Allogenic Peripheral Blood Derived Mesenchymal Stem Cells (MSCs) Enhance Bone Regeneration in Rabbit Ulna Critical-Sized Bone Defect Model

Mesenchymal stem cells (MSCs) were demonstrated to exist within peripheral blood (PB) of several mammalian species including human, guinea pig, mice, rat, and rabbit. Whether or not the PB derived MSCs (PBMSCs) could enhance the regeneration of large bone defects have not been reported. In this study, rabbit MSCs were obtained from mononuclear cells (MNCs) cultures of both the PB and bone marrow (BM) origin. The number of PBMSCs was relatively lower, with the colony forming efficiency (CFE) ranging from 1.2-13 per million MNCs. Under specific inductive conditions, PBMSCs differentiated into osteoblasts, chondrocytes, and adipocytes, showing multi- differentiation ability similar to BMMSCs. Bilateral 20 mm critical-sized bone defects were created in the ulnae of twelve 6-month old New Zealand white rabbits. The defects were treated with allogenic PBMSCs/Skelite (porous calcium phosphate resorbable substitute), BMMSCs/Skelite, PBMNCs/Skelite, Skelite alone and left empty for 12 weeks. Bone regeneration was evaluated by serial radiography, peripheral quantitative computed tomography (pQCT), and histological examinations. The x-ray scores and the pQCT total bone mineral density in the PBMSCs/Skelite and BMMSCs/Skelite treated groups were significantly greater than those of the PBMNCs/Skelite and Skelite alone groups (p

Two Birds, One Stone: Combining Student Assessment and Socio-Legal Research

We describe here a method of assessment for students. A number of short-comings of traditional assessment methods, especially essays and examinations, are discussed and an alternative assessment method, the student project, is suggested. The method aims not just to overcome the short-comings of more traditional methods, but also to provide over-worked and under-resourced academics with viable primary data for socio-legal research work. Limitations to the method are discussed, with proposals for minimising the impact of these limitations. The whole �student project� approach is also discussed with reference to the Quality Assurance Agency benchmark standards for law degrees, standards which are expected of all institutions in the UK.

Safety and Pharmacokinetics of Dapivirine Delivery From Matrix and Reservoir Intravaginal Rings to HIV-Negative Women

Vaginal microbicides for the prevention of HIV transmission may be an important option for protecting women from infection. Incorporation of dapivirine, a lead candidate nonnucleoside reverse transcriptase inhibitor, into intravaginal rings (IVRs) for sustained mucosal delivery may increase microbicide product adherence and efficacy compared with conventional vaginal formulations. Twentyfour
healthy HIV-negative women 18–35 years of age were randomly assigned (1:1:1) to dapivirine matrix IVR, dapivirine reservoir IVR, or placebo IVR. Dapivirine concentrations were measured in plasma
and vaginal fluid samples collected at sequential time points over the 33-day study period (28 days of IVR use, 5 days of follow-up). Safety was assessed by pelvic/colposcopic examinations, clinical laboratory tests, and adverse events. Both IVR types were safe and well tolerated with similar adverse events observed in the placebo and dapivirine groups. Dapivirine from both IVR types was successfully distributed throughout the lower genital tract at concentrations over 4 logs greater than the EC50 against wild-type HIV-1 (LAI) in MT4 cells. Maximum concentration (Cmax) and area under the concentration–time curve (AUC) values were significantly higher with the matrix than reservoir IVR. Mean plasma concentrations of dapivirine were ,2 ng/mL. These findings suggest that IVR delivery of microbicides is a viable option meriting further study.

