Aus der chirurgischen Klinik in G~ttingen. Ueber freie Kt~rper in den Gelenken. Von Prof, ~'Snig. 1. Die Corpora mobilia im Ellenbogengelenk. Die Geschichte der beweglichen Kuorpel-Knochenk~rper, der Corpora mobilia, in den menschlichen Gelenken, der Gelenkmiiuse, wie sie in naiver Weise auf Grund ihrer nicht selten an die raschen Bewegungen einer Maus erinnernden Wanderungen innerhalb der Gelenksiicke yon unseren Vorfahren ffenannt wurden, hat noch mancho dunkle Seite. Erst seit die Antiseptik uns erlaubt, diesolben nicht nur aus den Gelenken zu entfernen, sondern auch (ifter einmal das Gelenk selbst anzusehen, in welchem sich der KiJrper aufh~ilt, sind wit Chirurffen in der Lage, aus der Beobachtung am Lebenden Gesichtspunkte fiir die Entstehung derselben zu gewinnen. Auch in Beziehung auf das Vorkommen dieser Kiirper in den verschiedenen Ge-Icnken hat sich unsere Erkenntniss seit jener Zeit erweitert, und wenn der Chirurg frtlher bei der Besprechung der , Gelenkmaus" so gut wie ausnahmslos an das Kniegelenk dachte, so wissen wir jetzt, dass die fraglichen Bildungen in alien Gelenken vorkommen. Ein Gelenk ist aber ganz besonders unter den gr(isseren Kiirpergelenken in Beziehung auf die Haufigkeit seiner Erkrankunff neben dem Kniegelenk zu nennen, eine Thatsache, aaf welche bereits andere Chirurgen, yon deutschen fienne ich besonders Carl Hueter, hingewiesen haben, ich meine das Ellenbogengelenk. Ich will nun hier zuniichst Beitrage zu der Geschichte der Fremdk~irper in diesem Gelenk, ffesttitzt auf klinische und anatomische Beobachtungen, geben. Denn ich glaube, dass es zur Erkliirung einer Reihe yon dunklen, meist in intermittirender Weise auftretenden Erkrankungen ftihrt, wenn man genaue Kenntniss dieser im Ganzen doch recht typischen Verh~ltnisse in dem fraglichen Gelenk sich aneignet. Es werden sich aus der

BackgroundOne of the key clinical features of Alzheimer’s disease (AD) is impairment in daily functioning. Patients with mild cognitive impairment (MCI) also commonly have mild problems performing complex tasks. Information and communication technology (ICT), particularly techniques involving imaging and video processing, is of interest in order to improve assessment. The overall aim of this study is to demonstrate that it is possible using a video monitoring system to obtain a quantifiable assessment of instrumental activities of daily living (IADLs) in AD and in MCI.MethodsThe aim of the study is to propose a daily activity scenario (DAS) score that detects functional impairment using ICTs in AD and MCI compared with normal control group (NC). Sixty-four participants over 65 years old were included: 16 AD matched with 10 NC for protocol 1 (P1) and 19 MCI matched with 19 NC for protocol 2 (P2). Each participant was asked to undertake a set of daily tasks in the setting of a “smart home” equipped with two video cameras and everyday objects for use in activities of daily living (8 IADLs for P1 and 11 for P2, plus 4 temporal execution constraints). The DAS score was then computed from quantitative and qualitative parameters collected from video recordings.ResultsIn P1, the DAS score differentiated AD (DASAD,P1 = 0.47, 95% confidence interval [CI] 0.38–0.56) from NC (DASNC,P1 = 0.71, 95% CI 0.68–0.74). In P2, the DAS score differentiated MCI (DASMCI,P2 = 0.11, 95% CI 0.05–0.16) and NC (DASNC,P2 = 0.36, 95% CI 0.26–0.45).ConclusionIn conclusion, this study outlines the interest of a novel tool coming from the ICT world for the assessment of functional impairment in AD and MCI. The derived DAS scores provide a pragmatic, ecological, objective measurement which may improve the prediction of future dementia, be used as an outcome measurement in clinical trials and lead to earlier therapeutic intervention.

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SUMMARYThe mutational pattern of IgV H and IgV L genes from synovial tissue B cell hybridomas (n ¼ 8) of patients (n ¼ 4) with rheumatoid arthritis (RA) was analysed, which had been produced by the electrofusion technique without prior in vitro stimulation. The molecular data were correlated with immunohistopathological data and parameters of local disease activity. The IgV H genes of the B cell hybridomas belonged to the V H 3 family (DP42; DP47, n ¼ 2; DP53), the V H 1 family (DP75), the V H 4 family (DP71) and the V H 5 family (DP73); 7/7 IgV H genes showed somatic mutations, the R/S ratio (CDR) was > 3 in 4/7 IgV H genes and the mean R/S ratio of all IgV H genes was 9·3 (CDR) and 1·0 (FR), suggesting an antigen-dependent selection. The IgV L /l genes belonged to the Vl1 family (DPL2, DPL5, DPL8nf), the Vl2 family (DPL11, n ¼ 2) and to the Vl6 family (IGLV6S1); 6/6 IgV L genes showed somatic mutations, the R/S ratio (CDR) was > 3 in 3/6 IgV L genes and the mean R/S ratio of all IgV L was 3·0 (CDR) and 2·3 (FR), suggesting an antigen-dependent selection. The synovial tissue exhibited germinal centres in the follicles (3/4), with the unique distribution of Ki-M4 þ follicular dendritic cells and Ki-67 þ proliferating cells and a dominance of IgA þ plasma cells (3/3). All patients were positive for RF in serum and exhibited severe local symptoms (swelling 4/4; warmth 4/4; effusion 2/4), whereas the hybridomas were negative for RF. Since B cell hybridomas showed hypermutation and affinity selection for IgV H and IgV L /l genes and the patients exhibited severe local symptoms with germinal centres in synovial tissue, this study indicates that an antigen-driven process is behind the B cell expansion in the synovial tissue of clinically affected joints. These mutated B hybridomas were negative for RF, thus suggesting that antigens different from RF are also involved in the local B cell expansion and in the chronic synovitis of RA.Keywords rheumatoid arthritis rheumatoid factors germinal centres V H and V L repertoire affinity maturation

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Abstract-The next step in the Wendelstein stellarator line is the large superconducting device Wendelstein 7-X, presently under construction in Greifswald. Steady-state operation is an intrinsic feature of stellarators, and one key element of the Wendelstein 7-X mission is to demonstrate steady-state operation at reactor relevant plasma conditions, as required for an economic fusion reactor. Such steady-state operation requires development of special technogies to be discussed in this paper.

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Pancreatic ductal adenocarcinoma (PDAC) is characterized by high drug resistance and poor prognosis. Novel therapeutic and stratification strategies are urgently needed. Here, we present an integration of in-depth genomic and transcriptomic characterization with drug screening and clinical outcome based on a catalogue of 51 patient-derived tumor organoids (PDOs) from resected PDAC. Known PDAC molecular subtypes and their prognostic value are conserved in organoids. Integration of transcriptomic and drug response profiles suggest a metabolism-mediated modulations of drug resistance. Copy number alterations on chromosome 13q and wild-type status of TP53 emerged as potential novel genomic biomarkers for sensitivity to 5-FU and oxaliplatin treatment, respectively. Functional testing of targeted drugs in PDOs revealed its additional value for genome-driven personalized oncology. Co-deletion of TP53/POLR2A increased vulnerability to RNA polymerase II inhibition, pointing to a promising target for personalized treatment in PDAC.