The effect of aerosols on the properties of clouds is a large source of uncertainty in predictions of weather and climate. These aerosol‐cloud interactions depend critically on the ability of aerosol ...particles to form cloud droplets. A challenge in modeling aerosol‐cloud interactions is the representation of interactions between turbulence and cloud microphysics. Turbulent mixing leads to small‐scale fluctuations in water vapor and temperature that are unresolved in large‐scale atmospheric models. To quantify the impact of turbulent fluctuations on cloud condensation nuclei (CCN) activation, we used a high‐resolution Large Eddy Simulation of a convective cloud chamber to drive particle‐based cloud microphysics simulations. We show small‐scale fluctuations strongly impact CCN activity. Once activated, the relatively long timescales of evaporation compared to fluctuations causes droplets to persist in subsaturated regions, which further increases droplet concentrations.
Plain Language Summary
Increases in cloud droplet number concentrations from human emissions of aerosol particles modify cloud properties, which strongly impacts Earth's energy balance. Large Eddy Simulations and Earth System Models are used to quantify these aerosol‐cloud interactions, but the spatial and temporal resolution of these models is too coarse to represent the impact of turbulence at the smallest scales. In this study, we show that small‐scale turbulent fluctuations lead to cloud droplet formation even when air is, on average, subsaturated, which would be impossible in conventional models of cloud microphysics. Our findings suggest that models that neglect turbulent fluctuations in supersaturation will underestimate cloud condensation nuclei activity under specific supersaturation regimes, which will may lead to error in modeled cloud properties.
Key Points
Small‐scale turbulence leads to variability in the supersaturation experienced by aerosol particles and cloud droplets within clouds
Turbulent fluctuations increase cloud droplet formation at low supersaturation levels in comparison with uniform environmental conditions
Atmospheric models that neglect supersaturation variability due to turbulence may underestimate the number concentration of cloud droplets
Abstract
Ewing sarcoma is a prototypical fusion transcription factor-associated pediatric cancer that expresses EWS/FLI or a highly related FET/ETS chimera. EWS/FLI dysregulates transcription to ...induce and maintain sarcomagenesis, but the mechanisms utilized are not fully understood. We therefore sought to define the global effects of EWS/FLI on chromatin conformation and transcription in Ewing sarcoma cells using a well-validated ‘knock-down/rescue’ model of EWS/FLI function in combination with next generation sequencing assays to evaluate how the chromatin landscape changes with loss, and recovery, of EWS/FLI expression. We found that EWS/FLI (and EWS/ERG) genomic localization is largely conserved across multiple patient-derived Ewing sarcoma cell lines. This EWS/FLI binding signature is associated with establishment of topologically-associated domain (TAD) boundaries, compartment activation, enhancer-promoter looping that involve both intra- and inter-TAD interactions, and gene activation. In addition, EWS/FLI co-localizes with the loop-extrusion factor cohesin to promote chromatin loops and TAD boundaries. Importantly, local chromatin features provide the basis for transcriptional heterogeneity in regulation of direct EWS/FLI target genes across different Ewing sarcoma cell lines. These data demonstrate a key role of EWS/FLI in mediating genome-wide changes in chromatin configuration and support the notion that fusion transcription factors serve as master regulators of three-dimensional reprogramming of chromatin.
Entrainment of dry air into clouds strongly influences cloud optical and precipitation properties and the response of clouds to aerosol perturbations. The response of cloud droplet size distributions ...to entrainment-mixing is examined in the Pi convection-cloud chamber that creates a turbulent, steady-state cloud. The experiments are conducted by injecting dry air with temperature (T
) and flow rate (Q
) through a flange in the top boundary, into the otherwise well-mixed cloud, to mimic the entrainment-mixing process. Due to the large-scale circulation, the downwind region is directly affected by entrained dry air, whereas the upwind region is representative of the background conditions. Droplet concentration (Cn) and liquid water content (L) decrease in the downwind region, but the difference in the mean diameter of droplets (D
) is small. The shape of cloud droplet size distributions relative to the injection point is unchanged, to within statistical uncertainty, resulting in a signature of inhomogeneous mixing, as expected for droplet evaporation times small compared to mixing time scales. As T
and Q
of entrained air increase, however, Cn, L, and D
of the whole cloud system decrease, resulting in a signature of homogeneous mixing. The apparent contradiction is understood as the cloud microphysical responses to entrainment and mixing differing on local and global scales: locally inhomogeneous and globally homogeneous. This implies that global versus local sampling of clouds can lead to seemingly contradictory results for mixing, which informs the long-standing debate about the microphysical response to entrainment and the parameterization of this process for coarse-resolution models.
We sought to characterize the typical recovery in physical function (PF) and pain interference (PI) after TKA using Patient-Reported Outcomes Measurement Information System (PROMIS) patient-reported ...outcome (PRO) measures.
Ninety-one patients were enrolled into an institutional review board -approved prospective observational study. PROs were obtained preoperatively and postoperatively at 6 weeks, 3 months, 6 months, and 1 year. PROs included the PROMIS PF computerized adaptive test (CAT) and the PROMIS PI CAT. Generalized estimating equations were used to evaluate outcomes over time.
