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Artificial intelligence (AI) solutions that automatically extract information from digital histology images have shown great promise for improving pathological diagnosis. Prior to routine use, it is important to evaluate their predictive performance and obtain regulatory approval. This assessment requires appropriate test datasets. However, compiling such datasets is challenging and specific recommendations are missing. A committee of various stakeholders, including commercial AI developers, pathologists, and researchers, discussed key aspects and conducted extensive literature reviews on test datasets in pathology. Here, we summarize the results and derive general recommendations on compiling test datasets. We address several questions: Which and how many images are needed? How to deal with low-prevalence subsets? How can potential bias be detected? How should datasets be reported? What are the regulatory requirements in different countries? The recommendations are intended to help AI developers demonstrate the utility of their products and to help pathologists and regulatory agencies verify reported performance measures. Further research is needed to formulate criteria for sufficiently representative test datasets so that AI solutions can operate with less user intervention and better support diagnostic workflows in the future.

Artificial intelligence (AI) solutions that automatically extract information from digital histology images have shown great promise for improving pathological diagnosis. Prior to routine use, it is important to evaluate their predictive performance and obtain regulatory approval. This assessment requires appropriate test datasets. However, compiling such datasets is challenging and specific recommendations are missing. A committee of various stakeholders, including commercial AI developers, pathologists, and researchers, discussed key aspects and conducted extensive literature reviews on test datasets in pathology. Here, we summarize the results and derive general recommendations on compiling test datasets. We address several questions: Which and how many images are needed? How to deal with low-prevalence subsets? How can potential bias be detected? How should datasets be reported? What are the regulatory requirements in different countries? The recommendations are intended to help AI developers demonstrate the utility of their products and to help pathologists and regulatory agencies verify reported performance measures. Further research is needed to formulate criteria for sufficiently representative test datasets so that AI solutions can operate with less user intervention and better support diagnostic workflows in the future.

The dynamical environment of the stratosphere, during the summer over North America, provides a natural integrator of the impact of convection in the lower stratosphere, as air can be confined for periods of a few days to more than a week. In situ data obtained during the NASA Dynamics and Chemistry of the Summer Stratosphere (DCOTSS) field campaign show increasing water vapor mixing ratios in background air as a function of time the air parcel spent within the North American Monsoon Anticyclone region. We find that water vapor added to the stratosphere by convection decreases with altitude and tends to drop below detectable limits by the 415 K isentrope in 2021 and the 430 K isentrope in 2022. Integrating between potential temperatures of 380 and 460 K we find that convection added between 20 and 32 Tg per summer to the stratosphere in 2021 and 2022. While the total amount is only 1%–4% of the amount ascending in the tropics across the tropical tropopause, small changes in the annual flux of water can have a significant effect on the radiation budget of the atmosphere. Locally, over North America we find that convection increased the water vapor mixing ratio at 380 K by as much as 40%. Tropopause‐penetrating convection is part of the yearly cycle of stratospheric water vapor and we suggest that it must be included in extratropical models to accurately predict future trends in stratospheric water vapor. Water vapor in the stratosphere is important for regulating Earth's climate and also influences the amount of ozone in the stratosphere. Most air rises into the stratosphere through the tropical tropopause where the excess water freezes out leaving very dry air. But air and water can also be injected into the stratosphere via strong convective storm systems. During the summer months, strong storms over the Sierra Madre Occidental and the central United States are known to produce many overshoots that can be seen with radar and satellite. A recent NASA airborne campaign called Dynamics and Chemistry of the Summer Stratosphere (DCOTSS) aimed to study this region. The aircraft was equipped with 12 different sensors measuring gases, aerosols, and meteorological variables. We use these measurements to look at the cumulative effect these storms have on the background air in the stratosphere and specifically calculate the amount of water vapor added by convection as a function of altitude above the tropopause. We find that water added by storms over North America is 1%–4% of the total amount ascending in the tropics. Over North America convection may account for as much as a 40% increase in lower stratospheric water vapor. Deep convection over North America lofts significant amounts of water to the lower stratosphereThe North American Monsoon Anticyclone (NAMA) provides a natural integrator of convective perturbations to the stratosphereConvective detrainment of water vapor and ice is quantified by looking at changes in background air as a function of time spent in the NAMA Deep convection over North America lofts significant amounts of water to the lower stratosphere The North American Monsoon Anticyclone (NAMA) provides a natural integrator of convective perturbations to the stratosphere Convective detrainment of water vapor and ice is quantified by looking at changes in background air as a function of time spent in the NAMA

