Imperfect identity

Questions of identity over time are often hard to answer. A long tradition has it that such questions are somehow soft: they have no unique, determinate answer, and disagreements about them are merely verbal. I argue that this claim is not the truism it is taken to be. Depending on how it is understood, it turns out either to be false or to presuppose a highly contentious metaphysical claim

Presentism and the flow of time

The paper examines the relations between presentism and the thesis concerning the existence of the flow of time. It tries to show that the presentist has to admit the existence of the passage of time and that the standard formulation of presentism as a singular thesis saying that only the present exists is insufficient because it does not allow the inference of the existence of the passage of time. Instead of this, the paper proposes a formulation of presentism with the aid of the notion of becoming; not only does a formulation state the existence of the flow of time in such a way as to avoid the question of the rate of the passage of time, it also allows the inference of the existence of only present things and events. The paper demonstrates that the proposed conception of presentism also has other virtues, such as homogeneity, non-triviality, and ability to express dynamicity of presentists’ image of the world which testify for it

Porcine and Canine von Willebrand Factor and von Willebrand Disease: Hemostasis, Thrombosis, and Atherosclerosis Studies

Use of animal models of inherited and induced von Willebrand factor (VWF) deficiency continues to advance the knowledge of VWF-related diseases: von Willebrand disease (VWD), thrombotic thrombocytopenic purpura (TTP), and coronary artery thrombosis. First, in humans, pigs, and dogs, VWF is essential for normal hemostasis; without VWF bleeding events are severe and can be fatal. Second, the ADAMTS13 cleavage site is preserved in all three species suggesting all use this mechanism for normal VWF multimer processing and that all are susceptible to TTP when ADAMTS13 function is reduced. Third, while the role of VWF in atherogenesis is debated, arterial thrombosis complicating atherosclerosis appears to be VWF-dependent. The differences in the VWF gene and protein between humans, pigs, and dogs are relatively few but important to consider in the design of VWF-focused experiments. These homologies and differences are reviewed in detail and their implications for research projects are discussed. The current status of porcine and canine VWD are also reviewed as well as their potential role in future studies of VWF-related disorders of hemostasis and thrombosis

The Virtues of Thisness Presentism

Presentists believe that only present things exist. But opponents insist this view has unacceptable implications: if only present things exist, we can’t express singular propositions about the past, since the obvious propositional constituents don’t exist, nor can we account for temporal passage, or the openness of the future. According to such opponents, and in spite of the apparent ‘common sense’ status of the view, presentism should be rejected on the basis of these unacceptable implications. In this paper, I present and defend a version of presentism (‘Thisness Presentism’) that avoids the unacceptable implications. The basic strategy I employ is familiar—I postulate presently existing entities to serve as surrogates (or ‘proxies’) for non-present entities—but some of the details of my proposal are more novel, and their application to these problems is certainly novel. One overarching thesis of this paper is that Thisness Presentism is preferable to other versions of presentism since it solves important problems facing standard iterations of the view. And I assume that this is a good positive reason in favour of the underlying thisness ontology

Procoagulant Microparticles in Dogs with Immune-Mediated Hemolytic Anemia

BACKGROUND: Studies of some human prothrombotic diseases suggest that phosphatidylserine-positive (PS+) and tissue factor-positive (TF+) microparticles (MPs) might play a role in the pathogenesis of thrombosis or serve as biomarkers of thrombotic risk. HYPOTHESIS/OBJECTIVES: To determine if circulating levels of PS+MP and procoagulant activity (PCA) associated with PS+MPs and TF+ MPs are increased in dogs with IMHA. ANIMALS: Fifteen dogs with primary or secondary IMHA and 17 clinically healthy dogs. METHODS: Prospective case-controlled observational study. Circulating PS+MPs were measured by flow cytometry. PCA associated with PS+MPs and TF+MPs was measured by thrombin and Factor Xa generating assays, respectively. RESULTS: Circulating numbers of PS+MPs were not significantly higher in dogs with IMHA [control median 251,000/μL (36,992-1,141,250/μL); IMHA median 361,990/μL (21,766-47,650,600/μL) P = .30]. However, PS+MP PCA [control median 2.2 (0.0-16.8) nM PS eq; IMHA median 8.596, (0-49.33 nM PS eq) P = .01] and TF+MP PCA [control median 0.0, (0.0-0.0 pg/mL); IMHA median 0.0; (0-22.34 pg/mL], P = .04) were increased. Intravascular hemolysis, which we showed might increase PS+ and TF+MP PCA, was evident in 3 of 5 dogs with PS+MP PCA and 2 of 4 dogs with TF+MP PCA higher than controls. Underlying disease in addition to IMHA was detected in 1 of 5 dogs with PS+PCA and 3 of 4 dogs with TF+MP PCA higher than controls. CONCLUSIONS AND CLINICAL IMPORTANCE: TF+ and PS+MP PCA is increased in some dogs with IMHA. Further studies that determine if measuring TF+ and PS+ MP PCA can help identify dogs at risk for thrombosis are warranted

Academic Senate - Meeting Minutes, 4/18/2017

<p>All values are presented with SD. Differences between <i>LDLR−/−</i> and the other two genotypes are significant where indicated, ANOVA: *p<0.05, **p<0.01.</p

A phase II prospective open-label escalating dose trial of recombinant interleukin-11 in mild von Willebrand disease

von Willebrand factor (VWF) is a multimeric glycoprotein that mediates platelet adhesion and is decreased in von Willebrand disease (VWD). 1-8 deamino-d-arginine vasopressin (DDAVP), the most common treatment for VWD, is limited by tachyphylaxis and inconvenience, and in 20% of the patients, unresponsiveness. Recombinant human interleukin-11 (rhIL-11), a gp-130 signalling cytokine with haematopoietic and anti-inflammatory activity, increases VWF antigen and its activity in heterozygous VWF+/− mice and dogs. To determine the biological efficacy and safety of rhIL-11 in non-bleeding human subjects with mild VWD, we conducted a phase II prospective open-label trial of rhIL-11 at 10, 25 and 50 μg kg−1 subcutaneously (s.c.), given daily for 7 days in nine subjects with mild VWD. VWF and factor VIII (FVIII) levels increased gradually and progressively after s.c. rhIL-11, which was sustained through 7 days of dosing to 1.5- to 3-fold over baseline. Following intravenous DDAVP, 0.3 μg kg−1, on day 7 there was a further boost in VWF and FVIII levels, suggesting that the mechanism of rhIL-11 differs from that of DDAVP. Platelet VWF mRNA expression measured by quantitative PCR increased from two- to eightfold over baseline, suggesting that the mechanism of rhIL-11 effect may be upregulation of VWF mRNA. VWF and FVIII levels returned to baseline by day 14. rhIL-11 was well tolerated with less than grade-1 hypertension, hypokalaemia and fluid retention. Recombinant IL-11 increases VWF levels in humans with mild VWD, justifying future clinical trials to determine its potential in preventing or reducing bleeding in this patient population

Improved kinetics of rIX-FP, a recombinant fusion protein linking factor IX with albumin, in cynomolgus monkeys and hemophilia B dogs: Improved kinetics of rIX-FP

Prophylaxis of hemophilia B, at present, requires multiple infusions of human factor IX (FIX) concentrates per week. A FIX molecule with a prolonged half-life has the potential to greatly improve convenience of, and adherence to, prophylaxis