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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.

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.

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.

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.

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.

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.

Left ventricular dyssynchrony can be assessed with phase parameters from radionuclide ventriculography (RNVG), including approximate entropy ( ApEn ). The input values used to calculate ApEn will affect the results significantly, so it is essential to optimise ApEn for the application. However to date, no optimisation for ApEn applied to images has been published. In this paper, generated data were used to simulate patient phase images, allowing the input parameters for ApEn to be tested and optimised in a controlled environment. Clinical images were then used to confirm that the selected parameters were appropriate. The results demonstrate the effect of input parameters for ApEn and the most appropriate use with RNVG phase images. This work demonstrates the importance of optimisation and standardisation when using ApEn as a measure of dyssynchrony.

Aerosols are a critical component of the Earth's atmosphere and can affect the climate of the Earth through their interactions with solar radiation and clouds. Cloud fraction (CF) and aerosol optical depth at 550 nm (AOD) from the MOderate Resolution Imaging Spectroradiometer (MODIS) are used with analogous cloud and aerosol properties from Historical Phase 5 of the Coupled Model Inter-comparison Project (CMIP5) model runs that explicitly include anthropogenic aerosols and parameterized cloud-aerosol interactions. The models underestimate AOD by approximately 15% and underestimate CF by approximately 10% overall on a global scale. A regional analysis is then used to evaluate model performance in two regions with known biomass burning activity and absorbing aerosol (South America, SAM; South Africa, SAF). In SAM, the models overestimate AOD by 4.8% and underestimate CF by 14%. In SAF, the models underestimate AOD by 35% and overestimate CF by 13.4%. Average annual cycles show that the monthly timing of AOD peaks closely match satellite data in both SAM and SAF for all except the CAM5 and GFDL models. Monthly timing of CF peaks closely match for all models (except GFDL) for SAM and SAF. Sorting monthly averaged 2° x 2.5° model or MODIS CF as a function of AOD does not result in the previously observed “boomerang” shaped CF vs. AOD relationships characteristic of regions with absorbing aerosols from biomass burning. Cloud-aerosol interactions, as observed using daily (or higher) temporal resolution data, is not reproducible at the spatial or temporal resolution provided by the CMIP5 models.

The article of record as published may be found at http://dx.doi.org/10.5194/acp-16-21-2016 Vertical transport associated with cumulus clouds is important to the redistribution of gases, particles, and energy, with subsequent consequences for many aspects of the climate system. Previous studies have suggested that detrainment from clouds can be comparable to the updraft mass flux, and thus represents an important contribution to vertical transport. In this study, we describe a new method to deduce the amounts of gross detrainment and entrainment experienced by non-precipitating cumulus clouds using aircraft observations. The method utilizes equations for three conserved variables: cloud mass, total water, and moist static energy. Optimizing these three equations leads to estimates of the mass fractions of adiabatic mixed-layer air, entrained air and detrained air that the sampled cloud has experienced. The method is applied to six flights of the CIRPAS Twin Otter during the Gulf of Mexico Atmospheric Composition and Climate Study (GoMACCS) which took place in the Houston, Texas region during the summer of 2006 during which 176 small, non-precipitating cumuli were sampled. Using our novel method, we find that, on average, these clouds were comprised of 30 to 70% mixed-layer air, with entrained air comprising most of the remainder. The mass fraction of detrained air was usually very small, less than 2 %, although values larger than 10% were found in 15% of clouds. Entrained and detrained air mass fractions both increased with altitude, consistent with some previous observational studies. The largest detrainment events were almost all associated with air that was at their level of neutral buoyancy, which has been hypothesized in previous modeling studies. This new method could be readily used with data from other previous aircraft campaigns to expand our understanding of detrainment for a variety of cloud systems. Physical Meteorology program of the National Science Foundation (AGS-1139746) CIRPAS Twin Otter team NOAA Physical Meteorology program of the National Science Foundation (AGS-1139746)