Hydration of the stratosphere by tropopause‐overshooting convection has received increasing interest due to the extreme concentrations of water vapor that can result and, ultimately, the climate warming potential such hydration provides. Previous work has recognized the importance of numerous dynamic and physical processes that control stratospheric water vapor delivery by convection. This study leverages recent comprehensive observations from the NASA Dynamics and Chemistry of the Summer Stratosphere (DCOTSS) field campaign to determine the frequency at which each process operates during real events. Specifically, a well‐established analysis technique known as tracer‐tracer correlation is applied to DCOTSS observations of ozone, water vapor, and potential temperature to identify the occurrence of known processes. It is found that approximately half of convectively‐driven stratospheric hydration samples show no indication of significant air mass transport and mixing, emphasizing the importance of ice sublimation to stratospheric water vapor delivery. Furthermore, the temperature of the upper troposphere and lower stratosphere environment and/or overshoot appears to be a commonly active constraint, since the approximate maximum possible water vapor concentration that can be reached in an air mass is limited to the saturation mixing ratio when ice is present. Finally, little evidence of relationships between dynamic and physical processes and their spatial distribution was found, implying that stratospheric water vapor delivery by convection is likely facilitated by a complex collection of processes in each overshooting event. Thunderstorms are capable of transporting air and water up to the second layer of Earth's atmosphere, the stratosphere. Resulting irreversible modifications to greenhouse gases that regulate climate, such as water vapor and ozone, are important to quantify and poorly understood. This study uses recently‐obtained aircraft observations to improve understanding of irreversible transport in thunderstorms and the environmental and storm factors that control it. By examining how multiple trace gases and other quantities co‐vary, it is found that half of observed stratospheric changes by thunderstorms only exhibit increases in water vapor, which is argued to be driven by transported ice. It is also found that the environmental temperature is an important constraint in any storm because it limits the amount of stratospheric water vapor change that can occur. Recent airborne observations reveal key dynamic and physical processes controlling the stratospheric delivery of water vapor by convectionIn situ observations suggest that water vapor is delivered routinely via both air transport and ice sublimationTemperature is an important constraint for water vapor delivery in any stratospheric environment Recent airborne observations reveal key dynamic and physical processes controlling the stratospheric delivery of water vapor by convection In situ observations suggest that water vapor is delivered routinely via both air transport and ice sublimation Temperature is an important constraint for water vapor delivery in any stratospheric environment

Mortality in children with kidney failure is higher in girls than boys with cardiovascular complications representing the most common causes of death. Pulse wave velocity (PWV), a measure of vascular stiffness, predicts cardiovascular mortality in adults. Here, PWV in children with kidney failure undergoing kidney replacement therapy was investigated to determine sex differences and potential contributing factors. Two-hundred thirty-five children (80 girls; 34%) undergoing transplantation (150 pre-emptive, 85 with prior dialysis) having at least one PWV measurement pre- and/or post-transplantation from a prospective cohort were analyzed. Longitudinal analyses (median/maximum follow-up time of 6/9 years) were performed for PWV z-scores (PWVz) using linear mixed regression models and further stratified by the categories of time: pre-kidney replacement therapy and post-transplantation. PWVz significantly increased by 0.094 per year and was significantly higher in girls (PWVz +0.295) compared to boys, independent of the underlying kidney disease. During pre-kidney replacement therapy, an average estimated GFR decline of 4 ml/min/1.73 m2per year was associated with a PWVz increase of 0.16 in girls only. Higher diastolic blood pressure and low density lipoprotein were independently associated with higher PWVz during pre-kidney replacement therapy in both sexes. In girls post-transplantation, an estimated GFR decline of 4ml/min/1.73m2per year pre-kidney replacement therapy and a longer time (over 12 months) to transplantation were significantly associated with higher PWVz of 0.22 and of 0.57, respectively. PWVz increased further after transplantation and was positively associated with time on dialysis and diastolic blood pressure in both sexes. Thus, our findings demonstrate that girls with advanced chronic kidney disease are more susceptible to develop vascular stiffening compared to boys, this difference persist after transplantation and might contribute to higher mortality rates seen in girls with kidney failure.

Glutamine synthetase (GS) catalyzes an ATP-dependent condensation of glutamate and ammonia to form glutamine. This reaction—and therefore GS—are indispensable for the hepatic nitrogen metabolism. Nitration of tyrosine 336 (Y336) inhibits human GS activity. GS nitration and the consequent loss of GS function are associated with a broad range of neurological diseases. The mechanism by which Y336 nitration inhibits GS, however, is not understood. Here, we show by means of unbiased MD simulations, binding, and configurational free energy computations that Y336 nitration hampers ATP binding but only in the deprotonated and negatively charged state of residue 336. By contrast, for the protonated and neutral state, our computations indicate an increased binding affinity for ATP. pKacomputations of nitrated Y336 within GS predict a pKaof ∼5.3. Thus, at physiological pH, nitrated Y336 exists almost exclusively in the deprotonated and negatively charged state. In vitroexperiments confirm these predictions, in that, the catalytic activity of nitrated GS is decreased at pH 7 and 6 but not at pH 4. These results indicate a novel, fully reversible, pH-sensitive mechanism for the regulation of GS activity by tyrosine nitration.

Wildfires are extreme events associated with weather, climate, and environment and have been increasing globally in frequency, burn season length, and burned area. It is of great interest to understand the impacts of wildfires on severe convective storms through releasing heat and aerosols into the atmosphere. We have developed a model capability that can account for the impact of sensible heat fluxes from wildfires on thermodynamics and is computationally efficient. The pyrocumulonimbus clouds associated with the Texas Mallard Fire on 11–12 May 2018 are well simulated by accounting for both heat and aerosols emitted from the wildfire. Both heat and aerosol effects increase low‐level temperatures and midlevel buoyancy and enhance convective intensity. Intensified convection along with more supercooled liquid condensate due to stronger vertical transport results in larger hailstones and enhanced lightning. The effects of heat flux on the convective extremes are more significant than those of aerosol emissions. The length of wildfire burning season and burned area have been increasing globally. Besides being a globally important source of aerosol particles that could impact clouds, precipitation, and radiation, wildfire activity heats the environment dramatically and can significantly perturb the environmental thermodynamics. However, this impact on environmental thermodynamics and the subsequent convection generated is poorly represented in models. We have developed and evaluated a model capability that accounts for the impact of heat flux from wildfires and is computationally efficient. We have used the new model to explore a pyrocumulonimbus event that occurred in Texas and Oklahoma on 11–12 May 2018 triggered by the Mallard Fire. The simulation accounting for effects of both heat flux and aerosol emissions from the wildfire predicts radar reflectivity, precipitation, hailstone size, and lightning reasonably well based on comparisons with observations. Both the heat flux and aerosol emissions from the wildfire increase low‐level temperatures and midlevel thermal buoyancy significantly, causing stronger upward motion that lifts more supercooled water to higher levels. The increase in available supercooled water for hail growth and invigorated updrafts leads to larger hail size and enhanced lightning. The effect of heat flux on storm intensity is considerably more significant than that of aerosol emissions. A new model capability to computationally efficiently account for the impact of heat flux on thermodynamics from wildfires in WRF‐Chem is developedBoth the heat and aerosol emissions from wildfires invigorate the pyroconvection, enlarge hail size, and enhance lightningEffects of heat from wildfire on convective intensity, hail size, and lightning are more significant than those of aerosol emissions

