Paris-Sorbonne University

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure or death from cardiovascular causes among patients with stable heart failure. However, the safety and efficacy of SGLT2 inhibitors when initiated soon after an episode of decompensated heart failure are unknown. METHODS: We performed a multicenter, double-blind trial in which patients with type 2 diabetes mellitus who were recently hospitalized for worsening heart failure were randomly assigned to receive sotagliflozin or placebo. The primary end point was the total number of deaths from cardiovascular causes and hospitalizations and urgent visits for heart failure (first and subsequent events). The trial ended early because of loss of funding from the sponsor. RESULTS: A total of 1222 patients underwent randomization (608 to the sotagliflozin group and 614 to the placebo group) and were followed for a median of 9.0 months; the first dose of sotagliflozin or placebo was administered before discharge in 48.8% and a median of 2 days after discharge in 51.2%. Among these patients, 600 primary end-point events occurred (245 in the sotagliflozin group and 355 in the placebo group). The rate (the number of events per 100 patient-years) of primary end-point events was lower in the sotagliflozin group than in the placebo group (51.0 vs. 76.3; hazard ratio, 0.67; 95% confidence interval [CI], 0.52 to 0.85; P<0.001). The rate of death from cardiovascular causes was 10.6 in the sotagliflozin group and 12.5 in the placebo group (hazard ratio, 0.84; 95% CI, 0.58 to 1.22); the rate of death from any cause was 13.5 in the sotagliflozin group and 16.3 in the placebo group (hazard ratio, 0.82; 95% CI, 0.59 to 1.14). Diarrhea was more common with sotagliflozin than with placebo (6.1% vs. 3.4%), as was severe hypoglycemia (1.5% vs. 0.3%). The percentage of patients with hypotension was similar in the sotagliflozin group and the placebo group (6.0% and 4.6%, respectively), as was the percentage with acute kidney injury (4.1% and 4.4%, respectively). The benefits of sotagliflozin were consistent in the prespecified subgroups of patients stratified according to the timing of the first dose. CONCLUSIONS: In patients with diabetes and recent worsening heart failure, sotagliflozin therapy, initiated before or shortly after discharge, resulted in a significantly lower total number of deaths from cardiovascular causes and hospitalizations and urgent visits for heart failure than placebo. (Funded by Sanofi and Lexicon Pharmaceuticals; SOLOIST-WHF ClinicalTrials.gov number, NCT03521934.).

Work on voice sciences over recent decades has led to a proliferation of acoustic parameters that are used quite selectively and are not always extracted in a similar fashion. With many independent teams working in different research areas, shared standards become an essential safeguard to ensure compliance with state-of-the-art methods allowing appropriate comparison of results across studies and potential integration and combination of extraction and recognition systems. In this paper we propose a basic standard acoustic parameter set for various areas of automatic voice analysis, such as paralinguistic or clinical speech analysis. In contrast to a large brute-force parameter set, we present a minimalistic set of voice parameters here. These were selected based on a) their potential to index affective physiological changes in voice production, b) their proven value in former studies as well as their automatic extractability, and c) their theoretical significance. The set is intended to provide a common baseline for evaluation of future research and eliminate differences caused by varying parameter sets or even different implementations of the same parameters. Our implementation is publicly available with the openSMILE toolkit. Comparative evaluations of the proposed feature set and large baseline feature sets of INTERSPEECH challenges show a high performance of the proposed set in relation to its size.

BACKGROUND: In the phase III IMpassion130 trial, combining atezolizumab with first-line nanoparticle albumin-bound-paclitaxel for advanced triple-negative breast cancer (aTNBC) showed a statistically significant progression-free survival (PFS) benefit in the intention-to-treat (ITT) and programmed death-ligand 1 (PD-L1)-positive populations, and a clinically meaningful overall survival (OS) effect in PD-L1-positive aTNBC. The phase III KEYNOTE-355 trial adding pembrolizumab to chemotherapy for aTNBC showed similar PFS effects. IMpassion131 evaluated first-line atezolizumab-paclitaxel in aTNBC. PATIENTS AND METHODS: (days 1, 8, 15), every 28 days until disease progression or unacceptable toxicity. Stratification factors were tumour PD-L1 status, prior taxane, liver metastases and geographical region. The primary endpoint was investigator-assessed PFS, tested hierarchically first in the PD-L1-positive [immune cell expression ≥1%, VENTANA PD-L1 (SP142) assay] population, and then in the ITT population. OS was a secondary endpoint. RESULTS: Of 651 randomised patients, 45% had PD-L1-positive aTNBC. At the primary PFS analysis, adding atezolizumab to paclitaxel did not improve investigator-assessed PFS in the PD-L1-positive population [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.60-1.12; P = 0.20; median PFS 6.0 months with atezolizumab-paclitaxel versus 5.7 months with placebo-paclitaxel]. In the PD-L1-positive population, atezolizumab-paclitaxel was associated with more favourable unconfirmed best overall response rate (63% versus 55% with placebo-paclitaxel) and median duration of response (7.2 versus 5.5 months, respectively). Final OS results showed no difference between arms (HR 1.11, 95% CI 0.76-1.64; median 22.1 months with atezolizumab-paclitaxel versus 28.3 months with placebo-paclitaxel in the PD-L1-positive population). Results in the ITT population were consistent with the PD-L1-positive population. The safety profile was consistent with known effects of each study drug. CONCLUSION: Combining atezolizumab with paclitaxel did not improve PFS or OS versus paclitaxel alone. CLINICALTRIALS.GOV: NCT03125902.

