A dynamical system approach to higher order gravity

The dynamical system approach has recently acquired great importance in the investigation on higher order theories of gravity. In this talk I review the main results and I give brief comments on the perspectives for further developments.Comment: 6 pages, 1 figure, 2 tables, talk given at IRGAC 2006, July 200

Bench-to-bedside review: Bacterial pneumonia with influenza - pathogenesis and clinical implications

Seasonal and pandemic influenza are frequently complicated by bacterial infections, causing additional hospitalization and mortality. Secondary bacterial respiratory infection can be subdivided into combined viral/bacterial pneumonia and post-influenza pneumonia, which differ in their pathogenesis. During combined viral/bacterial infection, the virus, the bacterium and the host interact with each other. Post-influenza pneumonia may, at least in part, be due to resolution of inflammation caused by the primary viral infection. These mechanisms restore tissue homeostasis but greatly impair the host response against unrelated bacterial pathogens. In this review we summarize the underlying mechanisms leading to combined viral/bacterial infection or post-influenza pneumonia and highlight important considerations for effective treatment of bacterial pneumonia during and shortly after influenza

Defining Uncertainty: A Conceptual Basis for Uncertainty Management in Model-Based Decision Support

The aim of this paper is to provide a conceptual basis for the systematic treatment of uncertainty in model-based decision support activities such as policy analysis, integrated assessment and risk assessment. It focuses on the uncertainty perceived from the point of view of those providing information to support policy decisions (i.e., the modellers’ view on uncertainty) – uncertainty regarding the analytical outcomes and conclusions of the decision support exercise. Within the regulatory and management sciences, there is neither commonly shared terminology nor full agreement on a typology of uncertainties. Our aim is to synthesise a wide variety of contributions on uncertainty in model-based decision support in order to provide an interdisciplinary theoretical framework for systematic uncertainty analysis. To that end we adopt a general definition of uncertainty as being any deviation from the unachievable ideal of completely deterministic knowledge of the relevant system. We further propose to discriminate among three dimensions of uncertainty: location, level and nature of uncertainty, and we harmonise existing typologies to further detail the concepts behind these three dimensions of uncertainty.We propose an uncertainty matrix as a heuristic tool to classify and report the various dimensions of uncertainty, thereby providing a conceptual framework for better communication among analysts as well as between them and policymakers and stakeholders. Understanding the various dimensions of uncertainty helps in identifying, articulating, and prioritising critical uncertainties, which is a crucial step to more adequate acknowledgement and treatment of uncertainty in decision support endeavours and more focused research on complex, inherently uncertain, policy issues

Mild hypoglycemia is independently associated with increased mortality in the critically ill

Introduction: Severe hypoglycemia (blood glucose concentration (BG) < 40 mg/dL) is independently associated with an increased risk of mortality in critically ill patients. The association of milder hypoglycemia (BG < 70 mg/dL) with mortality is less clear.Methods: Prospectively collected data from two observational cohorts in the USA and in The Netherlands, and from the prospective GLUCONTROL trial were analyzed. Hospital mortality was the primary endpoint.Results: We analyzed data from 6,240 patients: 3,263 admitted to Stamford Hospital (ST), 2,063 admitted to three institutions in The Netherlands (NL) and 914 who participated in the GLUCONTROL trial (GL). The percentage of patients with hypoglycemia varied from 18% to 65% among the different cohorts. Patients with hypoglycemia experienced higher mortality than did those without hypoglycemia even after stratification by severity of illness, diagnostic category, diabetic status, mean BG during intensive care unit (ICU) admission and coefficient of variation (CV) as a reflection of glycemic variability. The relative risk (RR, 95% confidence interval) of mortality associated with minimum BG < 40, 40 to 54 and 55 to 69 mg/dL compared to patients with minimum BG 80 to 109 mg/dL was 3.55 (3.02 to 4.17), 2.70 (2.31 to 3.14) and 2.18 (1.87 to 2.53), respectively (all P < 0.0001). The RR of mortality associated with any hypoglycemia < 70 mg/dL was 3.28 (2.78 to 3.87) (P < 0.0001), 1.30 (1.12 to 1.50) (P = 0.0005) and 2.11 (1.62 to 2.74) (P < 0.0001) for the ST, NL and GL cohorts, respectively. Multivariate regression analysis demonstrated that minimum BG < 70 mg/dL, 40 to 69 mg/dL and < 40 mg/dL were independently associated with increased risk of mortality for the entire cohort of 6,240 patients (odds ratio (OR) (95% confidence interval (CI)) 1.78 (1.39 to 2.27) P < 0.0001), 1.29 (1.11 to 1.51) P = 0.0011 and 1.87 (1.46 to 2.40) P < 0.0001) respectively.Conclusions: Mild hypoglycemia was associated with a significantly increased risk of mortality in an international cohort of critically ill patients. Efforts to reduce the occurrence of hypoglycemia in critically ill patients may reduce mortality. © 2011 Krinsley et al. licensee BioMed Central Ltd.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

