Showing papers by "University of Paris published in 2006"

Type, Density, and Location of Immune Cells Within Human Colorectal Tumors Predict Clinical Outcome

Abstract: The role of the adaptive immune response in controlling the growth and recurrence of human tumors has been controversial. We characterized the tumor-infiltrating immune cells in large cohorts of human colorectal cancers by gene expression profiling and in situ immunohistochemical staining. Collectively, the immunological data (the type, density, and location of immune cells within the tumor samples) were found to be a better predictor of patient survival than the histopathological methods currently used to stage colorectal cancer. The results were validated in two additional patient populations. These data support the hypothesis that the adaptive immune response influences the behavior of human tumors. In situ analysis of tumor-infiltrating immune cells may therefore be a valuable prognostic tool in the treatment of colorectal cancer and possibly other malignancies.

Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia

Abstract: BACKGROUND: The cause of chronic myeloid leukemia (CML) is a constitutively active BCR-ABL tyrosine kinase. Imatinib inhibits this kinase, and in a short-term study was superior to interferon alfa ...

Ranibizumab versus Verteporfin for Neovascular Age-Related Macular Degeneration

Abstract: Of the 423 patients enrolled, 94.3% of those given 0.3 mg of ranibizumab and 96.4% of those given 0.5 mg lost fewer than 15 letters, as compared with 64.3% of those in the verteporfin group (P<0.001 for each comparison). Visual acuity improved by 15 letters or more in 35.7% of the 0.3-mg group and 40.3% of the 0.5-mg group, as compared with 5.6% of the verteporfin group (P<0.001 for each comparison). Mean visual acuity increased by 8.5 letters in the 0.3-mg group and 11.3 letters in the 0.5-mg group, as compared with a decrease of 9.5 letters in the verteporfin group (P<0.001 for each comparison). Among 140 patients treated with 0.5 mg of ranibizumab, presumed endophthalmitis occurred in 2 patients (1.4%) and serious uveitis in 1 (0.7%). Conclusions Ranibizumab was superior to verteporfin as intravitreal treatment of predominantly classic neovascular age-related macular degeneration, with low rates of serious ocular adverse events. Treatment improved visual acuity on average at 1 year. (ClinicalTrials. gov number, NCT00061594.)

Clopidogrel and Aspirin versus Aspirin Alone for the Prevention of Atherothrombotic Events

Abstract: Background Dual antiplatelet therapy with clopidogrel plus low-dose aspirin has not been studied in a broad population of patients at high risk for atherothrombotic events. Methods We randomly assigned 15,603 patients with either clinically evident cardiovascular disease or multiple risk factors to receive clopidogrel (75 mg per day) plus low-dose aspirin (75 to 162 mg per day) or placebo plus low-dose aspirin and followed them for a median of 28 months. The primary efficacy end point was a composite of myocardial infarction, stroke, or death from cardiovascular causes. Results The rate of the primary efficacy end point was 6.8 percent with clopidogrel plus aspirin and 7.3 percent with placebo plus aspirin (relative risk, 0.93; 95 percent confidence interval, 0.83 to 1.05; P = 0.22). The respective rate of the principal secondary efficacy end point, which included hospitalizations for ischemic events, was 16.7 percent and 17.9 percent (relative risk, 0.92; 95 percent confidence interval, 0.86 to 0.995; P = 0.04), and the rate of severe bleeding was 1.7 percent and 1.3 percent (relative risk, 1.25; 95 percent confidence interval, 0.97 to 1.61 percent; P = 0.09). The rate of the primary end point among patients with multiple risk factors was 6.6 percent with clopidogrel and 5.5 percent with placebo (relative risk, 1.2; 95 percent confidence interval, 0.91 to 1.59; P = 0.20) and the rate of death from cardiovascular causes also was higher with clopidogrel (3.9 percent vs. 2.2 percent, P = 0.01). In the subgroup with clinically evident atherothrombosis, the rate was 6.9 percent with clopidogrel and 7.9 percent with placebo (relative risk, 0.88; 95 percent confidence interval, 0.77 to 0.998; P = 0.046). Conclusions In this trial, there was a suggestion of benefit with clopidogrel treatment in patients with symptomatic atherothrombosis and a suggestion of harm in patients with multiple risk factors. Overall, clopidogrel plus aspirin was not significantly more effective than aspirin alone in reducing the rate of myocardial infarction, stroke, or death from cardiovascular causes. (ClinicalTrials.gov number, NCT00050817.)

