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Summary Background The WHO VISION 2020 global initiative against blindness, launched in 2000, prioritised childhood visual disability by aiming to end avoidable childhood blindness by 2020. However, progress has been hampered by the global paucity of epidemiological data concerning childhood visual disability. The British Childhood Visual Impairment and Blindness Study 2 (BCVIS2) was done to address this evidence gap. Methods BCVIS2 was a prospective UK-wide, cross-sectional, observational study to establish an inception cohort of children newly diagnosed with visual impairment. Ophthalmologists and paediatricians reported cases from 89 hospitals and community centres across the UK. We included children aged 18 years or younger who were newly diagnosed with any condition causing impaired visual acuity to a level of 0·5 logMAR or worse (worse than 6/18 Snellen) in each eye, or equivalent vision as assessed by standard qualitative measures, between Oct 1, 2015, and Nov 1, 2016. Eligible children were notified simultaneously but independently by their managing ophthalmologists and paediatricians via the two national active surveillance schemes, the British Ophthalmological Surveillance Unit and the British Paediatric Surveillance Unit. Standardised detailed demographic, socioeconomic, and clinical data about detection, management, and treatment were collected at diagnosis and 1 year later. We calculated incidence estimates and relative rates by key sociodemographic factors. We did descriptive analyses of underlying ophthalmic disorders and non-ophthalmic comorbidities. Findings 61 (7%) of 845 eligible children initially notified were ineligible at follow-up because of improved vision after treatment. Thus, the study sample comprised 784 children with permanent newly-diagnosed all-cause visual impairment, severe visual impairment, or blindness. 559 (72%) of 778 children had clinically significant non-ophthalmic impairments or conditions. 28 (4%) of 784 children died within a year after diagnosis of visual disability (all had underlying systemic disorders). Incidence of visual disability in the first year of life was 5·19 per 10 000 children (95% CI 4·71–5·72), almost ten times higher than among 1-to-4-year-olds and between 20 times and 100 times higher than in the older age groups. The overall cumulative incidence (or lifetime risk) of visual impairment, severe visual impairment, or blindness was 10·03 per 10 000 children (9·35–10·76). Incidence rates were higher for those from any ethnic minority group, the lowest quintile of socioeconomic status, and those born preterm or with low birthweight. 345 (44%) of 784 children had a single affected anatomical site. Disorders of the brain and visual pathways affected 378 (48%) of 784 children. Interpretation BCVIS2 provides a contemporary snapshot of the heterogeneity, multi-morbidity, and vulnerability associated with childhood visual disability in a high-income country. These findings could facilitate developing and delivering health care and planning of interventional research. Our findings highlight the importance of including childhood visual disability as a sentinel event and metric in global child health initiatives. Funding Fight for Sight, National Institute for Health Research, and Ulverscroft Foundation.

Neoliberal ideologies, marketization and performative regimes associated with recent reforms in universities have exerted considerable pressure on academic working conditions and subjects in recent years. While analysing these pressures is important, it is also productive to consider the ways in which academics engage in moments of resistance by mobilising resources beyond those of critique. This paper therefore focuses on joy and positive affect in the everyday moments of academic life. It utilises the feminist methodology of collective biography to explore ways of making the restricted spaces of our working day more expansive and finding within them unexpected openings for joy. Our analysis of the stories included in this paper traces the mercurial and ambiguous affective atmospheres of academic work. We suggest that joy is founded upon connections with others, that it arises in different academic spaces and that it can lead to revised knowing of ourselves. We argue that the glimpses of joy evident in this paper provoke affective attunement within the everyday, sensitizing us to other fragments of joy and providing strategies to strengthen that resistance.

Policymakers and school leaders seek to improve the quality of teaching through curriculum innovations and professional development programmes, increasingly drawing on evidence‐based approaches. For innovations involving teacher professional learning, a causal connection is posited between professional development activities, teacher engagement in them, changed practices and outcomes for learners. However, implementation and teachers’ engagement in professional development activity varies. Reasons for this include the influence of both the local and wider systemic environment in which the activity takes place and actors’ relationships to these environments. Currently, both environments and actors’ relationships are often shaped by performativity discourses and pressures. Typical implementation and process evaluation methodologies are limited by a focus on the easily measurable, often using tools that do not support fine‐grained understanding of how actors’ situations, purposes and systemic influences, and the interrelationships between these, mediate and shape different degrees of participation. Developing more in‐depth accounts are hindered by a relative lack of theorisation of context in relation to professional development. The paper uses a set of theoretical constructs to provide a stronger account of the variation and engagement in participation in such activity, with particular attention paid to the way school and teachers’ positioning within performativity systems influences participation. Constructs employed are teachers and schools’ positioning in terms of relative degrees of systemic privilege or disadvantage—understood as economic, cultural, social and symbolic capital—figured worlds and system coupling.

