Long-term outcomes of index cryoballoon ablation or point-by-point radiofrequency ablation in patients with atrial fibrillation and systolic heart failure.

Catheter ablation is an established effective approach for the treatment of atrial fibrillation (AF) in patients with heart failure, however, the role of cryoablation in this setting is unclear. Procedural success and left ventricular systolic dysfunction (LVEF) improvement in patients with LVEF ≤ 45% undergoing index catheter ablation with cryoablation were evaluated. Freedom from AF recurrence was seen in 43% rising to 59% following repeat procedure. There were significant improvements in LVEF and functional status at long-term follow-up. Results were comparable to a contemporaneous cohort of heart failure patients undergoing index ablation with radiofrequency ablation. Cryoablation is an effective first-line AF ablation approach in the setting of heart failure.

The association between labour epidural case volume and the rate of accidental dural puncture.

Accidental dural puncture is a recognised complication of labour epidural placement and can cause a debilitating headache. We examined the association between labour epidural case volume and accidental dural puncture rate in specialist anaesthetists and anaesthesia trainees. We performed a retrospective cohort study of labour epidural and combined spinal-epidural nerve blocks performed between 1 July 2013 and 31 December 2017 at Waitemata District Health Board, Auckland, New Zealand. The mean (SD) annual number of obstetric epidural and combined spinal-epidural procedures for high-case volume specialists was 44.2 (15.0), and for low-case volume specialists was 10.0 (6.8), after accounting for caesarean section combined spinal-epidural procedures. Analysis of 7976 labour epidural and combined spinal-epidural procedure records revealed a total of 92 accidental dural punctures (1.2%). The accidental dural puncture rate (95%CI) in high-case volume specialists was 0.6% (0.4-0.9%) and in low-case volume specialists 2.4% (1.4-3.9%), indicating probable skill decay. The odds of accidental dural puncture were 3.77 times higher for low- compared with high-case volume specialists (95%CI 1.72-8.28, p = 0.001). Amongst trainees, novices had a significantly higher accidental dural puncture complication rate (3.1%) compared with registrars (1.2%), OR (95%CI) 0.39 (0.18-0.84), p = 0.016, or fellows (1.1%), 0.35 (0.16-0.76), p = 0.008. Accidental dural puncture complication rates decreased once trainees progressed past the 'novice' training stage.

Longitudinal wave attenuation in polycrystals with elongated grains: 3D numerical and analytical modeling.

This work develops a second-order approximation (SOA) model and a three-dimensional (3D) finite element (FE) model to calculate scattering-induced attenuation for elastic wave propagation in polycrystals with elongated grains of arbitrary crystal symmetry. The SOA model accounts for some degree of multiple scattering, whereas the 3D FE model includes all scattering possibilities. The SOA model incorporates the accurate geometric two-point correlation function obtained from the FE material systems to enable comparative studies between the two models. Also, the analytical Rayleigh and stochastic asymptotes are presented to provide explicit insights into propagation behaviors. Quantitative agreement is found between the FE and analytical models for all evaluated cases. In particular, the FE simulations support the SOA model prediction that grain shape does not exert influence on attenuation in the Rayleigh regime and its effect emerges as frequency increases to the stochastic regime showing anisotropy in attenuation. This attenuation anisotropy intensifies with the increase in frequency, but it exhibits a complicated behavior as frequency transits into the geometric regime. Wavefield fluctuations captured from the FE simulations are provided to help observe these complex scattering behaviors. The proportionality of attenuation to elastic scattering factors is also quantitatively evaluated.

Klebsiella pneumoniae ST307 with OXA-181: threat of a high-risk clone and promiscuous plasmid in a resource-constrained healthcare setting.

INTRODUCTION: Klebsiella pneumoniae with OXA-48-like enzymes were introduced into Tshwane Tertiary Hospital (TTH) (Pretoria, South Africa) during September 2015, causing nosocomial outbreaks. METHODS: PCR methodologies and WGS were used to characterize K. pneumoniae with carbapenemases (n = 124) from TTH (July 2015-December 2016). RESULTS: PCR was used to track K. pneumoniae ST307 with OXA-181 among 60% of carbapenemase-positive isolates in different wards/units over time and showed the transmission of IncX3 plasmids to other K. pneumoniae clones. WGS identified different ST307 clades: 307_OXA181 (consisting of two lineages, A and B) with OXA-181 on IncX3 plasmids (named p72_X3_OXA181) and clade 307_VIM with VIM-1 on IncFII plasmids. Clade 307_OXA181 lineage B was responsible for the rapid increase and transmission of OXA-181 K. pneumoniae in various wards/units throughout TTH, while the numbers of clade 307_OXA181 lineage A and clade 307_VIM remained low. Separate outbreaks were due to K. pneumoniae ST17 and ST29 with p72_X3_OXA181 plasmids. CONCLUSIONS: The high-risk clone K. pneumoniae ST307 with OXA-181 rapidly spread to different wards/units despite infection and prevention measures. ST307 clades and lineages seemingly acted differently in outbreak situations. This study also highlighted the threat of promiscuous plasmids such as p72_X3_OXA181.

