[The role of HFNC oxygen in pre-oxygenation prior to intubation and the practice of invasive procedures]. / Place de l'oxygénothérapie haut débit dans la pré-oxygénation pour l'intubation et la pratique des gestes invasifs.

Over recent years, High Flow Nasal Cannula (HFNC) oxygen therapy has been more and more extensively applied in numerous medical settings, and it is now carried out in invasive procedures such as pre-oxygenation before orotracheal intubation, often leading to complications. More generally, pre-oxygenation is aimed at maintaining the highest possible oxygen saturation for extended periods of time. With this in mind, HFNC seems as effective as standard oxygen delivery with regard to hematosis in patients with mild or moderate hypoxemia, and it presents the advantage of reducing the adverse events associated with intubation. That said, during pre-oxygenation of patients with severe hypoxemia, non-invasive ventilation (NIV) is probably more effective than HFNC, especially in the prevention of respiratory events. However, in patients with little or no hypoxemia undergoing risky procedures such as bronchial endoscopy, HFNC allows better oxygen saturation than standard methods. To summarize, even though NIV remains useful in unstable patients, especially in decreasing desaturation episodes, HFNC could represent a reasonable alternative in case of poor tolerance, allowing continuous oxygenation of patients requiring digestive endoscopy or trans-esophageal ultrasound.

Agriculture increases the bioavailability of silicon, a beneficial element for crop, in temperate soils.

Crops may take benefits from silicon (Si) uptake in soil. Plant available Si (PAS) can be affected by natural weathering processes or by anthropogenic forces such as agriculture. The soil parameters that control the pool of PAS are still poorly documented, particularly in temperate climates. In this study, we documented PAS in France, based on statistical analysis of Si extracted by CaCl2 (SiCaCl2) and topsoil characteristics from an extensive dataset. We showed that cultivation increased SiCaCl2 for soils developed on sediments, that cover 73% of France. This increase is due to liming for non-carbonated soils on sediments that are slightly acidic to acidic when non-cultivated. The analysis performed on non-cultivated soils confirmed that SiCaCl2 increased with the < 2 µm fraction and pH but only for soils with a < 2 µm fraction ranging from 50 to 325 g kg-1. This increase may be explained by the < 2 µm fraction mineralogy, i.e. nature of the clay minerals and iron oxide content. Finally, we suggest that 4% of French soils used for wheat cultivation could be deficient in SiCaCl2.

Compliance to oral nutritional supplementation decreases the risk of hospitalisation in malnourished older adults without extra health care cost: Prospective observational cohort study.

BACKGROUND & AIMS: Malnutrition affects 5-10% of elderly people living in the community. A few studies suggest that nutritional intervention may reduce health care costs. The present study included malnourished elderly patients living at home. It aimed to compare health care costs between patients that were prescribed ONS by their general practitioner and those who were not, and to assess the effect of ONS prescription on the risk of hospitalisation. METHODS: This prospective multicentre observational study included malnourished patients ≥70 years old who lived at home. Patients were defined as malnourished if they presented with one or more of the following criteria: weight loss ≥5% in 1 month, weight loss ≥10% in 6 months, BMI <21 kg/m2, albuminemia <35 g/L or Short-Form MNA ≤ 7. Their general practitioners prescribed an ONS, or not, according to their usual practice. Health care costs were recorded during a 6-month period. Other collected data were diseases, disability, self-perception of current health status, quality of life (QoL), nutritional status, appetite and compliance to ONS. A propensity score method was used to compare costs and risk of hospitalisation to adjust for potential confounding factors and control for selection bias. RESULTS: We analysed 191 patients. At baseline, the 133 patients (70%) who were prescribed ONS were more disabled (p < 0.001) and had poorer perception of their health (p = 0.02), lower QoL (p = 0.04) and lower appetite (p < 0.001) than the 58 patients (30%) who were not prescribed ONS. At 6 months, appetite had improved more in the ONS prescription group (p = 0.001). Weight change was not different between groups. Patients prescribed ONS were more frequently hospitalised (OR 2.518, 95% CI: [1.088; 5.829] hosp; p = 0.03). Analyses of adjusted populations revealed no differences in health care costs between groups. In the ONS prescription group, we identified that health care costs were lower (p = 0.042) in patients with an energy intake from ONS ≥ 500 kcal/d (1389 ± 264 €) vs. < 500 kcal/d (3502 ± 839 €). The risk of hospitalisation was reduced 3 and 5 times when the intake from ONS was ≥30 g of protein/day or ≥500 kcal/d, respectively. CONCLUSIONS: ONS prescription in malnourished elderly patients generated no extra heath care cost. High energy and protein intake from ONS was associated with a reduced risk of hospitalisation and health care costs.

