Les paramètres du cycle vital de Physa acuta (Gastropoda, Mollusca) en milieu expérimental.

The values of the life history parameters expressed in the Lotka's equation were measured in the experimental conditions (20ºC, food ad libitum) for the aquatic pumonate Physa acuta. The estimated fitness value allows the population to double in about 4 weeks. The life cycle is very short (about 3 times shorter than for Lymnaea peregra in similar conditions) because of the important relative size of the eggs, a very high growth rate and an early maturity. This kind of strategy seems adaptive in eutrophic and temporary pools, where the adult mortality is important and density-independant. While the longevity shows very poor correlations with all other parameters, adult size, age at maturity and fecundity are strongly correlated. Structural and functionnal interpetations of these correlations are proposed. A mixed strategy seems a good hypothesis for this usually bivoltine species: the little-size, early-maturity and high-fecondity strategy may be selected during the summer, and the big-size, delayed-maturity and poor fecundity strategy during the winter

Fate of TLR-1/TLR-2 agonist functionalised pDNA nanoparticles upon deposition at the human bronchial epithelium in vitro.

BACKGROUND: Plasmid DNA vaccination is a promising approach, but studies in non-human primates and humans failed to achieve protective immunity. To optimise this technology further with focus on pulmonary administration, we developed and evaluated an adjuvant-equipped DNA carrier system based on the biopolymer chitosan. In more detail, the uptake and accompanying immune response of adjuvant Pam3Cys (Toll-like receptor-1/2 agonist) decorated chitosan DNA nanoparticles (NP) were explored by using a three-dimensional (3D) cell culture model of the human epithelial barrier. Pam3Cys functionalised and non-functionalised chitosan DNA NP were sprayed by a microsprayer onto the surface of 3D cell cultures and uptake of NP by epithelial and immune cells (blood monocyte-derived dendritic cells (MDDC) and macrophages (MDM)) was visualised by confocal laser scanning microscopy. In addition, immune activation by TLR pathway was monitored by analysis of interleukin-8 and tumor necrosis factor-α secretions (ELISA). RESULTS: At first, a high uptake rate into antigen-presenting cells (MDDC: 16-17%; MDM: 68-75%) was obtained. Although no significant difference in uptake patterns was observed for Pam3Cys adjuvant functionalised and non-functionalised DNA NP, ELISA of interleukin-8 and tumor necrosis factor-α demonstrated clearly that Pam3Cys functionalisation elicited an overall higher immune response with the ranking of Pam3Cys chitosan DNA NPâeuro0/00>âeuro0/00chitosan DNA NPâeuro0/00=âeuro0/00DNA unloaded chitosan NPâeuro0/00>âeuro0/00control (culture medium). CONCLUSIONS: Chitosan-based DNA delivery enables uptake into abluminal MDDC, which are the most immune competent cells in the human lung for the induction of antigen-specific immunity. In addition, Pam3Cys adjuvant functionalisation of chitosan DNA NP enhances significantly an environment favoring recruitment of immune cells together with a Th1 associated (cellular) immune response due to elevated IL-8 and TNF-α levels. The latter renders this DNA delivery approach attractive for potential DNA vaccination against intracellular pathogens in the lung (e.g., Mycobacterium tuberculosis or influenza virus).

Entrepreneurial success and failure: Confidence and fallible judgement

Excess entry or the high failure rate of market-entry decisions is often attributed tooverconfidence exhibited by entreprene urs. We show analytically that whereas excess entryis an inevitable consequence of imperfect assessments of entrepreneurial skill, it does notimply overconfidence. Judgmental fallibility leads to excess entry even when everyone isunderconfident. Self-selection implies greater confidence (but not necessarilyoverconfidence) among those who start new businesses than those who do not and amongsuccessful entrants than failures. Our results question claims that entrepreneurs areoverconfident and emphasize the need to understand the role of judgmental fallibility inproducing economic outcomes.

Excess entry, ambiguity seeking and competence: An experimental investigation

Excess entry refers to the high failure rate of new entrepreneurial ventures. Economic explanations suggest 'hit and run' entrants and risk-seeking behavior. A psychological explanation is that people (entrepreneurs) are overconfident in their abilities (Camerer & Lovallo, 1999). Characterizing entry decisions as ambiguous gambles, we alternatively suggest following Heath and Tversky (1991) that people seek ambiguity when the source of uncertainty is related to their competence. Overconfidence, as such, plays no role. This hypothesis is confirmed in an experimental study that also documents the phenomenon of reference group neglect. Finally, we emphasize the utility that people gain from engaging in activities that contribute to a sense of competence. This is an important force in economic activity that deserves more explicit attention.

