Severe Disseminated Coagulopathy Caused by Adenocarcinoma with Bone Marrow Metastasis

Background: Patients with mucin-producing adenocarcinoma have an increased risk for venous and arterial thrombosis. When these patients present with thrombocytopenia, disseminated intravascular coagulopathy (DIC) is often the underlying cause. Case Report: We report 2 patients who were admitted due to bleeding symptoms of unknown cause, in whom further workup revealed adenocarcinoma-induced DIC. Conclusion: In elderly patients presenting with signs of DIC, such as reduced fibrinogen levels, elevated prothrombin time, elevated D-dimer, and thrombocytopenia, without any obvious reason (e.g., sepsis), adenocarcinoma-associated coagulopathy should be considered as the underlying cause. Paradoxically, in these patients bleeding symptoms improve when the patient is sufficiently anti-coagulated with low molecular weight heparin. Treatment of the underlying disease is of central importance in controlling acute or chronic DIC associated with malignant diseases and chemotherapy should be started as soon as possible

Efficacy of Trabectedin in Patients with Advanced or Metastatic Alveolar Soft-Part Sarcoma

Background: Alveolar soft-part sarcoma (ASPS) is a rare sarcoma often occurring in young patients that is characterized by the unbalanced translocation der(17)t(X;17) (p11;q25). Although itusuallyshowsan indolent clinical course, the prognosis is usually poor in advanced disease. Since standard chemotherapy regimens used in soft-tissue sarcomas lack efficacy in ASPS, new therapeutic options are needed. We investigated the efficacy of trabectedin, which has demonstrated activity in a variety of cancer types including some of the most prevalent translocation-related sarcomas. Patients and Methods: 7 patients with metastatic or advanced ASPS treated with trabectedin in the Sarcoma Center Berlin-Brandenburg and the University Hospital of Greifswald were analyzed for median progression-free survival (mPFS), overall survival (OS), and therapy-related toxicity. Results: In 6 patients with documented disease progression, disease stabilization was reached with trabectedin; only 1 patient experienced progressive disease. The mPFS and OS were 7 months and 21 months, respectively, since the start of trabectedin treatment. Overall, no severe Common Toxicity Criteria (CTC) grade 3 or 4 toxicity was observed. Conclusions: The poor prognosis of patients with ASPS has so far been due to the unavailability of effective systemic treatments. Trabectedin can be considered the only currently registered drug with clinical activity in this disease

Mucositis after Reduced Intensity Conditioning and Allogeneic Stem Cell Transplantation

Background: Therapyrelated mucositis is associated with considerable morbidity. This complication following allogeneic stem cell therapy (alloSCT) is less severe after reduced intense conditioning (RIC); however, even here it may be serious. Methods: 52 patients (male: n = 35 (67%), female: n = 17 (33%)) at a median age of 62 years (35–73 years) underwent alloSCT after RIC. Conditioning was either total body irradiation (TBI)2Gy/±fludarabine (n = 33, 63.5%) or chemotherapy based. Graftversushost disease (GvHD) prophylaxis was carried out with cyclosporine A ± mycophenolate mofetil (MMF). 45 patients (87%) received shortcourse methotrexate (MTX). Mucositis was graded according to the Bearman and the World Health Organisation (WHO) scale. A variety of parameters were correlated with mucositis. Results: The Bearman and WHO scales showed excellent correlation. Mucositis was significantly more severe after chemotherapybased conditioning compared to conditioning with TBI2Gy/±fludarabine (p < 0.002) as well as in cases with an increase in creatinine levels above the upper normal value (UNV) on day +1 after SCT (p < 0.05). Furthermore, the severity correlated with time to engraftment of leucocytes (correlation coefficient (cc) = 0.26, p < 0.02) and thrombocytes (cc = 0.38, p < 0.001). Conclusions: The conditioning regimen and increased creatinine levels at day +1 were identified as factors predicting the severity of mucositis after RICSCT. Creatinine levels on day +1 after SCT may help identify patients at risk for severe mucositis in the further course of transplantation

Gemcitabine and Docetaxel for Epithelioid Sarcoma: Results from a Retrospective, Multi-Institutional Analysis