Overall survival results of AGO-OVAR16: A phase 3 study of maintenance pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced ovarian cancer.

OBJECTIVE: The AGO-OVAR16 study was designed to test the efficacy, safety, and tolerability of pazopanib maintenance after first-line chemotherapy in patients with newly diagnosed advanced ovarian cancer (AOC). METHODS: Nine hundred and forty patients with histologically confirmed AOC, International Federation of Gynecology and Obstetrics (FIGO) stage II-IV, were randomized in a 1:1 ratio to receive either 800 mg pazopanib once daily or placebo for up to 24 months, unless there was disease progression, toxicity, withdrawal of consent, or death. The primary endpoint (investigator-assessed progression-free survival [PFS]) was met and previously reported. The results of final analyses of overall survival (OS) are reported here. RESULTS: A third OS interim analysis showed futility and led to study closure and a final OS analysis after last patient last visit. At the time of the final OS analysis, 494 (89.7% of the planned 551) events had occurred. No difference was observed in OS between pazopanib and placebo. The hazard ratio (HR) was 0.960 (95% confidence interval [CI]: 0.805-1.145), and the median OS from randomization was 59.1 months in pazopanib and 64.0 months in placebo arms. For the East Asian patients, similar to the first three interim OS analyses, a numerical negative trend was observed favoring placebo (HR, 1.332; 95% CI: 0.863-2.054). Exploratory analyses showed a trend for a longer time to first subsequent anti-cancer therapy or death with pazopanib over placebo (HR, 0.829; 95% CI: 0.713-0.965), with a median estimate of 19.0 and 14.5 months, respectively. No new safety signals were observed. CONCLUSION: Although pazopanib prolonged PFS, this was not associated with improvement in median OS. CLINICAL TRIAL INFORMATION: ClinicalTrials.gov: NCT00866697.

Are There Categories of Corneal Shapes?

This study investigates the possible existence of different natural corneal shape categories. This is important to better describe cornea for both diagnostic and therapeutic assessments. We started by describing corneal shape of different populations as a function of influencing clinical data i.e. age, ametropia and gender. This was done by averaging Zernike polynomial (ZP) decomposition of the anterior surfaces in each subgroup. The results showed small but significant differences of shape that are supported by the literature. This motivated us to examine the feasibility of characterizing the normal corneal shape with an automatic method of clustering independent of any clinical a priori knowledge. Since we did not know beforehand the number of corneal categories, agglomerative hierarchical clustering was applied on ZP coefficients for a large database. The dendrogram based on the Ward's distance was evaluated with two different clustering validity indexes (coefficient of determination R2 and semi partial R2 (SPR2). The optimal number of categories was around four showing corneal shapes ranging from flatter to steeper.

Phase II study of the PI3K inhibitor BKM120 in patients with advanced or recurrent endometrial carcinoma: a stratified type I-type II study from the GINECO group.

