Compendium-Wide Analysis of Pseudomonas aeruginosa Core and Accessory Genes Reveals Transcriptional Patterns across Strains PAO1 and PA14.

Pseudomonas aeruginosa is an opportunistic pathogen that causes difficult-to-treat infections. Two well-studied divergent P. aeruginosa strain types, PAO1 and PA14, have significant genomic heterogeneity, including diverse accessory genes present in only some strains. Genome content comparisons find core genes that are conserved across both PAO1 and PA14 strains and accessory genes that are present in only a subset of PAO1 and PA14 strains. Here, we use recently assembled transcriptome compendia of publicly available P. aeruginosa RNA sequencing (RNA-seq) samples to create two smaller compendia consisting of only strain PAO1 or strain PA14 samples with each aligned to their cognate reference genome. We confirmed strain annotations and identified other samples for inclusion by assessing each sample\u27s median expression of PAO1-only or PA14-only accessory genes. We then compared the patterns of core gene expression in each strain. To do so, we developed a method by which we analyzed genes in terms of which genes showed similar expression patterns across strain types. We found that some core genes had consistent correlated expression patterns across both compendia, while others were less stable in an interstrain comparison. For each accessory gene, we also determined core genes with correlated expression patterns. We found that stable core genes had fewer coexpressed neighbors that were accessory genes. Overall, this approach for analyzing expression patterns across strain types can be extended to other groups of genes, like phage genes, or applied for analyzing patterns beyond groups of strains, such as samples with different traits, to reveal a deeper understanding of regulation

Genetic and Dietary Factors Influencing the Progression of Nuclear Cataract.

PURPOSE: To determine the heritability of nuclear cataract progression and to explore prospectively the effect of dietary micronutrients on the progression of nuclear cataract. DESIGN: Prospective cohort study. PARTICIPANTS: Cross-sectional nuclear cataract and dietary measurements were available for 2054 white female twins from the TwinsUK cohort. Follow-up cataract measurements were available for 324 of the twins (151 monozygotic and 173 dizygotic twins). METHODS: Nuclear cataract was measured using a quantitative measure of nuclear density obtained from digital Scheimpflug images. Dietary data were available from EPIC food frequency questionnaires. Heritability was modeled using maximum likelihood structural equation twin modeling. Association between nuclear cataract change and micronutrients was investigated using linear and multinomial regression analysis. The mean interval between baseline and follow-up examination was 9.4 years. MAIN OUTCOME MEASURES: Nuclear cataract progression. RESULTS: The best-fitting model estimated that the heritability of nuclear cataract progression was 35% (95% confidence interval [CI], 13-54), and individual environmental factors explained the remaining 65% (95% CI, 46-87) of variance. Dietary vitamin C was protective against both nuclear cataract at baseline and nuclear cataract progression (β = -0.0002, P = 0.01 and β = -0.001, P = 0.03, respectively), whereas manganese and intake of micronutrient supplements were protective against nuclear cataract at baseline only (β = -0.009, P = 0.03 and β = -0.03, P = 0.01, respectively). CONCLUSIONS: Genetic factors explained 35% of the variation in progression of nuclear cataract over a 10-year period. Environmental factors accounted for the remaining variance, and in particular, dietary vitamin C protected against cataract progression assessed approximately 10 years after baseline

Unsupervised Extraction of Stable Expression Signatures from Public Compendia with an Ensemble of Neural Networks

Cross-experiment comparisons in public data compendia are challenged by unmatched conditions and technical noise. The ADAGE method, which performs unsupervised integration with denoising autoencoder neural networks, can identify biological patterns, but because ADAGE models, like many neural networks, are over-parameterized, different ADAGE models perform equally well. To enhance model robustness and better build signatures consistent with biological pathways, we developed an ensemble ADAGE (eADAGE) that integrated stable signatures across models. We applied eADAGE to a compendium of Pseudomonas aeruginosa gene expression profiling experiments performed in 78 media. eADAGE revealed a phosphate starvation response controlled by PhoB in media with moderate phosphate and predicted that a second stimulus provided by the sensor kinase, KinB, is required for this PhoB activation. We validated this relationship using both targeted and unbiased genetic approaches. eADAGE, which captures stable biological patterns, enables cross-experiment comparisons that can highlight measured but undiscovered relationships.Gordon and Betty Moore Foundation (GBMF 4552)National Institutes of Health (U.S.) (grant R01-AI091702)Cystic Fibrosis Foundation (STANTO15R0

