Future prospects for SPECT imaging using the radiolanthanide terbium-155 — production and preclinical evaluation in tumor-bearing mice

We assessed the suitability of the radiolanthanide 155 Tb (t1/2 = 5.32 days, Eγ = 87 keV (32%), 105 keV (25%)) in combination with variable tumor targeted biomolecules using preclinical SPECT imaging. Methods 155Tb was produced at ISOLDE (CERN, Geneva, Switzerland) by high-energy (~ 1.4 GeV) proton irradiation of a tantalum target followed by ionization and on-line mass separation. 155 Tb was separated from isobar and pseudo-isobar impurities by cation exchange chromatography. Four tumor targeting molecules – a somatostatin analog (DOTATATE), a minigastrin analog (MD), a folate derivative (cm09) and an anti-L1-CAM antibody (chCE7) – were radiolabeled with 155 Tb. Imaging studies were performed in nude mice bearing AR42J, cholecystokinin-2 receptor expressing A431, KB, IGROV-1 and SKOV-3ip tumor xenografts using a dedicated small-animal SPECT/CT scanner. Results The total yield of the two-step separation process of 155 Tb was 86%. 155 Tb was obtained in a physiological l-lactate solution suitable for direct labeling processes. The 155 Tb-labeled tumor targeted biomolecules were obtained at a reasonable specific activity and high purity (> 95%). 155 Tb gave high quality, high resolution tomographic images. SPECT/CT experiments allowed excellent visualization of AR42J and CCK-2 receptor-expressing A431 tumors xenografts in mice after injection of 155 Tb-DOTATATE and 155 Tb-MD, respectively. The relatively long physical half-life of 155 Tb matched in particular the biological half-lives of 155 Tb-cm09 and 155 Tb-DTPA-chCE7 allowing SPECT imaging of KB tumors, IGROV-1 and SKOV-3ip tumors even several days after administration. Conclusions The radiolanthanide 155 Tb may be of particular interest for low-dose SPECT prior to therapy with a therapeutic match such as the β--emitting radiolanthanides 177Lu, 161 Tb, 166Ho, and the pseudo-radiolanthanide 90Y.

Improvement of cardiac function with device-based diaphragmatic stimulation in chronic heart failure patients: the randomized, open-label, crossover Epiphrenic II Pilot Trial.

AIMS Device-based pacing-induced diaphragmatic stimulation (PIDS) may have therapeutic potential for chronic heart failure (HF) patients. We studied the effects of PIDS on cardiac function and functional outcomes. METHODS AND RESULTS In 24 chronic HF patients with CRT, an additional electrode was attached to the left diaphragm. Randomized into two groups, patients received the following PIDS modes for 3 weeks in a different sequence: (i) PIDS off (control group); (ii) PIDS 0 ms mode (PIDS simultaneously with ventricular CRT pulse); or (iii) PIDS optimized mode (PIDS with optimized delay to ventricular CRT pulse). For PIDS optimization, acoustic cardiography was used. Effects of each PIDS mode on dyspnoea, power during exercise testing, and LVEF were assessed. Dyspnoea improved with the PIDS 0 ms mode (P = 0.057) and the PIDS optimized mode (P = 0.034) as compared with the control group. Maximal power increased from median 100.5 W in the control group to 104.0 W in the PIDS 0 ms mode (P = 0.092) and 109.5 W in the PIDS optimized mode (P = 0.022). Median LVEF was 33.5% in the control group, 33.0% in the PIDS 0 ms mode, and 37.0% in the PIDS optimized mode (P = 0.763 and P = 0.009 as compared with the control group, respectively). PIDS was asymptomatic in all patients. CONCLUSION PIDS improves dyspnoea, working capacity, and LVEF in chronic HF patients over a 3 week period in addition to CRT. This pilot study demonstrates proof of principle of an innovative technology which should be confirmed in a larger sample. TRIAL REGISTRATION NCT00769678.

Tastend von Gott reden : drei systematisch-theologische Antrittsvorlesungen aus Bern

Nach Gott tasten ist die Grundbewegung, die die drei in diesem Band versammelten Vorlesungen verknüpft und für die Paul Klees «Engel, noch tastend» zum hermeneutischen Leitbild wird. Torsten Meireis, inspiriert durch Karl Barth, reflektiert inmitten religiöser und weltanschaulicher Pluralität ein moralisches Verhalten, das dem Handeln des in Jesus Christus offenbaren Gottes entspricht. Wegweisend wird ihm dabei ein dreifacher Begriff des Guten: unverfügbares, intendiertes und realisiertes Gutes. Um angesichts des Sinnverlustes religiöser Rede dennoch nicht von Gott zu schweigen, plädiert Andreas Krebs, angeregt durch Ludwig Wittgensteins Spätphilosophie, für ein «halbes Sagen, halbes Verstehen», das sich in der Nähe zur Sprache der Poesie weiss – eine Gottesrede, die sich ihrer selbst nicht mehr sicher ist und gerade so Gott Gewicht zu geben sucht. Als Baustein einer um den Eigennamen kreisenden Eschatologie entwirft Magdalene L. Frettlöh die Hoffnung auf eine als neuschöpferischen göttlichen Namensruf an die Toten verstandene Auferweckung. Diese schliesst Rettung wie Verwandlung des irdischen Lebens ein.

