Insufficient Overlap Research Articles

Determining Free Energy Differences Through Non-Linear Morphing

The Bennett Acceptance Ratio (BAR) method is widely used to estimate the free energy difference between two given states of a many-body system, such as a macromolecule, where Molecular Dynamics or Monte Carlo simulations are typically used for sampling. Because insufficient phase space overlap of the two states can lead to large biases in the results, the calculation is commonly split up into several smaller steps using intermediate states defined along a so-called morphing path — typically a linear interpolation between the start and the end states' Hamiltonians. Here, using BAR, we develop an optimization scheme to find the path that yields the most accurate free energy values from the much more general class of paths that includes also non-linear interpolations. For a broad range of one-dimensional test systems, we show that the free energy sampling error can be decreased by 25% to 35% compared to linear interpolations, with a theoretical upper limit of 50%. Further, correlations arising from using the same sample in one state to evaluate differences to more than one other state can be taken into account. Finally, we demonstrate that the optimization is still valid for a large number of intermediate states with very sparse sampling for each, enabling further optimization by trading off sampling versus number of intermediate states.

3-Dimensional inkjet printing of macro structures from silver nanoparticles

The adoption of additive manufacturing technology is gaining interest for processing precious metals. In this study, the capability of inkjet printing was explored to fabricate macroscopic parts from commercial silver nanoparticle ink (AgNPs). A bespoke JETx® three dimensional (3D) inkjet printing machine was used to print and subsequently sinter up to 1000 layers of AgNPs using an infrared source. Examination of the sample using X-ray computed tomography and scanning electron microscopy revealed the existence of both micro- and nano-scale pores within the structure. Pinning effect, residual surface temperature, insufficient droplet overlap and surface defects were the key factors contributing to the voids. Elemental mapping confirmed the structure to be composed of 87% of silver along with carbon and oxygen. The 750dpi sample showed a 25% reduction in nanopores and 77% lower micro-pores compared to the 600dpi sample. In terms of hardness, the 750dpi sample was 29% harder than the 600dpi sample, showcasing samples with higher print resolution can contribute towards less voids and improved mechanical properties. Thus by demonstrating the possibility to fabricate dense parts from AgNPs using inkjet technology, this study opens a novel route for processing nano-scale particulates and precious metals in 3D.

Efficient Strategy for the Calculation of Solvation Free Energies in Water and Chloroform at the Quantum Mechanical/Molecular Mechanical Level

The partitioning of solute molecules between immiscible solvents with significantly different polarities is of great importance. The polarization between the solute and solvent molecules plays an essential role in determining the solubility of the solute, which makes computational studies utilizing molecular mechanics (MM) rather difficult. In contrast, quantum mechanics (QM) can provide more reliable predictions. In this work, the partition coefficients of the side chain analogs of some amino acids between water and chloroform were computed. The QM solvation free energies were calculated indirectly via a series of MM states using the multistate Bennett acceptance ratio (MBAR) and the MM-to-QM corrections were applied at the two endpoints using thermodynamic perturbation (TP). Previously, it has been shown (Jia et al. J. Chem. Theory Comput. 2016, 12, 499-511) that this method provides the minimal variance in the results without running QM simulations. However, if there is insufficient overlap in phase space between the MM and QM Hamiltonians, this method fails. In this work, we propose, for the first time, a quantity termed the reweighting entropy that serves as a metric for the reliability of the TP calculations. If the reweighting entropy is below a certain threshold (0.65 for the solvation free energy calculations in this work), this MM-to-QM correction should be avoided and two alternative methods can be employed by either introducing a semiempirical state or conducting nonequilibrium simulations. However, the results show that the QM methods are not guaranteed to yield better results than the MM methods. Further improvement of the QM methods are imperative, especially the treatment of the van der Waals and the electrostatic interactions between the QM region and the MM region in the first shell. We also propose a scheme for the calculation of the van der Waals parameters for the solute molecules in nonaqueous solvent, which improves the quality of the computed thermodynamic properties. Furthermore, the force field parameters for the sulfur-containing molecules are also optimized.