Universities are dominated by marketisation, individualisation and competition, forces inimical to individual flourishing and collaborative endeavours. This article presents four stories from a collective biography workshop in which a group of women academics explored everyday moments in their university lives. The stories are grim tales of damage, silencing, frustration and cynicism, whose affects continue to reverberate. The article makes two contributions to higher education research. One, its focus on mundane moments offers insights into embodied dynamics of gender, power and affect within the neoliberal university. Two, it demonstrates how collective biography as a feminist methodology can mobilise increased awareness of shared experiences and, thereby, enable participants to work together to recognise and contest the affective grimness of their workplaces.

These abstracts are of research papers published in the Proceedings of the day conference held at Manchester Metropolitan University, Manchester, 27 February 2016. The full research papers are avai...

Increasingly, policymakers seek to improve the quality of teaching through curriculum innovations and continuing professional development (CPD) programmes. However, engagement by schools and teachers varies due to mediating influences of neoliberal policies. In this article, we contribute to understanding how these tendencies affect participation. Problematising the notion of context, we examine ways in which systemic influences interacted with participation in a government-funded mathematics professional and curriculum development programme and also with participants’ purposes.\ud A 3-level clustered Randomised Controlled Trial (RCT) and an implementation and process evaluation were augmented by in-depth case studies, cross-case analysis and the application of theoretical constructs to interpret findings. Theories of capital, figured worlds and systemic coupling are utilised to theorise context.\ud Different levels of engagement are partly explainable by: the interaction of schools' relative systemic advantage and disadvantage; their orientation and coupling to performativity regimes; and the alignment or dissonance between continuing professional development or change programmes and the pedagogical and CPD cultures and purposes of the ‘actors’ (schools, departments and teachers). Performativity concerns restricted what were considered legitimate outcomes in some case study schools. This depended on teachers and schools' positioning in terms of relative degrees of systemic privilege or disadvantage - understood as economic, cultural, social and symbolic capital - and also in terms of figured worlds and system coupling. The case studies provide insights into how collaborative professional learning can be fostered more productively. Methodologically, we demonstrate the power of combining methodologies and applying explanatory social theory to augment quasi-experimental paradigms.

Globalisation and neoliberal political agendas currently dominate educational policies and practices in, amongst others, many Anglophone and northern European countries including England, with discourses of the market and performance circulating widely and having become established regimes of truth. This demands sustained critique of hegemonic, taken-for-granted understandings and an exploration of how the lived experience of neoliberalism can be disrupted. In this chapter, we utilise the tools of genealogy to develop a history of the present, focussing particularly on the variation in autonomy revealed through a study of mathematics curriculum development. Juxtaposing stories from teachers involved in the Smile mathematics curriculum development project in England in the 1970s and 1980s with responses from currently serving teachers to the experience of performativity we highlight differences in teacher autonomy over time. We conclude by discussing the possibilities for teachers to mobilise such stories in their resistance to dominant, neo-liberal discourses.

In this chapter we are concerned to understand the connection that can occur for primary school children between relevant practical, “hands-on” engagement with the material world in partnership with others and the development of mathematical commitment, enthusiasm and understanding. We draw on our personal experiences of children who, as part of a theory driven intervention, prepared for a mathematical exhibition by working on extended tasks which they then displayed and explained. We use the writings of David Jardine on time and Peter Applebaum on work to aid our thinking. We point to how absorbing, extended practical work recognises and calls forth our humanity and can provide purposeful spaces for making mathematics.

Despite the centrality of teacher professional learning in efforts to raise student attainment, little is known about how learning is experienced by individual teachers. This paper uses narrative approaches to explore the professional life history of a mathematics teacher who began teaching in England in the late 1990s. The significance of context is revealed, the inspection regime emerging as a powerful force, shaping professional identity and restricting opportunities for collaboration. Such professional life narratives are a rich resource for biographical work, offering a means to better understand the broader socio-political processes affecting teachers’ lives, a crucial step in increasing autonomy.

