Search

Two new gold compounds with bis(phosphino)metallocene ligands were prepared and characterized by NMR and X-ray crystallography. These and related compounds are catalysts in formation of disubstituted furans from terminal alkynes and pyridine-N-oxide.

PURPOSE OF THE STUDY Facing the increasing number of priary and revision hip arthroplasties, the therapy of complex osseus defects becomes a crucial issue. Large acetabular defects cannot be treated with standard implant. Individual, customized implants based on 3D computed tomography (CT) scans are used for reconstruction. However, high complication and revision rates come along with final favorable outcomes. MATERIAL AND METHODS Eight patients underwent primary or revision total hip arthroplasty by an anterolateral surgical approach using patient matched implants based on 3D CT scans. Six patients with a Paprosky type IIIB acetabular defect, one patient with a nonunion acetabular and femoral neck fracture and one patient with a severe hip dysplasia were included. The clinical data and the Merle d'Aubigné score assessing the clinical outcome pre- and postoperatively were analyzed retrospectively. RESULTS Patient matched implants were used for eight patients (four male and four female). The mean Merle d'Aubigné score improved from 8.1 (range 2-11) pre-operatively to 13 (range 9-17) at the final follow-up (p0.01). Postoperative complications were recorded in 3 cases. CONCLUSIONS Customized implants of severe acetabular defects provide a solution with a favorable outcome. Nevertheless, dislocation presents a significant complication. A reduction of complications in order to achieve the optimal custome-made implant is desirable. Key words: revision arthroplasty, patient-matched implants, Paprosky IIIB defects, clinical outcome.

Background Guideline directed medical therapy (GDMT) is the recommended initial treatment for secondary mitral regurgitation (SMR), however supported by only little comprehensive evidence. This study therefore sought to assess the effect of GDMT titration on SMR and to identify specific substance combinations able to reduce SMR severity. Methods We included 261 patients who completed two visits with an echocardiographic exam available within one month at each visit. After comprehensively defining GDMT titration as well as SMR reduction, logistic regression analysis was applied in order to assess the effects of overall GDMT titration and specific substance combinations on SMR severity. Results SMR severity improved by at least one degree in 39.3% of patients with subsequent titration of GDMT and was accompanied by reverse remodelling and clinical improvement. The effects of GDMT titration were significantly associated with SMR reduction (adj. OR 0.31, 95% CI 0.13–0.71, P=0.006). Moreover, ARNI as well as the combined dosage effects of (i) renin angiotensin system inhibitors (RASi) and mineralocorticoid-receptor antagonists (MRA), (ii) betablockers (BB) and MRA, as well as (iii) RASi, BB, and MRA were all significantly associated with SMR improvement (P Conclusions The present study provides comprehensive evidence for the effectiveness of contemporary GDMT to specifically improve SMR. Our data indicates that GDMT titration conveys a threefold increased chance of reducing SMR severity. Moreover, the dosage effects of ARNI, as well as the combination of RASi and MRA, BB and MRA, and all three substances in aggregate are able to significantly improve SMR. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): FWF - Austrian Science Fund

Background Secondary tricuspid regurgitation (sTR) is the most frequent valvular heart disease and has significant impact on mortality. A high burden of comorbidities often worsens the already dismal prognosis of sTR, while tricuspid interventions remain underused and initiated too late. Objectives To examine the most powerful predictors of all-cause mortality in moderate and severe sTR using machine learning techniques and to provide a streamlined approach to risk-stratification using readily available clinical, echocardiographic and laboratory parameters. Methods This large-scale, long-term observational study included 3359 moderate and 1509 severe sTR patients encompassing the entire heart failure spectrum (preserved, mid-range and reduced ejection fraction). A random survival forest was applied to investigate the most important predictors and group patients according to their number of adverse features (Figure 1). Results The identified predictors and thresholds, that were associated with significantly worse mortality were higher age (≥75 in moderate and ≥70 years in moderate and severe sTR respectively), higher NT-proBNP (≥4000 pg/ml), increased high sensitivity C-reactive protein (≥1.0 mg/dl), serum albumin Conclusion This study presents a streamlined, machine learning-derived and internally validated approach to risk-stratification in patients with moderate and severe sTR, that adds important prognostic information to aid clinical decision-making. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Austrian Science Fund

