Implantation of the biodegradable polymer biolimus-eluting stent in patients with high SYNTAX score is associated with decreased cardiac mortality compared to a permanent polymer sirolimus-eluting stent: two year follow-up results from the "all-comers" LEADERS trial

Background: The SYNTAX score (SXscore) has been shown to be an effective predictor of clinical outcomes in patients undergoing percutaneous coronary intervention (PCI). Methods and results: The SXscore was prospectively collected in 1,397 of the 1,707 patients enrolled in the “all-comers” LEADERS trial (patients post-surgical revascularisation were excluded). Post hoc analysis was performed by stratifying clinical outcomes at two-year follow-up, according to one of three SXscore tertiles: SXlow ≤8 (n=464), 816 (n=461). At two-year follow-up the rate of major adverse cardiovascular events was 18.4%, 12.0% and 9.4% in the SXhigh, SXmid, and SXlow tertile, respectively (HR 1.45; CI 1.21-1.74; p<0.01). There was a significantly higher rate of cardiac death in patients in the highest SXscore tertile (7% SXhigh versus 2.4% SXmid versus 1.8% SXlow; HR 2.22; CI 1.5-3.27; p<0.001). Within the SXhigh tertile the rate of cardiac death was significantly lower in patients treated with the biolimus-eluting stent compared with the sirolimus-eluting stent (4.7% versus 9.6%, HR 0.48; CI 0.23-0.99; p=0.046). Conclusions: The SXscore when applied to an “all-comers” patient population allows for prospective risk stratification of patients undergoing PCI up to two years follow-up. In addition, the SXscore appears to separate the performance of devices in high risk patient groups.

Two-year follow-up of patients undergoing transcatheter aortic valve implantation using a self-expanding valve prosthesis

The purpose of this study was to evaluate the safety, device performance, and clinical outcome up to 2 years for patients undergoing transcatheter aortic valve implantation (TAVI).

Neuropsychological problems after paediatric stroke: two year follow-up of Swiss children

AIM: The aim of this study was to obtain information about neurological and cognitive outcome for a population-based group of children after paediatric ischaemic stroke. METHODS: Data from the Swiss neuropaediatric stroke registry (SNPSR), from 1.1.2000 to 1.7.2002, including children (AIS 1) and neonates (AIS 2). At 18-24 months after a stroke, a follow-up examination was performed including a history, neurological and neuropsychological assessment. RESULTS: 33/48 children (22 AIS 1, 11 AIS 2) participated in the study. Neurological outcome was good in 16/33. After childhood stroke mean IQ levels were normal (94), but 6 children had IQ < 85 (50-82) and neuropsychological problems were present in 75%. Performance IQ (93) was reduced compared to verbal IQ (101, p = 0.121) due to problems in the domain of processing speed (89.5); auditory short-term memory was especially affected. Effects on school career were common. Outcome was worse in children after right-sided infarction. Children suffering from stroke in mid-childhood had the best prognosis. There was no clear relationship between outcome and localisation of the lesion. After neonatal stroke 7/11 children showed normal development and epilepsy indicated a worse prognosis in the remaining 4. CONCLUSION: After paediatric stroke neuropsychological problems are present in about 75% of children. Younger age at stroke as well as an emergence of epilepsy were predictors for worse prognosis.

Large Sample Theory for Semiparametric Regression Models with Two-Phase, Outcome Dependent Sampling

Outcome-dependent, two-phase sampling designs can dramatically reduce the costs of observational studies by judicious selection of the most informative subjects for purposes of detailed covariate measurement. Here we derive asymptotic information bounds and the form of the efficient score and influence functions for the semiparametric regression models studied by Lawless, Kalbfleisch, and Wild (1999) under two-phase sampling designs. We show that the maximum likelihood estimators for both the parametric and nonparametric parts of the model are asymptotically normal and efficient. The efficient influence function for the parametric part aggress with the more general information bound calculations of Robins, Hsieh, and Newey (1995). By verifying the conditions of Murphy and Van der Vaart (2000) for a least favorable parametric submodel, we provide asymptotic justification for statistical inference based on profile likelihood.

