Haemarthrosis of the ankle in haemophilia A and B: prevalence, impact and intervention

Haemophilia is an X-linked recessive genetic disorder characterised by bleeding within soft tissue and joints. Multi-joint disease is a common feature of severe haemophilia where the ankle is prone to haemarthrosis and haemarthropathy, but little is known about the effect on individual joints, impact on health-related quality of life (HRQoL) and foot and ankle outcome measures. A multi-methods approach was used to improve the understanding of ankle haemarthrosis and resultant haemarthropathy. The prevalence of ankle haemarthrosis and incidence at individual joints with concurrent joint health in patients compliant with prophylaxis without an active inhibitor were investigated. Approximately 60% and 40% of people with haemophilia A and B respectively experienced a minimum of one haemarthrosis over the 12 month study period. Whilst haemarthrosis incidence at individual joints was similar, the ankle was the most affected by haemarthropathy. A multi-centre patient questionnaire of the impact of ankle haemarthrosis and haemarthropathy identified that HRQoL and foot and ankle outcome measures were poor regardless of haemophilia type, severity or treatment regime. A consultant survey identified adequate access to Musculoskeletal (MSK) services across the UK. However, only 12% and 49% of patients used footwear and foot orthoses respectively. Finally, a biomechanical study was established in a healthy cohort of males, the kinetic and kinematic effect of the Leeds Ankle Stabilising Enhanced Rocker intervention, a footwear and foot orthoses intervention used clinically in the management of haemophilia. Significant reductions in the primary outcome of ankle moment of force were reported when compared to a trainer, with a minimal effect on proximal joints. The work presented in this thesis improves the understanding of the current prevalence, incidence and impact of ankle haemarthrosis and haemarthropathy. Gaps in the access to MSK services have been identified and the mechanism of action of a targeted intervention has been established, providing a basis for future research in a pathological cohort with ankle haemarthropathy

Diffusion mechanisms for silicon di-interstitials

Tight-binding molecular dynamics and density-functional simulations on silicon seeded with a di-interstitial reveal its detailed diffusion mechanisms. The lowest-energy di-interstitial performs a translation/rotation diffusion-step with a barrier of 0.3 eV and a prefactor of 11 THz followed by a reorientation diffusion step with a 90 meV barrier and a 2300 THz prefactor. The intermediate reorientation steps allow di-interstitials to diffuse isotropically along all possible bond directions in the diamond lattice. The dominating diffusion barrier of 0.3 eV is not inconsistent with the experimental value of 0.6±0.2 eV. In addition, this lowest energy di-interstitial may diffuse to neighboring sites through an intermediate structure which is the bound state of two single interstitials. The process in which migrating single interstitials combine into a di-interstitial is exothermic with almost zero energy barrier

Parameterized Littlewood-Paley operators with variable kernels on Hardy spaces and weak Hardy spaces

In this paper, by using the atomic decomposition theory of Hardy space and weak Hardy space, we discuss the boundedness of parameterized Littlewood-Paley operator with variable kernel on these spaces.Comment: 15 pages. arXiv admin note: text overlap with arXiv:1711.0961

The relationship between subchondral bone cysts and cartilage health in the Tibiotalar joint: A finite element analysis

Background: Subchondral bone cysts are a common presentation in ankle haemarthropathy. The relationship with ankle joint health has however not previously been investigated. The aim of this study was to assess the influence of subchondral bone cysts of differing shapes, volumes and depths on joint health. Methods: Chronologically sequential Magnetic Resonance imaging scans of four hemophilic ankles with subchondral bone cysts present (N = 18) were used to build patient specific finite element models under two cystic conditions to assess their influence on cartilage contact pressures. Variables such as location, volume and depth were considered individually, to investigate whether certain cystic conditions may be more detrimental to cartilage health. Findings: Significant quantifiable contact redistribution was seen in the presence of subchondral bone cysts and this redistribution reflected the shape and size of the cysts, however, with the presence of cysts in both bones in 10 of the 18 cases a direct relationship to volume could not be correlated. Interpretation: This work demonstrated a redistribution of contact pressures in the presence of subchondral bone cysts. This alteration to loading history could be linked to cartilage degeneration due to the biological response to abnormal loading

Morphological variation of the hemophilic talus

Flattening of the trochlear tali is clinically observed as structural and functional changes advance in patients with hemarthropathy of the ankle. However, the degree of this flattening has not yet been quantified, and distribution of the morphological changes across the talus not yet defined. Chronologically sequential MR images of both a hemophilic patient group (N = 5) and a single scan from a nondiseased, sex-matched, control group (N = 11) were used to take four measurements of the trochlear talus morphology at three locations (medial, central and lateral) along the sagittal plane. Three ratios of interest were defined from these to assess whether the talar dome flattens with disease. The control group MRI measurements were validated against literature data obtained from CT scans or planar X-Rays. The influence of disease on talar morphology was assessed by direct comparison of the hemophilic cases with the control group. The values for all three ratios, in all locations, differed between the control and the hemophilic group. Flattening was indicated in the hemophilic group in the medial and lateral talus, but differences in the central talus were not statistically significant. This work demonstrates that morphological assessment of the talus from MR images is similar to that from CT scans or planar X-Rays. Talar flattening does occur with hemarthropathy, especially at the medial and lateral edges of the joint surface. General flattening of the trochlear talus was confirmed in this small patient sample, however the degree and rate of change is unique to each ankle