Characteristics and outcome of knee prosthetic joint infections (PJI): A 10-year cohort study (2000-2009)

Background: Prosthetic joint infections (PJI) lead to significant long-term morbidity with high cost of healthcare. We evaluated characteristics of infections and the infection and functional outcome of knee PJI over a 10-year period. Methods: All patients hospitalized at our institution from 1/2000 through 12/2009 with knee PJI (defined as growth of the same microorganism in ≥2 tissue or synovial fluid cultures, visible purulence, sinus tract or acute inflammation on tissue histopathology) were included. Patients, their relatives and/or treating physicians were contacted to determine the outcome. Results: During the study period, 61 patients with knee PJI were identified. The median age at the time of diagnosis of infection was 73 y (range, 53-94 y); 52% were men. Median hospital stay was 37 d (range, 1-145 d). Most reasons for primary arthroplasty was osteoarthritis (n = 48), trauma (n = 9) and rheumatoid arthritis (n = 4). 23 primary surgeries (40%) were performed at CHUV, 34 (60%) elsewhere. After surgery, 8 PJI were early (<3 months), 16 delayed (3-24 months) and 33 late (>24 months). PJI were treated with (i) open or arthroscopic debridement with prosthesis retention in 26 (46%), (ii) one-stage exchange in 1, (iii) two-stage exchange in 22 (39%) and (iv) prosthesis removal in 8 (14%). Isolated pathogens were S. aureus (13), coagulase-negative staphylococci (10), streptococci (5), enterococci (3), gram-negative rods (3) and anaerobes (3). Patients were followed for a median of 3.1 years, 2 patients died (unrelated to PJI). The outcome of infection was favorable in 50 patients (88%), whereas the functional outcome was favorable in 33 patients (58%). Conclusions: With the current treatment concept, the high cure rate of infection (88%) is associated with a less favorable functional outcome o 58%. Earlier surgical intervention and more rapid and improved diagnosis of infection may improve the functional outcome of PJI.

The effect of environment on development and survival of pupae of the necrophagous fly Ophyra albuquerquei Lopes (Diptera, Muscidae)

The effect of environment on development and survival of pupae of the necrophagous fly Ophyra albuquerquei Lopes (Diptera, Muscidae). Species of Ophyra Robineau-Desvoidy, 1830 are found in decomposing bodies, usually in fresh, bloated and decay stages. Ophyra albuquerquei Lopes, for example, can be found in animal carcasses. The influence of environmental factors has not been evaluated in puparia of O. albuquerquei. Thus, the focus of this work was motivated by the need for models to predict the development of a necrophagous insect as a function of abiotic factors. Colonies of O. albuquerquei were maintained in the laboratory to obtain pupae. On the tenth day of each month 200 pupae, divided equally into 10 glass jars, were exposed to the environment and checked daily for adult emergence of each sample. We concluded that the high survival rate observed suggested that the diets used for rearing the larvae and maintaining the adults were appropriate. Also, the data adjusted to robust generalized linear models and there were no interruptions of O. albuquerquei pupae development within the limits of temperatures studied in southern Rio Grande do Sul, given the high survival presented.

Energy consumption of European and African shrews

Is the extremely high oxygen consumption of shrews due to an unusually high basal metabolism? In an attempt to answer this long-standing question, we have measured the oxygen consumption of 13 species of shrews of different origin: from Europe - Sorex araneus, S. Minutus, Neomys fodiens, Crocidura russula, and Suncus etruscus; from Africa - Crocidura bottegi, C. bicolor, C. jouvenetae; C. poensis, C. theresae, C. Wimmeri, C. flavescens, and C. giffardi, The measurements, taken over a period of 20-30 minutes, were made in small, closed-system chambers at 25°C. The metabolic rat our shrews of the subfamily Soricinae lies between the eman and minimum values of the Soricini (M=126.2 W0.52 cal/h and M=82.6 W0.53 cal/h, respectively), as recorded in the literature. Zhe average for the African Crocidurinae is much lower (M= 43.6 W0.67). The metabolic rate of the European Croccidura russula agrees with that of the African species. Thus, the Crocidurinae are characterized by a relatively low metabolic rate; the Soricinae, and in particular the tribe of the Soricini, by an extremely high metabolic rate. The tribes Neomyini and Blarinini occupy an intermediate position. These differences are also to be found at the level of the basal metabolism. This main difference between the two sub-families can most likely be explained by evolution in geographical isolation under differential climatic conditions: the Crocidurinae having evolved in tropical Africa and the Soricinae in temperate Eurasia

