Association between inflammatory mediators and response to inhaled nitric oxide in a model of endotoxin-induced lung injury

INTRODUCTION: Inhaled nitric oxide (INO) allows selective pulmonary vasodilation in acute respiratory distress syndrome and improves PaO2 by redistribution of pulmonary blood flow towards better ventilated parenchyma. One-third of patients are nonresponders to INO, however, and it is difficult to predict who will respond. The aim of the present study was to identify, within a panel of inflammatory mediators released during endotoxin-induced lung injury, specific mediators that are associated with a PaO2 response to INO. METHODS: After animal ethics committee approval, pigs were anesthetized and exposed to 2 hours of endotoxin infusion. Levels of cytokines, prostanoid, leucotriene and endothelin-1 (ET-1) were sampled prior to endotoxin exposure and hourly thereafter. All animals were exposed to 40 ppm INO: 28 animals were exposed at either 4 hours or 6 hours and a subgroup of nine animals was exposed both at 4 hours and 6 hours after onset of endotoxin infusion. RESULTS: Based on the response to INO, the animals were retrospectively placed into a responder group (increase in PaO2 > or = 20%) or a nonresponder group. All mediators increased with endotoxin infusion although no significant differences were seen between responders and nonresponders. There was a mean difference in ET-1, however, with lower levels in the nonresponder group than in the responder group, 0.1 pg/ml versus 3.0 pg/ml. Moreover, five animals in the group exposed twice to INO switched from responder to nonresponder and had decreased ET-1 levels (3.0 (2.5 to 7.5) pg/ml versus 0.1 (0.1 to 2.1) pg/ml, P < 0.05). The pulmonary artery pressure and ET-1 level were higher in future responders to INO. CONCLUSIONS: ET-1 may therefore be involved in mediating the response to INO

Real-Time Gait Phase Detection on Wearable Devices for Real-World Free-Living Gait

Detecting gait phases with wearables unobtrusively and reliably in real-time is important for clinical gait rehabilitation and early diagnosis of neurological diseases. Due to hardware limitations of microcontrollers in wearable devices (e.g., memory and computation power), reliable real-time gait phase detection on the microcontrollers remains a challenge, especially for long-term real-world free-living gait. In this work, a novel algorithm based on a reduced support vector machine (RSVM) and a finite state machine (FSM) is developed to address this. The RSVM is developed by exploiting the cascaded K-means clustering to reduce the model size and computation time of a standard SVM by 88% and a factor of 36, with only minor degradation in gait phase prediction accuracy of around 4%. For each gait phase prediction from the RSVM, the FSM is designed to validate the prediction and correct misclassifications. The developed algorithm is implemented on a microcontroller of a wearable device and its real-time (on the fly) classification performance is evaluated by twenty healthy subjects walking along a predefined real-world route with uncontrolled free-living gait. It shows a promising real-time performance with an accuracy of 91.51%, a sensitivity of 91.70%, and a specificity of 95.77%. The algorithm also demonstrates its robustness with varying walking conditions

Power politics and princely debts: why Germany's common currency failed, 1549-56

Using new sources, this article examines how in the years around 1550 Charles V and the imperial estates came close to creating a common currency for the Holy Roman Empire. The article analyses whose interests prevailed in the negotiations and how, despite the resistance of some important actors, the Imperial diet of 1551 was able to unanimously agree on the currency bill. It also analyses why the common currency still failed: This was the case because of the desire of many princes to ease the repayment of their debts by establishing a bimetallic currency, and even more importantly because of Charles V's attempt to weaken the Elector of Saxony by undervaluing the taler. In this, Charles exploited the diet's implicit ex-ante agreement with him to set the rates at which old money was allowed to continue in circulation. His manipulations provoked resistance, raised the costs of implementing the common currency, and caused its failure