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Skeletal dysplasias collectively affect a large number of patients worldwide. The majority of these disorders cause growth anomalies. Hence, assessing skeletal maturity via determining the bone age (BA) is one of the most valuable tools for their diagnoses. Moreover, consecutive BA assessments are crucial for monitoring the pediatric growth of patients with such disorders, especially for timing hormone treatments or orthopedic interventions. However, manual BA assessment is time-consuming and suffers from high intra-and inter-rater variability. This is further exacerbated by genetic disorders causing severe skeletal malformations. While numerous approaches to automatize BA assessment were proposed, few were validated for BA assessment on children with abnormal development. In this work, we present Deeplasia, an open-source prior-free deep-learning ensemble approach. After training on the public RSNA BA dataset, we achieve state-of-the-art performance with a mean absolute difference (MAD) of 3.87 months based on the average of six different reference ratings. Next, we demonstrate that Deeplasia generalizes to an unseen dataset of 568 X-ray images from 189 patients with molecularly confirmed diagnoses of seven different genetic bone disorders (including Achondroplasia and Hypochondroplasia) achieving a MAD of 5.84 months w.r.t. to the average of two references. Further, using longitudinal data from a subset of the cohort (149 images), we estimate the test-retest precision of our model ensemble to be at least at the human expert level (2.74 months). We conclude that Deeplasia suits assessing and monitoring the BA in patients with skeletal dysplasias.

Historic buildings are complex structures in which all the composing elements work together. Studies of heritage structures after seismic events have shown that timber roof structures strongly influence the seismic response of masonry structures, being able to reduce or enhance the out-of-plane displacement of the structure. Starting from these observations, three different types of roof structures, from the eighteenth, nineteenth and twentieth centuries, were introduced in the finite-element simulation software SCIA Engineer. The roof structures were subsequently placed on the same eighteenth-century masonry building with a ground floor and two upper floors, respecting its geometric features. Simulations were performed considering successively rigid, hinged or sliding connections between the roof and the masonry structure. At the same time, the traditionally crafted joints of the roof structures were consecutively modelled as hinged, rigid and semi-rigid (determined using three different methods). Ultimately, the top horizontal displacement, inter-storey drift and damage level of the masonry structure were compared. The main aims of this study were to observe if roof structures have an influence on the seismic behaviour of masonry buildings and to determine if selected parameters suffer any changes depending on the roof structure type, the roof–wall connections and joints’ axial stiffness.

Context Prediction of adult height (AH) is important in clinical management of short children. The conventional methods of Bayley-Pinneau (BP) or Roche-Wainer-Thissen (RWT) have limitations. Objective We aimed to develop a set of algorithms for AH prediction in patients with idiopathic short stature (ISS) which are specific for combinations of predicting variables. Methods Demographic and auxologic data were collected in childhood (1980s) and at AH (1990s). Data were collected by Dutch and German referral centers for pediatric endocrinology. A total of 292 subjects with ISS (219 male, 73 female) were enrolled. The population was randomly split into modeling (n = 235) and validation (n = 57) cohorts. Linear multi-regression analysis was performed with predicted AH (PAH) as response variable and combinations of chronological age (CA), baseline height, parental heights, relative bone age (BA/CA), birth weight, and sex as exploratory variables. Results Ten models including different exploratory variables were selected with adjusted R² ranging from 0.84 to 0.78 and prediction errors from 3.16 to 3.68 cm. Applied to the validation cohort, mean residuals (PAH minus observed AH) ranged from −0.29 to −0.82 cm, while the conventional methods showed some overprediction (BP: +0.53 cm; RWT: +1.33 cm; projected AH: +3.81 cm). There was no significant trend of residuals with PAH or any exploratory variables, in contrast to BP and projected AH. Conclusion This set of 10 multi-regression algorithms, developed specifically for children with ISS, provides a flexible tool for AH prediction with better accuracy than the conventional methods.

In most patients with chronic myeloid leukemia (CML) clonal cells can be kept under control by BCR::ABL1 tyrosine kinase inhibitors (TKI). However, overt resistance or intolerance against these TKI may occur. We identified the epigenetic reader BRD4 and its downstream-effector MYC as growth regulators and therapeutic targets in CML cells. BRD4 and MYC were found to be expressed in primary CML cells, CD34

Chronic myelomonocytic leukemia (CMML) is a stem cell-derived neoplasm characterized by dysplasia, uncontrolled expansion of monocytes and a substantial risk to transform to secondary acute myeloid leukemia (sAML). So far, little is known about CMML-initiating cells. We found that leukemic stem cells (LSC) in CMML reside in a CD34+/CD38– fraction of the malignant clone. Whereas CD34+/CD38– cells engrafted NSGS mice with overt CMML, no CMML was produced by CD34+/CD38+ progenitors or the bulk of CD34– monocytes. CMML LSC invariably expressed CD33, CD117, CD123 and CD133. In a subset of patients, CMML LSC also displayed CD52, IL-1RAP and/or CLL-1. CMML LSC did not express CD25 or CD26. However, in sAML following CMML, the LSC also expressed CD25 and high levels of CD114, CD123 and IL-1RAP. No correlations between LSC phenotypes, CMML-variant, mutation-profiles, or clinical course were identified. Pre-incubation of CMML LSC with gemtuzumab-ozogamicin or venetoclax resulted in decreased growth and impaired engraftment in NSGS mice. Together, CMML LSC are CD34+/CD38– cells that express a distinct profile of surface markers and target-antigens. During progression to sAML, LSC acquire or upregulate certain cytokine receptors, including CD25, CD114 and CD123. Characterization of CMML LSC should facilitate their enrichment and the development of LSC-eradicating therapies.

