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Capturing the spatial distribution of high-intensity rainfall over short-time intervals is critical for accurately assessing the efficacy of urban stormwater drainage systems. In a stochastic simulation framework, one method of generating realistic rainfall fields is by multiplicative random cascade (MRC) models. Estimation of MRC model parameters has typically relied on radar imagery or, less frequently, rainfall fields interpolated from dense rain gauge networks. However, such data are not always available. Furthermore, the literature is lacking estimation procedures for spatially incomplete datasets. Therefore, we proposed a simple method of calibrating an MRC model when only data from a moderately dense network of rain gauges are available, rather than from the full rainfall field. The number of gauges need only be sufficient to adequately estimate the variance in the ratio of the rain rate at the rain gauges to the areal average rain rate across the entire spatial domain. In our example for Warsaw, Poland, we used 25 gauges over an area of approximately 1600 km². MRC models calibrated using the proposed method were used to downscale 15-min rainfall rates from a 20 by 20 km area to the scale of the rain gauge capture area. Frequency distributions of observed and simulated 15-min rainfall at the gauge scale were very similar. Moreover, the spatial covariance structure of rainfall rates, as characterized by the semivariogram, was reproduced after allowing the probability density of the random cascade generator to vary with spatial scale. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop and establish a new system of laparoscopic fluorometry for the purpose of investigating the intestinal microcirculation. In 25 pigs (German Landrace, 16–25 kg body weight), ischemia was established in two segments (A, irreversible; B, reversible ischemia; C, internal control) of the small intestine by a laparoscopic technique. Microcirculation in the segments was assessed by laparoscopy at a second-look operation 24 h later by means of the fluorescence system Endoscan. The fluorescence of the three bowel segments was measured by arbitrary dye fluorescence units (DFU) 15 min after starting reperfusion, before and after injection of sodium fluorescein (NaFlu, 0.25 mg/kg body weight). The dividing line between viable and nonviable bowel tissue was established from the inflow and outflow rates of NaFlu with the aid of ROC (receiver operating characteristic) curves. The specificity and sensitivity of the new method were evaluated by correlating the results with the viability of each intestinal segment as predicted by three laparoscopically experienced surgeons and by histological examination. By means of the calculated separation sharpness (fluorescence index at 2 min >0.5, outflow factor of NaFlu at 10 min >20%), the overall predictions of intestinal viability in all 25 animals achieved a sensitivity of 93.5% and a specificity of 94.1% by laparoscopic fluorometry, versus a sensitivity of 70.8% and a specificity of 87.5% for the prediction of bowel viability by ordinary laparoscopic technique. Used as an adjunct to conventional laparoscopy, laparoscopic fluorometry brought significant gains in sensitivity and specificity in the distinction between reversible and irreversible intestinal ischemia. [ABSTRACT FROM AUTHOR]

The adequate assessment of the thermal performance of a building requires the knowledge of its characteristics within its inserted context, making it possible to verify the actual and future performance of the building. Therefore, this study aims to analyse the energy efficiency of a public university building located in southern Brazil. The assessment was carried out according to the Brazilian Technical Regulation for Energy Efficiency Labelling of Commercial, Services and Public Buildings (RTQ-C). In this study, the building envelopment was evaluated under the actual condition and in the reference condition, using the simplified method. The constructive parameters of the building were obtained from the architectural project and technical standards, although the assigned climatic group of the building was defined based on the Brazilian bioclimatic zones. In the end, it was possible to identify the energetic efficiency level of the envelopment through the total annual thermal load of the building in its actual condition. Considering the urban and climatic context, as well as constructive characteristics of the building, strategies were proposed that can be adopted even in the project planning stage, aiming to improve the classification of the envelopment and to meet the energy efficiency policies of the country.

