ALBERT

Description: Background: Bacteria grown on semi-solid media can build two types of multicellular structures, depending on the circumstances. Bodies (colonies) arise when a single clone is grown axenically (germ-free), whereas multispecies chimeric consortia contain monoclonal microcolonies of participants. Growth of an axenic colony, mutual interactions of colonies, and negotiation of the morphospace in consortial ecosystems are results of intricate regulatory and metabolic networks. Multicellular structures developed by Serratia sp. are characteristically shaped and colored, forming patterns that reflect their growth conditions (in particular medium composition and the presence of other bacteria). Results: Building on our previous work, we developed a model system for studying ontogeny of multicellular bacterial structures formed by five Serratia sp. morphotypes of two species grown in either "germ-free" or "gnotobiotic" settings (i.e. in the presence of bacteria of other conspecific morphotype, other Serratia species, or E. coli). Monoclonal bodies show regular and reproducible macroscopic appearance of the colony, as well as microscopic pattern of its growing margin. Standard development can be modified in a characteristic and reproducible manner in close vicinity of other bacterial structures (or in the presence of their products). Encounters of colonies with neighbors of a different morphotype or species reveal relationships of dominance, cooperation, or submission; multiple interactions can be summarized in "rock -- paper -- scissors" network of interrelationships. Chimerical (mixed) plantings consisting of two morphotypes usually produced a "consortium" whose structure is consistent with the model derived from interaction patterns observed in colonies. Conclusions: Our results suggest that development of a bacterial colony can be considered analogous to embryogenesis in animals, plants, or fungi: to proceed, early stages require thorough insulation from the rest of the biosphere. Only later, the newly developing body gets connected to the ecological interactions in the biosphere. Mixed "anlagen" cannot accomplish the first, germ-free phase of development; hence, they will result in the consortium of small colonies. To map early development and subsequent interactions with the rest of the biospheric web, simplified gnotobiotic systems described here may turn to be of general use, complementing similar studies on developing multicellular eukaryots under germ-free or gnotobiotic conditions.

Description: Arid regions in the Old World Dry Belt are assumed to be marginal regions, not only in ecological terms, but also economically and socially. Such views in geography, archaeology, and sociology are—despite the real limits of living in arid landscapes—partly influenced by derivates of Central Place Theory as developed for European medieval city-based economies. For other historical time periods and regions, this narrative inhibited socio-economic research with data-based and non-biased approaches. This paper aims, in two arid Graeco-Roman landscapes, to show how far approaches from landscape archaeology and social network analysis combined with the “small world phenomenon” can help to overcome a dichotomic view on core places and their areas, and understand settlement patterns and economic practices in a nuanced way. With Hauran in Southern Syria and Marmarica in NW-Egypt, I revise the concept of marginality, and look for qualitatively and spatially defined relationships between settlements, for both resource management and social organization. This ‘un-central’ perspective on arid landscapes provides insights on how arid regions functioned economically and socially due to a particular spatial concept and connection with their (scarce) resources, mainly water.