Toxicological Impact Studies Based on Escherichia coli Bacteria in Ultrafine ZnO Nanoparticles Colloidal Medium

Abstract: We report here preliminary studies of biocidal effects and cellular internalization of ZnO nanoparticles on Escherichia coli bacteria. ZnO nanoparticles were synthesized in di(ethylene glycol) (DEG) medium by forced hydrolysis of ionic Zn2+ salts. Particle size and shape were controlled by addition of small molecules and macromolecules such as tri-n-octylphosphine oxide, sodium dodecyl sulfate, polyoxyethylene stearyl ether, and bovine serum albumin. Transmission electron microscopy (TEM) and X-ray diffraction analyses were used to characterize particle structure, size, and morphology. Bactericidal tests were performed in Luria-Bertani medium on solid agar plates and in liquid systems with different concentrations of small and macromolecules and also with ZnO nanoparticles. TEM analyses of bacteria thin sections were used to study biocidal action of ZnO materials. The results confirmed that E. coli cells after contact with DEG and ZnO were damaged showing a Gram-negative triple membrane disorganization. This behavior causes the increase of membrane permeability leading to accumulation of ZnO nanoparticles in the bacterial membrane and also cellular internalization of these nanoparticles.

Global Mineralogical and Aqueous Mars History Derived from OMEGA/Mars Express Data

Abstract: Global mineralogical mapping of Mars by the Observatoire pour la Mineralogie, l'Eau, les Glaces et l'Activite (OMEGA) instrument on the European Space Agency's Mars Express spacecraft provides new information on Mars' geological and climatic history. Phyllosilicates formed by aqueous alteration very early in the planet's history (the "phyllocian" era) are found in the oldest terrains; sulfates were formed in a second era (the "theiikian" era) in an acidic environment. Beginning about 3.5 billion years ago, the last era (the "siderikian") is dominated by the formation of anhydrous ferric oxides in a slow superficial weathering, without liquid water playing a major role across the planet.

International Prevalence, Recognition, and Treatment of Cardiovascular Risk Factors in Outpatients With Atherothrombosis

Abstract: ContextAtherothrombosis is the leading cause of cardiovascular morbidity and mortality around the globe. To date, no single international database has characterized the atherosclerosis risk factor profile or treatment intensity of individuals with atherothrombosis.ObjectiveTo determine whether atherosclerosis risk factor prevalence and treatment would demonstrate comparable patterns in many countries around the world.Design, Setting, and ParticipantsThe Reduction of Atherothrombosis for Continued Health (REACH) Registry collected data on atherosclerosis risk factors and treatment. A total of 67 888 patients aged 45 years or older from 5473 physician practices in 44 countries had either established arterial disease (coronary artery disease [CAD], n = 40 258; cerebrovascular disease, n = 18 843; peripheral arterial disease, n = 8273) or 3 or more risk factors for atherothrombosis (n = 12 389) between 2003 and 2004.Main Outcome MeasuresBaseline prevalence of atherosclerosis risk factors, medication use, and degree of risk factor control.ResultsAtherothrombotic patients throughout the world had similar risk factor profiles: a high proportion with hypertension (81.8%), hypercholesterolemia (72.4%), and diabetes (44.3%). The prevalence of overweight (39.8%), obesity (26.6%), and morbid obesity (3.6%) were similar in most geographic locales, but was highest in North America (overweight: 37.1%, obese: 36.5%, and morbidly obese: 5.8%; P<.001 vs other regions). Patients were generally undertreated with statins (69.4% overall; range: 56.4% for cerebrovascular disease to 76.2% for CAD), antiplatelet agents (78.6% overall; range: 53.9% for ≥3 risk factors to 85.6% for CAD), and other evidence-based risk reduction therapies. Current tobacco use in patients with established vascular disease was substantial (14.4%). Undertreated hypertension (50.0% with elevated blood pressure at baseline), undiagnosed hyperglycemia (4.9%), and impaired fasting glucose (36.5% in those not known to be diabetic) were common. Among those with symptomatic atherothrombosis, 15.9% had symptomatic polyvascular disease.ConclusionThis large, international, contemporary database shows that classic cardiovascular risk factors are consistent and common but are largely undertreated and undercontrolled in many regions of the world.

