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Purpose: Genital lymphedema is a chronic debilitating condition associated with highly impaired health-related quality of life (QoL). This prospective multi-center study evaluated the use of a new compressive garment in patients with secondary and primary genital lymphedema. Methods: 32 patients prospectively enrolled were advised to wear the compressive garment for 12 weeks (day and night). The primary endpoint was change in patient-reported QoL at 12 weeks via the patient global impression of change (PGI-C) instrument. Secondary outcomes included change in other QoL measures at 12 weeks (VAS, LyQLI and EQ-5D questionnaires), lymphedema severity (Genital Lymphedema Score (GLS)) and physician assessment (Clinical Global Impression- Improvement (CGI-I)). Safety and tolerability were also assessed. Results: After 12 weeks, improvement was reported in 78.6% of patients (PGI-C). Physician assessment (CGI-I) indicated clinical improvement in 82.8% of patients. Patient assessment of lymphedema symptoms showed a significant decrease in discomfort (p = 0.02) and swelling (p = 0.01). Significant declines in mean global GLS scores (p < 0.0001), and in the proportion of patients reporting heaviness, tightness, swelling or urinary dysfunction (p < 0.05 for all) were also observed. LyQLI scores decreased (indicating improved QoL) in each of the physical, psychosocial (p = 0.05) and practical domains. The compressive garment was well tolerated with high compliance and adverse events (due to swelling or discomfort) led to permanent discontinuation in only 3 patients. Conclusions: Use of a new genital compression garment over 12 weeks improves QoL and clinical measures in patients with genital lymphedema (NCT04602559; Registration: 10/20/2020).

La periode de sept mois et demi durant laquelle l’Academie royale des sciences s’est formee concretement demeure mal connue. Les activites accomplies alors au sein de l’organisation naissante ont ete particulierement negligees par les historiens. En s’appuyant notamment sur le premier cahier de travail parisien de Huygens, cet article montre que toute une serie d’ecrits academiques jusqu’ici mal dates relevent en fait de la periode de formation de l’institution. A partir d’une documentation largement renouvelee, il presente ensuite pour la premiere fois dans leur veritable succession chronologique et dans le contexte des principales etapes organisationnelles les travaux academiques de cette periode tels qu’ils apparaissent desormais.

Développer les compétences langagières des élèves par l’utilisation des images en maternelle peut paraitre évident, leur utilisation est systématique dans tous les domaines d’apprentissage. Mais on se rend compte assez rapidement que leur discours varie en fonction du regard qu’ils portent sur l’image en elle-même : description globale, description d’un élément marquant, évocation personnelle, interprétation... À une question précise de l’enseignant, on peut obtenir dix réponses complètement différentes en fonction de ce que les élèves regardent ou perçoivent dans l’image. Ne pourrait-on pas « organiser » ce regard et par la même occasion, faire évoluer le niveau de langage vers plus de précision ? Apprendre à déchiffrer une image, comme on déchiffre un texte pour le comprendre, c’est aussi réfléchir à comment elle a été fabriquée, c’est chercher un détail parmi un ensemble pour y déceler un indice, et c’est surtout comprendre ce que l’auteur a délibérément voulu faire passer comme message grâce à des procédés techniques. Rendre explicite les messages que l’artiste ou l’auteur veut véhiculer, nécessite un décentrement, une prise de recul qui n’est pas forcément possible à tout âge. Les élèves de moyenne section de maternelle en ont-ils la capacité ?

Autotaxin is a circulating enzyme with a major role in the production of lysophosphatic acid (LPA) species in blood. A role for the autotaxin/LPA axis has been suggested in many disease areas including pulmonary fibrosis. Structural modifications of the known autotaxin inhibitor lead compound 1, to attenuate hERG inhibition, remove CYP3A4 time-dependent inhibition, and improve pharmacokinetic properties, led to the identification of clinical candidate GLPG1690 (11). Compound 11 was able to cause a sustained reduction of LPA levels in plasma in vivo and was shown to be efficacious in a bleomycin-induced pulmonary fibrosis model in mice and in reducing extracellular matrix deposition in the lung while also reducing LPA 18:2 content in bronchoalveolar lavage fluid. Compound 11 is currently being evaluated in an exploratory phase 2a study in idiopathic pulmonary fibrosis patients.