Enterococcal endocarditis in the beginning of the 21st century: analysis from the International Collaboration on Endocarditis-Prospective Cohort Study.

Enterococci are reportedly the third most common group of endocarditis-causing pathogens but data on enterococcal infective endocarditis (IE) are limited. The aim of this study was to analyse the characteristics and prognostic factors of enterococcal IE within the International Collaboration on Endocarditis. In this multicentre, prospective observational cohort study of 4974 adults with definite IE recorded from June 2000 to September 2006, 500 patients had enterococcal IE. Their characteristics were described and compared with those of oral and group D streptococcal IE. Prognostic factors for enterococcal IE were analysed using multivariable Cox regression models. The patients' mean age was 65 years and 361/500 were male. Twenty-three per cent (117/500) of cases were healthcare related. Enterococcal IE were more frequent than oral and group D streptococcal IE in North America. The 1-year mortality rate was 28.9% (144/500). E. faecalis accounted for 90% (453/500) of enterococcal IE. Resistance to vancomycin was observed in 12 strains, eight of which were observed in North America, where they accounted for 10% (8/79) of enterococcal strains, and was more frequent in E. faecium than in E. faecalis (3/16 vs. 7/364 , p 0.01). Variables significantly associated with 1-year mortality were heart failure (HR 2.4, 95% CI 1.7--3.5, p <0.0001), stroke (HR 1.9, 95% CI 1.3--2.8, p 0.001) and age (HR 1.02 per 1-year increment, 95% CI 1.01--1.04, p 0.002). Surgery was not associated with better outcome. Enterococci are an important cause of IE, with a high mortality rate. Healthcare association and vancomycin resistance are common in particular in North America.

Long-term treatment of eosinophilic esophagitis esophagitis with budesonide

BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic-inflammatory disease of the esophagus, characterized by esophagus-related symptoms and a dense tissue eosinophilia, both refractory to proton pump inhibitors. Topical corticosteroids have proven effective in inducing clinical and histologic remission. However, a long-term strategy for the management of this chronic disease is not yet defined. METHODS: In a randomized, double-blind, placebocontrolled, long-term trial, we evaluated the efficacy of twice-daily 0.25 mg swallowed budesonide in maintaining a remission in adult EoE with prior response to induction therapy. Pre- and post-treatment disease activity was assessed clinically, endoscopically, histologically, by immunofluorescence and by high-resolution endosonography. The primary end point was the ability to maintain histologic remission (<5 eos/hpf) of EoE in. Secondary end points were the efficacy on symptom control and on tissue remodeling as well as the determination of the safety of long-term esophageal administration of topical corticosteroids. RESULTS: During a 50-week therapy of quiescent EoE with low-dose budesonide the esophageal eosinophil load (ECP staining) increased from 1.1 to 29.9 eos/hpf, but under placebo the increase was significantly larger (0.5 to 51.1 eos/hpf; p=0.01). At the end of the studyperiod, 35.7% (5/14) of the budesonide patients were in complete and 14.3% (2/14) in partial histologic remission; with placebo no patient was in complete and 28.6% (4/14) were in partial remission (p=0.0647). The increase of the symptom score was markedly lower in budesonide- (0.79 to 2.29 points) than in placebo-patients (0.71 to 4.00 points; p=0.0875). The median time to relapse of symptoms was >125 days in the budesonide and 95 days in the placebo group (p = 0.14). Measured by high-resolution endosonography, all EoE patients had pre-treatment a highly thickened esophageal wall compared with healthy controls (3.05±1.08 mm vs. 2.18±0.35 mm; p<0.0001). Long-term topical budesonide reduced mainly the thickness of the superficial wall layers (mucosa, 0.75 mm to 0.45 mm; p=0.025) whereas the response of the deeper layers was less pronounced (submucosa 1.31 to 1.08 mm; p=0.19 and muscularis 0.82 to 0.76 mm; p=0.72). Budesonide did not evoke any mucosal atrophy. CONCLUSIONS: This study clearly demonstrates that 1) Untreated eosinophil inflammation results in an impressive remodeling of the esophagus; 2) A therapy is therefore needed; 3) The high relapse rate after short-term therapy requires a long-term management and 4) Maintenance treatment with budesonide is well tolerated and keeps half of the patients in remission.

