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The process of human embryonic mammary development gives rise to the structures in which mammary cells share a developmental lineage with skin epithelial cells such as keratinocytes. As some breast carcinomas have previously been shown to express high levels of involucrin, a marker of keratinocyte differentiation, we hypothesised that some breast tumours may de-differentiate to a keratinocyte-derived ‘evolutionary history’. To confirm our hypothesis, we investigated the frequency of involucrin expression along with that of Brk, a tyrosine kinase expressed in up to 86% of breast carcinomas whose normal expression patterns are restricted to differentiating epithelial cells, most notably those in the skin (keratinocytes) and the gastrointestinal tract. We found that involucrin, a keratinocyte differentiation marker, was expressed in a high proportion (78%) of breast carcinoma samples and cell lines. Interestingly, tumour samples found to express high levels of involucrin were also shown to express Brk. 1,25-dihydroxyvitamin D3, a known differentiation agent and potential anti-cancer agent, decreased proliferation in the breast cancer cell lines that expressed both involucrin and Brk, whereas the Brk/involucrin negative cell lines tested were less susceptible. In addition, responses to 1,25-dihydroxyvitamin D3 were not correlated with vitamin D receptor expression. These data contribute to the growing body of evidence suggesting that cellular responses to 1,25-dihydroxyvitamin D3 are potentially independent of vitamin D receptor status and provide an insight into potential markers, such as Brk and/or involucrin that could predict therapeutic responses to 1,25-dihydroxyvitamin D3.

Washington was the first state to require all licensed general medical and behavioral health care professionals (HCPs) to complete training in suicide assessment, management, and treatment. Results from pretest and posttest surveys of 873 HCPs participating in All Patients Safe, a 6-hour online training course, are presented. Improvements in knowledge and attitudes about suicide and confidence in treating at-risk individuals were observed, demonstrating the effectiveness of delivering large-scale training to HCPs to fulfill state requirements. Future work should examine the impact of training on clinical practices and the role of training in improving patient care.

South Africa has the largest number of people living with HIV worldwide. South Africa has implemented five population-based HIV prevalence surveys since 2002 aimed at understanding the dynamics and the trends of the epidemic. This paper presents key findings from the fifth HIV prevalence, incidence, and behaviour survey conducted in 2017 following policy, programme, and epidemic change since the prior survey was conducted in 2012. A cross-sectional population-based household survey collected behavioural and biomedical data on all members of the eligible households. A total of 39,132 respondents from 11,776 households were eligible to participate, of whom 93.6% agreed to be interviewed, and 61.1% provided blood specimens. The provided blood specimens were used to determine HIV status, HIV incidence, viral load, exposure to antiretroviral treatment, and HIV drug resistance. Overall HIV incidence among persons aged 2 years and above was 0.48% which translates to an estimated 231,000 new infections in 2017. HIV prevalence was 14.0% translating to 7.9 million people living with HIV. Antiretroviral (ARV) exposure was 62.3%, with the lowest exposure among those aged 15 to 24 years (39.9%) with 10% lower ARV coverage among males compared to females. Viral suppression among those on treatment was high (87.3%), whilst HIV population viral load suppression was much lower (62.3%). In terms of risk behaviours, 13.6% of youth reported having had an early sexual debut (first sex before the age of 15 years), with more males reporting having done so (19.5%) than females (7.6%). Age-disparate relationships, defined as having a sexual partner 5+ years different from oneself,) among adolescents were more common among females (35.8%) than males (1.5%). Self-reported multiple sexual partnerships (MSPs), defined as having more than one sexual partner in the previous 12 months, were more commonly reported by males (25.5%) than females (9.0%). Condom use at last sexual encounter was highest among males than females. Three quarters (75.2%) of people reported they had ever been tested for HIV, with more females (79.3%) having had done so than males (70.9%). Two-thirds of respondents (66.8%) self-reported having tested for HIV in the past 12 months. Finally, 61.6% of males in the survey self-reported as having been circumcised, with circumcision being more common among youth aged 15–24 years (70.2%), Black Africans (68.9%), and those living in both rural informal (tribal) areas (65%) and urban areas (61.9%). Slightly more (51.2%) male circumcisions were reported to have occurred in a medical setting than in traditional settings (44.8%), with more young males aged 15–24 (62.6%) and men aged 25–49 (51.5%) reporting to have done so compared to most men aged 50 and older (57.1%) who reported that they had undergone circumcision in a traditional setting. The results of this survey show that strides have been made in controlling the HIV epidemic, especially in the reduction of HIV incidence, HIV testing, and treatment. Although condom use at last sex act remains unchanged, there continue to be some challenges with the lack of significant behaviour change as people, especially youth, continue to engage in risky behaviour and delay treatment initiation. Therefore, there is a need to develop or scale up targeted intervention programmes to increase HIV testing further and put more people living with HIV on treatment as well as prevent risky behaviours that put young people at risk of HIV infection.