Safety and efficacy of the hybrid approach in coronary chronic total occlusion percutaneous coronary intervention: The Hybrid Video Registry

Objectives The aim of the Hybrid Video Registry (HVR) is to assess the acute safety and efficacy of the Hybrid Approach in comparison to other contemporary methods of CTO‐PCI. Background: Recently, multiple techniques in Percutaneous Coronary Intervention (PCI) for coronary Chronic Total Occlusions (CTO) have been synthesized into a method referred to as the “Hybrid Approach”. Methods About 194 video‐taped timed live cases from CTO‐PCI training workshops were analyzed by independent data abstractors and compared to three contemporary CTO‐PCI registries stratified by case complexity based on the J‐CTO score. Results Overall procedural success was 95% of all cases attempted with an excellent safety profile. In the most complex lesion subset, which made up 45% of all HVR cases, success was 92.8%, which was significantly higher than either the Royal Bromptom (78.9%), or Japanese‐CTO (73.3%) registries, P = 0.04 Hybrid vs. Royal Brompton, P = 0.006 Hybrid vs. Japanese‐CTO). The Hybrid Approach was also associated with shorter procedure times and lower contrast utilization. Conclusions In a real world angiographic registry of complex CTOs, the Hybrid Approach to CTO‐PCI is safe, and may be superior to other contemporary approaches to CTO intervention with respect to procedural success and efficiency among a diverse group of operators and lesion complexity

Prevalence and Outcomes of Percutaneous Coronary Interventions for Ostial Chronic Total Occlusions: Insights From a Multicenter Chronic Total Occlusion Registry

Ostial chronic total occlusions (CTOs) can be challenging to recanalize.We sought to examine the prevalence, angiographic presentation, and procedural outcomes of ostial (side-branch ostial and aorto-ostial) CTOs among 1000 CTO percutaneous coronary interventions (PCIs) performed in 971 patients between 2015 and 2017 at 14 centres in the US, Europe, and Russia.Ostial CTOs represented 16.9% of all CTO PCIs: 9.6% were aorto-ostial, and 7.3% were side-branch ostial occlusions. Compared with nonostial CTOs, ostial CTOs were longer (44 ± 33 vs 29 ± 19 mm, P < 0.001) and more likely to have proximal-cap ambiguity (55% vs 33%, P < 0.001), moderate/severe calcification (67% vs 45%, P < 0.001), a diffusely diseased distal vessel (41% vs 26%, P < 0.001), interventional collaterals (64% vs 53%, P = 0.012), and previous coronary artery bypass graft surgery (CABG) (51% vs 27%, P < 0.001). The retrograde approach was used more often in ostial CTOs (54% vs 29%, P < 0.001) and was more often the final successful crossing strategy (30% vs 18%, P = 0.003). Technical (81% vs 84%, P = 0.280), and procedural (77% vs 83%, P = 0.112) success rates and the incidence of in-hospital major complication were similar (4.8% vs 2.2%, P = 0.108), yet in-hospital mortality (3.0% vs 0.5%, P = 0.010) and stroke (1.2% vs 0.0%, P = 0.030) were higher in the ostial CTO PCI group. In multivariable analysis, ostial CTO location was not independently associated with higher risk for in-hospital major complications (adjusted odds ratio 1.27, 95% confidence intervals 0.37 to 4.51, P = 0.694).Ostial CTOs can be recanalized with similar rates of success as nonostial CTOs but are more complex, more likely to require retrograde crossing and may be associated with numerically higher risk for major in-hospital complications

In-hospital Outcomes of Attempting More Than One Chronic Total Coronary Occlusion Through Percutaneous Intervention During the Same Procedure

