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Background Radionuclide ventriculography (RNVG) can be used to quantify mechanical dyssynchrony and may be a valuable adjunct in the assessment of heart failure with reduced ejection fraction (HFrEF). The study aims to investigate the effect of beta-blockers on mechanical dyssynchrony using novel RNVG phase parameters. Methods A retrospective study was carried out in a group of 98 patients with HFrEF. LVEF and dyssynchrony were assessed pre and post beta-blockade. Dyssynchrony was assessed using synchrony, entropy, phase standard deviation, approximate entropy, and sample entropy from planar RNVG phase images. Subgroups split by ischemic etiology were also investigated. Results An improvement in dyssynchrony and LVEF was measured six months post beta-blockade for both ischemic and non-ischemic groups. Conclusions A significant improvement in dyssynchrony and LVEF was measured post beta-blockade using novel measures of dyssynchrony.

Aerosol–cloud–precipitation interactions (ACIs) provide the greatest source of uncertainties in predicting changes in Earth's energy budget due to poor representation of marine stratocumulus and the associated ACIs in climate models. Using in situ data from 329 cloud profiles across 24 research flights from the NASA ObseRvations of Aerosols above CLouds and their intEractionS (ORACLES) field campaign in September 2016, August 2017, and October 2018, it is shown that contact between above-cloud biomass burning aerosols and marine stratocumulus over the Southeast Atlantic Ocean was associated with precipitation suppression and a decrease in the precipitation susceptibility (So) to aerosols. The 173 “contact” profiles with aerosol concentration (Na) greater than 500 cm−3 within 100 m above cloud tops had a 50 % lower precipitation rate (Rp) and a 20 % lower So, on average, compared to 156 “separated” profiles with Na less than 500 cm−3 up to at least 100 m above cloud tops. Contact and separated profiles had statistically significant differences in droplet concentration (Nc) and effective radius (Re) (95 % confidence intervals from a two-sample t test are reported). Contact profiles had 84 to 90 cm−3 higher Nc and 1.4 to 1.6 µm lower Re compared to separated profiles. In clean boundary layers (below-cloud Na less than 350 cm−3), contact profiles had 25 to 31 cm−3 higher Nc and 0.2 to 0.5 µm lower Re. In polluted boundary layers (below-cloud Na exceeding 350 cm−3), contact profiles had 98 to 108 cm−3 higher Nc and 1.6 to 1.8 µm lower Re. On the other hand, contact and separated profiles had statistically insignificant differences between the average liquid water path, cloud thickness, and meteorological parameters like surface temperature, lower tropospheric stability, and estimated inversion strength. These results suggest the changes in cloud microphysical properties were driven by ACIs rather than meteorological effects, and adjustments to existing relationships between Rp and Nc in model parameterizations should be considered to account for the role of ACIs.

Metabolic dysfunction and excess accumulation of adipose tissue are detrimental side effects from breast cancer treatment. Diet and physical activity are important treatments for metabolic abnormalities, yet patient compliance can be challenging during chemotherapy treatment. Time-restricted eating (TRE) is a feasible dietary pattern where eating is restricted to 8 h/d with water-only fasting for the remaining 16 h. The purpose of this study is to evaluate the effect of a multimodal intervention consisting of TRE, healthy eating, and reduced sedentary time during chemotherapy treatment for early-stage (I–III) breast cancer on accumulation of visceral fat (primary outcome), other fat deposition locations, metabolic syndrome and cardiovascular disease risk (secondary outcomes) compared with usual care. The study will be a two-site, two-arm, parallel-group superiority randomised control trial enrolling 130 women scheduled for chemotherapy for early-stage breast cancer. The intervention will be delivered by telephone, including 30–60-minute calls with a registered dietitian who will provide instructions on TRE, education and counselling on healthy eating, and goal setting for reducing sedentary time. The comparison group will receive usual cancer and supportive care including a single group-based nutrition class and healthy eating and physical activity guidelines. MRI, blood draws and assessment of blood pressure will be performed at baseline, after chemotherapy (primary end point), and 2-year follow-up. If our intervention is successful in attenuating the effect of chemotherapy on visceral fat accumulation and cardiometabolic dysfunction, it has the potential to reduce risk of cardiometabolic disease and related mortality among breast cancer survivors.

SummaryMitochondria are semi-autonomous organelles that serve as hubs for aerobic energy metabolism. The biogenesis of the respiratory (OXPHOS) system relies on nuclear-encoded factors, which regulate the transcription, processing and translation of mitochondrial (mt)RNAs. These include proteins of primordial origin, as well as eukaryotic-type RNA-binding families recruited from the host genomes to function in mitogenome expression. Pentatricopeptide repeat (PPR) proteins constitute a major gene-family in angiosperms that is pivotal in many aspects of mtRNA metabolism, such as editing, splicing or stability. Here, we report the analysis ofMITOCHONDRIA STABILITY/PROCESSING PPR FACTOR1(MSP1, At4g20090), a canonical mitochondria-localized PPR protein that is necessary for mitochondrial biogenesis and embryo-development. Functional complementation confirmed that the phenotypes result from a disruption of theMSP1gene. As a loss-of-function allele ofArabidopsis MSP1leads to seed abortion, we employed an embryo-rescue method for the molecular characterization ofmsp1mutants. Our data show thatmsp1embryo-development fails to proceed beyond the heart-torpedo transition stage as a consequence of a severe nad1 pre-RNA processing-defect, resulting in the loss of respiratory complex I (CI) activity. The maturation ofnad1involves the processing of three RNA-fragments,nad1.1, nad1.2andnad1.3. Based on biochemical analyses and the mtRNA profiles in wild-type andmsp1plants, we concluded that through its association with a specific site innad1.1, MSP1 facilitates the generation of its 3’-terminus and stabilizes it -a prerequisite fornad1exons a-b splicing. Our data substantiate the importance of mtRNA metabolism for the biogenesis of the respiratory machinery during early-plant development.