The quality of reporting practice guidelines is often poor, and there is no widely accepted guidance or standards for such reporting in health care. The international RIGHT (Reporting Items for practice Guidelines in HealThcare) Working Group was established to address this gap. The group followed an existing framework for developing guidelines for health research reporting and the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) Network approach. It developed a checklist and an explanation and elaboration statement. The RIGHT checklist includes 22 items that are considered essential for good reporting of practice guidelines: basic information (items 1 to 4), background (items 5 to 9), evidence (items 10 to 12), recommendations (items 13 to 15), review and quality assurance (items 16 and 17), funding and declaration and management of interests (items 18 and 19), and other information (items 20 to 22). The RIGHT checklist can assist developers in reporting guidelines, support journal editors and peer reviewers when considering guideline reports, and help health care practitioners understand and implement a guideline.

This article provides unprecedented direct evidence from large‐scale survey data on both the intensity (how much?) and direction (to whom?) of income comparisons. Income comparisons are considered to be at least somewhat important by three‐quarters of Europeans. They are associated with both lower levels of subjective well‐being and a greater demand for income redistribution. The rich compare less and are happier than average when they do, which latter is consistent with relative income theory. With respect to the direction of comparisons, colleagues are the most frequently‐cited reference group. Those who compare to colleagues are happier than those who compare to other benchmarks.

Musically trained and untrained listeners were required to listen to 27 musical excerpts and to group those that conveyed a similar emotional meaning (Experiment 1). The groupings were transformed into a matrix of emotional dissimilarity that was analysed through multidimensional scaling methods (MDS). A 3-dimensional space was found to provide a good fit of the data, with arousal and emotional valence as the primary dimensions. Experiments 2 and 3 confirmed the consistency of this 3-dimensional space using excerpts of only 1 second duration. The overall findings indicate that emotional responses to music are very stable within and between participants, and are weakly influenced by musical expertise and excerpt duration. These findings are discussed in light of a cognitive account of musical emotion.

As Covid-19 spreads across the world, governments turn a hopeful eye towards research and development of a vaccine against this new disease. But it is one thing to make a vaccine available, and it is quite another to convince the public to take the shot, as the precedent of the 2009 H1N1 influenza illustrated. In this paper, we present the results of four online surveys conducted in April 2020 in representative samples of the French population 18 years of age and over (N = 5018). These surveys were conducted during a period when the French population was on lockdown and the daily number of deaths attributed to the virus reached its peak. We found that if a vaccine against the new coronavirus became available, almost a quarter of respondents would not use it. We also found that attitudes to this vaccine were correlated significantly with political partisanship and engagement with the political system. Attitudes towards this future vaccine did not follow the traditional mapping of political attitudes along a Left-Right axis. The rift seems to be between people who feel close to governing parties (Centre, Left and Right) on the one hand, and, on the other, people who feel close to Far-Left and Far-Right parties as well as people who do not feel close to any party. We draw on the French sociological literature on ordinary attitudes to politics to discuss our results as well as the cultural pathways via which political beliefs can affect perceptions of vaccines during the COVID-19 pandemic.

▪ Abstract Skepticism toward sociology has grown over recent years. The attention granted to rational choice theory (RCT) is, to a large extent, a reaction against this situation. Without doubt, RCT is a productive instrument, but it fails signally in explaining positive nontrivial beliefs as well as normative nonconsequential beliefs. RCT's failures are due to its move to use too narrow a definition of rationality. A model can be developed that combines the advantages of the RCT (mainly providing self-sufficient explanations), without falling victim to its shortcomings. This model is implicitly used in classical and modern sociological works that are considered to be illuminating and valid.

