Dual-loop circuits in postoperative atrial macro re-entrant tachycardias

Background Patients late after open-heart surgery may develop dual-loop reentrant atrial arrhythmias, and mapping and catheter ablation remain challenging despite computer-assisted mapping techniques. Objectives The purpose of the study was to demonstrate the prevalence and characteristics of dual-loop reentrant arrhythmias, and to define the optimal mapping and ablation strategy. Methods Fourty consecutive patients (mean age 52+/-12 years) with intra-atrial reentrant tachycardia (IART) after open-heart surgery (with an incision of the right atrial free wall) were studied. Dual-loop IART was defined as the presence of two simultaneous atrial circuits. Following an abrupt tachycardia change during radiofrequency (RF) ablation, electrical disconnection of the targeted reentry isthmus from the remaining circuit was demonstrated by entrainment mapping. Furthermore, the second circuit loop was localized using electroanatomic mapping and/or entrainment mapping. Results Dual-loop IART was demonstrated in 8 patients (20%, 5 patients with congenital heart disease, 3 with acquired heart disease). Dual-loop IART included an isthmus-dependant atrial flutter combined with a reentry related to the atriotomy scar. The diagnosis of dual-loop IART required the comparison of entrainment mapping before and after tachycardiamodification. Overall, 35 patients had successful RF ablation (88%). Success rates were lower in patients with dual-loop IART than in patient without dual-loop IART. Ablation failures in 3 patients with dual-loop IART were related to the inability to properly transect the second tachycardia isthmus in the right atrial free wall. Conclusions Dual-loop IART is relatively common after heart surgery involving a right atriotomy. Abrupt tachycardia change and specific entrainment mapping maneuvers demonstrate these circuits. Electroanatomic mapping appears to be important to assist catheter ablation of periatriotomy circuits.

Closed-loop control of mean arterial blood pressure during surgery with alfentanil: clinical evaluation of a novel model-based predictive controller

BACKGROUND: In contrast to hypnosis, there is no surrogate parameter for analgesia in anesthetized patients. Opioids are titrated to suppress blood pressure response to noxious stimulation. The authors evaluated a novel model predictive controller for closed-loop administration of alfentanil using mean arterial blood pressure and predicted plasma alfentanil concentration (Cp Alf) as input parameters. METHODS: The authors studied 13 healthy patients scheduled to undergo minor lumbar and cervical spine surgery. After induction with propofol, alfentanil, and mivacurium and tracheal intubation, isoflurane was titrated to maintain the Bispectral Index at 55 (+/- 5), and the alfentanil administration was switched from manual to closed-loop control. The controller adjusted the alfentanil infusion rate to maintain the mean arterial blood pressure near the set-point (70 mmHg) while minimizing the Cp Alf toward the set-point plasma alfentanil concentration (Cp Alfref) (100 ng/ml). RESULTS: Two patients were excluded because of loss of arterial pressure signal and protocol violation. The alfentanil infusion was closed-loop controlled for a mean (SD) of 98.9 (1.5)% of presurgery time and 95.5 (4.3)% of surgery time. The mean (SD) end-tidal isoflurane concentrations were 0.78 (0.1) and 0.86 (0.1) vol%, the Cp Alf values were 122 (35) and 181 (58) ng/ml, and the Bispectral Index values were 51 (9) and 52 (4) before surgery and during surgery, respectively. The mean (SD) absolute deviations of mean arterial blood pressure were 7.6 (2.6) and 10.0 (4.2) mmHg (P = 0.262), and the median performance error, median absolute performance error, and wobble were 4.2 (6.2) and 8.8 (9.4)% (P = 0.002), 7.9 (3.8) and 11.8 (6.3)% (P = 0.129), and 14.5 (8.4) and 5.7 (1.2)% (P = 0.002) before surgery and during surgery, respectively. A post hoc simulation showed that the Cp Alfref decreased the predicted Cp Alf compared with mean arterial blood pressure alone. CONCLUSION: The authors' controller has a similar set-point precision as previous hypnotic controllers and provides adequate alfentanil dosing during surgery. It may help to standardize opioid dosing in research and may be a further step toward a multiple input-multiple output controller.

