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In September 2017, we conducted a proton-transfer-reaction mass-spectrometry (PTR-MS) intercomparison campaign at the CESAR observatory, a rural site in the central Netherlands near the village of Cabauw. Nine research groups deployed a total of 11 instruments covering a wide range of instrument types and performance. We applied a new calibration method based on fast injection of a gas standard through a sample loop. This approach allows calibrations on timescales of seconds, and within a few minutes an automated sequence can be run allowing one to retrieve diagnostic parameters that indicate the performance status. We developed a method to retrieve the mass-dependent transmission from the fast calibrations, which is an essential characteristic of PTR-MS instruments, limiting the potential to calculate concentrations based on counting statistics and simple reaction kinetics in the reactor/drift tube. Our measurements show that PTR-MS instruments follow the simple reaction kinetics if operated in the standard range for pressures and temperature of the reaction chamber (i.e. 1–4 mbar, 30–120∘, respectively), as well as a reduced field strength E∕N in the range of 100–160 Td. If artefacts can be ruled out, it becomes possible to quantify the signals of uncalibrated organics with accuracies better than ±30 %. The simple reaction kinetics approach produces less accurate results at E∕N levels below 100 Td, because significant fractions of primary ions form water hydronium clusters. Deprotonation through reactive collisions of protonated organics with water molecules needs to be considered when the collision energy is a substantial fraction of the exoergicity of the proton transfer reaction and/or if protonated organics undergo many collisions with water molecules.

Abstract Background Acute infectious conjunctivitis is a common condition most frequently caused by viruses or bacteria. Clinical outcome assessments have been used to assess signs and symptoms of bacterial and viral conjunctivitis, but have not been evaluated for content validity. We aimed to develop content-valid patient- (PRO) and observer-reported outcome (ObsRO) instruments to assess symptoms of ocular discomfort associated with viral or bacterial conjunctivitis in adult and pediatric patients. Methods Draft items were developed from a previous review of published studies from 2001 to 2015. Patients and caregivers of patients with a diagnosis of viral or bacterial conjunctivitis within the past 6 months were recruited. Concept elicitation with open-ended questions explored signs and symptoms, followed by cognitive interviewing to assess clarity and relevance of the draft items. Patients aged ≥8 years were interviewed for the PRO; parents/caregivers of children aged 1–10 years were interviewed for the ObsRO. Interviews were conducted in three rounds to allow changes. Concept saturation was documented using a saturation grid. Cognitive interview data were analyzed iteratively and focused on clarity, relevance and inconsistent interpretation of the instrument’s content. Results Overall, 23 patients or parents/caregivers participated (round 1, n = 10; round 2, n = 6; round 3, n = 7). Data saturation was reached by the 16th interview. The most frequent spontaneously reported signs/symptoms were: discharge, red/pink eyes, itchiness, swelling/puffiness, watery eyes, pain, burning and foreign body sensation. Itching, pain/burning/stinging and foreign body sensation were most commonly reported as the top three most bothersome symptoms. Interview results indicated that items on pain, itching and foreign body sensation for the PRO and pain or discomfort for the ObsRO were relevant to the patients’ experience of conjunctivitis and were clear and easy to understand. Conclusions PRO and ObsRO items were found to be clear, relevant and appropriate in assessing key viral and bacterial conjunctivitis symptoms in adult and pediatric patients.

Primary biological aerosol particles (PBAPs) are an abundant subset of atmospheric aerosol particles which comprise viruses, bacteria, fungal spores, pollen, and fragments such as plant and animal debris. The abundance and diversity of these particles remain poorly constrained, causing significant uncertainties for modelling scenarios and for understanding the potential implications of these particles in different environments. PBAP concentrations were studied at four different sites in the United Kingdom (Weybourne, Davidstow, Capel Dewi, and Chilbolton) using an ultraviolet light-induced fluorescence (UV-LIF) instrument, the Wideband Integrated Bioaerosol Spectrometer (WIBS), versions 3 and 4. Using hierarchical agglomerative cluster (HAC) analysis, particles were statistically discriminated. Fluorescent particles and clusters were then analysed by comparing to laboratory data of known particle types, assessing their diurnal variation and examining their relationship to the meteorological variables temperature, relative humidity, wind speed, and wind direction. Using local land cover types, sources of the suspected fluorescent particles and clusters were then identified. Most sites exhibited a wet discharged fungal spore dominance, with the exception of one site, Davidstow, which had higher concentrations of bacteria, suggested to result from the presence of a local dairy factory and farm. Differences were identified as to the sources of wet discharged fungal spores, with particles originating from arable and horticultural land at Chilbolton, and improved grassland areas at Weybourne. Total fluorescent particles at Capel Dewi were inferred to comprise two sources, with bacteria originating from the broadleaf and coniferous woodland and wet discharged fungal spores from nearby improved grassland areas, similar to Weybourne. The use of the HAC method and a higher fluorescence threshold (9 standard deviations instead of 3) produced clusters which were considered to be biological following the complete analysis. More published data and information on the reaction of different speciated biological particle types to fluctuations in meteorological conditions, such as relative humidity and temperature, would aid particle type characterisation in studies such as this.

Background: Atopic dermatitis (AD) is a common and chronic, pruritic inflammatory skin condition that affects all age groups. There was a dearth of consensus document on AD for Indian practitioners. This article aims to provide an evidence-based consensus statement for the management of AD with a special reference to the Indian context. This guideline includes updated definition, etiological factors, classification, and management of atopic dermatitis. Methodology: The preparation of guidelines was done in multiple phases. Indian Dermatology Expert Board Members (DEBM), recommended by the Skin Allergy Society of India, prepared 26 evidence-based recommendations for AD. An extensive literature search was done in MEDLINE, Google scholar, Cochrane, and other resources. Articles published in the past 10 years were reviewed and recommendations were graded based on the quality of evidence as per GRADE. After forming the initial structure, DEBM met in Mumbai and gave their decisions on an agree and disagree scale with an Indian perspective. Finally, their suggestions were compiled for preparing the article. After DEBM finalized the draft, a treatment algorithm was formulated for the management of AD. Results: DEBM suggested a working definition for AD. The panel agreed that moisturizers should be used as mainstay of therapy and should be continued in all lines of therapy and in maintenance phase. Topical corticosteroids and topical calcineurin inhibitors should be considered as the first line of treatment. Among systemic therapies, cyclosporin should be considered first line, followed by azathioprine, methotrexate, and mycophenolate mofetil. Phototherapy can be an effecive alternative. Empirical food restriction was recommended against. Conclusion: These guidelines should form a reference for the management of patients with AD in an evidence-based manner.