Backgrounds Bioprosthetic valve dysfunction (BVD) is a major concern regarding transcatheter aortic valve implantation (TAVI) in low-risk patients. Aims To assess incidence, determinants, modes, and outcome of early to mid-term BVD after TAVI in relation with life expectancy. Methods Consecutive TAVI recipients (2007–2020) with a post-interventional follow-up ≥1-year were prospectively included. BVD components and bioprosthetic valve failure (BVF) were assessed according to updated Valve-Academic-Research-Consortium-3 criteria. Echocardiographic and laboratory follow-up was performed prior to discharge, at 3- and 12-months, and yearly thereafter. BVD/BVF and all-cause death served as endpoints. Average life expectancy was calculated from National Open Health Data and patients were stratified according to tertiles (1st: 9.7y). Results Of 1047 patients (81.6±6.8 y/o, 52.7% female, EuroSCORE II 4.5±2.5), ≥2 follow-ups were available from 622 (serial echo cohort). After a median echo follow-up of 12.2 months, incidence rates of BVD and BVF were 8.4% [95% confidence interval 6.7–10.3], and 3.5% [2.5–4.9] per valve-year, respectively, without differences between life expectancy tertiles (Figure 1). BVD incidence was double within the first year of implant (9.9% [7.7–12.6] per valve-year; mostly non-structural VD) vs. beyond (4.8% [3.1–7.2] per valve-year; structural and non-structural VD). Valve-in-valve procedure, and stenosis severity (both p0.5) predisposed for BVD. After 4.4±3.0 years, mortality was 36.7%. Time-dependent BVD/BVF were independently associated with outcome for patients in the first (adjusted hazard ratio [AHR] 1.72 [1.06–2.88]/ 2.97 [1.72–6.22]) and second (AHR 1.96 [1.02–3.73]/ 2.31 [1.00–5.30]), but not the third tertile of life expectancy (AHR 1.42 [0.66–3.12]/ 1.84 [0.71–4.79]; Figure 1). Conclusions In this large prospective observational cohort, early to mid-term BVD after TAVI occurred at the same rate across the spectrum of life expectancy and was not prognostic among those with the longest life expectancy. Funding Acknowledgement Type of funding sources: None.

Background/AimsThe optic nerve development during the critical postnatal weeks of preterm infants is unclear. We aimed to investigate the change of retinal nerve fibre layer (RNFL) in preterm infants.MethodsWe used an investigational handheld optical coherence tomography (OCT) system to serially image awake preterm infants between 30 and 60 weeks postmenstrual age (PMA) at the bedside. We assessed RNFL thickness in the papillomacular bundle and nasal macular ganglion cell layer+inner plexiform layer (GCL+IPL) thickness. We applied a segmented mixed model to analyse the change in the thickness of RNFL and GCL+IPL as a function of PMA.ResultsFrom 631 OCT imaging sessions of 101 infants (201 eyes), RNFL thickness followed a biphasic model between 30 and 60 weeks, with an estimated transition at 37.8 weeks PMA (95% CI: 37.0 to 38.6). RNFL thickness increased at 1.8 μm/week (95% CI: 1.6 to 2.1) before 37.8 weeks and decreased at −0.3 μm/week (95% CI: −0.5 to −0.2) afterwards. GCL+IPL thickness followed a similar biphasic model, in which the thickness increased at 2.9 μm/week (95% CI: 2.5 to 3.2) before 39.5 weeks PMA (95% CI: 38.8 to 40.1) and then decreased at −0.8 μm/week (95% CI: −0.9 to −0.6).ConclusionWe demonstrate the feasibility of monitoring RNFL and GCL+IPL thickness from OCT during the postnatal weeks of preterm infants. Thicknesses follow a biphasic model with a transition age at 37.8 and 39.5 weeks PMA, respectively. These findings may shed light on optic nerve development in preterm infants and assist future study designs.

Stroke associated with transcatheter aortic valve replacement (TAVR) is a potentially devastating complication. Until recently, the Sentinel™ Cerebral Protection System (CPS; Boston Scientific) has been the only commercially available device for mechanical prevention of TAVR-related stroke. However, its effectiveness is still undetermined. Methods Between January 2019 and August 2020 consecutive patients were randomly assigned to TAVR with or without Sentinel™ in a 1:1 fashion. We defined as primary endpoint clinically detectable cerebrovascular events within 72 hours after TAVR, and as secondary endpoints LOS and 12-month mortality. Logistic and linear regression analyses were used to assess associations of Sentinel™ use with endpoints. Results Of 411 patients (80±7 y/o, 47.4% female, EuroSCORE II 6.3±5.9%), Sentinel™ was used in 213 (51.8%), with both filters correctly deployed in 189 (46.0%). 20 (4.9%) cerebrovascular events were recorded, 10 (2.4%) of which were disabling strokes. Sentinel™ reduced cerebrovascular events in univariate analysis by 71% (OR 0.29, 95% CI 0.11–0.82; p=0.02) and after multivariate adjustment by 75% (adj. OR 0.25; 95% CI 0.08–0.80; p=0.02). Sentinel™ use was also significantly associated with shorter LOS (8.4±9.6 versus 6.7±6.1 days; p=0.03) and lower 12-month all-cause mortality (15.7% versus 7.5%, p=0.01). Conclusions In the present prospective all-comers TAVR cohort, Sentinel™ significantly 1) reduced cerebrovascular events, 2) shortened LOS, and 3) improved 12-month survival. These data promote the use of a CPS when implanting TAVR valves. Funding Acknowledgement Type of funding sources: None.