Abstract Background Runx proteins are developmentally important metazoan transcription factors that form a heterodimeric complex with the non-homologous protein Core Binding Factor β (CBFβ). CBFβ allosterically enhances Runx DNA binding but does not bind DNA itself. We report the initial characterization of SpCBFβ, the heterodimeric partner of SpRunt-1 from the sea urchin Stronylocentrotus purpuratus. Results SpCBFβ is remarkably similar to its mammalian homologues, and like them it enhances the DNA binding of the Runt domain. SpCBFβ is entirely of zygotic provenance and its expression is similar that of SpRunt-1, accumulating globally at late blastula stage then later localizing to endoderm and oral ectoderm. Unlike SpRunt-1, however, SpCBFβ is enriched in the endodermal mid- and hindgut of the pluteus larva, and is not highly expressed in the foregut and ciliated band. We showed previously that morpholino antisense-mediated knockdown of SpRunt-1 leads to differentiation defects, as well as to extensive post-blastula stage apoptosis caused by under-expression of the Runx target gene SpPKC1. In contrast, we show here that knockdown of SpCBFβ does not negatively impact cell survival or SpPKC1 expression, although it does lead to differentiation defects similar to those associated with SpRunt-1 deficiency. Moreover, SpRunt-1 containing a single amino acid substitution that abolishes its ability to interact with SpCBFβ retains the ability to rescue cell survival in SpRunt-1 morphant embryos. Chromatin immunoprecipitation shows that while the CyIIIa promoter engages both proteins, the SpPKC1 promoter only engages SpRunt-1. Conclusion SpCBFβ is a facultative Runx partner that appears to be required specifically for cell differentiation.

Abstract Background Runx transcription factors play critical roles in the developmental control of cell fate and contribute variously as oncoproteins and tumor suppressors to leukemia and other cancers. To discover fundamental Runx functions in the cell biology of animal development, we have employed morpholino antisense-mediated knockdown of the sea urchin Runx protein SpRunt-1. Previously we showed that embryos depleted of SpRunt-1 arrest development at early gastrula stage and underexpress the conventional protein kinase C SpPKC1. Results We report here that SpRunt-1 deficiency leads to ectopic cell proliferation and extensive apoptosis. Suppression of the apoptosis by pharmacological inhibition of caspase-3 prevents the ectopic proliferation and rescues gastrulation, indicating that many of the overt defects obtained by knockdown of SpRunt-1 are secondary to the apoptosis. Inhibition or knockdown of SpPKC1 also causes apoptosis, while cell survival is rescued in SpRunt-1 morphant embryos coinjected with SpPKC1 mRNA, suggesting that the apoptosis associated with SpRunt-1 deficiency is caused by the deficit in SpPKC1 expression. Chromatin immunoprecipitation indicates that SpRunt-1 interacts physically with SpPKC1 in vivo, and cis-regulatory analysis shows that this interaction activates SpPKC1 transcription. Conclusions Our results show that Runx-dependent activation of SpPKC1 is essential for maintaining protein kinase C activity at levels conducive to cell survival during embryogenesis.

Background: Society is experiencing an increasing shift in the age distribution and accordingly, increased resuscitation rates of patients over 80 years and older. In 2022, more than 34% of people resuscitated in Germany were older than 80 years, although older age is considered a poor predictor for the outcome of cardiopulmonary resuscitation (CPR). Professional societies provide ethical recommendations on when resuscitation may be considered futile and should be terminated. However, the extent to which these recommendations are implemented is unclear., Methods: Retrospective evaluation of pre-hospital documentation of out-of-hospital resuscitations in patients ≥ 80 years of age in the period 01/01/2014-12/31/2022 in one German county combined with data of the German Resuscitation Registry. For statistical testing, the significance level was set at p < 0.05., Results: In total 578 cases were analyzed. Return of spontaneous circulation (ROSC): 26% (n = 148). Survival to discharge: 6.1% (n = 35). Median CPR duration: 17 min (10-28 min). The older the patients were, the worse the survival rate (p = 0.05) and the shorter the time to termination (p < 0.0001). No patient over 90 years of age was discharged alive. Resuscitation was also significantly shorter until termination with poorer ASA (American Society of Anesthesiologists) score (p < 0.001). Residents resuscitated significantly longer than specialists (p = 0.02). In surviving patients, there was a significant correlation between short CPR duration and good cerebral performance category (CPC) value: Median CPC1/2 = 5 min [3-10 min] vs. CPC 3/4 = 18 min [10-21 min]; p = 0.01., Interpretation: Old age and poor health status is associated with shorter CPR duration until termination and older age is associated with poorer prognosis in out-of-hospital cardiac arrest (OHCA) concerning the possibility of return of spontaneous circulation (ROSC) and survival. A short resuscitation time is associated with a better CPC value. Therefore, when resuscitating patients over 80 years of age, even greater care should be taken to ensure that reversible causes are quickly corrected in order to achieve a ROSC and a good neurological outcome. Alternatively, resuscitation should be terminated promptly, as good survival can no longer be guaranteed. Resuscitation lasting more than 20 min should be avoided in any case, in line with the termination of resuscitation (ToR) criteria., (© 2024. The Author(s).)