Pre-operative risk factors for post-operative ventilation and their influence on survival after pancreaticoduodenectomy for malignancy are unknown.

Urinary catheterization is one of the most common medical procedures that makes a patient susceptible to infection due to biofilm formation on the urinary catheter. Catheter associated urinary tract infections (CAUTIs) are responsible for over 1 million cases in the United States alone and cost the healthcare industry more than $350 million every year. This work presents a liquid-infused nitric-oxide-releasing (LINORel) urinary catheter fabricated by incorporating the nitric oxide (NO) donor S-nitroso-N-acetylpenicillamine (SNAP) and silicone oil into commercial silicone Foley catheters through a two-stage swelling process. This synergistic combination improves NO-releasing materials by providing minimal SNAP leaching and a more controlled release of NO while incorporating the nonfouling characteristics of liquid-infused materials. The LINORel urinary catheter was successful in sustaining a controlled NO release over a 60 day period under physiological conditions with minimal SNAP leaching during the initial 24 h period, 0.49 ± 0.0061%. The LINORel-UC proved successful in reducing bacterial adhesion and biofilm formation for Gram positive Staphylococcus aureus(98.49 ± 2.06%) over a 7 day period in a drip flow bioreactor environment. Overall, this study presents a desirable combination that incorporates the antifouling advantages of liquid-infused materials with the active release of a bactericidal agent, an uncharted territory in aiding to prevent the risk of CAUTIs.

Conventional fluorescent tubes are increasingly being replaced with innovative light-emitting diodes (LEDs) for lighting poultry houses. However, little is known about whether the flicker frequencies of LED luminaires are potential stressors in poultry husbandry. The term “light flicker” describes the fluctuations in the brightness of an electrically operated light source caused by the design and/or control of the light source. In this context, the critical flicker frequency (CFF) characterizes the frequency at which a sequence of light flashes is perceived as continuous light. It is known that CFF in birds is higher than that in humans and that light flicker can affect behavioral patterns and stress levels in several bird species. As there is a lack of knowledge about the impact of flicker frequency on fattening turkeys, this study aimed to investigate the effects of flicker frequency on the behavior, performance, and stress response in male turkeys. In 3 trials, a total of 1,646 male day-old turkey poults of the strain B.U.T. 6 with intact beaks were reared for 20 wk in 12 barn compartments of 18 m² each. Each barn compartment was illuminated using 2 full-spectrum LED lamps. Flicker frequencies of 165 Hz, 500 Hz, and 16 kHz were set in the luminaires to illuminate the compartments. Analyses of feather corticosterone concentration were performed on fully grown third-generation primaries (P 3) of 5 turkeys from each compartment. No significant differences were found in the development of live weight, feed consumption, or prevalence of injured or killed turkeys by conspecifics reared under the above flicker frequencies. The flicker frequencies also did not significantly influence feather corticosterone concentrations in the primaries of the turkeys. In conclusion, the present results indicate that flicker frequencies of 165 Hz or higher have no detrimental effect on growth performance, injurious pecking, or endocrine stress response in male turkeys and, thus, may be suitable for use as animal-friendly lighting.

The European Union (EU) began developing climate policy in the 1990s. Since then, it has built up a broad portfolio of mitigation policy measures and governance tools, including legally binding targets to reduce greenhouse gas (GHG) emissions, and policy measures addressing emissions trading, renewable energy, energy efficiency, and more. In 2019, the European Commission—the EU's executive arm—published the European Green Deal (EGD), an overarching policy framework to achieve the goal of climate neutrality by 2050. The EGD aims to push EU climate policy and governance far beyond incremental policy development. In this article, we ask: does the EGD represent a break from past patterns of EU climate governance? We argue that it maintains several past patterns, but nevertheless breaks from other established policy and governance trends. We review insights from politicization and new institutionalist theoretical lenses to help us understand these findings. We reveal certain tensions and challenges inherent in the EU's climate governance approach—around speed and coherence, effectiveness and just transition—that highlight future research needs, and raise questions about the EU's ability to implement its climate policy goals. This article is categorized under:Policy and Governance > Multilevel and Transnational Climate Change Governance A timeline of three decades of evolving climate policy in the European Union, including renewable energy, energy efficiency, emissions trading and other policies, until the European Green Deal that was published in 2019.

The National Cancer Institute Imaging Data Commons is part of the broader Cancer Research Data Commons infrastructure that hosts publicly available cancer imaging data co-located with analysis and exploration resources, with strong emphasis on data harmonization, establishing best practices for cancer imaging data management, and developing use cases to support transparent, reproducible, and scalable imaging research.

