Kinetics of atrial repolarization alternans in a free-behaving ovine model.

Kinetics of Atrial Repolarization Alternans. INTRODUCTION: Repolarization alternans (Re-ALT), a beat-to-beat alternation in action potential repolarization, promotes dispersion of repolarization, wavebreaks, and reentry. Recently, Re-ALT has been shown to play an important role in the transition from rapid pacing to atrial fibrillation (AF) in humans. The detailed kinetics of atrial Re-ALT, however, has not been reported so far. We developed a chronic free-behaving ovine pacing model to study the kinetics of atrial Re-ALT as a function of pacing rate. METHODS: Thirteen sheep were chronically implanted with 2 pacemakers for the recording of broadband right atrial unipolar electrograms and delivery of rapid pacing protocols. Beat-to-beat differences in the atrial T-wave apex amplitude as a measure of Re-ALT and activation time were analyzed at incremental pacing rates until the effective refractory period (ERP) defined as stable 2:1 capture. RESULTS: Atrial Re-ALT appeared intermittently but without periodicity, and increased in amplitude as a function of pacing rate until ERP. Intermittent 2:1 atrial capture was observed at pacing cycle lengths 40 ms above ERP, and increased in duration as a function of pacing rate. Episodes of rapid pacing-induced AF were rare, and were preceded by Re-ALT or complex oscillations of atrial repolarization, but without intermittent capture. CONCLUSION: We show in vivo that atrial Re-ALT developed and increased in magnitude with rate until stable 2:1 capture. In rare instances where capture failure did not occur, Re-ALT and complex oscillations of repolarization surged and preceded AF initiation. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1003-1012, September 2012).

Diagnostic contribution of cardiac magnetic resonance in patients with acute coronary syndrome and culprit-free angiograms.

BACKGROUND: In spite of robust knowledge about underlying ischemic myocardial damage, acute coronary syndromes (ACS) with culprit-free angiograms raise diagnostic concerns. The present study aimed to evaluate the additional value of cardiac magnetic resonance (CMR) over commonly available non-CMR standard tests, for the differentiation of myocardial injury in patients with ACS and non-obstructed coronary arteries. MATERIAL/METHODS: Patients with ACS, elevated hs-TnT, and a culprit-free angiogram were prospectively enrolled into the study between January 2009 and July 2013. After initial evaluation with standard tests (ECG, echocardiography, hs-TnT) and provisional exclusion of acute myocardial infarction (AMI) in coronary angiogram, patients were referred for CMR with the suspicion of myocarditis or Takotsubo cardiomyopathy (TTC). According to the result of CMR, patients were reclassified as having myocarditis, AMI, TTC, or non-injured myocardium as assessed by late gadolinium enhancement. RESULTS: Out of 5110 patients admitted with ACS, 75 had normal coronary angiograms and entered the study; 69 of them (92%) were suspected for myocarditis and 6 (8%) for TTC. After CMR, 49 patients were finally diagnosed with myocarditis (65%), 3 with TTC (4%), 7 with AMI (9%), and 16 (21%) with non-injured myocardium. The provisional diagnosis was changed or excluded in 23 patients (31%), with a 9% rate of unrecognized AMI. CONCLUSIONS: The study results suggest that the evaluation of patients with ACS and culprit-free angiogram should be complemented by a CMR examination, if available, because the initial work-up with non-CMR tests leads to a significant proportion of misdiagnosed AMI.

In vitro combination of human and bovine free secretory component with IgA of various species.

The free form of the secretory component usually associated with secretory IgA can be isolated from human and bovine milk. These free secretory components of different origin combine in vitro with human polymeric myeloma IgA, with mouse myeloma IgA, and with the serum IgA of nine different mammalian species.

Prediction of free imatinib concentrations based on total plasma concentrations in patients with gastrointestinal stromal tumours.

