Global Burden Related to Nitrous Oxide Exposure in Medical and Recreational Settings: A Systematic Review and Individual Patient Data Meta-Analysis.

The risk of adverse effects of nitrous oxide (N2O) exposure is insufficiently recognized despite its widespread use. These effects are mainly reported through case reports. We conducted an individual patient data meta-analysis to assess the prevalence of clinical, laboratory, and magnetic resonance findings in association with N2O exposure in medical and recreational settings. We calculated the pooled estimates for the studied outcomes and assessed the potential bias related to population stratification using principal component analysis. Eighty-five publications met the inclusion criteria and reported on 100 patients with a median age of 27 years and 57% of recreational users. The most frequent outcomes were subacute combined degeneration (28%), myelopathy (26%), and generalized demyelinating polyneuropathy (23%). A T2 signal hyperintensity in the spinal cord was reported in 68% (57.2-78.8%) of patients. The most frequent clinical manifestations included paresthesia (80%; 72.0-88.0%), unsteady gait (58%; 48.2-67.8%), and weakness (43%; 33.1-52.9%). At least one hematological abnormality was retrieved in 71.7% (59.9-83.4%) of patients. Most patients had vitamin B12 deficiency: vitamin B12 <150 pmol/L (70.7%; 60.7-80.8%), homocysteine >15 µmol/L (90.3%; 79.3-100%), and methylmalonic acid >0.4 µmol/L (93.8%; 80.4-100%). Consistently, 85% of patients exhibited a possibly or probably deficient vitamin B12 status according to the cB12 scoring system. N2O can produce severe outcomes, with neurological or hematological disorders in almost all published cases. More than half of them are reported in the setting of recreational use. The N2O-related burden is dominated by vitamin B12 deficiency. This highlights the need to evaluate whether correcting B12 deficiency would prevent N2O-related toxicity, particularly in countries with a high prevalence of B12 deficiency

Semaine d'Etude Mathématiques et Entreprises 1 : Modèles de comparaison quantitative de matrices 3D

Air Liquide dispose de jeux de données représentant des champs de quantité de dépôt de particules sur les poumons. Ces données proviennent de mesures 3D (obtenues via SPECT, Single Photon Emission Computer Tomography) du dépôt d'un aérosol contenant des particules radio-labellisées préalablement inhalé par les patients étudiés. Le sujet proposé ici consiste à se demander quelles sont les méthodes permettant de comparer de façon quantitative et systématique les résultats des observations, qui sont donnés sous la forme de matrices 3D correspondant à la quantité de particules estimée dans chaque voxel

Identification of a Variable Number of Tandem Repeats Polymorphism and Characterization of LEF-1 Response Elements in the Promoter of the IDO1 Gene

Indoleamine 2,3-dioxygenase (IDO) catalyzes the first and rate-limiting step of the kynurenine pathway that is an important component of immunomodulatory and neuromodulatory processes. The IDO1 gene is highly inducible by IFN-γ and TNF-α through interaction with cis-acting regulatory elements of the promoter region. Accordingly, functional polymorphisms in the IDO1 promoter could partly explain the interindividual variability in IDO expression that has been previously documented.A PCR-sequencing strategy, applied to DNA samples from healthy Caucasians, allowed us to identify a VNTR polymorphism in the IDO1 promoter, which correlates significantly with serum tryptophan concentration, controlled partially by IDO activity, in female subjects, but not in males. Although this VNTR does not appear to affect basal or cytokine-induced promoter activity in gene reporter assays, it contains novel cis-acting elements. Three putative LEF-1 binding sites, one being located within the VNTR repeat motif, were predicted in silico and confirmed by chromatin immunoprecipitation. Overexpression of LEF-1 in luciferase assays confirmed an interaction between LEF-1 and the predicted transcription factor binding sites, and modification of the LEF-1 core sequence within the VNTR repeat motif, by site-directed mutagenesis, resulted in an increase in promoter activity.The identification of a VNTR in the IDO1 promoter revealed a cis-acting element interacting with the most downstream factor of the Wnt signaling pathway, suggesting novel mechanisms of regulation of IDO1 expression. These data offer new insights, and suggest further studies, into the role of IDO in various pathological conditions, particularly in cancer where IDO and the Wnt pathway are strongly dysregulated

Clastic patterned ground in Lomonosov crater, Mars: examining fracture controlled formation mechanisms

The area surrounding Lomonosov crater on Mars has a high density of seemingly organised boulder patterns. These form seemingly sorted polygons and stripes within kilometre scale blockfields, patches of boulder strewn ground which are common across the Martian high latitudes. Several hypotheses have been suggested to explain the formation of clastic patterned ground on Mars. It has been proposed that these structures could have formed through freeze-thaw sorting, or conversely by the interaction of boulders with underlying fracture polygons. In this investigation a series of sites were examined to evaluate whether boulder patterns appear to be controlled by the distribution of underlying fractures and test the fracture control hypotheses for their formation. It was decided to focus on this suite of mechanisms as they are characterised by a clear morphological relationship, namely the presence of an underlying fracture network which can easily be evaluated over a large area. It was found that in the majority of examples at these sites did not exhibit fracture control. Although fractures were present at many sites there were very few sites where the fracture network appeared to be controlling the boulder distribution. In general these were not the sites with the best examples of organization, suggesting that the fracture control mechanisms are not the dominant geomorphic process organising the boulders in this area