Herein, the UV light photocatalytic activity of an Au101NC-AlSrTiO3-rGO nanocomposite comprising 1 wt% rGO, 0.05 wt% Au101(PPh3)21Cl5 (Au101NC), and AlSrTiO3 evaluated for H2 production. The synthesis of Au101NC-AlSrTiO3-rGO nanocomposite followed two distinct routes: (1) Au101NC was first mixed with AlSrTiO3 followed by the addition of rGO (Au101NC-AlSrTiO3:rGO) and (2) Au101NC was first mixed with rGO followed by the addition of AlSrTiO3 (Au101NC-rGO:AlSrTiO3). Both prepared samples were annealed in air at 210 °C for 15 min. Inductively coupled plasma mass spectrometry and high-resolution scanning transmission electron microscopy showed that the Au101NC adhered almost exclusively to the rGO in the nanocomposite and maintained a size less than 2 nm. Under UV light irradiation, the Au101NC-AlSrTiO3:rGO nanocomposite produced H2 at a rate 12 times greater than Au101NC-AlSrTiO3 and 64 times greater than AlSrTiO3. The enhanced photocatalytic activity is attributed to the small particle size and high loading of Au101NC, which is achieved by non-covalent binding to rGO. These results show that significant improvements can be made to AlSrTiO3-based photocatalysts that use cluster co-catalysts by the addition of rGO as an electron mediator to achieve high cluster loading and limited agglomeration of the clusters.

The impact of gut microbiota–targeted interventions on the incidence, duration, and severity of respiratory tract infections (RTIs) in nonelderly adults, and factors moderating any such effects, are unclear. This systematic review and meta-analysis aimed to determine the effects of orally ingested probiotics, prebiotics, and synbiotics compared with placebo on RTI incidence, duration, and severity in nonelderly adults, and to identify potential sources of heterogeneity. Studies were identified by searching CENTRAL, PubMed, Scopus, and Web of Science up to December 2021. English-language, peer-reviewed publications of randomized, placebo-controlled studies that tested an orally ingested probiotic, prebiotic, or synbiotic intervention of any dose for ≥1 wk in adults aged 18–65 y were included. Results were synthesized using intention-to-treat and per-protocol random-effects meta-analysis. Heterogeneity was explored by subgroup meta-analysis and meta-regression. Risk of bias was assessed using the Cochrane risk-of-bias assessment tool for randomized trials version 2 (RoB2). Forty-two manuscripts reporting effects of probiotics (n = 38), prebiotics (n = 2), synbiotics (n = 1) or multiple -biotic types (n = 1) were identified (n = 9179 subjects). Probiotics reduced the risk of experiencing ≥1 RTI (relative risk = 0.91; 95% CI: 0.84, 0.98; P = 0.01), and total days (rate ratio = 0.77; 95% CI: 0.71, 0.83; P

This commentary highlights the challenges of clinical trials, especially as related to trials on exercise for older adults with advanced cancer, and comments on the study by Mikkelsen et al.

Southern Africa produces almost a third of the Earth's biomass burning (BB) aerosol particles, yet the fate of these particles and their influence on regional and global climate is poorly understood. ORACLES (ObseRvations of Aerosols above CLouds and their intEractionS) is a 5-year NASA EVS-2 (Earth Venture Suborbital-2) investigation with three intensive observation periods designed to study key atmospheric processes that determine the climate impacts of these aerosols. During the Southern Hemisphere winter and spring (June–October), aerosol particles reaching 3–5 km in altitude are transported westward over the southeast Atlantic, where they interact with one of the largest subtropical stratocumulus (Sc) cloud decks in the world. The representation of these interactions in climate models remains highly uncertain in part due to a scarcity of observational constraints on aerosol and cloud properties, as well as due to the parameterized treatment of physical processes. Three ORACLES deployments by the NASA P-3 aircraft in September 2016, August 2017, and October 2018 (totaling ∼350 science flight hours), augmented by the deployment of the NASA ER-2 aircraft for remote sensing in September 2016 (totaling ∼100 science flight hours), were intended to help fill this observational gap. ORACLES focuses on three fundamental science themes centered on the climate effects of African BB aerosols: (a) direct aerosol radiative effects, (b) effects of aerosol absorption on atmospheric circulation and clouds, and (c) aerosol–cloud microphysical interactions. This paper summarizes the ORACLES science objectives, describes the project implementation, provides an overview of the flights and measurements in each deployment, and highlights the integrative modeling efforts from cloud to global scales to address science objectives. Significant new findings on the vertical structure of BB aerosol physical and chemical properties, chemical aging, cloud condensation nuclei, rain and precipitation statistics, and aerosol indirect effects are emphasized, but their detailed descriptions are the subject of separate publications. The main purpose of this paper is to familiarize the broader scientific community with the ORACLES project and the dataset it produced.

