Experimental Investigation of Microcontroller-Based Acoustic Temperature Transducer Systems.

Temperature transducers are commonly used to monitor process parameters that are controlled by various types of industrial controllers. The purpose of this study is to design and model a simple microcontroller-based acoustic temperature transducer based on the variations of resonance conditions in a cylindrical resonance tube. The transducer's operation is based on the generation of an acoustic standing wave in the free resonance mode of generation within a cylindrical resonance tube which is converted into a train of pulses using Schmitt trigger circuit. The frequency of the generated standing wave (i.e., the train of pulses) is measured by the Arduino Uno microcontroller, where a digital pin is used to acquire pulses that are counted using a build-in software function in an Arduino IDE environment. Experimental results are performed for three sizes of diameters to investigate the effect of the diameter of resonance tube on the obtained results. The maximum nonlinearity error according to Full-Scale Deflection (FSD) is about 2.3 percent, and the relative error of the transducer is evaluated using experimental findings and the regression model. The circuit simplicity and design of the suggested transducer, as well as the linearity of its measurements, are notable.

Prototyping a System for Truck Differential Lock Control.

The article deals with the development of a mechatronic system for locking vehicle differentials. An important benefit of this system is that it prevents the jamming of the vehicle in difficult adhesion conditions. The system recognizes such a situation much sooner than the driver and is able to respond immediately, ensuring smooth driving in off-road or snowy conditions. This article describes the control algorithm of this mechatronic system, which is designed for firefighting, military, or civilian vehicles with a drivetrain configuration of up to 10 × 10, and also explains the input signal processing and the control of actuators. The main part of this article concerns prototype testing on a vehicle. The results are an evaluation of one of the many experiments and monitor the proper function of the developed mechatronic system.

Ultrasound-guided versus conventional femoral venipuncture for catheter ablation of atrial fibrillation: a multicentre randomized efficacy and safety trial (ULTRA-FAST trial).

Aims: Complications of catheter ablation for atrial fibrillation (AF) are frequently related to vascular access. We hypothesized that ultrasound-guided (USG) venipuncture may facilitate the procedure and reduce complication rates. Methods and results: We conducted a multicentre, randomized trial in patients undergoing catheter ablation for AF on uninterrupted anticoagulation therapy. The study enrolled consecutive 320 patients (age: 63 ± 8 years; male: 62%) and were randomized to USG or conventional venipuncture in 1:1 fashion. It was prematurely terminated due to substantially lower-than-expected complication rates, which doubled the population size needed to maintain statistical power. While the complication rates did not differ between two study arms (0.6% vs. 1.9%, P = 0.62), intra-procedural outcome measures were in favour of the USG approach (puncture time, 288 vs. 369 s, P < 0.001; first pass success, 74% vs. 20%, P < 0.001; extra puncture attempts 0.5 vs. 2.1, P < 0.001; inadvertent arterial puncture 0.07 vs. 0.25, P < 0.001; unsuccessful cannulation 0.6% vs. 14%, P < 0.001). Though these measures varied between trainees (49% of procedures) and expert operators, between-arm differences (except for unsuccessful cannulation) were comparably significant in favour of USG approach for both subgroups. Conclusions: Ultrasound-guided puncture of femoral veins was associated with preferable intra-procedural outcomes, though the major complication rates were not reduced. Both trainees and expert operators benefited from the USG strategy. (www.clinicaltrials.gov ID: NCT02834221).

Safety of pulsed field ablation in more than 17,000 patients with atrial fibrillation in the MANIFEST-17K study.

Pulsed field ablation (PFA) is an emerging technology for the treatment of atrial fibrillation (AF), for which pre-clinical and early-stage clinical data are suggestive of some degree of preferentiality to myocardial tissue ablation without damage to adjacent structures. Here in the MANIFEST-17K study we assessed the safety of PFA by studying the post-approval use of this treatment modality. Of the 116 centers performing post-approval PFA with a pentaspline catheter, data were received from 106 centers (91.4% participation) regarding 17,642 patients undergoing PFA (mean age 64, 34.7% female, 57.8% paroxysmal AF and 35.2% persistent AF). No esophageal complications, pulmonary vein stenosis or persistent phrenic palsy was reported (transient palsy was reported in 0.06% of patients; 11 of 17,642). Major complications, reported for ~1% of patients (173 of 17,642), were pericardial tamponade (0.36%; 63 of 17,642) and vascular events (0.30%; 53 of 17,642). Stroke was rare (0.12%; 22 of 17,642) and death was even rarer (0.03%; 5 of 17,642). Unexpected complications of PFA were coronary arterial spasm in 0.14% of patients (25 of 17,642) and hemolysis-related acute renal failure necessitating hemodialysis in 0.03% of patients (5 of 17,642). Taken together, these data indicate that PFA demonstrates a favorable safety profile by avoiding much of the collateral damage seen with conventional thermal ablation. PFA has the potential to be transformative for the management of patients with AF.