Real-time closed-loop electrophysiology: towards new frontiers in in vitro investigations in the neurosciences

Reflected at any level of organization of the central nervous system, most of the processes ranging from ion channels to neuronal networks occur in a closed loop, where the input to the system depends on its output. In contrast, most in vitro preparations and experimental protocols operate autonomously, and do not depend on the output of the studied system. Thanks to the progress in digital signal processing and real-time computing, it is now possible to artificially close the loop and investigate biophysical processes and mechanisms under increased realism. In this contribution, we review some of the most relevant examples of a new trend in in vitro electrophysiology, ranging from the use of dynamic-clamp to multi-electrode distributed feedback stimulation. We are convinced these represents the beginning of new frontiers for the in vitro investigation of the brain, promising to open the still existing borders between theoretical and experimental approaches while taking advantage of cutting edge technologies.

Phylogenetic relationships of German heavy draught horse breeds inferred from mitochondrial DNA D-loop variation

We analysed a 610-bp mitochondrial (mt)DNA D-loop fragment in a sample of German draught horse breeds and compared the polymorphic sites with sequences from Arabian, Hanoverian, Exmoor, Icelandic, Sorraia and Przewalski's Horses as well as with Suffolk, Shire and Belgian horses. In a total of 65 horses, 70 polymorphic sites representing 47 haplotypes were observed. The average percentage of polymorphic sites was 11.5% for the mtDNA fragment analysed. In the nine different draught horse breeds including South German, Mecklenburg, Saxon Thuringa coldblood, Rhenisch German, Schleswig Draught Horse, Black Forest Horse, Shire, Suffolk and Belgian, 61 polymorphic sites and 24 haplotypes were found. The phylogenetic analysis failed to show monophyletic groups for the draught horses. The analysis indicated that the draught horse populations investigated consist of diverse genetic groups with respect to their maternal lineage.

Angiopoietin-1 and angiopoietin-2 share the same binding domains in the Tie-2 receptor involving the first Ig-like loop and the epidermal growth factor-like repeats

Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) have been identified as ligands with different effector functions of the vascular assembly and maturation-mediating receptor tyrosine kinase Tie-2. To understand the molecular interactions of the angiopoietins with their receptor, we have studied the binding of Ang-1 and Ang-2 to the Tie-2 receptor. Enzyme-linked immunosorbent assay-based competition assays and co-immunoprecipitation experiments analyzing the binding of Ang-1 and Ang-2 to truncation mutants of the extracellular domain of Tie-2 showed that the first Ig-like loop of Tie-2 in combination with the epidermal growth factor (EGF)-like repeats (amino acids 1-360) is required for angiopoietin binding. The first Ig-like domain or the EGF-like repeats alone are not capable of binding Ang-1 and Ang-2. Concomitantly, we made the surprising finding that Tie-2 exon-2 knockout mice do express a mutated Tie-2 protein that lacks 104 amino acids of the first Ig-like domain. This mutant Tie-2 receptor is functionally inactive as shown by the lack of ligand binding and receptor phosphorylation. Collectively, the data show that the first 104 amino acids of the Tie-2 receptor are essential but not sufficient for angiopoietin binding. Conversely, the first 360 amino acids (Ig-like domain plus EGF-like repeats) of the Tie-2 receptor are necessary and sufficient to bind both Ang-1 and Ang-2, which suggests that differential receptor binding is not likely to be responsible for the different functions of Ang-1 and Ang-2.

Two neighboring residues of loop A of the alpha1 subunit point towards the benzodiazepine binding site of GABAA receptors

Benzodiazepines are widely used drugs exerting sedative, anxiolytic, muscle relaxant, and anticonvulsant effects by acting through specific high affinity binding sites on some GABA(A) receptors. It is important to understand how these ligands are positioned in this binding site. We are especially interested here in the conformation of loop A of the alpha(1)beta(2)gamma(2) GABA(A) receptor containing a key residue for the interaction of benzodiazepines: alpha(1)H101. We describe a direct interaction of alpha(1)N102 with a diazepam- and an imidazobenzodiazepine-derivative. Our observations help to better understand the conformation of this region of the benzodiazepine pocket in GABA(A) receptor.

