes, thereby producing substantially lower levels of harmful and potentially harmful constituents, while providing the nicotine, taste, ritual, and a sensory experience that closely parallel those of cigarettes. Phillip Morris International has published the results from a broad clinical assessment program, which was established to scientifically substantiate the harm reduction potential of the THS among adult healthy smokers switching to the THS. The program is now progressing toward including adult smokers with smoking-related diseases. OBJECTIVE The goal of this study is to demonstrate favorable changes of periodontal endpoints in response to mechanical periodontal therapy in patients with generalized chronic periodontitis who completely switched to THS use compared with continued cigarette smoking. METHODS This is a randomized controlled two-arm parallel-group multicenter Japanese study conducted in patients with chronic generalized periodontitis who switch from cigarettes to THS compared with smokers continuing to smoke cigarettes for 6 months. The patients were treated with mechanical periodontal therapy as per standard of care in Japan. The primary objective of the study is to demonstrate the beneficial effect of switching to THS use compared with continued cigarette smoking on pocket depth (PD) reduction in all sites with an initial PD≥4 mm. The secondary objectives include evaluation of other periodontal parameters (eg, clinical attachment level or gingival inflammation) and overall oral health status upon switching to THS. Safety was monitored throughout the study. RESULTS In total, 172 subjects were randomized to the cigarette (n=86) or THS (n=86) groups, and all 172 completed the study. The conduct phase of the study is completed, while data cleaning and analyses are ongoing. CONCLUSIONS This study is the first to test a heat-not-burn tobacco product in smokers with an already established disease. The results should further strengthen the evidence that switching to THS can significantly reduce the risk of smoking-related diseases if favorable changes in the evolution of chronic generalized periodontitis after mechanical therapy are found when compared with continued cigarette smoking. CLINICALTRIAL ClinicalTrials.gov NCT03364751; https://clinicaltrials.gov/ct2/show/NCT03364751 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/15350

International audience; Although grinding is a widespread operation in industrial processes, it remains poorly understood. The properties of the resulting particles and the milling efficiency not only depends on material properties and loading dynamics, but also on the stress transmission from the grinder to the particles [1]. The development of grinding technologies has followed to a large extend an empirical know-how and many efforts are still needed to better understand the comminution of particles. This objective can only be achieved by increasing the knowledge of the phenomena occurring during the milling in particular the competitiveness between the fragmentation and the agglomeration phenomena [2].In this work, the key parameters influencing comminution mechanisms and the energy efficiency for grinding are investigated based on an extensive experimental study in different grinding devices. An energy evolution inspired by Rittinger model but taking into account the agglomeration phenomena was proposed and used to compare the milling of mineral, vegetal and their co-milling.

International audience; With their potent regenerative and protective capacities, stem cell-derived conditioned media emerged as an effective alternative to cell therapy, and have a prospect to be manufactured as pharmaceutical products for tissue regeneration applications. Our study investigates the neuroregenerative potential of human dental pulp cells (DPCs) conditioned medium (CM) and defines an optimization strategy of DPC-CM for enhanced neuronal outgrowth. Primary sensory neurons from mouse dorsal root ganglia were cultured with or without DPC-CM, and the lengths of βIII-tubulin positive neurites were measured. The impacts of several manufacturing features as the duration of cell conditioning, CM storage, and preconditioning of DPCs with some factors on CM functional activity were assessed on neurite length. We observed that DPC-CM significantly enhanced neurites outgrowth of sensory neurons in a concentration-dependent manner. The frozen storage of DPC-CM had no impact on experimental outcomes and 48 h of DPC conditioning is optimal for an effective activity of CM. To further understand the regenerative feature of DPC-CM, we studied DPC secretome by human growth factor antibody array analysis and revealed the presence of several factors involved in either neurogenesis, neuroprotection, angiogenesis, and osteogenesis. The conditioning of DPCs with the B-27 supplement enhanced significantly the neuroregenerative effect of their secretome by changing its composition in growth factors. Here, we show that DPC-CM significantly stimulate neurite outgrowth in primary sensory neurons. Moreover, we identified secreted protein candidates that can potentially promote this promising regenerative feature of DPC-CM.