Understanding gastric forces calculated from high-resolution pill tracking.

Although other methods exist for monitoring gastrointestinal motility and contractility, this study exclusively provides direct and quantitative measurements of the forces experienced by an orally ingested pill. We report motive forces and torques calculated from real-time, in vivo measurements of the movement of a magnetic pill in the stomachs of fasted and fed humans. Three-dimensional net force and two-dimensional net torque vectors as a function of time data during gastric residence are evaluated using instantaneous translational and rotational position data. Additionally, the net force calculations described can be applied to high-resolution pill tracking acquired by any modality. The fraction of time pills experience ranges of forces and torques are analyzed and correlate with the physiological phases of gastric digestion. We also report the maximum forces and torques experienced in vivo by pills as a quantitative measure of the amount of force pills experience during the muscular contractions leading to gastric emptying. Results calculated from human data are compared with small and large animal models with a translational research focus. The reported magnitude and direction of gastric forces experienced by pills in healthy stomachs serves as a baseline for comparison with pathophysiological states. Of clinical significance, the directionality associated with force vector data may be useful in determining the muscle groups associated with gastrointestinal dysmotility. Additionally, the quantitative comparison between human and animal models improves insight into comparative gastric contractility that will aid rational pill design and provide a quantitative framework for interpreting gastroretentive oral formulation test results.

Effect of Ply Orientation on the Mechanical Performance of Carbon Fibre Honeycomb Cores.

Carbon fibres used as a honeycomb core material (subject to a proper in-depth analysis of their reinforcement patterns) allows solving the thermo-dimensional stability problem of the units for space systems. Based on the results of numerical simulations with the support of finite element analysis, the paper provides an evaluation of the accuracy of analytical dependencies for the determination of the moduli of elasticity of a carbon fibre honeycomb core in tension/compression and shear. It is shown that a carbon fibre honeycomb reinforcement pattern has a significant impact on the mechanical performance of the carbon fibre honeycomb core. For example, for honeycombs measuring 10 mm in height, the maximum shear modulus values corresponding to the reinforcement pattern of ±45° exceed the minimum values for a reinforcement pattern of 0° and 90° by more than 5 times in the XOZ plane and 4 times for the shear modulus in the YOZ plane. The maximum modulus of the elasticity of the honeycomb core in the transverse tension, corresponding to a reinforcement pattern of ±75°, exceeds the minimum modulus for the reinforcement pattern of ±15° more than 3 times. We observe a decrease in the values of the mechanical performance of the carbon fibre honeycomb core depending on its height. With a honeycomb reinforcement pattern of ±45°, the decrease in the shear modulus is 10% in the XOZ plane and 15% in the YOZ plane. The reduction in the modulus of elasticity in the transverse tension for the reinforcement pattern does not exceed 5%. It is shown that in order to ensure high-level moduli of elasticity with respect to tension/compression and shear at the same time, it is necessary to focus on a reinforcement pattern of ±64°. The paper covers the development of the experimental prototype technology that produces carbon fibre honeycomb cores and structures for aerospace applications. It is shown by experiments that the use of a larger number of thin layers of unidirectional carbon fibres provides more than a 2-time reduction in honeycomb density while maintaining high values of strength and stiffness. Our findings can permit a significant expansion of the area of application relative to this class of honeycomb cores in aerospace engineering.

Local electrogram delay recorded from left ventricular lead at implant predicts response to cardiac resynchronization therapy: retrospective study with 1 year follow up.