Symptomatic intracranial haemorrhage after intra-arterial thrombolysis in acute ischaemic stroke: assessment of 294 patients treated with urokinase

BACKGROUND: The PROACT II trial showed that intra-arterial thrombolysis (IAT) is effective for treatment of acute ischaemic stroke attributable to M1 and M2 segment occlusions. Incidence of symptomatic intracranial haemorrhage (sICH) was 10%. OBJECTIVE: To evaluate the risk and predictors of sICH after IAT by using urokinase in a large number of patients presenting with the whole spectrum of cerebral vessel occlusions. METHODS: 294 patients with stroke treated with intra-arterial urokinase were retrospectively analysed. The risk of sICH as well as bleeding characteristics were assessed. Demographic and radiological data, time to treatment, urokinase dose, recanalisation rates, stroke aetiology and severity were analysed for predictors. RESULTS: sICH occurred in 14 of 294 (4.8%) patients. The median National Institute of Health Stroke Scale score of all patients was 15. All but one sICH were located in the infarcted brain tissue, and no sICH occurred in patients with peripheral vessel occlusions (M3 or M4 segments of the middle cerebral artery). Poor collaterals (p = 0.001), early signs of ischaemia on computed tomography (p = 0.003), higher urokinase dose (p = 0.019), lower recanalisation rate (p = 0.02) and higher diastolic blood pressure on admission (p = 0.04) were found to be correlated with sICH on univariate analysis. On multivariate analysis, poor collaterals (p = 0.004), urokinase dose (p = 0.021) and early signs on computed tomography (p = 0.026) remained predictors of sICH. CONCLUSIONS: With regard to the whole spectrum of cerebral vessel occlusions, an incidence of <5% sICH after IAT is distinctly low. This result underlines the important role of IAT in the treatment of acute stroke.

Quality of life in stroke survivors after local intra-arterial thrombolysis

Background: We aimed to assess quality of life (QOL) and its predictors in stroke survivors after local intra-arterial thrombolysis (IAT) as well as to measure QOL according to the site of pretreatment vessel occlusion. Methods: From January 2000 to April 2004, 175 consecutive patients underwent IAT for acute ischemic stroke. Clinical and radiological data were collected prospectively. We contacted 135 stroke survivors after a mean of 923 (+/-431) days, 132 responded. QOL, assessed with EuroQol (EQ-5D), and functional abilities, measured with the modified Rankin Scale (mRS) and the Barthel Index, were compared, and predictors of QOL were analyzed. Results: Measured with EQ-5D, 56% of the patients reported a good QOL (EQ-5D Index >/=70). Low mRS and high Barthel Index scores at follow-up were associated with better overall QOL (Kendall's tau >0.5). Nevertheless, 25% of the functionally independent patients (mRS 0-2) indicated a markedly impaired QOL (EQ-5D Index <70) and 10% of disabled patients indicated good QOL. QOL was significantly lower in patients with occlusion of the internal carotid artery compared to patients with occlusion of the basilar artery or the M1, M2 or M3/4 segment of the middle cerebral artery (EQ-5D Index: p = 0.005). A high National Institute of Health Stroke Scale score on admission and occlusion of the internal carotid artery were independent predictors of impaired QOL (p < 0.05). Conclusion: More than half of the stroke survivors treated with IAT reported a good QOL, mostly survivors with mild disabilities. QOL assessment gives information that is not provided by traditional outcome scores. Our results support guidelines to measure QOL in stroke research. Copyright (c) 2008 S. Karger AG, Basel.

Filtration and oxidation characteristics of a diesel oxidation catalyst and a catalyzed particulate filter : development of a 1-D 2-layer model

