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.

New Sorex araneus karyotypes from Germany and the postglacial recolonization of central Europe

New G-banded karyotypes from populations of the common shrew Sorex araneus Linnaeus, 1758 provide a clearer picture of the distribution of chromosome races in central Europe. As expected according to their occurrence in neighbouring countries, the Jutland (kq, no), Laska (k/o) and Drnholec (ko, nr) races are also found in Germany. A new chromosome race "Rugen" (kq) is described from this Baltic Island. Together with the previously recorded races Ulm and Mooswald (kr), six chromosome races are now known from Germany. The resulting distribution pattern is characterized by high frequencies of different race-specific metacentrics at the periphery of the country and clines with decreasing frequencies towards the centre which is occupied by the Ulm race. This race is acrocentric for all chromosome arms involved in the observed race-specific fusions and represents a buffer between the surrounding, more metacentric races. According to the present distribution of these metacentrics, a scenario for the postglacial recolonization of central Europe by S. araneus populations on three different routes is proposed: from the east along the northern slopes of the Carpathian Arc, from the south-east along the Danube Valley and from the south-west through the Upper Rhine Valley.

Cost-effectiveness of low-molecular-weight heparin for secondary prophylaxis of cancer-related venous thromboembolism.

Although extended secondary prophylaxis with low-molecular-weight heparin was recently shown to be more effective than warfarin for cancer-related venous thromboembolism, its cost-effectiveness compared to traditional prophylaxis with warfarin is uncertain. We built a decision analytic model to evaluate the clinical and economic outcomes of a 6-month course of low-molecular-weight heparin or warfarin therapy in 65-year-old patients with cancer-related venous thromboembolism. We used probability estimates and utilities reported in the literature and published cost data. Using a US societal perspective, we compared strategies based on quality-adjusted life-years (QALYs) and lifetime costs. The incremental cost-effectiveness ratio of low-molecular-weight heparin compared with warfarin was 149,865 dollars/QALY. Low-molecular-weight heparin yielded a quality-adjusted life expectancy of 1.097 QALYs at the cost of 15,329 dollars. Overall, 46% (7108 dollars) of the total costs associated with low-molecular-weight heparin were attributable to pharmacy costs. Although the low-molecular-weigh heparin strategy achieved a higher incremental quality-adjusted life expectancy than the warfarin strategy (difference of 0.051 QALYs), this clinical benefit was offset by a substantial cost increment of 7,609 dollars. Cost-effectiveness results were sensitive to variation of the early mortality risks associated with low-molecular-weight heparin and warfarin and the pharmacy costs for low-molecular-weight heparin. Based on the best available evidence, secondary prophylaxis with low-molecular-weight heparin is more effective than warfarin for cancer-related venous thromboembolism. However, because of the substantial pharmacy costs of extended low-molecular-weight heparin prophylaxis in the US, this treatment is relatively expensive compared with warfarin.

Optimized venous return with a self-expanding cannula: from computational fluid dynamics to clinical application.

The Smart canula concept allows for collapsed cannula insertion, and self-expansion within a vein of the body. (A) Computational fluid dynamics, and (B) bovine experiments (76+/-3.8 kg) were performed for comparative analyses, prior to (C) the first clinical application. For an 18F access, a given flow of 4 l/min (A) resulted in a pressure drop of 49 mmHg for smart cannula versus 140 mmHg for control. The corresponding Reynolds numbers are 680 versus 1170, respectively. (B) For an access of 28F, the maximal flow for smart cannula was 5.8+/-0.5 l/min versus 4.0+/-0.1 l/min for standard (P<0.0001), for 24F 5.5+/-0.6 l/min versus 3.2+/-0.4 l/min (P<0.0001), and for 20F 4.1+/-0.3 l/min versus 1.6+/-0.3 l/min (P<0.0001). The flow obtained with the smart cannula was 270+/-45% (20F), 172+/-26% (24F), and 134+/-13% (28F) of standard (one-way ANOVA, P=0.014). (C) First clinical application (1.42 m2) with a smart cannula showed 3.55 l/min (100% predicted) without additional fluids. All three assessment steps confirm the superior performance of the smart cannula design.