Introduction: Primary cutaneous amyloidosis (PCA) can be classified into four principal categories: macular amyloidosis, lichen amyloidosis, biphasic, and nodular amyloidosis. Some unusual variants such as widespread diffuse hyperpigmentation without papules, poikiloderma like involvement, lesions following Blaschko's line, etc., have also been reported. However, not much data are available regarding the demography, epidemiology, clinical patterns, and distribution and histopathological findings, especially from the eastern part of India. Aims: We conducted a cross-sectional, institution-based study to evaluate clinicopathological pattern and factors of PCA in eastern India. Materials and Methods: We recorded clinical and histopathological findings of 100 consecutive patients of PCA presenting to a tertiary care institution of Kolkata in eastern India. Results: We found female patients of PCA outnumber male (M:F =1:1.9) with majority of patients being young adults (56%) between 20 and 40 years of age. More than half (54%) of the patients were pruritic. The severity of pruritus is significantly more associated with lichenoid and biphasic variants over macular amyloidosis. Positive family history was recorded in 17% of cases. Macular variant was the most common variant constituting 48% of the total PCA. We also found that the association with history of friction and scrubbing and photo-exposure were statistically insignificant. However, duration of the disease has statistically significant association with the disease morphology. Congo red stain showed these deposits as reddish orange substance in 28 patients out of 64 patients' samples on which Congo red could be performed. Conclusion: Our study revealed that many concepts of pathogenesis of PCA including friction and photoexposure might have lesser importance. However, morphological types were significantly associated with the duration of the disease and symptom severity.

In May 2020, the European Commission announced a proposal for a mandatory front-of-pack label (FoPL) for all European Union (EU) countries. Indeed, FoPLs have been recognized by several public institutions as a cost-effective measure to guide consumers toward nutritionally favorable food products. The aim of this study was to compare the performance and consumer preference of two FoPLs currently proposed or implemented in EU countries, the interpretive format Nutri-Score and the non-interpretive format NutrInform Battery, among Italian consumers. The experimental study was conducted in 2021 on a representative sample of 1064 Italian adults (mean age = 46.5 ± 14.1 years; 48% men). Participants were randomized to either Nutri-Score or NutrInform and had to fill out an online questionnaire testing their objective understanding of the FoPL on three food categories (breakfast products, breakfast cereals and added fats) as well as purchase intention, subjective understanding and perception. Multivariable logistic regressions and t-tests were used to analyze the answers. In terms of the capacity of participants to identify the most nutritionally favorable products, Nutri-Score outperformed NutrInform in all food categories, with the highest odds ratio being observed for added fats (OR = 21.7 [15.3–31.1], p < 0.0001). Overall, with Nutri-Score, Italian participants were more likely to intend to purchase nutritionally favorable products than with NutrInform (OR = 5.29 [4.02–6.97], p < 0.0001). Focusing on olive oil, participants of the Nutri-Score group had higher purchase intention of olive oil compared to those in the NutrInform group (OR = 1.92 [1.42–2.60], p < 0.0001) after manipulating the label. The interpretive format Nutri-Score appears to be a more efficient tool than NutrInform for orienting Italian consumers towards more nutritionally favorable food choices.

Contamination of agricultural soil by arsenic (As) is a serious menace to environmental safety and global food security. Symbiotic plant–microbe interaction, such as arbuscular mycorrhiza (AM), is a promising approach to minimize hazards of As contamination in agricultural soil. Even though the potential of AM fungi (AMF) in redeeming As tolerance and improving growth is well recognized, the detailed metabolic and physiological mechanisms behind such beneficial effects are far from being completely unraveled. The present study investigated the ability of an AM fungus, Rhizophagus intraradices, in mitigating As-mediated negative effects on photosynthesis and sugar metabolism in wheat (Triticum aestivum) subjected to three levels of As, viz., 0, 25, and 50 mg As kg–1 of soil, supplied as sodium arsenate. As exposure caused significant decrease in photosynthetic pigments, Hill reaction activity, and gas exchange parameters such as net photosynthetic rate, stomatal conductance, transpiration rate, and intercellular CO2 concentration. In addition, As exposure also altered the activities of starch-hydrolyzing, sucrose-synthesizing, and sucrose-degrading enzymes in leaves. Colonization by R. intraradices not only promoted plant growth but also restored As-mediated impairments in plant physiology. The symbiosis augmented the concentration of photosynthetic pigments, enhanced Hill reaction activity, and improved leaf gas exchange parameters and water use efficiency of T. aestivum even at high dose of 50 mg As kg–1 of soil. Furthermore, inoculation with R. intraradices also restored As-mediated alteration in sugar metabolism by modulating the activities of starch phosphorylase, α-amylase, β-amylase, acid invertase, sucrose synthase, and sucrose-phosphate synthase in leaves. This ensured improved sugar and starch levels in mycorrhizal plants. Overall, the study advocates the potential of R. intraradices in bio-amelioration of As-induced physiological disturbances in wheat plant.

The development of social robots has the potential to address significant societal concerns, however, most people have limited experience of such technology. The present research investigated whether techniques borrowed from the psychology of intergroup relations – namely direct and extended contact – affect people's attitudes towards robots. Participants were provided with either direct contact with a social robot or extended contact (these participants watched a video recorded by a friend who had met the robot) before their explicit and implicit attitudes towards robots were measured. Results indicated that direct contact affected both explicit and implicit attitudes, while extended contact affected implicit attitudes. The implication of these findings is that contact with a robot, direct or indirect, can change attitudes; much as previous research has shown that contact with a person who is a member of an out-group can change attitudes towards that group. We conclude that methods and theories from the study of human intergroup relationships can be usefully applied to understand attitudes toward social robots.