The Western United States is experiencing historic drought, increasing pressure on water management systems. Agricultural production that relies on surface water flows is therefore imperiled, requiring new innovations and partnerships in order to adapt and survive. In Arizona, some agriculture continues to rely on historic, low-tech irrigation infrastructure such as hand-dug open ditches that divert river water to flood fields. These ditch systems are managed through both formal ditch companies and informal associations. To address changing water availability and needs, ditch users regularly "tinker" with water infrastructure, experimenting and making changes beyond the original infrastructure plans. Such changes are informed and driven by local social relationships and realities of the physical infrastructure. These dynamics are critical to understanding the adaptive capacity and flexibility of the water system; however, they are challenging to recognize and record. In this paper, we apply the emerging conceptualization of sociotechnical tinkering to examine the adaptive management of irrigation ditches in the Verde Valley of Arizona. We find evidence that water users frequently tinker with their water delivery and monitoring infrastructure to respond to and anticipate changes in water availability. Viewed through the lens of sociotechnical tinkering, these interactions are understood as the material manifestations of situated practice and actor agency within a water management system. This case study contributes to literature on adaptive environmental management and the hydrosocial cycle.

This paper examines the effect of having a third-party scientific expert present in stakeholder interviews. The study was conducted as part of a larger project on stakeholder engagement for natural resource management in the Verde Valley region of Arizona. We employed an experimental design, conducting stakeholder interviews both with and without an identified scientific expert present. Our sample consisted of 12 pairs of interviewees (24 total participants) who we matched based on their occupation, sex, and spatial proximity. For each pair, the scientific expert was present as a third party in one interview and absent in the other. We used a word-based coding strategy to code all interview responses for three known areas of sensitivity among the study population (risk, gatekeeping, and competence). We then performed both quantitative and qualitative analyses to compare responses across the two interview groups. We found that the presence of a scientific expert did not have a statistically significant effect on the mention of sensitive topics among stakeholders. However, our qualitative results show that the presence of a scientific expert had subtle influences on the ways that stakeholders discussed sensitive topics, particularly in placing emphasis on their own credibility and knowledge. Our findings indicate that researchers may be able to pursue collaborative, interdisciplinary research designs with multiple researchers present during interviews without concerns of strongly influencing data elicitation on sensitive topics. However, researchers should be cognizant of the subtle ways in which the presence of a third-party expert may influence the credibility claims and knowledge assertions made by respondents when a third-party expert is present during stakeholder interviews.

This study compares the efficiency of two analytic approaches—qualitative and quantitative—to social network analysis for identifying stakeholder groups. Social network data were collected from 23 water and agriculture stakeholders in Arizona, USA, and analyzed quantitatively and qualitatively. Analysis of the sample in the original order of data collection found qualitative analysis was more efficient, in that it yielded a stable result—the identification of four stakeholder groups—within 16 interviews. In contrast, the quantitative analysis did not produce a stable result after 23 interviews. Repeated analyses with randomized order and reverse order samples found qualitative approaches yielded more stable results, took about the same number of interviews to yield results, and produced slightly fewer stakeholder groups compared to quantitative approaches. Our findings suggest that, in resource-constrained projects, qualitative social network analysis for identifying stakeholder groups can provide an efficient alternative to conventional quantitative social network analysis.