Objective: Epithelioid sarcoma (ES) presents unique clinical features in comparison to other sarcoma subtypes. Data regarding the benefits of chemotherapy are very limited. Combination regimens using gemcitabine and docetaxel (Gem/Doce) have proven to be effective, especially in uterine and nonuterine leiomyosarcoma. Yet, there is no available data on the efficacy of Gem/Doce in ES. Methods: A retrospective analysis of the three participating institutions was performed. Twenty-eight patients with an ES diagnosis presented at one of the participating institutions between 1989 and 2012. Of this group, 17 patients received chemotherapy. Results: Patients' median overall survival (OS) after the beginning of palliative chemotherapy was 21 months, and the 1-year OS was 87%. Twelve patients received Gem/Doce with a clinical benefit rate of 83%. The median progression-free survival (PFS) was 8 months for all patients receiving Gem/Doce. The best response was complete remission in 1 patient and partial remission in 6 patients. All 6 patients receiving Gem/Doce as a first-line treatment showed measurable responses with a median PFS of 9 months. Conclusions: In this retrospective study, Gem/Doce was an effective chemotherapeutic regimen for ES. Prospective studies are needed to better assess the effects of this combination drug therapy

The old, unique C1 chondrite Flensburg - Insight into the first processes of aqueous alteration, brecciation, and the diversity of water-bearing parent bodies and lithologies

On September 12, 2019 at 12:49:48 (UT) a bolide was observed by hundreds of eye-witnesses from the Netherlands, Germany, Belgium, Denmark and the UK. One day later a small meteorite stone was found by accident in Flensburg. The presence of short-lived cosmogenic radionuclides with half-lives as short as 16 days proves the recent exposure of the found object to cosmic rays in space linking it clearly to the bolide event. An exceptionally short exposure time of ~5000 years was determined. The 24.5 g stone has a fresh black fusion crust, a low density of <2 g/cm^3, and a magnetic susceptibility of logX = 4.35 (X in 10^-9 m^3/kg). The rock consists of relict chondrules and clusters of sulfide and magnetite grains set in a fine-grained matrix. The most abundant phases are phyllosilicates. Carbonates (~3.9 vol.%) occur as calcites, dolomites, and a Na-rich phase. The relict chondrules (often surrounded by sulfide laths) are free of anhydrous silicates and contain abundant serpentine. Lithic clasts are also surrounded by similar sulfide laths partly intergrown with carbonates. 53^Mn-^53Cr ages of carbonates in Flensburg indicate that brecciation and contemporaneous formation of the pyrrhotite-carbonate intergrowths by hydrothermal activities occurred no later than 4564.6 +- 1.0 Ma (using the angrite D'Orbigny as the Mn-Cr age anchor). This corresponds to 2.6 +- 1.0 or 3.4 +- 1.0 Ma after formation of CAIs, depending on the exact absolute age of CAIs. This is the oldest dated evidence for brecciation and carbonate formation, which likely occurred during parent body growth and incipient heating due to decay of 26Al. In the three oxygen isotope diagram, Flensburg plots at the 16O-rich end of the CM chondrite field and in the transition field to CV-CK-CR chondrites. The mass-dependent Te isotopic composition of Flensburg is slightly different from mean CM chondrites and is most similar to those of the ungrouped C2 chondrite Tagish Lake. On the other hand, 50Ti and 54Cr isotope anomalies indicate that Flensburg is similar to CM chondrites, as do the ~10 wt.% H2O of the bulk material. Yet, the bulk Zn, Cu, and Pb concentrations are about 30% lower than those of mean CM chondrites. The He, Ne, and Ar isotopes of Flensburg show no solar wind contribution; its trapped noble gas signature is similar to that of CMs with a slightly lower concentration of 20Netr. Based on the bulk H, C, and N elemental abundances and isotopic compositions, Flensburg is unique among chondrites, because it has the lightest bulk H and N isotopic compositions of any type 1 or 2 chondrite investigated so far. Moreover, the number of soluble organic compounds in Flensburg is even lower than that of the brecciated CI chondrite Orgueil. The extraordinary significance of Flensburg is evident from the observation that it represents the oldest chondrite sample in which the contemporaneous episodes of aqueous alteration and brecciation have been preserved. The characterization of a large variety of carbonaceous chondrites with different alteration histories is important for interpreting returned samples from the OSIRIS-REx and Hayabusa 2 missions.This work is partly funded by the Deutsche Forschungs- gemeinschaft (DFG, German Research Foundation) – Project-ID 263649064 – TRR 170 (A.B., C.B., T.K.); this is TRR170 Publication No. 119. M.S. and C.M. thank the Swiss National Science Foundation (SNF) for support. The work of H.B. and M.S. has been in parts carried out within the framework of the NCCR PlanetS supported by SNF. D.H. thanks F. Langenhorst for support and access to the FIB-SEM and TEM facilities at FSU-IGW, which are funded by the DFG via grant LA830/14-1. D.F. (CIW) acknowledges the support of the NASA awards 80NSSC19K0559 and 80NSSC20K0344