Purpose Interprofessional education (IPE) is demonstrated to improve patient outcomes in a variety of health care fields and clinical settings. However, the extent and effectiveness of IPE in radiation oncology is undefined. This systematic literature review identifies reports of radiation oncology IPE and summarizes the outcomes of those initiatives. Methods The literature was queried through PubMed using search terms focusing on IPE targeted toward radiation oncologists, radiation therapists, nurses, medical physicists, and medical dosimetrists in the undergraduate medical education, graduate medical education, and continuing medical education settings. IPE was defined as any educational initiative designed to improve understanding or teamwork efficiency between the learners of interest. Because of the lack of published material pertaining to IPE in radiation oncology, noninterventional, descriptive studies were included. Results Of 1,306 articles screened, 4 were included in the qualitative analysis. Radiation therapists were included in IPE most frequently (four articles), followed by radiation oncologists, nurses, physicists, and dosimetrists (one article each). IPE initiatives identified ranged from descriptive surveys and written source review to IPE workshops and longitudinal IPE curricula with quantified outcomes. Descriptive studies viewed IPE positively, and all studies collecting quantitative data demonstrated positive outcomes. Undergraduate health profession students were included most frequently (three articles), followed by practicing professionals (one article). No articles reported IPE in the graduate medical education setting. Conclusions This systematic review demonstrates that despite the general association of IPE with improved outcomes, radiation oncology IPE initiatives are lacking. There is a significant opportunity to further develop radiation oncology IPE.

The generation of high magnetic fields requires materials with high electric conductivity and good strength properties. Cu/Nb composites are considered to be good candidates for this purpose. In this work we aim to predict, from theory, the dependence of electric conductivity on the microstructure, most notably on the layer thickness and grain sizes. We also conducted experiments to calibrate and validate our simulations. Bimetal interfaces and grain boundaries are confirmed to have the largest impact on conductivity in this composite material. In this approach, a distribution of the layer thickness is accounted for in order to better model the experimentally observed microstructure. Because layer thicknesses below the mean free path of Cu significantly degrade the conductivity, an average layer thickness larger than expected may be needed to meet conductivity requirements in order to minimize these smaller layers in the distribution. We also investigate the effect of variations in volume fraction of Nb and temperature on the material's conductivity., 18 pages, 5 figures, 2 tables; v2 minor clarifications

Background/aimsNeonatal insults from systemic diseases have been implicated in the pathway of impaired neurodevelopment in preterm infants. We aimed to investigate the associations between systemic health factors and retinal nerve fibre layer (RNFL) thickness in preterm infants.MethodsWe prospectively enrolled infants and imaged both eyes at 36±1 weeks postmenstrual age (PMA) using a hand-held optical coherence tomography system at the bedside in the Duke intensive care nurseries. We evaluated associations between RNFL thickness and 29 systemic health factors using univariable and multivariable regression models.Results83 infants with RNFL thickness measures were included in this study. Based on the multivariable model, RNFL thickness was positively associated with infant weight at imaging and was negatively associated with sepsis/necrotising enterocolitis (NEC). RNFL thickness was 10.4 µm (95% CI −15.9 to −4.9) lower in infants with than without sepsis/NEC in the univariable analysis (pConclusionsLow infant weight and sepsis/NEC were independently associated with thinner RNFL in preterm infants at 36 weeks PMA. To our knowledge, this study is the first to suggest that sepsis/NEC may affect retinal neurodevelopment. Future longitudinal studies are needed to investigate this relationship further.

Pulsed nuclear magnetic resonance (NMR) is widely used in high-precision magnetic field measurements. The absolute value of the magnetic field is determined from the precession frequency of nuclear magnetic moments. The Hilbert transform is one of the methods that have been used to extract the phase function from the observed free induction decay (FID) signal and then its frequency. In this paper, a detailed implementation of a Hilbert-transform based FID frequency extraction method is described, and it is briefly compared with other commonly used frequency extraction methods. How artifacts and noise level in the FID signal affect the extracted phase function are derived analytically. A method of mitigating the artifacts in the extracted phase function of an FID is discussed. Correlations between noises of the phase function samples are studied for different noise spectra. We discovered that the error covariance matrix for the extracted phase function is nearly singular and improper for constructing the χ 2 used in the fitting routine. A down-sampling method for fixing the singular covariance matrix has been developed, so that the minimum χ 2 -fit yields properly the statistical uncertainty of the extracted frequency. Other practical methods of obtaining the statistical uncertainty are also discussed.