Placing political economy: organising opposition to free trade before the abolition of the Corn Laws

The unfurling of global capitalism – and its attendant effects – has long been fertile intellectual terrain for geographers. But whilst studies of the processes and mechanisms of globalisation undoubtedly assume a talismanic importance in the discipline, geographers, with few exceptions, have left examinations of early economic liberalism to historians. One such critically important episode in the evolution of the liberal economic project was the repeal of the so-called 'Corn Laws' in 1846. Whilst the precise impact of the Manchester-based Anti-Corn Law League (ACLL) continues to be a matter of conjecture, Eric Sheppard has asserted that their particular take on political economy managed to assume a 'truth-like status' and worldwide universality. But the ACLL's campaign represents only one, albeit decisive, stage in the long intellectual and practical struggle between 'protectionists' and the disciples of free trade. Studies of the non-'Manchester' components have tended to focus squarely upon national politics. This paper examines a pivotal attempt in 1838 by Lord Melbourne's Government to experiment with the effective elimination of import duties on fresh fruit. Unlike most agricultural commodities, table fruit was produced in a tightly defined area, thus allowing the Government's experiment to play out, in theory, without national political fallout. Whilst the Government's clandestine actions left little time for a concerted opposition to develop, Kentish fruit growers soon organised. A formidable lobby was forged that drew wide local support yet also evolved beyond the original 'epistemic community'. Whilst the coalition failed in their efforts to reintroduce protective duties, their actions allow us to see how protectionist ideologies and policies were vivified through practices at many different spatial scales and to better understand the complex spatiality of protectionist takes on political economy. Their campaign also changed – at least in the short term – the course of British mercantile policy.

Where there is smoke, there is (the potential for) fire: soft indicators of research and policy impact

There is a growing literature examining the impact of research on informing policy, and of research and policy on practice. Research and policy do not have the same types of impact on practice but can be evaluated using similar approaches. Sometimes the literature provides a platform for methodological debate but mostly it is concerned with how research can link to improvements in the process and outcomes of education, how it can promote innovative policies and practice, and how it may be successfully disseminated. Whether research-informed or research-based, policy and its implementation is often assessed on such 'hard' indicators of impact as changes in the number of students gaining five or more A to C grades in national examinations or a percentage fall in the number of exclusions in inner city schools. Such measures are necessarily crude, with large samples smoothing out errors and disguising instances of significant success or failure. Even when 'measurable' in such a fashion, however, the impact of any educational change or intervention may require a period of years to become observable. This paper considers circumstances in which short-term change may be implausible or difficult to observe. It explores how impact is currently theorized and researched and promotes the concept of 'soft' indicators of impact in circumstances in which the pursuit of conventional quantitative and qualitative evidence is rendered impractical within a reasonable cost and timeframe. Such indicators are characterized by their avowedly subjective, anecdotal and impressionistic provenance and have particular importance in the context of complex community education issues where the assessment of any impact often faces considerable problems of access. These indicators include the testimonies of those on whom the research intervention or policy focuses (for example, students, adult learners), the formative effects that are often reported (for example, by head teachers, community leaders) and media coverage. The collation and convergence of a wide variety of soft indicators (Where there is smoke …) is argued to offer a credible means of identifying subtle processes that are often neglected as evidence of potential and actual impact (… there is fire).

The chronic fatigue syndrome: A comparative pathway analysis

In this paper, we introduce a method to detect pathological pathways of a disease. We aim to identify biological processes rather than single genes affected by the chronic fatigue syndrome (CFS). So far, CFS has neither diagnostic clinical signals nor abnormalities that could be diagnosed by laboratory examinations. It is also unclear if the CFS represents one disease or can be subdivided in different categories. We use information from clinical trials, the gene ontology (GO) database as well as gene expression data to identify undirected dependency graphs (UDGs) representing biological processes according to the GO database. The structural comparison of UDGs of sick versus non-sick patients allows us to make predictions about the modification of pathways due to pathogenesis.

The level playing field: the impact of assessment practice on professional development

Context: The effects of assessment practice on students’ learning are unclear, particularly regarding professional development. Corralling in objective structured clinical examinations (OSCEs) is designed to reduce illicit passing of examination information. Candidates completing an examination are kept secluded until the next cohort of examinees has begun. We used the introduction of corralling as a context in which to explore social influences on examination misconduct, with the aims of improving understanding of the hidden effects of assessment, and evaluating the acceptability of corralling from the student perspective.