[Introduction to] Native Voices: American Indian Identity and Resistance

Native peoples of North America still face an uncertain future due to their unstable political, legal, and economic positions. Views of their predicament, however, continue to be dominated by non-Indian writers. In response, a dozen Native American writers here reclaim their rightful role as influential voices in the debates about Native communities at the dawn of a new millennium. These scholars examine crucial issues of politics, law, and religion in the context of ongoing Native American resistance to the dominant culture. They particularly show how the writings of Vine Deloria, Jr., have shaped and challenged American Indian scholarship in these areas since the 1960s. They provide key insights into Deloria\u27s thought, while introducing some of the critical issues still confronting Native nations today. Collectively, these essays take up four important themes: indigenous societies as the embodiment of cultures of resistance, legal resistance to western oppression against indigenous nations, contemporary Native religious practices, and Native intellectual challenges to academia. Individual chapters address indigenous perspectives on topics usually treated (and often misunderstood).https://scholarship.richmond.edu/bookshelf/1333/thumbnail.jp

RIG-I-like Receptors Direct Inflammatory Macrophage Polarization against West Nile Virus Infection.

RIG-I-Like Receptors (RLRs) RIG-I, MDA5, and LGP2, are vital pathogen recognition receptors in the defense against RNA viruses. West Nile Virus (WNV) infections continue to grow in the US. Here, we use a systems biology approach to define the contributions of each RLR in the innate immune response to WNV. Genome-wide RNAseq and bioinformatics analyses of macrophages from mice lacking either RLR reveal that the RLRs drive distinct immune gene activation and response polarization to mediate an M1/inflammatory signature while suppressing the M2/wound healing phenotype. While LGP2 functions to modulate inflammatory signaling, RIG-I and MDA5 together are essential for M1 macrophage polarization in vivo and the control of WNV infection through potential downstream control of ATF4 and SMAD4 to regulate target gene expression for cell polarization. These analyses reveal the RLR-driven signature of macrophage polarization, innate immune protection, and immune programming against WNV infection

Evolution and Expression of MYB Genes in Diploid and Polyploid Cotton

R2R3-MYB transcription factors have been implicated in a diversity of plant-specific processes. Among the functions attributed to myb factors is the determination of cell shape, including regulation of trichome length and density. Because myb transcription factors are likely to play a role in cotton fiber development, the molecular evolutionary properties of six MYB genes previously shown to be expressed in cotton fiber initiation were examined. In accordance with their presumed central role, each of the genes display conservative substitution patterns and limited sequence divergence in diploid members of the genus Gossypium, and this pattern is conserved in allotetraploid cottons. In contrast to highly reiterated rDNA repeats, GhMYB homologues (duplicated gene pairs) exhibit no evidence of concerted evolution, but instead appear to evolve independently in the allopolyploid nucleus. Expression patterns for the MYB genes were examined in several organs to determine if there have been changes in expression patterns between the diploids (G. raimondii and G. arboreum) and the tetraploid (G. hirsutum) or between the duplicated copies in the tetraploid. Spatial and temporal expression patterns appear to have been evolutionarily conserved, both during divergence of the diploid parents of allopolyploid cotton and following polyploid formation. However, the duplicated copies of MYB1 in the tetraploid are not expressed at equal levels or equivalently in all organs, suggesting possible functional differentiation

Cyberinfrastructure, Science Gateways, Campus Bridging, and Cloud Computing

Computers accelerate our ability to achieve scientific breakthroughs. As technology evolves and new research needs come to light, the role for cyberinfrastructure as “knowledge” infrastructure continues to expand. This article defines and discusses cyberinfrastructure and the related topics of science gateways and campus bridging; identifies future challenges in cyberinfrastructure; and discusses challenges and opportunities related to the evolution of cyberinfrastructure, “big data” (datacentric, data-enabled, and data-intensive research and data analytics), and cloud computing.This material is based upon work supported by the National Science Foundation under grants 0504075, 0451237, 0723054, 1062432, 0116050, 0521433, 0503697, and 1053575, and several IBM Shared University Research grants and support provided by Lilly Endowment, Inc. for the Indiana University Pervasive Technology Institute. Any opinions, findings and conclusions or recommendations expressed herein are those of the authors and do not necessarily reflect the views of the supporting agencies