The Fermi National Accelerator Laboratory has measured the anomalous precession frequency $a^{}_\mu = (g^{}_\mu-2)/2$ of the muon to a combined precision of 0.46 parts per million with data collected during its first physics run in 2018. This paper documents the measurement of the magnetic field in the muon storage ring. The magnetic field is monitored by nuclear magnetic resonance systems and calibrated in terms of the equivalent proton spin precession frequency in a spherical water sample at 34.7$^\circ$C. The measured field is weighted by the muon distribution resulting in $\tilde{\omega}'^{}_p$, the denominator in the ratio $\omega^{}_a$/$\tilde{\omega}'^{}_p$ that together with known fundamental constants yields $a^{}_\mu$. The reported uncertainty on $\tilde{\omega}'^{}_p$ for the Run-1 data set is 114 ppb consisting of uncertainty contributions from frequency extraction, calibration, mapping, tracking, and averaging of 56 ppb, and contributions from fast transient fields of 99 ppb., Comment: Added one citation and corrected missing normalization in Eqs (35) and (36)

This paper presents the beam dynamics systematic corrections and their uncertainties for the Run-1 data set of the Fermilab Muon g-2 Experiment. Two corrections to the measured muon precession frequency $\omega_a^m$ are associated with well-known effects owing to the use of electrostatic quadrupole (ESQ) vertical focusing in the storage ring. An average vertically oriented motional magnetic field is felt by relativistic muons passing transversely through the radial electric field components created by the ESQ system. The correction depends on the stored momentum distribution and the tunes of the ring, which has relatively weak vertical focusing. Vertical betatron motions imply that the muons do not orbit the ring in a plane exactly orthogonal to the vertical magnetic field direction. A correction is necessary to account for an average pitch angle associated with their trajectories. A third small correction is necessary because muons that escape the ring during the storage time are slightly biased in initial spin phase compared to the parent distribution. Finally, because two high-voltage resistors in the ESQ network had longer than designed RC time constants, the vertical and horizontal centroids and envelopes of the stored muon beam drifted slightly, but coherently, during each storage ring fill. This led to the discovery of an important phase-acceptance relationship that requires a correction. The sum of the corrections to $\omega_a^m$ is 0.50 $\pm$ 0.09 ppm; the uncertainty is small compared to the 0.43 ppm statistical precision of $\omega_a^m$., Comment: 35 pages, 29 figures. Accepted by Phys. Rev. Accel. Beams

Individuals with skin of color make up the majority of the world's population and a rapidly expanding section of the US population. Future dermatologists must be knowledgeable about dermatologic conditions presenting in patients of various ethnic backgrounds. A 10-question survey was emailed to 109 dermatology residency programs to assess if dermatologists in-training feel that their residency curriculum sufficiently gives them exposure to and education on patients with skin of color. Forty-three residents completed the survey from 5 regions of the United States. Resident responses differed by region. Residents from areas with less diversity were more likely to agree that dedicated skin of color clinics and rotations are important to gain competency compared to residents from areas with more diversity.

We report development of a highly accurate (parts per billion) absolute magnetometer based on $^{3}\mathrm{He}$ NMR. Optical pumping polarizes the spins, long coherence times provide high sensitivity, and the $^{3}\mathrm{He}$ electron shell effectively isolates the nuclear spin providing accuracy limited only by corrections including materials, sample shape, and magnetization. Our magnetometer was used to confirm calibration, to 32 ppb, of the magnetic-field sensors used in recent measurements of the muon magnetic moment anomaly $({g}_{\ensuremath{\mu}}\ensuremath{-}2)$, which differs from the standard model by 2.4 ppm. With independent determination of the magnetic moment of $^{3}\mathrm{He}$, this work will lead the way to a new absolute magnetometry standard.

Individuals with skin of color make up the majority of the world's population and a rapidly expanding section of the US population. Future dermatologists must be knowledgeable about dermatologic conditions presenting in patients of various ethnic backgrounds. A 10-question survey was emailed to 109 dermatology residency programs to assess if dermatologists in-training feel that their residency curriculum sufficiently gives them exposure to and education on patients with skin of color. Forty-three residents completed the survey from 5 regions of the United States. Resident responses differed by region. Residents from areas with less diversity were more likely to agree that dedicated skin of color clinics and rotations are important to gain competency compared to residents from areas with more diversity.

Macular images of infants with early-onset edema (occurring at or before 33 weeks' postmenstrual age [PMA]) and infants with late-onset edema (at or after 36 weeks' PMA) were compared. At first appearance, early-onset edema has a more severe morphology, with foveal bulging and elongated cystoid spaces than late-onset edema, which presents as small cystoid spaces outside the foveal center. Morphological variations may be an indicator of the underlying cause of edema in preterm infants. The presence of mostly parafoveal small cystoid spaces in the late-onset edema group may be suggestive of an association with neurological injury.

Introduction Bivalvular functional regurgitation (BVFR) defined as concomitant mitral and tricuspid insufficiency has not been described or systematically assessed before. The present study therefore sought to define incidence, impact and natural history of BVFR in heart failure with reduced ejection fraction (HFrEF) to provide the foundation for risk assessment and directions for potential treatment strategies. Methods We enrolled 1021 consecutive patients with HFrEF under guideline-directed medical therapy and performed comprehensive echocardiographic and neurohumoral profiling. Mitral and tricuspid regurgitation was quantified by an integrated approach comprising valve morphology, width of the proximal regurgitant jet, proximal flow convergence, and pulmonary venous flow. All-cause mortality during a five-year follow up served as the primary endpoint. Results Thirty percent of patients suffered from moderate or severe BVFR. Long-term mortality increased with the presence and severity of FR with severe BVFR representing the highest risk-subset (P Conclusion This long-term outcome study shows the multi-faceted nature of FR and defines BVFR as an important clinical entity associated with impaired functional class, adverse cardiac remodeling and excess risk of mortality. Moderate BVFR conveys similar risk as isolated severe FR reflecting the deleterious impact of the global regurgitant load on the failing heart and the need of an integrated understanding for risk-assessment. Abstract 552 Figure 1 (Panel A and B)