AIM: Total imatinib concentrations are currently measured for the therapeutic drug monitoring of imatinib, whereas only free drug equilibrates with cells for pharmacological action. Due to technical and cost limitations, routine measurement of free concentrations is generally not performed. In this study, free and total imatinib concentrations were measured to establish a model allowing the confident prediction of imatinib free concentrations based on total concentrations and plasma proteins measurements. METHODS: One hundred and fifty total and free plasma concentrations of imatinib were measured in 49 patients with gastrointestinal stromal tumours. A population pharmacokinetic model was built up to characterize mean total and free concentrations with inter-patient and intrapatient variability, while taking into account α1 -acid glycoprotein (AGP) and human serum albumin (HSA) concentrations, in addition to other demographic and environmental covariates. RESULTS: A one compartment model with first order absorption was used to characterize total and free imatinib concentrations. Only AGP influenced imatinib total clearance. Imatinib free concentrations were best predicted using a non-linear binding model to AGP, with a dissociation constant Kd of 319 ng ml(-1) , assuming a 1:1 molar binding ratio. The addition of HSA in the equation did not improve the prediction of imatinib unbound concentrations. CONCLUSION: Although free concentration monitoring is probably more appropriate than total concentrations, it requires an additional ultrafiltration step and sensitive analytical technology, not always available in clinical laboratories. The model proposed might represent a convenient approach to estimate imatinib free concentrations. However, therapeutic ranges for free imatinib concentrations remain to be established before it enters into routine practice.

Laser scanning evaluation of atrophy after autologous free muscle transfer.

Denervated muscle tissue undergoes morphologic changes that result in atrophy. The amount of muscle atrophy after denervation following free muscle transfer has not been measured so far. Therefore, the amount of muscle atrophy in human free muscle transfer for lower extremity reconstruction was measured in a series of 10 patients. Three-dimensional laser surface scanning was used to measure flap volume changes 2 weeks as well as 6 and 12 months after the operation. None of the muscles transferred was re-innervated.All muscles healed uneventfully without signs of compromised perfusion resulting in partial flap loss. The muscle volume decreased to 30 ± 4% and 19 ± 4% 6 and 12 months, respectively, after the operation, ie, the volume decreased by approximately 80% within a 12-month period.Denervated free muscle flap tissue undergoes massive atrophy of approximately 80%, mostly within the first 6 months.

Shall a free public library be established? : Iowa public library laws, 1914

This leaflet gives information on how to start a free public library in a community. Includes regulations and related laws dealing with libraries.

Three essays on major trends in a slow clockspeed industry : the case of industrial automation

The motivation for this research initiated from the abrupt rise and fall of minicomputers which were initially used both for industrial automation and business applications due to their significantly lower cost than their predecessors, the mainframes. Later industrial automation developed its own vertically integrated hardware and software to address the application needs of uninterrupted operations, real-time control and resilience to harsh environmental conditions. This has led to the creation of an independent industry, namely industrial automation used in PLC, DCS, SCADA and robot control systems. This industry employs today over 200'000 people in a profitable slow clockspeed context in contrast to the two mainstream computing industries of information technology (IT) focused on business applications and telecommunications focused on communications networks and hand-held devices. Already in 1990s it was foreseen that IT and communication would merge into one Information and communication industry (ICT). The fundamental question of the thesis is: Could industrial automation leverage a common technology platform with the newly formed ICT industry? Computer systems dominated by complex instruction set computers (CISC) were challenged during 1990s with higher performance reduced instruction set computers (RISC). RISC started to evolve parallel to the constant advancement of Moore's law. These developments created the high performance and low energy consumption System-on-Chip architecture (SoC). Unlike to the CISC processors RISC processor architecture is a separate industry from the RISC chip manufacturing industry. It also has several hardware independent software platforms consisting of integrated operating system, development environment, user interface and application market which enables customers to have more choices due to hardware independent real time capable software applications. An architecture disruption merged and the smartphone and tablet market were formed with new rules and new key players in the ICT industry. Today there are more RISC computer systems running Linux (or other Unix variants) than any other computer system. The astonishing rise of SoC based technologies and related software platforms in smartphones created in unit terms the largest installed base ever seen in the history of computers and is now being further extended by tablets. An underlying additional element of this transition is the increasing role of open source technologies both in software and hardware. This has driven the microprocessor based personal computer industry with few dominating closed operating system platforms into a steep decline. A significant factor in this process has been the separation of processor architecture and processor chip production and operating systems and application development platforms merger into integrated software platforms with proprietary application markets. Furthermore the pay-by-click marketing has changed the way applications development is compensated: Three essays on major trends in a slow clockspeed industry: The case of industrial automation 2014 freeware, ad based or licensed - all at a lower price and used by a wider customer base than ever before. Moreover, the concept of software maintenance contract is very remote in the app world. However, as a slow clockspeed industry, industrial automation has remained intact during the disruptions based on SoC and related software platforms in the ICT industries. Industrial automation incumbents continue to supply systems based on vertically integrated systems consisting of proprietary software and proprietary mainly microprocessor based hardware. They enjoy admirable profitability levels on a very narrow customer base due to strong technology-enabled customer lock-in and customers' high risk leverage as their production is dependent on fault-free operation of the industrial automation systems. When will this balance of power be disrupted? The thesis suggests how industrial automation could join the mainstream ICT industry and create an information, communication and automation (ICAT) industry. Lately the Internet of Things (loT) and weightless networks, a new standard leveraging frequency channels earlier occupied by TV broadcasting, have gradually started to change the rigid world of Machine to Machine (M2M) interaction. It is foreseeable that enough momentum will be created that the industrial automation market will in due course face an architecture disruption empowered by these new trends. This thesis examines the current state of industrial automation subject to the competition between the incumbents firstly through a research on cost competitiveness efforts in captive outsourcing of engineering, research and development and secondly researching process re- engineering in the case of complex system global software support. Thirdly we investigate the industry actors', namely customers, incumbents and newcomers, views on the future direction of industrial automation and conclude with our assessments of the possible routes industrial automation could advance taking into account the looming rise of the Internet of Things (loT) and weightless networks. Industrial automation is an industry dominated by a handful of global players each of them focusing on maintaining their own proprietary solutions. The rise of de facto standards like IBM PC, Unix and Linux and SoC leveraged by IBM, Compaq, Dell, HP, ARM, Apple, Google, Samsung and others have created new markets of personal computers, smartphone and tablets and will eventually also impact industrial automation through game changing commoditization and related control point and business model changes. This trend will inevitably continue, but the transition to a commoditized industrial automation will not happen in the near future.