Pathology laboratories are increasingly using digital workflows. This has the potential of increasing laboratory efficiency, but the digitization process also involves major challenges. Several reports have been published describing the individual experiences of specific laboratories with the digitization process. However, a comprehensive overview of the lessons learned is still lacking. We provide an overview of the lessons learned for different aspects of the digitization process, including digital case management, digital slide reading, and computer-aided slide reading. We also cover metrics used for monitoring performance and pitfalls and corresponding values observed in practice. The overview is intended to help pathologists, information technology decision makers, and administrators to benefit from the experiences of others and to implement the digitization process in an optimal way to make their own laboratory future-proof.

Visceral leishmaniasis causes considerable mortality and morbidity in many parts of the world. There is an urgent need for the development of new, effective treatments for this disease. Here we describe the development of an anti-leishmanial drug-like chemical series based on a pyrazolopyrimidine scaffold. The leading compound from this series (7, DDD853651/GSK3186899) is efficacious in a mouse model of visceral leishmaniasis, has suitable physicochemical, pharmacokinetic and toxicological properties for further development, and has been declared a preclinical candidate. Detailed mode-of-action studies indicate that compounds from this series act principally by inhibiting the parasite cdc-2-related kinase 12 (CRK12), thus defining a druggable target for visceral leishmaniasis.

Deep convective transport of gaseous precursors to ozone (O3) and aerosols to the upper troposphere is affected by liquid phase and mixed‐phase scavenging, entrainment of free tropospheric air and aqueous chemistry. The contributions of these processes are examined using aircraft measurements obtained in storm inflow and outflow during the 2012 Deep Convective Clouds and Chemistry (DC3) experiment combined with high‐resolution (dx≤3 km) WRF‐Chem simulations of a severe storm, an air mass storm, and a mesoscale convective system (MCS). The simulation results for the MCS suggest that formaldehyde (CH2O) is not retained in ice when cloud water freezes, in agreement with previous studies of the severe storm. By analyzing WRF‐Chem trajectories, the effects of scavenging, entrainment, and aqueous chemistry on outflow mixing ratios of CH2O, methyl hydroperoxide (CH3OOH), and hydrogen peroxide (H2O2) are quantified. Liquid phase microphysical scavenging was the dominant process reducing CH2O and H2O2outflow mixing ratios in all three storms. Aqueous chemistry did not significantly affect outflow mixing ratios of all three species. In the severe storm and MCS, the higher than expected reductions in CH3OOH mixing ratios in the storm cores were primarily due to entrainment of low‐background CH3OOH. In the air mass storm, lower CH3OOH and H2O2scavenging efficiencies (SEs) than in the MCS were partly due to entrainment of higher background CH3OOH and H2O2. Overestimated rain and hail production in WRF‐Chem reduces the confidence in ice retention fraction values determined for the peroxides and CH2O. Methyl hydroperoxide mixing ratios are decreased mainly by entrainment and liquid phase and mixed‐phase scavengingHydrogen peroxide and formaldehyde mixing ratios affected more by liquid phase scavenging than by entrainment or aqueous chemistryOverestimated rain/hail production in WRF‐Chem reduces confidence in ice retention fraction values determined for peroxides and formaldehyde

Water vapor's contribution to Earth's radiative forcing is most sensitive to changes in its lower stratosphere concentration. One recognized pathway for rapid increases in stratospheric water vapor is tropopause‐overshooting convection. Since this pathway has been rarely sampled, the NASA Dynamics and Chemistry of the Summer Stratosphere (DCOTSS) field project focused on obtaining in situ observations of stratospheric air recently affected by convection over the United States. This study reports on the extreme altitudes to which convective hydration was observed. The data show that the overworld stratosphere is routinely hydrated by convection and that past documented records of stratospheric heights of convective hydration were exceeded during several DCOTSS flights. The most extreme event sampled is highlighted, for which stratospheric water vapor was increased by up to 26% at an altitude of 19.25 km, a potential temperature of 463 K, and an ozone mixing ratio >1500 ppbv. When thunderstorms reach into the second layer of the atmosphere above Earth's surface, the stratosphere, they may impact the concentration and distribution of trace gases that are important to chemistry and climate. One gas that is routinely affected during these events is water vapor, which is typically scarce in the stratosphere. This study presents new aircraft observations of extreme heights in the stratosphere moistened by these thunderstorms. Since increases in stratospheric water vapor positively contribute to warming of Earth's climate and can activate chemistry that destroys ozone, better understanding of this phenomenon helps refine our understanding of its role in the climate system. The new aircraft observations provide clear evidence that water vapor is enhanced by thunderstorms at higher levels in the stratosphere than previously recognized. Tropopause‐overshooting convection in the United States hydrates the stratosphere to exceptional heightsObservations of the height of stratospheric convective hydration during the Dynamics and Chemistry of the Summer Stratosphere field campaign exceed all prior global recordsThe overworld stratosphere is routinely hydrated by midlatitude overshooting convection Tropopause‐overshooting convection in the United States hydrates the stratosphere to exceptional heights Observations of the height of stratospheric convective hydration during the Dynamics and Chemistry of the Summer Stratosphere field campaign exceed all prior global records The overworld stratosphere is routinely hydrated by midlatitude overshooting convection