Description: Introduction: Fibrin degradation products, D-Dimer and X-oligomers, are biomarkers for activation of coagulation. D-Dimer testing is recommended as an additional diagnostic tool for proximal deep vein thrombosis (DVT) and pulmonary embolism (PE), in conjunction with clinical presentation and pre-test probability (Lim, et al. Blood Adv. 2018). D-Dimer levels naturally increase in patients over the age of 50 years, which reduces the specificity of D-Dimer levels as a diagnostic aid for proximal DVT and PE in older patients. We conducted a study to assess the diagnostic accuracy of the Tina-quant® D-Dimer Gen.2 (D-DI2; Roche Diagnostics) assay in patients with a low or intermediate pretest probability for proximal DVT or PE (Bertsch, et al. ISTH 2020; abstract PB0600). An exploratory objective of the study was to evaluate the diagnostic accuracy of the D-DI2 assay in the total study population after applying an age-adjusted cut-off value for patients aged 〉50 years. Methods: This prospective, observational, multi-center study was conducted between July 2017 and August 2019. Samples were collected at six European hospitals or specialist referral centers, or purchased from a commercial vendor (BioPartners Inc.). The 3.2% citrated plasma samples were analyzed at a central site using the D-DI2 assay on the cobas t 711 analyzer (Roche Diagnostics). Eligible patients were aged ≥18 years, presenting with symptoms suggestive of proximal DVT and/or PE, and with a low or intermediate pretest probability of DVT or PE by Wells score. Main exclusion criteria included DVT and/or PE symptoms for 〉7 days or a previous diagnosis of DVT and/or PE. DVT and/or PE were diagnosed according to local imaging protocols and standard-of-care procedures, in line with current clinical guidelines. Patients were followed-up for ≥90 days after hospital discharge to verify the clinical diagnosis and record any adverse events. In the primary analysis, a D-DI2 assay cut-off value of 0.5 μg fibrinogen equivalent units (FEU)/mL was applied across all patients, regardless of age. For the purpose of this exploratory analysis, age-adjusted cut-off values were calculated by multiplying age by 0.01 μg FEU/mL for patients aged 〉50 years. Results: In total, 2516 patients were included in the analysis (1741 DVT cohort; 775 PE cohort); of these, 1538 patients were aged 〉50 years (996 DVT cohort; 542 PE cohort) and the D-DI2 assay cut-off values for these patients were age-adjusted accordingly. The parameters for diagnostic accuracy for both the DVT and PE cohorts, unadjusted and age-adjusted values, are provided in the Table. Both negative predictive value (NPV) and sensitivity remained high after adjustment for age across both cohorts; however, there were slight decreases compared with the unadjusted values. Positive predictive value (PPV) was increased in both cohorts after age adjustment when compared with the unadjusted values. A reduction in false positives were reported for both the DVT (27%) and PE (26%) cohorts when adjusted for age compared with the unadjusted values. After age-adjustment, the number of false negatives in the total study population increased slightly in the DVT cohort (from zero to one case) and in the PE cohort (from one to five cases). Overall, specificity was increased when the results were adjusted for age. Conclusions: In our study population, when used in conjunction with a low or intermediate pretest probability for DVT and/or PE according to Wells criteria, the D-DI2 assay identifies patients at very low risk for proximal DVT and PE. Adjustment of the cut-off value for age resulted in a slight decrease in NPV, though still below the diagnostic threshold. The benefit of a reduction in false positives observed after age adjustment has the potential to prevent further unnecessary diagnostic procedures for patients. Disclosures Bertsch: Nuremberg General Hospital/Paracelsus Medical University: Current Employment. Blaschke:BMBF: Research Funding; Innovationsfonds: Research Funding; DGINA: Membership on an entity's Board of Directors or advisory committees. Body:University of Manchester: Current Employment; Beckman Coulter: Consultancy; LumiraDx: Consultancy; Roche Diagnostics: Consultancy; Siemens Healthineers: Consultancy; Abbott Point of Care: Consultancy; Abbott Point of Care: Research Funding; Roche Diagnostics: Research Funding; American Association of Clinical Chemistry (sponsored session from Roche, Abbott, ET Healthcare, Ortho, Siemens, Beckman): Speakers Bureau; LumiraDx advisory committee: Membership on an entity's Board of Directors or advisory committees; Creavo (chair of Trial Steering Committee): Membership on an entity's Board of Directors or advisory committees. Davidson:Roche Diagnostics International: Current Employment. Rieger:Roche Diagnostics GmbH: Current Employment. Horner:Salford Royal NHS Foundation Trust: Current Employment. Sonner:Roche Diagnostics GmbH: Consultancy; TRIGA-S Scientific Solutions: Current Employment. Sun:Roche Diagnostics GmbH: Current Employment. Turnes:ICON Clinical Research UK Ltd: Current Employment. Hoffman:Roche Diagnostics GmbH, Germany: Current Employment.

Description: Background Pituitary dwarfism (PD) in German Shepherd dogs (GSD) is a rare endocrinopathy. Cause and inheritance of the disease are well characterized, but the overall survival time, presence of concurrent diseases, quality of life (QoL) and influence of different treatment options on those parameters is still not well investigated. The aim of this study was to obtain data regarding the disease pattern of GSD with PD and to investigate the impact of treatment. Methods 47 dogs with dwarfism (presumably PD) and 94 unaffected GSD serving as controls were enrolled. Data were collected via a standardized questionnaire, which every owner of a participating dog had completed. Dogs with PD were grouped based on three categories of treatment: Group 1 (untreated), group 2 (treated with levothyroxine), group 3 (treated with thyroxine and progestogens or with growth hormone (GH)). Groups were compared using One-Way-Anova, Kruskal-Wallis test or Wilcoxon-rank-sum test. Categorical analysis was performed using Two-Sample-Chi-Squared-test. Results Dogs treated with thyroxine and gestagen or GH were significantly taller and heavier compared to all other dogs with PD. Quality of life was best in dogs with PD treated with thyroxine and similar to unaffected GSD. Treatment increased survival time in dogs with PD independent of the treatment strategy. Dogs receiving thyroxine and progestogens or GH did not develop chronic kidney disease (CKD). Conclusion GSD with PD should be treated at least for their secondary hypothyroidism to increase survival time. Additional treatment with progestogens or GH improves body size and seems to protect against the occurrence of CKD.