New high-technology products for the treatment of haemophilia

This review will focus on new technologies in development that promise to lead to further advances in haemophilia therapeutics. There has been continued interest in the bioengineering of recombinant factor VIII (rFVIII) and factor IX (rFIX) with improved function to overcome some of the limitations in current treatment, the high costs of therapy and to increase availability to a broader world haemophilia population. Bioengineered forms of rFVIII, rFIX or alternative haemostatic molecules may ultimately have an impact on improving the efficacy of therapeutic strategies for the haemophilias by improving biosynthesis and secretion, functional activity, half-life and immunogenicity. Preventing and suppressing inhibitors to factor (F) VIII remain a challenge for both clinicians and scientists. Recent experiments have shown that it is possible to obtain anti-idiotypic antibodies with a number of desirable properties: (i) strong binding avidity to FVIII inhibitors; (ii) neutralization of inhibitory activity both in vitro and in vivo ; (iii) cross-reactivity with antibodies from unrelated patients, and (iv) no interference with FVIII function. An alternative, although complementary approach, makes use of peptides derived from filamentous-phage random libraries. Mimotopes of FVIII can be obtained, which bind to the paratope of inhibitory activity and neutralize their activity both in vitro and in vivo . In this paper, we review advanced genetic strategies for haemophilia therapy. Until recently the traditional concept for gene transfer of inherited and acquired haematological diseases has been focused on how best to obtain stable insertion of a cDNA into a target-cell genome, allowing expression of a therapeutic protein. However, as gene-transfer vector systems continue to improve, the requirement for regulated gene transcription and hence regulated protein expression will become more critical. Inappropriate protein expression levels or expression of transferred cDNAs in non-intended cell types or tissues may lead to target-cell toxicity or activation of unwanted host immune responses. Regulated protein expression requires that the transferred gene be transferred with its own regulatory cassette that allows for gene transcription and translation approaching that of the normal gene in its endogenous context. New molecular techniques, in particular the use of RNA molecules, now allow for transcription of corrective genes that mimic the normal state.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75577/1/j.1365-2516.2004.00996.x.pd

Fingerprinting Soft Materials: A Framework for Characterizing Nonlinear Viscoelasticity

We introduce a comprehensive scheme to physically quantify both viscous and elastic rheological nonlinearities simultaneously, using an imposed large amplitude oscillatory shear (LAOS) strain. The new framework naturally lends a physical interpretation to commonly reported Fourier coefficients of the nonlinear stress response. Additionally, we address the ambiguities inherent in the standard definitions of viscoelastic moduli when extended into the nonlinear regime, and define new measures which reveal behavior that is obscured by conventional techniques.Comment: 10 pages, 3 figures, full-page double-space preprint forma

Structured smoking cessation training for health professionals on cardiology wards: a prospective study.

Background: Smoking is a major cardiovascular risk factor, and smoking cessation is imperative for patients hospitalised with a cardiovascular event. This study aimed to evaluate a systems-based approach to helping hospitalised smokers quit and to identify implementation barriers. Design: Prospective intervention study followed by qualitative analysis of staff interviews Methods: The prospective intervention study assessed the effects of implementing standard operating procedures (SOPs) for the provision of counselling and pharmacotherapy to smokers admitted to cardiology wards on counselling frequency. In addition, a qualitative analysis of staff interviews was undertaken to examine determinants of physician and nurse behaviour; this sought to understand barriers in terms of motivation, capability and/or opportunity. Results: A total of 150 smoking patients were included in the study (75 before and 75 after SOP implementation). Before the implementation of SOPs, the proportion of patients reporting to have received cessation counselling from physicians and nurses was 6.7% and 1.3%, respectively. Following SOP implementation, these proportions increased to 38.7% (p < 0.001) and 2.7% (p = 0.56), respectively. Qualitative analysis revealed that lack of motivation, e.g. role incongruence, appeared to be a major barrier. Conclusions: Introduction of a set of standard operating procedures for smoking cessation advice was effective with physicians but not nurses. Analysis of barriers to implementation highlighted lack of motivation rather than capability or opportunity as a major factor that would need to be addressed

Explorations in anatomy: the remains from Royal London Hospital

This paper considers the faunal remains from recent excavations at the Royal London Hospital. The remains date to the beginning of the 19th century and offer an insight into the life of the hospital's patients and practices of the attached medical school. Many of the animal remains consist of partially dissected skeletons, including the unique finds of Hermann's tortoise (Testudo hermanni) and Cercopithecus monkey. The hospital diet and developments in comparative anatomy are discussed by integrating the results with documentary research. They show that zooarchaeological study of later post-medieval material can significantly enhance our understanding of the exploitation of animals in this perio

Simultaneous localisation and mapping on a multi-degree of freedom biomimetic whiskered robot

A biomimetic mobile robot called “Shrewbot” has been built as part of a neuroethological study of the mammalian facial whisker sensory system. This platform has been used to further evaluate the problem space of whisker based tactile Simultaneous Localisation And Mapping (tSLAM). Shrewbot uses a biomorphic 3-dimensional array of active whiskers and a model of action selection based on tactile sensory attention to explore a circular walled arena sparsely populated with simple geometric shapes. Datasets taken during this exploration have been used to parameterise an approach to localisation and mapping based on probabilistic occupancy grids. We present the results of this work and conclude that simultaneous localisation and mapping is possible given only noisy odometry and tactile information from a 3-dimensional array of active biomimetic whiskers and no prior information of features in the environment

The DRIFT 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.Comment: Proceedings of the 3rd International conference on Directional Detection of Dark Matter (CYGNUS 2011), Aussois, France, 8-10 June 201

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.

Graphite foam for cooling of automotive power electronics

Abstract -Hybrid and fuel cell vehicles utilize the Si-based IGBT (Integrated Gate Bipolar Transistor) controller which must dissipate about 100 W/cm 2 heat and maintain a temperature below 125°C. The application of porous, high thermal conductivity carbon foam, a new class of advanced lightweight material, to the thermal management of this electronic system and the use of micro-and nano-scale thermal measurement methods for analyzing thermal transport in electronics are presented. Development of advanced carbon foam with different pore structure by variation of the foaming pressure is discussed. The use of carbon foam to remove the heat generated in power electronics has been studied in three approaches: 1) forced air convection, 2) water cooled heat exchanger, and 3) thermosyphoning