The haematopoietic stem cell niche:new insights into the mechanisms regulating haematopoietic stem cell behaviour

The concept of the haematopoietic stem cell (HSC) niche was formulated by Schofield in the 1970s, as a region within the bone marrow containing functional cell types that can maintain HSC potency throughout life. Since then, ongoing research has identified numerous cell types and a plethora of signals that not only maintain HSCs, but also dictate their behaviour with respect to homeostatic requirements and exogenous stresses. It has been proposed that there are endosteal and vascular niches within the bone marrow, which are thought to regulate different HSC populations. However, recent data depicts a more complicated picture, with functional crosstalk between cells in these two regions. In this review, recent research into the endosteal/vascular cell types and signals regulating HSC behaviour are considered, together with the possibility of a single subcompartmentalised niche.

The effect of ageing on in vivo human ciliary muscle morphology and contractility

Purpose. To assess the effect of ageing on in vivo human ciliary muscle morphology and contractility during accommodation. Methods. Seventy-nine subjects, aged 19–70 years were recruited. High-resolution images were acquired of nasal and temporal ciliary muscle in the relaxed state, and at stimulus vergence levels of -4 and -8 D, using anterior segment optical coherence tomography (AS-OCT). Objective refractions and axial lengths were also recorded. Linear regression analysis was performed to determine the effect of age on nasal and temporal ciliary muscle morphologic characteristics. Results. Ciliary muscle anterior length decreased significantly with age both nasally (R = 0.461, P = 0.001) and temporally (R = 0.619, P < 0.001) in emmetropic eyes. In a subset of 37 participants, ciliary muscle maximum width increased significantly with age, by 2.8 µm/year nasally (R = 0.54, P < 0.001) and 3.0 µm/year temporally (R = 0.44, P = 0.007), while the distance from the inner apex of the ciliary muscle to the scleral spur decreased significantly with age on both the nasal and temporal aspects (R = 0.47; P = 0.004 and R = 0.43; P = 0.009, respectively). During accommodation, changes to ciliary muscle thickness and length remained constant throughout life. Conclusions. The human ciliary muscle undergoes age-dependent changes in morphology that suggest an antero-inwards displacement of muscle mass, particularly in emmetropic eyes. However, the morphologic changes observed appear not to affect the ability of the muscle to contract during accommodation, even in established presbyopes, thus supporting a lenticular model of presbyopia development.

Embedding e-portfolios for effective lifelong learning:a case study

Lifelong learning is a ‘keystone’ of educational policies (Faure, 1972) where the emphasis on learning shifts from teacher to learner. Higher Education (HE) institutions should be committed to developing lifelong learning, that is promoting learning that is flexible, diverse and relevant at different times, and in different places, and is pursued throughout life. Therefore the HE sector needs to develop effective strategies to encourage engagement in meaningful learning for diverse student populations. The use of e-portfolios, as a ‘purposeful aggregation of digital items’ (Sutherland & Powell, 2007), can meet the needs of the student community by encouraging reflection, the recording of experiences and achievements, and personal development planning (PDP). The use of e-portfolios also promotes inclusivity in learning as it provides students with the opportunity to articulate their aspirations and take the first steps along the pathway of lifelong learning. However, ensuring the uptake of opportunities within their learning is more complex than the students simply having access to the software. Therefore it is argued here that crucial to the effective uptake and engagement of the e-portfolio is embedding it purposefully within the curriculum. In order to investigate effective implementation of e-portfolios an explanatory case study on their use was carried out, initially focusing on 3 groups of students engaged in work-based learning and professional practice. The 3 groups had e-Portfolios embedded and assessed at different levels. Group 1 did not have the e-Portfolio embedded into their curriculum nor was the e-Portfolio assessed. Group 2 had the e-Portfolio embedded into the curriculum and formatively assessed. Group 3 also had the e-Portfolio embedded into the curriculum and were summatively assessed. Results suggest that the use of e-Portfolios needs to be integral to curriculum design in modules rather than used as an additional tool. In addition to this more user engagement was found in group 2 where the e-Portfolio was formatively assessed only. The implications of this case study are further discussed in terms of curriculum development.