Correction to: Merkel Cell Carcinoma Outcomes: Does AJCC8 Underestimate Survival?

C.R. Farley and M.C. Perez contributed equally to this publication and are co-first authors. J.S. Zager and M.C. Lowe contributed equally to this publication and are co-corresponding authors.

Merkel Cell Carcinoma Outcomes: Does AJCC8 Underestimate Survival?

INTRODUCTION: The eighth edition of the American Joint Committee on Cancer (AJCC8) Staging Manual provides important information for staging and prognostication; however, survival estimates for patients with Stage I-III Merkel cell carcinoma (MCC), a rare disease, may be as practical using data from large-volume centers as that collated for the AJCC analysis. As such, we compared our institutional outcomes to AJCC8. METHODS: Patients who presented from 2005 to 2017 with MCC to two high-volume centers were included. Demographics, clinicopathologic characteristics, survival and recurrence data were compiled, and outcomes compared to AJCC8. RESULTS: A total of 409 patients were included. Median age was 75 (range 29-98) years, and 68% were male. Median follow-up was 16 months (0-157). Five-year overall survival (OS) was 70%; 5-year disease-specific survival (DSS) was 84%. When stratified by extent of disease, 5-year OS was higher for patients with local disease compared to those with nodal disease (72.6% vs 62.7%, p=0.005). Similarly, patients with local disease had higher 5-year DSS than those with nodal disease (90.1% vs 76.8%, p=0.002). Five-year recurrence-free survival was 59.2% for all patients, 65.0% for local disease and 48.3% for nodal disease (p=0.033). CONCLUSIONS: Here, MCC patients with local or nodal disease have substantially higher OS rates than predicted in AJCC8 (5-year: 72.6% vs 50.6%; 62.7% vs 35.4%, respectively). Importantly, 5-year DSS was significantly better than the OS rates reported presently and in AJCC8. As clinicians and patients rely on AJCC to accurately prognosticate and guide treatment decisions, these estimates should be reassessed and updated to more accurately predict survival outcomes.

Stabilization of Metastatic Uterine Leiomyosarcoma Using Pembrolizumab.

The estimated 5-year survival rate for patients with stage IV uterine leiomyosarcoma is 29%, with a median survival of <1 year. This report describes a patient with stage IVB leiomyosarcoma who experienced stable disease for 15 months on pembrolizumab. A woman aged 62 years, gravida 2 para 2, with postmenopausal bleeding and a necrotic uterine fibroid underwent a dilation and curettage and was diagnosed with uterine leiomyosarcoma. CT imaging showed pulmonary and bony metastasis. She underwent surgical staging with biopsy-proved stage IVB disease. A mixed partial response was noted using first- and second-line chemotherapy. Molecular tumor profiling confirmed PD-L1 expression. The patient was started on pembrolizumab, and at the time of writing she is status post 23 cycles with stable disease. Pembrolizumab was well tolerated and aided prolonged disease stabilization.

Attenuation and velocity of elastic waves in polycrystals with generally anisotropic grains: Analytic and numerical modeling.

Better understanding of elastic wave propagation in polycrystals has interest for applications in seismology and nondestructive material characterization. In this study, a second-order wave propagation (SOA) model that considers forward multiple scattering events is developed for macroscopically isotropic polycrystals with equiaxed grains of arbitrary anisotropy (triclinic). It predicts scattering-induced wave attenuation and dispersion of phase velocity. The SOA model implements the generalized two-point correlation (TPC) function, which relates to the actual numeric TPC of simulated microstructure. The analytical Rayleigh and stochastic asymptotes for both attenuation and phase velocity are derived for triclinic symmetry grains, which elucidate the effects of the elastic scattering factors and the generalized TPC in different frequency regimes. Also, the computationally efficient far field approximation attenuation model is obtained for this case; it shows good agreement with the SOA model in all frequency ranges. To assess the analytical models, a three-dimensional (3D) finite element (FE) model for triclinic polycrystals is developed and implemented on simulated 3D triclinic polycrystalline aggregates. Quantitative agreement is observed between the analytical and the FE simulations for both the attenuation and phase velocity. Also, the quasi-static velocities obtained from the SOA and FE models are in excellent agreement with the static self-consistent velocity.