Background: Brain lipid metabolism appears critical for cognitive aging, but whether alterations in the lipidome relate to cognitive decline remains unclear at the system level. Methods: We studied participants from the Three-City study, a multicentric cohort of older persons, free of dementia at time of blood sampling, and who provided repeated measures of cognition over 12 subsequent years. We measured 189 serum lipids from 13 lipid classes using shotgun lipidomics in a case-control sample on cognitive decline (matched on age, sex and level of education) nested within the Bordeaux study center (discovery, n = 418). Associations with cognitive decline were investigated using bootstrapped penalized regression, and tested for validation in the Dijon study center (validation, n = 314). Findings: Among 17 lipids identified in the discovery stage, lower levels of the triglyceride TAG50:5, and of four membrane lipids (sphingomyelin SM40:2,2, phosphatidylethanolamine PE38:5(18:1/20:4), ether-phosphatidylethanolamine PEO34:3(16:1/18:2), and ether-phosphatidylcholine PCO34:1(16:1/18:0)), and higher levels of PCO32:0(16:0/16:0), were associated with greater odds of cognitive decline, and replicated in our validation sample. Interpretation: These findings indicate that in the blood lipidome of non-demented older persons, a specific profile of lipids involved in membrane fluidity, myelination, and lipid rafts, is associated with subsequent cognitive decline. Funding: The complete list of funders is available at the end of the manuscript, in the Acknowledgement section.

Bacillus thuringiensis (Bt) belongs to the Bacillus cereus (Bc) group, well known as an etiological agent of foodborne outbreaks (FBOs). Bt distinguishes itself from other Bc by its ability to synthesize insecticidal crystals. However, the search for these crystals is not routinely performed in food safety or clinical investigation, and the actual involvement of Bt in the occurrence of FBOs is not known. In the present study, we reveal that Bt was detected in the context of 49 FBOs declared in France between 2007 and 2017. In 19 of these FBOs, Bt was the only microorganism detected, making it the most likely causal agent. Searching for its putative origin of contamination, we noticed that more than 50% of Bt isolates were collected from dishes containing raw vegetables, in particular tomatoes (48%). Moreover, the genomic characterization of isolates showed that most FBO-associated Bt isolates exhibited a quantified genomic proximity to Bt strains, used as biopesticides, especially those from subspecies aizawai and kurstaki. Taken together, these results strengthen the hypothesis of an agricultural origin for the Bt contamination and call for further investigations on Bt pesticides.

Hydrological variability (HA) in the river due to damming is well explored but there is a dearth of research about the HA on the riparian wetland. Time series data scarcity perhaps withstands against such research. The present work intended to measure the degree of HA of the river using flow data of gauge station and riparian wetland using time-series remote sensing data derived wetland indices as a proxy of water depth. For the first time, it is attempted to measure the degree of HA of wetland at pixel levels multi-analytical approaches like image-based hydrological attributes integration (HAI) approach, Histogram comparison approach (HCA), and Range of variability approach (RVA). The result has demonstrated that both river and wetlands have experienced significant HA after damming over the Atreyee river basin of India and Bangladesh. The degree of HA of the river in pre-monsoon and post-monsoon seasons respectively are 35.73% and 20.90% as per HCA and 27% and 28% as per RVA. In the wetland, this degree is quite higher (>66%) as per HCA and

PurposeGender minority (GM) adolescents, who have a different gender identity than their sex assigned at birth, may use substances as a coping strategy in response to GM-related stressors. This study examined longitudinal effects of gender minority stressors on substance use in GM adolescents, and related risk factors (internalized transphobia, depressive symptoms, anxious symptoms) and protective factors (resilience, gender-related pride, family functioning, social support, gender-related community connectedness).MethodsParticipants were 30 GM adolescents, ages 13-17 years, from the U.S. community-based longitudinal Trans Teen and Family Narratives Project. Participants completed an online survey every 6 months across 2 years (5 waves; data collected 2015-2019).ResultsExposure to gender minority stressors was associated with higher odds of alcohol use. Across models, internalized transphobia (risk factor), resilience (protective factor), and gender-related pride (protective factor) were the most significant mediators of associations between gender minority stressors and substance use. Family functioning and social support (protective factors) significantly moderated the association between gender minority stressors and alcohol use, such that family functioning and social support were protective for alcohol use at lower levels of gender minority stress, but not at higher levels.ConclusionResults suggest that GM adolescents engage in substance use as a coping strategy in response to gender minority stressors. A number of hypothesized risk and protective factors mediated or moderated these associations. Future interventions with GM adolescents should focus efforts on addressing internalized transphobia as a risk factor and strengthening resilience, gender-related pride, and family functioning as protective factors for substance use.

Quantifying geological processes has greatly benefited from the development and use of thermochronometric methods over the last fifty years. Among them is the (U-Th)/He dating method, which is based on the production and retention, within a crystal structure, of radiogenic 4He atoms associated with the alpha decay of U, Th and Sm nuclei. While apatite has been the main target of (U-Th)/He studies focusing on exhumation and burial processes in the upper levels of the continental crust (~50–120 °C), the development of (U-Th)/He methods for typical phases of igneous and metamorphic rocks (e.g., zircon and titanite) or mafic and ultramafic rocks (e.g., magnetite) over the last two decades has opened up a myriad of geological applications at higher temperatures (>100–300 °C). Thanks to the understanding of the role of radiation damage in He diffusion and retention for U-Th-poor and rich mineral phases, the application of (U-Th)/He thermochronometry to exhumation processes and continental evolution through deep time is now mainstream. This contribution reviews the (U-Th)/He thermochronometer principle and the influence of radiation damage in modifying the diffusion behavior. It presents applications of (U-Th)/He dating to problems in tectonic and surface processes at shallow to middle crustal depths (>100–300 °C). New and promising applications using a combination of methods will stimulate a research avenue in the future.