Background and Objectives: In case of out-of-hospital cardiac arrest (OHCA) personnel of the emergency medical services (EMS) are regularly confronted with advanced directives (AD) and do-not-attempt-resuscitation (DNACPR) orders. The authors conducted a retrospective analysis of EMS operation protocols to examine the prevalence of DNACPR in case of OHCA and the influence of a presented DNACPR on CPR-duration, performed Advanced-Life-Support (ALS) measures and decision making., Materials and Methods: Retrospective analysis of prehospital medical documentation of all resuscitation incidents in a German county with 250,000 inhabitants from 1 January 2016 to 31 December 2022. Combined with data from the structured CPR team-feedback database patients characteristics, measures and course of the CPR were analysed. Statistic testing with significance level p < 0.05., Results: In total n = 1,474 CPR events were analysed. Patients with DNACPR vs. no DNACPR: n = 263 (17.8%) vs. n = 1,211 (82.2%). Age: 80.0 ± 10.3 years vs. 68.0 ± 13.9 years; p < 0.001. Patients with ASA-status III/IV: n = 214 (81.3%) vs. n = 616 (50.9%); p < 0.001. Initial layperson-CPR: n = 148 (56.3%) vs. n = 647 (55.7%); p = 0.40. Airway management: n = 185 (70.3%) vs. n = 1,069 (88.3%); p < 0.001. With DNACPR CPR-duration initiated layperson-CPR vs. no layperson-CPR: 19:14 min (10:43-25:55 min) vs. 12:40 min (06:35-20:03 min); p < 0.001., Conclusion: In case of CPR EMS-personnel are often confronted with DNACPR-orders. Patients are older and have more previous diseases than patients without DNACPR. Initiated layperson-CPR might lead to misinterpretation of patients will with impact on CPR-duration and unwanted measures. Awareness of this issue should be created through measures such as training programs in particular to train staff in the interpretation and legal admissibility of ADs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To determine factors indicating testing frequency and positive test results in a Division I sports department intrapandemic., Design: Retrospective analysis., Setting: A single Division I collegiate sports department., Patients: All student-athlete (n = 437), student staff (n = 89), and adult staff (n = 202) members of the sports department. Total cohort (n = 728)., Interventions: The authors analyzed the independent variables of local positive rates, sport characteristics, and campus events for impact on the volume of the departmental testing and positive rates., Main Outcome Measures: Measured dependent variables of the volume of departmental testing and positive rates were analyzed., Results: Positive predictive rates (PPRs) largely differed from local, off-campus rates in timing and duration (59.52%: P < 0.05). Overall, 20633 tests were administered with 201 positive results (0.97% PPR). Student-athlete numbers were highest in all categories, followed by adult then student staff. Greater proportions of contact sports became positive (53.03%: P < 0.001) and all-male sports (47.69%: P < 0.001). No comparative difference was seen for teams using fomites (19.15%: P = 0.403). Spring sports teams had the lowest percentage of the team positive (22.22%: P < 0.001). Winter sports had the highest PPR (1.15%), all occurring during team-controlled activities. Playing sports indoors did not increase inside team-controlled activity positive rates ( P = 0.066)., Conclusions: Longitudinal changes in local, off-campus infection rates partially affected sports departmental positive results while testing rates were more influenced by sport and university schedule. Testing resources should be directed toward high-risk sports, which included contact sports (football, basketball, and soccer), all-male teams, both Winter and indoor sports inside team-controlled activities, and sports with long periods of time outside team-controlled activities., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Superfluid helium nanodroplets are an ideal environment for the formation of metastable, self-organized dopant nanostructures. However, the presence of vortices often hinders their formation. Here, we demonstrate the generation of vortex-free helium nanodroplets and explore the size range in which they can be produced. From x-ray diffraction images of xenon-doped droplets, we identify that single compact structures, assigned to vortex-free aggregation, prevail up to 10^{8} atoms per droplet. This finding builds the basis for exploring the assembly of far-from-equilibrium nanostructures at low temperatures.

