Antibodies as new factors in the immunological process of venous thrombosis

Die tiefe Venenthrombose (TVT) entsteht nicht allein durch eine pathologische Blutgerinnung, sondern wird primär durch eine Entzündungsreaktion mit massiver Rekrutierung von Zellen der unspezifischen Immunabwehr ausgelöst. In der vorliegenden Dissertation wurde, mit Hilfe eines etablierten Mausmodells zur Untersuchung der zellulären und molekularen Entstehungsmechanismen der tiefen Venenthrombose (TVT), der Einfluss von Antikörpermolekülen auf die Bildung venöser Thromben untersucht - einer weiteren wichtigen Komponente in immunologischen Prozessen und bekannter Auslöser verschiedener pathologischer Geschehen. Dabei stellte sich heraus, dass Antikörpermoleküle die Entstehung venöser Thromben im Mausmodell beeinflussen: In Mäusen ohne Antikörper war die Thrombusbildung massiv beeinträchtigt und konnte durch Antikörper-Substitution wiederhergestellt werden. Es wurde eine starke Korrelation zwischen IgM-Serumspiegel und Thrombusgewicht sowie eine Beteiligung natürlicher Antikörper festgestellt. Die zugrunde liegenden Mechanismen konnten bereits in Ansätzen aufgeklärt werden: Beteiligte Antikörpermoleküle scheinen an Strukturen des hypoxischen Endothels zu binden und Einfluss zu nehmen auf die initiale Thrombozytenrekrutierung, auf die Leukozytenakkumulation im Thrombus wie auch auf die Fibrinbildung und –stabilisierung. Die gewonnenen Ergebnisse weisen demnach darauf hin, dass bestimmte Antikörpermoleküle in der Lage sind, die Entstehung einer TVT zu begünstigen. Dieses Wissen und eingehendere Forschung kann dazu beitragen, zukünftig neue prognostische Faktoren für das Auftreten venöser Thrombose zu gewinnen und Behandlungsstrategien zu entwickeln, welche die unerwünschten Nebenwirkungen einer alleinigen Hemmung der Blutgerinnung umgehen.Deep vein thrombosis (DVT) is not exclusively triggered by activation of blood coagulation, but mainly develops due to an immunological process involving massive recruitment of innate immune cells. In this thesis an established mouse model for investigation of cellular and molecular mechanisms in the development of DVT was used to study the effects of antibodies - important players in immunity and well known trigger of different pathologic processes. It could be demonstrated that antibody molecules have a significant impact on the development of venous thrombosis in this mouse model: In mice without any antibodies the development of venous thrombi was massively impaired and could be restored by antibody-substitution. A strong correlation between IgM-serum-levels and thrombus weight as well as the participation of natural antibodies were detected. The underlying mechanisms could already be elucidated to some extend: Involved antibody-molecules seem to bind to structures of the hypoxic endothelium and to influence the initial platelet-recruitment, leukocyte-accumulation in venous thrombi as well as fibrin formation and stabilization. These results indicate that certain antibody molecules are able to promote the development of DVT. This knowledge and further intensive studies might contribute to obtain new predictors for DVT-occurrence and can help in the development of new therapeutic strategies that avoid problems related to an exclusive inhibition of blood coagulation

The Iowa Homemaker vol.1, no.2

Table of Contents The Unbidden Guest - Malnutrition by Gladys Dodge, page 1 Wedded at Sunset in June by Clara Jordon, page 2 A Child’s Book Shelf by Lillian Shaben, page 3 Whole Wheat Bread for Health by Florence E. Busse, page 4 Beads, the Latest Accessory to Dress by Johanna M. Hansen, page 5 Putting Organdies to the Test by Vivian Moe and Mildred Elder, page 6 The Right Place for Everything by Helen Easter, page 7 Before Leaving Home for the Summer by Elizabeth Storm, page 7 Safeguarding Your Pocket Book by Marjorie Miller, page

IQB-Bildungstrend 2016

Im Skalenhandbuch werden die Erhebungsinstrumente dokumentiert, die im IQB-Bildungstrend 2016 in den Fächern Deutsch und Mathematik in der Primarstufe eingesetzt wurden. Die Bildungstrend-Studien des IQB sind Teil der Gesamtstrategie der Kultusministerkonferenz zum Bildungsmonitoring. Sie werden regelmäßig durchgeführt, um zu überprüfen, inwieweit die Schülerinnen und Schüler in den einzelnen Ländern in der Bundesrepublik Deutschland die in den länderübergreifend verbindlichen Bildungsstandards formulierten Kompetenzziele erreicht haben. Mit dem IQB-Bildungstrend 2016 war es erstmalig möglich, für das Erreichen der Standards in den Fächern Deutsch und Mathematik in der 4. Jahrgangsstufe Trends zu berichten (Vergleich der Erhebungsjahre 2011 und 2016)

IQB-Bildungstrend 2018

Im Skalenhandbuch werden die Erhebungsinstrumente dokumentiert, die im IQB-Bildungstrend 2018 in den Fächern Mathematik, Biologie, Chemie und Physik in der Sekundarstufe I eingesetzt wurden. Die Bildungstrend-Studien des IQB sind Teil der Gesamtstrategie der Kultusministerkonferenz zum Bildungsmonitoring. Sie werden regelmäßig durchgeführt, um zu überprüfen, inwieweit die Schülerinnen und Schüler in den einzelnen Ländern in der Bundesrepublik Deutschland die in den länderübergreifend verbindlichen Bildungsstandards formulierten Kompetenzziele erreicht haben. Mit dem IQB-Bildungstrend 2018 war es erstmalig möglich, für das Erreichen der Standards im Fach Mathematik und in den naturwissenschaftlichen Fächern in der 9. Jahrgangsstufe Trends zu berichten (Vergleich der Erhebungsjahre 2012 und 2018)