Elastic wave velocity dispersion in polycrystals with elongated grains: Theoretical and numerical analysis.

The phase velocity dispersion of longitudinal waves in polycrystals with elongated grains of arbitrary crystallographic symmetry is studied in all frequency ranges by the theoretical second-order approximation (SOA) and numerical three-dimensional finite element (FE) models. The SOA and FE models are found to be in excellent agreement for three studied polycrystals: cubic Al, Inconel, and a triclinic material system. A simple Born approximation for the velocity, not containing the Cauchy integrals, and the explicit analytical quasi-static velocity limit (Rayleigh asymptote) are derived. As confirmed by the FE simulations, the velocity limit provides an accurate velocity estimate in the low-frequency regime where the phase velocity is nearly constant on frequency; however, it exhibits dependence on the propagation angle. As frequency increases, the phase velocity increases towards the stochastic regime and then, with further frequency increase, behaves differently depending on the propagation direction. It remains nearly constant for the wave propagation in the direction of the smaller ellipsoidal grain radius and decreases in the grain elongation direction. In the Rayleigh and stochastic frequency regimes, the directional velocity change shows proportionalities to the two elastic scattering factors even for the polycrystal with the triclinic grain symmetry.

Maximizing the accuracy of finite element simulation of elastic wave propagation in polycrystals.

Three-dimensional finite element (FE) modelling, with representation of materials at grain scale in realistic sample volumes, is capable of accurately describing elastic wave propagation and scattering within polycrystals. A broader and better future use of this FE method requires several important topics to be fully understood, and this work presents studies addressing this aim. The first topic concerns the determination of effective media parameters, namely, scattering induced attenuation and phase velocity, from measured coherent waves. This work evaluates two determination approaches, through-transmission and fitting, and it is found that these approaches are practically equivalent and can thus be used interchangeably. For the second topic of estimating modelling errors and uncertainties, this work performs thorough analytical and numerical studies to estimate those caused by both FE approximations and statistical considerations. It is demonstrated that the errors and uncertainties can be well suppressed by using a proper combination of modelling parameters. For the last topic of incorporating FE model information into theoretical models, this work presents elaborated investigations and shows that to improve agreement between the FE and theoretical models, the symmetry boundary conditions used in FE models need to be considered in the two-point correlation function, which is required by theoretical models.

Numerical and analytic modelling of elastodynamic scattering within polycrystalline materials.

The elastodynamic behavior of polycrystalline cubic materials is studied through the fundamental propagation properties, the attenuation and wave speed, of a longitudinal wave. Predictions made by different analytical models are compared to both numerical and experimental results. The numerical model is based on a three-dimensional Finite Element (FE) simulation which provides a full-physics solution to the scattering problem. The three main analytical models include the Far-Field Approximation (FFA), the Self-Consistent Approximation (SCA) to the reference medium, and the herein derived Second Order Approximation (SOA). The classic Stanke and Kino model is also included, which by comparison to the SOA, reveals the importance of the distribution of length-scales described in terms of the two-point correlation function in determining scattering behavior. Further comparison with the FE model demonstrates that the FFA provides a simple but satisfactory approximation, whereas the SOA shows all-around excellent agreement. The experimental wave velocity data evaluated against the SOA and SC reveal a better agreement when the Voigt reference is used in second order models. The use of full-physics numerical simulations has enabled the study of wave behavior in these random media which will be important to inform the ongoing development of analytical models and the understanding of observations.

Opportunities for faculty-librarian collaboration in an expanded dentistry curriculum.

With the increased emphasis on evidence based practice, developing information literacy skills earlier in health care education programmes is widely accepted. However finding opportunities for relevant teaching can present challenges, often leading to a lack of integration. In this paper, guest writers Sean Stone and colleagues from Indiana University discuss their involvement with an expanded dental hygiene curriculum in the University School of Dentistry. This expansion has provided the opportunity to plan integration of information and oral health literacy instruction and evidence based practice across the new curriculum, and provide transferable skills for any major. In particular, the paper addresses the developmental work the health librarian team engaged in from course design, delivery and assessment to improve student preparedness for evidence based practice. H.S.

Belatacept-Resistant Rejection Is Associated With CD28+ Memory CD8 T Cells.