Backround:Patients with metastatic endometrial carcinoma have a poor prognosis and PIK3CA mutations and amplifications are common in these cancers. This study evaluated the efficacy and safety of the pure PI3K inhibitor BKM120 in advanced or recurrent endometrial carcinoma. METHODS: This phase II, multicentre, single-arm, double strata (histological low grade (LG) or high grade (HG)) open-label study enrolled patients with histologically confirmed advanced or recurrent endometrial carcinoma who had received not more than one prior chemotherapy regimen. Patients received initially BKM120 100 mg tablets once daily. Primary end points were proportion of patients free of progression at 2 months (HG strata) or at 3 months (LG strata), objective response rate (ORR), and safety. RESULTS: A total of 40 patients were enrolled, of whom 16 patients had received BKM120 at 100 mg. Because of high toxicities (cutaneous rash (54%), depressive events (47%), and anxiety (40%), the IDMC has proposed to stop recruitment at 100 mg and to continue the clinical trial with a lower dose of 60 mg per day. In addition, 24 patients (median age 67 years old) were newly enrolled (14 in the LG strata and 10 in the HG strata). Rate of nonprogression at 2 months in the HG strata was 70% and at 3 months was 60% in the LG strata. Median progression-free survival (PFS) for all patients is 4.5 months (CI 95% 2.8-6.1), and the median PFS for LG strata is 8.3 months compared with 3.8 months for the HG strata. No response was reported. At 60 mg per day, the most commonly reported treatment-related adverse events (AEs) were hyperglycaemia (58%), cognitive (31%), digestive (28%), hepatic liver functions (26%), and rash (23%). The most commonly reported treatment-related grade ⩾3 AEs were HTA (17%), hyperglycaemia (17%), and increased alanine aminotransferase (24%). Five patients (21%) stopped BKM120 for toxicity. CONCLUSIONS: The BKM120 was associated with an unfavourable safety profile and minimal antitumour activity in monotherapy in advanced or recurrent endometrial carcinoma. The clinical trial was stopped before end of recruitment for toxicity.

Validity and sensitivity of the longitudinal asymmetry index to detect gait asymmetry using Microsoft Kinect data.

Gait asymmetry information is a key point in disease screening and follow-up. Constant Relative Phase (CRP) has been used to quantify within-stride asymmetry index, which requires noise-free and accurate motion capture, which is difficult to obtain in clinical settings. This study explores a new index, the Longitudinal Asymmetry Index (ILong) which is derived using data from a low-cost depth camera (Kinect). ILong is based on depth images averaged over several gait cycles, rather than derived joint positions or angles. This study aims to evaluate (1) the validity of CRP computed with Kinect, (2) the validity and sensitivity of ILong for measuring gait asymmetry based solely on data provided by a depth camera, (3) the clinical applicability of a posteriorly mounted camera system to avoid occlusion caused by the standard front-fitted treadmill consoles and (4) the number of strides needed to reliably calculate ILong. The gait of 15 subjects was recorded concurrently with a marker-based system (MBS) and Kinect, and asymmetry was artificially reproduced by introducing a 5cm sole attached to one foot. CRP computed with Kinect was not reliable. ILong detected this disturbed gait reliably and could be computed from a posteriorly placed Kinect without loss of validity. A minimum of five strides was needed to achieve a correlation coefficient of 0.9 between standard MBS and low-cost depth camera based ILong. ILong provides a clinically pragmatic method for measuring gait asymmetry, with application for improved patient care through enhanced disease, screening, diagnosis and monitoring.

Survival after pathogen exposure in group-living insects: don't forget the stress of social isolation!

A major cost of group-living is its inherent risk of pathogen infection. To limit this risk, many group-living animals have developed the capability to prophylactically boost their immune system in the presence of group members and/or to mount collective defences against pathogens. These two phenomena, called density-dependent prophylaxis and social immunity, respectively, are often used to explain why, in group-living species, individuals survive better in groups than in isolation. However, this survival difference may also reflect an alternative and often overlooked process: a cost of social isolation on individuals' capability to fight against infections. Here, we disentangled the effects of density-dependent prophylaxis, social immunity and stress of social isolation on the survival after pathogen exposure in group-living adults of the European earwig Forficula auricularia. By manipulating the presence of group members both before and after pathogen exposure, we demonstrated that the cost of being isolated after infection, but not the benefits of social immunity or density-dependent prophylaxis, explained the survival of females. Specifically, females kept constantly in groups or constantly isolated had higher survival rates than females that were first in groups and then isolated after infection. Our results also showed that this cost of social isolation was absent in males and that social isolation did not reduce the survival of noninfected individuals. Overall, this study gives a new perspective on the role of pathogens in social evolution, as it suggests that an apparently nonadaptive, personal immune process may promote the maintenance of group-living under pathogenic environments.

Work-related discussions between French rheumatologists and their rheumatoid arthritis patients.