Ecological temporal stability of Staphylococcus aureus nasal carriage.

We described the colonization dynamics of Staphylococcus aureus in a group of 266 healthy carriers over a period of approximately 1 year. We used precise genotyping methods, i.e., amplified fragment length polymorphism (AFLP), spa typing, and double-locus sequence typing (DLST), to detect changes in strain identity. Strain change took place rather rarely: out of 89 carriers who had initially been colonized, only 7 acquired a strain different from the original one. Approximately one-third of the carriers eliminated the colonization, and a similar number became newly colonized. Some of these events probably represent detection failure rather than genuine colonization loss or acquisition. Lower bacterial counts were associated with increased probability of eliminating the colonization. We have confirmed a high mutation rate in the spa locus: 6 out of 53 strains underwent mutation in the spa locus. There was no overall change in S. aureus genotype composition.

Phytochrome interacting factors 4 and 5 redundantly limit seedling de-etiolation in continuous far-red light.

Phytochromes are red/far-red photosensors that regulate numerous developmental programs in plants. Among them, phytochrome A (phyA) is essential to enable seedling de-etiolation under continuous far-red (FR) light, a condition that mimics the environment under a dense canopy. The ecological relevance of this response is demonstrated by the high mortality rate of phyA mutant plants that germinate in deep vegetational shade. phyA signaling involves direct interaction of the photoreceptor with phytochrome-interacting factors PIF1 and PIF3, members of the bHLH transcription factor family. Here we investigated the involvement of PIF4 and PIF5 in phyA signaling, and found that they redundantly control de-etiolation in FR light. The pif4 pif5 double mutant is hypersensitive to low fluence rates of FR light. This phenotype is dependent on FR light perception by phyA, but does not rely on alterations in the phyA level. Our microarray analysis shows that PIF4 and PIF5 are part of an inhibitory mechanism that represses the expression of some light-responsive genes in the dark, and that they are also needed for full expression of several growth-related genes in the light. Unlike PIF1 and PIF3, PIF4 and PIF5 are not degraded in response to FR light, indicating that they are light-regulated by a different mechanism. Our genetic analysis suggests that this is achieved through sequestration of these PIFs by the closely related bHLH transcription factor HFR1 (long hypocotyl in FR light).

Effect of grade on disease-free survival and overall survival in FIGO stage I adenocarcinoma of the endometrium.

OBJECTIVE: To analyse the effect of differentiation on disease-free survival (DFS) and overall survival (OS) in patients with stage I adenocarcinoma of the endometrium. PATIENTS AND METHODS: From 1979 to 1995, 350 patients with FIGO stage IA-IC with well (G1), moderately (G2) or poorly (G3) differentiated tumors were treated with surgery and high dose-rate brachytherapy with or without external radiation. Median age was 65 years (39-86 years). RESULTS: The 5-year DFS was 88+/-3% for the G1 tumors, 77+/-4% for the G2 tumors, and 67+/-7% for the G3 tumors (P=0.0049). With regard to the events contributing to DFS, the 5-year cumulative percentage of local relapse was 4.6% for the G1 tumors, 9.0% for the G2 tumors, and 4.6% (P=0.027) for the G3 tumors. Cumulative percentage of metastasis was 1.4, 6.3 and 7.2% (P<0.001), respectively, whereas percentages of death were 6.0, 7.9 and 20.7% (P<0.001). The 5-year OS was 91+/-3, 83+/-4 and 76+/-7%, respectively (P=0.0018). In terms of multivariate hazard ratios (HR), the relative differences between the three differentiation groups correspond to an increase of 77% of the risk of occurrence of either of the three events considered for the DFS (HR=1.77, 95% CI [0.94-3.33]), (P=0.078) for the G2 tumors and of 163% (HR=2.63, 95% CI [1.27-5.43]), (P=0.009) for the G3 tumors with respect to the G1 tumors. The estimated relative hazards for OS are, respectively, in line with those for DFS: HR=1.51 (P=0.282) for the G2 tumors; and HR=3.37 (P=0.003) for the G3 tumors. CONCLUSION: Patients with grade 1 tumors are those least exposed to either local relapse, metastasis, or death. In contrast patients with grade 2 tumors seem to be at higher risk of metastasis, whereas patients with grade 3 tumors appear at higher risk of death. Since we have looked at the first of three competing events (local relapse, metastasis and death), this suggests that patients with grade 3 tumors probably progress to death so fast that local relapse, if any, cannot be observed.