BACKGROUND: Considerable proportion of patients does not respond to the cardiac resynchronization therapy (CRT). This study investigated clinical relevance of left ventricular electrode local electrogram delay from the beginning of QRS (QLV). We hypothesized that longer QLV indicating more optimal lead placement in the late activated regions is associated with the higher probability of positive CRT response. METHODS: We conducted a retrospective, single-centre analysis of 161 consecutive patients with heart failure and LBBB or nonspecific intraventricular conduction delay (IVCD) treated with CRT. We routinely intend to implant the LV lead in a region with long QLV. Clinical response to CRT, left ventricular (LV) reverse remodelling (i.e. decrease in LV end-systolic diameter - LVESD ≥10%) and reduction in plasma level of NT-proBNP >30% at 12-month post-implant were the study endpoints. We analyzed association between pre-implant variables and the study endpoints. RESULTS: Clinical CRT response rate reached 58%, 84% and 92% in the lowest (≤105 ms), middle (106-130 ms) and the highest (>130 ms) QLV tertile (p < 0.0001), respectively. Longer QRS duration (p = 0.002), smaller LVESD and a non-ischemic cardiomyopathy (both p = 0.02) were also univariately associated with positive clinical CRT response. In a multivariate analysis, QLV remained the strongest predictor of clinical CRT response (p < 0.00001), followed by LVESD (p = 0.01) and etiology of LV dysfunction (p = 0.04). Comparable predictive power of QLV for LV reverse remodelling and NT-proBNP response rates was observed. CONCLUSION: LV lead position assessed by duration of the QLV interval was found the strongest independent predictor of beneficial clinical response to CRT.

Effect of Heating Conditions during Moulding on Residual Stress-Strain Behaviour of a Composite Panel.

Currently, we observe extensive use of products made of polymeric composite materials in various industries. These materials are being increasingly used to manufacture large-sized structural parts that bear significant loads. However, increase in the volume of composites used in critical structures is impeded by the instability of properties of the resulting products. In most cases, the reason for this is the residual thermal stress-strain behaviour of the composite structure. This paper deals with the development of a method to predict the residual stress-strain behaviour depending on the heating conditions and distribution of the temperature field over the thickness of the moulded composite package. The method establishes the relationship between moulding process parameters and the effect of the auxiliary and basic equipment on the distribution of the temperature field, stresses, and strains in the moulded product. It is shown that the rate of temperature change at the stage of heating has its effect on the amount of residual deformation of the structure. Experimental studies have been carried out to determine the influence of several factors (rates of heating and cooling) on the residual deflection of the composite panel. Experimental data proves that specimens moulded under conditions of an increased heating rate get a greater deflection than those moulded at a lower heating rate. The error of results during the full-scale experiment did not exceed 6.8%. Our results provide an opportunity to determine the residual thermal stress-strain behaviour of the moulded structure with the required degree of accuracy without a series of experiments. It allows us to significantly simplify the practical implementation of the developed method and avoid any additional production costs.

Influence of Geometric Parameters of Conical Acrylic Portholes on Their Stress-Strain Behaviour.

Translucent elements in the form of truncated cones, which are made of organic glass, are widely used in the structures of portholes, submersible vessels, space vehicles, pressure chambers, teleboxes and other types of technical equipment. The decisive factor in designing portholes is to ensure the strength of their translucent elements. In order to reduce the weight of portholes and, accordingly, to increase the payload, it is necessary to optimise the geometric parameters of the translucent elements, which include the tapering angle and the ratio of thickness to radius of the smaller base. The paper deals with development of the applied (engineering) method for determining the stress-strain behaviour of the conical translucent elements of portholes made of organic glass under the action of a uniform hydrostatic pressure. Finite-element modelling of the translucent element of the conical porthole is performed, with the calculation of its stress-strain behaviour. External hydrostatic pressure of 10 MPa, absence of loads from the inside and continuous sliding of the translucent element with friction along the conical supporting surface of the porthole metal body are the boundary conditions for the computational model. Full-scale tests of translucent elements of portholes made of organic glass were performed under the action of uniform hydrostatic pressure. Analysis of the influence of geometric characteristics of the portholes on stress-strain behaviour showed that the increase in the tapering angle at the constant relative thickness of the translucent element reduced its axial displacement in all cases. Equivalent stresses acquire minimum values when the tapering angle is in the range from 75° to 105° (when the relative thickness increases, the optimal tapering angle becomes smaller). It is shown that the developed method for determination of the stress-strain behaviour of the conical translucent elements of portholes made of organic glass reflects the real picture of deformation and agrees with the results of full-scale tests. Results of the work allow us to choose the rational parameters of the translucent element for increasing the reliability of portholes through the creation of an effective distribution of stresses and strains in the translucent element, and improving its optical characteristics due to a relatively small deflection in operation.