BACKGROUND: Rheumatoid arthritis (RA) causes significant impairment of physical function, and thus adversely affects patients' ability to work. AIMS: To document how often work limitations are discussed by rheumatologists and RA patients during consultations. METHODS: We conducted an observational study in a sample of French rheumatologists and in a parallel sample of patients recruited by pharmacists. We asked all rheumatologists in France practising in private practice or mixed practice (private practice and hospital) to participate in a telephone survey about their most recent consultation with an RA patient. Randomly selected pharmacists recruited RA patients to complete a questionnaire about their most recent consultation with their rheumatologist. We included patients aged 20-59, with a paid job or unemployed. We calculated the proportion of consultations including work-related discussions in both samples. RESULTS: Of the 1737 rheumatologists contacted, 153 (9%) described consultations with eligible patients. Of the 1200 pharmacists contacted, 39 (3%) recruited 81 RA patients. The proportion of consultations including work-related discussions was 50% [95% confidence interval (CI) 42-58%] in the rheumatologist sample and 52% (95% CI 41-63%) in the patient sample. The most frequent subject of discussion (88%) was physical problems related to work in both samples. CONCLUSIONS: This is the first study to document the proportion of consultations where rheumatologists and their RA patients discuss work. Both specialists and patients reported that work was discussed in one in every two consultations.

Silicon alleviates Cd stress of wheat seedlings (Triticum turgidum L. cv. Claudio) grown in hydroponics.

We investigated the potential role of silicon in improving tolerance and decreasing cadmium (Cd) toxicity in durum wheat (Triticum turgidum L. durum) either through a reduced Cd uptake or exclusion/sequestration in non-metabolic tissues. For this, plants were grown in hydroponic conditions for 10 days either in presence or absence of 1 mM Si and for 11 additional days in various Cd concentrations (0, 0.5, 5.0 and 50 µM). After harvesting, morphological and physiological parameters as well as elemental concentrations were recorded. Cadmium caused reduction in growth parameters, photosynthetic pigments and mineral nutrient concentrations both in shoots and roots. Shoot and root contents of malate, citrate and aconitate increased, while contents of phosphate, nitrate and sulphate decreased with increasing Cd concentrations in plants. Addition of Si to the nutrient solution mitigated these adverse effects: Cd concentration in shoots decreased while concentration of Cd adsorbed at the root cell apoplasmic level increased together with Zn uptake by roots. Overall, total Cd uptake decreased in presence of Si. There was no co-localisation of Cd and Si either at the shoot or at the root levels. No Cd was detected in leaf phytoliths. In roots, Cd was mainly detected in the cortical parenchyma and Si at the endodermis level, while analysis of the outer thin root surface of the plants grown in the 50 µM Cd + 1 mM Si treatment highlighted non-homogeneous Cd and Si enrichments. These data strongly suggest the existence of a root localised protection mechanism consisting in armoring the root surface by Si- and Cd-bearing compounds and in limiting root-shoot translocation.

Negative association between parental care and sibling cooperation in earwigs: a new perspective on the early evolution of family life?

The evolution of family life requires net fitness benefits for offspring, which are commonly assumed to mainly derive from parental care. However, an additional source of benefits for offspring is often overlooked: cooperative interactions among juvenile siblings. In this study, we examined how sibling cooperation and parental care could jointly contribute to the early evolution of family life. Specifically, we tested whether the level of food transferred among siblings (sibling cooperation) in the European earwig Forficula auricularia (1) depends on the level of maternal food provisioning (parental care) and (2) is translated into offspring survival, as well as female investment into future reproduction. We show that higher levels of sibling food transfer were associated with lower levels of maternal food provisioning, possibly reflecting a compensatory relationship between sibling cooperation and maternal care. Furthermore, the level of sibling food transfer did not influence offspring survival, but was associated with negative effects on the production of the second and terminal clutch by the tending mothers. These findings indicate that sibling cooperation could mitigate the detrimental effects on offspring survival that result from being tended by low-quality mothers. More generally, they are in line with the hypothesis that sibling cooperation is an ancestral behaviour that can be retained to compensate for insufficient levels of parental investment.

Controls of DSi in streams and reservoirs along the Kaveri River, South India.