Context There is ongoing debate regarding the optimal length of medical training, with concern about the cost of prolonged training. Two simultaneous tracks currently exist in Australia: direct entry from high school and graduate entry for students with a bachelor degree. Medical schools are switching to graduate entry based on maturity, academic preparedness and career-choice surety. We tested the assumption that graduate entry is better by exploring student preferences, coping, burnout, empathy and alcohol use. Methods From a potential pool of 2188 participants, enrolled at five Australian medical schools, a convenience sample of 688 (31%) first and second year students completed a survey in the middle of the academic year. Participants answered questions about demographics, satisfaction and coping and completed three validated instruments. Results Over 90% of students preferred their own entry-type, though more graduate-entry students were satisfied with their programme (82.4% versus 65.3%, p

Purpose – The purpose of this paper is to describe the present interest in the current and predicted business models of Massive Open Online Courses (MOOC); the business models that are being used by MOOC platforms and MOOC providers; discussion of the key issues and challenges; predictions about the future MOOC business models from the perspectives of platforms, providers and consumers. Design/methodology/approach – Review of the current literature for business models and costs for MOOCs and including the business models of higher education and possible future of the higher education system. Findings – The findings of this paper show that most MOOCs are currently based upon a “freemium” model where content is provided freely and additional services are charged for; that there are already a range of different “flavours” of MOOC and that this range is likely to further develop over time with some clear winners emerging; and that completely free and open MOOCs are not likely to be the focus of growth in the future, rather MOOCs that are sustained through charges to customers. Practical implications – To inform the debate about likely future business models and to help greater understanding of possible business models for MOOCs to inform decision-making by managers at universities. Originality/value – To inform the debate about likely future business models and to help greater understanding of possible business models for MOOCs to inform decision-making by managers at universities.

This small-scale pilot research project investigates the prevalence of Speech Language and Communication Difficulties in a sample of children attending a Youth Offending Service in the UK. Using the CELF-4, approximately 90% of the sample displayed some form of language difficulty and, overall, this population displayed mild to moderate difficulties in this area. Youth Offending Team staff questionnaires were also analysed and it was found that staff have little understanding of the difficulties presented by the children on their caseloads, despite reporting that they felt confident in this area. Implications for practice and potential roles for educational psychologists are discussed.

Background. The spontaneous recoding of visual stimuli into a phonological code to aid short-term retention has been associated with progress in learning to read (Palmer, 2000b). Aim. This study examined whether there was a comparable association with the development of writing skills. Sample. One hundred eight children (64 males) in the second year of the UK educational system (mean age 5:8 years, SD = 4 months) were recruited to the study. Methods. The children participated in tasks to assess their general cognitive abilities, reading skills, and their predominant short-term memory (STM) strategy for retaining visually presented stimuli. On the basis of their memory profile, children were classified as either engaging in verbal recoding of the stimuli (N = 31) or not (N = 77). Writing performance was indexed as alphabet transcription, spelling, and early text production skills. Results. Children classified as verbal recoders demonstrated better spelling performance and produced more individual letters, words, and T-units in their texts than did children who persisted with a visual memory strategy. In contrast, the alphabet transcription abilities of the groups did not differ. Hierarchical regression analyses revealed that variance in text production skills was associated with STM capacity and that moreover, significant independent variance in the number of words and T-units in the children's texts was predicted by individual differences in verbal recoding abilities. Conclusion. The results suggest that the development of verbal recoding skills in STM may play a role in children's early progress in writing, particularly their text generation skills.

In high hyperdiploid acute lymphoblastic leukemia (ALL), the concurrence of specific trisomies confers a more favorable outcome than hyperdiploidy alone. Interphase fluorescence in situ hybridization (FISH) complements conventional cytogenetics (CC) through its sensitivity and ability to detect chromosome aberrations in nondividing cells. To overcome the limits of manual I-FISH, we developed an automated four-color I-FISH approach and assessed its ability to detect concurrent aneuploidies in ALL. I-FISH was performed using centromeric probes for chromosomes 4, 6, 10, and 17. Parameters established for nucleus selection and signal detection were evaluated. Cutoff values were determined. Combinations of aneuploidies were considered relevant when each aneuploidy was individually significant. Results obtained in 10 patient samples were compared with those obtained with CC. Various combinations of aneuploidies were identified. All clones detected by CC were observed also by I-FISH, and I-FISH revealed numerous additional abnormal clones in all patients, ranging from ≤1% to 31.6% of cells analyzed. We conclude that four-color automated I-FISH permits the identification of concurrent aneuploidies of potential prognostic significance. Large numbers of cells can be analyzed rapidly. The large number of nuclei scored revealed a high level of chromosome variability both at diagnosis and relapse, the prognostic significance of which is of considerable clinical interest and merits further evaluation.