Purpose – The purpose of this paper is to outline an innovative method of delivering staff development in an higher education (HE) setting. The paper evaluates the processes behind the “Focus on Inspiring Teaching” week and outlines its initial impact on staff. Design/methodology/approach – This is a descriptive case study which highlights how an immersive staff development event can be used to enable HE teaching practitioners to utilise more inspiring approaches to teaching and learning. The paper draws on questionnaire evaluations (n = 43). Findings – The paper highlights how staff development events can be used to foster communities of practice for teaching staff. For this to be successful, staff needs to be committed to reflecting on their own practice and be sufficiently engaged to partake actively of staff development events. By establishing these communities, inspiring practice in teaching can be developed with successful outcomes. The paper outlines a model for staff development which could be established in other HE settings. Practical implications – Immersive staff development events are effective in achieving sustainable impact. To achieve success effective leadership and a team of committed teaching staff are needed. Success was also fostered by not making sessions compulsory whereby the staff could opt in for sessions to fit around teaching schedules. Originality/value – This paper will be of interest to those working in staff development and training and academic managers. It indicates how immersive staff development can have a positive impact on staff practice to bring about improvements to the student experience.

The use of cytokines as therapeutic agents is important, given their potent biological effects. However, this very potency, coupled with the pleiotropic nature and short half-life of these molecules, has limited their therapeutic use. Strategies to increase the half-life and to decrease toxicity are necessary to allow effective treatment with these molecules.A number of strategies are used to overcome the natural limitations of cytokines, including PEGylation, encapsulation in liposomes, fusion to targeting peptides or antibodies and latent cytokines. Latent cytokines are engineered using the latency-associated peptide of transforming growth factor-β to produce therapeutic cytokines/peptides that are released only at the site of disease by cleavage with disease-induced matrix metalloproteinases. The principles underlying the latent cytokine technology are described and are compared to other methods of cytokine delivery. The potential of this technology for developing novel therapeutic strategies for the treatment of diseases with an inflammatory-mediated component is discussed.Methods of therapeutic cytokine delivery are addressed. The latent cytokine technology holds significant advantages over other methods of drug delivery by providing simultaneously increased half-life and localised drug delivery without systemic effects. Cytokines that failed clinical trials should be reassessed using this delivery system.

Background Latent cytokines are engineered by fusing the latency associated peptide (LAP) derived from transforming growth factor-β (TGF-β) with the therapeutic cytokine, in this case interferon-β (IFN-β), via an inflammation-specific matrix metalloproteinase (MMP) cleavage site. Objectives To demonstrate latency and specific delivery in vivo and to compare therapeutic efficacy of aggrecanase-mediated release of latent IFN-β in arthritic joints to the original MMP-specific release. Methods Recombinant fusion proteins with MMP, aggrecanase or devoid of cleavage site were expressed in CHO cells, purified and characterised in vitro by Western blotting and anti-viral protection assays. Therapeutic efficacy and half-life were assessed in vivo using the mouse collagen-induced arthritis model (CIA) of rheumatoid arthritis and a model of acute paw inflammation, respectively. Transgenic mice with an IFN-regulated luciferase gene were used to assess latency in vivo and targeted delivery to sites of disease. Results Efficient localised delivery of IFN-β to inflamed paws, with low levels of systemic delivery, was demonstrated in transgenic mice using latent IFN-β. Engineering of latent IFN-β with an aggrecanase-sensitive cleavage site resulted in efficient cleavage by ADAMTS-4, ADAMTS-5 and synovial fluid from arthritic patients, with an extended half-life similar to the MMP-specific molecule and greater therapeutic efficacy in the CIA model. Conclusions Latent cytokines require cleavage in vivo for therapeutic efficacy, and they are delivered in a dose dependent fashion only to arthritic joints. The aggrecanase-specific cleavage site is a viable alternative to the MMP cleavage site for the targeting of latent cytokines to arthritic joints.