The structure and dynamics of isolated nanosamples in free flight can be directly visualized via single-shot coherent diffractive imaging using the intense and short pulses of x-ray free-electron lasers. Wide-angle scattering images encode three-dimensional (3D) morphological information of the samples, but its retrieval remains a challenge. Up to now, effective 3D morphology reconstructions from single shots were only achieved via fitting with highly constrained models, requiring a priori knowledge about possible geometries. Here, we present a much more generic imaging approach. Relying on a model that allows for any sample morphology described by a convex polyhedron, we reconstruct wide-angle diffraction patterns from individual silver nanoparticles. In addition to known structural motives with high symmetries, we retrieve imperfect shapes and agglomerates that were not previously accessible. Our results open unexplored routes toward true 3D structure determination of single nanoparticles and, ultimately, 3D movies of ultrafast nanoscale dynamics.

Single-shot coherent diffraction imaging of isolated nanosized particles has seen remarkable success in recent years, yielding in-situ measurements with ultra-high spatial and temporal resolution. The progress of high-repetition-rate sources for intense X-ray pulses has further enabled recording datasets containing millions of diffraction images, which are needed for the structure determination of specimens with greater structural variety and dynamic experiments. The size of the datasets, however, represents a monumental problem for their analysis. Here, we present an automatized approach for finding semantic similarities in coherent diffraction images without relying on human expert labeling. By introducing the concept of projection learning, we extend self-supervised contrastive learning to the context of coherent diffraction imaging and achieve a dimensionality reduction producing semantically meaningful embeddings that align with physical intuition. The method yields substantial improvements compared to previous approaches, paving the way toward real-time and large-scale analysis of coherent diffraction experiments at X-ray free-electron lasers., Competing Interests: Competing interestsThe authors declare no competing financial or non-financial interests., (© The Author(s) 2023, corrected publication 2023.)

Single-shot coherent diffraction imaging (CDI) is a powerful approach to characterize the structure and dynamics of isolated nanoscale objects such as single viruses, aerosols, nanocrystals and droplets. Using X-ray wavelengths, the diffraction images in CDI experiments usually cover only small scattering angles of a few degrees. These small-angle patterns represent the magnitude of the Fourier transform of the 2D projection of the sample's electron density, which can be reconstructed efficiently but lacks any depth information. In cases where the diffracted signal can be measured up to scattering angles exceeding ∼10°, i.e. in the wide-angle regime, some 3D morphological information of the target is contained in a single-shot diffraction pattern. However, the extraction of the 3D structural information is no longer straightforward and defines the key challenge in wide-angle CDI. So far, the most convenient approach relies on iterative forward fitting of the scattering pattern using scattering simulations. Here the Scatman is presented, an approximate and fast numerical tool for the simulation and iterative fitting of wide-angle scattering images of isolated samples. Furthermore, the open-source software implementation of the Scatman algorithm, PyScatman , is published and described in detail. The Scatman approach, which has already been applied in previous work for forward-fitting-based shape retrieval, adopts the multi-slice Fourier transform method. The effects of optical properties are partially included, yielding quantitative results for small, isolated and weakly interacting samples. PyScatman is capable of computing wide-angle scattering patterns in a few milliseconds even on consumer-level computing hardware, potentially enabling new data analysis schemes for wide-angle coherent diffraction experiments., (© Alessandro Colombo et al. 2022.)

We report about the prehospital treatment of an 82-year-old man with septic shock as a complication of acute pancreatitis. Initially only an advanced life support ambulance was on scene. After the primary assessment, the team decided to call for an emergency-physician-staffed helicopter. Because of the long estimated time of arrival on scene, the paramedics had to stabilize the patient without the physician. Therefore, they requested telemetric support. Despite massive centralization and difficult circumstances, the team succeeded to stabilize the patient in ongoing consultation of the tele-emergency physician. This cooperation made immediate und uneventful transportation after arrival of the helicopter possible., (© The Author(s) 2021.)