Year-End Clinic Handoffs: A National Survey of Academic Internal Medicine Programs.

While there has been increasing emphasis and innovation nationwide in training residents in inpatient handoffs, very little is known about the practice and preparation for year-end clinic handoffs of residency outpatient continuity practices. Thus, the latter remains an identified, yet nationally unaddressed, patient safety concern. The 2014 annual Association of Program Directors in Internal Medicine (APDIM) survey included seven items for assessing the current year-end clinic handoff practices of internal medicine residency programs throughout the country. Nationwide survey. All internal medicine program directors registered with APDIM. Descriptive statistics of programs and tools used to formulate a year-end handoff in the ambulatory setting, methods for evaluating the process, patient safety and quality measures incorporated within the process, and barriers to conducting year-end handoffs. Of the 361 APDIM member programs, 214 (59%) completed the Transitions of Care Year-End Clinic Handoffs section of the survey. Only 34% of respondent programs reported having a year-end ambulatory handoff system, and 4% reported assessing residents for competency in this area. The top three barriers to developing a year-end handoff system were insufficient overlap between graduating and incoming residents, inability to schedule patients with new residents in advance, and time constraints for residents, attendings, and support staff. Most internal medicine programs do not have a year-end clinic handoff system in place. Greater attention to clinic handoffs and resident assessment of this care transition is needed.

Prediction of lack-of-fusion porosity for powder bed fusion

A geometry-based simulation is used to predict porosity caused by insufficient overlap of melt pools (lack of fusion) in powder bed fusion. The inputs into the simulation are hatch spacing, layer thickness, and melt-pool cross-sectional area. Melt-pool areas used in the simulations can be obtained from experiments, or estimated with the analytical Rosenthal equation. The necessary material constants, including absorptivity for laser-based melting, have been collated for alloy steels, aluminum alloys and titanium alloys. Comparison with several data sets from the literature shows that the simulations correctly predict process conditions at which lack-of-fusion porosity becomes apparent, as well as the rate at which porosity increases with changes in process conditions such as beam speed, layer thickness and hatch spacing.

Multimodal registration of remotely sensed images based on Jeffrey’s divergence

Entropy-based measures (e.g., mutual information, also known as Kullback-Leiber divergence), which quantify the similarity between two signals, are widely used as similarity measures for image registration. Although they are proven superior to many classical statistical measures, entropy-based measures, such as mutual information, may fail to yield the optimum registration if the multimodal image pair has insufficient scene overlap region. To overcome this challenge, we proposed using the symmetric form of Kullback-Leiber divergence, namely Jeffrey’s divergence, as the similarity measure in practical multimodal image registration tasks. Mathematical analysis was performed to investigate the causes accounting for the limitation of mutual information when dealing with insufficient scene overlap image pairs. Experimental registrations of SPOT image, Landsat TM image, ALOS PalSAR image, and DEM data were carried out to compare the performance of Jeffrey’s divergence and mutual information. Results indicate that Jeffrey’s divergence is capable of providing larger feasible search space, which is favorable for exploring optimum transformation parameters in a larger range. This superiority of Jeffrey’s divergence was further confirmed by a series of paradigms. Thus, the proposed model is more applicable for registering image pairs that are greatly misaligned or have an insufficient scene overlap region.

3-D surface properties of glacier penitentes over an ablation season, measured using a Microsoft Xbox Kinect