Recently, newer therapies have been designed to more specifically target rejection in an effort to improve efficacy and limit unwanted toxicity. Belatacept, a CD28-CD80/86 specific reagent, is associated with superior patient survival and graft function compared with traditional therapy, but its adoption as a mainstay immunosuppressive therapy has been tempered by increased rejection rates. It is essential that the underlying mechanisms associated with this rejection be elucidated before belatacept is more widely used. To that end, we designed a study in a nonhuman primate kidney transplant model where animals were treated with either a belatacept- or a tacrolimus-based immunosuppressive regimen. Interestingly, we found that elevated pretransplant frequencies of CD28+ CD8+ TEMRA cells are associated with rejection on belatacept but not tacrolimus treatment. Further analysis showed that the CD28+ CD8+ TEMRA cells rapidly lose CD28 expression after transplant in those animals that go on to reject with the allograft infiltrate being predominantly CD28- . These data suggest that CD28+ memory T cells may be resistant to belatacept, capable of further differentiation including loss of CD28 expression while maintaining effector function. The unique signaling requirements of CD28+ memory T cells provide opportunities for the development of targeted therapies, which may synergize with belatacept to prevent costimulation-independent rejection.

The symmetry and coupling properties of solutions in general anisotropic multilayer waveguides.

Multilayered plate and shell structures play an important role in many engineering settings where, for instance, coated pipes are commonplace such as in the petrochemical, aerospace, and power generation industries. There are numerous demands, and indeed requirements, on nondestructive evaluation (NDE) to detect defects or to measure material properties using guided waves; to choose the most suitable inspection approach, it is essential to know the properties of the guided wave solutions for any given multilayered system and this requires dispersion curves computed reliably, robustly, and accurately. Here, the circumstances are elucidated, and possible layer combinations, under which guided wave solutions, in multilayered systems composed of generally anisotropic layers in flat and cylindrical geometries, have specific properties of coupling and parity; the partial wave decomposition of the wave field is utilised to unravel the behaviour. A classification into five families is introduced and the authors claim that this is the fundamental way to approach generally anisotropic waveguides. This coupling and parity provides information to be used in the design of more efficient and robust dispersion curve tracing algorithms. A critical benefit is that the analysis enables the separation of solutions into categories for which dispersion curves do not cross; this allows the curves to be calculated simply and without ambiguity.

A multiband approach for accurate numerical simulation of frequency dependent ultrasonic wave propagation in the time domain.

Finite element (FE) simulations are popular for studying propagation and scattering of ultrasonic waves in nondestructive evaluation. For a large number of degrees of freedom, time domain FE simulations are much more efficient than the equivalent frequency domain solution. However, unlike frequency domain simulations, time domain simulations are often poor at representing the speed and the attenuation of waves if the material is strongly damping or highly dispersive. Here, the authors demonstrate efficient and accurate representation of propagated and scattered waves, achieved by combining a set of time domain solutions that are obtained for a set of frequency ranges known as bands, such that, in combination, the authors' multiband solution accurately represents the whole wave spectrum. Consequently, high accuracy is achieved, at minor computational cost, using a modest number of bands. The multiband technique is implemented for ultrasonic wave propagation in highly attenuating polyethylene material, using three frequency bands, and can yield a reduction in empirical acoustic properties fractional error compared with respective time domain simulations, in propagation duration, of a factor of 1.4, and in full-width-half-maximum, of a factor of 10. Last, the accuracy of this approach is further exemplified in a wave scattering simulation.

Ultrasonic attenuation and phase velocity of high-density polyethylene pipe material.

Knowledge of acoustic properties is crucial for ultrasonic or sonic imaging and signal detection in nondestructive evaluation (NDE), medical imaging, and seismology. Accurately and reliably obtaining these is particularly challenging for the NDE of high-density polyethylene (HDPE), such as is used in many water or gas pipes, because the properties vary greatly with frequency, temperature, direction and spatial location. Therefore the work reported here was undertaken in order to establish a basis for such a multiparameter description. The approach is general but the study specifically addresses HDPE and includes measured data values. Applicable to any such multiparameter acoustic properties dataset is a devised regression method that uses a neural network algorithm. This algorithm includes constraints to respect the Kramers-Kronig causality relationship between speed and attenuation of waves in a viscoelastic medium. These constrained acoustic properties are fully described in a multidimensional parameter space to vary with frequency, depth, temperature, and direction. The resulting uncertainties in acoustic properties dependence on the above variables are better than 4% and 2%, respectively, for attenuation and phase velocity and therefore can prevent major defect imaging errors.

Dual islet transplantation modeling of the instant blood-mediated inflammatory reaction.