ObjectiveTo facilitate the targeting to inflammation sites of small anti-inflammatory peptides, with short half-lives, by fusion with the latency-associated peptide (LAP) of transforming growth factor β1 through a cleavable matrix metalloproteinase (MMP) linker. This design improves efficacy, overcoming the limitations to their clinical use.MethodsWe generated latent forms of vasoactive intestinal peptide (VIP), α-melanocyte-stimulating hormone (MSH) and γ3MSH by fusion to LAP through an MMP cleavage site using recombinant DNA technology. The biological activities of these latent therapeutics were studied in vivo using monosodium urate (MSU)-induced peritonitis and collagen-induced arthritis (CIA) models. We assessed gene therapy and purified protein therapy.ResultsThe recruitment of the polymorphonuclear cells induced by MSU injection into mouse peritoneal cavity was reduced by 35% with γ3MSH (1 nmol), whereas administration of a much lower dose of purified latent LAP–MMP–γ3MSH (0.03 nmol) attenuated leucocyte influx by 50%. Intramuscular gene delivery of plasmids coding LAP–MMP–VIP and LAP–MMP–αMSH at disease onset reduced the development of CIA compared with LAP–MMP, which does not contain any therapeutic moiety. Histological analysis confirmed a significantly lower degree of inflammation, bone and cartilage erosion in groups treated with LAP–MMP–VIP or LAP–MMP–αMSH. Antibody titres to collagen type II and inflammatory cytokine production were also reduced in these two groups.ConclusionIncorporation of small anti-inflammatory peptides within the LAP shell and delivered as recombinant protein or through gene therapy can control inflammatory and arthritic disease. This platform delivery can be developed to control human arthritides and other autoimmune diseases.

This small-scale study details the development and execution of a system of inclusive education in 20th and 21st century in Poland. A detailed review of the literature and employment of in-depth semi-structured interviews aimed to establish how inclusion is defined and operationalised in Poland. In addition, the study sought to establish how the teachers' levels of professional development and personal attitudes towards inclusion were influencing the evolution of this important educational initiative. The data from the study detail that the concept of inclusion is not well known in Poland, and that integrative education still dominates educational thinking. The study provides data to suggest integration in Poland works well in the early stages of education, but that it struggles to provide for and integrate older children into the mainstream educational settings. The research concludes that Poland has taken an important but perhaps faltering step towards educating all children in the mainstream schools.

Cytokines are mediators of cell communication. Their therapeutic use requires frequent high doses to achieve effective local biological levels. However, the clinical use of some cytokines is limited because of their pleiotropism, which can result in unwanted side effects. Here, we review novel protein engineering technologies that overcome these limitations and enable the targeting of cytokines to specific sites. One such technology uses antibody-based recognition to direct the cytokine to a particular tissue, and another creates encapsulated latent cytokines that are released only at the site of disease. The latter method requires the overexpression of matrix-metalloproteinases, thereby exploiting the severity of the pathological process to regulate drug delivery. Because these technologies are based on the expression of fusion proteins, their application can be extended to other biologicals and can be delivered by gene therapy.

Animal models of autoimmune disease have been developed that mimic some aspects of the pathophysiology of human disease. These models have increased our understanding of possible mechanisms of pathogenesis at the molecular and cellular level and have been important in the testing, development and validation of new immunotherapies. The susceptibility to develop disease in the majority of these models is polygenic as is the case in humans. The exceptions to this rule are gene knock outs and transgenic models of particular genes which, in particular genetic backgrounds, have also contributed to the understanding of single gene function and their possible contribution to pathogenesis. Gene therapy approaches that target immune functions are being developed with encouraging results, despite the polygenic nature of these diseases. Basically this novel immuno-genetic therapy harnesses the knowledge of immunology with the myriad of biotechnological breakthroughs in vector design and delivery. Autoimmune disease is the result of genetic dysregulation which could be controlled by gene therapy. Here we summarize the genetic basis of these human diseases as well as some of the best characterized murine models. We discuss the strategies for their treatment using immuno- and gene therapy.

Targeting cytokines to sites of disease has clear advantages because it increases their therapeutic index. We designed fusion proteins of the latent-associated peptide (LAP) derived from TGF-β with various cytokines via a matrix metalloproteinase (MMP) cleavage site. This design confers latency, increased half-life and targeting to sites of inflammation. The aim of this study is to determine whether this approach can be applied to cytokines of different molecular structures and sizes.Mature cytokines cloned downstream of LAP and a MMP cleavage site were expressed in 293T cells and assessed for latency and biological activity by Western blotting and bioassay.We demonstrate here that fusion proteins of TGF-β, erythropoietin, IL-1ra, IL-10, IL-4, BMP-7, IGF1 and IL-17 were rendered latent by fusion to LAP, requiring cleavage to become active in respective bioassays. As further proof of principle, we also show that delivery of engineered TGF-β can inhibit experimental autoimmune encephalomyelitis and that this approach can be used to efficiently deliver cytokines to the brain and spinal cord in mice with this disease.The latent cytokine approach can be successfully applied to a range of molecules, including cytokines of different molecular structure and mass, growth factors and a cytokine antagonist.