Analytical interference of 4-hydroxy-3-methoxymethamphetamine with the measurement of plasma free normetanephrine by ultra-high pressure liquid chromatography-tandem mass spectrometry.

OBJECTIVES: The diagnosis of pheochromocytoma relies on the measurement of plasma free metanephrines assay whose reliability has been considerably improved by ultra-high pressure liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). Here we report an analytical interference occurring between 4-hydroxy-3-methoxymethamphetamine (HMMA), a metabolite of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy"), and normetanephrine (NMN) since they share a common pharmacophore resulting in the same product ion after fragmentation. DESIGN AND METHODS: Synthetic HMMA was spiked into plasma samples containing various concentrations of NMN and the intensity of the interference was determined by UPLC-MS/MS before and after improvement of the analytical method. RESULTS: Using a careful adjustment of chromatographic conditions including the change of the UPLC analytical column, we were able to distinguish both compounds. HMMA interference for NMN determination should be seriously considered since MDMA activates the sympathetic nervous system and if confounded with NMN may lead to false-positive tests when performing a differential diagnostic of pheochromocytoma.

Creation and Validation of Chronojump-Boscosystem: A Free Tool to Measure Vertical Jumps

Measuring the height of the vertical jump is an indicator of the strength and power of the lower body. The technological tools available to measure the vertical jump are black boxes and are not open to third-party verification or adaptation. We propose the creation of a measurement system called Chronojump-Boscosystem, consisting of open hardware and free software. Methods: A microcontroller was created and validated using a square wave generator and an oscilloscope. Two types of contact platforms were developed using different materials. These platforms were validated by the minimum pressure required for activation at different points by a strain gauge, together with the on/off time of our platforms in respect of the Ergojump-Boscosystem platform by a sample of 8 subjects performing submaximal jumps with one foot on each platform. Agile methodologies were used to develop and validate the software. Results: All the tools fall under the free software / open hardware guidelines and are, in that sense, free. The microcontroller margin of error is 0.1%. The validity of the fiberglass platform is 0.95 (ICC). The management software contains nearly 113.000 lines of code and is available in 7 languages.

Free and total plasma levels of lopinavir during pregnancy, at delivery and postpartum: implications for dosage adjustments in pregnant women.