Determine in cardiac amyloid (CA) patients, whether cardiac CT derived extracellular volume (ECV) correlates with that obtained by MRI. Perform this correlation with single (SECT) versus dual energy (DECT) CT and evaluate whether a single sample volume ECV-measure was as reliable as a global (16 segment) assessment.CA patients who had undergone a clinical cardiac MRI (CMR) were recruited prospectively. SECT and DECT cardiac scans were performed. Three ECG-triggered prospective SECT scans were acquired: non-contrast, arterial-phase contrast and 5-minute delayed images. A DECT scan was performed at 7 min. Post processing was used to determine ECV. Analyses of SECT or DECT global ECV versus CMR were performed using the Pearson correlation coefficient, Bland Altman analysis and Intraclass correlation coefficient (ICC). Similar analyses were performed to examine the performance of single-segment sampling by SECT or DECT versus CMR.25 patients were recruited, mean age was 80.0 ± 7.1 years, 80 % were male, 21 patients had transthyretin- CA, 4 had light chain- CA. Correlations were close with both SECT or DECT global ECV versus CMR (r = 0.79 and 0.88 respectively, p 0.001 for both). Reliability of both SECT and DECT to assess global ECV in comparison to CMR was good: ICC for SECT was 0.88 (95 % CI 0.73-0.95) and 0.93 (95 % CI 0.82-0.97) for DECT. For single volume sampling techniques: correlations were close with both SECT or DECT versus CMR (r = 0.60 and 0.72 respectively, p 0.01 for both) There was no difference in ICC for SECT (0.74, 95 %CI 0.41-0.88) versus DECT (0.84, 95 % CI 0.63-0.93). Wider confidence intervals were noted for ICC with single versus global CT derived ECV assessment. Mean effective radiation dose was for SECT was 5.49 ± 8.04 mSv and 6.90 ± 3.01 mSv for DECT dual energy CT (p = 0.75).Global ECV values derived by both DECT or SECT correlated with those obtained by CMR and demonstrated good reliability by ICC in a population of CA patients. DECT and SECT single sampling derived ECV values also demonstrated close correlation and good reliability but the ICCs for single sampling had wider confidence intervals than global ECV assessment.

Structural isomerism of [Au9(PPh3)8]3+ has been studied experimentally, mostly concerning the symmetry of the Au9 core. Recently, the C4 isomer of [Au9(PPh3)8]3+ has been shown to exist in solution...

A retrospective cohort study considered patients 18 or more years of age diagnosed between January 2007 and May 2018 with unresectable stage iii non-small-cell lung cancer (nsclc) who received combined chemoradiation (crt). Survival was analyzed using the Kaplan&ndash, Meier method to determine median overall (os) and progression-free survival (pfs) and the associated 95% confidence intervals (cis). Cox regression analysis was performed to identify factors prognostic for survival, including age, sex, smoking status, Eastern Cooperative Oncology Group performance status (ecog ps), histology, treatment type, tumour size, and nodal status. Of 226 patients diagnosed with unresectable stage iii disease, 134 (59%) received combined crt. Mean age was 63 years, most patients were white, were current smokers, had an ecog ps of 0 or 1, and had nonsquamous histology. Median pfs was 7.03 months (95% ci: 5.6 months to 8.5 months), and os for the cohort was 18.7 months (95% ci: 12.4 months to 24.8 months). Of those patients, 78% would have been eligible for durvalumab consolidation therapy. Univariate analysis demonstrated a significant os benefit (p = 0.010) for concurrent crt (ccrt) compared with sequential crt (scrt). Disease-specific survival remained significantly better in the ccrt group (p = 0.004). No difference in pfs was found between the ccrt and scrt groups. In addition, tumour size and nodal involvement were significant discriminating factors for survival (p < 0.05). In this patient cohort, 64% of patients progressed and received subsequent therapy. Based on multivariate analysis, tumour size and nodal station were the only factors predictive of survival in patients with unresectable stage iii nsclc treated with crt. Combined crt has been the standard treatment for unresectable stage iii nsclc. In our study, a trend of better survival was seen for ccrt compared with scrt. Factors predictive of survival in patients with stage iii disease treated with crt were tumour size and nodal station. Most patients with stage iii disease would potentially be eligible for durvalumab maintenance therapy based on the eligibility criteria from the pacific trial. The use and effectiveness of novel treatments will have to be further studied in our real-world patient population and similar populations elsewhere.

Although Markus Barth was a productive author and is known widely through his published written work, he was also, for many decades, a teacher of formative importance for generations of seminary and university students in both the United States and Switzerland. This essay shares personal reflections on Markus Barth’s profile as a biblical and theological educator and thereby introduces readers to something of his influential personal and theological style.

The shape of ordered ministry remains an ecumenical stumbling stone. There is a wide gap between churches ordered by the threefold ministry of bishop-priest-deacon and churches ordered by different patterns of ministry. It may be possible to narrow the gap by detecting a pervasive threefold ministry of episcope/keygma-didache/diakonos in both presbyterial and congregational ordered churches. That recognition can prompt ecumenical exchanges concerning the relationship between office and function. The case of Reformed and Presbyterian churches, among the least open to bishops, is examined, recovering the possibility of personal episcope that can open episcopal, presbyterial, and associational churches to deepening mutuality and forms of reconciliation.