The development of novel protein therapeutics relies on the ability to express appreciable amounts of correctly folded recombinant proteins. Latent IFN-β is engineered using the latency-associated peptide (LAP) of transforming growth factor β1 (TGF-β1) to maintain IFN-β in a biologically inactive form until such time as it is released at sites of inflammation by matrix metalloproteinase activity (see Adams et al., 2003). CHO cells cultured in suspension were used for expression of latent IFN-β to allow medium scale transient transfection. However, the recombinant protein expressed in this system consisted of a mixture of properly linked disulphide dimers and monomers. The ratio of dimer:monomer produced could be significantly altered towards increased dimer production by the addition of L-cystine to the CHO culture medium. The total yield of latent IFN-β was increased by co-transfection of plasmid coding for the simian virus (SV) 40 large T antigen to the plasmid with the SV40 origin of replication expressing latent IFN-β DNA. These results provide valuable new insights for developing protocols to produce substantial quantities of latent cytokine dimers in CHO cells in suspension.

There is considerable evidence to show that strabismus patients report their quality of life (QoL) as lower than normal controls. While the majority of patients with strabismus are treated with surgery there are a number of cases where surgery is not possible and good long-term ocular alignment can be maintained with repeated injections of botulinum toxin.65 patients who had undergone over 25 injections of botulinum toxin A for long-term control of their deviation were identified and asked to fill in and return the Adult Strabismus questionnaire (AS-20) to assess their QoL.46 questionnaires were available for analysis. The mean AS-20 score in our patients compared favourably with that reported for normal controls and was much higher than that reported for patients with strabismus.Long-term injections with botulinum toxin A is a good treatment for maintaining ocular alignment if squint surgery is not indicated and those patients receiving treatment score near the level of normal controls in QoL terms.

To facilitate the targeting to inflammation sites of small anti-inflammatory peptides, with short half-lives, by fusion with the latency-associated peptide (LAP) of transforming growth factor β1 through a cleavable matrix metalloproteinase (MMP) linker. This design improves efficacy, overcoming the limitations to their clinical use.We generated latent forms of vasoactive intestinal peptide (VIP), α-melanocyte-stimulating hormone (MSH) and γ(3)MSH by fusion to LAP through an MMP cleavage site using recombinant DNA technology. The biological activities of these latent therapeutics were studied in vivo using monosodium urate (MSU)-induced peritonitis and collagen-induced arthritis (CIA) models. We assessed gene therapy and purified protein therapy.The recruitment of the polymorphonuclear cells induced by MSU injection into mouse peritoneal cavity was reduced by 35% with γ(3)MSH (1 nmol), whereas administration of a much lower dose of purified latent LAP-MMP-γ(3)MSH (0.03 nmol) attenuated leucocyte influx by 50%. Intramuscular gene delivery of plasmids coding LAP-MMP-VIP and LAP-MMP-αMSH at disease onset reduced the development of CIA compared with LAP-MMP, which does not contain any therapeutic moiety. Histological analysis confirmed a significantly lower degree of inflammation, bone and cartilage erosion in groups treated with LAP-MMP-VIP or LAP-MMP-αMSH. Antibody titres to collagen type II and inflammatory cytokine production were also reduced in these two groups.Incorporation of small anti-inflammatory peptides within the LAP shell and delivered as recombinant protein or through gene therapy can control inflammatory and arthritic disease. This platform delivery can be developed to control human arthritides and other autoimmune diseases.

Extract: The holy grail of drug development is to design a magic bullet that will deliver a therapeutic agent only to the site of disease with minimal side effects. This is of great importance in particular when it refers to biological agents such as cytokines that have pleiotropic actions in different tissues. Cytokines are local mediators of cell-to-cell communication. Their expression is transient and they have a short half-life. Therefore, to overcome the pharmacokinetic limitations of cytokines, they are given subcutaneously to reduce side effects. However, by this route they lose their potency. In order to use cytokines for therapeutic purposes they have to be administered frequently at high doses to achieve biologically active concentrations locally at the required sites of a disease.

