(89)Zr, a radiometal nuclide with high potential for molecular imaging with PET: chemistry, applications and remaining challenges.

Molecular imaging-and especially Positron Emission Tomography (PET)-is of increasing importance for the diagnosis of various diseases and thus is experiencing increasing dissemination. Consequently, there is a growing demand for appropriate PET tracers which allow for a specific accumulation in the target structure as well as its visualization and exhibit decay characteristics matching their in vivo pharmacokinetics. To meet this demand, the development of new targeting vectors as well as the use of uncommon radionuclides becomes increasingly important. Uncommon nuclides in this regard enable the utilization of various selectively accumulating bioactive molecules such as peptides, antibodies, their fragments, other proteins and artificial structures for PET imaging in personalized medicine. Among these radionuclides, 89Zr (t1/2 = 3.27 days and mean Eβ+ = 0.389 MeV) has attracted increasing attention within the last years due to its favorably long half-life, which enables imaging at late time-points, being especially favorable in case of slowly-accumulating targeting vectors. This review outlines the recent developments in the field of 89Zr-labeled bioactive molecules, their potential and application in PET imaging and beyond, as well as remaining challenges

Enhanced Pro-apoptotic Effects of Fe(II)-Modified IVIG on Human Neutrophils.

Mild modification of intravenous immunoglobulin (IVIG) has been reported to result in enhanced polyspecificity and leveraged therapeutic effects in animal models of inflammation. Here, we observed that IVIG modification by ferrous ions, heme or low pH exposure, shifted the repertoires of specificities in different directions. Ferrous ions exposed Fe(II)-IVIG, but not heme or low pH exposed IVIG, showed increased pro-apoptotic effects on neutrophil granulocytes that relied on a FAS-dependent mechanism. These effects were also observed in human neutrophils primed by inflammatory mediators or rheumatoid arthritis joint fluid in vitro, or patient neutrophils ex vivo from acute Crohn's disease. These observations indicate that IVIG-mediated effects on cells can be enhanced by IVIG modification, yet specific modification conditions may be required to target specific molecular pathways and eventually to enhance the therapeutic potential

(89)Zr, a radiometal nuclide with high potential for molecular imaging with PET: chemistry, applications and remaining challenges.

Molecular imaging-and especially Positron Emission Tomography (PET)-is of increasing importance for the diagnosis of various diseases and thus is experiencing increasing dissemination. Consequently, there is a growing demand for appropriate PET tracers which allow for a specific accumulation in the target structure as well as its visualization and exhibit decay characteristics matching their in vivo pharmacokinetics. To meet this demand, the development of new targeting vectors as well as the use of uncommon radionuclides becomes increasingly important. Uncommon nuclides in this regard enable the utilization of various selectively accumulating bioactive molecules such as peptides, antibodies, their fragments, other proteins and artificial structures for PET imaging in personalized medicine. Among these radionuclides, 89Zr (t1/2 = 3.27 days and mean Eβ+ = 0.389 MeV) has attracted increasing attention within the last years due to its favorably long half-life, which enables imaging at late time-points, being especially favorable in case of slowly-accumulating targeting vectors. This review outlines the recent developments in the field of 89Zr-labeled bioactive molecules, their potential and application in PET imaging and beyond, as well as remaining challenges