Methods: A questionnaire was administered to students corralled post-OSCE for the first time. Eleven semi-structured interviews were subsequently conducted. Questionnaire data were analysed for descriptive statistics and thematic analysis of interview transcripts was carried out.

Results: The questionnaire response rate was 95.4% (251/263). Before corralling, 80.9% (203/251) of students were aware of the sharing of information among peers and 78.5% (197/251) agreed that such misconduct was unprofessional. The majority were in favour of corralling (90.8%, 228/251). Four themes emerged from the semi-structured interviews: the student network versus the individual; assessment-driven culture; the deferring of professionalism, and the ‘level playing field’. Students saw interaction within the student network, on a background of assessment-driven culture, as the key driver in examination misconduct. Conforming to the rules of the social network was prioritised over individual agency, although the mismatch between the rules of the network and the dominant professional discourse caused some conflict for individuals. Deferred professionalism (described as the practice of taking on the norms of professional behaviour only when qualified) was a rationalisation used to minimise this conflict. Corralling provided a ‘level playing field’ in which the influences of the network were minimised.

Conclusions: Examination misconduct is thus a complex social construction with implications for individual learners in terms of professional development. Corralling is one mechanism for addressing misconduct that is acceptable to students, but assessment processes have important hidden effects which educators should acknowledge.

Keeping it real! Enhancing realism in standardised patient OSCE stations

Background: Objective structured clinical examinations (OSCEs) are a
commonly used method of assessing clinical competency in healthcare education. They can providean opportunity to observe candidates interacting with patients.
There are many challenges in using real patients in OSCEs, and increasingly standardised patients are being used as a preference. However, by using standardised patients there is a risk of making the encounter arti?cial and removed from actual clinical practice.
Context: Efforts made in terms of cognitive, auditory, visual, tactile, psychological and emotional cues can minimise the differences between a simulated
and real clinical scenario. However, a number of factors, including feasibility, cost and usability, need to be considered if such techniques are to be practicable
within an OSCE framework.
Innovation: This article describes a series of techniques that have been used in our institution to enhance the realism of a standardised patient encounter in an
OSCE. Efforts in preparing standardised patient roles, and how they portray these roles, will be considered. A wide variety of equipment can also be used in
combination with a patient and the surrounding environment, which can further enhance the authenticity of the simulated scenario.
Implications: By enhancing the realism in simulated patient OSCE encounters, there is potential to trigger more authentic conscious responses from candidates and implicit reactions that the candidates themselves may be less
aware of. Furthermore, using such techniques may allow faculty members to select scenarios that were previously not thought possible in an OSCE

Enacting National Concerns: Accounts of the 2002 Golden Jubilee

Although the study of national identity in social psychology has examined the various ways in which the national group is ‘imagined’, little attention has been paid to the many collective national commemorations, celebrations and rituals of state assumed to unite the nation. This is surprising given the number of celebrations and commemorations which fill the calendars of modern nations
throughout the world and which are assumed by social scientists to play some part in the reproduction of the national community. Taking the British Royal Golden Jubilee celebrations of 2002, the present study examines how understandings of Anglo-British national identity are manifest in conversational
interviews during and after these events. In line with previous examinations of Anglo-Britishness, our respondents typically resisted imagining the national community as a homogenous whole and distanced themselves from depictions of the Jubilee as a nationalistic event. Support for the Jubilee was contingent upon the event being apolitical and inclusive.We suggest that such collective
national events could potentially facilitate ways of imagining the national community in terms of diversity and inclusivity rather than homogeneity and exclusivity.