Characterization of Transglutaminase 2 in macrophage clearance of apoptotic cells

Removal of dead or diseased cells is crucial feature of apoptosis for managing many biological processes such as tissue remodelling, tissue homeostasis and resolution and control of immune responses throughout life. Tissue transglutaminase (TG2) is a protein crosslinking enzyme that has been implicated in apoptotic cell clearance but also mediates many important cell functions including cell adhesion, migration and monocyte-macrophage differentiation. Cell surface-associated TG2 regulates cell adhesion and migration, via its association with receptors such as syndecan-4, ß1 and ß3 integrin. Whilst defective apoptotic cell clearance has been described in TG2-deficient mice, the precise extracellular role of TG2 in apoptotic cell clearance remains ill-defined. This thesis addresses macrophage TG2 in cell corpse clearance. TG2 expression (cytosolic and cell surface) in human macrophages was revealed and data demonstrate that loss of TG2 activity through the use of inhibitors of function, including cellimpermeable inhibitors significantly inhibit the ability of macrophages to clear apoptotic cells (AC). This includes reduced macrophage recruitment to and binding of apoptotic cells. Association studies reveal TG2-syndecan-4 interaction through heparan sulphate side chains, and knockdown of syndecan-4 reduces cell surface TG2 activity and apoptotic cell clearance. Furthermore, inhibition of TG2 activity reduces crosslinking of CD44, reported to augment AC clearance. Thus it defines for the first time a role for TG2 activity at the cell surface of human macrophages in multiple stages of AC clearance and proposed that TG2, in association with heparan sulphates, may exert its effect on AC clearance via crosslinking of CD44.

Encouraging the intellectual craft of living research:tattoos, theory and time

This chapter contributes to the anthology on learning to research - researching to learn because it emphases a need to design curricula that enables living research, and on-going researcher development, rather than one that restricts student and staff activities, within a marketised approach towards time. In recent decades higher education (HE) has come to be valued for its contribution to the global economy. Referred to as the neo-liberal university, a strong prioritisation has been placed on meeting the needs of industry by providing a better workforce. This perspective emphasises the role of a degree in HE to secure future material affluence, rather than to study as an on-going investment in the self (Molesworth , Nixon & Scullion, 2009: 280). Students are treated primarily as consumers in this model, where through their tuition fees they purchase a product, rather than benefit from the transformative potential university education offers for the whole of life.Given that HE is now measured by the numbers of students it attracts, and later places into well-paid jobs, there is an intense pressure on time, which has led to a method where the learning experiences of students are broken down into discrete modules. Whilst this provides consistency, students can come to view research processes in a fragmented way within the modular system. Topics are presented chronologically, week-by-week and students simply complete a set of tasks to ‘have a degree’, rather than to ‘be learners’ (Molesworth , Nixon & Scullion, 2009: 277) who are living their research, in relation to their own past, present and future. The idea of living research in this context is my own adaptation of an approach suggested by C. Wright Mills (1959) in The Sociological Imagination. Mills advises that successful scholars do not split their work from the rest of their lives, but treat scholarship as a choice of how to live, as well as a choice of career. The marketised slant in HE thus creates a tension firstly, for students who are learning to research. Mills would encourage them to be creative, not instrumental, in their use of time, yet they are journeying through a system that is structured for a swift progression towards a high paid job, rather than crafted for reflexive inquiry, that transforms their understanding throughout life. Many universities are placing a strong focus on discrete skills for student employability, but I suggest that embedding the transformative skills emphasised by Mills empowers students and builds their confidence to help them make connections that aid their employability. Secondly, the marketised approach creates a problem for staff designing the curriculum, if students do not easily make links across time over their years of study and whole programmes. By researching to learn, staff can discover new methods to apply in their design of the curriculum, to help students make important and creative connections across their programmes of study.

Intergroup relations in action: questions asked about lesbian, gay and bisexual issues in diversity training

This paper focuses on the questions which heterosexual trainees ask about lesbian, gay and bisexual (LGB) experience within diversity training about LGB issues. Drawing on a data corpus of 162 questions asked by trainees in 13 tape-recorded training sessions, questions were coded into six categories: (1) general understanding questions; (2) questions about the trainer's life, experience and practices; (3) professional practice questions; (4) questions about lesbian and gay related legislation, policies and procedures; (5) questions about specific people and projects and (6) questions about the meanings, derivations and correct use of terms and symbols. Real questions are compared with the decontexualized questions (and answers to them) that are provided in training manuals and it is demonstrated that these questions differ markedly from how questions actually get asked and how they actually get answered. Recommendations are provided for improving training and the argument made for turning towards analyses of the real world in action, especially when considering intergroup relations. Copyright © 2008 John Wiley & Sons, Ltd.