The X-ray free-electron lasers that became available during the last decade, like the European XFEL (EuXFEL), place high demands on their instrumentation. Especially at low photon energies below 1 keV, detectors with high sensitivity, and consequently low noise and high quantum efficiency, are required to enable facility users to fully exploit the scientific potential of the photon source. A 1-Megapixel pnCCD detector with a 1024 × 1024 pixel format has been installed and commissioned for imaging applications at the Nano-Sized Quantum System (NQS) station of the Small Quantum System (SQS) instrument at EuXFEL. The instrument is currently operating in the energy range between 0.5 and 3 keV and the NQS station is designed for investigations of the interaction of intense FEL pulses with clusters, nano-particles and small bio-molecules, by combining photo-ion and photo-electron spectroscopy with coherent diffraction imaging techniques. The core of the imaging detector is a pn-type charge coupled device (pnCCD) with a pixel pitch of 75 µm × 75 µm. Depending on the experimental scenario, the pnCCD enables imaging of single photons thanks to its very low electronic noise of 3 e - and high quantum efficiency. Here an overview on the EuXFEL pnCCD detector and the results from the commissioning and first user operation at the SQS experiment in June 2019 are presented. The detailed descriptions of the detector design and capabilities, its implementation at EuXFEL both mechanically and from the controls side as well as important data correction steps aim to provide useful background for users planning and analyzing experiments at EuXFEL and may serve as a benchmark for comparing and planning future endstations at other FELs., (open access.)

Aim of the Study: For out-of-hospital-cardiac-arrest (OHCA) due to ventricular fibrillation (VF) guidelines recommend early defibrillation followed by chest compressions for two minutes before analyzing shock success. If rhythm analysis reveals VF again, it is obscure whether VF persisted or reoccurred within the two-minutes-cycle of chest compressions after successful defibrillation. We investigated the time of VF-recurrence in OHCA., Methods: We examined all cases of OHCA presenting with initial VF rhythm at arrival of ALS-ambulance (Marburg-Biedenkopf-County, 246.648 inhabitants) from January 2014 to March 2018. Three independent investigators analyzed corpuls3® ECG-recordings. We included ECG-data from CPR-beginning until four minutes after the third shock. VF termination was defined as the absence of a VF-waveform within 5 s of shock delivery. VF recurrence was defined as the presence of a VF-waveform in the interval 5 s post shock delivery., Results: We included 185 shocks in 82 patients. 74.1% (n = 137) of all shocks terminated VF, but VF recurred in 81% (n = 111). The median (IQR) time of VF-recurrences was 27 s (13.5 s/80.5 s) after shock. 51.4% (n = 57) of VF-recurrence occurred 5-30 s after shock, 13.5% (n = 15) VF-recurrence occurred 31-60 s after shock, 21.6% (n = 24) of VF-recurrence occurred 61-120 s after shock, 13.5% (n = 15) of VF-recurrence occurred 121-240 s after shock., Conclusions: Although VF was terminated by defibrillation in 74.1%, VF recurred in 81% subsequent to the chest compression interval. Thus, VF reappears frequently and early. It is unclear to which extend chest compressions influence VF-relapse. Further studies need to re-evaluate the algorithm, timing of antiarrhythmic therapy or novel defibrillation strategies to minimize refibrillation during shockable OHCA., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: In Europe, survival-rates after out-of-hospital cardiac arrest (OHCA) vary widely between regions. Whether a system dispatching First Responders (FRs; main FR-types: firefighters, police officers, citizen-responders) is present or not may be associated with survival-rates. This study aimed to assess the association between having a dispatched FR-system and rates of return of spontaneous circulation (ROSC) and survival across Europe., Methods: Results of an inventory of dispatched FR-systems for OHCA in Europe were combined with aggregate ROSC and survival data from the EuReCa-TWO study and additionally collected data. Regression analysis (weighted on number of patients included per region) was performed to study the association between having a dispatched FR-system and ROSC and survival-rates to hospital discharge in the total population and in patients with shockable initial rhythm, witnessed OHCA and bystander cardiopulmonary resuscitation (CPR; Utstein comparator group). For regions without a dispatched FR-system, the theoretical survival-rate if a dispatched FR-system would have existed was estimated., Findings: We included 27 European regions. There were 15,859 OHCAs in the total group and 2,326 OHCAs in the Utstein comparator group. Aggregate ROSC and survival-rates were significantly higher in regions with an FR-system compared to regions without (ROSC: 36% [95%CI 35%-37%] vs. 24% [95%CI 23%-25%]; P <0.001; survival in total population [ N =15.859]: 13% [95%CI 12%-15%] vs. 5% [95%CI 4%-6%]; P <0.001; survival in Utstein comparator group [ N =2326]: 33% [95%CI 30%-36%] vs. 18% [95%CI 16%-20%]; P <0.001), and in regions with more than one FR-type compared to regions with only one FR-type. All main FR-types were associated with higher survival-rates (all P <0.050)., Interpretation: European regions with dispatched FRs showed higher ROSC and survival-rates than regions without., Funding: This project/work has received funding from the European Union's Horizon 2020 research and innovation programme under acronym ESCAPE-NET, registered under grant agreement No 733381 (IO, HLT and MTB) and the European Union's COST programme under acronym PARQ, registered under grant agreement No CA19137 (IO, DC, HLT, MTB). HLT and MTB were supported by a grant from the Netherlands CardioVascular Research Initiative, Dutch Heart Foundation, Dutch Federation of University Medical Centres, Netherlands Organization for Health Research and Development, Royal Netherlands Academy of Sciences - CVON2017-15 RESCUED (HLT), and CVON2018-30 Predict2 (HLT and MTB)., Competing Interests: The authors have nothing to declare., (© 2020 The Author(s).)