Remeis casolans per a bèsties i humans: medicina i veterinària popular a la catalunya central

Treball de recerca realitzat per un alumne d’ensenyament secundari i guardonat amb un Premi CIRIT per fomentar l'esperit científic del Jovent l’any 2008. Consisteix en un diccionari informàtic que recull plantes i productes, cadascun amb les seves propietats medicinals i altres usos que se’ls atribueixen popularment i la forma de preparar remeis i aplicar-los per a cada malaltia o afecció. La informació s’ha extret de les entrevistes fetes a informants d’entre 60 i 90 anys del Bages, Berguedà i Solsonès, i es complementa amb un herbari i una mostra de preparacions dels remeis.

Official Central Bank Interventions in the Foreign Exchange Markets: A DCC Approach with Exogenous Variables

This paper assesses the impact of official central bank interventions (CBIs) on exchange rate returns, their volatility and bilateral correlations. By exploiting the recent publication of intervention data by the Bank of England, this study is able to investigate fficial interventions by a total number of four central banks, while the previous studies have been limited to three (the Federal Reserve, Bundesbank and Bank of Japan). The results of the existing literature are reappraised and refined. In particular, unilateral CBI is found to be more successful than coordinated CBI. The likely implications of these findings are then discussed.

Does the euro dominate Central and Eastern European money markets?

The so-called German Dominance Hypothesis (GDH) claimed that Bundesbank policies were transmitted into other European Monetary System (EMS) interest rates during the pre-euro era. We reformulate this hypothesis for the Central and Eastern European (CEE) countries that are on the verge of accessing the eurozone. We test this \Euro Dominance Hypothesis (EDH)" in a novel way using a global vector autoregressive (GVAR) approach that combines country-speci c error correction models in a global system. We nd that euro area monetary policies are transmitted into CEE interest rates which provides evidence for monetary integration between the eurozone and CEE countries. Our framework also allows for introducing global monetary shocks to provide empirical evidence regarding the e ects of the recent nancial crisis on monetary integration in Europe.

Flebotomíneos (Diptera: Psychodidae) no estado de Roraima, Brasil: I. espécies coletadas nas regiões sul e central

Durante 1987, nas regiões sul e central do Estado de Roraima, foram realizadas coletas de flebotomineos nas bases de árvores e em armadilhas CDC colocadas a 1,5 e 10m de altura do solo. Foram obtidos 2812 espécimes, de 45 espécies: 35 na região sul e 27 na região cental; 18 espécies foram comuns as duas áreas e 21 estão sendo aqui assinaladas pela primeira vez no Estado. A presente publicação eleva a 54 o número de espécies conhecidad no Estado.

Evolució del poblament i organització del territori a la Catalunya interior durant l'Antiguitat Tardana i l'Alta Edat Mitjana: els casos de la Catalunya Central (Bages, Berguedà i Solsonès) i la Garrotxa (segles V-X)

Projecte de recerca elaborat a partir d’una estada a la Université de Toulouse 2 – Le Mirail entre gener i juny del 2007. En concret, l’estada efectuada ha suposat la integració de qui signa aquesta memòria dins l’equip al-Andalus/Hispaniae, dirigit pel professor Philippe Sénac, una de les diverses branques que conformen el grup FRAMESPA d’aquella universitat, unitat de recerca adscrita al CNRS (UMR 5136). El títol proposat per al contingut de la recerca en la sol•licitud presentada, Evolució del poblament i organització del territori a la Catalunya interior a l’Alta Edat Mitjana, encapçalava un pla de treball que tenia per objectiu la recopilació i l’anàlisi de dades arqueològiques i textuals que oferissin un escenari a partir del qual establir una seqüència evolutiva en relació a les diferents tendències pel que fa al poblament tardoantic i altmedieval en dues zones diferenciades com són les conques mitjanes dels rius Llobregat i Cardener, a la Catalunya Central, i la capçalera del riu Fluvià, a la Garrotxa. Així, s’han pogut detectar, a partir de la contrastació de les diferents dades, fenòmens diversos que reflecteixen la incidència dels successius canvis històrics a nivell territorial i de poblament.

