N-Cadherin cleavage during activated hepatic stellate cell apoptosis is inhibited by tissue inhibitor of metalloproteinase-1. [In supplement: 11th International Symposium on the Cells of the Hepatic Sinusoid and their Relation to Other Cells]

Apoptosis of hepatic stellate cells (HSC) has previously been shown to occur during spontaneous resolution of experimental liver fibrosis. TIMP-1 has also been shown to have a key role because of its ability to inhibit apoptosis of HSC via matrix metalloproteinase (MMP) inhibition. This has led to further study of novel substrates for MMPs that might impact on HSC survival. N-Cadherin is known to mediate cell-cell contacts in fibroblasts. In this study we demonstrate that N-Cadherin is expressed by activated rat HSC. Furthermore, during apoptosis of HSC, the N-Cadherin is cleaved into smaller fragments. Apoptosis of HSC may be inhibited by TIMP-1. This is associated with reduced fragmentation of N-Cadherin. N-Cadherin may have an important role in supporting HSC survival while N-Cadherin cleavage may play a part in promoting HSC apoptosis in recovery from liver fibrosis

Patterns of place:an integrated approach for the design and evaluation of real and virtual environments

This chapter describes an approach to the development of virtual representations of real places. The work was funded under the European Union’s €20 m Future and Emerging Technologies theme of the 5th Framework Programme, “Presence”. The aim of the project, called BENOGO, was to develop a novel technology based on real-time image-based rendering (IBR) for representing places in virtual environments. The specific focus of the work presented here concerned how to capture the essential features of real places, and how to represent that knowledge, so that the team developing the IBR-based virtual environments could produce an environment that was as realistic as possible. This involved the development and evaluation of a number of virtual environments and the evolution of two complementary techniques; the Place Probe and Patterns of place

Implications of abnormal abdominal wall computed tomographic angiography findings on postmastectomy free flap breast reconstruction.

BACKGROUND: Preoperative computed tomography angiography (CTA) of the abdominal wall vessels is used when planning free flap breast reconstruction (FFBR) because it provides a surgical road map which facilitates flap harvest. However, there are few reports on the effect of abnormal findings on the operative plan. METHODS: We conducted a retrospective study of all FFBRs performed at a tertiary referral center over a 6-year period (November 2011 to June 2017). One consultant radiologist reported on the findings. Details on patient demographics, CTA reports, and intraoperative details were collected. RESULTS: Two hundred patients received preoperative CTAs. Fourteen percent of patients (n=28) had abnormal findings. Of these findings, 18% were vascular anomalies; 36% tumorrelated and 46% were "miscellaneous." In four patients, findings subsequently prevented surgery; they comprised a mesenteric artery aneurysm, absent deep inferior epigastric (DIE) vessels, bilateral occluded DIE arteries, and significant bone metastases. Another patient had no suitable vessels for a free flap and the surgical plan converted to a pedicled transverse rectus abdominis musculocutaneous flap. The remaining incidental findings had no impact on the surgical plan or appropriateness of FFBR. More than one in 10 of those with abnormal findings went on to have further imaging before their operation. CONCLUSIONS: CTA in FFBR can have a wider impact than facilitating surgical planning and reducing operative times. Incidental findings can influence the surgical plan, and in some instances, avoid doomed-to-fail and unsafe surgery. It is therefore important that these scans are reported by an experienced radiologist

Bilateral risk-reducing mastectomy and reconstruction–A 12-year review of methodological trends and outcomes at a tertiary referral centre

INTRODUCTION: Bilateral risk-reducing mastectomy (BRRM) involves removal of healthy breast tissue to substantially decrease the risk of developing breast cancer in individuals with greater susceptibility due to a strong family history or genetic mutation. This retrospective study evaluates cases of BRRM and associated reconstruction performed at a tertiary centre, with emphasis on mastectomy and reconstructive trends. METHODS: A retrospective review of all BRRM cases performed between January 2010 and May 2022 was conducted, with two separate cohorts corresponding to the earlier (group 1) and later (group 2) portion of the time-period. Data collected included demographics, genetic test results, family history of breast/ovarian cancer, co-morbidities, mastectomy type, reconstruction type, surgical histopathology findings and post-operative complications. RESULTS: A total of 82 patients (group 1 = 41, group 2 = 41) underwent BRRM. The proportion of nipple-sparing mastectomy increased from 14.6% to 56.1% between the two time periods with a reduction in skin-sparing mastectomies from 75.6% to 20.3% (p<0.001). Of the 80 patients who opted to undergo reconstruction, there was a significant decrease in combined flap-implant reconstructions (19.51% to 0%, p<0.01). Importantly, for implant-only reconstruction, there were significant increases in prepectoral approaches (p = 0.0267) and use of acellular dermal matrix (ADM) (48.15% to 90.63%, p<0.001). CONCLUSION: This study documents recent increases in nipple-sparing techniques for BRRM compared to more traditional skin-sparing methods. Concurrently, reconstruction following RRM has become predominantly implant-based without a flap, coinciding with more widespread usage of ADM. This is consistent with national trends towards fewer complex autologous procedures