CAVE:Cerebral artery–vein segmentation in digital subtraction angiography

Cerebral X-ray digital subtraction angiography (DSA) is a widely used imaging technique in patients with neurovascular disease, allowing for vessel and flow visualization with high spatio-temporal resolution. Automatic artery–vein segmentation in DSA plays a fundamental role in vascular analysis with quantitative biomarker extraction, facilitating a wide range of clinical applications. The widely adopted U-Net applied on static DSA frames often struggles with disentangling vessels from subtraction artifacts. Further, it falls short in effectively separating arteries and veins as it disregards the temporal perspectives inherent in DSA. To address these limitations, we propose to simultaneously leverage spatial vasculature and temporal cerebral flow characteristics to segment arteries and veins in DSA. The proposed network, coined CAVE, encodes a 2D+time DSA series using spatial modules, aggregates all the features using temporal modules, and decodes it into 2D segmentation maps. On a large multi-center clinical dataset, CAVE achieves a vessel segmentation Dice of 0.84 (±0.04) and an artery–vein segmentation Dice of 0.79 (±0.06). CAVE surpasses traditional Frangi-based k-means clustering (P &lt; 0.001) and U-Net (P &lt; 0.001) by a significant margin, demonstrating the advantages of harvesting spatio-temporal features. This study represents the first investigation into automatic artery–vein segmentation in DSA using deep learning. The code is publicly available at https://github.com/RuishengSu/CAVE_DSA.</p

autoTICI: Automatic Brain Tissue Reperfusion Scoring on 2D DSA Images of Acute Ischemic Stroke Patients

The Thrombolysis in Cerebral Infarction (TICI) score is an important metric for reperfusion therapy assessment in acute ischemic stroke. It is commonly used as a technical outcome measure after endovascular treatment (EVT). Existing TICI scores are defined in coarse ordinal grades based on visual inspection, leading to inter- and intra-observer variation. In this work, we present autoTICI, an automatic and quantitative TICI scoring method. First, each digital subtraction angiography (DSA) sequence is separated into four phases (non-contrast, arterial, parenchymal and venous phase) using a multi-path convolutional neural network (CNN), which exploits spatio-temporal features. The network also incorporates sequence level label dependencies in the form of a state-transition matrix. Next, a minimum intensity map (MINIP) is computed using the motion corrected arterial and parenchymal frames. On the MINIP image, vessel, perfusion and background pixels are segmented. Finally, we quantify the autoTICI score as the ratio of reperfused pixels after EVT. On a routinely acquired multi-center dataset, the proposed autoTICI shows good correlation with the extended TICI (eTICI) reference with an average area under the curve (AUC) score of 0.81. The AUC score is 0.90 with respect to the dichotomized eTICI. In terms of clinical outcome prediction, we demonstrate that autoTICI is overall comparable to eTICI.Comment: 10 pages; submitted to IEEE TM

Nebulized heparin in burn patients with inhalation trauma : safety and feasibility

Background: Pulmonary hypercoagulopathy is intrinsic to inhalation trauma. Nebulized heparin could theoretically be beneficial in patients with inhalation injury, but current data are conflicting. We aimed to investigate the safety, feasibility, and effectiveness of nebulized heparin. Methods: International multicenter, double-blind, placebo-controlled randomized clinical trial in specialized burn care centers. Adult patients with inhalation trauma received nebulizations of unfractionated heparin (25,000 international unit (IU), 5 mL) or placebo (0.9% NaCl, 5 mL) every four hours for 14 days or until extubation. The primary outcome was the number of ventilator-free days at day 28 post-admission. Here, we report on the secondary outcomes related to safety and feasibility. Results: The study was prematurely stopped after inclusion of 13 patients (heparin N = 7, placebo N = 6) due to low recruitment and high costs associated with the trial medication. Therefore, no analyses on effectiveness were performed. In the heparin group, serious respiratory problems occurred due to saturation of the expiratory filter following nebulizations. In total, 129 out of 427 scheduled nebulizations were withheld in the heparin group (in 3 patients) and 45 out of 299 scheduled nebulizations were withheld in the placebo group (in 2 patients). Blood-stained sputum or expected increased bleeding risks were the most frequent reasons to withhold nebulizations. Conclusion: In this prematurely stopped trial, we encountered important safety and feasibility issues related to frequent heparin nebulizations in burn patients with inhalation trauma. This should be taken into account when heparin nebulizations are considered in these patients

Vps3 and Vps8 control integrin trafficking from early to recycling endosomes and regulate integrin-dependent functions

Recycling endosomes maintain plasma membrane homeostasis and are important for cell polarity, migration, and cytokinesis. Yet, the molecular machineries that drive endocytic recycling remain largely unclear. The CORVET complex is a multi-subunit tether required for fusion between early endosomes. Here we show that the CORVET-specific subunits Vps3 and Vps8 also regulate vesicular transport from early to recycling endosomes. Vps3 and Vps8 localise to Rab4-positive recycling vesicles and co-localise with the CHEVI complex on Rab11-positive recycling endosomes. Depletion of Vps3 or Vps8 does not affect transferrin recycling, but delays the delivery of internalised integrins to recycling endosomes and their subsequent return to the plasma membrane. Consequently, Vps3/8 depletion results in defects in integrin-dependent cell adhesion and spreading, focal adhesion formation, and cell migration. These data reveal a role for Vps3 and Vps8 in a specialised recycling pathway important for integrin trafficking