In Osterreich erkrankt fast jeder 25. Spitalspatient an einem Krankenhauskeim. Eine Studie sieht die Nation im Kampf gegen nosokomiale Infektionen im guten Mittelfeld. Ojan Assadian, Prasident der Osterreichischen Gesellschaft fur Krankenhaushygiene, erklart, warum die Umsetzung von wirksamen Hygienemasnahmen so muhsam ist.

Arthrose ist eine der häufigsten Erkrankungen des Bewegungsapparats beim Hund. Rund 20 % aller Hunde erkranken im Laufe ihres Lebens daran [1]. Schmerzen und Einschränkungen in der Beweglichkeit sind die Folge. Neue Erkenntnisse in der Pathophysiologie und Diagnostik ermöglichen eine individuell gelenks- und patientenspezifisch angepasste Therapie mittels multimodalem Management. Neben medikamentellen Methoden sind hier physikalische und manuelle Methoden zu nennen. Der Physiotherapie kommt dabei eine zentrale Rolle zu.

It is generally acknowledged that heritage buildings were built by taking their environment into consideration, and therefore they have a high resilience towards various climatic factors. The increasing negative effect of the climate change on the state of conservation of valuable heritage buildings has already been recognized by heritage protection organizations, such as: The United Nations Educational, Scientific and Cultural Organization (UNESCO), The International Council on Monuments and Sites (ICOMOS), as well as by the climate change related organizations, such as: The Intergovernmental Panel on Climate Change (IPCC). The recent extreme events, which took place in the western part of Romania, reinforced the importance of the study of the effect of the climate change on the state of conservation of the built heritage. On the 17th of September 2017, a severe wind, with peak wind velocities exceeding 122 km/h (33.8 m/s) affected the heritage structures of the historic city, Timisoara. In this area, most of the city and of the nearby villages, buildings date back from the 18th century. Among the most affected buildings by the storm were the 19th century village churches. The high wind velocities mainly led to the failure of the superior part of the church towers, i.e.: belfry, spire, main roof structure. The paper aims to analyze the failure mechanisms of the towers and of the roof structures of the historic churches, from this part of Romania, affected by the high wind velocities of this particular storm.

In einem Landeskrankenhaus wird einem Patienten das falsche Bein amputiert. Gegen derartige Verwechslungen wirken spezielle Sicherheitskonzepte. Allerdings werden diese ignoriert.

Historic timber roof structures represent some of the most complex structural solutions of Europe’s history. They were built, until the early 19th century, in a close connection with their surround...

Historic buildings have a high resilience in time due to the fact that they were designed by taking into consideration the environment and all the local conditions. However, nowadays not only their environment is changing fast. According to a current climatic change analysis, the climate all over the world has already suffered a severe change and, unfortunately, future scenarios indicate an even worse situation. The main effects of the climate change are as follows: high and long lasting temperatures during summer, precipitation pattern change, intensification of the local winds. To which we can add more intense or even frequent extreme events, such as: drought, abundant precipitation, snowfalls and hailstorms. All these changes have a heavily impact not only on the historic buildings, but also on the economy and society. The main purpose of this study to analyse the climatic change on different types of historic buildings, the way in which natural factors increase the degradation and the failure of the building structures/historic architectural details and how it can affect the aesthetics of the historic urban centres. The subject of the research was a small town in Romania, Oravita, which was chosen due to its diversity of its historical heritage and its special climatic condition. The study focused on simple buildings as well as on archaeological sites, railroads, bridges and dams.

Timisoara is a growing city in the western part of Romania, in a seismic area, with a lot of masonry buildings with historical and cultural value, with interesting structural elements such as vaults, arches, slabs, walls, that were affected by earthquakes, subsidence of foundations, negative human actions or lack of interventions. Masonry historical structures in Banat seismic area present particular failure mechanisms, so there is a need for new, modern, fast, easy-to-apply and reversible consolidation methods. With this type of methods is possible to assure the local and global resistance, ductility, stability and rigidity for historical buildings. This article shows the consolidation methods that were applied on the buildings Sf. Gheorghe 3 and 4, in the historical centre of Timisoara, on masonry structures with historical value. The solutions that were applied are using new, innovative fibre-reinforced composite materials, in order to repair the existing damages and prevent further ones. The consolidation solutions with these new composite materials reduce the buildings vulnerability and present the advantage of being fast and easy to be executed.

Background Mastocytoma are frequently diagnosed cutaneous neoplasms in dogs. In non-resectable mastocytoma patients, novel targeted drugs are often applied. The transcription factor STAT5 has been implicated in the survival of human neoplastic mast cells (MC). Our study evaluated the JAK2/STAT5 pathway as a novel target in canine mastocytoma. Materials and Methods We employed inhibitors of JAK2 (R763, TG101348, AZD1480, ruxolitinib) and STAT5 (pimozide, piceatannol) and evaluated their effects on 2 mastocytoma cell lines, C2 and NI-1. Results Activated JAK2 and STAT5 were detected in both cell lines. The drugs applied were found to inhibit proliferation and survival in these cells with the following rank-order of potency: R763 > TG101348 > AZD1480 > pimozide > ruxolitinib > piceatannol. Moreover, synergistic anti-neoplastic effects were obtained by combining pimozide with KIT-targeting drugs (toceranib, masitinib, nilotinib, midostaurin) in NI-1 cells. Conclusion The JAK2/STAT5 pathway is a novel potential target of therapy in canine mastocytoma.

Extreme actions represent a high risk for buildings belonging to historic urban areas and archaeological sites. Because of the conformation of the buildings, the low quality of used materials and the current state of conservation, these buildings tend to be very vulnerable to horizontal forces generated during earthquakes and terrorist attacks. This article analyses the mechanisms caused by extreme actions that are capable to generate a considerable degree of damage or even collapse of international cultural heritage buildings from historic urban centers and sites.