There is an increasing body of evidence showing that land use may affect the concentration and flux of dissolved silica (DSi) and amorphous, biogenic Si particles (ASi/BSi) in surface waters. Here, we present a study of riverine waters collected within the Kaveri River Basin, which has a long history of land occupation with +43% population increase in the watershed during the last 30 years associated with agricultural practices including canal irrigation from reservoirs and, more recently, bore well pumping. We report total dissolved solids (TDS) and suspended material (TSM) for 15 river stations and 5 reservoirs along the Kaveri itself and its main tributaries sampled during pre-monsoon, monsoon and post-monsoon periods in 2006 and 2007. The TDS in the Kaveri River globally increases from the upper reaches (humid to sub-humid climate) to the lower reaches (semi-arid climate), and at a given station from monsoon (M) to hot season (HS). The DSi concentrations range from 129 µmol L(-1) (M) to 390 µmol L(-1) (HS) in the main Kaveri stream and reaches up to 686 µmol L(-1) in the Shimsha River (HS). Our results indicate that DSi and the main solutes of the Kaveri River have not drastically changed since the last 30 years despite the population increase. The pollution index of Van der Weijden and Pacheco (2006) ranges from 13% to 54% but DSi does not seem to be affected by domestic wastewater. ASi is mostly composed of diatoms and phytoliths that both play roles in controlling DSi. We suggest that DSi and ASi delivered to the cultivated areas through irrigation from reservoir may have two important consequences: increasing Si bioavailability for crops and limiting Si flux to the ocean.

Effect of silicon on wheat seedlings (Triticum turgidum L.) grown in hydroponics and exposed to 0 to 30 µM Cu.

MAIN CONCLUSION: Aqueous Si limits Cu uptake by a Si-accumulating plant via physicochemical mechanisms occurring at the root level. Sufficient Si supply may alleviate Cu toxicity in Cu-contaminated soils. Little information is available on the role of silicon (Si) in copper (Cu) tolerance while Cu toxicity is widespread in crops grown on Cu-contaminated soils. A hydroponic study was set up to investigate the influence of Si on Cu tolerance in durum wheat (Triticum turgidum L.) grown in 0, 0.7, 7.0 and 30 µM Cu without and with 1.0 mM Si, and to identify the mechanisms involved in mitigation of Cu toxicity. Si supply alleviated Cu toxicity in durum wheat at 30 µM Cu, while Cu significantly increased Si concentration in roots. Root length, photosynthetic pigments concentrations, macroelements, and organic anions (malate, acetate and aconitate) in roots, were also increased. Desorption experiments, XPS analysis of the outer thin root surface (≤100 Å) and µXRF analyses showed that Si increased adsorption of Cu at the root surface as well as Cu accumulation in the epidermis while Cu was localised in the central cylinder when Si was not applied. Copper was not detected in phytoliths. This study provides evidences for Si-mediated alleviation of Cu toxicity in durum wheat. It also shows that Si supplementation to plants exposed to increasing levels of Cu in solution induces non-simultaneous changes in physiological parameters. We propose a three-step mechanism occurring mainly at the root level and limiting Cu uptake and translocation to shoots: (i) increased Cu adsorption onto the outer thin layer root surface and immobilisation in the vicinity of root epidermis, (ii) increased Cu complexation by both inorganic and organic anions such as aconitate and, (iii) limitation of translocation through an enhanced thickening of a Si-loaded endodermis.

Is it possible to improve the breaking bad news skills of residents when a relative is present? A randomised study.