The association of maternal-infant interactive behavior, dyadic frontal alpha asymmetry, and maternal anxiety in a smartphone-adapted still face paradigm

Mother-infant interactions form a strong basis for emotion regulation development in infants. These interactions can be affected by various factors, including maternal postnatal anxiety. Electroencephalography (EEG) hyperscanning allows for simultaneous assessment of mother-infant brain-to-behavior association during stressful events, such as the still-face paradigm (SFP). This study aimed at investigating dyadic interactive behavior and brain-to-behavior association across SFP and identifying neural correlates of mother-infant interactions in the context of maternal postnatal anxiety. We measured frontal alpha asymmetry (FAA), a physiological correlate of emotion regulation and a potential marker of risk for psychopathology. To emulate real-life interactions, EEG and behavioral data were collected from 38 mother-infant dyads during a smartphone-adapted dual-SFP. Although the behavioral data showed a clear still-face effect for the smartphone-adapted SFP, this was not reflected in the infant or maternal FAA. Brain-to-behavior data showed higher infant negative affect being associated with more infant leftward FAA during the still-face episodes. Finally, mothers with higher postnatal anxiety showed more right FAA during the first still-face episode, suggesting negative affectivity and a need to withdraw from the situation. Our results form a baseline for further research assessing the effects of maternal postnatal anxiety on infants' FAA and dyadic interactive behavior

Study protocol: evaluation of a parenting and stress management programme: a randomised controlled trial of Triple P discussion groups and stress control

<br>Background: Children displaying psychosocial problems are at an increased risk of negative developmental outcomes. Parenting practices are closely linked with child development and behaviour, and parenting programmes have been recommended in the treatment of child psychosocial problems. However, parental mental health also needs to be addressed when delivering parenting programmes as it is linked with parenting practices, child outcomes, and treatment outcomes of parenting programmes. This paper describes the protocol of a study examining the effects of a combined intervention of a parenting programme and a cognitive behavioural intervention for mental health problems.</br> <br>Methods: The effects of a combined intervention of Triple P Discussion Groups and Stress Control will be examined using a randomised controlled trial design. Parents with a child aged 3?8?years will be recruited to take part in the study. After obtaining informed consent and pre-intervention measures, participants will be randomly assigned to either an intervention or a waitlist condition. The two primary outcomes for this study are change in dysfunctional/ineffective parenting practices and change in symptoms of depression, anxiety, and stress. Secondary outcomes are child behaviour problems, parenting experiences, parental self-efficacy, family relationships, and positive parental mental health. Demographic information, participant satisfaction with the intervention, and treatment fidelity data will also be collected. Data will be collected at pre-intervention, mid-intervention, post-intervention, and 3-month follow-up.</br> <br>Discussion: The aim of this paper is to describe the study protocol of a randomised controlled trial evaluating the effects of a combined intervention of Triple P Discussion Groups and Stress Control in comparison to a waitlist condition. This study is important because it will provide evidence about the effects of this combined intervention for parents with 3?8?year old children. The results of the study could be used to inform policy about parenting support and support for parents with mental health problems. Trial registration ClinicalTrial.gov: NCT01777724, UTN: U1111-1137-1053.</br&gt

Magnitude and temporal variations of socioeconomic inequalities in the quality of life after early breast cancer: results from the multicentric French CANTO Cohort

PURPOSE: Socioeconomic status (SES) influences the survival outcomes of patients with early breast cancer (EBC). However, limited research investigates social inequalities in their quality of life (QoL). This study examines the socioeconomic inequalities in QoL after an EBC diagnosis and their time trends. PATIENTS AND METHODS: We used data from the French prospective multicentric CANTO cohort (ClinicalTrials.gov identifier: NCT01993498), including women with EBC enrolled between 2012 and 2018. QoL was assessed using the European Organisation for Research and Treatment of Cancer QoL Core 30 questionnaire (QLQ-C30). summary score at diagnosis and 1 and 2 years postdiagnosis. We considered three indicators of SES separately: self-reported financial difficulties, household income, and educational level. We first analyzed the trajectories of the QLQ-C30 summary score by SES group. Then, social inequalities in QLQ-C30 summary score and their time trends were quantified using the regression-based slope index of inequality (SII), representing the absolute change in the outcome along socioeconomic gradient extremes. The analyses were adjusted for age at diagnosis, Charlson Comorbidity Index, disease stage, and type of local and systemic treatment. RESULTS: Among the 5,915 included patients with data on QoL at diagnosis and at the 2-year follow-up, social inequalities in QLQ-C30 summary score at baseline were statistically significant for all SES indicators (SIIfinancial difficulties = -7.6 [-8.9; -6.2], SIIincome = -4.0 [-5.2; -2.8]), SIIeducation = -1.9 [-3.1; -0.7]). These inequalities significantly increased (interaction P <.05) in year 1 and year 2 postdiagnosis, irrespective of prediagnosis health, tumor characteristics, and treatment. Similar results were observed in subgroups defined by menopausal status and type of adjuvant systemic treatment. CONCLUSION: The magnitude of preexisting inequalities in QoL increased over time after EBC diagnosis, emphasizing the importance of considering social determinants of health during comprehensive cancer care planning.info:eu-repo/semantics/publishedVersio