Two-Phase Flow In Microchannels: Morphology And Interface Phenomena

The existence and morphology, as well as the dynamics of micro-scale gas-liquid interfaces is investigated numerically and experimentally. These studies can be used to assess liquid management issues in microsystems such as PEMFC gas flow channels, and are meant to open new research perspectives in two-phase flow, particularly in film deposition on non-wetting surfaces. For example the critical plug volume data can be used to deliver desired length plugs, or to determine the plug formation frequency. The dynamics of gas-liquid interfaces, of interest for applications involving small passages (e.g. heat exchangers, phase separators and filtration systems), was investigated using high-speed microscopy - a method that also proved useful for the study of film deposition processes. The existence limit for a liquid plug forming in a mixed wetting channel is determined by numerical simulations using Surface Evolver. The plug model simulate actual conditions in the gas flow channels of PEM fuel cells, the wetting of the gas diffusion layer (GDL) side of the channel being different from the wetting of the bipolar plate walls. The minimum plug volume, denoted as critical volume is computed for a series of GDL and bipolar plate wetting properties. Critical volume data is meant to assist in the water management of PEMFC, when corroborated with experimental data. The effect of cross section geometry is assessed by computing the critical volume in square and trapezoidal channels. Droplet simulations show that water can be passively removed from the GDL surface towards the bipolar plate if we take advantage on differing wetting properties between the two surfaces, to possibly avoid the gas transport blockage through the GDL. High speed microscopy was employed in two-phase and film deposition experiments with water in round and square capillary tubes. Periodic interface destabilization was observed and the existence of compression waves in the gas phase is discussed by taking into consideration a naturally occurring convergent-divergent nozzle formed by the flowing liquid phase. The effect of channel geometry and wetting properties was investigated through two-phase water-air flow in square and round microchannels, having three static contact angles of 20, 80 and 105 degrees. Four different flow regimes are observed for a fixed flow rate, this being thought to be caused by the wetting behavior of liquid flowing in the corners as well as the liquid film stability. Film deposition experiments in wetting and non-wetting round microchannels show that a thicker film is deposited for wetting conditions departing from the ideal 0 degrees contact angle. A film thickness dependence with the contact angle theta as well as the Capillary number, in the form h_R ~ Ca^(2/3)/ cos(theta) is inferred from scaling arguments, for contact angles smaller than 36 degrees. Non-wetting film deposition experiments reveal that a film significantly thicker than the wetting Bretherton film is deposited. A hydraulic jump occurs if critical conditions are met, as given by a proposed nondimensional parameter similar to the Froude number. Film thickness correlations are also found by matching the measured and the proposed velocity derived in the shock theory. The surface wetting as well as the presence of the shock cause morphological changes in the Taylor bubble flow.

DEVELOPMENT OF CONFOCAL IMAGING TECHNIQUES FOR PROBING INTERFACIAL DYNAMICS IN MICROSCALE, GAS-LIQUID, TWO-PHASE FLOW

Micro-scale, two-phase flow is found in a variety of devices such as Lab-on-a-chip, bio-chips, micro-heat exchangers, and fuel cells. Knowledge of the fluid behavior near the dynamic gas-liquid interface is required for developing accurate predictive models. Light is distorted near a curved gas-liquid interface preventing accurate measurement of interfacial shape and internal liquid velocities. This research focused on the development of experimental methods designed to isolate and probe dynamic liquid films and measure velocity fields near a moving gas-liquid interface. A high-speed, reflectance, swept-field confocal (RSFC) imaging system was developed for imaging near curved surfaces. Experimental studies of dynamic gas-liquid interface of micro-scale, two-phase flow were conducted in three phases. Dynamic liquid film thicknesses of segmented, two-phase flow were measured using the RSFC and compared to a classic film thickness deposition model. Flow fields near a steadily moving meniscus were measured using RSFC and particle tracking velocimetry. The RSFC provided high speed imaging near the menisci without distortion caused the gas-liquid interface. Finally, interfacial morphology for internal two-phase flow and droplet evaporation were measured using interferograms produced by the RSFC imaging technique. Each technique can be used independently or simultaneously when.

Trajectory of posttraumatic stress disorder caused by myocardial infarction: a two-year follow-up study

OBJECTIVE: A substantial proportion of patients develop posttraumatic stress disorder (PTSD) following myocardial infarction (MI). Previous research on the trajectory over time of PTSD in post-MI patients is scant and refers to self-rated posttraumatic symptoms. The aim of this study was to investigate the longitudinal course of an interviewer-rated diagnosis of PTSD and PTSD symptom severity following MI. METHODS: Study participants were 40 patients (78% men, mean age 54 +/- 8 years) who were diagnosed with PTSD using the Clinician-administered PTSD Scale (CAPS) after an average of 5 +/- 4 months (range 2-16 months) following an index MI. After a mean follow-up of 26 +/- 6 months (range 12-36 months), 24 patients underwent a second diagnostic interview. RESULTS: Two-thirds of patients (n = 16) still qualified for a diagnosis of PTSD at follow-up. In all 24 patients, total PTSD symptoms (p = 0.001), re-experiencing symptoms (p < 0.001), avoidance symptoms (p = 0.015), and, with borderline significance, hyperarousal symptoms (p < 0.06) had all decreased over time. However, in the subgroup of the 16 patients who had retained PTSD diagnostic status at follow-up, symptoms of avoidance (p = 0.23) and of hyperarousal (p = 0.48) showed no longitudinal decline. Longer duration of follow-up was associated with a greater decrease in avoidance symptoms (p = 0.029) and, with borderline significance, in re-experiencing symptoms (p < 0.07) across all patients. CONCLUSION: Although PTSD symptomatology waned over time and in relation to longer follow-up, two-thirds of patients still qualified for a diagnosis of PTSD 2 years after the initial diagnosis. In post-MI patients, clinical PTSD is a considerably persistent condition.