BACKGROUND: Although patients with cancer are often accompanied by a relative during breaking bad news (BBN) consultations, little is known regarding the efficacy of training programmes designed to teach residents the communication skills needed to break bad news in a triadic consultation. METHODS: Residents were randomly assigned to a 40-h dyadic and triadic communication skills training programme (n=48) or a waiting list (n=47). A simulated BBN triadic consultation was audiotaped at baseline, and after training for the training group, and 8 months after baseline for the waiting list group. Transcripts were analysed using content analysis software (LaComm). A coder determined the moment of bad news delivery and the relative's first turn of speech regarding the bad news. A generalised estimating equation was used to evaluate residents' communication skills, BBN timing, and the relative's inclusion in the consultation. RESULTS: Ninety-five residents were included. After training, the duration of the pre-delivery phase was found to be longer for the trained residents (relative risk (RR)=3.04; P<0.001). The simulated relative's first turn of speech about the bad news came more often during the pre-delivery phase (RR=6.68; P=0.008), and was more often initiated by the trained residents (RR=19.17; P<0.001). Trained residents also used more assessment (RR=1.83; P<0.001) and supportive utterances (RR=1.58; P<0.001). CONCLUSION: This study demonstrates that a training programme that focuses on the practice of dyadic and triadic communication skills can improve the communication skills of the participating residents in a BBN triadic consultation. Such a training should be included in resident curriculum.

Inbreeding depression in an insect with maternal care: influences of family interactions, life stage and offspring sex.

Although inbreeding is commonly known to depress individual fitness, the severity of inbreeding depression varies considerably across species. Among the factors contributing to this variation, family interactions, life stage and sex of offspring have been proposed, but their joint influence on inbreeding depression remains poorly understood. Here, we demonstrate that these three factors jointly shape inbreeding depression in the European earwig, Forficula auricularia. Using a series of cross-breeding, split-clutch and brood size manipulation experiments conducted over two generations, we first showed that sib mating (leading to inbred offspring) did not influence the reproductive success of earwig parents. Second, the presence of tending mothers and the strength of sibling competition (i.e. brood size) did not influence the expression of inbreeding depression in the inbred offspring. By contrast, our results revealed that inbreeding dramatically depressed the reproductive success of inbred adult male offspring, but only had little effect on the reproductive success of inbred adult female offspring. Overall, this study demonstrates limited effects of family interactions on inbreeding depression in this species and emphasizes the importance of disentangling effects of sib mating early and late during development to better understand the evolution of mating systems and population dynamics.

Oxygen deficient centers in silica: optical properties within many-body perturbation theory.

The electronic and optical properties of neutral oxygen vacancies, also called oxygen deficient centers (ODC(I)s), have been investigated in pure and germanium doped silica (both amorphous and α-quartz) through first-principles calculations. By means of density functional theory and many-body perturbation theory (GW approximation and the solution of the Bethe-Salpeter equation), we obtain the atomic and electronic structures as well as the optical absorption spectra of pure and Ge-doped silica in the presence of ODCs (SiODC(I)s and GeODC(I)s); our study allows us to interpret and explain the very nature of the optical features in experimental absorption spectra. The theoretical optical absorption signatures of these defects show excellent agreement with experiments for the SiODC(I)s, i.e. two absorption bands arise around 7.6 eV due to transitions between the defect levels. Our theoretical results also explain the experimental difficulty in measuring the GeODC(I) absorption band in Ge-doped silica, which was in fact tentatively assigned to a broad and very weak absorption signature, located between 7.5 and 8.5 eV. The influence of Ge-doping induced disorder on the nature of the defect-related optical transitions is discussed. We find that even if the atomic and electronic structures of SiODC(I) and GeODC(I) defects are relatively similar, the slight network distortion induced by the presence of the Ge atom, together with the increase in the Ge-Si bond asymmetry, completely changes the nature of the optical absorption edge.

When there seem to be no predetermining factors: early child and proximal family risk predicting externalizing behavior in young children incurring no distal family risk.

The main objective of the current study was to examine the impact of two child risk factors, i.e. personality and inhibition, and two proximal family risk factors, i.e. parenting and attachment, and the impact of their cumulative effect on later externalizing behavior among young children incurring no distal family risk. Data were collected in a longitudinal two-wave design from 161 non-referred and referred children aged three to five years at the onset of the study. All of the children were raised in families of middle to high socio-economic status, i.e. their parents were educated to a middle to high level, had access to the job market and lived together as couples. The four risk domains were assessed at the onset of the study, while EB was rated both at the onset of the study and in the 24-month follow-up. Results confirmed that the four risk domains were each both correlates of EB and efficient at discriminating non-referred from referred children; that their combination regardless of their content (cumulative risk) provided a strong prediction of both later EB and non-referred vs referred sample membership. The results are discussed both for research and clinical purposes.