Following the general warming trend in Greenland, an increase in calving rates, retreat and ice flow has been observed at ocean-terminating outlet glaciers. These changes contribute substantially to the current mass loss of the Greenland Ice Sheet. In order to constrain models of ice dynamics as well as estimates of mass change, detailed knowledge of geometry and ice flow is needed, in particular on the rapidly changing tongues of ocean-terminating outlet glaciers. In this study, we validate velocity estimates and spatial patterns close to the calving terminus of such an outlet derived from an iterative offset-tracking method based on synthetic aperture radar (SAR) intensity data with a collection of three independent reference measurements of glacier flow. These reference datasets are comprised of measurements from differential GPS, a terrestrial radar interferometer (TRI) and repeated unmanned aerial vehicle (UAV) surveys. Our approach to SAR velocity processing aims at achieving a relatively fine grid spacing and a high temporal resolution in order to best resolve the steep velocity gradients in the terminus area and aims to exploit the 12 d repeat interval of the single-satellite Sentinel-1A sensor. Results from images of the medium-sized ocean-terminating outlet glacier Eqip Sermia acquired by Sentinel-1A and RADARSAT-2 exhibit a mean difference of 11.5 % when compared to the corresponding GPS measurements. An areal comparison of our SAR velocity fields with independently generated velocity maps from TRI and UAV surveys showed good agreement in magnitude and spatial patterns, with mean differences smaller than 0.7 m d−1. In comparison with existing operational velocity products, our SAR-derived velocities show an improved spatial velocity pattern near the margins and calving front. There 8 % to 30 % higher surface ice velocities are produced, which has implications on ice fluxes and on mass budget estimates of similarly sized outlet glaciers. Further, we show that offset tracking from SAR intensity data at relatively low spatio-temporal sampling intervals is a valid method to derive glacier flow fields for fast-flowing glacier termini of outlet glaciers and, given the repeat period of 12 d of the Sentinel-1A sensor (6 d with Sentinel-1B), has the potential to be applied operationally in a quasi-continuous mode.

Individuals with high physical activity levels, such as athletes and military personnel, are likely to experience periods of low muscle glycogen content. Reductions in glycogen stores are associated with impaired physical performance. Lower glycogen stores in these populations are likely due to sustained aerobic exercise coupled with sub-optimal carbohydrate or energy intake. Consuming exogenous carbohydrate during aerobic exercise may be an effective intervention to sustain physical performance during periods of low glycogen. However, research is limited in the area of carbohydrate recommendations to fuel performance during periods of sub-optimal carbohydrate and energy intake. Additionally, the studies that have investigated the effects of low glycogen stores on exogenous carbohydrate oxidation have yielded conflicting results. Discrepancies between studies may be the result of glycogen stores being lowered by restricting carbohydrate or restricting energy intake. This narrative review discusses the influence of low glycogen status resulting from carbohydrate restriction versus energy restriction on exogenous carbohydrate oxidation and examines the potential mechanism resulting in divergent responses in exogenous carbohydrate oxidation. Results from this review indicate that rates of exogenous carbohydrate oxidation can be maintained when glycogen content is lower following carbohydrate restrictions, but may be reduced following energy restriction. Reductions in exogenous carbohydrate oxidation following energy restriction appear to result from lower insulin sensitivity and glucose uptake. Exogenous carbohydrate may thus be an effective intervention to sustain performance following short-term energy adequate carbohydrate restriction, but may not be an effective ergogenic aid when glycogen stores are low due to energy restriction.

Aerosol-cloud-precipitation interactions (ACIs) provide the greatest source of uncertainties in predicting changes in Earth’s energy budget due to poor representation of marine stratocumulus and the associated ACIs in climate models. Using in situ data from 329 cloud profiles across 24 research flights from the NASA ObseRvations of Aerosols above CLouds and their intEractionS (ORACLES) field campaign in September 2016, August 2017, and October 2018, it is shown that contact between above-cloud biomass-burning aerosols and marine stratocumulus over the southeast Atlantic Ocean was associated with precipitation suppression and a decrease in the precipitation susceptibility (So) to aerosols. The 173 “contact” profiles with aerosol concentration (Na) greater than 500 cm−3 within 100 m above cloud tops had 50 % lower precipitation rate (Rp) and 20 % lower So, on average, compared to 156 “separated” profiles with Na less than 500 cm−3 up to at least 100 m above cloud tops. Contact and separated profiles had statistically significant differences in droplet concentration (Nc) and effective radius (Re) (95 % confidence intervals from a two-sample t-test are reported). Contact profiles had 84 to 90 cm−3 higher Nc and 1.4 to 1.6 μm lower Re compared to separated profiles. In clean boundary layers (below-cloud Na less than 350 cm−3), contact profiles had 25 to 31 cm−3 higher Nc and 0.2 to 0.5 μm lower Re. In polluted boundary layers (below-cloud Na exceeding 350 cm−3), contact profiles had 98 to 108 cm−3 higher Nc and 1.6 to 1.8 μm lower Re. On the other hand, contact and separated profiles had statistically insignificant differences between the average liquid water path, cloud thickness, and meteorological parameters like surface temperature, lower tropospheric stability, and estimated inversion strength. These results suggest the changes in cloud properties were driven by ACIs rather than meteorological effects, and the existing relationships between Rp and Nc must be adjusted to account for the role of ACIs.

Exercise-based, multimodal rehabilitation programming similar to that used in the existing models of cardiac or pulmonary rehabilitation or prehabilitation is a holistic potential solution to address the range of physical, psychological, and existential (e.g., as their diagnosis relates to potential death) stressors associated with a cancer diagnosis and subsequent treatment. The purpose of this study was to systematically evaluate the structure and format of any type of exercise-based, multimodal rehabilitation programs used in individuals with cancer and the evidence base for their real-world effectiveness on metrics of physical (e.g., cardiorespiratory fitness, blood pressure) and psychological (e.g., health-related quality of life) health. Very few of the 33 included exercise-based, multimodal rehabilitation programs employed intervention components, education topics, and program support staff that were multi-disciplinary or cancer-specific. In particular, a greater emphasis on nutrition care, and the evaluation and management of psychosocial distress and CVD risk factors, with cancer-specific adaptations, would broaden and maximize the holistic health benefits of exercise-based rehabilitation. Despite these opportunities for improvement, exercise-based, multimodal rehabilitation programs utilized under real-world settings in individuals with cancer produced clinically meaningful and large effect sizes for cardiorespiratory fitness (VO2peak, ±2.9 mL/kg/min, 95% CI = 2.6 to 3.3) and 6-minute walk distance (+47 meters, 95% CI = 23 to 71), and medium effect sizes for various measures of cancer-specific, health-related quality of life. However, there were no changes to blood pressure, body mass index, or lung function. Overall, these findings suggest that exercise-based, multimodal rehabilitation is a real-world therapy that improves physical and psychological health among individuals with cancer, but the holistic health benefits of this intervention would likely be enhanced by addressing nutrition, psychosocial concerns, and risk factor management through education and counselling with consideration of the needs of an individual with cancer.