There was no difference in the preoperative and 6-week postoperative T-scores for the PF CAT (P = .410). However, all subsequent postoperative T-scores were greater than the preoperative T-score (all, P < 0.05). There was a significant reduction in PI CAT T-scores between the preoperative and all subsequent postoperative T-scores (all, P < .05). A clinically important difference in PF CAT T-scores (β = 5.44, 95% confidence interval 4.10-6.80; P < .001) and PI CAT T-scores (β = −7.46, 95% confidence interval −9.52 to −5.40; P < 0.001) was seen between the preoperative and 3-month postoperative visits. Sixty-three percent of the improvement in PF occurred by 3 months, and 89% had occurred by 6 months. The majority of reduction in PI (68%) occurred by 3 months and 90% had occurred by 6 months.
The greatest magnitude of improvement in both PF and PI occurred within the first 3 months. After 6 months, patients might expect modest improvements in PF and mild reductions of PI. Patients and surgeons should use this information for setting expectations, planning for recovery, and improving care.
Background
With as many as 25% of patients reporting residual knee symptoms after primary total knee arthroplasty (TKA), alternative implant designs and surgical techniques have been proposed to ...further reduce these symptoms. There is growing evidence that retention of the anterior cruciate ligament (ACL) results in more natural knee kinematics; thus, implants with more normal joint mechanics could provide improved physical function postoperatively and reduce the amount of residual symptoms. Advancements in the bicruciate-retaining (BCR) TKA implant design have been made, and based on these, we wished to compare the BCR with a more traditional cruciate-retaining (CR) implant.
Questions/purposes
(1) Was there a difference in the risk of reoperation after primary TKA between BCR and CR implant designs? (2) Was there a difference in the radiographic findings of radiolucent lines (RLLs) between the implant designs? (3) Was there a difference in patient-reported and clinical outcomes between the two implant designs?
Methods
Between January 2013 and May 2014, two surgeons performed 475 primary TKAs. During this time, 78 (16%) of these were performed with BCR implants and 294 (62%) with CR implants; the remainder were performed with anterior-stabilized or more constrained designs as a result of increased deformity and/or ligamentous deficiencies. During this period, the general indications for BCR TKA were arthritic knees with only slight to moderate deformity and sufficient ligamentous integrity of both the ACL and posterior cruciate ligament. The indications for CR TKA were similar other than these patients presented with a deficient ACL. A total of 66 (85%) of the BCR and 237 (81%) of the CR TKAs were available for followup at a minimum of 12 months or when reoperation occurred before 12 months (mean, 18 months; range, 2–32 months). With the numbers available, there were no differences between the groups in terms of age and sex, but the patients undergoing CR TKA had a greater mean body mass index (33 ± 7 versus 31 ± 5 kg/m
2
, p = 0.032). The frequency of early reoperation was compared between the groups as were radiographic evidence of RLL, patient-reported outcomes, and knee range of motion (ROM).
Results
Knees in the BCR group had a higher frequency of all-cause revision (5% three of 66 versus 1.3% three of 237; hazard ratio (HR), 7.44; 95% confidence interval CI, 1.24–44.80; p = 0.028). Knees in the BCR group had a higher frequency of irrigation and débridement with component retention (HR, 0.07; 95% CI, 0.02–0.28; p < 0.001). No differences were found between groups for subsequent manipulation (HR, 0.34; 95% CI, 0.08–1.42; p = 0.137). The proportion of RLLs was greater in the BCR group (HR, 2.93; 95% CI, 1.62–5.32; p < 0.001) compared with the CR group. There were no differences between the groups in terms of the Physical Function Computerized Adaptive Test scores, Global10 scores or knee ROM outcomes.
Conclusions
Preliminary short-term findings suggest the BCR implant has inferior survivorship and concerning radiographic findings when compared with a conventional CR implant with respect to complications after primary TKA. These findings raise concerns about the new BCR design; however, further randomized trials are necessary to determine superiority between alternative implant designs.
Level of Evidence
Level III, therapeutic study.
This study aimed to describe the trajectory of recovery based on patient-reported outcomes (PROs) and objective metrics of physical activity measures over the first 12 months post–total knee ...arthroplasty (TKA).
In total, 1,005 participants who underwent a primary unilateral TKA surgery between November 2018 and September 2021 from a multisite prospective study were analyzed. Generalized estimating equations were used to evaluate PROs and objective physical activity measures over time.
All Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS JR), EuroQol-5D (EQ-5D), and steps per day scores were greater than preoperative scores (P < .05). The flights of stairs per day, gait speed, and walking asymmetry all declined at 1 month (all, P < .001). However, all subsequent scores improved by 6 months (all, P < .01).
The greatest clinically important differences from previous visit in KOOS JR (β = 18.1; 95% Confidence Interval (CI) = 17.2, 19.0), EQ-5D (β = 0.11; 95% CI = 0.10, 0.12), steps per day (β = 1,169.3; 95% CI = 1,012.7, 1,325.9), gait speed (β = −0.05; 95% CI = −0.06, −0.03), and walking asymmetry (β = 0.00; 95% CI = −0.03, 0.03) were observed at 3 months.