BACKGROUND—Flu vaccination in otherwise healthy infants and young children is important to prevent severe disease, as well as to control epidemic spread of influenza infection. AIMS—To examine the safety and immunogenicity of a paediatric presentation of a purified, inactivated, triton split influenza vaccine. METHODS—Two doses of the vaccine, provided in prefilled syringes of 0.25 ml, were administered, one month apart, to 67 children under 3 years of age. RESULTS—Nine cases of immediate reaction to vaccination (macules/papules) were observed after the second injection only. During the study period, 9% of children experienced at least one delayed local reaction, and 28% of children presented at least one systemic reaction. Almost all reactions were mild and transient. Immunogenicity results surpassed the European Community recommendations for a 0.50 ml dose of vaccine in adults. CONCLUSION—This paediatric formulation of inactivated flu vaccine appears safe and immunogenic in children from 6 months to 3 years of age; the convenient presentation in a prefilled syringe of 0.25ml volume will facilitate administration of the dose recommended for young children.

This research concerns the development of an Negotiation Support Systems (NSS) based on a multi-criteria conceptual framework of the negotiation and developed according to a multi-agent architecture from Distributed Artificial Intelligence (DAI). A first prototype of such a system, NegocIAD, has already been developed [8], but the weakness of its assistance to the negotiation process have led us to revise the conceptual framework in order to define a more relevant assistance to the negotiation process. This paper presents this new conceptual framework defined in order to develop a new prototype. First, we point out the originality of our multi-criteria and multi-agent approach, the general architecture and the limitations of NegocIAD. Then we present the new multi-criteria conceptual framework mainly based on the definition and the use of projection plans (group Gaia plans) emerging from principal component analysis (PCA) already proposed in a single decision maker context in extension of the Promethee method. In the next part, we develop the possible levels of use of these plans during the negotiation process and the type of assistance provided to the mediator. This assistance is mainly based on the elaboration and the interpretation of group Gaia plans for which we propose a set of interpretation rules and the outline of a method to make use of these rules for a relevant support to the mediator in the management of the negotiation process. Finally, we conclude on the perspectives of our future researches and developments for the new generation of our prototype in a multi-agent architecture context.

Resume Trois etudes comparatives en double aveugle ont ete effectuees chez des professionnels de sante, des collegiens et d'anciens malades tuberculeux. Chaque sujet recevait une dose de chacune des deux tuberculines (RT 23 de reference OMS 2 UT, et PPD Merieux 10 UI) par voie intradermique, et etait donc son propre temoin. Les reactions ont ete observees a la 72e heure, et ont ete releves les effets secondaires locaux et generaux. La tuberculine Merieux 10 UI donne lieu a des reactions prurigineuses 2 a 3 fois plus frequemment que la tuberculine RT 23 2 UT. Le diametre moyen d'induration est en moyenne plus important, et le pourcentage de sujets a reaction negative (

*† ‡ An experimental investigation was conducted to determine the effect of adding serrated edges to straight cavities at a freestream Mach number of 2. The investigation used pressure sensitive paint (PSP) and unsteady pressure measurements to investigate the cavity flow field. The length to depth ratio (l/d) of the cavity was 8. This paper describes the PSP measurements, which were conducted for a range of Reynolds numbers for both straight edge cavities and those with the addition of serrations to the leading and trailing edges. The experimental technique, which used commercial PSPs and in-situ calibrations to account for spatial non-uniformities in illumination and temporal non-uniformities in surface temperature, is described in detail. While subtle differences were observed in the cavity flow field and in the measured surface pressure distributions, the leading and trailing edge modifications were not observed to have a significant effect.