BackgroundResearch studies are establishing the use of smartphone sensing to measure mental well-being. Smartphone sensor information captures behavioral patterns, and its analysis helps reveal well-being changes. Depression in diabetes goes highly underdiagnosed and underreported. The comorbidity has been associated with increased mortality and worse clinical outcomes, including poor glycemic control and self-management. Clinical-only intervention has been found to have a very modest effect on diabetes management among people with depression. Smartphone technologies could play a significant role in complementing comorbid care. ObjectiveThis study aimed to analyze the association between smartphone-sensing parameters and symptoms of depression and to explore an approach to risk-stratify people with diabetes. MethodsA cross-sectional observational study (Project SHADO—Analyzing Social and Health Attributes through Daily Digital Observation) was conducted on 47 participants with diabetes. The study’s smartphone-sensing app passively collected data regarding activity, mobility, sleep, and communication from each participant. Self-reported symptoms of depression using a validated Patient Health Questionnaire-9 (PHQ-9) were collected once every 2 weeks from all participants. A descriptive analysis was performed to understand the representation of the participants. A univariate analysis was performed on each derived sensing variable to compare behavioral changes between depression states—those with self-reported major depression (PHQ-9>9) and those with none (PHQ-9≤9). A classification predictive modeling, using supervised machine-learning methods, was explored using derived sensing variables as input to construct and compare classifiers that could risk-stratify people with diabetes based on symptoms of depression. ResultsA noticeably high prevalence of self-reported depression (30 out of 47 participants, 63%) was found among the participants. Between depression states, a significant difference was found for average activity rates (daytime) between participant-day instances with symptoms of major depression (mean 16.06 [SD 14.90]) and those with none (mean 18.79 [SD 16.72]), P=.005. For average number of people called (calls made and received), a significant difference was found between participant-day instances with symptoms of major depression (mean 5.08 [SD 3.83]) and those with none (mean 8.59 [SD 7.05]), P

Introduction: Soft tissue vascular anomalies present a diagnostic challenge. In these anomalies, imaging is crucial for therapeutic planning and improvement of prognosis. Ultrasound (US) and Contrast-Enhanced Magnetic Resonance Imaging (CEMRI) are both widely utilised and are valuable imaging modalities, both having distinct advantages and limitations in evaluation of such lesions. Aim: To evaluate soft tissue vascular anomalies using US and CEMRI and assess their agreement in characterisation of these lesions. Materials and Methods: The prospective study included 75 patients with vascular anomalies evaluated by means of US and CEMRI: 71 underwent both US and MRI, three underwent US alone, and one patient underwent MRI alone. Patients of all ages were included. Lesions were characterised based on imaging findings and vascular perfusion characteristics. Histopathological evaluation was done in all patients. Receiver Operating Characteristic (ROC) analysis was used for differentiating data. The agreement of US and CEMRI with histopathological diagnosis were assessed using kappa statistics. Results: Among the soft tissue vascular anomalies, 17 were haemangiomas, 55 were vascular malformations and 3 were other vascular tumours. Majority of the lesions were venous malformations (n=26; 34.66%). A cut-off value of 17.5 cm/sec of peak venous velocity using Colour Doppler showed 100% sensitivity in differentiating Arterio-Venous Malformations (AVM) from haemangiomas using ROC curves. Agreement expressed as kappa was 0.884 (95% CI 0.794-0.973) for US and 0.923 (95% CI 0.850-0.996) for CEMRI demonstrating near perfect agreement with histopathology in both. Conclusion: The findings of this study indicate that both US and CEMRI are accurate in detection and characterisation of soft tissue vascular anomalies showing comparable level of agreement. US may be the preferred imaging modality as it is widely available, relatively inexpensive and non invasive. Contrast enhanced MRI may be reserved as a complementary technique in cases wherein lesion categorisation or extent is ambiguous during diagnosis.

The age-associated reduction in the proliferation of neural stem cells (NSCs) has been associated with cognitive decline. Numerous factors have been shown to modulate this process, including dietary components. Frequent consumption of caffeine has been correlated with an increased risk of cognitive decline, but further evidence of a negative effect on hippocampal progenitor proliferation is limited to animal models. Here, we used a human hippocampal progenitor cell line to investigate the effects of caffeine on hippocampal progenitor integrity and proliferation specifically. The effects of five caffeine concentrations (0 mM = control, 0.1 mM ∼ 150 mg, 0.25 mM ∼ 400 mg, 0.5 mM ∼ 750 mg, and 1.0 mM ∼ 1500 mg) were measured following acute (1 day) and repeated (3 days) exposure. Immunocytochemistry was used to quantify hippocampal progenitor integrity (i.e., SOX2- and Nestin-positive cells), proliferation (i.e., Ki67-positive cells), cell count (i.e., DAPI-positive cells), and apoptosis (i.e., CC3-positive cells). We found that progenitor integrity was significantly reduced in supraphysiological caffeine conditions (i.e., 1.0 mM ∼ 1500 mg), but relative to the lowest caffeine condition (i.e., 0.1 mM ∼ 150 mg) only. Moreover, repeated exposure to supraphysiological caffeine concentrations (i.e., 1.0 mM ∼ 1500 mg) was found to affect proliferation, significantly reducing % Ki67-positive cells relative to control and lower caffeine dose conditions (i.e., 0.1 mM ∼ 150 mg and 0.25 mM ∼ 400 mg). Caffeine treatment did not influence apoptosis and there were no significant differences in any measure between lower doses of caffeine (i.e., 0.1 mM, 0.25 mM, 0.5 mM) – representative of daily human caffeine intake – and control conditions. Our study demonstrates that dietary components such as caffeine can influence NSC integrity and proliferation and may be indicative of a mechanism by which diet affects cognitive outcomes.