Is there a universal hierarchy of the senses, such that some senses (e.g., vision) are more accessible to consciousness and linguistic description than others (e.g., smell)? The long-standing presumption in Western thought has been that vision and audition are more objective than the other senses, serving as the basis of knowledge and understanding, whereas touch, taste, and smell are crude and of little value. This predicts that humans ought to be better at communicating about sight and hearing than the other senses, and decades of work based on English and related languages certainly suggests this is true. However, how well does this reflect the diversity of languages and communities worldwide? To test whether there is a universal hierarchy of the senses, stimuli from the five basic senses were used to elicit descriptions in 20 diverse languages, including 3 unrelated sign languages. We found that languages differ fundamentally in which sensory domains they linguistically code systematically, and how they do so. The tendency for better coding in some domains can be explained in part by cultural preoccupations. Although languages seem free to elaborate specific sensory domains, some general tendencies emerge: for example, with some exceptions, smell is poorly coded. The surprise is that, despite the gradual phylogenetic accumulation of the senses, and the imbalances in the neural tissue dedicated to them, no single hierarchy of the senses imposes itself upon language.

The European Cooperation in Science and Technology (COST) provides an ideal framework to establish multi-disciplinary research networks. COST Action BM1203 (EU-ROS) represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better understanding redox biology and medicine and, in the long run, to finding new therapeutic strategies to target dysregulated redox processes in various diseases. This report highlights the major achievements of EU-ROS as well as research updates and new perspectives arising from its members. The EU-ROS consortium comprised more than 140 active members who worked together for four years on the topics briefly described below. The formation of reactive oxygen and nitrogen species (RONS) is an established hallmark of our aerobic environment and metabolism but RONS also act as messengers via redox regulation of essential cellular processes. The fact that many diseases have been found to be associated with oxidative stress established the theory of oxidative stress as a trigger of diseases that can be corrected by antioxidant therapy. However, while experimental studies support this thesis, clinical studies still generate controversial results, due to complex pathophysiology of oxidative stress in humans. For future improvement of antioxidant therapy and better understanding of redox-associated disease progression detailed knowledge on the sources and targets of RONS formation and discrimination of their detrimental or beneficial roles is required. In order to advance this important area of biology and medicine, highly synergistic approaches combining a variety of diverse and contrasting disciplines are needed.

"This book searches for the sources and means for a disciplined practical approach to exploring human experience. The spirit of this book is pragmatic and relies on a Husserlian phenomenology primarily understood as a method of exploring our experience. The authors do not aim at a neo-Kantian a priori 'new theory' of experience but instead they describe a concrete activity: how we examine what we live through, how we become aware of our own mental life."--BOOK JACKET.

