Banks Community Emergency Response Team (CERT) Project Proposal

This proposal examines the challenges the Banks Fire District is faced with if a catastrophic event, such as a Cascadia Subduction Zone (CSZ) earthquake were to strike the Pacific Northwest. The District has concerns surrounding the potential response and recovery challenges during a major disaster. The District is open to expanding its jurisdiction\u27s capabilities with a solution that would benefit the District and Banks community members without compromising the District mission and core values. The District realizes that due to the nature of a CSZ, it will not have the resource capability to respond to the emergency needs of the community. This proposal identifies the threats and hazards to Banks and the surrounding communities that have the potential to disrupt life, infrastructure, and business. The project proposal offers potential solutions and recommendations on how the community can become better prepared for a disaster by engaging the community in emergency preparedness activities so the Banks community can stabilize themselves, family, and neighborhoods until first responders arrive

Accumulation of Tissue Factor Into Developing Thrombi In Vivo Is Dependent Upon Microparticle P-Selectin Glycoprotein Ligand 1 And Platelet P-Selectin

Using a laser-induced endothelial injury model, we examined thrombus formation in the microcirculation of wild-type and genetically altered mice by real-time in vivo microscopy to analyze this complex physiologic process in a system that includes the vessel wall, the presence of flowing blood, and the absence of anticoagulants. We observe P-selectin expression, tissue factor accumulation, and fibrin generation after platelet localization in the developing thrombus in arterioles of wild-type mice. However, mice lacking P-selectin glycoprotein ligand 1 (PSGL-1) or P-selectin, or wild-type mice infused with blocking P-selectin antibodies, developed platelet thrombi containing minimal tissue factor and fibrin. To explore the delivery of tissue factor into a developing thrombus, we identified monocyte-derived microparticles in human platelet–poor plasma that express tissue factor, PSGL-1, and CD14. Fluorescently labeled mouse microparticles infused into a recipient mouse localized within the developing thrombus, indicating that one pathway for the initiation of blood coagulation in vivo involves the accumulation of tissue factor– and PSGL-1–containing microparticles in the platelet thrombus expressing P-selectin. These monocyte-derived microparticles bind to activated platelets in an interaction mediated by platelet P-selectin and microparticle PSGL-1. We propose that PSGL-1 plays a role in blood coagulation in addition to its known role in leukocyte trafficking

Accumulation of Tissue Factor into Developing Thrombi In Vivo Is Dependent upon Microparticle P-Selectin Glycoprotein Ligand 1 and Platelet P-Selectin

Using a laser-induced endothelial injury model, we examined thrombus formation in the microcirculation of wild-type and genetically altered mice by real-time in vivo microscopy to analyze this complex physiologic process in a system that includes the vessel wall, the presence of flowing blood, and the absence of anticoagulants. We observe P-selectin expression, tissue factor accumulation, and fibrin generation after platelet localization in the developing thrombus in arterioles of wild-type mice. However, mice lacking P-selectin glycoprotein ligand 1 (PSGL-1) or P-selectin, or wild-type mice infused with blocking P-selectin antibodies, developed platelet thrombi containing minimal tissue factor and fibrin. To explore the delivery of tissue factor into a developing thrombus, we identified monocyte-derived microparticles in human platelet–poor plasma that express tissue factor, PSGL-1, and CD14. Fluorescently labeled mouse microparticles infused into a recipient mouse localized within the developing thrombus, indicating that one pathway for the initiation of blood coagulation in vivo involves the accumulation of tissue factor– and PSGL-1–containing microparticles in the platelet thrombus expressing P-selectin. These monocyte-derived microparticles bind to activated platelets in an interaction mediated by platelet P-selectin and microparticle PSGL-1. We propose that PSGL-1 plays a role in blood coagulation in addition to its known role in leukocyte trafficking

M & L Jaargang 11/2

GeneriekTeresa Patricio, Jose Maria Rubio en Pierre Smars De woning Hankar (met nota over de tuin door Herman Van den Bossche). [The Hankar House at Brussels.]Op nog maar luttele maanden van de honderdste verjaardag van het mythisch dubbel Art Nouveau-manifest van Victor Horta èn Paul Hankar, vraagt precies het eigen woonhuis van deze laatste beangstigd om een tweede levenskans.Nauwgezet speurwerk liet Teresa Patricio, Jose Maria Rubio en Pierre Smars alvast toe de onverhoopte bewaringstoestand èn onthullende kwaliteiten van dit cult-huis te onderkennen.Hun suggestie tot restauratie van essentieel geachte ruimten grijpt ongetwijfeld een zeldzame kans aan om het schaarse nog bewaard gebleven oeuvre van Hankar ook daadwerkelijk te rehabiliteren.Ludo Meesters De heuvelrug tussen Herentals en Kasterlee. [The range of hills between Herentals and Kasterlee.]Toponiemen als Kruisberg, Bosbergen, Galgenberg, Langenberg of Hoge Berg lijken niet meteen te verwijzen naar een karakteristiek Vlaams landschap, ook al blijken ze beperkt tot kleine oneffenheden van een uitgestrekte heuvelrug langsheen de Kleine Nete. Een omvangrijk landduincomplex en suggestieve plaatsnamen als Snepkensvijlver, Schoutenheide, Lavendelven, Koningsbos of Goor Akkers wijzen hoe dan ook ondubbelzinnig op de aanwezige troeven voor de oprichting van een regionaal landschapspark. Aldus althans Ludo Meesters, die met concrete beschermings- en beheersvoorstellen plant, mens en dier op vreedzame wijze op deze plek ziet cohabiteren.Maurits Timperman en Miek Goossens m.m.v. Marc Vandendries Huize Rutsaert in Veurne (met nota over Het onderzoek naar de originele polychromie door M. Buyle). [The Rutsaert House in Veurne.]Samen met zovele \u27onnuttige\u27 lotgenoten zou ook het witte nonnenklooster te Veurne op last van Jozef II in 1783 de deuren sluiten.Vrijwel meteen omgebouwd tot een merkwaardige staalkaart van Frans classicisme, zou Huize-Rutsaert niet enkel haar verleden niet totaal verloochenen, maar voortaan een markante opeenvolging van bewoners kennen.Naar aanleiding van de gevelrestauratie gaat historicus Maurits Timperman hier, samen met Miek Goossens en Marc Vandendries, nader op in.SummaryM&L Binnenkran