Stratosphere‐troposphere exchange (STE) is important to the global radiation budget because it is capable of inducing significant changes in trace greenhouse gases such as ozone and water vapor. In the extratropics, stratosphere‐to‐troposphere—or downward—transport (STT) dominates and is routinely driven by upper‐troposphere jet circulations and cyclones. Tropopause‐overshooting convection provides a more rapid STE pathway, but STT in convection is less understood and targeted observations are limited to a handful of fortuitous aircraft encounters. In this study, we seek to improve understanding of STT near thunderstorm anvils using balloon observations of ozone, ground‐based radar observations, visible satellite imagery, and model output. Radar and satellite imagery are used to identify and ultimately target convection driving the “ozone‐wrapping” process. Herein, observations from a single mesoscale convective system in central Oklahoma are reported. A significant ozone enhancement 40%–60% greater than background concentrations in the free troposphere was observed during the balloon ascent underneath and within the anvil of the storm. Backwards particle trajectories were calculated to rule out other sources of this feature such as long‐range transport of stratospheric air and smoke pollution from nearby wildfires. To our knowledge, this work presents the first targeted ozonesonde launch and sampling of this STT process. Ozone is an important greenhouse gas in the atmosphere that contributes to global climate change. Thunderstorms are one of many processes that transport stratospheric air (high in ozone) to the troposphere, but few studies examine the extent to which thunderstorms impact ozone concentrations in the upper troposphere via this process. In this study, we use novel balloon observations of ozone and additional observations of a storm and its environment to measure ozone change in the upper troposphere. During the passage of a large thunderstorm complex in central Oklahoma on 2 May 2022, our balloon observations measured significant ozone enhancement 40%–60% greater than background concentrations near the periphery of the storm in the upper troposphere. Other potential sources of this feature such as long‐range transport of stratospheric air and smoke pollution from nearby wildfires were ruled out. To our knowledge, this work presents the first targeted balloon launch and sampling of high ozone in the troposphere that was transported from the stratosphere by a thunderstorm. The first known successful balloon sampling of the anvil wrapping stratosphere‐to‐troposphere transport process in midlatitude convectionOzone enhancements within the observed anvil wrapping are 40%–60% greater than background troposphere concentrationsSimilar ozone enhancements are found within the observed storm anvil The first known successful balloon sampling of the anvil wrapping stratosphere‐to‐troposphere transport process in midlatitude convection Ozone enhancements within the observed anvil wrapping are 40%–60% greater than background troposphere concentrations Similar ozone enhancements are found within the observed storm anvil

Convection that penetrates the tropopause (overshooting convection) rapidly transports air from the lower troposphere to the lower stratosphere, potentially mixing air between the two layers. This exchange of air can have a substantial impact on the composition, radiation, and chemistry of the upper troposphere and lower stratosphere (UTLS). In order to improve our understanding of the role convection plays in the transport of trace gases across the tropopause, this study presents a 10 year analysis of overshooting convection for the eastern two thirds of the contiguous United States for March through August of 2004 to 2013 based on radar observations. Echo top altitudes are estimated at hourly intervals using high‐resolution, three‐dimensional, gridded, radar reflectivity fields created by merging observations from available radars in the National Oceanic and Atmospheric Administration Next Generation Weather Radar (NEXRAD) network. Overshooting convection is identified by comparing echo top altitudes with tropopause altitudes derived from the ERA‐Interim reanalysis. It is found that overshooting convection is most common in the central United States, with a weak secondary maximum along the southeast coast. The maximum number of overshooting events occur consistently between 2200 and 0200 UTC. Most overshooting events occur in May, June, and July when convection is deepest and the tropopause altitude is relatively low. Approximately 45% of the analyzed overshooting events (those with echo tops at least 1 km above the tropopause) have echo tops extending above the 380 K level into the stratospheric overworld. A new analysis of NEXRAD radar data shows the spatial and temporal occurrence of tropopause‐overshooting convection over the United StatesTen years of high‐resolution gridded NEXRAD data (GridRad) are now available through the NCAR Research Data ArchiveOvershooting convection is most common over the central United States; almost half of observed overshooting events reach 380 K or higher

On 27 August 2013, during the Studies of Emissions and Atmospheric Composition, Clouds and Climate Coupling by Regional Surveys field mission, NASA's ER‐2 research aircraft encountered a region of enhanced water vapor, extending over a depth of approximately 2 km and a minimum areal extent of 20,000 km2in the stratosphere (375 K to 415 K potential temperature), south of the Great Lakes (42°N, 90°W). Water vapor mixing ratios in this plume, measured by the Harvard Water Vapor instrument, constitute the highest values recorded in situ at these potential temperatures and latitudes. An analysis of geostationary satellite imagery in combination with trajectory calculations links this water vapor enhancement to its source, a deep tropopause‐penetrating convective storm system that developed over Minnesota 20 h prior to the aircraft plume encounter. High resolution, ground‐based radar data reveal that this system was composed of multiple individual storms, each with convective turrets that extended to a maximum of ~4 km above the tropopause level for several hours. In situ water vapor data show that this storm system irreversibly delivered between 6.6 kt and 13.5 kt of water to the stratosphere. This constitutes a 20–25% increase in water vapor abundance in a column extending from 115 hP to 70 hPa over the plume area. Both in situ and satellite climatologies show a high frequency of localized water vapor enhancements over the central U.S. in summer, suggesting that deep convection can contribute to the stratospheric water budget over this region and season. A plume containing highly elevated water vapor concentrations was observed in situ in the stratosphere over the U.S. in summerUsing a combination of diverse data sets, the observed enhancement in stratospheric humidity is linked to a deep convective storm systemThe quantity of water vapor irreversibly delivered to the lower stratosphere by this convective storm system is calculated