The KOOS JR, EQ-5D, and steps per day measures showed earlier improvements than other physical activity metrics, with the greatest magnitude of improvement within the first 3 months post-TKA. The greatest magnitude of improvement in walking asymmetry was not observed until 6 months, while gait speed and flights of stairs per day were not observed until 12 months. This data may further help provide expectation setting information to patients before surgery, and may aid in identifying outliers to the normal recovery curve who may benefit from targeted interventions.
Microphysical processes are important for the development of clouds and thus Earth's climate. For example, turbulent fluctuations in the water vapor mixing ratio, r, and temperature, T, cause ...fluctuations in the saturation ratio, S. Because S is the driving factor in the condensational growth of droplets, fluctuations may broaden the cloud droplet size distribution due to individual droplets experiencing different growth rates. The small-scale turbulent fluctuations in the atmosphere that are relevant to cloud droplets are difficult to quantify through field measurements. We investigate these processes in the laboratory using Michigan Tech's Π Chamber. The Π Chamber utilizes Rayleigh–Bénard convection (RBC) to create the turbulent conditions inherent in clouds. In RBC it is common for a large-scale circulation (LSC) to form. As a consequence of the LSC, the temperature field of the chamber is not spatially uniform. In this paper, we characterize the LSC in the Π Chamber and show how it affects the shape of the distributions of r, T, and S. The LSC was found to follow a single roll with an updraft and downdraft along opposing walls of the chamber. Near the updraft (downdraft), the distributions of T and r were positively (negatively) skewed. At each measuring position, S consistently had a negatively skewed distribution, with the downdraft being the most negative.
Objective
To develop machine learning (ML) models capable of predicting ICU admission and extended length of stay (LOS) after torso (chest, abdomen, or pelvis) trauma, by using clinical and/or ...imaging data.
Materials and methods
This was a retrospective study of 840 adult patients admitted to a level 1 trauma center after injury to the torso over the course of 1 year. Clinical parameters included age, sex, vital signs, clinical scores, and laboratory values. Imaging data consisted of any injury present on CT. The two outcomes of interest were ICU admission and extended LOS, defined as more than the median LOS in the dataset. We developed and tested artificial neural network (ANN) and support vector machine (SVM) models, and predictive performance was evaluated by area under the receiver operating characteristic (ROC) curve (AUC).
Results
The AUCs of SVM and ANN models to predict ICU admission were up to 0.87 ± 0.03 and 0.78 ± 0.02, respectively. The AUCs of SVM and ANN models to predict extended LOS were up to 0.80 ± 0.04 and 0.81 ± 0.05, respectively. Predictions based on imaging alone or imaging with clinical parameters were consistently more accurate than those based solely on clinical parameters.
Conclusions
The best performing models incorporated imaging findings and outperformed those with clinical findings alone. ML models have the potential to help predict outcomes in trauma by integrating clinical and imaging findings, although further research may be needed to optimize their performance.
Key Points
• Artificial neural network and support vector machine–based models were used to predict the intensive care unit admission and extended length of stay after trauma to the torso.
• Our input data consisted of clinical parameters and CT imaging findings derived from radiology reports, and we found that combining the two significantly enhanced the prediction of both outcomes with either model.
• The highest accuracy (83%) and highest area under the receiver operating characteristic curve (0.87) were obtained for artificial neural networks and support vector machines, respectively, by combining clinical and imaging features in the prediction of intensive care unit admission.
Ewing sarcoma is an aggressive bone cancer of children and young adults defined by the presence of a chromosomal translocation: t(11;22)(q24;q12). The encoded protein, EWS/FLI, fuses the ...amino-terminal domain of EWS to the carboxyl-terminus of FLI. The EWS portion is an intrinsically disordered transcriptional regulatory domain, while the FLI portion contains an ETS DNA-binding domain and two flanking regions of unknown function. Early studies using non-Ewing sarcoma models provided conflicting information on the roles of each domain of FLI in EWS/FLI oncogenic function. We therefore sought to define the specific contributions of each FLI domain to EWS/FLI activity in a well-validated Ewing sarcoma model and, in doing so, to better understand Ewing sarcoma development mediated by the fusion protein. We analyzed a series of engineered EWS/FLI mutants with alterations in the FLI portion using a variety of assays. Fluorescence anisotropy, CUT&RUN, and ATAC-sequencing experiments revealed that the isolated ETS domain is sufficient to maintain the normal DNA-binding and chromatin accessibility function of EWS/FLI. In contrast, RNA-sequencing and soft agar colony formation assays revealed that the ETS domain alone was insufficient for transcriptional regulatory and oncogenic transformation functions of the fusion protein. We found that an additional alpha-helix immediately downstream of the ETS domain is required for full transcriptional regulation and EWS/FLI-mediated oncogenesis. These data demonstrate a previously unknown role for FLI in transcriptional regulation that is distinct from its DNA-binding activity. This activity is critical for the cancer-causing function of EWS/FLI and may lead to novel therapeutic approaches.
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