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

Increased complexity of Tmem16a/Anoctamin 1 transcript alternative splicing

<p>Abstract</p> <p>Background</p> <p>TMEM16A (Anoctamin 1; ANO1) is an eight transmembrane protein that functions as a calcium-activated chloride channel. <it>TMEM16A </it>in human exhibits alternatively spliced exons (6b, 13 and 15), which confer important roles in the regulation of channel function. Mouse <it>Tmem16a </it>is reported to consist of 25 exons that code for a 956 amino acid protein. In this study our aim was to provide details of mouse <it>Tmem16a </it>genomic structure and to investigate if <it>Tmem16a </it>transcript undergoes alternative splicing to generate channel diversity.</p> <p>Results</p> <p>We identified <it>Tmem16a </it>transcript variants consisting of alternative exons 6b, 10, 13, 14, 15 and 18. Our findings indicate that many of these exons are expressed in various combinations and that these splicing events are mostly conserved between mouse and human. In addition, we confirmed the expression of these exon variants in other mouse tissues. Additional splicing events were identified including a novel conserved exon 13b, tandem splice sites of exon 1 and 21 and two intron retention events.</p> <p>Conclusion</p> <p>Our results suggest that <it>Tmem16a </it>gene is significantly more complex than previously described. The complexity is especially evident in the region spanning exons 6 through 16 where a number of the alternative splicing events are thought to affect calcium sensitivity, voltage dependence and the kinetics of activation and deactivation of this calcium-activated chloride channel. The identification of multiple <it>Tmem16a </it>splice variants suggests that alternative splicing is an exquisite mechanism that operates to diversify TMEM16A channel function in both physiological and pathophysiological conditions.</p

On Dresses and Diadems: Female Discourse and the Politicized Body in Jana Sterbak’s Thread Drawings and Artworks

This thesis investigates the motivations and manifestations of female discourse and body politic in Czech-Canadian artist Jana Sterbak’s sketches and artworks from the 1980s.The analysis focuses on four artworks: Corona Laurea (1983), Hot Crown (1983-98), I Want You to Feel the Way I Do… (The Dress) (1984-85) and Standard Lives (1988). I argue that by analyzing the sketches as a separate entity and then in juxtaposition to the artwork, one can grasp the deeper, concealed meanings which Sterbak has hidden through the use of subversive text, imagery and material substance. This usually has to do with the traditionally feminine forms of clothing and adornment, specifically dresses and crowns in what are some of the artist’s most recognizable artworks. In this thesis, supported by the concepts of narratology developed by Mieke Bal and the relationship between language and the female body as Lesley Jeffries and Jane Ussher have explored in their research, I will examine Sterbak’s on-going reflections on the politics of the female body that begin with the artist’s initial conception in the process of what she calls her “thread drawings.

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

Emicizumab prophylaxis to facilitate anticoagulant therapy for management of intra‐atrial thrombosis in severe haemophilia with an inhibitor

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149546/1/hae13721.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149546/2/hae13721_am.pd

Reduction of inhibitor titres by infusion of FVIII gene transduced tolerogenic dendritic cells in haemophilic mice

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72521/1/j.1365-2516.2009.01996_2.x.pd

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

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

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