We have engineered a latent mouse interferon beta (mIFNbeta) using the latency associated peptide (LAP) of transforming growth factor beta1 (TGF-beta1) to protect the cytokine and avoid its interaction with its receptors. This approach improves the pharmacokinetic properties and reduces the pleiotropic effects limiting the current therapeutic use of cytokines. IFNbeta was fused to the LAP using two flexible linkers flanking a matrix metalloproteinase (MMP) cleavage site for the specific release of IFNbeta at disease sites. In order to improve the hydrolysis rate of the cleavage site, 15 different cleavable linkers were introduced in the LAP-mIFNbeta construct. The kinetic parameters relative to the linker cleavage by MMP-1 and MMP-3 were measured by an ELISA method. Among the modifications done, one of the constructs bearing the activation site of pro-MMPs was the best substrate for both enzymes. The introduction of a hydrophilic sequence derived from the furin cleavage site of the anthrax toxin protective antigen increased the sensitivity to MMP-3 to up to 29-fold. These data suggest that this strategy could be useful for improving the effectiveness of the delivery and targeting of protein therapeutics.

Continued concern over attainment and participation in secondary school mathematics has led to a focus on improving the quality of teaching and student outcomes through a variety of professional le...

Mesenchymal precursor cells found in the blood (BMPCs) of normal persons adhere to plastic and glass and proliferate logarithmically in DMEM-20% fetal calf serum (FCS) without growth factors. They form cells with fibroblast-like and stromal morphology, which is not affected by eliminating CD34, CD3, or CD14 cells. Osteogenic supplements (dexamethasone, ascorbic acid, and β-glycerophosphate) added to the culture inhibited fibroblast formation, and BMPCs assumed the cuboidal shape of osteoblasts. After 5 days in supplemented medium, the elutriated cells displayed alkaline phosphatase (AP), and the addition of bone morphogenetic protein (BMP)2 (1 ng) doubled AP production (P < 0.04). Two weeks later, 30% of the cells were very large and reacted with anti-osteocalcin antibody. The same cultures also contained sudanophlic adipocytes and multinucleated giant cells that stained for tartrate-resistant acid phosphatase (TRAP) and vitronectin receptors. Cultured BMPCs immunostain with antibodies to vimentin, type I collagen, and BMP receptors, heterodimeric structures expressed on mesenchymal lineage cells. In addition, BMPCs stain with anti-CD105 (endoglin), a putative marker for bone-marrow mesenchymal stem cells (MSCs)., Introduction: Adult human bone marrow contains a minority population of MSCs that contribute to the regeneration of tissues such as bone, cartilage, muscle, ligaments, tendons, fat, and stroma. Evidence that these MSCs are pluripotent, rather than being a mixture of committed progenitor cells each with a restricted potential, includes their rapid proliferation in culture, a characteristic morphology, the presence of typical marker proteins, and their consistent differentiation into various mesenchymal lineages. These attributes are maintained through multiple passages and are identifiable in individual stem cells. Aims: Since stem cells are present in both the bone marrow and other tissues, we thought it possible that cells with a similar appearance and pluripotent mesenchymal potential would be present in the blood. We applied techniques used successfully with marrow MSCs to identify similar cells in elutriation fractions of normal human blood. Methods: BMPCs were elutriated by diluting the buffy coats from 500 ml of anticoagulant-treated, platelet-depleted blood 1:4 in RPMI-1640 medium (RPMI) and layering 25-ml portions over 20 ml of Lymphoprep™. These samples were centrifuged at 2000 rpm for 20 min. The leukocyte-rich interface cells were collected, made up to 20 ml in RPMI, and separated by density-gradient centrifugation. The interface cells, now depleted of red blood cells, were collected, resuspended in 50 ml of sterile RMPI and 5% heat-inactivated FCS, and introduced into the sample line of the flow system of a Beckman JE-50 cell elutriator charged with elutriation buffer. The chamber was centrifuged at 25 000 rpm at 10°C and the flow rate adjusted to 12 ml/min. After about 150 ml had been collected, the flow rate was increased by 1 ml/min. Fractions nos. 1-6 (flow rates of 12-16 ml/min) contained most of the lymphocytes. Monocytes usually appeared in fractions 6 or 7 (as determined by flow cytometric analysis in a fluorescence-activated cell sorter (FACS). BMPCs were concentrated in fractions 7 and 8, along with monocytes and lymphocytes. Elutriation