Anti‐Oxidants Improve Factor Viii Folding And Secretion And Reduce Cell Toxicity And Inflammation In Vivo In Mice

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106094/1/jth02905.pd

Efficient Secretion Of Bioengineered Coagulation Factor Viii Into The Milk Of Transgenic Animals

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106071/1/jth01670.pd

Hemophilia gene therapy knowledge and perceptions: Results of an international survey

Background Hemophilia gene therapy is a rapidly evolving therapeutic approach in which a number of programs are approaching clinical development completion. Objective The aim of this study was to evaluate knowledge and perceptions of a variety of health care practitioners and scientists about gene therapy for hemophilia. Methods This survey study was conducted February 1 to 18, 2019. Survey participants were members of the ISTH, European Hemophilia Consortium, European Hematology Association, or European Association for Hemophilia and Allied Disorders with valid email contacts. The online survey consisted of 36 questions covering demographic information, perceptions and knowledge of gene therapy for hemophilia, and educational preferences. Survey results were summarized using descriptive statistics. Results Of the 5117 survey recipients, 201 responded from 55 countries (4% response rate). Most respondents (66%) were physicians, and 59% were physicians directly involved in the care of people with hemophilia. Among physician respondents directly involved in hemophilia care, 35% lacked the ability to explain the science of adeno-associated viral gene therapy for hemophilia, and 40% indicated limited ability or lack of comfort answering patient questions about gene therapy for hemophilia based on clinical trial results to date. Overall, 75% of survey respondents answered 10 single-answer knowledge questions correctly, 13% incorrectly, and 12% were unsure of the correct answers. Conclusions This survey highlighted knowledge gaps and educational needs related to gene therapy for hemophilia and, along with other inputs, has informed the development of "Gene Therapy in Hemophilia: An ISTH Education Initiative.

Minimal dataset for post-registration surveillance of new drugs in hemophilia: communication from the SSC of the ISTH

Clinical epidemiolog

The Drift Directional Dark Matter Experiments

The current status of the DRIFT (Directional Recoil Identification From Tracks) experiment at Boulby Mine is presented, including the latest limits on the WIMP spin-dependent cross-section from 1.5 kg days of running with a mixture of CS2 and CF4. Planned upgrades to DRIFT IId are detailed, along with ongoing work towards DRIFT III, which aims to be the world's first 10 m3-scale directional Dark Matter detector

Radon in the DRIFT-II directional dark matter TPC: emanation, detection and mitigation

Radon gas emanating from materials is of interest in environmental science and also a major concern in rare event non-accelerator particle physics experiments such as dark matter and double beta decay searches, where it is a major source of background. Notable for dark matter experiments is the production of radon progeny recoils (RPRs), the low energy (~ 100 keV) recoils of radon daughter isotopes, which can mimic the signal expected from WIMP interactions. Presented here are results of measurements of radon emanation from detector materials in the 1 m3 DRIFT-II directional dark matter gas time projection chamber experiment. Construction and operation of a radon emanation facility for this work is described, along with an analysis to continuously monitor DRIFT data for the presence of internal 222Rn and 218Po. Applying this analysis to historical DRIFT data, we show how systematic substitution of detector materials for alternatives, selected by this device for low radon emanation, has resulted in a factor of ~ 10 reduction in internal radon rates. Levels are found to be consistent with the sum from separate radon emanation measurements of the internal materials and also with direct measurement using an attached alpha spectrometer. The current DRIFT detector, DRIFT-IId, is found to have sensitivity to 222Rn of 2.5 μBql−1 with current analysis efficiency, potentially opening up DRIFT technology as a new tool for sensitive radon assay of materials

Estimating the risk of thrombotic events in people with congenital hemophilia A using US claims data

Aim: Compare thrombotic risk in people with congenital hemophilia A (PwcHA) to the general non-hemophilia A (HA) population. Patients & methods: US claims databases were analyzed to identify PwcHA. Incidence rates of myocardial infarction, pulmonary embolism, ischemic stroke, deep vein thrombosis and device-related thrombosis were compared with a matched cohort without HA. Results: Over 3490 PwcHA were identified and 16,380 individuals matched. PwcHA had a similar incidence of myocardial infarction and pulmonary embolism compared with the non-HA population, but a slightly higher incidence of ischemic stroke and deep vein thrombosis. The incidence of device-related thrombosis was significantly higher in PwcHA. Conclusion: This analysis suggests that PwcHA are not protected against thrombosis, and provides context to evaluate thrombotic risk of HA treatments.Tweetable abstract People with #hemophilia A are not protected against thrombotic events and should be monitored for thrombotic risk factors; the thrombotic risk of hemophilia A treatments should also be evaluated

In vitro kinetics of factor VIII activity in patients with mild haemophilia A and a discrepancy between one-stage and two-stage factor VIII assay results

In some mild haemophilia A patients (discrepant haemophilia), factor VIII coagulant activity (FVIII:C) levels, by one-stage assay are more than double than those by two-stage assay. This may be due to the longer incubation times (10-12 min) in the two-stage assay. This study aimed to determine the time course of the activation phase of the two-stage assay, using both classical coagulation and chromogenic detection methods. In both systems, for equivalent patients (equivalent FVIII:C levels by one-stage and two-stage assays, n = 6, all different mutations), similar FVIII:C results were obtained with short- or long-incubation times. In contrast, plasma from discrepant patients (n = 8, five different mutations) showed higher FVIII:C at shorter incubation times than after longer incubation times. In the chromogenic assay, FVIII:C levels were higher after incubation for 2 min (23-56%, mean 41%) than after 10 min (19-41%, mean 29%). In the classical coagulation assay, FVIII:C levels were higher at shorter incubation times (21-64%, mean 37%) than with the longer incubation times usually used (13-29%, mean 23%). These time-course experiments have verified that the longer incubation time used in the two-stage assay is at least partly responsible for the lower FVIII:C measured by that assay in discrepant haemophilia.Susan E. Rodgers, Elizabeth M. Duncan, Denise M. Barbulescu, Diana M. Quinn, John V. Lloy