Radionuclide ventriculography (RNVG) can be used to quantify mechanical dyssynchrony and may be a valuable adjunct in the assessment of heart failure with reduced ejection fraction (HFrEF). The study aims to investigate the effect of beta-blockers on mechanical dyssynchrony using novel RNVG phase parameters.A retrospective study was carried out in a group of 98 patients with HFrEF. LVEF and dyssynchrony were assessed pre and post beta-blockade. Dyssynchrony was assessed using synchrony, entropy, phase standard deviation, approximate entropy, and sample entropy from planar RNVG phase images. Subgroups split by ischemic etiology were also investigated.An improvement in dyssynchrony and LVEF was measured six months post beta-blockade for both ischemic and non-ischemic groups.A significant improvement in dyssynchrony and LVEF was measured post beta-blockade using novel measures of dyssynchrony.

Ploidy transitions through whole genome duplication have shaped evolution by allowing the sub- and neo-functionalization of redundant copies of highly conserved genes to express novel traits. The nuclear:cytoplasmic (n:c) ratio is maintained in polyploid vertebrates resulting in larger cells, but body size is maintained by a concomitant reduction in cell number. Ploidy can be manipulated easily in most teleosts, and the zebrafish, already well established as a model system for biomedical research, is therefore an excellent system in which to study the effects of increased cell size and reduced cell numbers in polyploids on development and physiology. Here we describe a novel technique using confocal microscopy to measure genome size and determine ploidy non-lethally at 48 h post-fertilization (hpf) in transgenic zebrafish expressing fluorescent histones. Volumetric analysis of myofiber nuclei using open-source software can reliably distinguish diploids and triploids from a mixed-ploidy pool of embryos for subsequent experimentation. We present an example of this by comparing heart rate between confirmed diploid and triploid embryos at 54 hpf.

Reverse Cumulative Distribution Curves (RCDCs) have proven to be a useful tool in summarizing immune response profiles in vaccine studies since their introduction by Reed, Meade, and Steinhoff (RMS) (1995). They are able to display virtually all of the treatment data and characterize summary statistics such as means or even their confidence intervals (CIs) that might be obscure. RMS mentioned their similarity to survival curves often used to summarize time-to-event data which are usually not normally distributed. The RCDCs, while intuitively pleasing and useful, contain important properties which allow for more powerful statistical applications. In this paper, we will suggest several widely used rank-based tests to compare the curves in the context of vaccine studies. These rank-based tests allow for comparisons between treatments, for stratified analyses, weighted analyses, and other modifications that make them the alternative of parametric analyses without the normality assumptions. Clinical trial identification: NCT01712984 and NCT01230957.

Weather creates numerous operational and safety hazards within the National Airspace System (NAS). In 2014, extreme weather events attributed 4.3% to the total number of delay minutes recorded by the Bureau of Transportation Statistics. When factoring weather’s impact on the NAS delays and aircraft arriving late delays, weather was responsible for 32.6% of the total number of delay minutes recorded. Hourly surface meteorological aviation routine weather reports (METARs) at major airports can be used to provide valuable insight into the likely causes of weather delays at individual airports. When combined with the Federal Aviation Administration’s (FAA’s) Operations Network (OPSNET) delay data, METARs can be used to identify the major causes of delays and to create delay climatologies for a specific airport. Also, patterns for delays and cancellations for the study period of 2003–15 can be identified for the individual airports included in this study. These patterns can be useful for operators and airport planners to optimize performance in the future.