Two-phase change in CO2, Antarctic temperature and global climate during Termination II

The end of the Last Glacial Maximum (Termination I), roughly 20 thousand years ago (ka), was marked by cooling in the Northern Hemisphere, a weakening of the Asian monsoon, a rise in atmospheric CO2 concentrations and warming over Antarctica. The sequence of events associated with the previous glacial–interglacial transition (Termination II), roughly 136 ka, is less well constrained. Here we present high-resolution records of atmospheric CO2 concentrations and isotopic composition of N2—an atmospheric temperature proxy—from air bubbles in the EPICA Dome C ice core that span Termination II. We find that atmospheric CO2 concentrations and Antarctic temperature started increasing in phase around 136 ka, but in a second phase of Termination II, from 130.5 to 129 ka, the rise in atmospheric CO2 concentrations lagged that of Antarctic temperature unequivocally. We suggest that during this second phase, the intensification of the low-latitude hydrological cycle resulted in the development of a CO2 sink, which counteracted the CO2 outgassing from the Southern Hemisphere oceans over this period.

Circumferential distribution of the neointima at six-month and two-year follow-up after a bioresorbable vascular scaffold implantation: a substudy of the ABSORB Cohort B Clinical Trial

Aims: To investigate the extent and the circumferential distribution of the neointima tissue developed following an Absorb bioresorbable vascular scaffold (BVS) implantation. Methods and results: Twenty-three patients who were treated with the Absorb BVS and had optical coherence tomographic examination after scaffold implantation, at six-month and at two-year follow-up, were included in the current analysis. The lumen and the scaffold borders were detected and the circumferential thickness of the neointima was measured at one degree intervals. The symmetry of the neointima was defined as: minimum/maximum thickness. The lumen area was decreased at six months compared to baseline but it did not change between six-month and two-year follow-up (baseline: 7.49 [6.13-8.00] mm2, six months: 6.31 (4.75-7.06) mm2, two years: 6.01 [4.67-7.11] mm2, p=0.373). However, the mean neointima thickness (six months: 189 [173-229] μm, two years: 258 [222-283] μm, p<0.0001) and the symmetry index of the neointima (six months: 0.06 [0.02-0.09], two years: 0.27 [0.24-0.36], p<0.0001) were increased at two years. Full circumferential coverage of the vessel wall by neointima tissue was seen in 91% of the studied frames at two years. Conclusions: This study demonstrates that after an Absorb BVS implantation neointima tissue develops that covers almost the whole circumference of the vessel wall. In contrast to the metallic stents, the neointima tissue does not compromise the luminal dimensions. Further research is required to evaluate the neointimal characteristics and assess the potential value of the device in passivating high-risk plaques.

Design of a Two-Phase buck converter with fourth-order output filter for envelope amplifiers of limited bandwidth

The use of techniques such as envelope tracking (ET) and envelope elimination and restoration (EER) can improve the efficiency of radio frequency power amplifiers (RFPA). In both cases, high-bandwidth DC/DC converters called envelope amplifiers (EA) are used to modulate the supply voltage of the RFPA. This paper addresses the analysis and design of a modified two-phase Buck converter optimized to operate as EA. The effects of multiphase operation on the tracking capabilities are analyzed. The use of a fourth-order output filter is proposed to increase the attenuation of the harmonics generated by the PWM operation, thus allowing a reduction of the ratio between the switching frequency and the converter bandwidth. The design of the output filter is addressed considering envelope tracking accuracy and distortion caused by the side bands arising from the nonlinear modulation process. Finally, the proposed analysis and design methods are supported by simulation results, as well as demonstrated by experiments obtained using two 100-W, 10-MHz, two-phase Buck EAs capable of accurately tracking a 1.5-MHz bandwidth OFDM signal.

Transgene organization in rice engineered through direct DNA transfer supports a two-phase integration mechanism mediated by the establishment of integration hot spots

Organization of transgenes in rice transformed through direct DNA transfer strongly suggests a two-phase integration mechanism. In the “preintegration” phase, transforming plasmid molecules (either intact or partial) are spliced together. This gives rise to rearranged transgenic sequences, which upon integration do not contain any interspersed plant genomic sequences. Subsequently, integration of transgenic DNA into the host genome is initiated. Our experiments suggest that the original site of integration acts as a hot spot, facilitating subsequent integration of successive transgenic molecules at the same locus. The resulting transgenic locus may have plant DNA separating the transgenic sequences. Our data indicate that transformation through direct DNA transfer, specifically particle bombardment, generally results in a single transgenic locus as a result of this two-phase integration mechanism. Transgenic plants generated through such processes may, therefore, be more amenable to breeding programs as the single transgenic locus will be easier to characterize genetically. Results from direct DNA transfer experiments suggest that in the absence of protein factors involved in exogenous DNA transfer through Agrobacterium, the qualitative and/or quantitative efficiency of transformation events is not compromised. Our results cast doubt on the role of Agrobacterium vir genes in the integration process.