Hypoxia induces precocious hatching in zebrafish, but we do not have a clear understanding of the molecular mechanisms regulating the activation of the hatching enzyme or how these mechanisms trigger precocious hatching under unfavorable environmental conditions. Using immunohistochemistry, pharmacological inhibition of matrix metalloproteinase 13 (Mmp13), and in vivo zymography, we show that Mmp13a is present in the hatching gland just as embryos become hatching competent and that Mmp13a activity is required for both normal hatching and hypoxia-induced precocious hatching. We conclude that Mmp13a likely functions in activating the hatching enzyme zymogen and that Mmp13a activity is necessary but not sufficient for hatching in zebrafish. This study highlights the broad nature of MMP function in development and provides a non-mammalian example of extra-embryonic processes mediated by MMP activity.

Aerosol–cloud interactions are complex, including albedo and lifetime effects that cause modifications to cloud characteristics. With most cloud–aerosol interactions focused on the previously stated phenomena, there has been no in–situ studies that focus explicitly on how aerosols can affect droplet clustering within clouds. This research therefore aims to gain a better understanding of how droplet clustering within cumulus clouds can be influenced by in–cloud droplet location (cloud edge vs. center) and aerosol number concentration. The pair–correlation function (PCF) is used to identify the magnitude of droplet clustering from data collected onboard the Center for interdisciplinary Remotely–Piloted Aircraft Studies (CIRPAS) Twin Otter aircraft, flown during the 2006 Gulf of Mexico Atmospheric Composition and Climate Study (GoMACCS). Time stamps (at 10−4 m spatial resolution) of cloud droplet arrival times were measured by the Artium Flight Phase–Doppler Interferometer (PDI). Using four complete days of data with 81 non–precipitating cloud penetrations organized into two flights of low (L1, L2) and high (H1, H2) pollution data shows more clustering near cloud edge as compared to cloud center for all four cases. Low pollution clouds are shown to have enhanced overall clustering, with flight L2 being solely responsible for this enhanced clustering. Analysis suggests cloud age plays a larger role in the clustering amount experienced than the aerosol number concentration, with dissipating clouds showing increased clustering as compared to growing or mature clouds. Results using a single, vertically developed cumulus cloud demonstrate more clustering near cloud top as compared to cloud base.

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 ObseRvtions 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. 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 are also expected to obscure the relationship between above-cloud smoke and cloud properties in parts of the southeast Atlantic, although 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.

Immune checkpoint inhibitors have revolutionized cancer therapy. Given their mechanism of action, immune-related adverse events have been associated with their use. We present the first documented case of pembrolizumab-induced grade IV neutropenia. A 73-year-old women known for myositis, Crohn's disease, and hypothyroidism and diagnosed with PD-L1 positive stage IV pulmonary adenocarcinoma is treated with Pembrolizumab. She develops grade IV neutropenia 2 weeks after her second infusion. She is therefore hospitalized and treated initially with corticosteroids, granulocyte colony-stimulating factor, and intravenous immunoglobulins. Given the persistent neutropenia, cyclosporine was added, but quickly stopped owing to fever. The patient recovered her neutrophils 6.5 weeks after her initial Pembrolizumab infusion and 12 days after admission. She has been subsequently successfully tapered off steroids with no recurrence after 3 months of follow-up. This is the first case of grade IV neutropenia secondary to Pembrolizumab. This case is of particular interest given the patient's pre-existing autoimmune history. Treatment of severe neutropenia due to other PD1 inhibitors has generally consisted of steroids, granulocyte colony-stimulating factor, intravenous immunoglobulins, mycophenolate mofetil, cyclosporine A, and anti-thymocyte globulins - though the benefits of immunosuppression are not clear and may be harmful given the infectious risks. Large studies are required to clarify the spectrum and optimal management of immune-related adverse events and overall risk/benefits of immune checkpoint inhibitors in patients with pre-existing autoimmunity.