This case study is based upon institutions that have a history of engagement with online and distance learning (ODL) that has developed over a number of years and has formed a key part of their organizational strategy. They have developed expertise in ODL by investing in the creation of fully online courses, in some cases for more than a decade. They are now investing in Massive Open Online Courses (MOOCs) and the case study explores how they are going about this. This type of institutions has many advantages in its readiness to follow new online courses in MOOC formats but may face particular challenges to its business model. The case study describes the decision-making that took place before investment in MOOCs was made, approaches to quality assurance, resourcing, partnerships, and accreditation.

This chapter describes the “institutional innovator” case study of MOOC development. In this case, the university has leadership that supports innovation at many different levels in the organization, and which supports its senior team and next tier of management to make decisions about new approaches to test out and adopt. This has led to innovation at two levels: larger-scale and more dramatic “step change” innovations when appropriate and more gradual, continuous improvement in other areas. The case study describes the strategic context and how MOOCs are becoming part of the university's strategy. It describes how decisions were made about investing in MOOCs, how governance works, resourcing issues, partnerships, and quality assurance.

This chapter defines MOOCs (Massive Open Online Courses) and other forms of online learning, and describes the history of MOOCs, how they were first developed by George Siemens and Stephen Downes and how they have evolved since. MOOCs are described as having two main types, xMOOCs (traditional) and cMOOCs (connectivist), but this distinction is becoming less relevant as new models for MOOC are rapidly being developed that combine elements of both or extend and change the model for one or the other. MOOCs are set in the context of the growth of online learning more generally, and statistics is provided for this and also for the growth of popularity in MOOCs. Common criticisms of MOOCs are analyzed and described, namely apparently poor retention rates and attempts to make sense of some of the discourse around this.

This chapter addresses the question How do different MOOCs (Massive Open Online Courses) vary from one another, and why have they been designed in a particular way? and examines four different MOOCs against a framework of learner background and intentions, technology infrastructure, and interactive learning environment. It discusses the choice of subject area for each MOOC and compares the intended audience and subsequent design decisions.

This chapter describes a case study of an imaginary university that is investing in the development of MOOCs. This group is termed the “cautious experimenters”—institutions that are in the top layer of universities globally in terms of national and international rankings, based mostly upon their research activity. They tend to be risk averse and wish to protect their current strong and stable position rather than to invest in innovation, but they also wish to keep up with their main competitors and not be left behind, so they are engaging cautiously with MOOCs and seeking to identify the benefits that they may bring in the future. The case study describes the decision making that took place before investment in MOOCs was made, approaches to quality assurance, resourcing, partnerships, and accreditation.

This chapter analyses and draws out the main conclusions from six case studies of MOOC implementation by universities. The case studies focus upon six types of universities: the entrepreneurs, the opportunists, the institutional innovators, the old hands with online and distance learning, those who are cautious about implementing MOOCs, and the “old guard” who do not wish to engage with MOOCs. It describes the most significant decisions that universities are making about MOOCs and describes the approaches that they are taking to planning and implementing them.

This chapter focuses upon data and analytics, which both have the potential to provide real added value to universities as they seek to reshape their offer and to differentiate themselves from their peers. Online learning and MOOCs, in particular, make it easier for universities to gather data about learning behavior and learners, and to apply analytic tools to the data in order to understand behavior, preferences, and problems. If the right tools are available and, most importantly, are applied to the right data in the right way, then they can be very powerful in helping institutions to understand their current students and to predict the future behaviors of both current and possible future students. The chapter describes some of the possible benefits and pitfalls of analytics, and examples of where analytics are being used well in higher education. It also discusses how data and analytics are relevant to MOOCs, where analytic tools are not yet mature.