Context. Realistic synthetic observations of theoretical source models are essential for our understanding of real observational data. In using synthetic data, one can verify the extent to which source parameters can be recovered and evaluate how various data corruption effects can be calibrated. These studies are the most important when proposing observations of new sources, in the characterization of the capabilities of new or upgraded instruments, and when verifying model-based theoretical predictions in a direct comparison with observational data. Aims. We present the SYnthetic Measurement creator for long Baseline Arrays (SYMBA), a novel synthetic data generation pipeline for Very Long Baseline Interferometry (VLBI) observations. SYMBA takes into account several realistic atmospheric, instrumental, and calibration effects. Methods. We used SYMBA to create synthetic observations for the Event Horizon Telescope (EHT), a millimetre VLBI array, which has recently captured the first image of a black hole shadow. After testing SYMBA with simple source and corruption models, we study the importance of including all corruption and calibration effects, compared to the addition of thermal noise only. Using synthetic data based on two example general relativistic magnetohydrodynamics (GRMHD) model images of M 87, we performed case studies to assess the image quality that can be obtained with the current and future EHT array for different weather conditions. Results. Our synthetic observations show that the effects of atmospheric and instrumental corruptions on the measured visibilities are significant. Despite these effects, we demonstrate how the overall structure of our GRMHD source models can be recovered robustly with the EHT2017 array after performing calibration steps, which include fringe fitting, a priori amplitude and network calibration, and self-calibration. With the planned addition of new stations to the EHT array in the coming years, images could be reconstructed with higher angular resolution and dynamic range. In our case study, these improvements allowed for a distinction between a thermal and a non-thermal GRMHD model based on salient features in reconstructed images. © 2020 ESO., This work is supported by the ERC Synergy Grant "BlackHoleCam: Imaging the Event Horizon of Black Holes" (Grant 610058). I. Natarajan and R. Deane are grateful for the support from the New Scientific Frontiers with Precision Radio Interferometry Fellowship awarded by the South African Radio Astronomy Observatory (SARAO), which is a facility of the National Research Foundation (NRF), an agency of the Department of Science and Technology (DST) of South Africa. The authors of the present paper further thank the following organizations and programmes: the Academy of Finland (projects 274477, 284495, 312496); the Advanced European Network of E-infrastructures for Astronomy with the SKA (AENEAS) project, supported by the European Commission Framework Programme Horizon 2020 Research and Innovation action under grant agreement 731016; the Alexander von Humboldt Stiftung; the Black Hole Initiative at Harvard University, through a grant (60477) from the John Templeton Foundation; the China Scholarship Council; Comision Nacional de Investigacio Cientifica y Tecnologica (CONICYT, Chile, via PIA ACT172033, Fondecyt 1171506, BASAL AFB-170002, ALMAconicyt 31140007); Consejo Nacional de Ciencia y Tecnologia (CONACYT, Mexico, projects 104497, 275201, 279006, 281692); the Delaney Family via the Delaney Family John A. Wheeler Chair at Perimeter Institute; Direccion General de Asuntos del Personal Academico-Universidad Nacional Autonoma de Mexico (DGAPA-UNAM, project IN112417); the Generalitat Valenciana postdoctoral grant APOSTD/2018/177; the Gordon and Betty Moore Foundation (grants GBMF-3561, GBMF-5278); the Istituto Nazionale di Fisica Nucleare (INFN) sezione di Napoli, iniziative specifiche TEONGRAV; the GenT Program (Generalitat Valenciana) under project CIDEGENT/2018/021; the International Max Planck Research School for Astronomy and Astrophysics at the Universities of Bonn and Cologne; the Jansky Fellowship program of the National Radio Astronomy Observatory (NRAO); the Japanese Government (Monbukagakusho: MEXT) Scholarship; the Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for JSPS Research Fellowship (JP17J08829); the Key Research Program of Frontier Sciences, Chinese Academy of Sciences (CAS, grants QYZDJ-SSW-SLH057, QYZDJ-SSW-SYS008); the Leverhulme Trust Early Career Research Fellowship; the Max-Planck-Gesellschaft (MPG); the Max Planck Partner Group of the MPG and the CAS; the MEXT/JSPS KAKENHI (grants 18KK0090, JP18K13594, JP18K03656, JP18H03721, 18K03709, 18H01245, 25120007); the MIT International Science and Technology Initiatives (MISTI) Funds; the Ministry of Science and Technology (MOST) of Taiwan (105-2112-M-001-025-MY3, 106-2112-M-001-011, 106-2119-M-001027, 107-2119-M-001-017, 107-2119-M-001-020, and 107-2119-M-110-005); the National Aeronautics and Space Administration (NASA, Fermi Guest Investigator grant 80NSSC17K0649); NASA through the NASA Hubble Fellowship grant #HST-HF2-51431.001-A awarded by the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc. , for NASA, under contract NAS5-26555; the National Institute of Natural Sciences (NINS) of Japan; the National Key Research and Development Program of China (grant 2016YFA0400704, 2016YFA0400702); the National Science Foundation (NSF, grants AST-0096454, AST-0352953, AST-0521233, AST-0705062, AST-0905844, AST-0922984, AST-1126433, AST-1140030, DGE-1144085, AST-1207704, AST-1207730, AST-1207752, MRI-1228509, OPP-1248097, AST-1310896, AST-1312651, AST-1337663, AST-1440254, AST-1555365, AST-1715061, AST-1615796, AST-1716327, OISE-1743747, AST-1816420); the Natural Science Foundation of China (grants 11573051, 11633006, 11650110427, 10625314, 11721303, 11725312, 11933007); the Natural Sciences and Engineering Research Council of Canada (NSERC, including a Discovery Grant and the NSERC Alexander Graham Bell Canada Graduate Scholarships-Doctoral Program); the National Youth Thousand Talents Program of China; the National Research Foundation of Korea (the Global PhD Fellowship Grant: grants NRF-2015H1A2A1033752, 