Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008.

OBJECTIVE: To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," published in 2004. DESIGN: Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding. METHODS: We used the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations. A strong recommendation (1) indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost) or clearly do not. Weak recommendations (2) indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations. RESULTS: Key recommendations, listed by category, include early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7-10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C); administration of either crystalloid or colloid fluid resuscitation (1B); fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure > or = 65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for postoperative patients). In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7-9 g/dL (1B); a low tidal volume (1B) and limitation of inspiratory plateau pressure strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C); head of bed elevation in mechanically ventilated patients unless contraindicated (1B); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A); to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C); protocols for weaning and sedation/analgesia (1B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B); avoidance of neuromuscular blockers, if at all possible (1B); institution of glycemic control (1B), targeting a blood glucose < 150 mg/dL after initial stabilization (2C); equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1A); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding using H2 blockers (1A) or proton pump inhibitors (1B); and consideration of limitation of support where appropriate (1D). Recommendations specific to pediatric severe sepsis include greater use of physical examination therapeutic end points (2C); dopamine as the first drug of choice for hypotension (2C); steroids only in children with suspected or proven adrenal insufficiency (2C); and a recommendation against the use of recombinant activated protein C in children (1B). CONCLUSIONS: There was strong agreement among a large cohort of international experts regarding many level 1 recommendations for the best current care of patients with severe sepsis. Evidenced-based recommendations regarding the acute management of sepsis and septic shock are the first step toward improved outcomes for this important group of critically ill patients.

An interpretation of the deep seismic lines from the Penninic Alps of Valais (Switzerland)

The upper part of three deep seismic lines running across the Penninic Swiss Alps of Valais have been studied. Numerous reflectors illustrate the nappe structure of this internal part of the orogen. These reflectors, even at great depths (20-25 km), can be correlated with outcropping geological features and are most likely produced by lithological boundaries rather than by mylonites zones, which are hardly reflective in such an environment. Our interpretations, largely constrained by projections of the outcropping geology, have improved our knowledge of the deep structure of this segment of the Alpine belt, enhancing the importance of the backfolding and the crustal scale deformation phase which produced the Rawil-Valpelline depression and the Aar-Toce culmination. Furthermore we have here the possibility of correlating seismic patterns produced by ductile folds with the outcropping structures.

Uptake of new treatment strategies for deep vein thrombosis: an international audit.

OBJECTIVE: Study of the uptake of new medical technologies provides useful information on the transfer of published evidence into usual practice. We conducted an audit of selected hospitals in three countries (Canada, France, and Switzerland) to identify clinical predictors of low-molecular-weight (LMW) heparin use and outpatient treatment, and to compare the pace of uptake of these new therapeutic approaches across hospitals. DESIGN: Historical review of medical records. SETTING AND PARTICIPANTS: We reviewed the medical records of 3043 patients diagnosed with deep vein thrombosis (DVT) in five Canadian, two French, and two Swiss teaching hospitals from 1994 to 1998. Measures. We explored independent clinical variables associated with LMW heparin use and outpatient treatment, and determined crude and adjusted rates of LMW heparin use and outpatient treatment across hospitals. RESULTS: For the years studied, the overall rates of LMW heparin use and outpatient treatment in the study sample were 34.1 and 15.8%, respectively, with higher rates of use in later years. Many comorbidities were negatively associated with outpatient treatment, and risk-adjusted rates of use of these new approaches varied significantly across hospitals. CONCLUSION: There has been a relatively rapid uptake of LMW heparins and outpatient treatment for DVT in their early years of availability, but the pace of uptake has varied considerably across hospitals and countries.

Superficial and deep changes of cellular mechanical properties following cytoskeleton disassembly.

The cytoskeleton, composed of actin filaments, intermediate filaments, and microtubules, is a highly dynamic supramolecular network actively involved in many essential biological mechanisms such as cellular structure, transport, movements, differentiation, and signaling. As a first step to characterize the biophysical changes associated with cytoskeleton functions, we have developed finite elements models of the organization of the cell that has allowed us to interpret atomic force microscopy (AFM) data at a higher resolution than that in previous work. Thus, by assuming that living cells behave mechanically as multilayered structures, we have been able to identify superficial and deep effects that could be related to actin and microtubule disassembly, respectively. In Cos-7 cells, actin destabilization with Cytochalasin D induced a decrease of the visco-elasticity close to the membrane surface, while destabilizing microtubules with Nocodazole produced a stiffness decrease only in deeper parts of the cell. In both cases, these effects were reversible. Cell softening was measurable with AFM at concentrations of the destabilizing agents that did not induce detectable effects on the cytoskeleton network when viewing the cells with fluorescent confocal microscopy. All experimental results could be simulated by our models. This technology opens the door to the study of the biophysical properties of signaling domains extending from the cell surface to deeper parts of the cell.