BACKGROUND: Physiological changes associated with pregnancy may alter antiretroviral plasma concentrations and might jeopardize prevention of mother-to-child HIV transmission. Lopinavir is one of the protease inhibitors more frequently prescribed during pregnancy in Europe. We described the free and total pharmacokinetics of lopinavir in HIV-infected pregnant and non-pregnant women, and evaluated whether significant alterations in its disposition and protein binding warrant systematic dosage adjustment. METHODS: Plasma samples were collected at first, second and third trimester of pregnancy, at delivery, in umbilical cord and postpartum. Lopinavir free and total plasma concentrations were measured by HPLC-MS/MS. Bayesian calculations were used to extrapolate total concentrations to trough (Cmin). RESULTS: A total of 42 HIV-positive pregnant women and 37 non-pregnant women on lopinavir/ritonavir were included in the study. Compared to postpartum and control values, total lopinavir Cmin was decreased moderately (31-39%) during pregnancy, and free Cmin minimally, showing significant alteration only at delivery (-35%). However, total and free Cmin remained in all patients above the target concentrations for wild-type virus of 1,000 ng/ml, and above the unbound IC50(WT) of 0.64-0.77 ng/ml of lopinavir, respectively. Lopinavir free fractions remained higher during pregnancy compared to postpartum and controls, and were influenced by α-1-acid-glycoprotein and albumin decrease. Free cord-to-mother ratio (0.43) was 2.7-fold higher than total cord-to-mother ratio (0.16), suggesting higher fetal exposure. CONCLUSIONS: The moderate decrease of total lopinavir concentrations during pregnancy is not associated with proportional decrease in free concentrations. Both reach a nadir at delivery, albeit not to an extent that would put treatment-naive women at risk of insufficient exposure to the free, pharmacologically active concentrations of lopinavir. No dosage adjustment is therefore needed during pregnancy as it is unlikely to further enhance treatment efficacy but could potentially increase the risk of maternal and fetal toxicity. Nonetheless, in case of viral resistance in treatment-experienced pregnant women, loss of virological control or questionable adherence, it is justified to consider lopinavir dosage adjustment based on total plasma concentration measurement.

Yield and performance of sugarcane in on-farm interface with rubber in Brazil

Agroforestry systems are indicated as an alternative for sugarcane (Saccharum officinarum) cultivation in Piracicaba, SP, Brazil, however there are not many field experiments on plant performance under these conditions in the world. The objective of this work was to assess crop yield and partitioning in a sugarcane-rubber (Hevea brasiliensis) interface in on-farm conditions. The availability of irradiance for the crop along the interface was simulated and its effe ct over sugarcane dry matter production was tested. Crop yield was negatively affected by distance of the trees, but development and sucrose were not affected. Above ground dry matter increased from 16.6 to 51.5 t ha-1 from trees. Partitioning did not have a defined standard, as harvest index increased from 0.85 to 0.93, but specific leaf area was not significant along the transect, ranging from 13.48 to 15.73 m² kg-1. Light is the main factor of competition between the trees and the crop, but the relative importance of below ground interactions increases closer to the trees. Feasibility of the system depends on maturity of the trees and management strategies.

Direct numerical simulations of interface dynamics to link capillary pressure and total surface energy

The flow of two immiscible fluids through a porous medium depends on the complex interplay between gravity, capillarity, and viscous forces. The interaction between these forces and the geometry of the medium gives rise to a variety of complex flow regimes that are difficult to describe using continuum models. Although a number of pore-scale models have been employed, a careful investigation of the macroscopic effects of pore-scale processes requires methods based on conservation principles in order to reduce the number of modeling assumptions. In this work we perform direct numerical simulations of drainage by solving Navier-Stokes equations in the pore space and employing the Volume Of Fluid (VOF) method to track the evolution of the fluid-fluid interface. After demonstrating that the method is able to deal with large viscosity contrasts and model the transition from stable flow to viscous fingering, we focus on the macroscopic capillary pressure and we compare different definitions of this quantity under quasi-static and dynamic conditions. We show that the difference between the intrinsic phase-average pressures, which is commonly used as definition of Darcy-scale capillary pressure, is subject to several limitations and it is not accurate in presence of viscous effects or trapping. In contrast, a definition based on the variation of the total surface energy provides an accurate estimate of the macroscopic capillary pressure. This definition, which links the capillary pressure to its physical origin, allows a better separation of viscous effects and does not depend on the presence of trapped fluid clusters.

Premsa gratuïta, un model de comunicació local = Free press, a local communication model

The relationship between non-institutional free press and local communication is quite particular since this type of press forms a very characteristic model of local communication, showing that advertising suffices to finance an information product addressed to a fairly well-defined readership as long as this product has a good advertising sales department and an effective distribution in its operating area. This paper discusses the present situation of the free press in Catalonia, where this phenomenon has been quite prominent. It points out the main features of this type of press and makes a review of its history, which runs from the euphoria of its early years and its expansion and consolidation, to the current crisis