If immunized with an antigen of interest, transgenic mice with large portions of unrearranged human immunoglobulin loci can produce fully human antigen-specific antibodies; several such antibodies ...are in clinical use. However, technical limitations inherent to conventional transgenic technology and sequence divergence between the human and mouse immunoglobulin constant regions limit the utility of these mice. Here, using repetitive cycles of genome engineering in embryonic stem cells, we have inserted the entire human immunoglobulin variable-gene repertoire (2.7 Mb) into the mouse genome, leaving the mouse constant regions intact. These transgenic mice are viable and fertile, with an immune system resembling that of wild-type mice. Antigen immunization results in production of high-affinity antibodies with long human-like complementarity-determining region 3 (CDR3H), broad epitope coverage and strong signatures of somatic hypermutation. These mice provide a robust system for the discovery of therapeutic human monoclonal antibodies; as a surrogate readout of the human antibody response, they may also aid vaccine design efforts.
“Sequential/Consequential” refers to my material-based, process-oriented approach to creating ceramic sculptures. A guiding principle of my thesis activities is centered around expressing temporal ...accumulation of the art making process in a visual dialogue. The working properties of clay have physical characteristics that change over time. Beginning first with a wet, malleable material, the transformation during drying and kiln firing create a stone-like final product. While in many cases the final product is just that, final, I explore how to expand upon that linear history. My creative process involves multiple components to create a visual dialogue that explores the idea of time being a cyclical entity. Incorporating video recording devices, material processing and still image photography, I illuminate how geologic processes that may take millennia to occur can be experienced in a few minutes.
Background:
Determining the success of joint fusion operations is often a diagnostic dilemma, and many factors may be considered. Most would agree that the broad categories of clinical success and ...radiographic success are likely most useful to determine the overall success of a joint fusion operation. Very little evidence exists to assist the surgeon in determining what constitutes a successful radiographic fusion. The aim of this study was to determine the extent of osseous bridging as measured by computed tomography (CT) that was associated with a good clinical outcome as measured by the 12-Item Short Form (SF-12), Foot Function Index (FFI), and American Orthopaedic Foot & Ankle Society (AOFAS) clinical outcomes questionnaires at 24 weeks.
Methods:
Patients who had isolated joint fusions were evaluated (n = 275) to determine the correlation of extent of osseous bridging with clinical outcome. The extent of osseous bridging across the joint in question was categorized as absent (0%-24%), minimal (25%-49%) moderate (50%-74%), or complete (75%-100%). Clinical outcome scores included the SF-12, FFI, and AOFAS outcomes score.
Results:
Patients evaluated to have at least minimal osseous bridging at fusion sites (25%-49%) on CT reported a clinically important improvement in SF-12, FFI, and AOFAS, whereas those with “absent” osseous bridging (0%-24%) did not report a clinically important improvement in outcome scores.
Conclusion:
This study suggests that osseous bridging of greater than 25% to 49% at the fusion site measured by CT may be necessary to consider a hindfoot or ankle fusion clinically successful.
Level of Evidence:
Level IV, case series.
Alan Milburn, the Chair of the Government's Social Mobility and Child Poverty Commission recently highlighted the role of education in progressing social mobility in Scotland; 'In my view it's a ...grave social injustice that only one in forty pupils from Scotland's most deprived households...got three As in their Highers in 2011, compared to one in ten across all income levels'. An analysis of the data on school leavers in Scotland also points towards a considerable inequality in access to higher education in particular. This paper reports on a research and development project that progressed the provision of intergenerational mentoring for young people from communities experiencing social and economic disadvantage. The findings affirm the role of research in such innovation and indicate that intergenerational mentoring offers a process, long awaited, through which young people can gain access to the different forms of social and cultural capital that are implicitly essential for progression into higher education.
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