We present an optical parametric chirped pulse amplification (OPCPA) system delivering 4.4 TW pulses centered at 810 nm with a sub-9 fs duration and a carrier-envelope phase stability of 350 mrad. The OPCPA setup pumped by sub-10 ps pulses from two Yb:YAG thin-disk lasers at 100 Hz repetition rate is optimized for a high conversion-efficiency. The terawatt pulses of the OPCPA are utilized for generating intense extreme ultraviolet (XUV) pulses by high-order harmonic generation, achieving XUV pulse energies approaching the microjoule level.

We have recorded the diffraction patterns from individual xenon clusters irradiated with intense extreme ultraviolet pulses to investigate the influence of light-induced electronic changes on the scattering response. The clusters were irradiated with short wavelength pulses in the wavelength regime of different 4d inner-shell resonances of neutral and ionic xenon, resulting in distinctly different optical properties from areas in the clusters with lower or higher charge states. The data show the emergence of a transient structure with a spatial extension of tens of nanometers within the otherwise homogeneous sample. Simulations indicate that ionization and nanoplasma formation result in a light-induced outer shell in the cluster with a strongly altered refractive index. The presented resonant scattering approach enables imaging of ultrafast electron dynamics on their natural timescale., (© 2020 Author(s).)

Differences in botulinum neurotoxin manufacturing, formulation, and potency evaluation can impact dose and biological activity, which ultimately affect duration of action. The potency of different labeled vials of incobotulinumtoxinA (Xeomin ® ; 50 U, 100 U, or 200 U vials; incobotA) versus onabotulinumtoxinA (BOTOX ® ; 100 U vial; onabotA) were compared on a unit-to-unit basis to assess biological activity using in vitro (light-chain activity high-performance liquid chromatography (LCA-HPLC) and cell-based potency assay (CBPA)) and in vivo (rat compound muscle action potential (cMAP) and mouse digit abduction score (DAS)) assays. Using LCA-HPLC, incobotA units displayed approximately 54% of the protease activity of label-stated equivalent onabotA units. Lower potency, reflected by higher EC 50 , ID 50 , and ED 50 values (pooled mean ± SEM), was displayed by incobotA compared to onabotA in the CBPA (EC 50 : incobotA 7.6 ± 0.7 U/mL; onabotA 5.9 ± 0.5 U/mL), cMAP (ID 50 : incobotA 0.078 ± 0.005 U/rat; onabotA 0.053 ± 0.004 U/rat), and DAS (ED 50 : incobotA 14.2 ± 0.5 U/kg; onabotA 8.7 ± 0.3 U/kg) assays. Lastly, in the DAS assay, onabotA had a longer duration of action compared to incobotA when dosed at label-stated equivalent units. In summary, onabotA consistently displayed greater biological activity than incobotA in two in vitro and two in vivo assays. Differences in the assay results do not support dose interchangeability between the two products., Competing Interests: A. Brideau-Andersen, M.F. Brin, R.S. Broide, D. Canty, B.P. Jacky, L. Le, G. Nicholson, C. Rhéaume, D. Rupp, and L.E. Steward are full-time employees of AbbVie and receive salary and/or stocks/stock options as compensation. M. Washburn and J. Wang were formerly full-time employees of Allergan (now AbbVie). W.G. Philipp-Dormston has been a scientific lecturer, clinical trial investigator, and consultant for Allergan, an AbbVie company, Galderma, and Merz. This study was sponsored by Allergan (prior to its acquisition by AbbVie), with study design, data collection, and data analysis being conducted by AbbVie employees. Data interpretation and publication decisions were determined by all authors.