Scale for the assessment and rating of ataxia: development of a new clinical scale.

Abstract: OBJECTIVE: To develop a reliable and valid clinical scale measuring the severity of ataxia. METHODS: The authors devised the Scale for the Assessment and Rating of Ataxia (SARA) and tested it in two trials of 167 and 119 patients with spinocerebellar ataxia. RESULTS: The mean time to administer SARA in patients was 14.2 +/- 7.5 minutes (range 5 to 40). Interrater reliability was high, with an intraclass coefficient (ICC) of 0.98. Test-retest reliability was high with an ICC of 0.90. Internal consistency was high as indicated by Cronbach's alpha of 0.94. Factorial analysis revealed that the rating results were determined by a single factor. SARA ratings showed a linear relation to global assessments using a visual analogue scale, suggesting linearity of the scale (p < 0.0001, r(2) = 0.98). SARA score increased with the disease stage (p < 0.001) and was closely correlated with the Barthel Index (r = -0.80, p < 0.001) and part IV (functional assessment) of the Unified Huntington's Disease Rating Scale (UHDRS-IV) (r = -0.89, p < 0.0001), whereas it had only a weak correlation with disease duration (r = 0.34, p < 0.0002). CONCLUSIONS: The Scale for the Assessment and Rating of Ataxia is a reliable and valid measure of ataxia, making it an appropriate primary outcome measure for clinical trials.

Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part I: technological concepts and evolution.

Abstract: Platelet-rich fibrin (PRF) belongs to a new generation of platelet concentrates geared to simplified preparation without biochemical blood handling. In this initial article, we describe the conceptual and technical evolution from fibrin glues to platelet concentrates. This retrospective analysis is necessary for the understanding of fibrin technologies and the evaluation of the biochemical properties of 3 generations of surgical additives, respectively fibrin adhesives, concentrated platelet-rich plasma (cPRP) and PRF. Indeed, the 3-dimensional fibrin architecture is deeply dependent on artificial clinical polymerization processes, such as massive bovine thrombin addition. Currently, the slow polymerization during PRF preparation seems to generate a fibrin network very similar to the natural one. Such a network leads to a more efficient cell migration and proliferation and thus cicatrization.

Genome Microevolution of Chikungunya Viruses Causing the Indian Ocean Outbreak

Abstract: A chikungunya virus outbreak of unprecedented magnitude is currently ongoing in Indian Ocean territories. In Reunion Island, this alphavirus has already infected about one-third of the human population. The main clinical symptom of the disease is a painful and invalidating poly-arthralgia. Besides the arthralgic form, 123 patients with a confirmed chikungunya infection have developed severe clinical signs, i.e., neurological signs or fulminant hepatitis.

The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria.

Abstract: BACKGROUND We tested the safety and efficacy of eculizumab, a humanized monoclonal antibody against terminal complement protein C5 that inhibits terminal complement activation, in patients with paroxysmal nocturnal hemoglobinuria (PNH). METHODS We conducted a double-blind, randomized, placebo-controlled, multicenter, phase 3 trial. Patients received either placebo or eculizumab intravenously; eculizumab was given at a dose of 600 mg weekly for 4 weeks, followed 1 week later by a 900-mg dose and then 900 mg every other week through week 26. The two primary end points were the stabilization of hemoglobin levels and the number of units of packed red cells transfused. Biochemical indicators of intravascular hemolysis and the patients' quality of life were also assessed. RESULTS Eighty-seven patients underwent randomization. Stabilization of hemoglobin levels in the absence of transfusions was achieved in 49% (21 of 43) of the patients assigned to eculizumab and none (0 of 44) of those assigned to placebo (P<0.001). During the study, a median of 0 units of packed red cells was administered in the eculizumab group, as compared with 10 units in the placebo group (P<0.001). Eculizumab reduced intravascular hemolysis, as shown by the 85.8% lower median area under the curve for lactate dehydrogenase plotted against time (in days) in the eculizumab group, as compared with the placebo group (58,587 vs. 411,822 U per liter; P<0.001). Clinically significant improvements were also found in the quality of life, as measured by scores on the Functional Assessment of Chronic Illness Therapy-Fatigue instrument (P<0.001) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. Of the 87 patients, 4 in the eculizumab group and 9 in the placebo group had serious adverse events, none of which were considered to be treatment-related; all these patients recovered without sequelae. CONCLUSIONS Eculizumab is an effective therapy for PNH.