fractions with more than 50% and less than 75% monocytes were collected and concentrated by centrifugation at 1200 rpm for 5 min, and the cell pellets were combined, reconstituted in DMEM plus 20% sterile heat-inactivated FCS, counted, washed in medium, repelleted, and then resuspended in DMEM to 5 × 106/ml and dispensed into either tissue-culture plastic slides or glass chamber slides. Cells thus obtained were observed in time-lapse cinematography, assayed for proliferation, and examined immunohistologically and histochemically, and their ability to become fibroblasts, osteoclasts, osteoblasts, and adipocytes was documented. Results: BMPCs were found in elutriation fractions containing less than 30% T cells and more than 60% monocytes from the blood of more than 100 normal persons. BMPCs adhered to plastic and glass and proliferated logarithmically in DMEM-20% FCS without added growth factors. The initial elutriate had only small, round, mononuclear cells; upon culture, these were replaced by fibroblast-like cells and large, round, stromal cells. The formation of cells with fibroblast-like and stromal morphology was not affected by eliminating CD34, CD3, or CD14 cells from the elutriation fraction. Osteogenic supplements (dexamethasone, ascorbic acid, and β-glycero-phosphate) added to the culture inhibited fibroblast formation, and BMPCs assumed the cuboidal shape of osteoblasts. After 5 days in supplemented medium, the elutriated cells displayed AP and its production was doubled by the addition of BMP2 (1 ng) (P < 0.04). Two weeks later, 30% of the cells were very large and reacted with anti-osteocalcin antibody. The same cultures contained two other types of cell: sudanophlic adipocytes and multinucleated giant cells, which stain for TRAP and vitronectin receptors (attributes of osteoclasts). Cultured BMPCs were immunostained by antibodies to vimentin, type I collagen, and BMP receptors (heterodimeric structures expressed on mesenchymal lineage cells). The cultured cells also stained strongly for the SH-2 (endoglin) antigen, a putative marker for marrow MSCs. BMPCs express the gene for SDF-1, a potent stroma-derived CXCα chemokine. Discussion: In the circulation of normal individuals is a small population of CD34- mononuclear cells that proliferate rapidly in culture as an adherent population with a variable morphology, display cytoskeletal, cytoplasmic, and surface markers of mesenchymal precursors, and differentiate into several lineages (fibroblasts, osteoblasts, and adipocytes). These are all features found in bone-marrow-derived MSCs. Therefore, autologous blood could provide cells useful for tissue engineering and gene therapy. In addition, the demonstration of similar cells in the inflammatory joint fluids and synovium of patients with rheumatoid arthritis (RA) suggests that these cells may play a role in the pathogenesis of RA.

EDITOR—The description in 1941 by an Australian ophthalmologist of congenital cataract occurring after rubella in pregnancy was one of the first clearly demonstrated risk factors for congenital anomalies in humans.1 Several of the major ophthalmic long term effects of prenatal rubella infection, such as cataract, microphthalmos, and retinopathy, are recognisable at birth or in early infancy.2 Their diagnosis in children is recognised to be important in identifying the population at …

Following a three-year staff development initiative within one faculty in a UK university, the authors reflected on inspiring teaching and the role that staff development can play in enhancing individual practice. Teaching is a core component of Higher Education and is complex and multi-faceted both theoretically and in practice. Through individual reflections to a set of pre-determined questions, a group of Higher Education teachers (n = 5) with a responsibility for the development of learning, teaching and assessment, share their thoughts, feelings and beliefs on inspiring teaching. The interpretive analysis of the data shows from a staff perspective that the notion of inspiring teaching has three main components which are all interrelated, those being; the actual teaching and learning experience; the design of the curriculum and the teacher/student relationship. Staff development initiatives were found to help people explore and develop their own teaching philosophy, to develop new practices and to share and learn from others. However, individual’s mindset, beliefs and attitudes were found to be a challenge. Teachers can frame their development around the different aspects of inspiring teaching and with support from senior leadership as well as a positive culture, teaching communities can work together towards inspiring teaching.