Cryoglobulins (CGs) are cold precipitating immunoglobulins, and hepatitis C virus (HCV) infection is its most common cause. The purpose of the study was to determine the contribution of HCV in a large cohort of CG. Biological characteristics and specificity of CGs in HCV patients were compared to non-HCV subjects. Cryoglobulin analysis included isotype, clonality, concentration, and rheumatoid factor (RF) in cryoprecipitate and serum complement and RF. This study is an extension of the study carried out on a cohort of 13,439 patients tested for CGs from all medical units, in which 1,675/13,439 (12.5%) patients had a CG, and 680/1,675 (40.6%) had HCV serology or viral load determination (HCV RNA). Among these 680 CG patients tested for HCV, 325 of 680 (47.8%) HCV patients (272 HCV RNA+ and 45 HCV RNA− patients) were compared to 355/680 (52.2%) non-HCV subjects. After a positive detection of CG, HCV status was determined only for 37.7% (256/680) of patients, allowing the diagnosis of a previously unknown HCV infection for 39.8% (102/256). Concentration of HCV RNA+ CGs (median = 80.5 mg/L) was significantly higher than that of HCV RNA− CG (median = 50.5 mg/L, p = 0.001) and HCV− CG (median = 32 mg/L, p < 0.0001). There was no difference of median CG concentration between HCV RNA− patients and non-HCV subjects. Rheumatoid factor titer was significantly higher in type II CG compared to type III CG in HCV RNA+ patients (254 ± 720 vs. 15 ± 21 IU/mL, p < 0.0001) and non-HCV subjects (333 ± 968 vs. 16.8 ± 26 IU/mL, p = 0.0004). Complement functional activity CH50 was lower in HCV RNA+ patients (36 ± 24 U/mL) and in HCV RNA− patients (32 ± 21 U/mL) than in non-HCV subjects (50 ± 25 U/mL, p = 0.001 and p = 0.004). In conclusion, HCV infection and treatment influence CG characteristics. It is essential, and far from always tested, to determine the HCV status of patients with mixed CG, and conversely to search for CG in patients with HCV infection.

A total diet study (TDS) was undertaken to estimate the chronic dietary exposure to pesticide residues and health risks for the French infants and young children below 3 years old. As a whole, 516 pesticides and metabolites were analysed in 309 food composite samples including 219 manufactured baby foods and 90 common foods, which cover 97% of infants and young children's diet. These composite samples were prepared using 5,484 food products purchased during all seasons from 2011 to 2012 and processed as consumed. Pesticide residues were detected in 67% of the samples and quantified in 27% of the baby food samples and in 60% of the common foods. Seventy-eight different pesticides were detected and 37 of these quantified at levels ranging from 0.02 to 594 µg/kg. The most frequently detected pesticides (greater than 5% samples) were (1) the fungicides 2-phenylphenol, azoxystrobin, boscalid, captan and its metabolite tetrahydrophthalimide, carbendazim, cyprodinil, difenoconazole, dodine, imazalil, metalaxyl, tebuconazole, thiabendazole, (2) the insecticides acetamiprid, pirimiphos-methyl and thiacloprid, (3) the herbicide metribuzin and (4) the synergist piperonyl butoxide. Dietary intakes were estimated for each of the 705 individuals studied and for 431 pesticides incl. 281 with a toxicological reference value (TRV). In the lower-bound scenario, which tends to underestimate the exposure, the TRV were never exceeded. In the upper-bound scenario that overestimates exposure, the estimated intakes exceeded the TRV for dieldrin and lindane (two persistent organic pollutants) and propylene thiourea, a metabolite of propineb. For these three substances, more sensitive analyses are needed to refine the assessment. For 17 other detected and/or prioritised pesticides, the risk could not be characterised due to the lack of a valid TRV, of certain food analyses or the absence of analytical standards for their metabolites. Keywords: Food safety, Infants and young children, Pesticide residues, Total diet study, Exposure assessment, Risk characterization

Although tectonic plates are usually considered as rigid blocks, intraplate deformation such as lithospheric buckling or diffuse brittle deformation has been recognized for a long time. However, the origin of these deformations remains puzzling. Indeed, whereas the chronology of deformation at plate boundaries can be constrained by numerous methods (syntectonic sedimentary record, thermochronology, etc.), dating of brittle structures (faults, veins, and joints) in the far-field domains remains challenging, preventing a global interpretation of the system as a whole. In this contribution, we have combined a tectonic study with a synkinematical geochronological study of fault-related calcites of the Grands Causses intraplate domain, north of the Pyrenean orogeny. We show that these faults record a much longer history of deformation than previously thought. The Mesozoic extension, usually attributed to an early Jurassic Tethysian rifting event, probably lasted until the Barremian-Aptian epoch, in response to the Pyrenean basin’s opening. The so-called “Pyrenean deformation” of the Grands Causses domain, usually associated with the paroxysm of deformation in the belt during the late Eocene, began much earlier, around 100 Ma, and lasted for more than 60-70 Ma. This study demonstrates the high sensitivity of an intraplate domain (Grands Causses area) to record extensional or compressional deformations occurring at the edge of neighbouring plates.

Purpose. The aim of this study was to assess the effect of intravitreal injections (IVI) of ranibizumab and aflibercept on the choroidal thickness (CT) in patients with treatment-naive diabetic macular edema (DME) before and after monthly IVI. Patients and Methods. Prospective monocenter study. Inclusion criteria were treatment-naive DME eyes without concomitant panretinal photocoagulation, associated with a decrease in best-corrected visual acuity ≤75 letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. DME was defined by a central retinal thickness ≥300 μm on swept-source OCT (Triton DRI OCT, Topcon Corporation, Itabashi, Japan). Patients received 5 IVI of ranibizumab or aflibercept. The primary endpoint was the change in the central subfield CT (CSCT) between inclusion (M0) and 1 month after the fifth IVI (M5). The secondary endpoint was the CT changes between M0 and M5 in other locations of the macular ETDRS grid. Results. Twenty-four eyes of 24 patients with a mean age of 61.1 years were included. Eleven and 13 patients were, respectively, treated with ranibizumab and aflibercept, and 86.4% had type 2 diabetes. The overall CSCT decreased significantly by −12 μm between M0 and M5 (231.7 μm at M0 and 219.7 μm at M5) (p=0.03). It decreased by −15.2 μm (p=0.02) in the aflibercept group (206.9 μm at M0 and 191.7 μm at M5) and by −7.3 μm (p=0.4) in the ranibizumab group (267.5 μm at M0 and 260.2 μm at M5). The CSCT decreased by −4.9 μm in noninjected contralateral eyes (242.3 μm at M0 and 237.4 μm at M5). CT changes between M0 and M5 in the superior, temporal, inferior, and nasal macular inner ring were significant in the aflibercept group but not in the ranibizumab and control groups. Conclusion. In DME patients, the CSCT decreases after 5 IVI of anti-VEGF, especially after aflibercept treatment.

