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\"The visual history of the American West calls to mind iconic artworks and nostalgia for the past. Art of the American Frontier presents more than 300 artworks and artifacts from 1830 to 1930, showcasing the premier collections of the Buffalo Bill Center of the West. The complicated history of westward expansion is presented through the iconography of the frontier, spanning Plains Indian materials, government survey photographs, and paintings by early artist-explorers. In the 20th century, a growing romance with the West is evident in the theatrics of Buffalo Bill Cody and his Wild West show, with its blend of popular culture and history that inspired numerous artists. The dialogue between the historical West and the nostalgia for it can be seen in highlights including Timothy O'Sullivan's government survey photographs, Frederic Remington's rare Impressionist landscape studies, and charming wax sculptures by Charles Russell. Complete with three essays and ten brief expositions on a range of art, culture, and history topics, this generously illustrated catalogue provides a comprehensive overview of 100 years of art from the American West. \"-- Provided by publisher.

Predicting the timing and size of natural snow avalanches is crucial for local and regional decision makers but remains one of the major challenges in avalanche forecasting. So far, forecasts are generally made by human experts interpreting a variety of data and drawing on their knowledge and experience. Using avalanche data from the Swiss Alps and one-dimensional physics-based snowpack simulations for virtual slopes, we developed a model predicting the probability of dry-snow avalanches occurring in the region surrounding automated weather stations based on the output of a recently developed instability model. This new avalanche day predictor was compared with benchmark models related to the amount of new snow. Evaluation on an independent data set demonstrated the importance of snow stratigraphy for natural avalanche release, as the avalanche day predictor outperformed the benchmark model based on the 3 d sum of new snow height (F1 scores: 0.71 and 0.65, respectively). The averaged predictions of both models resulted in the best performance (F1 score: 0.75). In a second step, we derived functions describing the probability for certain avalanche size classes. Using the 24 h new snow height as proxy of avalanche failure depth yielded the best estimator of typical (median) observed avalanche size, while the depth of the deepest weak layer, detected using the instability model, provided the better indicator regarding the largest observed avalanche size. Validation of the avalanche size estimator on an independent data set of avalanche observations confirmed these findings. Furthermore, comparing the predictions of the avalanche day predictors and avalanche size estimators with a 21-year data set of re-analysed regional avalanche danger levels showed increasing probabilities for natural avalanches and increasing avalanche size with increasing danger level. We conclude that these models may be valuable tools to support forecasting the occurrence of natural dry-snow avalanches.

\"Experience the spectacle of Venice and its rich history as a glassmaking capital through Sargent, Whistler, and Venetian Glass: American Artists and the Magic of Murano. This exhibition catalogue is the first comprehensive examination of the American Grand Tour to Venice in the late nineteenth century, revealing the glass furnaces and their new creative boom as a vibrant facet of the city's allure. This gorgeously illustrated catalogue features paintings and prints by John Singer Sargent, James McNeill Whistler, Frank Duveneck, Thomas Moran, William Merritt Chase, Maurice Prendergast, Maxfield Parrish, Louise Cox, and Ellen Day Hale alongside rarely seen Venetian glass mosaic portraits and glass cups, vases, and urns by the leading Murano glassmakers. Reuniting these exquisitely crafted objects with paintings, etchings, and drawings from the same milieu, this catalogue recovers and explains their past significance. Five new essays from experts in the history of American art and of Venetian glass provide the first combined survey of fine and decorative arts from the Venetian Grand Tour, offering a unique and valuable contribution to the fields of American Art and nineteenth-century cultural history. Ultimately, this project demonstrates the lasting impact of the nineteenth-century Venetian glass revival on American art, literature, and education, as well as period concepts of gender and social class.\"-- Provided by publisher.

Mutation rate is a crucial evolutionary parameter that has typically been treated as a constant in population genetic analyses. However, the propensity to mutate is likely to vary among co-existing individuals within a population, due to genetic polymorphisms, heterogeneous environmental influences, and random physiological fluctuations. We review the evidence for mutation rate heterogeneity and explore its consequences by extending classic population genetic models to allow an arbitrary distribution of mutation rate among individuals, either with or without inheritance. With this general new framework, we rigorously establish the effects of heterogeneity at various evolutionary timescales. In a single generation, variation of mutation rate about the mean increases the probability of producing zero or many simultaneous mutations on a genome. Over multiple generations of mutation and selection, heterogeneity accelerates the appearance of both deleterious and beneficial multi-point mutants. At mutation-selection balance, higher-order mutant frequencies are likewise boosted, while lower-order mutants exhibit subtler effects; nonetheless, population mean fitness is always enhanced. We quantify the dependencies on moments of the mutation rate distribution and selection coefficients, and clarify the role of mutation rate inheritance. While typical methods of estimating mutation rate will recover only the population mean, analyses assuming mutation rate is fixed to this mean could underestimate the potential for multi-locus adaptation, including medically relevant evolution in pathogenic and cancerous populations. We discuss the potential to empirically parameterize mutation rate distributions, which have to date hardly been quantified.