Whole life performance assessment: critical success factors

Whole life costing (WLC) has become the best practice in construction procurement and it is likely to be a major issue in predicting whole life costs of a construction project accurately. However, different expectations from different organizations throughout a project's life and the lack of data, monitoring targets, and long-term interest for many key players are obstacles to be overcome if WLC is to be implemented. A questionnaire survey was undertaken to investigate a set of ten common factors and 188 individual factors. These were grouped into eight critical categories (project scope, time, cost, quality, contract/administration, human resource, risk, and health and safety) by project phase, as perceived by the clients, contractors and subcontractors in order to identify critical success factors for whole life performance assessment (WLPA). Using a relative importance index, the top ten critical factors for each category, from the perspective of project participants, were analyzed and ranked. Their agreement on those categories and factors were analyzed using Spearman's rank correlation. All participants identify “Type of Project” as the most common critical factor in the eight categories for WLPA. Using the relative index ranking technique and weighted average methods, it was found that the most critical individual factors in each category were: “clarity of contract” (scope); “fixed construction period” (time); “precise project budget estimate” (cost); “material quality” (quality); “mutual/trusting relationships” (contract/administration); “leadership/team management” (human resource); and “management of work safety on site” (health and safety). There was relatively a high agreement on these categories among all participants. Obviously, with 80 critical factors of WLPA, there is a stronger positive relationship between client and contactor rather than contractor and subcontractor, client and subcontractor. Putting these critical factors into a criteria matrix can facilitate an initial framework of WLPA in order to aid decision making in the public sector in South Korea for evaluation/selection process of a construction project at the bid stage.

Learning for life:educational provision at Cadbury, 1831-1981

Cadbury showed concern for the welfare of its labour force in a variety of ways and not least in the provision of educational and educative-recreational facilities. The firm regarded the education of employees as having a positive effect on the efficiency of the business at the same time as being of benefit to the individual, the local community and the nation. The life-long education of people was seen as essential for personal fulfilament, social improvement, economic competitiveness and the proper functioning of democratic procedures. The educational system built up at Cadbury, and the philosophy on which it was founded, acquired both a domestic and international reputation. Its main components were the day continuation education of juniors; the Bournville Works Evening Institute; vocational and non-vocational scholarships; emphasis on the primary importance of general education as a basis for life, work and technical training; stress on equality of educational opportunity for females; and leisure and sporting amenities which the firm felt to be educative in the sense that they contributed to personal psychological and physical development and social skills. The system was primarily shaped and constructed in the first three decades of the twentieth century and went into decline and eventual demise in the 1960's and 1970's as a result of economic pressures, social changes, enhanced state arrangements for education, shifts in Cadbury management thinking and the merger with Schweppes in 1969.

Intercultural training for international placements

Despite its increasing popularity, much intercultural training is not developed with the same level of rigour as training in other areas. Further, research on intercultural training has brought inconsistent results about the effectiveness of such training. This PhD thesis develops a rigorous model of intercultural training and applies it to the preparation of British students going on work/study placements in France and Germany. It investigates the reasons for inconsistent training success by looking at the cognitive learning processes in intercultural training, relating them to training goals, and by examining the short- and long-term transfer of intercultural training into real-life encounters with people from other cultures. Two cognitive trainings based on critical incidents were designed for online delivery. The training content relied on cultural practice dimensions from the GWBE study (House, Hanges, Javidan, Dorfman & Gupta, 2004). Of the two trainings, the 'singlemode training' aimed to develop declarative knowledge, which is necessary to analyse and understand other cultures. The 'concurrent training' aimed to develop declarative and procedural knowledge, which is needed to develop skills for dealing with difficult situations in a culturally appropriate way. Participants (N-48) were randomly assigned to one of the two training conditions. Declarative learning appeared as a process of steady knowledge increase, while procedural learning involved cognitive re-categorisation rather than knowledge increase. In a negotiation role play with host-country nationals directly after the online training, participants of the concurrent training exhibited a more initiative negotiation style than participants of the single-mode training. Comparing cultural adjustment and performance of training participants during their time abroad with an untrained control group, participants of the concurrent training showed the qualitatively best development in adjustment and performance. Besides intercultural training, multicultural personality traits were assessed and proved to be a powerful predictor of adjustment and, indirectly, of performance abroad.