A Review of Poloxamer 407 Pharmaceutical and Pharmacological Characteristics

Abstract: Poloxamer 407 copolymer (ethylene oxide and propylene oxide blocks) shows thermoreversible properties, which is of the utmost interest in optimising drug formulation (fluid state at room temperature facilitating administration and gel state above sol-gel transition temperature at body temperature promoting prolonged release of pharmacological agents). Pharmaceutical evaluation consists in determining the rheological behaviour (flow curve or oscillatory studies), sol-gel transition temperature, in vitro drug release using either synthetic or physiological membrane and (bio)adhesion characteristics. Poloxamer 407 formulations led to enhanced solubilisation of poorly water-soluble drugs and prolonged release profile for many galenic applications (e.g., oral, rectal, topical, ophthalmic, nasal and injectable preparations) but did not clearly show any relevant advantages when used alone. Combination with other excipients like Poloxamer 188 or mucoadhesive polymers promotes Poloxamer 407 action by optimising sol-gel transition temperature or increasing bioadhesive properties. Inclusion of liposomes or micro(nano)particles in Poloxamer 407 formulations offers interesting prospects, as well. Besides these promising data, Poloxamer 407 has been held responsible for lipidic profile alteration and possible renal toxicity, which compromises its development for parenteral applications. In addition, new findings have demonstrated immuno-modulation and cytotoxicity-promoting properties of Poloxamer 407 revealing significant pharmacological interest and, hence, human trials are in progress to specify these potential applications.

Cassini Observes the Active South Pole of Enceladus

Abstract: Cassini has identified a geologically active province at the south pole of Saturn's moon Enceladus. In images acquired by the Imaging Science Subsystem (ISS), this region is circumscribed by a chain of folded ridges and troughs at ∼55°S latitude. The terrain southward of this boundary is distinguished by its albedo and color contrasts, elevated temperatures, extreme geologic youth, and narrow tectonic rifts that exhibit coarse-grained ice and coincide with the hottest temperatures measured in the region. Jets of fine icy particles that supply Saturn's E ring emanate from this province, carried aloft by water vapor probably venting from subsurface reservoirs of liquid water. The shape of Enceladus suggests a possible intense heating epoch in the past by capture into a 1:4 secondary spin/orbit resonance.

Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part II: platelet-related biologic features.

Abstract: Platelet-rich fibrin (PRF) belongs to a new generation of platelet concentrates, with simplified processing and without biochemical blood handling. In this second article, we investigate the platelet-associated features of this biomaterial. During PRF processing by centrifugation, platelets are activated and their massive degranulation implies a very significant cytokine release. Concentrated platelet-rich plasma platelet cytokines have already been quantified in many technologic configurations. To carry out a comparative study, we therefore undertook to quantify PDGF-BB, TGFβ-1, and IGF-I within PPP (platelet-poor plasma) supernatant and PRF clot exudate serum. These initial analyses revealed that slow fibrin polymerization during PRF processing leads to the intrinsic incorporation of platelet cytokines and glycanic chains in the fibrin meshes. This result would imply that PRF, unlike the other platelet concentrates, would be able to progressively release cytokines during fibrin matrix remodeling; such a mechanism might explain the clinically observed healing properties of PRF.

Platelet-rich fibrin (PRF): A second-generation platelet concentrate. Part IV: Clinical effects on tissue healing

Abstract: Platelet-rich fibrin (PRF) belongs to a new generation of platelet concentrates, with simplified processing and without biochemical blood handling. In this fourth article, investigation is made into the previously evaluated biology of PRF with the first established clinical results, to determine the potential fields of application for this biomaterial. The reasoning is structured around 4 fundamental events of cicatrization, namely, angiogenesis, immune control, circulating stem cells trapping, and wound-covering epithelialization. All of the known clinical applications of PRF highlight an accelerated tissue cicatrization due to the development of effective neovascularization, accelerated wound closing with fast cicatricial tissue remodelling, and nearly total absence of infectious events. This initial research therefore makes it possible to plan several future PRF applications, including plastic and bone surgery, provided that the real effects are evaluated both impartially and rigorously.