The benefits of providing MOOCs are not just about income generation and research has shown that many universities are investing in MOOCs with the hope of longer-term benefits rather than just short-term income generation. This chapter discusses some of the most frequently cited reasons for MOOC investment that were given by universities interviewed during this research activity. These “softer” outcomes included relationship building, profile-raising and fulfilment of strategies for public engagement and public good and similar objectives, and there is also the motivation to engage in practical experiments that may involve many thousands of online learners in order to get a better understanding of what works well in online learning. Universities need to think strategically when they are planning their MOOC activity in order to be clear what they plan to achieve and how they can get most benefit from the investment of time and money. The chapter includes examples of how specific universities are getting additional value from their MOOC investment.

This chapter describes the purpose of the six fictional case studies of approaches to Massive Open Online Courses (MOOCs) that are included in the subsequent six chapters. It explains the purpose of the case studies and their format. The purpose of the case studies is to inform others about the approach that other institutions across the globe are taking to MOOCs, and whether they are engaging in one of six different ways—whether they are old hands, opportunists, entrepreneurs, institutional innovators, cautious experimenters, or the old guard.

This chapter explores the design of massive Open Online Courses (MOOCs) from a learner's perspective. It discusses key issues including the motivation of learners in an online environment; it describes the concept of “learning design” and how it can be used to help plan online learning, and how to use learning design approaches to plan the design of MOOCs. It talks about learner support in the MOOC environment and the issues to consider in providing support to MOOC learners. Finally, it discusses MOOC content and some of the issues relating to reusing existing content in MOOCs, and so-called “flipping the classroom.”

Although the business models for Massive Open Online Courses (MOOCs) are still unproven and largely unclear, MOOCs have attracted a huge amount of interest as a potentially disruptive way to change higher education as a marketplace. Traditional universities may be challenged by the growth in online learning of which MOOCs are a part. However, other sectors are also becoming interested in the possibility that the higher education market will be opened up as online learning becomes more widespread. There is also much interest generated by the potential “unbundling” of higher education, where the various components of the higher education experience may be offered by a range of providers rather than just by one. This chapter discusses some of the potential entrants into the higher education market and the challenges that this may present to the current providers of higher education.

This chapter describes the costings that may be involved in creating and running a MOOC. It goes beyond the ballpark estimates that are being shared by some MOOC providers to analyze the activites that are involved in running MOOCs and suggest ways to estimate potential costs, using the Stanford analytics framework that describes a MOOC in terms of interactive learning environment; learner background and intentions; technology infrastructure; and evidence-based improvement. The chapter includes a checklist to use for estimating MOOC costs to help business planning.

This chapter presents as a case study an imaginary university that is responding opportunistically to the current interest in MOOCs. In this case study, the focus is upon institutions that have invested in overseas campuses and that therefore have an active and growing student population outside their home nation. This presents a particular set of opportunities and challenges with regard to online learning, when compared with universities that are mainly focused upon a single campus. This chapter describes how MOOCs are providing a tool, through a Small, Private Open Course to support students, and also university staff, in new ways. It describes how decisions were made about investing in MOOCs, how governance works, resourcing issues, partnerships, and quality assurance.

The creation of sustainable business models for MOOCs is one of the most discussed and contentious issues that has arisen so far in MOOC history. This chapter describes and discusses the income generation models that are being used by the three main MOOC providers, Coursera, edX and Udacity, and also the UK's FutureLearn platform, with the most commonly used models being charged-for certification, secure assessments and charges for recommending third-party services. For each MOOC provider, there is discussion about what the business models being used might offer to their university partners in terms of income stream, including which financial model or models are being used to allocate any income generated. The chapter then examines the range of income generation opportunities that may be available to universities who are providing MOOCs directly rather than working through one of the major platforms, including accreditation, proctored examinations, 'conversion' of MOOC students into fee-paying students. There is also discussion of some of the less direct benefits that may be enjoyed by universities who run MOOCs, such as better customer engagement leading to more applications.

This chapter draws upon the experience gained by universities in creating MOOCs. It draws upon six case studies to provide guidance on the main steps involved in devising and implementing an MOOC strategy. It is based upon established good practice for program and project management, using the terminology that is common to the PRINCE2 and Managing Successful Programmes management methodologies.