The experience of living with age related macular degeneration:A longitudinal study into the impact of age related macular degeneration on quality of life

In this thesis I contribute to the understanding of the experience of living with Age-Related Macular Degeneration (AMD) and its impact on quality of life through the use of a pragmatically guided mixed methods approach. AMD is a condition resulting in the loss of central vision in old age which can have a huge impact on the lives of patients. This thesis includes: literature reviewing; qualitative meta-synthesis; surveys and descriptive statistics; observation; and analysis of in-depth interviewing, in order to build a picture of what it is like for older people to live with AMD. I present the findings from six separate studies each designed to answer specific research questions. I begin with a mixed methods study to determine how well the most commonly used measure of quality of life for AMD patients’ represents patient experiences. I then go on to investigate the experiences of patients with AMD through a meta-synthesis of qualitative research and finally present four of my own empirical studies three of which investigate the experiences of patients with different types of AMD: early dry AMD, treatable wet AMD and advanced wet AMD and the final study investigates what it is like for a couple living together with AMD. Throughout the qualitative studies I use Interpretative Phenomenological Analysis (IPA) to develop an understanding of the experiences and life contexts of patients with AMD. Through rigorous analysis, I identify a range of themes which highlight the shared and divergent experiences of individuals with AMD and the need to acknowledge patients’ past, present and potential future life contexts and experiences when providing services to older people with AMD. I relate the findings of the six studies to the wider psychological literature on chronic illness and make recommendations for services for patients with AMD to be provided holistically within a lifeworld-led health care model.

Professionalism in higher education:important not only for lawyers

This article considers how, in light of the changing legal profession and higher education, academia could address professionalism training. The authors put forward an argument that, if professionalism is to be understood as a set of skills, values and attitudes required for any lawyer, it is now a good time to consider how these could be taught and assessed in law and non-law degrees. The formation of professional values and attitudes is a long process that continues throughout a person’s life. The earlier students are exposed to professional values, attitudes and skills, the better the quality of service these future lawyers will provide to the public. Taking into account the Legal Education and Training Review (LETR) recommendations, the article suggests some practical ways as to how professionalism could be developed in higher education.

Interventions for nurses caring for a child who has an unexpected acute life threatening event (ALTE) in hospital

Introduction: Caring for a child who has an unexpected ALTE in hospital can be stressful. An ALTE may include a cardiac arrest, respiratory arrest or call for immediate assistance. An international survey of practice was conducted to identify any existing interventions to inform a PhD program of work aimed at reducing the stress from these events through preparation and support. Purpose: The purpose of the survey was threefold: (1) Describe ‘normal’ practice when it comes to preparing staff or providing psychological support after caring for a child who has had an ALTE. (2) Determine if there are any interventions to prepare clinical staff for potential psychological effects of caring for a child who has an ALTE. (3) Determine if there are any interventions to provide support for clinical staff after caring for a child who has an ALTE. Material - Methods: An 18 item semi structured questionnaire was designed for the study to allow respondent to describe practices within their institution and outline their opinions and professional experiences. Clinicians from selected children’s and adult hospitals in Australia, Canada, New Zealand, United Kingdom and the United States of America were contacted by telephone. Following consent they were given the option to complete the survey via the telephone, by post or online. Results: Of the 61 hospitals approached 44 (72%) clinicians responded. Eighteen (41%) respondents identified interventions in place to prepare nurses for an ALTE ranging from (but not limited to) ad hoc discussions during life support training through to structured simulation training. Thirty-six (82%) respondents identified that they had interventions in place to support nurses after an ALTE ranging from (but not limited to) debriefing through to structured case reviews. Conclusions: Interventions varied across institutions, with no outcome or evaluation data for the interventions published to date.