The E989 Muon g-2 experiment at Fermilab aims to measure the anomalous magnetic moment, a$_\mu$, of the muon with a precision of 140 parts-per-billion. This requires a precise measurement of both the anomalous spin precession frequency, $\omega_a$, and the average magnetic field in terms of the equivalent, free proton Larmor frequency, $\omega_p$. The measurement of $\omega_p$ with a total systematic uncertainty of 70 parts-per-billion involves a combination of various NMR probes. There are 378 probes in fixed locations constantly monitoring field drifts. A water-based probe provides the calibration in terms of $\omega_p$. A crucial element for the multi-step measurement of $\omega_p$ is the regular mapping of the magnetic field over the muon storage region. The former E821 experiment at Brookhaven employed an in-vacuum field mapping system equipped with 17 NMR probes, which was developed by the University of Heidelberg. We have refurbished and upgraded this system with new probes and electronics. The upgrades include a new communication scheme incorporating time-division multiplexing to separate the important NMR reference clock from the data communication. The addition digitization of the NMR signals replaced the hardware-implemented zero-crossing counting of the E821 system. The digitized signals offer new capabilities in the NMR frequency analysis and its related systematic uncertainties. While the mechanical systems that move the field mapper around the ring have been mostly refurbished, the motion control system was completely replaced with a custom-built electronics centered around a commercial Galil motion controller. Both the field mapping NMR system and its motion control were successfully commissioned at Fermilab and have been in reliable operation during the first data taking periods. This article provides details of the upgrades of the field mapper and its performance.

We reviewed common artifacts and outliers in pediatric structural optical coherence tomography (OCT).

This chapter provides an introduction to research in pediatric optical coherence tomography (OCT).

The ability of adherent cells to sense changes in the mechanical properties of their extracellular environments is critical to numerous aspects of their physiology. It has been well documented that cell attachment and spreading are sensitive to substrate stiffness. Here, we demonstrate that this behavior is actually biphasic, with a transition that occurs around a Young's modulus of ∼7 kPa. Furthermore, we demonstrate that, contrary to established assumptions, this property is independent of myosin II activity. Rather, we find that cell spreading on soft substrates is inhibited due to reduced myosin-II independent nascent adhesion formation within the lamellipodium. Cells on soft substrates display normal leading-edge protrusion activity, but these protrusions are not stabilized due to impaired adhesion assembly. Enhancing integrin-ECM affinity through addition of Mn2+ recovers nascent adhesion assembly and cell spreading on soft substrates. Using a computational model to simulate nascent adhesion assembly, we find that biophysical properties of the integrin-ECM bond are optimized to stabilize interactions above a threshold matrix stiffness that is consistent with the experimental observations. Together, these results suggest that myosin II-independent forces in the lamellipodium are responsible for mechanosensation by regulating new adhesion assembly, which, in turn, directly controls cell spreading. This myosin II-independent mechanism of substrate stiffness sensing could potentially regulate a number of other stiffness-sensitive processes.

IMPACT: This study helps translate investigational bedside optical coherence tomography into improved diagnosis and care of preterm infants at risk for retinopathy of prematurity. OBJECTIVES/GOALS: In retinopathy of prematurity screening, fundus photography may be of limited quality in eyes with dark fundus pigmentation (FP). The goal of this study was to evaluate the impact of FP on overall scan quality and retinal layer visibility on investigational bedside optical coherence tomography (OCT) in preterm infants. METHODS/STUDY POPULATION: We analyzed 846 OCT scans captured prospectively from 188 eyes of 94 preterm infants enrolled in the BabySTEPS study (NCT02887157). Trained ophthalmologists, masked to OCT findings, determined FP (blond, medium, or dark). Expert graders, masked to FP, evaluated OCT images for: 1) overall OCT quality (excellent, acceptable, poor, or unusable); and 2) all age-appropriate retinal layers visible (yes or no). To assess the association of FP with OCT quality (excellent/acceptable or poor/unusable) and retinal layer visibility, we performed multivariable logistic regression modeling, adjusting for biologic and demographic confounders and correlations from repeated OCT scans and paired eyes. RESULTS/ANTICIPATED RESULTS: Mean birthweight was 964 (SD=283) grams, mean gestational age was 27.8 (SD=2.6) weeks, 48 (51%) infants were male, and 51 (54%) were non-white. On exam, 72 (38%) eyes had blond FP, 92 (49%) had medium, and 24 (13%) had dark. OCT quality was excellent or acceptable in 725 scans (86%) and all age-appropriate retinal layers were visible in 781 scans (92%). Compared to eyes with blond FP, eyes with medium and dark FP did not have higher odds of poor/unusable OCT scan quality (adjusted OR 0.87 [95% CI 0.50-1.48] and 0.49 [95% CI 0.16-1.55], respectively) or not all age-appropriate retinal layers visible on OCT (adjusted OR 1.17 [95% CI 0.39-3.51] and 0.57 [95% CI 0.15-2.20], respectively). DISCUSSION/SIGNIFICANCE OF FINDINGS: Medium and dark FP did not impact overall scan quality or age-appropriate retinal layer visibility on investigational bedside OCT in preterm infants. This study supports the feasibility of using OCT to analyze retinal microanatomy in diverse populations of preterm infants with a range of FP.