Preterm cerebellar growth impairment after postnatal exposure to glucocorticoids

As survival rates of preterm newborns improve as a result of better medical management, these children increasingly show impaired cognition. These adverse cognitive outcomes are associated with decreases in the volume of the cerebellum. Because animals exhibit reduced preterm cerebellar growth after perinatal exposure to glucocorticoids, we sought to determine whether glucocorticoid exposure and other modifiable factors increased the risk for these adverse outcomes in human neonates. We studied 172 preterm neonatal infants from two medical centers, the University of British Columbia and the University of California, San Francisco, by performing serial magnetic resonance imaging examinations near birth and again near term-equivalent age. After we adjusted for associated clinical factors, antenatal betamethasone was not associated with changes in cerebellar volume. Postnatal exposure to clinically routine doses of hydrocortisone or dexamethasone was associated with impaired cerebellar, but not cerebral, growth. Alterations in treatment after preterm birth, particularly glucocorticoid exposure, may help to decrease risk for adverse neurological outcome after preterm birth.

Treatment of age-related subfoveal neovascular membranes by teletherapy:a pilot study

This investigation was designed to determine whether low dose radiation to the macular region could influence the natural course of age-related subfoveal neovascularisation. Nineteen patients with subfoveal membranes due to age-related macular degeneration (ARMD) were treated with 10 or 15 Gy of 6 MV photons and seven patients who declined treatment were followed up as controls. Six controls and all treated patients had completed follow up times of at least 12 months. Visual acuity was maintained or improved in 78% and 63% of treated patients at their 6 and 12 month follow up examinations respectively. By contrast visual acuity showed steady deterioration in six of seven controls. Significant neovascular membrane regression, as measured by image analysis, was recorded in 68% and 77% of treated patients at 6 and 12 months post-radiation, whereas the membranes in all seven control patients showed progressive enlargement. This study suggests that low doses of radiation can maintain central vision and induce regression of subfoveal neovascular membranes of ARMD in a significant proportion of patients. We now believe it appropriate to proceed to a prospective randomised study to test this hypothesis further.

Temporary tattoos:a novel OSCE assessment tool

Background: There are many issues regarding the use of real patients in objective structured clinical examinations (OSCEs). In dermatology OSCE stations, standardised patients (SPs) with clinical photographs are often used. Temporary transfer tattoos can potentially simulate skin lesions when applied to an SP. This study aims to appraise the use of temporary malignant melanoma tattoos within an OSCE framework. Method: Within an 11-station OSCE, a temporary malignant melanoma tattoo was developed and applied to SPs in a 'skin lesion' OSCE station. A questionnaire captured the opinions of the candidate, SP and examiners, and the degree of perceived realism of each station was determined. Standard post hoc OSCE analysis determined the psychometric reliability of the stations. Results: The response rates were 95.9 per cent of candidates and 100 per cent of the examiners and SPs. The 'skin lesion' station achieved the highest realism score compared with other stations: 89.0 per cent of candidates felt that the skin lesion appeared realistic; only 28 per cent of candidates had ever seen a melanoma before in training. The psychometric performance of the melanoma station was comparable with, and in many instances better than, other OSCE stations. Discussion: Transfer tattoo technology facilitates a realistic dermatology OSCE station encounter. Temporary tattoos, alongside trained SPs, provide an authentic, standardised and reliable experience, allowing the assessment of integrated dermatology clinical skills.

The view from over there:reframing the OSCE through the experience of standardised patient raters

Ratings awarded by standardised patients (SPs) in UK objective structured clinical examinations (OSCEs) are typically based on humanistic (non-technical) skills and are complementary to clinician-examiner ratings. In psychometric terms, SP ratings appear to differ from examiner ratings and improve reliability. For the first time, we used qualitative methods from a constructivist perspective to explore SP experiences of rating, and consider how these impact our understanding of assessment.

An experimental study of quinine blindness

An experimental model of quinine induced blindness is presented. Electrophysiological, angiographical and morphological examinations were made. The occurrence of blindness and any recovery from blindness was dependent upon the dose of quinine taken. As no evidence of acute retinal ischaemia was found it is concluded that quinine is retinotoxic.