Behçet's disease (BD) is a multisystem, chronic-relapsing, inflammatory disorder classified among the vasculitides [ 1 , 2 ]. It has a worldwide distribution being more prevalent in the Middle East, Far East and the Mediterranean basin [ 3 ]. The diagnosis is entirely based on clinical grounds since no pathognomonic laboratory findings exist. International study group classification criteria used for BD patients participating in research protocols depend on the presence of recurrent oral ulceration plus any two of the following: recurrent genital ulcerations, ocular lesions (anterior or posterior uveitis, or cells in the vitreous on slit lamp examination, or retinal vasculitis), typical skin lesions (erythema nodosum, pseudofollicullitis) and a positive pathergy (skin hyperreactivity) test [ 4 , 5 ]. The clinical picture of BD is diverse and while recurrent mucocutaneous lesions are usually the only symptoms at the onset of the disease, most patients develop ocular and/or articular, vascular, central nervous system and gastrointestinal inflammation later on. Vital organ involvement may lead, despite treatment, not only to severe morbidity but also to increased mortality especially among young males [ 1 , 2 , 6 ]. Adequately powered, randomized, controlled clinical trials are few in BD. This is especially true for the use of anti-tumour necrosis factor (TNF) agents, which reportedly result in impressive remissions in BD patients, especially in those with manifestations refractory to conventional treatments. During the last 6 yrs, over 70 publications have appeared in the English literature suggesting that inhibition of TNF actions, using mainly the anti-TNF monoclonal antibody infliximab, is a promising therapeutic approach for this disease. However, the current evidence of therapeutic efficacy is low grade, and there is only one randomized trial available, which assessed the effects of the soluble TNF receptor etanercept in mucocutaneous manifestations and found it to be very effective [ 7 ]. An expert panel meeting was held in May 2006, in order to review the currently available treatment options for BD and the unmet medical needs for those patients with severe disease, and to develop a consensus on the positioning of anti-TNF agents in their treatment. Clinical scientists who have contributed with relevant publications and physicians with specific expertise in BD management participated in the discussion, aiming: (i) to assess the available information on the efficacy of anti-TNF therapies, alone or in combination therapy with currently used regimens, in the treatment of BD; and (ii) to formulate recommendations for optimal use of anti-TNF agents in these patients, filling gaps in evidence with their expert opinion. An extended summary of the discussion and the conclusions reached is presented herein, intended to help physicians in their practice with BD patients. These recommendations do not constitute treatment guidelines but aim to improve the uniformity of clinical practice in the management of BD, until higher grades of evidence are obtained. Several effective anti-inflammatory and immunosuppressive regimens for BD currently exist, but none results in disease cure [ 1 , 2 , 8 , 9 ]. Moreover, the long-term use of these regimens can be associated with significant adverse effects, especially in those patients in whom treatment is introduced at a young age [ 8 , 9 ]. Physicians taking care of patients with BD should be aware that the disease is intermittent in its manifestations in the majority of patients, and that symptoms vary both in their recurrence rate and healing time; accordingly, the therapeutic approach should be strictly individualized. Although the course of BD is unpredictable, spontaneous remissions often occur and the disease may even burn out in some patients with time [ 6 ]. Still, a significant proportion of patients may suffer a progressive disease course resulting eventually in permanent organ damage [ 1 , 6 , 9 ]. No prognostic criteria to identify these patients exist, although there is evidence that young men are at higher risk in general [ 6 ], particularly with respect to losing useful vision, or developing vascular and neurological manifestations [ 10 ], than women. Moreover, there are no established criteria to define the subgroup of patients with severe BD. However, most physicians consider that patients with vital organs at threat, mainly with ocular, parenchymal, neurological and major vascular involvement have severe disease. In addition, some patients with chronic articular and mucocutaneous manifestations, which significantly impair their quality of life, can also be classified as having severe disease. Controlled studies have shown that colchicine [ 11 ], thalidomide [ 12 ], dapsone [ 13 ], azathioprine [ 14 ], interferon-alpha [ 15 ] and etanercept [ 7 ] are effective to some degree in treating various mucocutaneous manifestations in patients who are not intolerant to these drugs. However, refractory, relapsing oral and genital ulcers are associated with marked physical and psychological morbidity in some patients, while oropharyngeal ulcers are frequently resistant to conventional treatment modalities and even life-threatening pharyngeal stenosis may rarely occur [ 16 ]. Scarring of deep vaginal ulcers, in which corticosteroids are not always effective [ 17 ], may lead to bladder or urethral fistulae. Vulval ulcerations occasionally may lead to labial destruction, while other cutaneous vasculitic lesions, namely Sweet's syndrome-like and pyoderma gangrenosum-like lesions, may also cause severe morbidity [ 16 ]. In contrast to available data for the management of mucocutaneous manifestations, similar data are more sparse in patients with vital organs at threat, such as eye or central nervous system. In these cases, combinations of high doses of corticosteroids and immunosuppressive drugs, including methotrexate, ciclosporin A (up to 10 mg/kg), azathioprine (up to 3 mg/kg), chlorambucil, or cyclophosphamide may be used, albeit not always successfully [ 8 , 9 , 18–20 ]. Importantly, in a 2-yr, randomized, placebo-controlled, double-blind study, restricted to male patients, in those enrolled in the study without eye involvement, azathioprine was significantly better than placebo in preventing the development of ocular disease [ 14 ]. In this study, azathioprine was also effective in those patients with eye disease at enrolment by reducing steroid requirements, maintaining visual acuity and reducing the number of hypopyon attacks [ 14 ]. A follow-up study of these patients 8 yrs later showed that early treatment with this agent was also efficacious in ocular disease at long term [ 21 ]. These results imply that continuous immunosuppressive therapy may control and perhaps, change the course of BD in some patients. The goal of management should be the initiation of an effective treatment as early as possible to avoid recurrences and irreversible damage to vital organs. With respect to sight-threatening ocular involvement, the first aim must be the effective and rapid suppression of intraocular inflammation to avoid development of permanent lesions in the retina and optic disc and second, the prevention, or decrease in the frequency and severity, of recurrent eye attacks. Two decades ago, 73% of patients with ocular disease developed permanent loss of vision within an average time of 3.5 yrs [ 22 ]. This risk has been significantly reduced in the 1990s, following the introduction of immunosuppressive regimens (azathioprine, cyclosporine, interferon-alpha, in combination or as monotherapy), which have improved the prognosis of ocular disease remarkably [ 6 , 8 , 9 ]. Despite this progress, many patients are intolerant to long-term use of these regimens, while corticosteroids, the mainstay of treatment for intraocular inflammation, frequently lead to important co-morbidities during chronic use, such as cataract formation and glaucoma, as well as to systemic side effects [ 8 , 9 ]. Clearly, the ideal immunosuppressive regimen for patients with severe BD should be not only effective but also safe for long-term use. Accumulating experience on two emerging therapeutic approaches, namely interferon-alpha [ 23–25 ] and anti-TNF agents [ 25 , 26 ] is currently available and justifies optimism for a better outcome of patients with severe BD. The anti-TNF monoclonal antibodies infliximab and adalimumab, and the soluble TNF receptor etanercept are widely used in the therapy of rheumatoid arthritis, spondyloarthropathies, Crohn's disease and psoriasis with an acceptable safety profile. A better understanding of the pleiotropic actions of TNF in chronic inflammatory conditions [ 27–29 ], as well as initial evidence implicating TNF in disease pathogenesis [ 31–33 ], has prompted trials of anti-TNF agents in patients with BD. The published experience summarized subsequently is derived mostly from independent investigator-initiated trials and uncontrolled case-series, involving about 300 patients with severe disease manifestations. Whilst non-randomized data should be interpreted with caution, in the vast majority of these patients the therapeutic response to anti-TNF treatment has been considered favourable. Of the reported patients with BD who have received anti-TNF agents so far, about 90% have been treated with infliximab, mostly for eye disease, given in parallel to concomitant therapy. Initially, to test the hypothesis that TNF may play a role in BD-associated ocular inflammation, three patients who developed sight-threatening panuveitis despite intensive immunosuppressive therapy were treated with a single infusion of infliximab (5 mg/kg) in addition to their immunosuppressive therapy, which was increased to maximum doses. A rapid and effective suppression of ocular inflammation, i.e. within the first 24 h following the infliximab infusion, was evident in these patients, as well as in two additional patients without increasing concomitant systemic therapy [ 34 ]. Such gratifying and rapid results in sight-threatening panuveitis were also reported in additional uncontrolled case series [ 35–45 ]. In general, anterior segment inflammation resolved faster than vitritis and retinal infiltrates, while retinal vasculitis healed within 2 weeks in the majority of patients. Infliximab was also successful in sporadic BD patients with scleromalacia perforans [ 46 ] and choroidal neovascular membrane [ 47 ]. Chronic cystoid macular oedema, one of the most treatment-resistant lesions complicating chronic ocular inflammation, has also been reported to be responsive to a single infliximab infusion in some patients with BD [ 48 ]. The long-term effects of repetitive infliximab infusions (used at a dose of 5 mg/kg, every 8 weeks in 33 of 41 patients in total) in preventing ocular relapses, maintaining visual acuity and the ability to taper immunosuppressive therapy in patients who were unresponsive or intolerant to standard immunosuppressive treatment, were evaluated in three independent, open-label, prospective, self-controlled studies [ 49–51 ]. It should be noted that two of these studies used historical data from retrospective review of charts but all patients had a pre-defined follow-up period that allowed for reporting the incidence of relapses and the final visual acuity [ 52 ]. In the first study, the mean number of ocular attacks in 15 patients during the previous 32 weeks was 2.5. Ocular disease went into complete remission during the following 32 weeks of continuous infliximab infusions in 60% of patients. Overall, the number of relapses during infliximab therapy decreased by 5-fold. Old, atrophic retinal lesions were not affected. The visual acuity in 25 relapsed eyes increased significantly from 0.1 at baseline to 0.4 at 32 weeks [ 49 ]. In 13 Japanese patients who were resistant to ciclosporin, the mean number of relapses, based on their frequency per 14 weeks, decreased from 3.96 to 0.98 and from 3.79 to 0.16, for those patients treated for 14 weeks with 5 mg/kg or 