Determination of the Composite Panel Moulding Pressure Value.

Currently, prefabricated panel structures are typical products made of polymeric composite materials. The integrity of the composite panels, their structure and accuracy of making a contour are largely associated with the manifestation of residual technological stresses. The above phenomena and associated stress-strain behaviour inevitably occur in the process of moulding of the composite products. However, their value, nature, time of occurrence and dynamics of growth can be fully controlled and regulated. The paper deals with the study of the effect of moulding pressure on the quality of a composite product. A dependence is presented that allows us to determine the time for the degassing of the polymeric composite material package at the given temperature and pressure to obtain a monolithic and nonporous structure. It is shown that the peak of the maximum volatile-matter yield for the considered binder types lies in the temperature range where the degree of curing does not exceed 10%; that is, the viscosity values do not prevent the removal of volatile fractions. The effect of moulding pressure on the values of the volume content of the reinforcing material has been studied, and the dependence of the required thickness of the absorbent layer on the parameters of the package of polymer composite material and pressure has been obtained. The dependence of the required thickness of absorbent layer on the parameters of the package of polymeric composite material and pressure has been obtained. The mathematical model developed by us provides an opportunity to predict the stress-strain behaviour of a composite structure at any time during the moulding process. The model is closely related to chemo-viscous and thermal models. It allowed us to synthetize a method for choosing the rational parameters of the moulding process (temperature, pressure, and time), materials of additional layers and equipment. The experiments proved the presence of several defects, such as de-lamination of edges, waviness, swelling and poor adhesion of upper layers in the specimen of the composite panel cooled stepwise in the absence of the vacuum pressure. The surface quality of the specimen of the panel cooled stepwise under vacuum pressure was significantly better, and no visible defects were observed. The obtained theoretical values of deflections, considering the change in physic-mechanical characteristics that depend on the temperature and rheonomic properties of the material, showed an error that did not exceed 7%, compared to the experimental data. Our results can be applied at the enterprises engaged in designing and manufacturing panel structures of polymeric composite materials.

The Study of Manufacturing Thermal Insulation Materials Based on Inorganic Polymers under Microwave Exposure.

The work is devoted to the creation of an energy-saving microwave technology of composite materials for thermal insulation based on an inorganic polymer-liquid glass-and the establishment of the formation patterns of their structure and properties, depending on the parameters of microwave radiation. Due to volumetric heating and the mechanism of "non-thermal" action of microwave radiation on processed objects, the duration of their heating is significantly reduced, and the performance properties of products are improved due to the modification of the structure of the liquid glass matrix under the influence of its irradiation with this type of energy. In the course of the research, the relationship between the processing conditions and the obtained properties of heat-insulating materials was established. The prospects of using the microwave electromagnetic field in the production of new building materials, expanding their range, and improving quality and competitiveness are shown, which is a priority for the modernization and innovative development of the construction industry.

Inadvertent QRS prolongation by an optimization device-based algorithm in patients with cardiac resynchronization therapy.

BACKGROUND: Device-based algorithms offer the potential for automated optimization of cardiac resynchronization therapy (CRT), but the process for accepting them into clinical use is currently still ad-hoc, rather than based on pre-clinical and clinical testing of specific features of validity. We investigated how the QuickOpt-guided VV delay (VVD) programming performs against the clinical and engineering heuristic of QRS complex shortening by CRT. METHODS: A prospective, 2-center study enrolled 37 consecutive patients with CRT. QRS complex duration (QRSd) was assessed during intrinsic atrioventricular conduction, synchronous biventricular pacing, and biventricular pacing with QuickOpt-proposed VVD. The measurements were done manually by electronic calipers in signal-averaged and magnified 12-lead QRS complexes. RESULTS: Native QRSd was 174 ± 22 ms. Biventricular pacing with empiric AVD and synchronous VVD resulted in QRSd 156 ± 20 ms, a significant narrowing from the baseline QRSd by 17 ± 27 ms, P = 0.0003. In 36 of 37 patients, the QuickOpt algorithm recommended left ventricular preexcitation with VVD of 42 ± 18 ms (median 40 ms; interquartile range 30-55 ms, P <0.00001). QRSd in biventricular pacing with QuickOpt-based VVD was significantly longer compared with synchronous biventricular pacing (168 ± 25 ms vs. 156 ± 20 ms; difference 12 ± 11ms; P <0.00001). This prolongation correlated with the absolute VVD value (R = 0.66, P <0.00001). CONCLUSIONS: QuickOpt algorithm systematically favours a left-preexcitation VVD which translates into a significant prolongation of the QRSd compared to synchronous biventricular pacing. There is no reason to believe that a manipulation that systematically widens QRSd should be considered to optimize physiology. Device-based CRT optimization algorithms should undergo systematic mechanistic pre-clinical evaluation in various scenarios before they are tested in large clinical studies.

