Phase Transitions and Computational Difficulty in Random Constraint Satisfaction Problems

We review the understanding of the random constraint satisfaction problems, focusing on the q-coloring of large random graphs, that has been achieved using the cavity method of the physicists. We also discuss the properties of the phase diagram in temperature, the connections with the glass transition phenomenology in physics, and the related algorithmic issues.Comment: 10 pages, Proceedings of the International Workshop on Statistical-Mechanical Informatics 2007, Kyoto (Japan) September 16-19, 200

Healthcare Resource Utilization and Associated Costs of German Patients with Diffuse Large B-Cell Lymphoma: A Retrospective Health Claims Data Analysis

Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin's lymphoma with increasing prevalence. Although the disease burden associated with DLBCL is high, only limited data on healthcare resource utilization (HCRU) and associated costs of German patients with DLBCL is available. Methods: Using a large claims database of the German statutory health insurance with 6.7 million enrollees, we identified patients who were newly diagnosed with DLBCL between 2011 and 2018 (index date). Treatment lines were identified based on a predefined set of medication. HCRU and related costs were collected for the entire post index period and per treatment line. Results: A total of 2495 incident DLBCL patients were eligible for the analysis. The average follow-up time after index was 41.7 months. During follow-up, 1991 patients started a first-line treatment, 868 a second-line treatment, and 354 a third-line treatment. Overall, patients spent on average (SD) 5.24 (6.17) days per month in hospital after index. While on anti-cancer treatment, this number increased to nine (10.9) in first-line, 8.7 (13.7) in second-line, and 9.4 (15.8) in third-line treatments. Overall costs per patient per month (PPPM) increased from (sic)421 (875.70) before to (sic)3695 (4652) after index. While on a treatment line, PPPM costs were (sic)17,170 (10,246) in first-line, (sic)13,362 (12,685) in second-line, and (sic)12,112 (16,173) in third-line treatments. Time-unadjusted absolute costs sum up to (sic)59,868 (43,331), (sic)35,870 (37,387), and (sic)28,832 (40,540) during first-line, second-line, and third-line treatments, respectively. The main cost drivers were hospitalizations (71% of total costs) and drug acquisition costs (18% of total costs). Conclusions: The financial burden of DLBCL in Germany is high, mainly due to hospitalization and drug costs. Therefore, there is a high medical need for new cost-effective therapeutic options that can lower the disease burden and remain financially viable to support the growing number of patients with this aggressive disease

Adherence and motility characteristics of clinical Acinetobacter baumannii isolates

Acinetobacter baumannii continues to be a major health problem especially in hospital settings. Herein, features that may play a role in persistence and disease potential were investigated in a collection of clinical A. baumannii strains from Australia. Twitching motility was found to be a common trait in A. baumannii international clone I strains and in abundant biofilm formers, whereas swarming motility was only observed in isolates not classified within the international clone lineages. Bioinformatic analysis of the type IV fimbriae revealed a correlation between PilA sequence homology and motility. A high level of variability in adherence to both abiotic surfaces and epithelial cells was found. We report for the first time the motility characteristics of a large number of A. baumannii isolates and present a direct comparison of A. baumannii binding to nasopharyngeal and lung epithelial cells.8 page(s

CMRF-56+ blood dendritic cells loaded with mRNA induce effective antigen-specific cytotoxic T lymphocyte responses

There are numerous transcriptional, proteomic and functional differences between monocyte-derived dendritic cells (Mo-DC) and primary blood dendritic cells (BDC). The CMRF-56 monoclonal antibody (mAb) recognizes a cell surface marker, which is upregulated on BDC following overnight culture. Given its unique ability to select a heterogeneous population of BDC, we engineered a human chimeric (h)CMRF-56 IgG4 mAb to isolate primary BDC for potential therapeutic vaccination. The ability to select multiple primary BDC subsets from patients and load them with in vitro transcribed (IVT) mRNA encoding tumor antigen might circumvent the issues limiting the efficacy of Mo-DC. After optimizing and validating the purification of hCMRF-56 BDC, we showed that transfection of hCMRF-56 BDC with mRNA resulted in efficient mRNA translation and antigen presentation by myeloid BDC subsets, while preserving superior DC functions compared to Mo-DC. Immune selected and transfected hCMRF-56 BDC migrated very efficiently in vitro and as effectively as cytokine matured Mo-DC in vivo. Compared to Mo-DC, hCMRF-56 BDC transfected with influenza matrix protein M1 displayed superior MHC peptide presentation and generated potent antigen specific CD8 T-cell recall responses, while Wilms tumor 1 (WT1) transfected CMRF-56 BDC generated effective primary autologous cytotoxic T-cell responses. The ability of the combined DC subsets within hCMRF-56 BDC to present mRNA delivered tumor antigens merits phase I evaluation as a reproducible generic platform for the next generation of active DC immune therapies