This chapter describes the current “MOOCosphere”, the international picture for Massive Online Open Course (MOOC) provision, which includes the three main MOOC platforms, Coursera, EdX, and Udacity, their history, focus, and current status. Some of the main MOOC platforms in Europe, in particular the UK MOOC platform, FutureLearn, are looked at and there is a focus on some of the other MOOC platforms that are available and their potential importance in the corporate world.

The “old guard” is made up of the very top universities in the world. These institutions are elite and research intensive. Some of them have been quick to engage with MOOCs and to lead the way, like the entrepreneurs, but this case study focuses upon an imaginary institution that is typical of those that have not engaged with MOOCs so far. We look at the context for this decision and why they reached it, and also what approach they may take in the future.

Contains fulltext : 50313.pdf (Publisher’s version ) (Closed access) We recently undertook expression profiling of all 19 human ADAMTS metalloproteinases (a disintegrin and metalloproteinase with thrombospondin motifs) in malignant and non-neoplastic breast tissue and showed that 11 of the ADAMTS genes are dysregulated in breast carcinoma. We identified a subgroup of ADAMTSs, based on functional and amino acid sequence similarity (ADAMTS1, 4, 5, 8 and 15), to be the focus of further study in breast carcinoma. Further RNA expression analysis by real-time PCR on a different cohort of 229 patients with breast cancer has identified ADAMTS8 as a predictor of poor overall survival (OS) (hazard ratio (HR) = 2.20, 95% C.I. = 1.29-3.74, p = 0.004) and confirmed ADAMTS15 as a predictor of prolonged relapse-free survival (RFS) (HR = 0.54, 95% C.I. = 0.32-0.89, p = 0.016). We explored the differences in survival of the 4 groups that could be categorized based on the expression levels of ADAMTS8 and ADAMTS15. For both RFS and OS, the group with high ADAMTS8 and low ADAMTS15 expression had a particularly poor prognosis. This group had a 3-fold higher chance of recurrence (HR = 3.03, 95% C.I. = 1.49-6.15, p = 0.001) and a greater than 5-fold higher chance of death (HR = 5.40, 95% C.I. = 2.16-13.5, p < 0.001) than the most favorable prognostic group. This prediction of poor prognosis by ADAMTS8 and ADAMTS15 expression was found to be independent of other classical clinicopathological factors. Results observed in FVB-PyMT mice, a robust transgenic model of highly metastatic breast carcinoma, fitted the expectation that relatively high expression levels of ADAMTS8 together with low expression levels of ADAMTS15 seen in human breast carcinoma are associated with a poor clinical outcome. In summary, ADAMTS8 and ADAMTS15 have emerged as novel predictors of survival in patients with breast carcinoma.

Objective To profile the expression of all known members of the matrix metalloproteinase (MMP), ADAMTS, and tissue inhibitor of metalloproteinases (TIMP) gene families in normal cartilage and cartilage from patients with osteoarthritis (OA). Methods Human cartilage was obtained from femoral heads at joint replacement for OA or following fracture to the femoral neck. Total RNA was purified, and gene expression was assayed using quantitative real-time polymerase chain reaction. Results Several members of the above gene families were regulated in OA. Genes that showed increased expression in OA were MMP13, MMP28, and ADAMTS16 (all at P < 0.001), MMP9, MMP16, ADAMTS2, and ADAMTS14 (all at P < 0.01), and MMP2, TIMP3, and ADAMTS12 (all at P < 0.05). Genes with decreased expression in OA were MMP1, MMP3, and ADAMTS1 (all at P < 0.001), MMP10, TIMP1, and ADAMTS9 (all at P < 0.01), and TIMP4, ADAMTS5, and ADAMTS15 (all at P < 0.05). Correlation analysis revealed that groups of genes across the gene families were coexpressed in cartilage. Conclusion This is the first comprehensive expression profile of all known MMP, ADAMTS, and TIMP genes in cartilage. Elucidation of patterns of expression provides a foundation with which to understand mechanisms of gene regulation in OA and potentially to refine the specificity of antiproteolytic therapies.