The tyrosine phosphatase CD148 is an essential positive regulator of platelet activation and thrombosis

Platelets play a fundamental role in hemostasis and thrombosis. They are also involved in pathologic conditions resulting from blocked blood vessels, including myocardial infarction and ischemic stroke. Platelet adhesion, activation, and aggregation at sites of vascular injury are regulated by a diverse repertoire of tyrosine kinase–linked and G protein–coupled receptors. Src family kinases (SFKs) play a central role in initiating and propagating signaling from several platelet surface receptors; however, the underlying mechanism of how SFK activity is regulated in platelets remains unclear. CD148 is the only receptor-like protein tyrosine phosphatase identified in platelets to date. In the present study, we show that mutant mice lacking CD148 exhibited a bleeding tendency and defective arterial thrombosis. Basal SFK activity was found to be markedly reduced in CD148-deficient platelets, resulting in a global hyporesponsiveness to agonists that signal through SFKs, including collagen and fibrinogen. G protein–coupled receptor responses to thrombin and other agonists were also marginally reduced. These results highlight CD148 as a global regulator of platelet activation and a novel antithrombotic drug targe

Impact of minimal residual disease status in patients with relapsed/refractory acute lymphoblastic leukemia treated with inotuzumab ozogamicin in the phase III INO-VATE trial.

Minimal residual disease (MRD) negativity is a key prognostic indicator of outcome in acute lymphocytic leukemia. In the INO-VATE trial (clinicaltrials.gov identifier: NCT01564784), patients with relapsed/refractory acute lymphocytic leukemia who received inotuzumab versus standard chemotherapy achieved greater remission and MRD-negativity rates as well as improved overall survival: hazard ratio 0.75, one-sided P = 0.0105. The current analysis assessed the prognostic value of MRD negativity at the end of inotuzumab treatment. All patients who received inotuzumab (n = 164) were included. Among patients with complete remission/complete remission with incomplete hematologic response (CR/CRi; n = 121), MRD-negative status (by multiparametric flow cytometry) was defined as <1 × 10-4 blasts/nucleated cells. MRD negativity was achieved in 76 patients at the end of treatment. Compared with MRD-positive, MRD-negative status with CR/CRi was associated with significantly improved overall survival and progression-free survival, respectively: hazard ratio (97.5% confidence interval; one-sided P-value) 0.512 (97.5% CI [0.313-0.835]; P = 0.0009) and 0.423 (97.5% CI [0.256-0.699]; P < 0.0001). Median overall survival was 14.1 versus 7.2 months, in the MRD-negative versus MRD-positive groups. Patients in first salvage who achieved MRD negativity at the end of treatment experienced significantly improved survival versus that seen in MRD-positive patients, particularly for those patients who proceeded to stem cell transplant. Among patients with relapsed/refractory acute lymphocytic leukemia who received inotuzumab, those with MRD-negative CR/CRi had the best survival outcomes

Cancer cell–derived microparticles bearing P-selectin glycoprotein ligand 1 accelerate thrombus formation in vivo

Recent publications have demonstrated the presence of tissue factor (TF)–bearing microparticles (MPs) in the blood of patients suffering from cancer. However, whether these MPs are involved in thrombosis remains unknown. We show that pancreatic and lung cancer cells produce MPs that express active TF and P-selectin glycoprotein ligand 1 (PSGL-1). Cancer cell–derived MPs aggregate platelets via a TF-dependent pathway. In vivo, cancer cell–derived MPs, but not their parent cells, infused into a living mouse accumulate at the site of injury and reduce tail bleeding time and the time to occlusion of venules and arterioles. This thrombotic state is also observed in mice developing tumors. In such mice, the amount of circulating platelet-, endothelial cell–, and cancer cell–derived MPs is increased. Endogenous cancer cell–derived MPs shed from the growing tumor are able to accumulate at the site of injury. Infusion of a blocking P-selectin antibody abolishes the thrombotic state observed after injection of MPs or in mice developing a tumor. Collectively, our results indicate that cancer cell–derived MPs bearing PSGL-1 and TF play a key role in thrombus formation in vivo. Targeting these MPs could be of clinical interest in the prevention of thrombosis and to limit formation of metastasis in cancer patients