Ultra deep blue: the ultimate chess player

Projecte d'adaptació del programa GNU Chess al sistema de grid computing 'Condor'. I amb això, es planteja un estudi sobre els algorismes de cerca i la seva aplicació en entorns distribuïts. Una sèrie de proves sobre unes mostres de una partida d'escacs contra el propi GNU Chess ens ajuden a posar de relleu els avantatges i inconvenients de cada un dels algorismes proposats.

Monetary and Fiscal Policy under Deep Habits

Recent work on optimal policy in sticky price models suggests that demand management through fiscal policy adds little to optimal monetary policy. We explore this consensus assignment in an economy subject to ‘deep’ habits at the level of individual goods where the counter-cyclicality of mark-ups this implies can result in government spending crowding-in private consumption in the short run. We explore the robustness of this mechanism to the existence of price discrimination in the supply of goods to the public and private sectors. We then describe optimal monetary and fiscal policy in our New Keynesian economy subject to the additional externality of deep habits and explore the ability of simple (but potentially nonlinear) policy rules to mimic fully optimal policy.

Siliceous deep-sea sponge Monorhaphis chuni: A potential paleoclimate archive in ancient animals

The deep-sea sponge Monorhaphis chuni forms giant basal spicules, which can reach lengths of 3 m; they represent the largest biogenic silica structures on Earth that is formed from an individual metazoan. The spicules offer a unique opportunity to record environmental change of past oceanic and climatic conditions. A giant spicule collected in the East China Sea in a depth of 1110 m was investigated. The oxygen isotopic composition and Mg/Ca ratios determined along center-to-surface segments are used as geochemical proxies for the assessment of seawater paleotemperatures. Calculations are based on the assumption that the calculated temperature near the surface of the spicule is identical with the average ambient temperature of 4 degrees C. A seawater temperature of 1.9 degrees C is inferred for the beginning of the lifespan of the Monorhaphis specimen. The temperature increases smoothly to 2.3 degrees C, to be followed by sharply increased and variable temperatures up to 6-10 degrees C. In the outer part of the spicule, the inferred seawater temperature is about 4 degrees C. The lifespan of the spicule can be estimated to 11,000 +/- 3000 years using the long-term trend of the inferred temperatures fitted to the seawater temperature age relationships since the Last Glacial Maximum. Specimens of Monorhaphis therefore represents one the oldest living animals on Earth. The remarkable temperature spikes of the ambient seawater occurring 9500-3100 years B.P. are explained by discharges of hydrothermal fluids in the neighborhood of the spicule. The irregular lamellar organization of the spicule and the elevated Mn concentrations during the high-temperature growth are consistent with a hydrothermal fluid input. (C) 2012 Elsevier B.V. All rights reserved.

Laser scanning-based recognition of rotational movements on a deep seated gravitational instability: The Cinque Torri case (North-Eastern Italian Alps)

The Cinque Torri group (Cortina d'Ampezzo, Italy) is an articulated system of unstable carbonatic rock monoliths located in a very important tourism area and therefore characterized by a significant risk. The instability phenomena involved represent an example of lateral spreading developed over a larger deep seated gravitational slope deformation (DSGSD) area. After the recent fall of a monolith of more than 10 000 m3, a scientific study was initiated to monitor the more unstable sectors and to characterize the past movements as a fundamental tool for predicting future movements and hazard assessment. To achieve greater insight on the ongoing lateral spreading process, a method for a quantitative analysis of rotational movements associated with the lateral spreading has been developed, applied and validated. The method is based on: i) detailed geometrical characterization of the area by means of laser scanner techniques; ii) recognition of the discontinuity sets and definition of a reference frame for each set, iii) correlation between the obtained reference frames related to a specific sector and a stable external reference frame, and iv) determination of the 3D rotations in terms of Euler angles to describe the present settlement of the Cinque Torri system with respect to the surrounding stable areas. In this way, significant information on the processes involved in the fragmentation and spreading of a former dolomitic plateau into different rock cliffs has been gained. The method is suitable to be applied to similar case studies.

