The impact of cold spells on the incidence of infectious gastroenteritis and relapse rates of inflammatory bowel disease: a retrospective controlled observational study

Goals: We aimed to assess the impact of very cold days on inflammatory bowel disease (IBD) flares and infectious gastroenteritis (IG). We defined a cold day using the World Meteorological definition of an ice day, which is a day with a maximum temperature below 0°C. Background: Recently, we have shown that heat waves increase the risk for IG and IBD flares. Study: We retrospectively collected data from 738 IBD and 786 IG patients admitted to the University Hospital of Zurich between 2001 and 2005 and from 506 patients with other noninfectious chronic intestinal inflammations as controls. Climate data were received by the Swiss Federal Office for Meteorology and Climatology. Results: There was no evidence for an increased risk of IBD flares (relative risk, RR = 0.99, 95% confidence interval, CI: 0.72-1.33, = 0.94) or IG flares (RR = 1.16, 95% CI: 087-1.52, = 0.30) on very cold days. This negative finding was confirmed in alternative formulations with lagged or cumulative (possibly lagged) effects. Conclusion: In this retrospective controlled observational study, no evidence for an increase in hospital admissions due to flares of IBD and IG during cold days was observed. This may be attributed to not relevantly altered bacterial growth conditions during cold days compared to heat waves

Schrumpfung und Urban Sprawl - analytische und planerische Problemstellungen

Das vorliegende UFZ-Diskussionspapier ist die Dokumentation des Workshops Schrumpfung und Urban Sprawl, der am 3. November 2003 am UFZ stattfand. Es führt damit eine Diskussions- und Forschungslinie fort, die in den 1990er Jahren durch Forscher und Praktiker aus unterschiedlichen Einrichtungen der Region Halle-Leipzig begründet wurde. Im Arbeitskreis Suburbanisierung wurden unter Koordination des UFZ disziplinäre Zugänge und praktische Erfahrungen zusammengeführt und daraus Handlungsempfehlungen abgeleitet. Zwischenzeitlich hat der Suburbanisierungsdruck, der noch Ende der 1990er Jahre konstatiert wurde, deutlich abgenommen nicht nur in der Region, sondern in ganz Ostdeutschland. Nichtsdestoweniger ist Suburbanisierung ein zentraler Gegenstand von raumbezogener Politik und räumlicher Planung geblieben und hat im Zusammenhang mit dem Thema Stadtumbau neue Relevanz gewonnen. So ist davon auszugehen, dass auch in der Region Halle-Leipzig die intensive Beschäftigung mit dem Problem der Suburbanisierung anhalten wird allerdings unter veränderten Vorzeichen. Im Mittelpunkt steht nunmehr die Frage, welche Anforderungen sich aus der Situation von demographischer und städtischer Schrumpfung für die wissenschaftliche und praktische Auseinandersetzung mit Suburbanisierung ergeben. So gilt es, unter anderem, zu klären, ob sich die Richtung von Sprawl unter Schrumpfungsbedingungen umkehrt, ob das Zusammenspiel von Schrumpfung und Sprawl zu einer neuen Stadtstruktur führt oder ob sich durch diese spezifische Situation die Segregationsmuster verändern. Auf dem Workshop selbst wurden vor allem die Möglichkeiten der Steuerung von Suburbanisierung bzw. Sprawl unter Schrumpfungsbedingungen behandelt. Dazu wurden Überlegungen und Ergebnisse, die im EU-Projekt URBS PANDENS am Fallbeispiel Leipzig gewonnen wurden, vorgestellt, diskutiert und mit Erfahrungen aus der Praxis bzw. aus einer anderen Region konfrontiert. Neben der empirischen Analyse spielt dabei ein im Rahmen von URBS PANDENS entwickeltes qualitatives Modell des Urban Sprawl eine zentrale Rolle. --

VEGFR2 and VEGFA polymorphisms are not associated with an inferior prognosis in Caucasian patients with aggressive B-cell lymphoma