Islet xenotransplantation is a potential treatment for diabetes without the limitations of tissue availability. Although successful experimentally, early islet loss remains substantial and attributed to an instant blood-mediated inflammatory reaction (IBMIR). This syndrome of islet destruction has been incompletely defined and characterization in pig-to-primate models has been hampered by logistical and statistical limitations of large animal studies. To further investigate IBMIR, we developed a novel in vivo dual islet transplant model to precisely characterize IBMIR as proof-of-concept that this model can serve to properly control experiments comparing modified xenoislet preparations. WT and α1,3-galactosyltransferase knockout (GTKO) neonatal porcine islets were studied in nonimmunosuppressed rhesus macaques. Inert polyethylene microspheres served as a control for the effects of portal embolization. Digital analysis of immunohistochemistry targeting IBMIR mediators was performed at 1 and 24 h after intraportal islet infusion. Early findings observed in transplanted islets include complement and antibody deposition, and infiltration by neutrophils, macrophages and platelets. Insulin, complement, antibody, neutrophils, macrophages and platelets were similar between GTKO and WT islets, with increasing macrophage infiltration at 24 h in both phenotypes. This model provides an objective and internally controlled study of distinct islet preparations and documents the temporal histology of IBMIR.

Influence of leaching on surface composition, microstructure, and valence band of single grain icosahedral Al-Cu-Fe quasicrystal.

The use of quasicrystals as precursors to catalysts for the steam reforming of methanol is potentially one of the most important applications of these new materials. To develop application as a technology requires a detailed understanding of the microscopic behavior of the catalyst. Here, we report the effect of leaching treatments on the surface microstructure, chemical composition, and valence band of the icosahedral (i-) Al-Cu-Fe quasicrystal in an attempt to prepare a model catalyst. The high symmetry fivefold surface of a single grain i-Al-Cu-Fe quasicrystal was leached with NaOH solution for varying times, and the resulting surface was characterized by x-ray photoelectron spectroscopy (XPS), ultraviolet photoelectron spectroscopy (UPS), scanning electron microscopy (SEM), and atomic force microscopy (AFM). The leaching treatments preferentially remove Al producing a capping layer consisting of Fe and Cu oxides. The subsurface layer contains elemental Fe and Cu in addition to the oxides. The quasicrystalline bulk structure beneath remains unchanged. The subsurface gradually becomes Fe3O4 rich with increasing leaching time. The surface after leaching exhibits micron sized dodecahedral cavities due to preferential leaching along the fivefold axis. Nanoparticles of the transition metals and their oxides are precipitated on the surface after leaching. The size of the nanoparticles is estimated by high resolution transmission microscopy to be 5-20 nm, which is in agreement with the AFM results. Selected area electron diffraction (SAED) confirms the crystalline nature of the nanoparticles. SAED further reveals the formation of an interface between the high atomic density lattice planes of nanoparticles and the quasicrystal. These results provide an important insight into the preparation of model catalysts of nanoparticles for steam reforming of methanol.

The atomic structure of low-index surfaces of the intermetallic compound InPd.

The intermetallic compound InPd (CsCl type of crystal structure with a broad compositional range) is considered as a candidate catalyst for the steam reforming of methanol. Single crystals of this phase have been grown to study the structure of its three low-index surfaces under ultra-high vacuum conditions, using low energy electron diffraction (LEED), X-ray photoemission spectroscopy (XPS), and scanning tunneling microscopy (STM). During surface preparation, preferential sputtering leads to a depletion of In within the top few layers for all three surfaces. The near-surface regions remain slightly Pd-rich until annealing to ∼580 K. A transition occurs between 580 and 660 K where In segregates towards the surface and the near-surface regions become slightly In-rich above ∼660 K. This transition is accompanied by a sharpening of LEED patterns and formation of flat step-terrace morphology, as observed by STM. Several superstructures have been identified for the different surfaces associated with this process. Annealing to higher temperatures (≥750 K) leads to faceting via thermal etching as shown for the (110) surface, with a bulk In composition close to the In-rich limit of the existence domain of the cubic phase. The Pd-rich InPd(111) is found to be consistent with a Pd-terminated bulk truncation model as shown by dynamical LEED analysis while, after annealing at higher temperature, the In-rich InPd(111) is consistent with an In-terminated bulk truncation, in agreement with density functional theory (DFT) calculations of the relative surface energies. More complex surface structures are observed for the (100) surface. Additionally, individual grains of a polycrystalline sample are characterized by micro-spot XPS and LEED as well as low-energy electron microscopy. Results from both individual grains and "global" measurements are interpreted based on comparison to our single crystals findings, DFT calculations and previous literature.