10 mg/kg of infliximab, respectively [ 50 ]. Similarly, in 13 Turkish patients who were relapsing despite treatment with the combination of azathioprine, ciclosporin and corticosteroids, the mean number of uveitis attacks during 6 months prior to infliximab decreased significantly during the 22-week infliximab infusion period [ 51 ]. In the majority of these patients [ 49–51 ], as well as in additional case-series [ 34–45 ] an immunosuppressive therapy sparing effect of infliximab was evident. In view of the paucity of effective and fast-acting therapies, these results led to the suggestion that infliximab is probably the best currently available treatment for BD patients with acute sight-threatening ocular inflammation [ 53 ]. It should be noted, however, that due to the lack of data it is not possible to at that infliximab has a faster effect in acute ocular inflammation than ciclosporin, or Infliximab was also efficacious in manifestations, such as oral and genital ulcers and/or in the majority of patients in three self-controlled studies [ 49–51 ]. case series and case that patients with severe mucocutaneous lesions rapid and to infliximab [ ], mostly using 5 mg/kg, or 3 patients with ulcers unresponsive [ ] and/or intolerant [ ] to conventional for the first time in all patients were resistant to conventional and were treated with infliximab alone [ , ] or as an therapy [ , , , ]. is only one in which developed during treatment with infliximab [ ]. In addition, effects of infliximab have been reported in sporadic patients with [ , , , ], as well as with severe gastrointestinal involvement [ ]. there is very published evidence [ ] and data [ 70 ] suggesting that infliximab is effective for patients with central nervous system involvement refractory to and No data in patients with vascular or of a single with in whom of infliximab was [ ]. In a study of male patients with BD, [ 7 ] reported that etanercept for 4 was effective in most mucocutaneous The had a effect on oral ulcers and lesions, and the response was evident as early as the first of the patients etanercept were of oral ulcers at the of the study with of the placebo the of lesions was evident in and of patients the and the decreased the number of genital ulcers and during the treatment the was not of the and the of these manifestations during the study a have these the other etanercept not the skin pathergy and the cutaneous response to which were the of the developed in some patients three months etanercept was During the follow-up more patients in the placebo group were to control disease No data were reported from this study on the efficacy of etanercept in eye involvement [ 7 ]. In other rapid of severe mucocutaneous manifestations [ , , ] and [ ] were noted following etanercept treatment, while who to to to infliximab treatment with rapid of ulcers and and marked in and [ ]. was also given to two with BD-associated A response was noted in the but not in the The a response following treatment with infliximab [ ]. data and that is effective in BD. [ ] reported BD patients with uveitis, on infliximab who were to therapy. of recurrence of uveitis, the outcome of this with The safety anti-TNF agents disease, and [ , ]. or long-term of infliximab was well in all BD patients published so The reported side effects were and not of therapy. However, two patients developed psoriasis [ ], two patients developed [ , 50 ] and one developed vitreous which not of infliximab [ ]. Moreover, formation of various which to be [ , 50 , ]. Importantly, ocular side effects such as cataract or in intraocular as well as of central nervous system or vascular have not been reported in patients with BD It is that not all patients with BD should be treated with anti-TNF agents, randomized trials that this approach is to current in of efficacy and management should be on the treatment of the most severe and the of therapy with the efficacy of a given physicians may to anti-TNF treatment in patients 1 as an therapy, with for The recommendations for optimal use presented on of patients, of anti-TNF agents, and treatment is given on the use of infliximab in patients with sight-threatening ocular disease. These recommendations be in the based on emerging for the of anti-TNF agents in BD a A single infusion of 5 300 three infusions of 5 mg/kg, at 4 and subsequently every weeks for to 2 25 for to 2 for the of anti-TNF agents in BD a A single infusion of 5 300 three infusions of 5 mg/kg, at 4 and subsequently every weeks for to 2 25 for to 2 for patients for anti-TNF treatment of BD should (i) a diagnosis of BD; (ii) presence of disease, including of previous of that have a efficacy in BD manifestations, or with low dose corticosteroids to dose presence of or to these conventional of to anti-TNF treatment. the first three criteria usually to the severe disease subgroup and are to from anti-TNF therapy. Although no established criteria to define the subgroup of those patients with severe BD exist, patients with two or more relapses of posterior uveitis or panuveitis per patients with low visual acuity due to chronic cystoid macular oedema, or patients with central nervous system disease this patients with inflammation, chronic and/or mucocutaneous manifestations significantly the quality of also from anti-TNF treatment. Although patients with major involvement are also considered as having severe disease with an increased not data are available about the efficacy of anti-TNF agents in this 1 anti-TNF agents have not been with other in controlled trials in any disease. evidence that the anti-TNF monoclonal antibodies and the soluble TNF receptor etanercept have efficacy in the treatment of rheumatoid [ ], but their efficacy is in Crohn's disease [ ], and in uveitis associated with other [ , ]. this etanercept had no significant efficacy over placebo in preventing uveitis relapses in patients with uveitis controlled by [ ]. The only randomized trial in BD that etanercept was efficacious in mucocutaneous disease [ 7 ]. data that infliximab be efficacious in severe mucocutaneous manifestations as there is a general that infliximab may be a better than etanercept in severe BD. A of infliximab infusion of 5 mg/kg) over etanercept is its onset of which is considered to be in case of sight-threatening ocular disease [ , ]. a efficacy of infliximab over etanercept true for disease manifestations due to the paucity of experience with is for anti-TNF therapy a baseline clinical should be to and disease, as well as for with as a first treatment should be in with an immunosuppressive to to disease control a remission is of an anti-TNF agent as an therapy, an decrease of the dose of concomitant immunosuppressive is not should follow-up at and of a remission should lead to in concomitant most in the of a the of the anti-TNF agent or the concomitant immunosuppressive may be Such a should be strictly individualized. in the three studies using repetitive infliximab infusions every 8 weeks, there were BD patients who relapsed the infliximab infusion [ 49–51 ], suggesting that infusions are for some patients to as also in other in which infliximab has been of antibodies infliximab in long-term treated patients may be associated with reduced of response to treatment [ 50 ], as in patients with [ ] or Crohn's disease [ ]. the of TNF is important to long-term especially in patients with a inflammatory disease course such as BD. the use of anti-TNF agents in patients with acute ocular inflammation, the available evidence and expert the following: anterior uveitis is usually treated with therapy In posterior uveitis with significant of visual acuity as well as in those with inflammation of the macular an of or a single infusion of infliximab, 5 mg/kg, may be to other a rapid of inflammation is In of posterior eye segment inflammation, high doses of corticosteroids are used by a single infusion of infliximab be used as a agent to a with the initiation of an immunosuppressive the suppression of ocular inflammation is immunosuppressive such as ciclosporin, or azathioprine, with can be used long-term to control recurrent attacks. can also be an treatment. In the of addition of azathioprine to ciclosporin, or may be a However, the ocular disease a combination of these immunosuppressive regimens with repetitive infusions of infliximab 5 mg/kg every weeks for to 2 should be It should be noted that there are no data continuous use of infliximab as In some patients efficacy of infliximab may with its use, the may to be decreased with to a patients with an or to infliximab can be to anti-TNF agent is since current experience is [ , ]. and of anti-TNF agents, namely acute and chronic or disease, and have been [ , ]. BD patients with mucocutaneous ulcers may an increased risk of is [ 16 ]. the distribution of BD in the an increased risk of with anti-TNF agents be in This risk be especially important for those patients with sight-threatening posterior uveitis who have no time for a it is that any with BD, who is to immunosuppressive and/or corticosteroids, should a for and be to the guidelines [ ]. are in of infusions of infliximab, but using treatment protocols these are in all [ , ]. anti-TNF therapy, it is important to information to the on the and of such treatment and to patients as as possible into the The published evidence on the use of anti-TNF agents in BD mainly of of the use of infliximab, evaluated as an therapy. The majority of patients from posterior segment ocular inflammation, controlled with available immunosuppressive therapy. With infliximab, a therapeutic effect was in patients with sight-threatening inflammation, including patients with retinal The paucity of effective and fast-acting particularly for patients with eye disease the of these by three independent, open-label, prospective, self-controlled repetitive infliximab infusions were also effective in preventing ocular relapses, maintaining visual acuity and immunosuppressive therapy in the majority of patients who had an response or were intolerant to conventional therapy. Infliximab was effective for manifestations in these patients, as well as in other patients with ulcers, arthritis, or central nervous system involvement and in a single with With use, there were no side effects The only randomized controlled trial was a study of etanercept in patients with mucocutaneous manifestations. was for most of these manifestations, but no data are at from this study on eye agents have a number of including of adverse and high However, based on the available physicians may to anti-TNF therapy to patients with BD. However, until results from powered, randomized controlled clinical trials are available, TNF agents should be used with only for patients with severe disease. with two or more relapses of posterior uveitis per low visual acuity due to chronic cystoid macular oedema, or disease and/or patients with inflammation, or and mucocutaneous manifestations that significantly the quality of life, this to the experience so far, infliximab to be more efficacious than etanercept in disease manifestations other than mucocutaneous or involvement, while data on are very Infliximab or etanercept is as an therapy for patients with BD, who are refractory or intolerant to immunosuppressive Moreover, a single infusion of infliximab (5 mg/kg), can be used as a agent for posterior eye segment inflammation, the of response is considered to be to retinal lesions and permanent visual In those ocular relapses are not controlled by azathioprine and/or ciclosporin, a therapy with infliximab at the dose of 5 mg/kg every weeks be used for to 2 no relapses occur These recommendations do not constitute treatment guidelines but are intended to improve practice uniformity and to help physicians in the management of BD patients, until higher grades of evidence are The expert panel meeting was by the and by an to by and for of has received for given at by all in Infliximab was in for the treatment of disease with refractory which not to conventional