Applying a User-centred Approach to Interactive Visualization Design

Analysing users in their context of work and finding out how and why they use different information resources is essential to provide interactive visualisation systems that match their goals and needs. Designers should actively involve the intended users throughout the whole process. This chapter presents a user-centered approach for the design of interactive visualisation systems. We describe three phases of the iterative visualisation design process: the early envisioning phase, the global specification hase, and the detailed specification phase. The whole design cycle is repeated until some criterion of success is reached. We discuss different techniques for the analysis of users, their tasks and domain. Subsequently, the design of prototypes and evaluation methods in visualisation practice are presented. Finally, we discuss the practical challenges in design and evaluation of collaborative visualisation environments. Our own case studies and those of others are used throughout the whole chapter to illustrate various approaches

User-centred design of flexible hypermedia for a mobile guide: Reflections on the hyperaudio experience

A user-centred design approach involves end-users from the very beginning. Considering users at the early stages compels designers to think in terms of utility and usability and helps develop the system on what is actually needed. This paper discusses the case of HyperAudio, a context-sensitive adaptive and mobile guide to museums developed in the late 90s. User requirements were collected via a survey to understand visitors’ profiles and visit styles in Natural Science museums. The knowledge acquired supported the specification of system requirements, helping defining user model, data structure and adaptive behaviour of the system. User requirements guided the design decisions on what could be implemented by using simple adaptable triggers and what instead needed more sophisticated adaptive techniques, a fundamental choice when all the computation must be done on a PDA. Graphical and interactive environments for developing and testing complex adaptive systems are discussed as a further step towards an iterative design that considers the user interaction a central point. The paper discusses how such an environment allows designers and developers to experiment with different system’s behaviours and to widely test it under realistic conditions by simulation of the actual context evolving over time. The understanding gained in HyperAudio is then considered in the perspective of the developments that followed that first experience: our findings seem still valid despite the passed time

Formative evaluation of a UK community-based sports intervention to prevent smoking among children and young people: SmokeFree Sports

Background Smoking is a leading cause of preventable morbidity and mortality in England. This formative research involved the evaluation of SmokeFree Sports (SFS), a novel community sport intervention to prevent smoking among children and young people (CYP). Methods SFS was implemented in five youth clubs situated in deprived communities, between February and June 2011, involving 246 CYP (6-18 years). Seventy-one CYP (median age=10.0 years, 56% male) and five youth club managers participated in this formative evaluation study, which utilised a mixed methods design. Results Smoking prevalence at baseline and post-intervention did not differ significantly (2.8% vs. 1.4%). However, positive educational effects were observed: A lower proportion of respondents believed that smoking cigarettes was associated with weight gain or loss (80.0% to 66.2%). A higher proportion of respondents felt that once a person started smoking it would definitely be difficult to quit (52.1% to 62%). Qualitative data revealed that CYP’s awareness of smoking factors increased while youth club managers provided suggestions for future implementation. Conclusions Sport may be a viable mechanism to educate CYP about elements of smoking and health. This study raises key characteristics for the implementation and evaluation of a definitive trial

Designing for Experiences in Blended Reality Environments for People with Dementia

Blended Reality environments have the potential to provide scalable solutions that are affordable, adaptable and easily deployable to support people with dementia. Use of these technologies is associated with experience of presence which is an experience with technologically mediated perceptions that generates a feeling of being there and the illusion of non-mediation. Our study examines what constitutes an experience of presence for people with dementia when they interact with MRTs. An observational study with ten participants (MoCA = 18 to 23, Age = 63 to 88 years) played a game of Tangram on Osmo. Six of these participants also played Young Conker on HoloLens. The experiences of the participants in the digital space, the physical space, and their attention crossover between the two spaces were coded in Noldus Observer XT 14.1. The study found four main themes that have an impact on the experience of presence in PwD – correspondences, effortless access to physical and digital content, awareness of reality and emergence. Correspondences between physical and digital spaces require PwD to have constant information about the state and nature of physical and digital content. The transitions between physical and digital should be seamless. PwD demonstrated positive experiences with Osmo, an augmented Virtuality technology while their experience with HoloLens, augmented reality technology was negative. The factors impacting experience of presence were prominent in Osmo while they were mostly absent in HoloLens throughout the game play. The outcomes of this study have resulted in a set of recommendations and guidelines for designers to design correspondences for experience of presence. We are currently working on developing prototypes using these guidelines for evaluations with PwD.AGE-WEL