Background Even though a plethora of systemic therapies have been proposed for necrobiotic xanthogranuloma (NXG), there is no systematic review on this topic in literature. Objective To review all existing literature on the systemic therapy of NXG in order to identify the most effective therapies. Methods All reported papers in the literature were screened for systemic treatments of NXG. Papers without proper description of the therapies, papers describing topical therapy, and articles without assessment of effectiveness were excluded. Subsequently, we analyzed 79 papers and a total of 175 cases. Results The most effective treatments for NXG are intravenous immunoglobulins (IVIG), corticosteroids, and combination therapies including corticosteroids. Conclusions Corticosteroids and IVIG should therefore be considered first-line treatments in patients with NXG.

The ability of a large ensemble of regional climate models to accurately simulate heat waves at the regional scale of Europe was evaluated. Within the EURO-CORDEX project, several state-of-the art models, including non-hydrostatic meso-scale models, were run for an extended time period (20 years) at high resolution (12 km), over a large domain allowing for the first time the simultaneous representation of atmospheric phenomena over a large range of spatial scales. Eight models were run in this configuration, and thirteen models were run at a classical resolution of 50 km. The models were driven with the same boundary conditions, the ERA-Interim re-analysis, and except for one simulation, no observations were assimilated in the inner domain. Results, which are compared with daily temperature and precipitation observations (ECA&D and E-OBS data sets) show that, even forced by the same re-analysis, the ensemble exhibits a large spread. A preliminary analysis of the sources of spread, using in particular simulations of the same model with different parameterizations, shows that the simulation of hot temperature is primarily sensitive to the convection and the microphysics schemes, which affect incoming energy and the Bowen ratio. Further, most models exhibit an overestimation of summertime temperature extremes in Mediterranean regions and an underestimation over Scandinavia. Even after bias removal, the simulated heat wave events were found to be too persistent, but a higher resolution reduced this deficiency. The amplitude of events as well as the variability beyond the 90th percentile threshold were found to be too strong in almost all simulations and increasing resolution did not generally improve this deficiency. Resolution increase was also shown to induce large-scale 90th percentile warming or cooling for some models, with beneficial or detrimental effects on the overall biases. Even though full causality cannot be established on the basis of this evaluation work, the drivers of such regional differences were shown to be linked to changes in precipitation due to resolution changes, affecting the energy partitioning. Finally, the inter-annual sequence of hot summers over central/southern Europe was found to be fairly well simulated in most experiments despite an overestimation of the number of hot days and of the variability. The accurate simulation of inter-annual variability for a few models is independent of the model bias. This indicates that internal variability of high summer temperatures should not play a major role in controlling inter-annual variability. Despite some improvements, especially along coastlines, the analyses conducted here did not allow us to generally conclude that a higher resolution is clearly beneficial for a correct representation of heat waves by regional climate models. Even though local-scale feedbacks should be better represented at high resolution, combinations of parameterizations have to be improved or adapted accordingly.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an extremely rare hematologic malignancy with an aggressive course and poor prognosis. Treatment remains challenging particularly in patients who are ineligible for stem cell transplantation due to resistance to conventional chemotherapy. The introduction of tagraxofusp, a CD123-directed cytotoxin, has significantly expanded therapeutic options and improved outcomes for patients with BPDCN. However, its use can be accompanied by notable adverse events, especially capillary leak syndrome, underscoring the need for careful patient selection and monitoring. Up to date, no data is available regarding the safety of tagraxofusp in patients with chronic kidney failure and cardiovascular co-morbidities. We present the case of a 79-year-old male who developed a solitary, rapidly progressing skin lesion on his lower back. The lesion represented the first manifestation of BPDCN with bone marrow infiltration and concomitant myelodysplastic syndrome (MDS). Molecular analysis identified mutations in CBL, TET2, ZRSR2 and KRAS. Non-eligible for stem cell transplantation, the patient was admitted to treatment with tagraxofusp in a dose-reduced protocol due to concomitant chronic kidney disease (CKD). After three doses of the first cycle, treatment needed to be stopped due to acute-on-chronic renal failure. After treatment disruption, kidney failure was completely restituted to pre-treatment levels. Notably, skin and bone marrow biopsies demonstrated a dermatologic complete response and partial remission of bone marrow infiltration. A watch and wait concept was followed, and prolonged therapy response was obtained for 8 months before relapse. To our knowledge, this is the first reported case demonstrating the use of tagraxofusp in a patient with BPDCN and advanced chronic kidney disease, showing that even a minimum of tolerated treatment dose can induce a sustained response. Despite the risk of adverse events, tagraxofusp should be considered a viable treatment option for elderly patients with poor performance status and significant comorbidities who are ineligible for intensive chemotherapy or stem cell transplantation, as even limited exposure may achieve meaningful clinical responses.

