104 research outputs found

    Droysen and the Prussian School of History

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    The Prussian School of History first predicted and advocated, then celebrated and defended, the unification of Germany by Prussia. Experts in German historiography and the history of German liberalism have often complained about the lack of a book, in any language, that traces the origins and explains the ideas of this school of history. Here is that book. Robert Southard finds that, for the Prussian School, history had an agenda. These historians generally expected history to complete its main tasks in their own time and country. The outcome of their politics was, really, an end of history —not a cessation to historical occurrences, but a cessation of onward historical movement because the historical process had already achieved its long-term, beneficent purposes. Leading us through the intricacies of important but untranslated works of J. G. Droysen, Max Duncker, Rudolph Hayn, and Heinrich von Sybel, Southard demonstrates their belief that the historical sequence was a continual unfolding of God\u27s plan. Indispensable for those interested in the history of German historical writing, this book also has major implications for understanding the history of political liberalism. Robert Southard (1945–2007) was professor of history at Earlham College. Illustrates well the links between historiography and the key issue of 19th-century German history—the reconstitution of a unified German state. —Choicehttps://uknowledge.uky.edu/upk_european_history/1007/thumbnail.jp

    Conventional intramuscular sedatives versus ziprasidone for severe agitation in adolescents: case-control study

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    <p>Abstract</p> <p>Objective</p> <p>The objective of this study was to compare intramuscular (IM) ziprasidone to conventional IM medications (haloperidol combined with lorazepam) for the treatment of severe agitation in adolescents (age 12–17).</p> <p>Methods</p> <p>We retrospectively identified consecutive severe agitation episodes (defined as requiring physical restraint) in adolescents treated with either IM ziprasidone or conventional IM agents in a psychiatric emergency room. For ziprasidone, the dosage was 20 mg for 23 episodes and 10 mg for 5 episodes. For 24 episodes treated with combined haloperidol and lorazepam, the dosages were 4.8 ± 0.3 SEM mg and 1.9 ± 0.4 mg respectively. Outcomes were the duration of restraint and need for adjunctive "rescue" medications within 60 minutes. These outcomes were decided prior to reviewing any records.</p> <p>Results</p> <p>No difference was found in restraint duration (ziprasidone, N = 28, 55 ± 5 minutes; haloperidol with lorazepam N = 24, 65 ± 7 minutes, P = NS). Use of "rescue" medications did not differ between the two groups. No changes in blood pressure were found, but pulse decreased 8.3 ± 2.4 for haloperidol with lorazepam and 8.9 ± 4.24 for ziprasidone (P = NS). No instances of excessive sedation or extra-pyramidal symptoms were documented.</p> <p>Conclusion</p> <p>In this study, IM ziprasidone appeared effective, well tolerated, and similar in clinical profile to combined conventional IM medications for treating severe agitation in adolescents. Given the reportedly favorable acute side effect profile of parenteral atypical agents, they may provide an alternative to conventional antipsychotics for treating acute agitation in both adult and adolescent populations. Future randomized, controlled studies are needed.</p

    Mechanisms of Response and Resistance to Combined Decitabine and Ipilimumab for Advanced Myeloid Disease

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    The challenge of eradicating leukemia in patients with acute myelogenous leukemia (AML) after initial cytoreduction has motivated modern efforts to combine synergistic active modalities including immunotherapy. Recently, the ETCTN/CTEP 10026 study tested the combination of the DNA methyltransferase inhibitor decitabine together with the immune checkpoint inhibitor ipilimumab for AML/myelodysplastic syndrome (MDS) either after allogeneic hematopoietic stem cell transplantation (HSCT) or in the HSCT-naïve setting. Integrative transcriptome-based analysis of 304 961 individual marrow-infiltrating cells for 18 of 48 subjects treated on study revealed the strong association of response with a high baseline ratio of T to AML cells. Clinical responses were predominantly driven by decitabine-induced cytoreduction. Evidence of immune activation was only apparent after ipilimumab exposure, which altered CD4+ T-cell gene expression, in line with ongoing T-cell differentiation and increased frequency of marrow-infiltrating regulatory T cells. For post-HSCT samples, relapse could be attributed to insufficient clearing of malignant clones in progenitor cell populations. In contrast to AML/MDS bone marrow, the transcriptomes of leukemia cutis samples from patients with durable remission after ipilimumab monotherapy showed evidence of increased infiltration with antigen-experienced resident memory T cells and higher expression of CTLA-4 and FOXP3. Altogether, activity of combined decitabine and ipilimumab is impacted by cellular expression states within the microenvironmental niche of leukemic cells. The inadequate elimination of leukemic progenitors mandates urgent development of novel approaches for targeting these cell populations to generate long-lasting responses. This trial was registered at www.clinicaltrials.gov as #NCT02890329

    The impact of non-equilibrium flow on the structure of turbulence over river dunes

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    This piece of research expands our description of how rivers flow over dunes on a river bed. Most of the scientific communities' research to date has used unnaturally steady conditions to measure how water moves over dunes. Yet these flow conditions are not strictly true to the variety of conditions nature produces, most importantly during floods. This research is the first detailed description of a wide range of flow states over dunes, and changes our present understanding of the structure of flow over dunes in rivers. Consequently, the scientific community will be able to use this new information to better model and simulate how rivers work, how they flood, and how they transport sediment towards the worlds deltas

    Spatially restricted drivers and transitional cell populations cooperate with the microenvironment in untreated and chemo-resistant pancreatic cancer

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    Pancreatic ductal adenocarcinoma is a lethal disease with limited treatment options and poor survival. We studied 83 spatial samples from 31 patients (11 treatment-naïve and 20 treated) using single-cell/nucleus RNA sequencing, bulk-proteogenomics, spatial transcriptomics and cellular imaging. Subpopulations of tumor cells exhibited signatures of proliferation, KRAS signaling, cell stress and epithelial-to-mesenchymal transition. Mapping mutations and copy number events distinguished tumor populations from normal and transitional cells, including acinar-to-ductal metaplasia and pancreatic intraepithelial neoplasia. Pathology-assisted deconvolution of spatial transcriptomic data identified tumor and transitional subpopulations with distinct histological features. We showed coordinated expression of TIGIT in exhausted and regulatory T cells and Nectin in tumor cells. Chemo-resistant samples contain a threefold enrichment of inflammatory cancer-associated fibroblasts that upregulate metallothioneins. Our study reveals a deeper understanding of the intricate substructure of pancreatic ductal adenocarcinoma tumors that could help improve therapy for patients with this disease
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