Abstract Rationale Frontline healthcare providers (HCPs) during the coronavirus disease (COVID-19) pandemic are at high risk of mental morbidity. Objectives To assess the prevalence of symptoms of anxiety, depression, and peritraumatic dissociation in HCPs. Methods This was a cross-sectional study in 21 ICUs in France between April 20, 2020, and May 21, 2020. The Hospital Anxiety and Depression Scale and the Peritraumatic Dissociative Experience Questionnaire were used. Factors independently associated with reported symptoms of mental health disorders were identified. Measurements and Main Results The response rate was 67%, with 1,058 respondents (median age 33 yr; 71% women; 68% nursing staff). The prevalence of symptoms of anxiety, depression, and peritraumatic dissociation was 50.4%, 30.4%, and 32%, respectively, with the highest rates in nurses. By multivariable analysis, male sex was independently associated with lower prevalence of symptoms of anxiety, depression, and peritraumatic dissociation (odds ratio of 0.58 [95% confidence interval, 0.42–0.79], 0.57 [95% confidence interval, 0.39–0.82], and 0.49 [95% confidence interval, 0.34–0.72], respectively). HCPs working in non–university-affiliated hospitals and nursing assistants were at high risk of symptoms of anxiety and peritraumatic dissociation. Importantly, we identified the following six modifiable determinants of symptoms of mental health disorders: fear of being infected, inability to rest, inability to care for family, struggling with difficult emotions, regret about the restrictions in visitation policies, and witnessing hasty end-of-life decisions. Conclusions HCPs experience high levels of psychological burden during the COVID-19 pandemic. Hospitals, ICU directors, and ICU staff must devise strategies to overcome the modifiable determinants of adverse mental illness symptoms.