Cet article traite de l’usage existentiel du verbe de perception voir. Nous montrons sous quelles conditions ce verbe peut être utilisé dans des énoncés thétiques pour exprimer l’existence (comme dans on voit des trèfles à quatre feuilles). La lecture existentielle de voir est conditionnée par la présence d’un ensemble de propriétés définitoires des constructions existentielles (sujet non référentiel, indéfinitude de l’objet, ancrage locatif). Nous mettons en évidence que pour satisfaire ces propriétés, les caractéristiques transitives de voir doivent être fortement affaiblies, tout particulièrement au niveau du sujet. Nous examinons dans quels contextes des commutations entre il y a et on voit sont possibles, et quel est l’apport spécifique, irréductible lié à l’usage de voir. Cette spécificité tient au fait que voir implique un actant sujet (le voyeur) qui, même réduit à un indéfini générique ou effacé dans une forme passive, persiste à divers degrés. Nous proposons d’expliquer certaines différences subtiles entre il y a et voir par cette inscription, même minimale, d’un observateur en lien avec l’assertion de l’existence ou de la présence d’une entité.

Traffic symbols are crucial part of the road infrastructure which are erected at the side of the roads that communicates basic instructions of the road with the help of simple visual graphics which can be understood in no time. As compared to previous decades, traffic congestion is a major issue faced in densely populated cities. Unfortunately, drivers may not notice these traffic signs due to adverse traffic conditions or ignorance which may cause accidents. Therefore, building an intelligent traffic sign recognition model is the need of the time. Besides contributing to the safety and comfort of drivers, traffic symbols recognition has important benefits for autonomous vehicles. In this paper, we have used simple CNN technique to recognize static as well as dynamic traffic symbols on the German Traffic Symbol Recognition Benchmark (GTSRB) dataset which has more than 40 classes of traffic symbols in different orientation and lightning condition. Further, a comparison of performance of CNN on static and dynamic input was done and the efficiency was compared. The experimental results show that the detection rate of the CNN model on static images is 96.15% which significantly higher than that of on dynamic images, which resulted in 95% accurate.

Exercises are highly essential in our everyday lives, especially when patients are in the middle of a healing process and need to speed up their body's recuperation. Exercise has become more important in our lives as a result of this. They provide the cornerstone for improving human capacities and extending their lives. Artificial Intelligence and Image Processing can be utilized to improve and supplement the workout process without the need for professional supervision. A software-based motion tracker can keep track of all the exercises you've done and provide you feedback on your posture while you're working out. Through computing data and analysis, the exercise's beneficial efficiency will be increased. The MediaPipe framework could be utilized for this application; in this machine learning model, points are plotted at several joints of the human body posture, and movement is tracked, stored, and analyzed. This detailed analysis of the body tracking could be used in the implementation of an application that could keep a track of the medical exercise of a registered individual. The software could be further improvised in such a manner that the registered user could be mapped to an authentic verified doctor having the access to the diagnosis reports and exercise history of the mapped patient using databases.

As a part of the Chemistry-Aerosol Mediterranean Experiment (ChArMEx) and Cyprus Aerosols and Gas Precursors (ENVI-Med CyAr) programs, this study aims primarily to provide an improved understanding of the sources and the fate of volatile organic compounds (VOCs) in the eastern Mediterranean. More than 60 VOCs, including biogenic species (isoprene and eight monoterpenes) and oxygenated VOCs, were measured during a 1-month intensive field campaign performed in March 2015 at the Cyprus Atmospheric Observatory (CAO), a regional background site in Cyprus. VOC measurements were conducted using complementary online and offline techniques. Biogenic VOCs (BVOCs) were principally imputed to local sources and characterized by compound-specific daily cycles such as diurnal maximum for isoprene and nocturnal maximum for α- and β-pinenes, in connection with the variability of emission sources. The simultaneous study of pinene and isoprene temporal evolution and meteorological parameters has shown that BVOC emissions were mainly controlled by ambient temperature, precipitation and relative humidity. It was found that isoprene daytime emissions at CAO depended on temperature and solar radiation changes, whereas nocturnal BVOC concentrations (e.g., from oak and pine forests) were more prone to the relative humidity and temperature changes. Significant changes in monoterpene mixing ratios occurred during and after rainfall. The second part of the study focused on new particle formation (NPF) events at CAO. BVOCs are known to potentially play a role in the growth as well as in the early stages of formation of new atmospheric particles. Based on observations of the particle size distribution performed with a differential mobility particle sizer (DMPS) and the total number concentrations of particles larger than 1 nm diameter measured by particle size magnifier (PSM), NPF events were found on 14 out of 20 days of the field campaign. For all possible proxy parameters (meteorological parameters, calculated H2SO4 and measured gaseous compounds) having a role in NPF, we present daily variations of different classes during nucleation event and non-event days. NPF can occur at various condensational sink (CS) values and both under polluted and clean atmospheric conditions. High H2SO4 concentrations coupled with high BVOC concentrations seemed to be one of the most favorable conditions to observe NPF at CAO in March 2015. NPF event days were characterized by either (1) a predominant anthropogenic influence (high concentrations of anthropogenic source tracers observed), (2) a predominant biogenic influence (high BVOC concentrations coupled with low anthropogenic tracer concentrations), (3) a mixed influence (high BVOC concentrations coupled with high anthropogenic tracer concentrations) and (4) a marine influence (both low BVOC and anthropogenic tracer concentrations). More pronounced NPF events were identified during mixed anthropogenic–biogenic conditions compared to the pure anthropogenic or biogenic ones, for the same levels of precursors. Analysis of a specific NPF period of the mixed influence type highlighted that BVOC interactions with anthropogenic compounds enhanced nucleation formation and growth of newly formed particles. During this period, the nucleation-mode particles may be formed by the combination of high H2SO4 and isoprene amounts, under favorable meteorological conditions (high temperature and solar radiation and low relative humidity) along with low CS. During the daytime, growth of the newly formed particles, not only sulfate but also oxygen-like organic aerosol (OOA) mass contributions, increased in the particle phase. High BVOC concentrations were observed during the night following NPF events, accompanied by an increase in CS and in semi-volatile OOA contributions, suggesting further BVOC contribution to aerosol nighttime growth by condensing onto pre-existing aerosols.