"Die Schweiz sollte eine aktivere Rolle spielen" (Interview mit Thomas Cottier von Andreas Valda)

Thomas Cottier, Experte für Handelsrecht, erklärt, warum die Pharmaindustrie beim Freihandelsabkommen mit Indien zu viel verlangt. Und warum die Schweiz bei internationalen Handelskonflikten mehr unternehmen müsste.

Solar forcing of North Atlantic surface temperature and salinity over the past millennium

There were several centennial-scale fluctuations in the climate and oceanography of the North Atlantic region over the past 1,000 years, including a period of relative cooling from about AD 1450 to 1850 known as the Little Ice Age1. These variations may be linked to changes in solar irradiance, amplified through feedbacks including the Atlantic meridional overturning circulation2. Changes in the return limb of the Atlantic meridional overturning circulation are reflected in water properties at the base of the mixed layer south of Iceland. Here we reconstruct thermocline temperature and salinity in this region from AD 818 to 1780 using paired δ18O and Mg/Ca ratio measurements of foraminifer shells from a subdecadally resolved marine sediment core. The reconstructed centennial-scale variations in hydrography correlate with variability in total solar irradiance. We find a similar correlation in a simulation of climate over the past 1,000 years. We infer that the hydrographic changes probably reflect variability in the strength of the subpolar gyre associated with changes in atmospheric circulation. Specifically, in the simulation, low solar irradiance promotes the development of frequent and persistent atmospheric blocking events, in which a quasi-stationary high-pressure system in the eastern North Atlantic modifies the flow of the westerly winds. We conclude that this process could have contributed to the consecutive cold winters documented in Europe during the Little Ice Age.

Schulpraktika in der Lehrerbildung. Theoretische Grundlagen, Konzeptionen, Prozesse und Effekte = Pedagogical field experiences in teacher education. Theoretical foundations, programmes, processes, and effects

Seit mehr als zwanzig Jahren werden in der tertiären Lehramtsausbildung Schulpraktika reformiert und neuerdings in ihrem zeitlichen Umfang relativ zur Studienzeit vergrößert. Zum Gegenstand reger Forschungsaktivitäten avancierten Schulpraktika jedoch erst im letzten Jahrzehnt. Hiermit werden ein Überblick über das Forschungsfeld (Grundlagen der schulpraktischen Komponenten der Lehrerbildung; Forschungsmethodik) vorgelegt und aktuelle Forschungsergebnisse zu zentralen Aspekten der Wirksamkeit von Praktika und Effekten von Mentoring präsentiert. In englischsprachigen bzw. deutschsprachigen Beiträgen wird der Forschungsstand in Deutschland, den Niederlanden, Österreich und der Schweiz sowie den USA aufgezeigt. Der Band richtet sich an Personen, die in der Lehrerbildung tätig sind, also an Dozent/inn/en in Hochschulen und Seminaren, an Lehrerbildungsforscher/innen sowie an Fachpersonen in der Bildungsadministration und interessierte Studierende.

True four-dimensional analysis of thoracic aortic displacement and distension using model-based segmentation of computed tomography angiography.

Previous analyses of aortic displacement and distension using computed tomography angiography (CTA) were performed on double-oblique multi-planar reformations and did not consider through-plane motion. The aim of this study was to overcome this limitation by using a novel computational approach for the assessment of thoracic aortic displacement and distension in their true four-dimensional extent. Vessel segmentation with landmark tracking was executed on CTA of 24 patients without evidence of aortic disease. Distension magnitudes and maximum displacement vectors (MDV) including their direction were analyzed at 5 aortic locations: left coronary artery (COR), mid-ascending aorta (ASC), brachiocephalic trunk (BCT), left subclavian artery (LSA), descending aorta (DES). Distension was highest for COR (2.3 ± 1.2 mm) and BCT (1.7 ± 1.1 mm) compared with ASC, LSA, and DES (p < 0.005). MDV decreased from COR to LSA (p < 0.005) and was highest for COR (6.2 ± 2.0 mm) and ASC (3.8 ± 1.9 mm). Displacement was directed towards left and anterior at COR and ASC. Craniocaudal displacement at COR and ASC was 1.3 ± 0.8 and 0.3 ± 0.3 mm. At BCT, LSA, and DES no predominant displacement direction was observable. Vessel displacement and wall distension are highest in the ascending aorta, and ascending aortic displacement is primarily directed towards left and anterior. Craniocaudal displacement remains low even close to the left cardiac ventricle.

Presse et prostitution à la lumière de Karl Kraus

Karl Kraus a repris, mais en l’amplifiant, la métaphore de Balzac qui compare la presse à une prostituée. Mais il élargit considérablement son propos dans une dénonciation de l’attitude hypocrite de la bourgeoisie et de la presse bourgeoise par rapport à la prostitution physique. Il développe pour ce faire une poétique où une pratique généralisée de l’antanaclase permet de dénoncer à la fois la presse et ses lieux communs par rapport aux prostituées.