This book searches for the sources and means for a disciplined practical approach to exploring human experience. The spirit of this book is pragmatic and relies on a Husserlian phenomenology primarily understood as a method of exploring our experience. The authors do not aim at a neo-Kantian a priori ‘new theory’ of experience but instead they describe a concrete activity: how we examine what we live through, how we become aware of our own mental life. The range of experiences of which we can become aware is vast: all the normal dimensions of human life (perception, motion, memory, imagination, speech, everyday social interactions), cognitive events that can be precisely defined as tasks in laboratory experiments (e.g., a protocol for visual attention), but also manifestations of mental life more fraught with meaning (dreaming, intense emotions, social tensions, altered states of consciousness). The central assertion in this work is that this immanent ability is habitually ignored or at best practiced unsystematically, that is to say, blindly. Exploring human experience amounts to developing and cultivating this basic ability through specific training. Only a hands-on, non-dogmatic approach can lead to progress, and that is what animates this book. (Series B)

Sociology and economics tend to focus more and more on the intermediaries involved in economic and social relations, in the shape of distributors, matchmakers, consultants, and evaluators. Once they are distinguished according to their forms, their types of intervention and their effects, the intermediaries are a helpful category in order to study the social organization of markets as well as the changes that operate on them, especially regarding the social and economic values of goods, individuals and organizations. We discuss in the first section the link between intermediaries and information, through an analysis of the functions they fulfill that may explain their emergence, as well as the opportunistic behavior of intermediaries in relation to information flows. In the second section, we adopt a more pragmatist perspective on issues of valuation mainly based on “economics of convention”, which emphasizes the collective dynamics of valuation. We show how intermediaries contribute to de!ne valuation through their different activities and foster valuation frames that can improve the coordination of actors, but also reorganize the markets in different ways. We suggest an analytical distinction between the distribution, the temporality and the generality of the frames, and raise the issue of the valuation power of market intermediaries, their legitimation and the eventual regulation of their activities.