We examine three case studies during the Deep Convective Clouds and Chemistry (DC3) field experiment when storm inflow and outflow air were sampled for aerosol subsaturated hygroscopicity and the real part of refractive index (n) with a Differential Aerosol Sizing and Hygroscopicity Probe (DASH‐SP) on the NASA DC‐8. Relative to inflow aerosol particles, outflow particles were more hygroscopic (by 0.03 based on the estimated κparameter) in one of the three storms examined. Two of three “control” flights with no storm convection reveal higher κvalues, albeit by only 0.02, at high altitude (> 8 km) versus < 4 km. Entrainment modeling shows that measured κvalues in the outflow of the three storm flights are higher than predicted values (by 0.03–0.11) based on knowledge of κvalues from the inflow and clear air adjacent to the storms. This suggests that other process(es) contributed to hygroscopicity enhancements such as secondary aerosol formation via aqueous‐phase chemistry. Values of nwere higher in the outflow of two of the three storm flights, reaching as high as 1.54. More statistically significant differences were observed in control flights (no storms) where ndecreased from 1.50–1.52 (< 4 km) to 1.49–1.50 (> 8 km). Chemical data show that enhanced hygroscopicity was coincident with lower organic mass fractions, higher sulfate mass fractions, and higher O:C ratios of organic aerosol. Refractive index did not correlate as well with available chemical data. Deep convection is shown to alter aerosol radiative properties, which has implications for aerosol effects on climate. Mean kappa values measured in outflows exceed those predicted by an altitude‐dependent entrainment modelRefractive index is lower aloft (> 8 km versus < 4 km) in nonstorm conditions with high statistical significance, unlike on storm days with inflow and outflow dataEnhanced hygroscopicity coincides with lower organic mass fraction, higher sulfate mass fraction, and higher O:C ratios of organic aerosol

Convective clouds are important for both the vertical redistribution of tropospheric trace gases and the removal, via microphysical scavenging, of soluble trace gas precursors of ozone. We investigate wet scavenging of formaldehyde (CH2O), hydrogen peroxide (H2O2), and methyl hydrogen peroxide (CH3OOH) in quasi‐marine and land convective storms over Texas, USA observed on 18 September 2013 during the 2013 SEAC4RS campaign. Cloud‐resolving simulations using the Weather Research and Forecasting model with Chemistry (WRF‐Chem) were performed to understand the effect of entrainment, scavenging efficiency (SE), and ice physics processes on these trace gases with varying solubility. While marine and land convection can have distinctly different microphysical properties, we did not find significant differences in the SEs of CH2O, H2O2, or CH3OOH. The SEs of 44%–53% for CH2O and 85%–90% for H2O2are consistent with our previous studies from SEAC4RS and the 2012 DC3 field experiment storms. Using WRF‐Chem simulations, the ice retention factor (rf) for CH2O was determined to be 0.5–0.9, which is higher than found in previous studies. We show that the CH2O rfis higher in airmass and multicell storms than in severe storms and hypothesize that ice shattering may affect CH2O rfvalues. The CH3OOH SEs (39%–73%) were higher than expected from Henry's Law equilibrium. While recent studies suggest that CH3OOH measurements have interference due to methane diol, we find that this interference cannot fully explain the higher‐than‐expected CH3OOH SEs determined here and during DC3, suggesting further research is needed to understand CH3OOH vertical redistribution. Thunderstorms are important mechanisms for the transport and removal of trace gases in the atmosphere. This study investigates the transport and removal processes of tropospheric ozone trace gas precursors in marine and land convective storms over Texas, USA. Numerical simulations were performed to understand storm processes affecting atmospheric gases with different solubilities. While marine and land storms can have distinctly different storm structure and updraft winds, we did not find significant differences in the amount of gases removed by these storms. The results show that the efficiency of the storm in removing gas from the atmosphere is consistent with our previous findings for moderate to severe storms over the US. In addition, the analysis showed when cloud drops freeze onto ice and snow particles that formaldehyde had more retention in the frozen particle in moderate storms compared to severe storms suggesting that there are many processes affecting this key ozone precursor in deep convection. The more soluble hydrogen peroxide did not show the same ice retention behavior because it is removed by precipitation in the warmer, liquid‐only region of the storm. Although marine and land convection have different microphysical properties, there are no relevant differences in the scavenging efficiencyWRF‐Chem simulations analysis shows ice retention factor for formaldehyde is higher than found in previous studiesMethyl hydrogen peroxide scavenging efficiencies are higher than expected from Henry's Law, even with potential measurement interference Although marine and land convection have different microphysical properties, there are no relevant differences in the scavenging efficiency WRF‐Chem simulations analysis shows ice retention factor for formaldehyde is higher than found in previous studies Methyl hydrogen peroxide scavenging efficiencies are higher than expected from Henry's Law, even with potential measurement interference

The intensity and phase reconstructed from digital in-line holograms by the convolution approach are analyzed. Distortions of particle images depending on their position in the plane transverse to the optical axis are identified. For this purpose, the object fields of numerically simulated particle holograms as well as of experimental data are reconstructed. The results of three-dimensional correlations of numerical and experimental data are superior when the numerically generated reference volumes are adapted to the transverse locations of the particle. Thus, proof is given that the characteristics of a particle image change distinctly with the transverse position of the particle and that the numerical model successfully simulates these changes. Hence, this knowledge can be integrated in future particle position detection algorithms.

In digital holographic particle image velocimetry, hologram truncation is a very prominent problem when the projection of the particle position to the sensor is close to the sensor edge. Using the convolution approach to reconstruct such a hologram yields a deformed particle image compared to a particle image resulting from a particle with a projection to the center of the sensor. This Letter shows that the deformation complicates particle position detection based on an algorithm originally developed for analog holography by Choo and Kang, and later applied to digital holography by Yang and Kang. This algorithm is refined for the detection of particle positions from the deformed images and applied to numerical and experimental data.

