De Rugia, Insula Maris Baltici, Disputatio Posterior

DE RUGIA, INSULA MARIS BALTICI, DISPUTATIO POSTERIOR De Rugia, Insula Maris Baltici, Disputatio Posterior ([1]r) Titelseite ([1]r) Text ([2]r

Advances in hemophilia care: report of two symposia at the Hemophilia 2010 World Congress

The World Federation of Hemophilia (WFH) 2010 World Congress held in Buenos Aires, Argentina, in July 2010, attracted more than 4,300 participants from 106 countries. This report summarizes two symposia held during the congress. The first, titled "Emerging Co-Morbidities in the Aging Hemophilia Population: Healthcare Challenges and Treatment Opportunities," chaired by Gerry Dolan, MD, and Jussara Almeida Cruz, MD, examined the co-morbidities experienced by the aging hemophilic patient population, such as cardiovascular disease, cancer, arthritis, osteoporosis, hypertension, and obesity. In addition, Bayer's products in preclinical and clinical development were reviewed, including a novel factor VIIa variant and a long-acting factor VIII molecule, i.e., one that has undergone site-specific PEGylation (attachment of polyethylene glycol [PEG] polymer chains to another molecule). The other symposium, titled "Practical Steps to Making Better Care for Hemophilia Patients a Reality," chaired by Carmen Altisent, MD, and Cesar Guerrero, RN, reviewed the steps that hemophilia caregivers can take to improve the care of their patients. Issues such as the treatment of hemarthroses, the role of the research nurse, and the management of pediatric patients transitioning to adulthood were discussed

Preclinical evaluation of a novel SHIP1 phosphatase activator for inhibition of PI3K signaling in malignant B cells

Purpose: PI3K signaling is a common feature of B-cell neoplasms, including chronic lymphocytic leukemia (CLL) and diffuse large B-cell lymphoma (DLBCL), and PI3K inhibitors have been introduced into the clinic. However, there remains a clear need to develop new strategies to target PI3K signaling. PI3K activity is countered by Src homology domain 2-containing inositol-50 - phosphatase 1 (SHIP1) and, here, we have characterized the activity of a novel SHIP1 activator, AQX-435, in preclinical models of B-cell malignancies. Experimental Design: In vitro activity of AQX-435 was evaluated using primary CLL cells and DLBCL-derived cell lines. In vivo activity of AQX-435, alone or in combination with the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib, was assessed using DLBCL cell line and patient-derived xenograft models. Results: Pharmacologic activation of SHIP1 using AQX-435 was sufficient to inhibit anti–IgM-induced PI3K-mediated signaling, including induction of AKT phosphorylation and MYC expression, without effects on upstream SYK phosphorylation. AQX-435 also cooperated with the BTK inhibitor ibrutinib to enhance inhibition of anti–IgM-induced AKT phosphorylation. AQX-435 induced caspase-dependent apoptosis of CLL cells preferentially as compared with normal B cells, and overcame in vitro survivalpromoting effects of microenvironmental stimuli. Finally, AQX435 reduced AKT phosphorylation and growth of DLBCL in vivo and cooperated with ibrutinib for tumor growth inhibition. Conclusions: Our results using AQX-435 demonstrate that SHIP1 activation may be an effective novel therapeutic strategy for treatment of B-cell neoplasms, alone or in combination with ibrutinib

Preclinical evaluation of a novel SHIP1 phosphatase activator for inhibition of PI3K signaling in malignant B-cells

PURPOSE: Phosphatidylinositol-3 kinase (PI3K) signaling is a common feature of B-cell neoplasms, including chronic lymphocytic leukemia (CLL) and diffuse large B-cell lymphoma (DLBCL), and PI3K inhibitors have been introduced into the clinic. However, there remains a clear need to develop new strategies to target PI3K signaling. PI3K activity is countered by Src homology domain 2-containing inositol-5'-phosphatase1 (SHIP1) and, here, we have characterized the activity of a novel SHIP1 activator, AQX-435, in pre-clinical models of B-cell malignancies.EXPERIMENTAL DESIGN: In vitro activity of AQX-435 was evaluated using primary CLLcellsand DLBCL-derived cell lines. In vivo activity of AQX-435, alone or in combination with the BTK inhibitor ibrutinib, was assessed using DLBCL cell line and patient-derived xenograft models.RESULTS: Pharmacological activation of SHIP1 using AQX-435 was sufficient to inhibit anti-IgM-induced PI3K-mediated signaling, including induction of AKT phosphorylation and MYC expression, without effects on upstream SYK phosphorylation. AQX-435 also co-operated with the BTK inhibitor ibrutinib to enhance inhibition of anti-IgM-induced AKT phosphorylation. AQX-435 induced caspase-dependent apoptosis of CLL cells preferentially as compared to normal B cells, and overcame in vitro survival promoting effects of microenvironmental stimuli. Finally, AQX-435 reduced AKT phosphorylation and growth of DLBCL in vivo,and co-operated with ibrutinib for tumor growth inhibition.CONCLUSIONS: Our results using AQX-435 demonstrate that SHIP1 activation may be an effective novel therapeutic strategy for treatment of B-cell neoplasms, alone or in combination with ibrutinib.</p

An Open, Large-Scale, Collaborative Effort to Estimate the Reproducibility of Psychological Science

Reproducibility is a defining feature of science. However, because of strong incentives for innovation and weak incentives for confirmation, direct replication is rarely practiced or published. The Reproducibility Project is an open, large-scale, collaborative effort to systematically examine the rate and predictors of reproducibility in psychological science. So far, 72 volunteer researchers from 41 institutions have organized to openly and transparently replicate studies published in three prominent psychological journals in 2008. Multiple methods will be used to evaluate the findings, calculate an empirical rate of replication, and investigate factors that predict reproducibility. Whatever the result, a better understanding of reproducibility will ultimately improve confidence in scientific methodology and findings

Reproducibility Project: Psychology

Reproducibility is a defining feature of science, but the extent to which it characterizes current research is unknown. We conducted replications of 100 experimental and correlational studies published in three psychology journals using high-powered designs and original materials when available

Data from: Estimating the reproducibility of psychological science

This record contains the underlying research data for the publication "Estimating the reproducibility of psychological science" and the full-text is available from: https://ink.library.smu.edu.sg/lkcsb_research/5257Reproducibility is a defining feature of science, but the extent to which it characterizes current research is unknown. We conducted replications of 100 experimental and correlational studies published in three psychology journals using high-powered designs and original materials when available. Replication effects were half the magnitude of original effects, representing a substantial decline. Ninety-seven percent of original studies had statistically significant results. Thirty-six percent of replications had statistically significant results; 47% of original effect sizes were in the 95% confidence interval of the replication effect size; 39% of effects were subjectively rated to have replicated the original result; and if no bias in original results is assumed, combining original and replication results left 68% with statistically significant effects. Correlational tests suggest that replication success was better predicted by the strength of original evidence than by characteristics of the original and replication teams