The frequency and outcomes of patients who underwent chronic total occlusion (CTO) percutaneous coronary intervention (PCI) of more than one CTO during the same procedure have received limited study. We compared the clinical and angiographic characteristics and procedural outcomes of patients who underwent treatment of single versus >1 CTOs during the same procedure in 20 centers from the United States, Europe, and Russia. A total of 2,955 patients were included: mean age was 65 ± 10 years and 85% were men with high prevalence of previous myocardial infarction (46%), and previous coronary artery bypass graft surgery (33%). More than one CTO lesions were attempted during the same procedure in 58 patients (2.0%) and 70% of them were located in different major epicardial arteries. Compared with patients who underwent PCI of a single CTO, those who underwent PCI of >1 CTOs during the same procedure had similar J-CTO (2.4 ± 1.3 vs 2.5 ± 1.3, p = 0.579) and Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (1.5 ± 1.2 vs 1.3 ± 1.0 p = 0.147) scores. The multi-CTO PCI group had similar technical success (86% vs 87%, p = 0.633), but higher risk of in-hospital major complications (10.3% vs 2.7%, p = 0.005), and consequently numerically lower procedural success (79% vs 85%, p = 0.197). The multi-CTO PCI group had higher in-hospital mortality (5.2% vs 0.5%, p = 0.005) and stroke (5.2%vs 0.2%, p 1 CTO lesions requiring revascularization, as treatment during a single procedure was associated with higher risk for periprocedural complications

Effect of varying skin surface electrode position on electroretinogram responses recorded using a handheld stimulating and recording system

Purpose A handheld device (the RETeval system, LKC Technologies) aims to increase the ease of electroretinogram (ERG) recording by using specially designed skin electrodes, rather than corneal electrodes. We explored effects of electrode position on response parameters recorded using this device. Methods Healthy adult twins were recruited from the TwinsUK cohort and underwent recording of light-adapted flicker ERGs (corresponding to international standard stimuli). In Group 1, skin electrodes were placed in a “comfortable” position, which was up to 20 mm below the lid margin. For subsequent participants (Group 2), the electrode was positioned 2 mm from the lid margin as recommended by the manufacturer. Amplitudes and peak times (averaged from both eyes) were compared between groups after age-matching and inclusion of only one twin per pair. Light-adapted flicker and flash ERGs were recorded for an additional 10 healthy subjects in two consecutive recording sessions: in the test eye, electrode position was varied from 2 to 10–20 mm below the lid margin between sessions; in the fellow (control) eye, the electrode was 2 mm below the lid margin throughout. Amplitudes and peak times (test eye normalised to control eye) were compared for the two sessions. Results Including one twin per pair, and age-matching yielded 28 individuals per group. Flicker ERG amplitudes were significantly lower for Group 1 than Group 2 participants (p = 0.0024). However, mean peak times did not differ between groups (p = 0.54). For the subjects in whom electrode position was changed between recording sessions, flash and flicker amplitudes were significantly lower when positioned further from the lid margin (p  0.5). Conclusions Moving the skin electrodes further from the lid margin significantly reduces response amplitudes, highlighting the importance of consistent electrode positioning. However, this does not significantly affect peak times. Thus, it may be feasible to adopt a more comfortable position in participants who cannot tolerate the recommended position if analysis is restricted to peak time parameters

TiEMPO: Open-source time-dependent end-to-end model for simulating ground-based submillimeter astronomical observations

The next technological breakthrough in millimeter-submillimeter astronomy is 3D imaging spectrometry with wide instantaneous spectral bandwidths and wide fields of view. The total optimization of the focal-plane instrument, the telescope, the observing strategy, and the signal-processing software must enable efficient removal of foreground emission from the Earth's atmosphere, which is time-dependent and highly nonlinear in frequency. Here we present TiEMPO: Time-Dependent End-to-End Model for Post-process Optimization of the DESHIMA Spectrometer. TiEMPO utilizes a dynamical model of the atmosphere and parametrized models of the astronomical source, the telescope, the instrument, and the detector. The output of TiEMPO is a time-stream of sky brightness temperature and detected power, which can be analyzed by standard signal-processing software. We first compare TiEMPO simulations with an on-sky measurement by the wideband DESHIMA spectrometer and find good agreement in the noise power spectral density and sensitivity. We then use TiEMPO to simulate the detection of a line emission spectrum of a high-redshift galaxy using the DESHIMA 2.0 spectrometer in development. The TiEMPO model is open source. Its modular and parametrized design enables users to adapt it to design and optimize the end-to-end performance of spectroscopic and photometric instruments on existing and future telescopes.Comment: Presented at SPIE Astronomical Telescopes + Instrumentation 2020. Full published paper, poster and video available at https://doi.org/10.1117/12.2561014 Open-source Python package of TiEMPO: https://pypi.org/project/tiempo-deshima/ Open-source code of TiEMPO: https://zenodo.org/record/4279086#.X_jAsdhKg2