Nanotechnology: intelligent design to treat complex disease.

Abstract: The purpose of this expert review is to discuss the impact of nanotechnology in the treatment of the major health threats including cancer, infections, metabolic diseases, autoimmune diseases, and inflammations. Indeed, during the past 30 years, the explosive growth of nanotechnology has burst into challenging innovations in pharmacology, the main input being the ability to perform temporal and spatial site-specific delivery. This has led to some marketed compounds through the last decade. Although the introduction of nanotechnology obviously permitted to step over numerous milestones toward the development of the "magic bullet" proposed a century ago by the immunologist Paul Ehrlich, there are, however, unresolved delivery problems to be still addressed. These scientific and technological locks are discussed along this review together with an analysis of the current situation concerning the industrial development.

NOTCH1 directly regulates c-MYC and activates a feed-forward-loop transcriptional network promoting leukemic cell growth

Abstract: The NOTCH1 signaling pathway directly links extracellular signals with transcriptional responses in the cell nucleus and plays a critical role during T cell development and in the pathogenesis over 50% of human T cell lymphoblastic leukemia (T-ALL) cases. However, little is known about the transcriptional programs activated by NOTCH1. Using an integrative systems biology approach we show that NOTCH1 controls a feed-forward-loop transcriptional network that promotes cell growth. Inhibition of NOTCH1 signaling in T-ALL cells led to a reduction in cell size and elicited a gene expression signature dominated by down-regulated biosynthetic pathway genes. By integrating gene expression array and ChIP-on-chip data, we show that NOTCH1 directly activates multiple biosynthetic routes and induces c-MYC gene expression. Reverse engineering of regulatory networks from expression profiles showed that NOTCH1 and c-MYC govern two directly interconnected transcriptional programs containing common target genes that together regulate the growth of primary T-ALL cells. These results identify c-MYC as an essential mediator of NOTCH1 signaling and integrate NOTCH1 activation with oncogenic signaling pathways upstream of c-MYC.

Efficacy and safety of adalimumab in patients with ankylosing spondylitis: results of a multicenter, randomized, double-blind, placebo-controlled trial.

Abstract: Objective To evaluate the safety and efficacy of adalimumab, a fully human recombinant IgG1 monoclonal antibody that specifically targets human tumor necrosis factor, in patients with active ankylosing spondylitis (AS). Methods This was a multicenter, randomized (2:1 ratio), double-blind, placebo-controlled study to evaluate a subcutaneous injection of adalimumab, 40 mg every other week, compared with placebo for 24 weeks. The primary efficacy end point was the percentage of patients with a 20% response according to the ASsessment in Ankylosing Spondylitis International Working Group criteria for improvement (ASAS20) at week 12. Secondary outcome measures included the ASAS20 at week 24 and multiple measures of disease activity, spinal mobility, and function, as well as ASAS partial remission. Results At week 12, 58.2% of adalimumab-treated patients (121 of 208) achieved an ASAS20 response, compared with 20.6% of placebo-treated patients (22 of 107) (P < 0.001). More patients in the adalimumab group (45.2% [94 of 208]) than in the placebo group (15.9% [17 of 107]) had at least a 50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index at week 12 (P < 0.001). Significant improvements in the ASAS40 response and the response according to the ASAS5/6 criteria at weeks 12 and 24 were also demonstrated (P < 0.001). Partial remission was achieved by more adalimumab-treated patients than placebo-treated patients (22.1% versus 5.6%; P < 0.001). Adalimumab-treated patients reported more adverse events (75.0% versus 59.8% of placebo-treated patients; P < 0.05), but there was no statistically significant difference in the incidence of infections. Most adverse events were mild or moderate in severity. Conclusion Adalimumab was well-tolerated during the 24-week study period and was associated with a significant and sustained reduction in the signs and symptoms of active AS.