Purpose Previous published data showed an impact of single‐nucleotide polymorphisms in the VEGF A and VEGFR2 genes on the survival of patients with various malignancies, among others diffuse large B‐cell lymphoma (DLBCL). Patients and Methods We investigated the role of four VEGF‐A and two VEGFR‐2 gene polymorphisms on the outcome of 273 patients with diffuse large B‐cell lymphoma who were treated with R‐CHOP within a prospective, randomized trial of the German High‐Grade Non‐Hodgkin Lymphoma Study Group (DSHNHL). The genomic DNA samples were analyzed using commercial DNA Probes (Applied Biosystems, USA) to detect single‐nucleotide polymorphisms in the VEGF A rs699947, rs1570360, rs2010963, rs3025039 and rs1870377, and rs2305948 in the VEGFR2 receptor. Hundred healthy blood donors served as a control. Results There was no difference between the SNP allele frequencies in lymphoma patients compared to the control group for all investigated SNPs. None of the investigated SNPs was significantly associated with EFS or OS. After adjusting for the International Prognostic Index risk factors in a multivariate analysis, these results could be confirmed. Conclusion Single‐nucleotide polymorphisms of the VEGF and VEGFR2 were not associated with a worse outcome in Caucasian patients with DLBCL

The Impact of Cold Spells on the Incidence of Infectious Gastroenteritis and Relapse Rates of Inflammatory Bowel Disease: A Retrospective Controlled Observational Study

Goals: We aimed to assess the impact of very cold days on inflammatory bowel disease (IBD) flares and infectious gastroenteritis (IG). We defined a cold day using the World Meteorological definition of an ice day, which is a day with a maximum temperature below 0°C. Background: Recently, we have shown that heat waves increase the risk for IG and IBD flares. Study: We retrospectively collected data from 738 IBD and 786 IG patients admitted to the University Hospital of Zurich between 2001 and 2005 and from 506 patients with other noninfectious chronic intestinal inflammations as controls. Climate data were received by the Swiss Federal Office for Meteorology and Climatology. Results: There was no evidence for an increased risk of IBD flares (relative risk, RR = 0.99, 95% confidence interval, CI: 0.72-1.33, = 0.94) or IG flares (RR = 1.16, 95% CI: 087-1.52, = 0.30) on very cold days. This negative finding was confirmed in alternative formulations with lagged or cumulative (possibly lagged) effects. Conclusion: In this retrospective controlled observational study, no evidence for an increase in hospital admissions due to flares of IBD and IG during cold days was observed. This may be attributed to not relevantly altered bacterial growth conditions during cold days compared to heat waves

Разработка и исследование алгоритмов построения карты местности по видеоизображению

Анализ существующих алгоритмов компьютерного зрения, направленных на построение карты, а также синтез нового алгоритма. Представлена разработка алгоритмов для построения карты местности и реализация в операционной системе для роботов.Analysis of existing computer vision algorithms of aimed at mapping, as well as the synthesis of a new algorithm. The development of algorithms for constructing a map of the terrain and implementation in the operating system for robots is presented

Characterization of an HLA-restricted and human cytomegalovirus-specific antibody repertoire with therapeutic potential

With an infection rate of 60–90%, the human cytomegalovirus (HCMV) is very common among adults but normally causes no symptoms. When T cell-mediated immunity is compromised, HCMV reactivation can lead to increased morbidity and mortality. HCMV antigens are processed and presented as peptides on the cell surface via HLA I complexes to the T cell receptor (TCR) of T cells. The generation of antibodies against HCMV peptides presented on HLA complexes (TCR-like antibodies) has been described, but is without therapeutic applications to date due to the polygenic and polymorphic nature of HLA genes. We set out to obtain antibodies specific for HLA/HCMV-peptides, covering the majority of HLA alleles present in European populations. Using phage display technology, we selected 10 Fabs, able to bind to HCMV-peptides presented in the 6 different HLA class I alleles A*0101, A*0201, A*2402, B*0702, B*0801 and B*3501. We demonstrate specific binding of all selected Fabs to HLA-typed lymphoblastoid cell lines (EBV-transformed B cells) and lymphocytes loaded with HCMV-peptides. After infection with HCMV, 4/10 tetramerized Fabs restricted to the alleles HLA-A*0101, HLA-A*0201 and HLA-B*0702 showed binding to infected primary fibroblasts. When linked to the pseudomonas exotoxin A, these Fab antibodies induce highly specific cytotoxicity in HLA matched cell lines loaded with HCMV peptides. TCR-like antibody repertoires therefore represent a promising new treatment modality for viral infections and may also have applications in the treatment of cancers

FDG PET/CT to detect bone marrow involvement in the initial staging of patients with aggressive non-Hodgkin lymphoma: results from the prospective, multicenter PETAL and OPTIMAL>60 trials