ummary Venous thromboembolism (VTE) is a common disease (~700 per 100 000) that is associated with significant risk of recurrence, chronic complications, and substantial mortality, with reported death rates of up to 40% at 10 years. The development of novel anticoagulants has revolutionized the treatment of acute VTE, while strategies for prevention and treatment of chronic complications still seek for such a landmark change. Impaired thrombus resolution is the common denominator behind VTE complications, which are postthrombotic syndrome (PTS) and chronic thromboembolic pulmonary hypertension (CTEPH). PTS and CTEPH are associated with substantial morbidity and high healthcare expenses. While PTS occurs in up to 50% of patients after symptomatic deep vein thrombosis, only a small and poorly defined number of patients are diagnosed with CTEPH after pulmonary embolism. This review is a comprehensive summary of VTE-related chronic complications, their epidemiology, diagnosis, and treatment.

OBJECTIVES/GOALS: The goal of this study is to evaluate and optimize the characterization of cystoid macular edema (CME) using an investigational swept source (SS)-OCT system. Our knowledge of CME in preterm infants is limited; optimizing its characterization is a critical step in understanding its impact on vision. METHODS/STUDY POPULATION: In this IRB-approved protocol, 118 preterm infants were imaged in the Duke intensive care nursery (ICN) with a novel lightweight, hand-held, high-speed, SS-OCT system following routine clinical eye exams. SS-OCT images were deidentified, automatically segmented using custom software (DOCTRAP), measured for several retinal layer thicknesses, and reviewed by masked expert graders for the presence and severity of CME. Reliability of SS-OCT measures will be assessed, and the association between CME status and retinal layer thicknesses will be calculated using logistic regression modeling. RESULTS/ANTICIPATED RESULTS: The prevalence of CME overall and by severity will be calculated. The distribution of several retinal layer thicknesses will be reported and compared by infant CME status and, when edema is present, by CME severity. Reproducibility and repeatability will be reported for objective variables, and intra-grader and inter-grader agreement will be reported for subjective variables. Multivariate logistic regression coefficients and odds ratios will be calculated for each retinal layer thickness variable. DISCUSSION/SIGNIFICANCE OF IMPACT: This study will use a novel SS-OCT system to identify retinal thickness measures that may be objective markers of CME status. This will refine the characterization of CME and provide a framework for correlating CME with functional outcomes like visual acuity. CONFLICT OF INTEREST DESCRIPTION: SC and CT have unlicensed patents on relevant technologies. CT receives royalties from Alcon and Hemosonics and consultation fees from EMMES.

The increasing demand for in-flight connectivity via satellite communications and the use of unmanned aircraft beyond line of sight pose the requirement for additional allocations in the non-exclusive Ka band satellite spectrum. This is to be decided by the International Telecommunications Union at the World Radio Conference 2019. With the terrestrial fixed service being the dominant interference source of the incumbent radio services in the Ka band satellite downlink, we simulate radio frequency interference due to emissions from multiple sources into an aeronautical receiver. Based on a specified reference scenario, we provide first order interference statistics for different flight altitudes. To this end, we approximate the sample probability density distributions of exhaustive interference scenario simulations using a log skew normal distribution to provide an analytical expression of probabilities for frequency coordination and system design.

Purpose Children with a history of prematurity often have poorly developed foveae but when during development foveal differences arise. We hypothesize that the course of foveal development is altered from the time of preterm birth. Methods Eyes of 102 preterm infants undergoing retinopathy of prematurity screening examinations in the STudy of Eye imaging in Premature infantS (BabySTEPS) (NCT02887157) were serially imaged between 30 and 42 weeks postmenstrual age (PMA) using handheld optical coherence tomography systems. Total retinal thickness, inner retinal layer (IRL) thickness, and outer retinal layer (ORL) thickness were measured at the foveal center and parafovea. Foveal put depth, IRL thickness, and ORL thickness were compared between infants born at different gestational ages using mixed effects models. Results Foveal pit depth and IRL thickness were inversely related to gestational age; on average, the most premature infants had the thickest IRL and shallowest pits at all PMAs. Differences were evident by 30 weeks PMA and persisted through 42 weeks PMA. The foveal pits of the most premature infants did not progressively deepen, and the IRLs did not continue to thin with increasing chronological age. Conclusions Foveation in extremely preterm infants is arrested from the earliest observed ages and fails to progress through term equivalent age. The developmental displacement of the IRL from the foveal center into the parafovea does not occur normally after preterm birth. These observations suggest that foveal hypoplasia seen in children with history of prematurity is due to disturbances in foveal development that manifest within weeks of birth.