Malmbanan Diaries

This booklet is a report for a case study visit during four day field trip, a group of nine PhD students and their supervisors – all part of the National Research School for Architecture and Planning in the Urban Landscape, APULA – set out to explore what may be considered the outback of Western Europe’s conurbations, the transnational region of Kiruna -Narvik.Both “remote” and “resourceful”, “threatened” and “thriving” (equally relative notions), this region seemed to offer possibilities to reflect upon many of the current tendencies influencing contemporary planning practice and research

Angiotensin II for the Treatment of Vasodilatory Shock

BACKGROUND Vasodilatory shock that does not respond to high-dose vasopressors is associated with high mortality. We investigated the effectiveness of angiotensin II for the treatment of patients with this condition. METHODS We randomly assigned patients with vasodilatory shock who were receiving more than 0.2 mu g of norepinephrine per kilogram of body weight per minute or the equivalent dose of another vasopressor to receive infusions of either angiotensin II or placebo. The primary end point was a response with respect to mean arterial pressure at hour 3 after the start of infusion, with response defined as an increase from baseline of at least 10 mm Hg or an increase to at least 75 mm Hg, without an increase in the dose of background vasopressors. RESULTS A total of 344 patients were assigned to one of the two regimens; 321 received a study intervention (163 received angiotensin II, and 158 received placebo) and were included in the analysis. The primary end point was reached by more patients in the angiotensin II group (114 of 163 patients, 69.9%) than in the placebo group (37 of 158 patients, 23.4%) (odds ratio, 7.95; 95% confidence interval [CI], 4.76 to 13.3; P<0.001). At 48 hours, the mean improvement in the cardiovascular Sequential Organ Failure Assessment (SOFA) score (scores range from 0 to 4, with higher scores indicating more severe dysfunction) was greater in the angiotensin II group than in the placebo group (-1.75 vs. -1.28, P = 0.01). Serious adverse events were reported in 60.7% of the patients in the angiotensin II group and in 67.1% in the placebo group. Death by day 28 occurred in 75 of 163 patients (46%) in the angiotensin II group and in 85 of 158 patients (54%) in the placebo group (hazard ratio, 0.78; 95% CI, 0.57 to 1.07; P = 0.12). CONCLUSIONS Angiotensin II effectively increased blood pressure in patients with vasodilatory shock that did not respond to high doses of conventional vasopressors. (Funded by La Jolla Pharmaceutical Company; ATHOS-3 ClinicalTrials.gov number, NCT02338843.)Peer reviewe

Differential limit on the extremely-high-energy cosmic neutrino flux in the presence of astrophysical background from nine years of IceCube data

We report a quasi-differential upper limit on the extremely-high-energy (EHE) neutrino flux above $5\times 10^{6}$ GeV based on an analysis of nine years of IceCube data. The astrophysical neutrino flux measured by IceCube extends to PeV energies, and it is a background flux when searching for an independent signal flux at higher energies, such as the cosmogenic neutrino signal. We have developed a new method to place robust limits on the EHE neutrino flux in the presence of an astrophysical background, whose spectrum has yet to be understood with high precision at PeV energies. A distinct event with a deposited energy above $10^{6}$ GeV was found in the new two-year sample, in addition to the one event previously found in the seven-year EHE neutrino search. These two events represent a neutrino flux that is incompatible with predictions for a cosmogenic neutrino flux and are considered to be an astrophysical background in the current study. The obtained limit is the most stringent to date in the energy range between $5 \times 10^{6}$ and $5 \times 10^{10}$ GeV. This result constrains neutrino models predicting a three-flavor neutrino flux of $E_\nu^2\phi_{\nu_e+\nu_\mu+\nu_\tau}\simeq2\times 10^{-8}\ {\rm GeV}/{\rm cm}^2\ \sec\ {\rm sr}$at$10^9\ {\rm GeV}$. A significant part of the parameter-space for EHE neutrino production scenarios assuming a proton-dominated composition of ultra-high-energy cosmic rays is excluded.Comment: The version accepted for publication in Physical Review

Investigation of two Fermi-LAT gamma-ray blazars coincident with high-energy neutrinos detected by IceCube

After the identification of the gamma-ray blazar TXS 0506+056 as the first compelling IceCube neutrino source candidate, we perform a systematic analysis of all high-energy neutrino events satisfying the IceCube realtime trigger criteria. We find one additional known gamma-ray source, the blazar GB6 J1040+0617, in spatial coincidence with a neutrino in this sample. The chance probability of this coincidence is 30% after trial correction. For the first time, we present a systematic study of the gamma-ray flux, spectral and optical variability, and multi-wavelength behavior of GB6 J1040+0617 and compare it to TXS 0506+056. We find that TXS 0506+056 shows strong flux variability in the Fermi-LAT gamma-ray band, being in an active state around the arrival of IceCube-170922A, but in a low state during the archival IceCube neutrino flare in 2014/15. In both cases the spectral shape is statistically compatible ($\leq 2\sigma$) with the average spectrum showing no indication of a significant relative increase of a high-energy component. While the association of GB6 J1040+0617 with the neutrino is consistent with background expectations, the source appears to be a plausible neutrino source candidate based on its energetics and multi-wavelength features, namely a bright optical flare and modestly increased gamma-ray activity. Finding one or two neutrinos originating from gamma-ray blazars in the given sample of high-energy neutrinos is consistent with previously derived limits of neutrino emission from gamma-ray blazars, indicating the sources of the majority of cosmic high-energy neutrinos remain unknown.Comment: 22 pages, 11 figures, 2 Table