Purpose Fluorine-18 fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG PET/CT) is the standard for staging aggressive non-Hodgkin lymphoma (NHL). Limited data from prospective studies is available to determine whether initial staging by FDG PET/CT provides treatment-relevant information of bone marrow (BM) involvement (BMI) and thus could spare BM biopsy (BMB). Methods Patients from PETAL (NCT00554164) and OPTIMAL>60 (NCT01478542) with aggressive B-cell NHL initially staged by FDG PET/CT and BMB were included in this pooled analysis. The reference standard to confirm BMI included a positive BMB and/or FDG PET/CT confirmed by targeted biopsy, complementary imaging (CT or magnetic resonance imaging), or concurrent disappearance of focal FDG-avid BM lesions with other lymphoma manifestations during immunochemotherapy. Results Among 930 patients, BMI was detected by BMB in 85 (prevalence 9%) and by FDG PET/CT in 185 (20%) cases, for a total of 221 cases (24%). All 185 PET-positive cases were true positive, and 709 of 745 PET-negative cases were true negative. For BMB and FDG PET/CT, sensitivity was 38% (95% confidence interval [CI]: 32–45%) and 84% (CI: 78–88%), specificity 100% (CI: 99–100%) and 100% (CI: 99–100%), positive predictive value 100% (CI: 96–100%) and 100% (CI: 98–100%), and negative predictive value 84% (CI: 81–86%) and 95% (CI: 93–97%), respectively. In all of the 36 PET-negative cases with confirmed BMI patients had other adverse factors according to IPI that precluded a change of standard treatment. Thus, the BMB would not have influenced the patient management. Conclusion In patients with aggressive B-cell NHL, routine BMB provides no critical staging information compared to FDG PET/CT and could therefore be omitted. Trial registration NCT00554164 and NCT0147854

Structural and kinetic basis for heightened immunogenicity of T cell vaccines

Analogue peptides with enhanced binding affinity to major histocompatibility class (MHC) I molecules are currently being used in cancer patients to elicit stronger T cell responses. However, it remains unclear as to how alterations of anchor residues may affect T cell receptor (TCR) recognition. We correlate functional, thermodynamic, and structural parameters of TCR–peptide–MHC binding and demonstrate the effect of anchor residue modifications of the human histocompatibility leukocyte antigens (HLA)–A2 tumor epitope NY–ESO-1157–165–SLLMWITQC on TCR recognition. The crystal structure of the wild-type peptide complexed with a specific TCR shows that TCR binding centers on two prominent, sequential, peptide sidechains, methionine–tryptophan. Cysteine-to-valine substitution at peptide position 9, while optimizing peptide binding to the MHC, repositions the peptide main chain and generates subtly enhanced interactions between the analogue peptide and the TCR. Binding analyses confirm tighter binding of the analogue peptide to HLA–A2 and improved soluble TCR binding. Recognition of analogue peptide stimulates faster polarization of lytic granules to the immunological synapse, reduces dependence on CD8 binding, and induces greater numbers of cross-reactive cytotoxic T lymphocyte to SLLMWITQC. These results provide important insights into heightened immunogenicity of analogue peptides and highlight the importance of incorporating structural data into the process of rational optimization of superagonist peptides for clinical trials

B-cell receptor reactivity against Rothia mucilaginosa in nodular lymphocyte-predominant Hodgkin lymphoma

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a Hodgkin lymphoma expressing functional B-cell receptors (BCR). Recently, we described a dual stimulation model of IgD+ lymphocyte-predominant cells by Moraxella catarrhalis antigen RpoC and its superantigen MID/hag, associated with extralong CDR3 and HLA-DRB1*04 or HLADRB1*07 haplotype. The aim of the present study was to extend the antigen screening to further bacteria and viruses. The fragment antibody-binding (Fab) regions of seven new and 15 previously reported cases were analyzed. The reactivity of non-Moraxella spp.-reactive Fab regions against lysates of Rothia mucilaginosa was observed in 5/22 (22.7%) cases. Galactofuranosyl transferase (Gltf) and 2,3-butanediol dehydrogenase (Bdh) of R. mucilaginosa were identified by comparative silver- and immuno-staining in two-dimensional gels, with subsequent mass spectrometry and validation by western blots and enzyme-linked immunosorbent assay. Both R. mucilaginosa Gltf and Bdh induced BCR pathway activation and proliferation in vitro. Apoptosis was induced by recombinant Gltf/ETA’-immunotoxin conjugates in DEV cells expressing recombinant R. mucilaginosa-reactive BCR. Reactivity against M. catarrhalis RpoC was confirmed in 3/7 newly expressed BCR (total 10/22 reactive to Moraxella spp.), resulting in 15/22 (68.2%) cases with BCR reactivity against defined bacterial antigens. These findings strengthen the hypothesis of bacterial trigger contributing to subsets of NLPHL