Effects of the Temperature-Time Regime of Curing of Composite Patch on Repair Process Efficiency.

Repair procedures with the use of composite patches are considered to be the most effective among the current technologies of repair of the structures of various applications. In the process of moulding-on of a patch made of polymeric composite material by means of curing, technological stresses arise in the patch. Determination of residual technological stresses is a priority task for the modelling of the repair process. Reduction of residual stresses can be achieved by optimization of the mode of repair patch curing. For meeting this objective, the method for determination of technological stresses, which arise in the structure under repair in the process of curing of a composite patch, has been developed. The method takes into account the shrinkage, change in physico-mechanical characteristics, rheological processes occurring in the binder during moulding process, and determination of stresses in the structure under repair at any time. Therefore, premature failure of the repair joint at the stage of repair can be avoided. It is shown that the method adequately describes the level of deformations and stresses in the structure being repaired at the stage of heating and holding of the composite patch. Increase in the moulding temperature leads to a reduction in residual stresses in the structure under repair. However, current stresses at the stages of heating and temperature holding are increased significantly. Reliability of assumptions and developed method is confirmed by the comparison with the experimental data. The obtained experimental graph of total deformation of the composite patch allowed us to clearly determine the moment of residual stress occurrence in the structure under repair. This moment matches quite exactly (with the discrepancy not exceeding 5 min) the gel point determined analytically based on dependence of the degree of curing on the moulding mode. Consequently, the research together with the results previously obtained allows making an integrated choice of geometric parameters of the repair composite patch and temperature-time regime of its curing in order to ensure the specified level of strength and stiffness of the structure under repair.

Self-Heating Mould for Composite Manufacturing.

The shipbuilding industry, engine manufacturing, aviation, rocket and space technology are promising fields of application for polymeric composite materials. Shape-generating moulding tools with internal heating are used for the creation of a more economically viable method of moulding of internally heated composite structures. The use of a fine-fibered resistive structure in the heated tools allows implementation of effective heating of the composite and elimination of the need for expensive and energy-intensive heating equipment. The aim of this paper was the reduction of energy consumption for internally heated moulding tools by choosing the optimal parameters for their resistive layer. A method for determination of the parameters of the moulding tool resistive layer was developed. This method allows calculation of the heating layer parameters and implementation of the specified time-temperature regime for moulding of the composite structure. It was shown that energy saving for the heated fiberglass shape-generating moulding tools was from 40 to 60%. It was found that the increase in the thickness of the moulded package of the polymeric composite material resulted not only in a higher supplied power for the heating system, but also in a complication of the method for system control, because of the growing exothermic effect of the binder curing reaction. For composite products based on Hysol EA 9396 binder, thicknesses more than 4 mm are critical, because it is not possible to cope with the self-heating effect only by cooling with ambient air already utilized at the twentieth minute of the moulding process. The influence of the physical and mechanical characteristics of the moulding tool material and stiffening ribs was analysed in terms of energy consumption and controllability of the heating system. Fiberglass shows the lowest energy consumption. Heating of the aluminium and steel moulding tools for the same purpose will require 20% and 45% more power, respectively. An increase in the number of stiffening ribs has a strong effect on the heat removal of the heating system. With a small number of aluminium ribs it is not possible to maintain the specified temperature-time regime for a fiberglass moulded package of 5 mm thick with the use of the equipment. However, when the number of stiffeners is increased to 10, the exothermic effect of the reaction becomes smoother and then the heating equipment can cope with the task. An experimental prototype of heating equipment of moulding tools for the manufacturing of structures of polymeric composite materials, as well as a flexible thermal blanket for repair of non-separable structures, were developed. The results can be the basis for a new method of optimal design of parameters of moulding tool structure at minimal heat removal to the environment.

Stress-Strain Behaviour of Reparable Composite Panel with Step-Variable Thickness.