Viscoelastometric Testing to Assess Hemostasis of COVID-19: A Systematic Review

Infection by SARS-CoV-2 is associated with a high risk of thrombosis. The laboratory documentation of hypercoagulability and impaired fibrinolysis remains a challenge. Our aim was to assess the potential usefulness of viscoelastometric testing (VET) to predict thrombotic events in COVID-19 patients according to the literature. We also (i) analyzed the impact of anticoagulation and the methods used to neutralize heparin, (ii) analyzed whether maximal clot mechanical strength brings more information than Clauss fibrinogen, and (iii) critically scrutinized the diagnosis of hypofibrinolysis. We performed a systematic search in PubMed and Scopus databases until 31st December 2020. VET methods and parameters, and patients' features and outcomes were extracted. VET was performed for 1063 patients (893 intensive care unit (ICU) and 170 non-ICU, 44 studies). There was extensive heterogeneity concerning study design, VET device used (ROTEM, TEG, Quantra and ClotPro) and reagents (with non-systematic use of heparin neutralization), timing of assay, and definition of hypercoagulable state. Notably, only 4 out of 25 studies using ROTEM reported data with heparinase (HEPTEM). The common findings were increased clot mechanical strength mainly due to excessive fibrinogen component and impaired to absent fibrinolysis, more conspicuous in the presence of an added plasminogen activator. Only 4 studies out of the 16 that addressed the point found an association of VETs with thrombotic events. So-called functional fibrinogen assessed by VETs showed a variable correlation with Clauss fibrinogen. Abnormal VET pattern, often evidenced despite standard prophylactic anticoagulation, tended to normalize after increased dosing. VET studies reported heterogeneity, and small sample sizes do not support an association between the poorly defined prothrombotic phenotype of COVID-19 and thrombotic events

The nitrogen, carbon and greenhouse gas budget of a grazed, cut and fertilised temperate grassland

Intensively managed grazed grasslands in temperate climates are globally important environments for the exchange of the greenhouse gases (GHGs) carbon dioxide (CO2), nitrous oxide (N2O) and methane (CH4). We assessed the N and C budget of a mostly grazed and occasionally cut and fertilised grassland in SE Scotland by measuring or modelling all relevant imports and exports to the field as well as changes in soil C and N stocks over time. The N budget was dominated by import from inorganic and organic fertilisers (21.9 g N m−2 a−1) and losses from leaching (5.3 g N m−2 a−1), N2 emissions (2.9 g N m−2 a−1), and NOx and NH3 volatilisation (3.9 g N m−2 a−1), while N2O emission was only 0.6 g N m−2 a−1. The efficiency of N use by animal products (meat and wool) averaged 9.9 % of total N input over only-grazed years (2004–2010). On average over 9 years (2002–2010), the balance of N fluxes suggested that 6.0 ± 5.9 g N m−2 a−1 (mean ± confidence interval at p > 0.95) were stored in the soil. The largest component of the C budget was the net ecosystem exchange of CO2 (NEE), at an average uptake rate of 218 ± 155 g C m−2 a−1 over the 9 years. This sink strength was offset by carbon export from the field mainly as grass offtake for silage (48.9 g C m−2 a−1) and leaching (16.4 g C m−2 a−1). The other export terms, CH4 emissions from the soil, manure applications and enteric fermentation, were negligible and only contributed to 0.02–4.2 % of the total C losses. Only a small fraction of C was incorporated into the body of the grazing animals. Inclusion of these C losses in the budget resulted in a C sink strength of 163 ± 140 g C m−2 a−1. By contrast, soil stock measurements taken in May 2004 and May 2011 indicated that the grassland sequestered N in the 0–60 cm soil layer at 4.51 ± 2.64 g N m−2 a−1 and lost C at a rate of 29.08 ± 38.19 g C m−2 a−1. Potential reasons for the discrepancy between these estimates are probably an underestimation of C losses, especially from leaching fluxes as well as from animal respiration. The average greenhouse gas (GHG) balance of the grassland was −366 ± 601 g CO2 eq. m−2 yr−1 and was strongly affected by CH4 and N2O emissions. The GHG sink strength of the NEE was reduced by 54 % by CH4 and N2O emissions. Estimated enteric fermentation from ruminating sheep proved to be an important CH4 source, exceeding the contribution of N2O to the GHG budget in some years