Die Deckung der pflegerischen Versorgungsbedarfe der Bevölkerung erfordert die Entwicklung innovativer Versorgungskonzepte. Pflege übernimmt erweiterte Aufgaben, die einen Ausbau von akademischen Ausbildungsangeboten erfordern.

Rapidly growing nontuberculous mycobacteria (RGNTM) have yet to be described in combat-related injuries. This study investigates the epidemiology, clinical findings, treatment, and outcomes of RGNTM infections among combat casualties wounded in Afghanistan from 2010 to 2012.

We examine wet scavenging of soluble trace gases in storms observed during the Deep Convective Clouds and Chemistry (DC3) field campaign. We conduct high‐resolution simulations with the Weather Research and Forecasting model with Chemistry (WRF‐Chem) of a severe storm in Oklahoma. The model represents well the storm location, size, and structure as compared with Next Generation Weather Radar reflectivity, and simulated CO transport is consistent with aircraft observations. Scavenging efficiencies (SEs) between inflow and outflow of soluble species are calculated from aircraft measurements and model simulations. Using a simple wet scavenging scheme, we simulate the SE of each soluble species within the error bars of the observations. The simulated SEs of all species except nitric acid (HNO3) are highly sensitive to the values specified for the fractions retained in ice when cloud water freezes. To reproduce the observations, we must assume zero ice retention for formaldehyde (CH2O) and hydrogen peroxide (H2O2) and complete retention for methyl hydrogen peroxide (CH3OOH) and sulfur dioxide (SO2), likely to compensate for the lack of aqueous chemistry in the model. We then compare scavenging efficiencies among storms that formed in Alabama and northeast Colorado and the Oklahoma storm. Significant differences in SEs are seen among storms and species. More scavenging of HNO3and less removal of CH3OOH are seen in storms with higher maximum flash rates, an indication of more graupel mass. Graupel is associated with mixed‐phase scavenging and lightning production of nitrogen oxides (NOx), processes that may explain the observed differences in HNO3and CH3OOH scavenging. Observed deep convective scavenging efficiencies simulated by simple schemeSimulated scavenging efficiencies highly sensitive to ice retention fractionScavenging efficiencies vary among storms with different microphysics

One of the objectives of the Deep Convective Clouds and Chemistry (DC3) field experiment was to determine the scavenging of soluble trace gases by thunderstorms. We present an analysis of scavenging of hydrogen peroxide (H2O2) and methyl hydrogen peroxide (CH3OOH) from six DC3 cases that occurred in Oklahoma and northeast Colorado. Estimates of H2O2scavenging efficiencies are comparable to previous studies ranging from 79 to 97% with relative uncertainties of 5–25%. CH3OOH scavenging efficiencies ranged from 12 to 84% with relative uncertainties of 18–558%. The wide range of CH3OOH scavenging efficiencies is surprising, as previous studies suggested that CH3OOH scavenging efficiencies would be <10%. Cloud chemistry model simulations of one DC3 storm produced CH3OOH scavenging efficiencies of 26–61% depending on the ice retention factor of CH3OOH during cloud drop freezing, suggesting ice physics impacts CH3OOH scavenging. The highest CH3OOH scavenging efficiencies occurred in two severe thunderstorms, but there is no obvious correlation between the CH3OOH scavenging efficiency and the storm thermodynamic environment. We found a moderate correlation between the estimated entrainment rates and CH3OOH scavenging efficiencies. Changes in gas‐phase chemistry due to lightning production of nitric oxide and aqueous‐phase chemistry have little effect on CH3OOH scavenging efficiencies. To determine why CH3OOH can be substantially removed from storms, future studies should examine effects of entrainment rate, retention of CH3OOH in frozen cloud particles during drop freezing, and lightning‐NOxproduction. Peroxide scavenging efficiencies derived from measurementsHydrogen peroxide is readily removed by stormsMethyl hydrogen peroxide scavenging correlated with cloud physics and entrainment rate

Supplemental Digital Content is available in the text.

Quantitative analysis of histologic slides is of importance for pathology and also to address surgical questions. Recently, a novel application was developed for the automated quantification of whole-slide images. The aim of this study was to test and validate the underlying image analysis algorithm with respect to user friendliness, accuracy, and transferability to different histologic scenarios. The algorithm splits the images into tiles of a predetermined size and identifies the tissue class of each tile. In the training procedure, the user specifies example tiles of the different tissue classes. In the subsequent analysis procedure, the algorithm classifies each tile into the previously specified classes. User friendliness was evaluated by recording training time and testing reproducibility of the training procedure of users with different background. Accuracy was determined with respect to single and batch analysis. Transferability was demonstrated by analyzing tissue of different organs (rat liver, kidney, small bowel, and spleen) and with different stainings (glutamine synthetase and hematoxylin-eosin). Users of different educational background could apply the program efficiently after a short introduction. When analyzing images with similar properties, accuracy of >90% was reached in single images as well as in batch mode. We demonstrated that the novel application is user friendly and very accurate. With the “training” procedure the application can be adapted to novel image characteristics simply by giving examples of relevant tissue structures. Therefore, it is suitable for the fast and efficient analysis of high numbers of fully digitalized histologic sections, potentially allowing “high-throughput” quantitative “histomic” analysis.