Physical layer security has captured increased interest in satellite communications, where low-gain mobile ground-receivers need to be supplied with high transmit powers from space stations. We investigate the potential of spatial modulation to protect multi-beam satellite downlinks from eavesdropping. Spatial modulation, widely studied in the context of terrestrial networks to provide increased spectral efficiency, uses the antenna indices of multi-antenna systems as additional carriers of information. Our analysis shows that spatial modulation can improve eavesdropping resistance, depending on the relative positioning of the unauthorized and legitimate receivers within the coverage of a multi-beam satellite. Additionally, the area where a legitimate receiver is able to capture the signal can be tuned by load balancing of the different satellite transponders.

PURPOSE: Macular atrophy and scar increase in prevalence during treatment for neovascular age-related macular degeneration (AMD) and are associated with poor visual acuity. We sought to identify the distribution of spectral domain optical coherence tomography (SDOCT)-determined features and subretinal lesion thicknesses at sites of macular scar or atrophy after two years of treatment in the Comparison of AMD Treatments Trials (CATT). DESIGN: Cross-sectional analysis PARTICIPANTS: CATT participants with SDOCT, color photograph and fluorescein angiogram (CP/FA) images at Year 2. METHODS: Sixty-eight study eyes at Year 2 in CATT, were selected based on image quality and CP/FA-determined predominant presence of: geographic atrophy (GA, n=25), non-GA (NGA, n=44), fibrotic scar (FS, n=26) or non-FS (NFS, n=7). CP/FA components were delineated by CP/FA readers; SDOCT morphologic features and thicknesses were delineated by OCT readers. Using custom software and graphic user interfaces, images were registered, overlaying features and components per pixel; differences were analyzed across groups. MAIN OUTCOME MEASURES: OCT features, CP/FA components, and retinal and subretinal lesion thicknesses at each pixel of regional overlays. RESULTS: SDOCT assessment of registered areas of pathology revealed the following: 1) retinal pigment epithelium atrophy (with or without residual lesion material) covered 75% of pixels designated as GA, 22% as NGA, 24% of NFS and 46% of FS (p

INTRODUCTION: Disruption of E-cadherin function and increased expression of vimentin and the transcriptional oncogene, SOX2, are thought to characterize epithelial to mesenchymal transition (EMT) in HNSCC that contributes to invasive and metastatic behavior. To determine if such changes relate to prognosis or host immune response, expression of these markers and correlations with clinical characteristics, histologic worst pattern of invasion (WPOI) and tumor infiltrating lymphocytes (TIL) and survival were assessed. METHODS: Immunohistologic expression of markers was determined in tissue microarrays from 274 previously untreated HNSCC patients. Expression was correlated with levels of TILs in microcores and WPOI in biopsy specimens. Correlations were assessed by Kruskal-Wallis testing and Spearman correlation coefficients where appropriate. Overall and relapse-free survival were analyzed with Cox proportional hazards models. Median follow up was 60.0 months. RESULTS: Loss of E-cadherin expression was significantly associated with low or absent SOX2 expression (R=0.433, p

We propose an evolution of the Mu2e experiment, called Mu2e-II, that would leverage advances in detector technology and utilize the increased proton intensity provided by the Fermilab PIP-II upgrade to improve the sensitivity for neutrinoless muon-to-electron conversion by one order of magnitude beyond the Mu2e experiment, providing the deepest probe of charged lepton flavor violation in the foreseeable future. Mu2e-II will use as much of the Mu2e infrastructure as possible, providing, where required, improvements to the Mu2e apparatus to accommodate the increased beam intensity and cope with the accompanying increase in backgrounds.

SummaryOxidative stress affects clinical outcome in patients with ST-elevation acute coronary syndrome (STE-ACS). Although high-density lipoprotein (HDL) particles are generally considered protective, deleterious properties of HDL have been observed in patients with acute myocardial infarction. Here, we analysed the association between pro oxidant HDL and all-cause mortality in STE-ACS patients. We determined the antioxidant function of HDL in 247 prospectively enrolled patients undergoing primary percutaneous coronary intervention for STE-ACS. Patients were stratified as by a pro-oxidant serum HDL oxidant index (HOI 1) or with an antioxidant serum HOI (HOL< 1) capacity. Multivariate regression analysis was used to relate HOI to survival. The median follow-up time was 23 months (IQR 14.4–40.0 months). Pro-oxidant HDL was observed in 44.1 % of STE-ACS patients and was independently associated with all-cause mortality with a hazard ratio of 3.30(95 %CI 1.50–7.27, p = 0.003). Mortality rates were higher in patients with baseline pro-oxidant HDL compared to patients with preserved HDL function at 30 days (11.9 % vs 2.2 %, p=0.002), and at 4 years (22.9 % vs 8.7 %, p=0.002). Elevated neutrophil counts were a strong and independent predictor for pro-oxidant HDL with an odds ratio per standard deviation of 1.50 (95 %CI 1.11–2.03, p=0.008), as was history of prior acute myocardial infarction, elevated triglycerides levels and reduced glomerular filtration rate. In conclusion, pro-oxidant HDL represents a strong and independent predictor of long-term as well as short-term all-cause mortality in STE-ACS patients. Elevated neutrophil counts predicted the presence of serum pro-oxidant HDL. The maintenance of HDL functions might be a promising therapeutic target in STE-ACS patients.