There is an urgent problem of finding an economically viable method of maintenance and restoration of the bearing capacity of structures of various applications. Repair of structures with patches made of polymeric composite materials is one of the most promising repair technologies. However, an improper choice of parameters of the composite patch leads to unjustified increase in the structure mass and the cost of its further operation. These situations result from the lack of reliable methods for developing the repair process, which take into account the influence of the patch geometry and conditions for performance of repair works on the bearing capacity of the repaired structure. The mathematical model of the reparable composite shell-type panel taking into account inhomogeneity of transverse shear deformations at stepped variation of its thickness has been developed. In contrast to the classical theory of layered shells, the model allows simplifying a three-dimensional problem by setting of the displacement field on the layers' interfaces and their linear interpolation over thickness of the panel, as well as considering the transverse shear deformations resulting from the strength, temperature, or shrinkage loading. According to results, the maximum rise in stresses in the case of a notched panel occurs in the weakened layer, and it is from this layer the failure of the structure will start. In the event of the patch, the panel surface opposite the reinforcement is the most loaded (i.e., susceptible to failure) surface. To confirm the reliability of the developed model, we compared the analytical calculations with the results of experimental and numerical studies of the deformed state of a panel of step-variable thickness by the method of holographic interferometry and modelling by the finite element method. Displacement fields available from experiments correspond to the predicted theoretical results. The resulting maximum error does not exceed 7%. The data obtained during numerical modelling allowed us to conclude that the accuracy of theoretical calculations is sufficient for engineering practice. Results of the work can be used to solve the practical problems such as determination of stress-strain behaviour of a damaged structure or structure after repair, specification of the permissible delamination dimensions, and defining of parameters of the bonded repair process.

Research and Development of Self-Contained Water Injection Systems.

Reducing fuel consumption and thus CO2 emissions is one of the most urgent tasks of current research in the field of internal combustion engines. Water Injection has proven its benefits to increase power or optimize fuel consumption of passenger cars. This technology enables knock mitigation to either increase the engine power output or raise the compression ratio and efficiency while enabling λ = 1 operation in the complete engine map to meet future emission targets. Current systems have limited container capacity. It is necessary to refill the water tank regularly. This also means that we cannot get the benefits of an engine with a higher compression ratio. For this reason, the self-contained system was investigated. This article is a methodology for finding the right design of a self-contained water injection system, but also a vehicle test that proves the function.

Burr-Hole Evacuation of Chronic Subdural Hematoma: Biophysically and Evidence-Based Technique Improvement.

Chronic subdural hematoma (CSDH) is one of the most common neurosurgical conditions. Despite ongoing efforts, recurrence and reoperation rates after surgical treatment remain high. We synthesize scientific evidence on the treatment of CSDH with biophysical principles and then propose a simple and effective surgical technique aiming to reduce the recurrence rate. Under local anesthesia, one burr hole is placed in the area above the maximum hematoma thickness. One drain is inserted into the dorsal direction to the deepest point of the hematoma cavity, and a second drain is inserted frontally into the highest point. Next, saline is gently instilled to the dorsal drain to eliminate air from the hematoma cavity through the frontal drain. Once saline has filled the frontal drain, the frontal drain is removed. The dorsal drain is left in situ for 48 h, and the pressure within the cavity may be adapted hydrostatically. We implemented evidence-based conclusions of previous studies and modified the classical burr-hole technique to reduce the recurrence rate. As a result, we developed a straightforward surgical procedure that is possible to perform under local anesthesia, suitable for everyday practice in rural and remote areas while working with limited resources. The novelty of this technique is in the purposeful reduction of postoperative pneumocephalus, a known independent factor of recurrence. Subdural air is eliminated during surgery using a two-drain system. Safety and efficacy of the technique need to be evaluated in future clinical trials.

Combination of left ventricular reverse remodeling and brain natriuretic peptide level at one year after cardiac resynchronization therapy predicts long-term clinical outcome.

