Evidence‐based guidelines support integrated disease management as the optimal model of haemophilia care

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/122450/1/hae12997_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/122450/2/hae12997.pd

Evidence‐based guidelines support integrated disease management as the optimal model of haemophilia care

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/122450/1/hae12997_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/122450/2/hae12997.pd

Empirically inspired simulated electro-mechanical model of the rat mystacial follicle-sinus complex

In whiskered animals, activity is evoked in the primary sensory afferent cells (trigeminal nerve) by mechanical stimulation of the whiskers. In some cell populations this activity is correlated well with continuous stimulus parameters such as whisker deflection magnitude, but in others it is observed to represent events such as whisker-stimulator contact or detachment. The transduction process is mediated by the mechanics of the whisker shaft and follicle-sinus complex (FSC), and the mechanics and electro-chemistry of mechanoreceptors within the FSC. An understanding of this transduction process and the nature of the primary neural codes generated is crucial for understanding more central sensory processing in the thalamus and cortex. However, the details of the peripheral processing are currently poorly understood. To overcome this deficiency in our knowledge, we constructed a simulated electro-mechanical model of the whisker-FSC-mechanoreceptor system in the rat and tested it against a variety of data drawn from the literature. The agreement was good enough to suggest that the model captures many of the key features of the peripheral whisker system in the rat

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

Self-adaptive context aware audio localization for robots using parallel cerebellar models

An audio sensor system is presented that uses multiple cerebellar models to determine the acoustic environment in which a robot is operating, allowing the robot to select appropriate models to calibrate its audio-motor map for the detected environment. The use of the adaptive filter model of the cerebellum in a variety of robotics applications has demonstrated the utility of the so-called cerebellar chip. This paper combines the notion of cerebellar calibration of a distorted audio-motor map with the use of multiple parallel models to predict the context (acoustic environment) within which the robot is operating. The system was able to correctly predict seven different acoustic contexts in almost 70% of cases tested

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

MCFD2, a second gene defective in combined factor V/factor VIII deficiency, encodes a novel ER protein that interacts with LMAN1 (ERGIC‐53) to form a cofactor‐specific sorting receptor

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106096/1/jth03926.pd

Thrombosis And Hemostasis Centers Pilot Sites Registry: Thrombophilia Screening In Children

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106147/1/jth03026.pd