GLUTX1, a novel mammalian glucose transporter expressed in the central nervous system and insulin-sensitive tissues.

Based on homology with GLUT1-5, we have isolated a cDNA for a novel glucose transporter, GLUTX1. This cDNA encodes a protein of 478 amino acids that shows between 29 and 32% identity with rat GLUT1-5 and 32-36% identity with plant and bacterial hexose transporters. Unlike GLUT1-5, GLUTX1 has a short extracellular loop between transmembrane domain (TM) 1 and TM2 and a long extracellular loop between TM9 and TM10 that contains the only N-glycosylation site. When expressed in Xenopus oocytes, GLUTX1 showed strong transport activity only after suppression of a dileucine internalization motif present in the amino-terminal region. Transport activity was inhibited by cytochalasin B and partly competed by D-fructose and D-galactose. The Michaelis-Menten constant for glucose was approximately 2 mM. When translated in reticulocytes lysates, GLUTX1 migrates as a 35-kDa protein that becomes glycosylated in the presence of microsomal membranes. Western blot analysis of GLUTX1 transiently expressed in HEK293T cells revealed a diffuse band with a molecular mass of 37-50 kDa that could be converted to a approximately 35-kDa polypeptide following enzymatic deglycosylation. Immunofluorescence microscopy detection of GLUTX1 transfected into HEK293T cells showed an intracellular staining. Mutation of the dileucine internalization motif induced expression of GLUTX1 at the cell surface. GLUTX1 mRNA was detected in testis, hypothalamus, cerebellum, brainstem, hippocampus, and adrenal gland. We hypothesize that, in a similar fashion to GLUT4, in vivo cell surface expression of GLUTX1 may be inducible by a hormonal or other stimulus.

Synanthropic trends in urban andextraurban taxocenoses of Sarcophaginae (Diptera) in three central european cities

An attempt has been made to characterize the synanthropic trends in Sarcophaginae of three Central European cities, viz. Brno, Bratislava and Budapest. The polar ordination of both sarcophagine taxa and of their taxocenoses revealed clear-cut trends towards culturophily and synanthropy in the male preconnubial aggregations of Sarchophaginae evidencing that this group of high Diptera represent an excellent model for the study of this phenomenon.

Marbles and carbonate rocks from central Morocco: a petrographic, mineralogical and geochemical study

Petrographic, mineralogical, and stable isotopes (delta C-13, delta O-18 values) compositions were used to characterise marbles and sedimentary carbonate rocks from central Morocco, which are considered to be a likely source of ornamental and building material from Roman time to the present day. This new data set was used in the frame of an archaeometric provenance study on Roman artefacts from the town of Thamusida (Kenitra, north Morocco), to assess the potential employment of these rocks for the manufacture of the archaeological materials. A representative set of samples from marbles and other carbonate rocks (limestone, dolostone) were collected in several quarries and outcrops in the Moroccan Meseta, in a region extending from the Meknes-Khenifra alignment to the Atlantic Ocean. All the samples were studied using a petrographic, mineralogical and geochemical methods. The petrographic and minerological investigations (optical microscopy, electron microscopy, X-ray diffraction) allowed to group the carbonate rocks in limestones, foliated limestone, diagenetic breccias and dolostone. The limestones could be further grouped as mudstones, wackestones-packstones, crinoid grainstones, oolitic grainstone and floatstones. Textural differences allowed to define marbles varieties. The stable carbon and oxygen isotope composition proved to be quite useful in the discrimination of marble sources, with apparently less discriminatory potential for carbonate rocks.

The Economics of CO2-EOR Cluster Developments in the UK Central North Sea/ Outer Moray Firth

NORTH SEA STUDY OCCASIONAL PAPER No. 123

The Signalling Channel of Central Bank Interventions: Modelling the Yen/US Dollar Exchange Rate

This paper presents a theoretical framework analysing the signalling channel of exchange rate interventions as an informational trigger. We develop an implicit target zone framework with learning in order to model the signalling channel. The theoretical premise of the model is that interventions convey signals that communicate information about the exchange rate objectives of central bank. The model is used to analyse the impact of Japanese FX interventions during the period 1999 -2011 on the yen/US dollar dynamics.