The Stubenberg meteorite—An LL6 chondrite fragmental breccia recovered soon after precise prediction of the strewn field

On March 6, 2016 at 21:36:51 UT, extended areas of Upper Austria, Bavaria (Germany) and the southwestern part of the Czech Republic were illuminated by a very bright bolide. This bolide was recorded by instruments in the Czech part of the European Fireball Network and it enabled complex and precise description of this event including prediction of the impact area. So far six meteorites totaling 1473 g have been found in the predicted area. The first pieces were recovered on March 12, 2016 on a field close to the village of Stubenberg (Bavaria). Stubenberg is a weakly shocked (S3) fragmental breccia consisting of abundant highly recrystallized rock fragments embedded in a clastic matrix. The texture, the large grain size of plagioclase, and the homogeneous compositions of olivine (Fa31.4) and pyroxene (Fs25.4) clearly indicate that Stubenberg is an LL6 chondrite breccia. This is consistent with the data on O, Ti, and Cr isotopes. Stubenberg does not contain solar wind-implanted noble gases. Data on the bulk chemistry, IR spectroscopy, cosmogenic nuclides, and organic components also indicate similarities to other metamorphosed LL chondrites. Noble gas studies reveal that the meteorite has a cosmic ray exposure (CRE) age of 36 ± 3 Ma and that most of the cosmogenic gases were produced in a meteoroid with a radius of at least 35 cm. This is larger than the size of the meteoroid which entered the Earth's atmosphere, which is constrained to <20 cm from short-lived radionuclide data. In combination, this might suggest a complex exposure history for Stubenberg.PostprintPeer reviewe

Artificial Conversational Companions A Requirements Analysis

This paper is based on several attempts to provide a definition of an Artificial Companion that can be found in the referenced literature. Although accepted by the research community, such descriptions set very high expectations of such agents, but they do not address the technical feasibility and the system limitations, that is why they need an elaborated and precise explanation. In this paper, we focus on computer agents that simulate human language behaviour, and are aimed to serve, to assist and to accompany their owner over a long period of time, that we call Artificial Conversational Companions. This is the first approach to analyse the effort required to meet the expectations of Artificial Conversational Companion and discuss the identified design issues

Towards Computational Models for a Long-term Interaction with an Artificial Conversational Companion

Abstract: In this paper we describe a design approach for an Artificial Conversational Companion according to ear-lier identified requirements of utility, adaptivity, conversational capabilities and long-term interaction. The Companion is aimed to help advanced learners of a foreign language to practice conversation via instant mes-senger dialogues. In order to model a meaningful long-term interaction with an Artificial Conversational Companion for this application case, it is necessary to understand how natural long-term interaction via chat between human language experts and language learners works. For this purpose, we created a corpus from instant messenger-based interactions between native speakers of German and advanced learners of German as a foreign language. We used methods from conversation analysis to identify rules of interaction. Examples from our data set are used to illustrate how particular requirements for the agent can be fulfilled. Finally, we outline how the identified patterns of interaction can be used for the design of an Artificial Conversational Companion.