The emissions, filtration and oxidation characteristics of a diesel oxidation catalyst (DOC) and a catalyzed particulate filter (CPF) in a Johnson Matthey catalyzed continuously regenerating trap (CCRT ®) were studied by using computational models. Experimental data needed to calibrate the models were obtained by characterization experiments with raw exhaust sampling from a Cummins ISM 2002 engine with variable geometry turbocharging (VGT) and programmed exhaust gas recirculation (EGR). The experiments were performed at 20, 40, 60 and 75% of full load (1120 Nm) at rated speed (2100 rpm), with and without the DOC upstream of the CPF. This was done to study the effect of temperature and CPF-inlet NO2 concentrations on particulate matter oxidation in the CCRT ®. A previously developed computational model was used to determine the kinetic parameters describing the oxidation characteristics of HCs, CO and NO in the DOC and the pressure drop across it. The model was calibrated at five temperatures in the range of 280 – 465° C, and exhaust volumetric flow rates of 0.447 – 0.843 act-m3/sec. The downstream HCs, CO and NO concentrations were predicted by the DOC model to within ±3 ppm. The HCs and CO oxidation kinetics in the temperature range of 280 - 465°C and an exhaust volumetric flow rate of 0.447 - 0.843 act-m3/sec can be represented by one ’apparent’ activation energy and pre-exponential factor. The NO oxidation kinetics in the same temperature and exhaust flow rate range can be represented by ’apparent’ activation energies and pre-exponential factors in two regimes. The DOC pressure drop was always predicted within 0.5 kPa by the model. The MTU 1-D 2-layer CPF model was enhanced in several ways to better model the performance of the CCRT ®. A model to simulate the oxidation of particulate inside the filter wall was developed. A particulate cake layer filtration model which describes particle filtration in terms of more fundamental parameters was developed and coupled to the wall oxidation model. To better model the particulate oxidation kinetics, a model to take into account the NO2 produced in the washcoat of the CPF was developed. The overall 1-D 2-layer model can be used to predict the pressure drop of the exhaust gas across the filter, the evolution of particulate mass inside the filter, the particulate mass oxidized, the filtration efficiency and the particle number distribution downstream of the CPF. The model was used to better understand the internal performance of the CCRT®, by determining the components of the total pressure drop across the filter, by classifying the total particulate matter in layer I, layer II, the filter wall, and by the means of oxidation i.e. by O2, NO2 entering the filter and by NO2 being produced in the filter. The CPF model was calibrated at four temperatures in the range of 280 – 465 °C, and exhaust volumetric flow rates of 0.447 – 0.843 act-m3/sec, in CPF-only and CCRT ® (DOC+CPF) configurations. The clean filter wall permeability was determined to be 2.00E-13 m2, which is in agreement with values in the literature for cordierite filters. The particulate packing density in the filter wall had values between 2.92 kg/m3 - 3.95 kg/m3 for all the loads. The mean pore size of the catalyst loaded filter wall was found to be 11.0 µm. The particulate cake packing densities and permeabilities, ranged from 131 kg/m3 - 134 kg/m3, and 0.42E-14 m2 and 2.00E-14 m2 respectively, and are in agreement with the Peclet number correlations in the literature. Particulate cake layer porosities determined from the particulate cake layer filtration model ranged between 0.841 and 0.814 and decreased with load, which is about 0.1 lower than experimental and more complex discrete particle simulations in the literature. The thickness of layer I was kept constant at 20 µm. The model kinetics in the CPF-only and CCRT ® configurations, showed that no ’catalyst effect’ with O2 was present. The kinetic parameters for the NO2-assisted oxidation of particulate in the CPF were determined from the simulation of transient temperature programmed oxidation data in the literature. It was determined that the thermal and NO2 kinetic parameters do not change with temperature, exhaust flow rate or NO2 concentrations. However, different kinetic parameters are used for particulate oxidation in the wall and on the wall. Model results showed that oxidation of particulate in the pores of the filter wall can cause disproportionate decreases in the filter pressure drop with respect to particulate mass. The wall oxidation model along with the particulate cake filtration model were developed to model the sudden and rapid decreases in pressure drop across the CPF. The particulate cake and wall filtration models result in higher particulate filtration efficiencies than with just the wall filtration model, with overall filtration efficiencies of 98-99% being predicted by the model. The pre-exponential factors for oxidation by NO2 did not change with temperature or NO2 concentrations because of the NO2 wall production model. In both CPF-only and CCRT ® configurations, the model showed NO2 and layer I to be the dominant means and dominant physical location of particulate oxidation respectively. However, at temperatures of 280 °C, NO2 is not a significant oxidizer of particulate matter, which is in agreement with studies in the literature. The model showed that 8.6 and 81.6% of the CPF-inlet particulate matter was oxidized after 5 hours at 20 and 75% load in CCRT® configuration. In CPF-only configuration at the same loads, the model showed that after 5 hours, 4.4 and 64.8% of the inlet particulate matter was oxidized. The increase in NO2 concentrations across the DOC contributes significantly to the oxidation of particulate in the CPF and is supplemented by the oxidation of NO to NO2 by the catalyst in the CPF, which increases the particulate oxidation rates. From the model, it was determined that the catalyst in the CPF modeslty increases the particulate oxidation rates in the range of 4.5 – 8.3% in the CCRT® configuration. Hence, the catalyst loading in the CPF of the CCRT® could possibly be reduced without significantly decreasing particulate oxidation rates leading to catalyst cost savings and better engine performance due to lower exhaust backpressures.