Purpose To develop methods to make precise comparisons of specific retinal features between and within spectral-domain (SD) OCT images, color fundus photography (CFP) images, and fluorescein angiography (FA) images in eyes treated with anti–vascular endothelial growth factor (VEGF) agents for neovascular age-related macular degeneration (nAMD). Design Retrospective study. Participants Patients with good study-eye images at the 104-week visit in the Comparison of Age-Related Macular Degeneration Treatments Trials. Methods Graders reviewed CFP and FA images and delineated areas of fibrotic or nonfibrotic scar and geographic atrophy (GA) or non-GA. Other graders reviewed SD-OCT images and delineated retinal and subretinal lesion characteristics. Using newly developed custom software and graphic user interfaces, the presence and thickness of each feature at each pixel on the en face view was determined. Main Outcome Measures Spectral-domain OCT findings versus CFP and FA lesion components from regional overlays. Results Per-eye distribution and thickness of SD-OCT features within CFP- and FA-established areas of scar and atrophy can be determined precisely, can be displayed in multiple formats, and can be extracted into pixel-specific data sets. These methods enable statistical analysis of imaging results within eyes and across eyes of different patients. For example, photoreceptor loss, subretinal lesion material, and thicknesses of photoreceptor layer and subretinal material across those SD-OCT features can be related precisely to CFP and FA regions of scar or atrophy. Conclusions Methods to integrate qualitative and quantitative retinal and subretinal changes to coincide with photographic and angiographic designations of the nAMD lesion areas and sequelae are integral for accurate assessments of posttreatment retinal morphologic features. These may lead to better understanding of disease progression and improved treatment strategies.

In saturated markets, small and medium wine estates face strong competition, not only from other domestic producers but also from international wine producers. Thus, small and medium wine estates are increasingly considering other distribution channels or new markets. In this context, ‘export’ as a strategic approach has gained popularity among those producers. The aim of this chapter is to elaborate on export strategies of small and medium sized wine estates, addressing their challenges and obstacles. We will conduct a literature review on market entry strategies and challenges of internationalization. Afterward we present a case study using the small Verband deutscher Pradikatsweinguter wine estate Georg Muller Stiftung, which has been active in China for roughly 10 years. Overall, it can be considered as one of the German benchmarks for exporting wine to China.

Thames Water is the largest water company in the UK. The company treats about 400,000 tonnes dry solids (tds) p.a. sewage sludge. The company's current strategic investment plans focus on improving treatment through enhanced digestion and reducing the wet mass of sludge recycled to land. Thames recognises sludge as a resource and is evaluating advanced options to unlock the full energy potential from sludge. Anaerobic digestion has been the foundation of sludge treatment and, in combination with combined heat and power, is the main process for recovering renewable energy in Thames Water and in the UK Water Industry. It is our view that sludge drying is an essential stage for advanced energy recovery process technologies such as pyrolysis or gasification. Efficient use of waste heat is critical to the economic and environmental sustainability of sludge management. Innovative technologies are a key part for the vision to convert a water company into a renewable energy provider.

Objective— Restoration of patency is a natural target of vascular remodeling after venous thrombosis that involves vascular endothelial cells and smooth muscle cells, as well as leukocytes. Acute pulmonary emboli usually resolve Approach and Results— Mice with an endothelial cell–specific conditional deletion of vascular endothelial growth factor receptor 2/kinase insert domain protein receptor were used in a model of stagnant flow venous thrombosis closely resembling human deep vein thrombosis. Biochemical and functional analyses were performed on pulmonary endarterectomy specimens from patients with CTEPH, a human model of nonresolving venous thromboembolism. Endothelial cell–specific deletion of kinase insert domain protein receptor and subsequent ablation of thrombus vascularization delayed thrombus resolution. In accordance with these findings, organized human CTEPH thrombi were largely devoid of vascular structures. Several vessel-specific genes, such as kinase insert domain protein receptor, vascular endothelial cadherin, and podoplanin, were expressed at lower levels in white CTEPH thrombi than in organizing deep vein thrombi and organizing thrombi from aortic aneurysms. In addition, red CTEPH thrombi attenuated the angiogenic response induced by vascular endothelial growth factor. Conclusions— In the present work, we propose a mechanism of thrombus nonresolution demonstrating that endothelial cell–specific deletion of kinase insert domain protein receptor abates thrombus vessel formation, misguiding thrombus resolution. Medical conditions associated with the development of CTEPH may be compromising early thrombus angiogenesis.