Tropical Intraseasonal Variability in 14 IPCC AR4 Climate Models. Part I: Convective Signals

Abstract: This study evaluates the tropical intraseasonal variability, especially the fidelity of Madden–Julian oscillation (MJO) simulations, in 14 coupled general circulation models (GCMs) participating in the Intergovernmental Panel on Climate Change (IPCC) Fourth Assessment Report (AR4). Eight years of daily precipitation from each model’s twentieth-century climate simulation are analyzed and compared with daily satellite-retrieved precipitation. Space–time spectral analysis is used to obtain the variance and phase speed of dominant convectively coupled equatorial waves, including the MJO, Kelvin, equatorial Rossby (ER), mixed Rossby–gravity (MRG), and eastward inertio–gravity (EIG) and westward inertio–gravity (WIG) waves. The variance and propagation of the MJO, defined as the eastward wavenumbers 1–6, 30–70-day mode, are examined in detail. The results show that current state-of-the-art GCMs still have significant problems and display a wide range of skill in simulating the tropical intraseasonal va...

Digital Image Correlation: from Displacement Measurement to Identification of Elastic Properties – a Review

Abstract: The current development of digital image correlation, whose displacement uncertainty is well below the pixel value, enables one to better characterise the behaviour of materials and the response of structures to external loads. A general presentation of the extraction of displacement fields from the knowledge of pictures taken at different instants of an experiment is given. Different strategies can be followed to achieve a sub-pixel uncertainty. From these measurements, new identification procedures are devised making use of full-field measures. A priori or a posteriori routes can be followed. They are illustrated on the analysis of a Brazilian test.

Excess mortality related to the August 2003 heat wave in France.

Abstract: Objectives: From August 1st to 20th, 2003, the mean maximum temperature in France exceeded the seasonal norm by 11–12°C on nine consecutive days. A major increase in mortality was then observed, which main epidemiological features are described herein. Methods: The number of deaths observed from August to November 2003 in France was compared to those expected on the basis of the mortality rates observed from 2000 to 2002 and the 2003 population estimates. Results: From August 1st to 20th, 2003, 15,000 excess deaths were observed. From 35 years age, the excess mortality was marked and increased with age. It was 15% higher in women than in men of comparable age as of age 45 years. Excess mortality at home and in retirement institutions was greater than that in hospitals. The mortality of widowed, single and divorced subjects was greater than that of married people. Deaths directly related to heat, heatstroke, hyperthermia and dehydration increased massively. Cardiovascular diseases, ill-defined morbid disorders, respiratory diseases and nervous system diseases also markedly contributed to the excess mortality. The geographic variations in mortality showed a clear age-dependent relationship with the number of very hot days. No harvesting effect was observed. Conclusions: Heat waves must be considered as a threat to European populations living in climates that are currently temperate. While the elderly and people living alone are particularly vulnerable to heat waves, no segment of the population may be considered protected from the risks associated with heat waves.

Effective sea-level rise and deltas: Causes of change and human dimension implications

Abstract: An assessment is made of contemporary effective sea-level rise (ESLR) for a sample of 40 deltas distributed worldwide. For any delta, ESLR is a net rate, defined by the combination of eustatic sea-level rise, the natural gross rate of fluvial sediment deposition and subsidence, and accelerated subsidence due to groundwater and hydrocarbon extraction. ESLR is estimated under present conditions using a digital data set of delta boundaries and a simple model of delta dynamics. The deltas in this study represent all major climate zones, levels of population density, and degrees of economic development. Collectively, the sampled deltas serve as the endpoint for river basins draining 30% of the Earth's landmass, and 42% of global terrestrial runoff. Nearly 300 million people inhabit these deltas. For the contemporary baseline, ESLR estimates range from 0.5 to 12.5 mm yr −1 . Decreased accretion of fluvial sediment resulting from upstream siltation of artificial impoundments and consumptive losses of runoff from irrigation are the primary determinants of ESLR in nearly 70% of the deltas. Approximately 20% of the deltas show accelerated subsidence, while only 12% show eustatic sea-level rise as the predominant effect. Extrapolating contemporary rates of ESLR through 2050 reveals that 8.7 million people and 28,000 km 2 of deltaic area in the sample set of deltas could suffer from enhanced inundation and increased coastal erosion. The population and area inundated rise significantly when considering increased flood risk due to storm surge. This study finds that direct anthropogenic effects determine ESLR in the majority of deltas studied, with a relatively less important role for eustatic sea-level rise. Serious challenges to human occupancy of deltaic regions worldwide are thus conveyed by factors which to date have been studied less comprehensively than the climate change–sea-level rise question. © 2005 Elsevier B.V. All rights reserved.