Psychology of intelligence services 4

Mit dem vorliegenden Band kann bereits der Vierte zum Thema Nachrichtendienstpsychologie herausgegeben werden. Nach Kenntnis der Herausgeber stoßen die Aufsatzsammlungen zu unterschiedlichen psychologischen Themen, die im Rahmen der nachrichtendienstlichen Arbeit von Interesse sind, auch außerhalb der Nachrichtendienste auf Interesse. Dies dürfte zum Teil darauf zurückzuführen sein, dass einige Themen inhaltliche Überschneidungen zu der Aufgabenstellung anderer Sicherheitsbehörden, wie z.B. der Polizeibehörden aufweisen. Aber auch innerhalb der Nachrichtendienste ergibt sich verstärkt die Notwendigkeit, bei der Lösung von Fragestellungen psychologische Erkenntnisse zu nutzen bzw. – auf dem speziellen Gebiet der Nachrichtendienstpsychologie – selbst zu generieren. Die Nachrichtendienste sind Bestandteil einer rechtsstaatlichen Struktur, die Gefahren für die Öffentlichkeit erkennen sollen. Dass auch Nachrichtendienste sich nicht vom wissenschaftlichen Fortschritt abkoppeln können, wenn sie dieser Aufgabe nachkommen wollen, ist evident. Wenn beispielsweise Gefahren für die öffentliche Sicherheit von Personen ausgehen, die sich ihrerseits psychologischer Mittel bedienen, müssen Sicherheitsbehörden klären, wie diese psychologischen Mittel eingesetzt werden und welche Wirkung sie entfalten, um ggf. Gegenstrategien vorzuschlagen. Aber auch ihr eigenes Instrumentarium müssen Nachrichtendienste ständig verbessern. Zentral dafür ist die Schulung der Mitarbeiterinnen und Mitarbeiter. Hierzu beizutragen ist eine Funktion der Reihe Nachrichtendienstpsychologie

tated record of the detailed examination of Mn deposits from DSDP Leg 41 (Holes 366, 366A, 367, 368, 369, 369A)

he forty-first cruise of Glomar Challenger was devoted to the study of the evolution of the eastern basins of the North Atlantic, off the continental margin of West Africa. As the available data a the time was showing that most litho-stratigraphic units in the deep basins of the Atlantic had enough lateral extension, the drilling of a limited number of sites in key areas would allow for large-scale regional interpretation. One of the sites was loacted in the Cape Verde deep Basin (Site 367) while others were located in shallower waters such as, the Sierra Leone Rise (Site 366), the Cape Verde Rise (Site 368) or the Continental Slope off Spanish Sahara (Site 369)

Predictors of temporary and permanent work disability in patients with inflammatory bowel disease: results of the swiss inflammatory bowel disease cohort study

BACKGROUND Inflammatory bowel disease can decrease the quality of life and induce work disability. We sought to (1) identify and quantify the predictors of disease-specific work disability in patients with inflammatory bowel disease and (2) assess the suitability of using cross-sectional data to predict future outcomes, using the Swiss Inflammatory Bowel Disease Cohort Study data. METHODS A total of 1187 patients were enrolled and followed up for an average of 13 months. Predictors included patient and disease characteristics and drug utilization. Potential predictors were identified through an expert panel and published literature. We estimated adjusted effect estimates with 95% confidence intervals using logistic and zero-inflated Poisson regression. RESULTS Overall, 699 (58.9%) experienced Crohn's disease and 488 (41.1%) had ulcerative colitis. Most important predictors for temporary work disability in patients with Crohn's disease included gender, disease duration, disease activity, C-reactive protein level, smoking, depressive symptoms, fistulas, extraintestinal manifestations, and the use of immunosuppressants/steroids. Temporary work disability in patients with ulcerative colitis was associated with age, disease duration, disease activity, and the use of steroids/antibiotics. In all patients, disease activity emerged as the only predictor of permanent work disability. Comparing data at enrollment versus follow-up yielded substantial differences regarding disability and predictors, with follow-up data showing greater predictor effects. CONCLUSIONS We identified predictors of work disability in patients with Crohn's disease and ulcerative colitis. Our findings can help in forecasting these disease courses and guide the choice of appropriate measures to prevent adverse outcomes. Comparing cross-sectional and longitudinal data showed that the conduction of cohort studies is inevitable for the examination of disability

IgA Triggers Cell Death of Neutrophils When Primed by Inflammatory Mediators

IVIG preparations consisting of pooled IgG are increasingly used for the treatment of autoimmune diseases. IVIG is known to regulate the viability of immune cells, including neutrophils. We report that plasma-derived IgA efficiently triggers death of neutrophils primed by cytokines or TLR agonists. IgA-mediated programmed neutrophil death was PI3K-, p38 MAPK–, and JNK-dependent and evoked anti-inflammatory cytokines in macrophage cocultures. Neutrophils from patients with acute Crohn's disease, rheumatoid arthritis, or sepsis were susceptible to both IgA- and IVIG-mediated death. In contrast to IVIG, IgA did not promote cell death of quiescent neutrophils. Our findings suggest that plasma-derived IgA might provide a therapeutic option for the treatment of neutrophil-associated inflammator