Biocompatibility of an x-shaped zirconium implant in deep sclerectomy in rabbits.

BACKGROUND: The aim of this study was to evaluate the mid-term biocompatibility of a new x-shaped implant made of zirconium in an animal model of glaucoma surgery. METHODS: Preoperatively, ultrasound biomicroscopy (UBM), intraocular pressure (IOP) and outflow facility (OF) data were acquired. Upon surgery, one eye was chosen randomly to receive an implant, while the other received none. Ten rabbits went through a 1-, 2-, 3-, 4- and 6-month follow-up. IOP was measured regularly, UBM performed at 1, 3 and 6 months after surgery. At the end of the follow-up, OF was again measured. Histology sections were analyzed. RESULTS: For both groups IOP control was satisfactory, while OF initially increased at month 1 to resume preoperative values thereafter. Eyes with implants had larger filtration blebs which decreased faster than in eyes without the implant. Drainage vessel density, inflammatory cell number and fibrosis were higher in tissues near the implant. CONCLUSIONS: The zirconium implant initially promoted the positive effects of the surgery (IOP control, OF increase). Nevertheless, after several months, foreign body reactions and fibrosis had occurred on some implants that restrained the early benefit of such a procedure. Modifications of the zirconium implant geometry could enhance the overall success rate.

Combined Ex-PRESS LR-50/IOL implantation in modified deep sclerectomy plus pharmacoemulsification for glaucoma associated with cataract

RAPPORT DE SYNTHESEBUTLe but de cette étude est de suivre prospectivement les résultats d'une sclérectomie profonde (SP) modifiée en utilisant le tube Ex-PRJESS LR-50, associée à une phacoémulsification avec implantation d'une lentille intraoculaire (LIO), dans la chirurgie combinée du glaucome et de la cataracte.METHODENous avons inclus dans l'étude 24 yeux de 24 patients présentant un glaucome médicalement non contrôlé et une cataracte justifiant son ablation.Une phacoémulsification avec implantation d'une LIO est effectuée. Puis le tube Ex-PRESS LR-50 est inséré au niveau du canal de Schlemm, dans la chambre antérieure, sous un volet scléral. Une SP postérieure partielle est ensuite pratiquée afin de créer une bulle de filtration intrasclérale.Le taux de succès complet a été défini par une pression intraoculaire (PIO) <18 mmHg sans traitement et le taux de succès relatif par une PIO <18 mmHg avec ou sans traitement. En cas de fibrose ou de kyste de la bulle de filtration, une injection sous-conjonctivale d'une solution de Mitomycin C à 0.02% est réalisée, avec ou sans needling.RESULTATSLe suivi moyen était de 40.1±10.8 [moyenne±DS] mois. En préopératoire, la PIO se situait à 18.1 ±5.3 mmHg; la meilleure acuité visuelle corrigée (MAVC) était mesurée à 0.6±0.3 (échelle de Snellen) et le nombre de médicaments hypotenseurs oculaires était de 2.3±1.1. La PIO a diminué de 25.4% à 24 mois et de 27.0% à 48 mois. A 24 mois, 19 patients (86.3%) avaient une MAVC supérieure ou égal à 0.5, et à 48 mois la MAVC était mesurée à 0.7±0.3. Lors de la dernière visite, le nombre moyen de médicaments se situait à 0.6±0.8 (p<0.05). Des injections sous conjonctivales d'une solution de Mitomycin C à 0.02% ont été nécessaires dans 5 yeux. Aucune érosion conjonctivale n'a été constatée. Deux complications majeures ont été observées. Une endophtalmie, deux jours après l'intervention chirurgicale avec phtisis secondaire du globe oculaire. Une obstruction du tube Ex-PRESS LR-50 par de la fibrine, ayant justifié son ablation avec SP classique en un autre site.CONCLUSIONLe tube Ex-PRESS LR-50 inséré dans la chambre antérieure avec une SP modifiée réduit efficacement la PIO dans la chirurgie combinée du glaucome et prévient l'érosion conjonctivale, une complication importante lorsque l'implant n'est pas couvert par un volet scléral.