Abstract. In this study, the first small-scale digital surface models (DSMs) of natural penitentes on a glacier surface were produced using a Microsoft Xbox Kinect sensor on Tapado Glacier, Chile (30°08′ S, 69°55′ W). The surfaces produced by the complete processing chain were within the error of standard terrestrial laser scanning techniques, but insufficient overlap between scanned sections that were mosaicked to cover the sampled areas can result in three-dimensional (3-D) positional errors of up to 0.3 m. Between November 2013 and January 2014 penitentes become fewer, wider and deeper, and the distribution of surface slope angles becomes more skewed to steep faces. Although these morphological changes cannot be captured by manual point measurements, mean surface lowering of the scanned areas was comparable to that derived from manual measurements of penitente surface height at a minimum density of 5 m−1 over a 5 m transverse profile. Roughness was computed on the 3-D surfaces by applying two previously published geometrical formulae: one for a 3-D surface and one for single profiles sampled from the surface. Morphometric analysis shows that skimming flow is persistent over penitentes, providing conditions conducive for the development of a distinct microclimate within the penitente troughs. For each method a range of ways of defining the representative roughness element height was used, and the calculations were done both with and without application of a zero displacement height offset to account for the likelihood of skimming air flow over the closely spaced penitentes. The computed roughness values are on the order of 0.01–0.10 m during the early part of the ablation season, increasing to 0.10–0.50 m after the end of December, in line with the roughest values previously published for glacier ice. Both the 3-D surface and profile methods of computing roughness are strongly dependent on wind direction. However, the two methods contradict each other in that the maximum roughness computed for the 3-D surface coincides with airflow across the penitente lineation, while maximum roughness computed for sampled profiles coincides with airflow along the penitente lineation. These findings highlight the importance of determining directional roughness and wind direction for strongly aligned surface features and also suggest more work is required to determine appropriate geometrical roughness formulae for linearized features.

Caring Alone? Social Capital and the Mental Health of Caregivers

This study analyzes the role of social capital in buffering the negative relationship between informal-care provision and mental health. Using data from the German Socio-Economic Panel (SOEP) and fixed-effect regression models, we show that those individuals who socialize more frequently enjoy better mental health. We also find that stronger social ties moderate the negative association between caregiving and mental well-being. The protective role of social capital appears to be particularly strong for caregivers with high time commitments or those who regularly perform voluntary work. The moderating role of social activities can neither be explained by the caregiver's observed characteristics correlated with social capital, nor by features of the caregiving process. However, the results might be driven by insufficient overlap in covariates between carers and non-carers, and the simultaneity between caring decisions and social activities. We relate our results to recent policy initiatives that aim to improve the carer's well-being. Utilization of caregiver-support services is still rather low. Our findings suggest that caregivers may prefer informal support provided by family, friends, or neighbors to public caregiver benefits. To corroborate this hypothesis, further research regarding the (causal) buffering effects of social capital in the context of informal care is needed.

Design of optocoupler for synthesizing four color spectra

LEDs with the advantage of high luminous efficacy and long life time show the potential of replacing traditional luminaire. Most commercial white LED light sources use blue or ultraviolet chip coated with emitting phosphor, but the sensitivity and instability of such phosphors has become a big issue. The typical RGB-LED by using individual chips has the problem of spatial separation and insufficient spectral overlap which leads to low CRI. This study suggests a novel and high-efficiency design of fiber optical optocoupler to synthesize four colors emitted by separate LEDs to provide the ideal light sources by adjusting the individual LEDs separately. By choosing different colored light to be synthesized, this optocoupler can be used as light sources which can be highly controlled to offer the best lighting conditions. Compared with other widely used commercial LED sources, this new design of light sources can be used in special experiments which require multi-spectral light.

Recommended Protected Time for Pediatric Fellowship Program Directors: A Needs Assessment Survey