INTRODUCTION: The aim of this study was to investigate the predictors of long-term clinical outcome of heart failure (HF) patients who survived first year after initiation of cardiac resynchronization therapy (CRT). METHODS: This was a single-center observational cohort study of CRT patients implanted because of symptomatic HF with reduced ejection fraction between 2005 and 2013. Left ventricle (LV) diameters and ejection fraction, New York Heart Association (NYHA) class, and level of N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) were assessed at baseline and 12 months after CRT implantation. Their predictive power for long-term HF hospitalization and mortality, and cardiac and all-cause mortality was investigated. RESULTS: A total of 315 patients with left bundle branch block or intraventricular conduction delay who survived >1 year after CRT implantation were analyzed in the current study. During a follow-up period of 4.8±2.1 years from CRT implantation, 35.2% patients died from cardiac (19.3%) or non-cardiac (15.9%) causes. Post-CRT LV ejection fraction and LV end-systolic diameter (either 12-month value or the change from baseline) were equally predictive for clinical events. For NT-proBNP, however, the 12-month level was a stronger predictor than the change from baseline. Both reverse LV remodeling and 12-month level of NT-proBNP were independent and comparable predictors of CRT-related clinical outcome, while NT-proBNP response had the strongest association with all-cause mortality. When post-CRT relative change of LV end-systolic diameter and 12-month level of NT-proBNP (dichotomized at -12.3% and 1230 ng/L, respectively) were combined, subgroups of very-high and very-low risk patients were identified. CONCLUSION: The level of NT-proBNP and reverse LV remodeling at one year after CRT are independent and complementary predictors of future clinical events. Their combination may help to improve the risk stratification of CRT patients.

Polymeric photosensitizer prodrugs for photodynamic therapy.

A targeting strategy based on the selective enzyme-mediated activation of polymeric photosensitizer prodrugs (PPP) within pathological tissue has led to the development of agents with the dual ability to detect and treat cancer. Herein, a detailed study of a simple model system for these prodrugs is described. We prepared "first-generation" PPP by directly tethering the photosensitizer (PS) pheophorbide a to poly-(L)-lysine via epsilon amide links and observed that by increasing the number of PS on a polymer chain, energy transfer between PS units improved leading to better quenching efficiency. Fragmentation of the PPP backbone by trypsin digestion gave rise to a pronounced fluorescence increase and to more efficient generation of reactive oxygen species upon light irradiation. In vitro tests using the T-24 bladder carcinoma cell line and ex vivo experiments using mouse intestines illustrated the remarkable and selective ability of these PPP to fluoresce and induce phototoxicity upon enzymatic activation. This work elucidated the basic physicochemical parameters, such as water solubility and quenching/activation behavior, required for the future elaboration of more adaptable "second-generation" PPP, in which the PS is tethered to a proteolytically stable polymer backbone via enzyme-specific peptide linkers. This polymer architecture offers great flexibility to tailor make the PPP to target any pathological tissue known to over-express a specific enzyme.

Arrhythmogenesis in the developing heart during anoxia-reoxygenation and hypothermia-rewarming: an in vitro model.

INTRODUCTION: The spatio-temporal pattern of arrhythmias in the embryonic/fetal heart subjected to a transient hypoxic or hypothermic stress remains to be established. METHODS AND RESULTS: Spontaneously beating hearts or isolated atria, ventricles, and conotruncus from 4-day-old chick embryos were subjected in vitro to 30-minute anoxia and 60-minute reoxygenation. Hearts were also submitted to 30-minute hypothermia (0-4 degrees C) and 60-minute rewarming. ECG disturbances and alterations of atrial and ventricular electromechanical delay (EMD) were systematically investigated. Baseline functional parameters were stable during at least 2 hours. Anoxia induced tachycardia, followed by bradycardia, atrial ectopy, first-, second-, and third-degree atrio-ventricular blocks and, finally, transient electromechanical arrest after 6.8 minutes, interquartile ranges (IQR) 3.1-16.2 (n = 8). Reoxygenation triggered also Wenckebach phenomenon and ventricular escape beats. At the onset of reoxygenation QT, PR, and ventricular EMD increased by 68%, 70%, and 250%, respectively, whereas atrial EMD was not altered. No fibrillations, no ventricular ectopic beats, and no electromechanical dissociation were observed. Arrhythmic activity of the isolated atria persisted throughout anoxia and upon reoxygenation, whereas activity of the isolated ventricles abruptly ceased after 5 minutes of anoxia and resumed after 5 minutes of reoxygenation. During hypothermia-rewarming, cardiac activity stopped at 17.9 degrees C, IQR 16.2-20.6 (n = 4) and resumed at the same temperature with no arrhythmias. All preparations fully recovered after 40 minutes of reoxygenation or rewarming. CONCLUSION: In the embryonic heart, arrhythmias mainly originated in the sinoatrial tissue and resembled those observed in the adult heart. Furthermore, oxygen readmission was by far more arrhythmogenic than rewarming and the chronotropic, dromotropic, and inotropic effects were fully reversible.