2015-R1D1A1A01056807, the Korea Research Fellowship Program: NRF-2015H1D3A1066561); the Netherlands Organization for Scientific Research (NWO) VICI award (grant 639.043.513) and Spinoza Prize SPI 78-409; the New Scientific Frontiers with Precision Radio Interferometry Fellowship awarded by the South African Radio Astronomy Observatory (SARAO), which is a facility of the National Research Foundation (NRF), an agency of the Department of Science and Technology (DST) of South Africa; the Onsala Space Observatory (OSO) national infrastructure, for the provisioning of its facilities/observational support (OSO receives funding through the Swedish Research Council under grant 2017-00648) the Perimeter Institute for Theoretical Physics (research at Perimeter Institute is supported by the Government of Canada through the Department of Innovation, Science and Economic Development and by the Province of Ontario through the Ministry of Research, Innovation and Science); the Princeton/Flatiron Postdoctoral Prize Fellowship; the Russian Science Foundation (grant 17-12-01029); the Spanish Ministerio de Economia y Competitividad (grants AYA2015-63939-C21-P, AYA2016-80889-P); the State Agency for Research of the Spanish MCIU through the "Center of Excellence Severo Ochoa" award for the Instituto de Astrofisica de Andalucia (SEV-2017-0709); the Toray Science Foundation; the US Department of Energy (USDOE) through the Los Alamos National Laboratory (operated by Triad National Security, LLC, for the National Nuclear Security Administration of the USDOE (Contract 89233218CNA000001)); the Italian Ministero dell'Istruzione Universita e Ricerca through the grant Progetti Premiali 2012-iALMA (CUP C52I13000140001); the European Union's Horizon 2020 research and innovation programme under grant agreement No 730562 RadioNet; ALMA North America Development Fund; the Academia Sinica; Chandra TM6-17006X. This work used the Extreme Science and Engineering Discovery Environment (XSEDE), supported by NSF grant ACI-1548562, and CyVerse, supported by NSF grants DBI-0735191, DBI-1265383, and DBI1743442. XSEDE Stampede2 resource at TACC was allocated through TGAST170024 and TG-AST080026N. XSEDE JetStream resource at PTI and TACC was allocated through AST170028. The simulations were performed in part on the SuperMUC cluster at the LRZ in Garching, on the LOEWE cluster in CSC in Frankfurt, and on the HazelHen cluster at the HLRS in Stuttgart. This research was enabled in part by support provided by Compute Ontario (http://computeontario.ca), Calcul Quebec (http://www. calculquebec.ca) and Compute Canada (http://www.computecanada.ca).We thank the sta ff at the participating observatories, correlation centers, and institutions for their enthusiastic support. This paper makes use of the following ALMA data: ADS/JAO.ALMA#2017.1.00841.V. ALMA is a partnership of the European Southern Observatory (ESO; Europe, representing its member states), NSF, and National Institutes of Natural Sciences of Japan, together with National Research Council (Canada), Ministry of Science and Technology (MOST; Taiwan), Academia Sinica Institute of Astronomy and Astrophysics (ASIAA; Taiwan), and Korea Astronomy and Space Science Institute (KASI; Republic of Korea), in cooperation with the Republic of Chile. The Joint ALMA Observatory is operated by ESO, Associated Universities, Inc. (AUI)/NRAO, and the National Astronomical Observatory of Japan (NAOJ). The NRAO is a facility of the NSF operated under cooperative agreement by AUI. APEX is a collaboration between the Max-Planck-Institut fur Radioastronomie (Germany), ESO, and the Onsala Space Observatory (Sweden). The SMA is a joint project between the SAO and ASIAA and is funded by the Smithsonian Institution and the Academia Sinica. The JCMT is operated by the East Asian Observatory on behalf of the NAOJ, ASIAA, and KASI, as well as the Ministry of Finance of China, Chinese Academy of Sciences, and the National Key R&D Program (No. 2017YFA0402700) of China. Additional funding support for the JCMT is provided by the Science and Technologies Facility Council (UK) and participating universities in the UK and Canada. The LMT is a project operated by the Instituto Nacional de Astrofisica, Optica, y Electronica (Mexico) and the University of Massachusetts at Amherst (USA). The IRAM 30m telescope on Pico Veleta, Spain is operated by IRAM and supported by CNRS (Centre National de la Recherche Scientifique, France), MPG (Max-Planck-Gesellschaft, Germany) and IGN (Instituto Geografico Nacional, Spain). The SMT is operated by the Arizona Radio Observatory, a part of the Steward Observatory of the University of Arizona, with financial support of operations from the State of Arizona and financial support for instrumentation development from the NSF. The SPT is supported by the National Science Foundation through grant PLR-1248097. Partial support is also provided by the NSF Physics Frontier Center grant PHY-1125897 to the Kavli Institute of Cosmological Physics at the University of Chicago, the Kavli Foundation and the Gordon and Betty Moore Foundation grant GBMF 947. The SPT hydrogen maser was provided on loan from the GLT, courtesy of ASIAA. The EHTC has received generous donations of FPGA chips from Xilinx Inc., under the Xilinx University Program. The EHTC has benefited from technology shared under open-source license by the Collaboration for Astronomy Signal Processing and Electronics Research (CASPER). The EHT project is grateful to T4Science and Microsemi for their assistance with Hydrogen Masers. This research has made use of NASA's Astrophysics Data System. We gratefully acknowledge the support provided by the extended staff of the ALMA, both from the inception of the ALMA Phasing Project through the observational campaigns of 2017 and 2018. We would like to thank A. Deller and W. Brisken for EHT-specific support with the use of DiFX. We acknowledge the significance that Maunakea, where the SMA and JCMT EHT stations are located, has for the indigenous Hawaiian people. The software presented in this work makes use of the Numpy (van derWalt et al. 2011), Scipy (Jones et al. 2001), Astropy (Astropy Collaboration 2013, 2018) libraries and the KERN software bundle (Molenaar & Smirnov 2018).