Abstract. How does the income of others affect my own welfare? This survey of the empirical literature stresses the contribution of subjective data to the understanding of this issue, with an attempt to disentangle direct effects (preference interdependence) from indirect informational effects. It shows that perceived mobility is central to the link between other people's income and individual satisfaction, as it determines individual opportunities and risks. Agents also appreciate the egalitarian nature of mobility itself, so that individual welfare depends on dynamic inequality rather than static income distribution. These studies illustrate how subjective data can bring information on aspects of utility and social interactions that are beyond the scope of the method based on action-revealed preferences.

The self-non-self theory has dominated immunology since the 1950s. In the 1990s, Matzinger and her colleagues suggested a new, competing theory, called the "danger theory." This theory has provoked mixed acclaim: enthusiasm and criticism. Here we assess the danger theory vis-à-vis recent experimental data on innate immunity, transplantation, cancers and tolerance to foreign entities, and try to elucidate more clearly whether danger is well defined.

Cahier ; 2004-004

BACKGROUND: Stenting of the intracranial venous sinuses is used as a treatment in certain cases of idiopathic intracranial hypertension (IIH). Interest in, and experience of, this technique is growing, particularly in recent years. We sought to provide an updated systematic review and meta-analysis of the use of venous stenting in these patients, examining clinical outcomes. METHODS: A literature search of venous stenting in IIH patients was performed. Using random-effects meta-analysis, we evaluated the following outcomes: clinical resolution of papilledema; headaches and pulsatile tinnitus; recurrence of symptoms after stenting; and complications. RESULTS: . Median follow-up was 18 months. The overall rate of improvement in papilloedema was 93.7% (95% CI 90.5% to 96.9%), while the overall rate of improvement or resolution of headache was 79.6% (95% CI 73.3% to 85.9%). Pulsatile tinnitus resolved in 90.3% (95% CI 83.8% to 96.70%), while the overall rate of recurrence of IIH symptoms after stenting was 9.8% (95% CI 6.7% to 13%). The rate of major complications was 1.9% (95% CI 0.07% to 3.1%). CONCLUSIONS: Venous sinus stenting in patients with IIH who are refractory to medical therapy appears to have an excellent safety profile and is associated with significant improvements in headaches, pulsatile tinnitus, and papilledema.

The unique features of gamma-delta (γδ) T cells, related to their antigen recognition capacity, their tissue tropism, and their cytotoxic function, make these cells ideal candidates that could be targeted to induce durable immunity in the context of different pathologies. In this review, we focus on the main characteristics of human γδ T-cell subsets in diseases and the key mechanisms that could be explored to target these cells.