A total of 1290 patients (Pts) undergoing general surgery were enrolled in a randomized, multicentre double-blind study in order to investigate the efficacy and safety of two different doses of a low molecular weight heparin (LMWH) (Logiparin) for the prevention of deep vein thrombosis. Patients were randomized to either 5,000 IU unfractionated heparin twice daily, 2,500 anti-Xa or 3,500 anti-Xa units of Logiparin once daily. Each treatment was given subcutaneously two hours before surgery and continued for seven to ten days. All coagulation tests were performed blindly in a core laboratory. Blood samples were collected before surgery and then 3 hours after injection on Day 3 and 5 after surgery. Anti-Xa amidolytic activities were significantly higher in the two LMW Heparin groups than in the unfractionated heparin group (mean peak levels +/- s.e.m. on Day 3: 0.097 +/- 0.004; 0.152 +/- 0.004 and 0.034 +/- 0.003 IU respectively). As expected a significant correlation was observed between anti-Xa activity and the dose of LMW Heparin injected. The correlation coefficient was higher when the doses were expressed in anti-Xa units/kg body weight. However, the body weight accounts for only 16% of the interindividual variability of anti-Xa activity. Therefore, there is no clear evidence to suggest that weight-adjusted doses should be recommended when this LMW Heparin is used as prophylactic treatment in general surgery. A weak negative correlation was found between anti-Xa activity and thrombosis as demonstrated by a positive radiolabelled fibrinogen uptake test and confirmed by positive phlebography. No significant correlation was demonstrated between anti-Xa activity and the occurrence of postoperative bleeding.

A total of 1290 patients were enrolled in a randomized multicentre double blind study in order to investigate the use of two doses of a new low molecular weight heparin, Logiparin®, in the prevention of deep vein thrombosis (DVT) in general surgery. Patients who were included had no contraindication to heparin therapy and had at least one of the recognized risk factors for DVT. Patients were randomized to receive unfractionated heparin (UH) 5000 units b.d., Logiparin 2500 units daily or Logiparin 3500 units daily. Each treatment was given subcutaneously 2h before surgery and continued for 7–10 days. Daily 125I-labelled fibrinogen uptake tests (FUTs) were performed from day 2 to day 7 to detect DVT, and phleboangiography was used to confirm the diagnosis. The wound was examined on a daily basis to check for haematoma formation, and all patients were followed up for 1 month after operation. All three treatment arms were well matched for age, sex, weight, diagnosis and type of operation performed. The three major inclusion criteria in the trial were malignancy, age over 60 years and a history of varicose veins. Positive FUTs (UH=4·2 per cent, Logiparin 2500 units daily = 7·9 per cent, Logiparin 3500 units daily = 3·7 per cent) and positive angiograms (UH=3·0 per cent, Logiparin 2500 units daily = 5·6 per cent, Logiparin 3500 units daily = 2·3 per cent) were significantly more common in the Logiparin 2500 units daily group than in the UH and Logiparin 3500 units daily groups. The rates of major complications (severe haemorrhage, death, pulmonary embolism, reintervention) were similar in the three groups.

A randomized, placebo-controlled trial was carried out to determine the effectiveness of acebutolol in preventing late death in high-risk patients surviving an acute myocardial infarction (MI). The average 1-year mortality rate in placebo groups of 9 trials of beta blockers in post-MI patients was 7.2% compared with 17% in a nonselected cohort of patients who had survived at least 7 days after an MI. The mandate for this trial was based on the fact that high-risk patients whose mortality rate exceeds 20% have not been enrolled in significant numbers in previous trials. It remains to be proved whether beta-blocking therapy in this patient population is beneficial. Selection of high-risk patients for inclusion in the trial was based on an algorithm set up from the Essai de Prevention Secondaire de l'Infarctus du Myocarde Registry. At the time of the second interim analysis, the mortality rate in the placebo group was 12%, lower than expected (greater than or equal to 20%). The trial was stopped; at that time, 309 patients had been allocated to placebo and 298 patients to acebutolol therapy. After 318 days, there were 17 deaths in the acebutolol-treated group and 34 in the placebo group, a reduction in total mortality of 48% (p = 0.019). There were 30 vascular deaths in the placebo group and 12 in the acebutolol group. Thus, cardiovascular mortality with acebutolol was reduced by 58% (p = 0.006). The incidence of all cardiovascular-related deaths was lower in the acebutolol-treated group. The total reduction in mortality did not appear to be correlated with secondary risk factors.(ABSTRACT TRUNCATED AT 250 WORDS)