Background Accurate diagnostic tools to identify patients at risk of cancer therapy-related cardiac dysfunction (CTRCD) are critical. For patients undergoing cardiotoxic cancer therapy, ejection fraction assessment using radionuclide ventriculography (RNVG) is commonly used for serial assessment of left ventricular (LV) function. Methods In this retrospective study, approximate entropy (ApEn), synchrony, entropy, and standard deviation from the phase histogram (phase SD) were investigated as potential early markers of LV dysfunction to predict CTRCD. These phase parameters were calculated from the baseline RNVG phase image for 177 breast cancer patients before commencing cardiotoxic therapy. Results Of the 177 patients, 11 had a decline in left ventricular ejection fraction (LVEF) of over 10% to an LVEF below 50% after treatment had commenced. This patient group had a significantly higher ApEn at baseline to those who maintained a normal LVEF throughout treatment. Of the parameters investigated, ApEn was superior for predicting the risk of CTRCD. Combining ApEn with the baseline LVEF further improved the discrimination between the groups. Conclusions The results suggest that RNVG phase analysis using approximate entropy may aid in the detection of sub-clinical LV contraction abnormalities, not detectable by baseline LVEF measurement, predicting a subsequent decline in LVEF.

Strong winds may uproot and break trees and represent a major natural disturbance for European forests. Wind disturbances have intensified over the last decades globally and are expected to further rise in view of the effects of climate change. Despite the importance of such natural disturbances, there are currently no spatially explicit databases of wind-related impact at a pan-European scale. Here, we present a new database of wind disturbances in European forests (FORWIND). FORWIND is comprised of more than 80 000 spatially delineated areas in Europe that were disturbed by wind in the period 2000–2018 and describes them in a harmonized and consistent geographical vector format. The database includes all major windstorms that occurred over the observational period (e.g. Gudrun, Kyrill, Klaus, Xynthia and Vaia) and represents approximately 30 % of the reported damaging wind events in Europe. Correlation analyses between the areas in FORWIND and land cover changes retrieved from the Landsat-based Global Forest Change dataset and the MODIS Global Disturbance Index corroborate the robustness of FORWIND. Spearman rank coefficients range between 0.27 and 0.48 (p value < 0.05). When recorded forest areas are rescaled based on their damage degree, correlation increases to 0.54. Wind-damaged growing stock volumes reported in national inventories (FORESTORM dataset) are generally higher than analogous metrics provided by FORWIND in combination with satellite-based biomass and country-scale statistics of growing stock volume. The potential of FORWIND is explored for a range of challenging topics and scientific fields, including scaling relations of wind damage, forest vulnerability modelling, remote sensing monitoring of forest disturbance, representation of uprooting and breakage of trees in large-scale land surface models, and hydrogeological risks following wind damage. Overall, FORWIND represents an essential and open-access spatial source that can be used to improve the understanding, detection and prediction of wind disturbances and the consequent impacts on forest ecosystems and the land–atmosphere system. Data sharing is encouraged in order to continuously update and improve FORWIND. The dataset is available at https://doi.org/10.6084/m9.figshare.9555008 (Forzieri et al., 2019).

The colocation of clouds and smoke over the southeast Atlantic Ocean during the southern African biomass burning season has numerous radiative implications, including microphysical modulation of the clouds if smoke is entrained into the marine boundary layer. NASA's ObseRvations of Aerosols above CLouds and their intEractionS (ORACLES) campaign is studying this system with aircraft in three field deployments between 2016 and 2018. Results from ORACLES-2016 show that the relationship between cloud droplet number concentration and smoke below cloud is consistent with previously reported values, whereas cloud droplet number concentration is only weakly associated with smoke immediately above cloud at the time of observation. By combining field observations, regional chemistry–climate modeling, and theoretical boundary layer aerosol budget equations, we show that the history of smoke entrainment (which has a characteristic mixing timescale on the order of days) helps explain variations in cloud properties for similar instantaneous above-cloud smoke environments. Precipitation processes can obscure the relationship between above-cloud smoke and cloud properties in parts of the southeast Atlantic, but marine boundary layer carbon monoxide concentrations for two case study flights suggest that smoke entrainment history drove the observed differences in cloud properties for those days. A Lagrangian framework following the clouds and accounting for the history of smoke entrainment and precipitation is likely necessary for quantitatively studying this system; an Eulerian framework (e.g., instantaneous correlation of A-train satellite observations) is unlikely to capture the true extent of smoke–cloud interaction in the southeast Atlantic.

A critical determinant of aircraft performance is density altitude, or the density given as a height above mean sea level, which is dependent on air temperature, pressure, and humidity. These meteorological variables change on various time scales (e.g., hourly, seasonal, and decadal) and are regionally impacted by large-scale climate variability as the result of phenomena such as El Niño–Southern Oscillation or the Arctic Oscillation. Here a statistical analysis is performed to determine the impacts of climate variability on seasonally averaged density altitude, a key metric used by pilots to determine aircraft performance and efficiency, as a function of El Niño–Southern Oscillation and the Arctic Oscillation using NCEP–NCAR reanalysis data and historical aviation meteorological records. Regressions show regional dependencies and impacts to density altitudes that vary as a function of season for both El Niño–Southern Oscillation and Arctic Oscillation cases. The results highlight the importance of understanding the regional nature of the impact of climate variability on density altitude and the potential impacts on aviation operations.

Supplemental Digital Content is available in the text., BACKGROUND: Continuous electroencephalogram monitoring is associated with lower mortality in critically ill patients; however, it is underused due to the resource-intensive nature of manually interpreting prolonged streams of continuous electroencephalogram data. Here, we present a novel real-time, machine learning–based alerting and monitoring system for epilepsy and seizures that dramatically reduces the amount of manual electroencephalogram review. METHODS: We developed a custom data reduction algorithm using a random forest and deployed it within an online cloud-based platform, which streams data and communicates interactively with caregivers via a web interface to display algorithm results. We developed real-time, machine learning–based alerting and monitoring system for epilepsy and seizures on continuous electroencephalogram recordings from 77 patients undergoing routine scalp ICU electroencephalogram monitoring and tested it on an additional 20 patients. RESULTS We achieved a mean seizure sensitivity of 84% in cross-validation and 85% in testing, as well as a mean specificity of 83% in cross-validation and 86% in testing, corresponding to a high level of data reduction. This study validates a platform for machine learning–assisted continuous electroencephalogram analysis and represents a meaningful step toward improving utility and decreasing cost of continuous electroencephalogram monitoring. We also make our high-quality annotated dataset of 97 ICU continuous electroencephalogram recordings public for others to validate and improve upon our methods.