V IEW F ROM THE A SSOCIATION OF P EDIATRIC P ROGRAM D IRECTORS Recommended Protected Time for Pediatric Fellowship Program Directors: A Needs Assessment Survey Geoffrey M. Fleming, MD; Michael M. Brook, MD; Bruce E. Herman, MD; Chris Kennedy, MD, PhD; Kathleen A. McGann, MD; Katherine E. Mason, MD; Pnina Weiss, MD; Angela L. Myers, MD, MPH From the Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tenn (Dr Fleming); University of California San Francisco, San Francisco, Calif (Dr Brook); Department of Pediatrics, Primary Children’s Hospital, University of Utah, Salt Lake City, Utah (Dr Herman); Children’s Mercy Kansas City, University of Missouri–Kansas City School of Medicine, Kansas City, Mo (Drs Kennedy and Myers); Department of Pediatrics, Duke University Medical Center, Durham, NC (Dr McGann); Department of Pediatrics, Case Western Reserve School of Medicine, Cleveland, Ohio (Dr Mason); and Department of Pediatrics, Yale University, New Haven, Conn (Dr Weiss) The authors declare that they have no conflict of interest. Address correspondence to Geoffrey M. Fleming, MD, Department of Pediatrics, Division of Critical Care Medicine, Vanderbilt University School of Medicine, 5112 DOT, 2200 Children’s Way, Nashville, TN 37232 (e-mail: geoffrey.fleming@vanderbilt.edu). A CADEMIC P EDIATRICS 2016;16:415–418 core program requirements: “The program director must devote a minimum of 0.5 FTE regardless of the size of the program.” 14 Core pediatric residency programs have recommendations for additional effort support in a graded increase on the basis of the size of the program and includes PDs, associate PDs, residency coordinators, and liaisons. Currently the “ACGME Program Requirements for Graduate Medical Education in the Subspecialties of Pediatrics” do not delineate any specific required time allotment for fellowship PDs but requires “sufficient pro- tected time.” 2 The goal of this study was to describe current time allotted for PDs in pediatric subspecialty fellowship training programs and to delineate the minimum time required for program administration to meet the regula- tions outlined by the ACGME. P EDIATRIC FELLOWSHIP TRAINING programs are the primary source of subspecialty practitioners who care for our nation’s children. There are 16 Accreditation Council for Graduate Medical Education (ACGME)-accredited pe- diatric subspecialties made up of 837 individual training programs that graduated over 8500 trainees from 2004 to 2013 in addition to those who graduated from combined board specialty programs that include a pediatric training component. 1 Explicit in the requirements for graduate medical education (GME) accreditation is the key role of the program director (PD), who is responsible for over- seeing all educational activities, assessing all trainee and faculty performance, maintaining and distributing all pro- gram policies and procedures, directing programmatic evaluation and process improvement, and monitoring compliance with all ACGME regulations. 2 Prior study has identified inadequate PD time as a barrier to complying with ACGME requirements in the nonpediatric subspe- cialties. 3 Dedicated administrative time has been identified as necessary for innovation and curricular design, and has been linked to ongoing accreditation by the ACGME. 4–12 The ACGME program requirements for core residency programs and many nonpediatric subspecialties now delin- eate program administration time requirements for PDs, associate PDs, and other support staff. The time allotted differs by specialty and varies in specification from hours per week to a percentage of total effort. 13 Current require- ments set forth by the ACGME range from 10% to 50% full-time equivalent (FTE) staff for the core medical and surgical specialties and for many of the subspecialty fel- lowships accredited by the American Board of Medical Specialties. For core pediatric residency programs, support of administrative efforts are specifically delineated in the A CADEMIC P EDIATRICS Copyright a 2016 by Academic Pediatric Association M ETHODS The study was conducted in 2 phases through the use of an anonymous national survey of fellowship PDs. An initial survey was created by the author group using a modified Delphi technique through 5 iterations and con- sisted of 23 items, including demographic data, definition of an FTE in the respondent’s institution, time allotted to administer the program, and the time needed by the respondent to administer their program. The survey was created in REDCap hosted by Vanderbilt University Med- ical Center. 15 This survey was distributed from August 20, 2013, to October 16, 2013, using the Association of Pediatric Program Directors (APPD) Fellowship Program Director (FPD) e-mail list. As a result of an initial low response rate, these data were considered pilot data. Volume 16, Number 5 July 2016

Estimation and optimization of loss-of-pair uncertainties based on PIV correlation functions