Development of Hardware-In-the-Loop Simulation System for Hybrid Electric Vehicle Study

The development of embedded control systems for a Hybrid Electric Vehicle (HEV) is a challenging task due to the multidisciplinary nature of HEV powertrain and its complex structures. Hardware-In-the-Loop (HIL) simulation provides an open and convenient environment for the modeling, prototyping, testing and analyzing HEV control systems. This thesis focuses on the development of such a HIL system for the hybrid electric vehicle study. The hardware architecture of the HIL system, including dSPACE eDrive HIL simulator, MicroAutoBox II and MotoTron Engine Control Module (ECM), is introduced. Software used in the system includes dSPACE Real-Time Interface (RTI) blockset, Automotive Simulation Models (ASM), Matlab/Simulink/Stateflow, Real-time Workshop, ControlDesk Next Generation, ModelDesk and MotoHawk/MotoTune. A case study of the development of control systems for a single shaft parallel hybrid electric vehicle is presented to summarize the functionality of this HIL system.

A TWO-STAGE MICROBIAL FUEL CELL SYSTEM TO CONVERT SOLID ORGANIC WASTE TO ELECTRICITY

Microbial fuel cell (MFC) research has focused mostly on producing electricity using soluble organic and inorganic substrates. This study focused on converting solid organic waste into electricity using a two-stage MFC process. In the first stage, a hydrolysis reactor produced soluble organic substrates from solid organic waste. The soluble substrates from the hydrolysis reactor were pumped to the second stage reactor: a continuous-flow, air-cathode MFC. Maximum power output (Pmax) of the MFC was 296 mW/m3 at a current density of 25.4 mA/m2 while being fed only leachate from the first stage reactor. Addition of phosphate buffer increased Pmax to 1,470 mW/m3 (89.4 mA/m2), although this result could not be duplicated with repeated polarization testing. The minimum internal resistance achieved was 77 Omega with leachate feed and 17 Omega with phosphate buffer. The low coulombic efficiency (

Is a sustaining rod necessary for diverting loop ileostomy?

Objective: Whether or not a protective stoma reduces the rate of anastomotic leakage after distal colorectal anastomosis is still discussed controversially. It does however facilitate clinical management once leakage has occurred. Loop ileostomies seem to be associated with a lower morbidity and a better quality of life compared to loop colostomies. Generally, diverting loop ileostomies are secured at skin level by means of a supporting device in order to prevent retraction of the ileostomy into the abdomen. However, due to the supporting rod, difficulties may occur in applying a stoma bag correctly and leakage of faeces onto the skin may occur even with correct eversion of the afferent limb. Our aim was to compare morbidity and time to self-sufficient stoma-care in patients having a loop ileostomy with rod to those without rod. Methods: A total of 60 patients necessitating loop ileostomy were analyzed. Patients received surgery in of the two involved institutions according to inhouse standard procedures. 30 patients had an ileostomy with rod (VCHK Inselspital) and a further 30 without rod (KSW Winterthur). Morbidity and time to self-sufficiency regarding stoma care was analyzed during the first 90 postoperative days. Morbidity was determined according to a scoring system ranging from 0 to 4 points for any given set of possible complications (bleeding, necrosis, skin irritation, abscess, stenosis, retraction, fistula, prolapse, parastomal hernia, incomplete diversion), where 0 = no complication and 4 = severe complication. Continuous variables were expressed as median (95% Confidence Interval). For comparisons between the groups the Mann-Whitney U test was used, between categorical variables the X2 test was applied. Results: There were no significant differences in length of hospital stay or time to self-sufficient stoma-care between the groups. Although not significant, patients with a rod ileostomy had a tendency towards more stoma-related complications as well as stoma-related reoperations. The number of patients reaching total self-sufficiency regarding stoma care was higher after rodless ileostomy. Conclusion: According to our data, rodless ileostomies seemto fare just as well as those with a supporting rod, with equal morbidity rates and more patients reaching self-sufficient stoma care. Therefore routine application of a rod for diverting loop ileostomy seems unnecessary