Treatment of eosinophilic esophagitis by dilation.

Treatment options for eosinophilic esophagitis (EoE) include drugs, diets and esophageal dilation. Esophageal dilation can be performed using either through-the-scope balloons or wire-guided bougies. Dilation can lead to long-lasting symptom improvement in EoE patients presenting with esophageal strictures. Esophageal strictures are most often diagnosed when the 8- to 9-mm outer diameter adult gastroscope cannot be passed any further or only against resistance. A defined esophageal diameter to be targeted by dilation is missing, but the majority of patients have considerable symptomatic improvement when a diameter of 16-18 mm has been reached. A high complication rate, especially regarding esophageal perforations, has been reported in small case series until 2006. Several large series were published in 2007 and later that demonstrated that the complication risk (especially esophageal perforation) was much lower than what was reported in earlier series. The procedure can therefore be regarded as safe when some simple precautions are followed. It is noteworthy that esophageal dilation does not influence the underlying eosinophil-predominant inflammation. Patients should be informed before the procedure that postprocedural retrosternal pain may occur for some days, but that it usually responds well to over-the-counter analgesics such as paracetamol. Dilation-related superficial lacerations of the mucosa should not be regarded and reported as complications, but instead represent a desired effect of the therapy. Patient tolerance and acceptance for esophageal dilation have been reported to be good.

Congenital diaphragmatic hernia: current status and review of the literature.

Treatment of congenital diaphragmatic hernia (CDH) challenges obstetricians, pediatric surgeons, and neonatologists. Persistent pulmonary hypertension (PPHT) associated with lung hypoplasia in CDH leads to a high mortality rate at birth. PPHT is principally due to an increased muscularization of the arterioles. Management of CDH has been greatly improved by the introduction of prenatal surgical intervention with tracheal obstruction (TO) and by more appropriate postnatal care. TO appears to accelerate fetal lung growth and to increase the number of capillary vessels and alveoli. Improvement of postnatal care over the last years is mainly due to the avoidance of lung injury by applying low peak inflation pressure during ventilation. The benefits of other drugs or technical improvements such as the use of inhaled nitric oxide or extracorporeal membrane oxygenation (ECMO) are still being debated and no single strategy is accepted worldwide. Despite intensive clinical and experimental research, the treatment of newborn with CDH remains difficult.

La fibrose rétropéritonéale, une maladie inflammatoire méconnue. Observations cliniques et revue de la littérature [Retroperitoneal fibrosis, an unrecognized inflammatory disease. Clinical observations and review of the literature]

Retroperitoneal fibrosis (RF) is a rare disease, typically with an insidious clinical course. The peak incidence is seen in patients 40 to 60 years of age and mostly in man. The characteristic finding in this disease is a periaortic fibrous mass that often surrounds the ureters. Although usually regarded as an obstructive uropathy, there has been growing recognition of the condition as a generalized disease. It may have a wide variety of manifestations including mediastinitis, thyroiditis and sclerosing cholangitis. The most common mode of presentation remains abdominal or flank pain with uremia, anemia and a high sedimentation rate. Although ultrasound and renal scintigraphy may contribute to the general evaluation of patients with RF, CT-scanner is the preferred imaging method. The multiplanar imaging capability of magnetic resonance may facilitate assessment of disease extent. The pathogenesis of the disease remains unknown. Steroids and, more recently tamoxifen, appear to be effective in the treatment of the RF. In most instances, RF does not lead to long-term morbidity or affect survival. The three cases of RF reported herein illustrate the varied mode of presentation and the response to the treatment.