Patient-ventilator asynchrony during assisted mechanical ventilation

Abstract: Objective The incidence, pathophysiology, and consequences of patient-ventilator asynchrony are poorly known. We assessed the incidence of patient-ventilator asynchrony during assisted mechanical ventilation and we identified associated factors.

ASAS/EULAR recommendations for the management of ankylosing spondylitis

Abstract: OBJECTIVE: To develop evidence based recommendations for the management of ankylosing spondylitis (AS) as a combined effort of the 'ASsessment in AS' international working group and the European League Against Rheumatism. METHODS: Each of the 22 participants was asked to contribute up to 15 propositions describing key clinical aspects of AS management. A Delphi process was used to select 10 final propositions. A systematic literature search was then performed to obtain scientific evidence for each proposition. Outcome data for efficacy, adverse effects, and cost effectiveness were abstracted. The effect size, relative risk, number needed to treat, and incremental cost effectiveness ratio were calculated. On the basis of the search results, 10 major recommendations for the management of AS were constructed. The strength of recommendation was assessed based on the strength of the literature evidence, risk-benefit trade-off, and clinical expertise. RESULTS: The final recommendations considered the use of non-steroidal anti-inflammatory drugs (NSAIDs) (conventional NSAIDs, coxibs, and co-prescription of gastroprotective agents), disease modifying antirheumatic drugs, treatments with biological agents, simple analgesics, local and systemic steroids, non-pharmacological treatment (including education, exercise, and physiotherapy), and surgical interventions. Three general recommendations were also included. Research evidence (categories I-IV) supported 11 interventions in the treatment of AS. Strength of recommendation varied, depending on the category of evidence and expert opinion. CONCLUSION: Ten key recommendations for the treatment of AS were developed and assessed using a combination of research based evidence and expert consensus. Regular updating will be carried out to keep abreast of new developments in the management of AS.

Herpes simplex virus encephalitis in human UNC-93B deficiency.

Abstract: Herpes simplex virus-1 (HSV-1) encephalitis (HSE) is the most common form of sporadic viral encephalitis in western countries. Its pathogenesis remains unclear, as it affects otherwise healthy patients and only a small minority of HSV-1-infected individuals. Here, we elucidate a genetic etiology for HSE in two children with autosomal recessive deficiency in the intracellular protein UNC-93B, resulting in impaired cellular interferon-alpha/beta and -lambda antiviral responses. HSE can result from a single-gene immunodeficiency that does not compromise immunity to most pathogens, unlike most known primary immunodeficiencies. Other severe infectious diseases may also reflect monogenic disorders of immunity.

Passive leg raising predicts fluid responsiveness in the critically ill.

Abstract: Objective:Passive leg raising (PLR) represents a “self-volume challenge” that could predict fluid response and might be useful when the respiratory variation of stroke volume cannot be used for that purpose. We hypothesized that the hemodynamic response to PLR predicts fluid responsiveness in mechan

"Finite-Element" Displacement Fields Analysis from Digital Images: Application to Portevin-Le Châtelier Bands

Abstract: A new methodology is proposed to estimate displacement fields from pairs of images (reference and strained) that evaluates continuous displacement fields. This approach is specialized to a finite-element decomposition, therefore providing a natural interface with a numerical modeling of the mechanical behavior used for identification purposes. The method is illustrated with the analysis of Portevin–Le Châtelier bands in an aluminum alloy sample subjected to a tensile test. A significant progress with respect to classical digital image correlation techniques is observed in terms of spatial resolution and uncertainty.

Effects of confinement on freezing and melting.

Abstract: We present a review of experimental, theoretical, and molecular simulation studies of confinement effects on freezing and melting We consider both simple and more complex adsorbates that are confined in various environments (slit or cylindrical pores and also disordered porous materials) The most commonly used molecular simulation, theoretical and experimental methods are first presented We also provide a brief description of the most widely used porous materials The current state of knowledge on the effects of confinement on structure and freezing temperature, and the appearance of new surface-driven and confinement-driven phases are then discussed We also address how confinement affects the glass transition