Floods due to intense rainfall are a major hazard to both people and infrastructure in western Norway. Here steep orography enhances precipitation and the complex terrain channels the runoff into narrow valleys and small rivers. In this study we investigate a major rainfall and flooding event in October 2014. We compare high-resolution numerical simulations with measurements from rain gauges deployed in the impacted region. Our study has two objectives: (i) to understand the dynamical processes that drove the high rainfall and (ii) the importance of high grid resolution to resolve intense rainfall in complex terrain. This is of great interest for numerical weather prediction and hydrological modelling. Our approach is to dynamically downscale the ERA-Interim reanalysis with the Weather Research and Forecasting model (WRF). We find that WRF gives a substantially better representation of precipitation both in terms of absolute values as well as spatial and temporal distributions than a coarse resolution reanalysis. The largest improvement between the WRF simulations is found when we decrease the horizontal model grid spacing from 9 km to 3 km. Only minor additional improvements are obtained when downscaling further to 1 km. We believe that this is mainly related to the orography in the study area and its representation in the model. Realistic representations of gravity waves and the seeder–feeder effect seem to play crucial roles in reproducing the precipitation distribution correctly. An analysis of associated wavelengths shows the importance of the shortest resolvable length scales. On these scales our simulations also show differences in accumulated precipitation of up to 300 mm over four days, further emphasising the need for resolving short wavelengths. Therefore, our results clearly demonstrate the need for high-resolution dynamical downscaling for extreme weather impact studies in regions with complex terrain.

ObjectiveThe purpose of this study was to compare the utility of two-dimensional high-resolution (2D), 3-dimensional with multiplanar reconstruction (3D MPR), and radially reformatted (RR) MRIs when evaluating the complexities of the hip joint in patients with femoroacetabular impingement (FAI). We hypothesized RR would be superior in detecting labral pathology and 2D would be superior in detecting transition zone and acetabular cartilage injury.Materials and methods2D, 3D MPR, and RR MRIs of 33 patients, who later underwent surgical treatment for FAI, were evaluated for sensitivity, specificity, and accuracy. Bland-Altman methods were used to estimate agreement between each method and the gold-standard, arthroscopic visualization of the hip joint, regarding the percentage of the hip joint affected by each injury type.Results3D MPR and RR groupings were associated with the highest sensitivity and accuracy for labral injury. 3D MPR demonstrated the smallest bias in assessing the percentage of joint affected by labral injury and was the most accurate in identifying acetabular cartilage injury, whereas RR had the smallest mean difference in assessing the percentage of joint affected by acetabular cartilage injury. 2D was the most accurate in identifying transition zone injuries, while RR was superior in assessing the percentage of the joint affected by transition zone injury.ConclusionsOur results suggest that including both 3D MPR and RR MRI groupings is favorable for accurate joint visualization and well-informed treatment planning, especially given that labral injury is a main source of pain and dysfunction for FAI patients.

The Innovative Strategies for Observations in the Arctic Atmospheric Boundary Layer Program (ISOBAR) is a research project investigating stable atmospheric boundary layer (SBL) processes, whose representation still poses significant challenges in state-of-the-art numerical weather prediction (NWP) models. In ISOBAR ground-based flux and profile observations are combined with boundary layer remote sensing methods and the extensive usage of different unmanned aircraft systems (UAS). During February 2017 and 2018 we carried out two major field campaigns over the sea ice of the northern Baltic Sea, close to the Finnish island of Hailuoto at 65°N. In total 14 intensive observational periods (IOPs) resulted in extensive SBL datasets with unprecedented spatiotemporal resolution, which will form the basis for various numerical modeling experiments. First results from the campaigns indicate numerous very stable boundary layer (VSBL) cases, characterized by strong stratification, weak winds, and clear skies, and give detailed insight in the temporal evolution and vertical structure of the entire SBL. The SBL is subject to rapid changes in its vertical structure, responding to a variety of different processes. In particular, we study cases involving a shear instability associated with a low-level jet, a rapid strong cooling event observed a few meters above ground, and a strong wave-breaking event that triggers intensive near-surface turbulence. Furthermore, we use observations from one IOP to validate three different atmospheric models. The unique finescale observations resulting from the ISOBAR observational approach will aid future research activities, focusing on a better understanding of the SBL and its implementation in numerical models.