The uncertainty quantification of particle image velocimetry (PIV) measurements is still an open problem, and to date, no consensus exists about the best suited approach. When the spatial resolution is not appropriate, the largest uncertainties are usually caused by flow gradients. But also the amount of loss-of-pairs due to out-of-plane flow motion and insufficient light-sheet overlap causes strong uncertainties in real experiments. In this paper, we show how the amount of loss-of-pairs can be quantified using the volume of the correlation function normalized by the volume of the autocorrelation function. The findings are an important step toward a reliable uncertainty estimation of instantaneous planar velocity fields computed from PIV and stereo-PIV data. Another important consequence of the analysis is that the results allow for the optimization of PIV and stereo-PIV setups in view of minimizing the total error. In particular, it is shown that the best results (concerning the relative uncertainty) can be achieved if the out-of-plane loss-of-correlation is smaller than one (F o ). The only exception is the case where the out-of-plane motion is exactly zero. The predictions are confirmed experimentally in the last part of the paper.

Investigations on the Shear Behavior of Bridge Girders made of Normal and Ultra-high Performance Fiber-Reinforced Concrete

To further analyze the shear behavior of continuous prestressed bridges, two research projects are currently being examined at the Chair of Concrete and Masonry Structures of TUM. While one project focuses on the actual bearing capacity of older existing bridges, the other one deals with the development of prefabricated prestressed UHPFRC I-beams utilizing different reinforcing concepts and materials. Alongside complex numerical investigations, a comprehensive experimental test series will be carried out. For all tests an innovative experimental setup is being developed, which allows full scale testing of concrete beams at reduced length using the substructure technique.On the one hand the shear resistance of slender prestressed ultra-high performance fiber-reinforced concrete (UHPFRC) bridge girders with very thin webs is investigated. For these I-shaped beams the shear behavior for different types of shear reinforcement, as well as the size effect for different cross-section heights is investigated.Furthermore, the influence of various types of shear reinforcement, especially outdated stirrups no longer permitted by current standards, on the shear capacity of existing bridges is being researched. In detail these stirrups, which can often be found in older bridges, are not closed or have insufficient overlap length. As the shear design is a major issue for the re-analyses of bridges in Germany where the provided stirrups do not meet current requirements, the impact of the stirrup geometry on the shear capacity of bridge girders made of normal strength concrete has to be investigated.The paper generally explains the above mentioned research projects and presents the results of preliminary investigations.

Determination of volumetric changes at an underground stone mine: a photogrammetry case study

Photogrammetry, as a tool for monitoring underground mine deformation, is an alternative to traditional point measurement devices, and may be capable of accurate measurements in situations where technologies such as laser scanning are unsuited, undesired, or cost-prohibitive. An underground limestone mine in Ohio is used as a test case for monitoring of structurally unstable pillars. Seven pillars were photographed over in a 63day period, punctuated by four visits. Using photogrammetry, point clouds of the mine geometry were obtained and triangulation surfaces were generated to determine volumes of change over time. Pillar spalling in the range of 0.29–4.03m3 of rock on individual rib faces was detected. Isolated incidents of rock expansion prior to failure, and the isolated failure of a weak shale band were also observed. Much of the pillars remained unchanged during the monitoring period, which is indicative of proper alignment in the triangulated surfaces. The photographs of some ribs were of either too poor quality or had insufficient overlap, and were not included. However, photogrammetry was successfully applied to multiple ribs in quantifying the pillar geometry change over time.

Assessment of the Sustainability of Water Resources Management: A Critical Review of the City Blueprint Approach