Background: Infants born extremely preterm are at high risk of developing bronchopulmonary dysplasia (BPD). This study aimed to assess the incremental health care burden of BPD and associated comorbidities among extremely preterm infants in the United States.Methods: Health service claims in the Premier Perspective database were retrospectively analyzed for infants born at ≤28 weeks gestation who were admitted to neonatal intensive care during birth hospitalization and survived to a postmenstrual age of ≥36 weeks. Gestational age (GA) at birth and BPD status of infants was determined based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes recorded in the database.Results: Of the 12,017 infants included, 4,904 (40.8%) had BPD. BPD increased with decreasing GA: 67.4% of infants born at

Abstract Background To unravel true links between diet and health, it is important that dietary exposure is accurately measured. Currently, mainly self-reporting methods (e.g. food frequency questionnaires and 24-h recalls) are used to assess food intake in epidemiological studies. However, these traditional instruments are subjective measures and contain well-known biases. Especially, estimating the intake of the group of confectionary products, such as products containing cocoa and liquorice, remains a challenge. The use biomarkers of food intake (BFIs) may provide a more objective measurement. However, an overview of current candidate biomarkers and their validity is missing for both cocoa- and liquorice-containing foods. Objective The purpose of the current study was to (1) identify currently described candidate BFIs for cocoa (products) and liquorice, (2) to evaluate the validity of these identified candidate BFIs and (3) to address further validation and/or identification work to be done. Methods This systematic review was based on a comprehensive literature search of three databases (PubMed, Scopus and ISI web of Science), to identify candidate BFIs. Via a second search step in the Human Metabolome Database (HMDB), the Food Database (FooDB) and Phenol-Explorer, the specificity of the candidate BFIs was evaluated, followed by an evaluation of the validity of the specific candidate BFIs, via pre-defined criteria. Results In total, 37 papers were included for cocoa and 8 papers for liquorice. For cocoa, 164 unique candidate BFIs were obtained, and for liquorice, four were identified in total. Despite the high number of identified BFIs for cocoa, none of the metabolites was specific. Therefore, the validity of these compounds was not further examined. For liquorice intake, 18-glycyrrhetinic acid (18-GA) was found to have the highest assumed validity. Conclusions For cocoa, specific BFIs were missing, mainly because the individual BFIs were also found in foods having a similar composition, such as tea (polyphenols) or coffee (caffeine). However, a combination of individual BFIs might lead to discriminating profiles between cocoa (products) and foods with a similar composition. Therefore, studies directly comparing the consumption of cocoa to these similar products are needed, enabling efforts to find a unique profile per product. For liquorice, we identified 18-GA as a promising BFI; however, important information on its validity is missing; thus, more research is necessary. Our findings indicate a need for more studies to determine acceptable BFIs for both cocoa and liquorice.

Aim: Sialic acid plays a central role in the functioning of biological systems, in stabilizing the glycoproteins and cellular membranes, assisting in cell–cell recognition and interaction. The aim of this study is to evaluate and compare the periodontal health status and salivary Sialic acid levels in patients suffering from chronic obstructive pulmonary diseases (COPD) and chronic periodontitis patients. Materials and Methods: Ninety subjects were included in the study, which were divided into the following groups, 30 in each group. Group 1: patients suffering from COPD and chronic periodontitis, Group 2: periodontitis patients without any systemic diseases Group 3: healthy subjects. Unstimulated whole saliva samples were collected around 9–10 AM; 2 h after the subjects had breakfast. The sialic acid content was determined by a combined modification of the thiobarbituric acid method of Skoza and Mohos. Results: The mean salivary sialic acid levels were least in the healthy group followed by the periodontitis group, and it was highest in the COPD group. Conclusions: We can thus conclude that promotion of dental care knowledge is very much essential in the prevention and treatment of COPD. Thus, estimation of levels of salivary sialic acid can be used as an adjunct to diagnose the current periodontal disease status and to assess the treatment outcomes in subjects with COPD and chronic periodontitis.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, is also known as drug induced hypersensitivity syndrome and by various other names. It is now recognised as one of the severe cutaneous adverse reaction (SCAR) and can be potentially life-threatening. Historically, it was most frequently linked with phenytoin and was initially described as phenytoin hypersensitivity syndrome. However, it was later found to be caused by various other medications. Anticonvulsants and sulfonamides are the most common offender. Characteristically DRESS has a latent period of 2 to 6 weeks. The pathophysiology remains incompletely understood but involves reactivation of viruses and activation of lymphocyte. It is manifested most commonly with a morbilliform cutaneous eruption with fever and lymphadenopathy. The severity of this syndrome is related to the systemic involvement, which can result in multi-organ failure. Most important step in the management of DRESS is early diagnosis and immediate cessation of the suspected offending drug. Patients of DRESS syndrome should be managed in an intensive care set up for appropriate supportive care and infection control. Topical corticosteroids can give symptomatic relief, but systemic therapy with steroid and other immunosuppressant is usually required.