In the frame of a multicenter controlled study comparing the efficacy of low-molecular-weight heparin to standard heparin in the prevention of postsurgical thrombosis, 94 phelbograms were centrally evaluated by two independent radiologists. Three months after the first central evaluation, a new reading was performed with the same radiologists, and discrepancies were adjudicated by a senior radiologist. The number of discrepancies between the first and the second evaluation was high: 33 interpretations (35%) had a least one difference, including 14 (14.9%) discrpeancies regarding the main issue, i.e. the presence of venous thrombosis. After the adjudication by the senior radiologist, this number decreased but was still large: 22 films (23.4%) with at least one discrepant item in all and 11 related to the presence of venous thrombosis. This report shows that venous thrombosis assessed by phlebography, which is usually considered as a golden standard in clinical trials, deserves a thorough quality control procedure.

To determine a possible influence on sodium balance or blood pressure of a normal treatment with dydrogesterone, a randomized cross-over double-blind study was performed on 22 healthy young women. Each woman had (in random order) 1 cycle of treatment with dydrogesterone (20 mg/day during the last 12 days of the menstrual cycle) and 1 with equivalent placebo. On days 15 and 27 of each cycle the following data were noted: weight, systolic (SBP) and diastolic (DBP) blood pressures (mean of 13 measurements during 1 hour), natriuresis, kaliuresis, plasma renin activity (PRA) and plasma aldosterone concentration (P ald). For each variable the difference between day 27 and day 15 was calculated. The comparison between progesterone and placebo influence was made on these differences. Neither for sodium balance nor for blood pressure were there any statistically significant differences between placebo and dydrogesterone. However, the confidence intervals of the difference were rather large. There is a need for a more extensive study to confirm the absence of influence of progesterone on sodium balance and blood pressure.

Picolet Guy. Une visite du jeune Saint-Simon à l'Observatoire de Paris. In: Cahiers Saint Simon, n°26, 1998. Ecrivains lecteurs des Mémoires pp. 59-68.

A combined experimental and theoretical study is here presented on the structure of genipin, a widely used molecule, whose applications range from natural cross-linker for proteins to regulating agent for drug delivery to precursor of natural dye. In particular the tridimensional structure of the genipin in solution has been studied by NMR spectroscopy and the experimental outcomes have been then supported by Density Functional Theory (DFT) calculations on the electronic structure and spectroscopic parameters. The equilibrium between open and closed-ring tautomers of genipin in solution has been also theoretically investigated. The mechanism of ring opening has been elucidated and the catalytic role of water has been clearly shown. Beyond the excellent agreement between experiments and theoretical calculations (in particular concerning 1H-NMR data), our results unravel the nature of the most stable isomer of genipin and related reactive species in solution.

A total of 1290 patients (Pts) undergoing general surgery were enrolled in a randomized, multicentre double-blind study in order to investigate the efficacy and safety of two different doses of a low molecular weight heparin (LMWH) (Logiparin) for the prevention of deep vein thrombosis. Patients were randomized to either 5,000 IU unfractionated heparin twice daily, 2,500 anti-Xa or 3,500 anti-Xa units of Logiparin once daily. Each treatment was given subcutaneously two hours before surgery and continued for seven to ten days. All coagulation tests were performed blindly in a core laboratory. Blood samples were collected before surgery and then 3 hours after injection on Day 3 and 5 after surgery. Anti-Xa amidolytic activities were significantly higher in the two LMW Heparin groups than in the unfractionated heparin group (mean peak levels +/- s.e.m. on Day 3: 0.097 +/- 0.004; 0.152 +/- 0.004 and 0.034 +/- 0.003 IU respectively). As expected a significant correlation was observed between anti-Xa activity and the dose of LMW Heparin injected. The correlation coefficient was higher when the doses were expressed in anti-Xa units/kg body weight. However, the body weight accounts for only 16% of the interindividual variability of anti-Xa activity. Therefore, there is no clear evidence to suggest that weight-adjusted doses should be recommended when this LMW Heparin is used as prophylactic treatment in general surgery. A weak negative correlation was found between anti-Xa activity and thrombosis as demonstrated by a positive radiolabelled fibrinogen uptake test and confirmed by positive phlebography. No significant correlation was demonstrated between anti-Xa activity and the occurrence of postoperative bleeding.