Climate change, urbanization and water pollution cause adverse effects and rehabilitation costs that may exceed the carrying capacity of cities. Currently, there is no internationally standardized indicator framework for urban Integrated Water Resources Management (IWRM). The City Blueprint® is a first attempt and aims to enhance the transition towards water-wise cities by city-to-city learning. This paper provides a three step revision of the City Blueprint Framework (CBF) based on data of 45 municipalities and regions in 27 countries: (1) A distinction has been made between trends and pressures (on which urban IWRM has a negligible influence) and IWRM performances. Therefore, a separate trends and pressures framework has been developed; (2) Only the purely performance-oriented indicators have been selected from the CBF. Furthermore, the indicator accuracy and boundaries have been re-assessed, and new indicators have been added; (3) By analyzing correlations and variances, the performance-oriented indicators have been rearranged in order to establish a proportional contribution of all indicators and categories to the overall score, i.e., the Blue City Index®. In conclusion, six indicators have been removed because of insufficient accuracy, overlap or lack of focus on IWRM. Seven indicators have been added, i.e., secondary and tertiary wastewater treatment, operation cost recovery, green space and three indicators concerning solid waste treatment. The geometric aggregation method has been selected because it emphasizes the need to improve the lowest scoring indicators. In conclusion, the improved CBF is more performance-oriented and therefore more suitable to assist cities in their transition towards water-wise cities.

4D Ultrasound Tracking of Liver and its Verification for TIPS Guidance.

In this work we describe a 4D registration method for on the fly stabilization of ultrasound volumes for improving image guidance for transjugular intrahepatic portosystemic shunt (TIPS) interventions. The purpose of the method is to enable a continuous visualization of the relevant anatomical planes (determined in a planning stage) in a free breathing patient during the intervention. This requires registration of the planning information to the interventional images, which is achieved in two steps. In the first step tracking is performed across the streaming input. An approximate transformation between the reference image and the incoming image is estimated by composing the intermediate transformations obtained from the tracking. In the second step a subsequent registration is performed between the reference image and the approximately transformed incoming image to account for the accumulation of error. The two step approach helps in reducing the search range and is robust under rotation. We additionally present an approach to initialize and verify the registration. Verification is required when the reference image (containing planning information) is acquired in the past and is not part of the (interventional) 4D ultrasound sequence. The verification score will help in invalidating the registration outcome, for instance, in the case of insufficient overlap or information between the registering images due to probe motion or loss of contact, respectively. We evaluate the method over thirteen 4D US sequences acquired from eight subjects. A graphics processing unit implementation runs the 4D tracking at 9 Hz with a mean registration error of 1.7 mm.

Appendix B

Appendix B

The illusion of requirements in software development

It is widely accepted that understanding system requirements is important for software development project success. However, this paper presents two novel challenges to the requirements concept. First, where many plausible approaches to achieving a goal are evident, there may be insufficient overlap between approaches to form requirements. Second, while all plausible approaches may have sufficient overlap to state requirements, we cannot know that unless all approaches are identified and we are sure that none have been missed. This suggest that many, if not most, software projects may have too few requirements drive the design process, and that analysts may misrepresent design decisions as requirements to compensate.

LOCAL NEIGHBORHOOD DEPRIVATION: NEW METHODS TO DEFINE NEIGHBORHOODS AND MEASURE DETERMINANTS OF POVERTY IN THE FRESNO ASTHMATIC CHILDREN'S ENVIRONMENT STUDY (FACES)

Background and Aims:Previous studies have demonstrated an association between neighborhood deprivation (often measured by the US Census), exposure to air pollution and asthma outcomes. However, what constitutes a neighborhood and how best to characterize local environments is subjective and evolving. A neighborhood is defined by a geographic boundary and thus, the appropriate scale and aggregation units must be considered in epidemiologic analyses. We aim to create individual neighborhoods based on walking distances from children‘s residences in the Fresno Asthmatic Children’s Environment Study (FACES) and to describe quantitatively neighborhood deprivation at the individual level. Methods:This study uses a geographic information system (GIS) to define neighborhoods and measure local, area-level deprivation in Fresno, CA from 2000-2008. Markers of deprivation in FACES include low grocery store availability, high density of alcohol outlets and cigarette sales permits, lack of schools and parks, inadequate public transit, lack of daycares, and eight census-derived variables. We use item response theory (IRT) with maximum likelihood estimation to develop a deprivation scale for study subjects’ neighborhoods (n=518) where geographic attributes are converted to positive and negative neighborhood influences. Results:The median IRT score for FACES participants is 0.16 (where scores range from -5 to 5 for low to high deprivation). The scores are correlated positively with census defined poverty (Spearman correlation rho=0.2) and may give a more complete picture of area-level deprivation than the census. Conclusions:IRT helps summarize multiple GIS inputs and describe more precisely local deprivation with a composite score. The advantage of using individual neighborhoods defined by walking distances versus census defined boundaries is that the individual neighborhoods partly solve the problem of non-identifiabilty, an issue of insufficient covariate overlap that plagues neighborhood research. Our future research will employ the IRT scores to determine if there is a relation between neighborhood deprivation and exposure to traffic and lung function among asthmatics in FACES.