Introduction: Mycobacterium leprae has a small genome and a tendency of persisting as a very low-grade infection. The authors have shown earlier, that the changes in TTC repeats, in M. leprae genome may contribute to the restriction of the pathogenicity of the bacterium and its survival strategy in case of pure neural Hansen's disease. We suspect, that a similar genomic reduction if happens in treated cases of Hansen's disease, can be a determining factor for developing persisters and relapse. Aim: The present study aimed to find out if there was any evidence of genomic reduction in treated cases of Hansen's disease that showed microbiological nonresponse. Methods: Skin biopsies were taken from treated cases of Hansen's disease at tertiary centers in Kolkata and at Raipur who had bacterial index (BI) unchanged or increased compared to their pretreatment BI. Analysis for the mutation in rpoB gene and folP1 gene were done to rule out rifampicin and dapsone resistance, respectively. The entire TTC repeat region of the bacteria was amplified by polymerase chain reaction and was subjected to sequencing. The obtained sequences were then analyzed by CLUSTALW. Results: A total of 127 patients were included in the study of which in 52 the BI remained same and 75 had an increase in BI, even after 6 months of completion of multidrug therapy. Among the samples, 2 had positive rpoB gene mutation. No mutation was found in the folP1 gene. The TTC repeat of both the rpoB-resistant samples was found to have 17 copies, which matched their pretreatment copy number. In other 125 cases, 60 cases showed no change from their pretreatment TTC number. Of those 65 samples that showed evidence of genomic reduction, 11 samples showed one copy, 41 showed 2 copies, and 13 showed 3 copies deletion. We also observed a significant regional variation. Conclusion: We concluded that there was evidence of genomic reduction, which might lead to microbiological nonresponse in treated cases of Hansen's disease. This indicated a possibility of future persistence and relapse.

Abstract Background Bioinformatic tools for the enrichment of ‘omics’ datasets facilitate interpretation and understanding of data. To date few are suitable for metabolomics datasets. The main objective of this work is to give a critical overview, for the first time, of the performance of these tools. To that aim, datasets from metabolomic repositories were selected and enriched data were created. Both types of data were analysed with these tools and outputs were thoroughly examined. Results An exploratory multivariate analysis of the most used tools for the enrichment of metabolite sets, based on a non-metric multidimensional scaling (NMDS) of Jaccard’s distances, was performed and mirrored their diversity. Codes (identifiers) of the metabolites of the datasets were searched in different metabolite databases (HMDB, KEGG, PubChem, ChEBI, BioCyc/HumanCyc, LipidMAPS, ChemSpider, METLIN and Recon2). The databases that presented more identifiers of the metabolites of the dataset were PubChem, followed by METLIN and ChEBI. However, these databases had duplicated entries and might present false positives. The performance of over-representation analysis (ORA) tools, including BioCyc/HumanCyc, ConsensusPathDB, IMPaLA, MBRole, MetaboAnalyst, Metabox, MetExplore, MPEA, PathVisio and Reactome and the mapping tool KEGGREST, was examined. Results were mostly consistent among tools and between real and enriched data despite the variability of the tools. Nevertheless, a few controversial results such as differences in the total number of metabolites were also found. Disease-based enrichment analyses were also assessed, but they were not found to be accurate probably due to the fact that metabolite disease sets are not up-to-date and the difficulty of predicting diseases from a list of metabolites. Conclusions We have extensively reviewed the state-of-the-art of the available range of tools for metabolomic datasets, the completeness of metabolite databases, the performance of ORA methods and disease-based analyses. Despite the variability of the tools, they provided consistent results independent of their analytic approach. However, more work on the completeness of metabolite and pathway databases is required, which strongly affects the accuracy of enrichment analyses. Improvements will be translated into more accurate and global insights of the metabolome.

Acute generalised exanthematous pustulosis (AGEP) is a severe cutaneous adverse reaction and is attributed to drugs in more than 90% of cases. It is a rare disease, with an estimated incidence of 1–5 patients per million per year. The clinical manifestations characterised by the rapid development of sterile pustular lesions, fever and leucocytosis. Number of drugs has been reported to be associated with AGEP, most common being the antibiotics. Histopathologically there is intraepidermal pustules and papillary dermal oedema with neutrophilic and eosinophilic infiltrations. Systemic involvement can be present in more severe cases. Early diagnosis with withdrawal of the causative drug is the most important step in the management. Treatment includes supportive care, prevention of antibiotics and use of a potent topical steroid.

Some cutaneous adverse drug reactions (CADRs) are severe life-threatening conditions due to multisystem involvements with a high morbidity and mortality rates ranging from 25 - 70% and require immediate medical care. But there are huge controversies regarding the management because large clinical trials are lacking. Most frequent discussion and division occur regarding the use of systemic corticosteroid as early intervention with corticosteroids controls inflammation. Corticosteroids are potent agents that target several intracellular processes to modify almost all components of inflammatory and immune responses but their impact on the long term disease course is not known. Controlled relapses of rash and hepatitis may occur as corticosteroids are tapered. A chronic HHV6 activation promoted by systemic steroids could explain these relapses. Second important issue is the use of antitubercular drugs (ATD) in case of CADR due to multidrug therapy of ATD. As both the tuberculosis and CADR are life threatening conditions and we can not spare treatment of tuberculosis for CADR, we should come to a conclusion which is not yet decided. In the same way the use of antileprotic MDT in CADR due to MDT raises a similar controversy. So, here we focus on those controversies and discuss the issues.

Psoriasis is a chronic immune-mediated inflammatory condition, affecting 2–3% of the population. In recent years, advent of biologics, including secukinumab, have been a major advancement in the management of difficult-to-treat plaque psoriasis. However, high cost of biologics is often a deterrent, especially for Indian socioeconomic condition. Apremilast is an oral phosphodiesterase 4 inhibitor that is safe for use along with many other systemic therapies of psoriasis, including biologics. We report two cases of psoriasis on secukinumab therapy for long duration with good response to therapy. Later, addition of apremilast, allowed halving the dose of secukinumab with maintenance of improvement.