Unique scintigraphic parameters for the evaluation of ventricular synchrony were derived, and their added value was determine compared with established measures. Indications for pacemaker therapy now include the treatment of severe congestive heart failure (CHF). Atrial triggered biventricular pacemakers reduce CHF symptoms and prolong life in patients with cardiomyopathy, severe CHF, left ventricular (LV) ejection fraction (EF) lower than 35%, and QRS greater than 120 milliseconds. Such pacing, or cardiac resynchronization therapy (CRT), seeks to reduce the heterogeneity and increase the synchrony of ventricular activation, conduction, and contraction. CRT has improved hemodynamics, increased exercise tolerance, reduced symptoms and the need for hospitalization, reversed ventricular remodeling, and reduced the all-cause mortality rate in CHF. However, CRT is costly, fails to improve symptoms or activity level in more than 30% of patients, and is applied blindly without individualization or consideration of lead placement sight. A variety of echocardiographic methods have sought to measure synchrony and its serial changes with CRT. A recent study presented evidence of the poor reproducibility of several widely applied echocardiographic measurements by which to determine ventricular synchrony. Magnetic resonance imaging has excellent resolution of regional wall motion and has been applied to assess ventricular synchrony and its response to pacing therapy. However, these methods are complex and are not well established or widely available, and magnetic resonance imaging has not been widely applied after pacing. An accurate and reproducible method is needed by which to objectively measure regional ventricular synchrony. Phase image analysis, a functional method based on the first Fourier harmonic fit of the gated blood pool time versus radioactivity curve, generates the parameters of amplitude (A), which parallels the extent of regional ventricular contraction or stroke volume, and phase angle (Ø), which represents the timing of regional contraction. It was applied early with demonstrated reproducibility to show the linkage between electrical and mechanical dyssynchrony and to characterize the contraction pattern in heart failure and its alteration with CRT. The SD of ventricular Ø, applied as a marker of synchrony, has been shown to demonstrate the beneficial effects of biventricular pacing, and its strong prognostic value has been shown in patients with congestive cardiomyopathy and CHF, superior to LVEF. The SD Ø may not be optimal for synchrony evaluation. We sought improved, more sensitive parameters to better differentiate synchrony among the spectrum of possible patterns of dyssynergy. We derived, initially evaluated, and here present new synchrony (S) and entropy (E) parameters, based on the phase method, to quantitate regional and global ventricular synchrony and applied them in simulation and clinical protocols.

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Major improvements in weld inspection are obtained using Phased Array technology with capability for beam steering, electronic scanning, focusing, and sweeping the ultrasonic beams. Electronic scanning is much faster than raster scanning, and can optimize angles and focusing to maximize defect detection. Pressure vessel (PV) inspections typically use “top, side, end” or “top, side, TOFD” views, though other imaging is possible. Special inspections can be performed, e.g., for specific defects, or increased coverage. Defects can be sized by pulse-echo as per code, by time-of-flight Diffraction or by back diffraction. New PV inspection codes, particularly ASME Code Case 2235, permit the use of advanced ultrasonic inspection techniques. Pipeline girth weld inspections use a unique inspection approach called “zone discrimination,” and have their own series of codes. While similar equipment is used in pipeline as in PV inspections, the pipeline philosophy is to tailor the inspection to the weld profile and predicted lack of fusion defects. Pipeline displays are specifically designed for near real-time data analysis. Both ASME CC 2235 and the pipeline codes permit the use of Fitness-For-Purpose, which reduces construction costs. Overall, phased array systems meet or exceed all PV and pipeline codes.

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Pipelines are now using Fitness-For-Service (FFS) for accept/reject of weld defects. FFS requires accurate measurement of defect height for Fracture Mechanics assessments. The standard pipeline weld inspection technique of radiography is incapable of such measurements. However, the newer technique of ultrasonics can measure defect height, in principle. Initially ultrasonic amplitude methods were used for height measurement, but these proved unreliable. Now diffraction methods, especially Time-Of-Flight-Diffraction (TOFD), are being used in conjunction. This paper reviews previous work — mainly large nuclear studies like PISC II — and published pipeline sizing studies. The best nuclear sizing was within a few millimetres, using diffraction. In contrast to nuclear, pipeline AUT uses zone discrimination, focused transducers, much thinner material and simpler analysis techniques. Current accuracies are typically ± 1 mm (terminology undefined), which correlates with the beam spot size and typical weld pass. Requests for accuracies of ± 0.3 mm are probably unachievable, though future R&D should significantly improve pipeline sizing.

The voltage-gated proton channel Hv1 regulates proton fluxes across membranes, thereby influencing pH-dependent processes. Plasmacytoid dendritic cells (pDCs) require a particularly tight regulation of endosomal pH to ensure strong type I IFN secretion exclusively during infection, avoiding autoimmunity. However, whether Hv1 is important for pH control in pDCs is presently unknown. In this study, we show that mouse pDCs require Hv1 to achieve potent type I IFN responses after the recognition of foreign DNA by endosomal TLR9. Genetic disruption of Hvcn1, which encodes Hv1, impaired mouse pDC activation by CpG oligonucleotides in vitro and in vivo, reducing IFN-a secretion and the induction of IFN-stimulated genes. Mechanistically, Hvcn1 deficiency delayed endosomal acidification and enhanced intracellular reactive oxygen species production, consequently limiting protease activity and TLR9 signaling. Our study reveals a critical role of Hv1 during innate immune responses and places this channel as a key modulator of type I IFN production, the hallmark function of pDCs, commending Hv1 as an attractive target for modulating type I IFN-driven autoimmunity.

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