Background Smoking is a significant risk factor for periodontal disease and tooth loss, as shown in several clinical studies comparing smokers and nonsmokers. Although only a few longitudinal studies have assessed the outcome of periodontal disease after smoking cessation, they indicated that recovery after nonsurgical treatment was more successful in those who had quit smoking. As part of tobacco harm reduction strategies, substituting cigarettes with alternative, less harmful tobacco products is an approach complementary to cessation for smokers who would otherwise continue to smoke. The Tobacco Heating System (THS), developed by Philip Morris International (commercialized as IQOS), is part of the heat-not-burn product category. The IQOS device electrically heats tobacco instead of burning it, at much lower temperatures than cigarettes, thereby producing substantially lower levels of harmful and potentially harmful constituents, while providing the nicotine, taste, ritual, and a sensory experience that closely parallel those of cigarettes. Phillip Morris International has published the results from a broad clinical assessment program, which was established to scientifically substantiate the harm reduction potential of the THS among adult healthy smokers switching to the THS. The program is now progressing toward including adult smokers with smoking-related diseases. Objective The goal of this study is to demonstrate favorable changes of periodontal endpoints in response to mechanical periodontal therapy in patients with generalized chronic periodontitis who completely switched to THS use compared with continued cigarette smoking. Methods This is a randomized controlled two-arm parallel-group multicenter Japanese study conducted in patients with chronic generalized periodontitis who switch from cigarettes to THS compared with smokers continuing to smoke cigarettes for 6 months. The patients were treated with mechanical periodontal therapy as per standard of care in Japan. The primary objective of the study is to demonstrate the beneficial effect of switching to THS use compared with continued cigarette smoking on pocket depth (PD) reduction in all sites with an initial PD≥4 mm. The secondary objectives include evaluation of other periodontal parameters (eg, clinical attachment level or gingival inflammation) and overall oral health status upon switching to THS. Safety was monitored throughout the study. Results In total, 172 subjects were randomized to the cigarette (n=86) or THS (n=86) groups, and all 172 completed the study. The conduct phase of the study is completed, while data cleaning and analyses are ongoing. Conclusions This study is the first to test a heat-not-burn tobacco product in smokers with an already established disease. The results should further strengthen the evidence that switching to THS can significantly reduce the risk of smoking-related diseases if favorable changes in the evolution of chronic generalized periodontitis after mechanical therapy are found when compared with continued cigarette smoking. Trial Registration ClinicalTrials.gov NCT03364751; https://clinicaltrials.gov/ct2/show/NCT03364751 International Registered Report Identifier (IRRID) DERR1-10.2196/15350

International audience; Geotagged photos posted on photo-sharing platforms have recently become a new source of information for analysing landscape preferences and investigating the aesthetic dimension of cultural ecosystem services. Most studies seek to explain photo density by landscape or spatial characteristics that might account for individual preferences and aesthetic criteria favoured by photographers. We focus instead on a “panorama level” of analysis, based on the assumption that photos represent preferential directions within a given panorama. The analysis consists in comparing the content of the photographed views with the content of the antipodal views (i.e. the view at 180°). We apply this method to a set of Flickr photos taken in the Lake Geneva region (Switzerland and France) characterised by landscape descriptors based on a visibility modelling approach. The results of discrete choice modelling at the global level are consistent with several key concepts of landscape preferences (e.g., openness, naturalness). The local analyses conducted at eight photo hotspots confirm the influence of open landscapes while revealing variations for certain other landscape characters depending on the geographical setting. We conclude that the panorama level approach combining geotagged photos and visibility modelling is suitable for identifying the landscape signature of the most appealing views. This signature could be used in further studies to detect the potential of visual amenities.

The availability of global and scalable tools to assess disabled pedestrian level of service (DPLoS) is a real need, yet still a challenge in today’s world. This is due to the lack of tools that can ease the measurement of a level of service adapted to disabled people, and also to the limitation concerns about the availability of information regarding the existing level of service, especially in real time. This paper describes preliminary results to progress on those needs. It also includes a design for a navigation tool that can help a disabled person move around a city by suggesting the most adapted routes according to the person’s disabilities. The main topics are how to use advanced computer vision technologies, and how to benefit from the prevalence of handheld devices. Our approach intends to show how crowdsourcing techniques can improve data quality by gathering and combining up-to-date data with valuable field observations.

This paper describes a method that uses georeferenced landscape pictures extracted from open picture collections for the determination of the population's interest in spatial features. The automated method takes into account the coordinates of the camera position as well as the azimuth angle, the focal length and the crop factor in order to calculate a field of view using a digital terrain model (DTM). This field of view can thereafter be used for the determination of interest in spatial features. In a case study involving more than 3'000 georeferenced pictures we investigate the potential of the method.

International audience; European restriction limits the hexavalent chromium content to not more than 3 mg/kg in leather products. Owing to the evolution of hexavalent chromium content in leathers over time, it’s difficult to guarantee the products will be harmless for consumers. The designing of an accelerated and representative artificial ageing procedure is therefore highly desirable. This article proposes a thorough study of the influence of storage conditions on the formation of hexavalent chromium in 4 bovine leathers. A factorial design of experiment was built with the following factors: temperature of 40–80 °C, relative humidity of 20–50%, presence or not of UV and exposure duration of 24–48 h. The results of these artificial ageings demonstrate that a high temperature, a dry atmosphere and the presence of light favor the formation of hexavalent chromium and that synergistic effects operate between temperature/humidity, temperature/UV and humidity/UV. At the same time, the leathers were subjected to a natural ageing for 12 months with a weekly hexavalent chromium analysis. The principal component analysis of the artificial ageing tests combined with the natural ageing tests, show that the artificial ageings 40 °C-50%RH-UV-48 h and 40 °C-20%RH-UV-24 h best simulate a natural ageing in the tannery, whatever the leather studied.