Graphitic materials are currently the state-of-the-art anode materials for lithium ion secondary batteries. By chemical modification, the electrochemical performance of the pristine materials can be improved. In this paper we report on the preparation of nanostructured copper particles on graphite by thermal decomposition of copper formate. With this technique a novel, simple and low cost method for a homogeneous deposition of nanostructured copper particles on graphite was established. Different amounts of copper were realized and their influence on the electrochemical behavior of the active material was investigated. The copper particles had a size distribution between 50 nm and 300 nm. Electrochemical measurements displayed an improved performance of the synthesized composite material compared to the pristine material. Cyclic voltammetry showed a suppressed cointercalation of solvated lithium and an increased formation of the solid electrolyte interphase (SEI). Battery cycling demonstrated an increased discharge capacity and cycling stability.

A significant source of ozone in the troposphere is transport from the stratosphere. The stratospheric contribution has been estimated mainly using global models that attribute the transport process largely to the global‐scale Brewer‐Dobson circulation and synoptic‐scale dynamics associated with upper tropospheric jet streams. We report observations from research aircraft that reveal additional transport of ozone‐rich stratospheric air downward into the upper troposphere by a leading‐line‐trailing‐stratiform mesoscale convective system with convection overshooting the tropopause altitude. The fine‐scale transport demonstrated by these observations poses a significant challenge to global models that currently do not resolve storm‐scale dynamics. Thus, the upper tropospheric ozone budget simulated by global chemistry‐climate models where large‐scale dynamics and photochemical production from lightning‐produced NO are the controlling factors may require modification. Tropopause‐reaching MCSs entrain ozone‐rich stratospheric air into troposphereAirborne lidar measurement is key to revealing this transport mechanismA missing transport pathway for ozone budget in major global models

Correctly ranking compounds according to their computed relative binding affinities will be of great value for decision making in the lead optimization phase of industrial drug discovery. However, the performance of existing computationally demanding binding free energy calculation methods in this context is largely unknown. We analyzed the performance of the molecular mechanics continuum solvent, the linear interaction energy (LIE), and the thermodynamic integration (TI) approach for three sets of compounds from industrial lead optimization projects. The data sets pose challenges typical for this early stage of drug discovery. None of the methods was sufficiently predictive when applied out of the box without considering these challenges. Detailed investigations of failures revealed critical points that are essential for good binding free energy predictions. When data set-specific features were considered accordingly, predictions valuable for lead optimization could be obtained for all approaches but LIE. Our findings lead to clear recommendations for when to use which of the above approaches. Our findings also stress the important role of expert knowledge in this process, not least for estimating the accuracy of prediction results by TI, using indicators such as the size and chemical structure of exchanged groups and the statistical error in the predictions. Such knowledge will be invaluable when it comes to the question which of the TI results can be trusted for decision making.

Tropopause‐overshooting convection in the midlatitudes rapidly transports lower troposphere air and cloud material to the upper troposphere and lower stratosphere (UTLS), with notable events resulting in the formation of above‐anvil cirrus plumes (AACPs). However, there is limited understanding of how transport driven by overshooting convection and AACP properties are modified by variations in UTLS environments, especially the extent of stratosphere‐to‐troposphere (i.e., downward) transport. Here, AACP development and UTLS transport sensitivities to lower stratosphere stability and the UTLS wind environment are evaluated. The Bryan Cloud Model is used to simulate midlatitude supercell convection and evaluate resulting UTLS composition changes within two common midlatitude thermodynamic environments: a single tropopause and a double tropopause, and two UTLS wind environments: one with a stronger stratospheric wind profile supportive of frequent gravity wave breaking and AACP development and the other with a weaker stratospheric wind profile to suppress gravity wave breaking and discourage AACP formation. Multiple passive tracers and water vapor concentrations are used to evaluate the exchange of air between the troposphere and stratosphere and transport confined to each layer. It is found that greater troposphere‐to‐stratosphere transport (TST) and stratospheric hydration occurs in storms with AACPs, while stratosphere‐to‐troposphere transport (STT) is greater in storms without AACPs. This STT is facilitated by a mechanical oscillation induced by the overshoot. AACP‐producing storms have increased downward transport of stratospheric overworld air to the lowermost stratosphere, which is enhanced within a double tropopause environment. More expansive AACPs, deeper overshoots, and greater TST also occurs in double tropopause environments. Stratosphere stability has a minimal impact on stratosphere‐to‐troposphere transport in overshooting convectionStratosphere‐to‐troposphere transport is greater in storms without above‐anvil cirrus plumesA mechanical oscillation induced by the overshoot facilitates stratosphere‐to‐troposphere transport Stratosphere stability has a minimal impact on stratosphere‐to‐troposphere transport in overshooting convection Stratosphere‐to‐troposphere transport is greater in storms without above‐anvil cirrus plumes A mechanical oscillation induced by the overshoot facilitates stratosphere‐to‐troposphere transport

MM-PBSA is a post-processing end-state method to calculate free energies of molecules in solution. MMPBSA.pyis a program written in Python for streamlining end-state free energy calculations using ensembles derived from molecular dynamics (MD) or Monte Carlo (MC) simulations. Several implicit solvation models are available with MMPBSA.py, including the Poisson–Boltzmann Model, the Generalized Born Model, and the Reference Interaction Site Model. Vibrational frequencies may be calculated using normal mode or quasi-harmonic analysis to approximate the solute entropy. Specific interactions can also be dissected using free energy decomposition or alanine scanning. A parallel implementation significantly speeds up the calculation by dividing frames evenly across available processors. MMPBSA.pyis an efficient, user-friendly program with the flexibility to accommodate the needs of users performing end-state free energy calculations. The source code can be downloaded at http://ambermd.org/with AmberTools, released under the GNU General Public License.