Contested hybridization of regulation: Failure of the Dutch regulatory system to protect minors from harmful media

The hybridization of regulatory modes and instruments is currently a popular way to improve public regulation. However, it is still unclear whether combinations of hard law and soft law, co-regulation, and legally enforced self-regulation really make regulation more effective. Using the analytical framework of the “really responsive regulation” approach, in this article we explore effectiveness problems in a hybrid regulatory system that tries to protect minors from harmful media. In our analysis of low compliance rates in the context of system failures, we argue that effectiveness problems seem to arise from poorly informed staff members, lack of internal and external controls, low rule enforcement, insufficient overlap between public and private interests, poor social responsibility in the Dutch media sector, deficiencies in the institutional framework, an inconsistent regulatory strategy, and inadequate responses from responsible regulators. Furthermore, based on our case study we argue that institutional dynamics of standard-setting activities can be detrimental to regulatory goal achievement if there is no compensation at the systemic level. Ongoing “regulatory care” through control, corrective responses, and rule enforcement seems to be crucial for a hybrid regulatory system to perform well.

A comparison of patient characteristics and 30-day mortality outcomes after transcatheter aortic valve implantation and surgical aortic valve replacement for the treatment of aortic stenosis: a two-centre study

It is unclear whether transcatheter aortic valve implantation (TAVI) addresses an unmet clinical need for those currently rejected for surgical aortic valve replacement (SAVR) and whether there is a subgroup of high-risk patients benefiting more from TAVI compared to SAVR. In this two-centre, prospective cohort study, we compared baseline characteristics and 30-day mortality between TAVI and SAVR in consecutive patients undergoing invasive treatment for aortic stenosis. We pre-specified different adjustment methods to examine the effect of TAVI as compared with SAVR on overall 30-day mortality: crude univariable logistic regression analysis, multivariable analysis adjusted for baseline characteristics, analysis adjusted for propensity scores, propensity score matched analysis, and weighted analysis using the inverse probability of treatment (IPT) as weights. A total of 1,122 patients were included in the study: 114 undergoing TAVI and 1,008 patients undergoing SAVR. The crude mortality rate was greater in the TAVI group (9.6% vs. 2.3%) yielding an odds ratio [OR] of 4.57 (95%-CI 2.17-9.65). Compared to patients undergoing SAVR, patients with TAVI were older, more likely to be in NYHA class III and IV, and had a considerably higher logistic EuroSCORE and more comorbid conditions. Adjusted OR depended on the method used to control for confounding and ranged from 0.60 (0.11-3.36) to 7.57 (0.91-63.0). We examined the distribution of propensity scores and found scores to overlap sufficiently only in a narrow range. In patients with sufficient overlap of propensity scores, adjusted OR ranged from 0.35 (0.04-2.72) to 3.17 (0.31 to 31.9). In patients with insufficient overlap, we consistently found increased odds of death associated with TAVI compared with SAVR irrespective of the method used to control confounding, with adjusted OR ranging from 5.88 (0.67-51.8) to 25.7 (0.88-750). Approximately one third of patients undergoing TAVI were found to be potentially eligible for a randomised comparison of TAVI versus SAVR. Both measured and unmeasured confounding limit the conclusions that can be drawn from observational comparisons of TAVI versus SAVR. Our study indicates that TAVI could be associated with either substantial benefits or harms. Randomised comparisons of TAVI versus SAVR are warranted.