The role of immunosuppression in long-term graft hepatitis and fibrosis after paediatric liver transplant comparison of two treatment protocols:comparison of two treatment protocols

Background and aims: We have previously demonstrated high rates of chronic allograft hepatitis and fibrosis in liver transplant patients on long-term cyclosporine monotherapy. We subsequently changed practice to add low-dose prednisolone to maintenance treatment with tacrolimus post-transplant. The aim of the study was to assess the impact of the immunosuppression change on graft histopathology.Methods: Patients treated in this era (Tac + Pred, 2000–2009, N = 128) were compared to a historical cohort, who had been maintained on a steroid-free, cyclosporine-based regime (CSA-Only, 1985–1996, N = 129). Protocol liver biopsies and laboratory tests were performed five- and ten-years post-transplant in both groups.Results: Compared to CSA-Only, the Tac + Pred cohort had significantly lower rates of chronic hepatitis (CH) at five (20% vs. 44%, p Conclusion: Increased immunosuppression effectively reduced chronic allograft hepatitis and fibrosis at five years, suggesting it is an immunologically driven variant of rejection. However, there was no significant reduction in the degree of fibrosis at ten years, indicating a multifactorial origin for long term graft fibrosis

Design, systemic change and navigating sustainable impacts

Design is experiencing a fundamental transformation, moving from a philosophy of disruption towards a period characterised by sustainability and accountability. Systemic change requires a commitment to the longer term, moving beyond quick fixes and rapid innovation to consider the broader contexts of design work, design interventions and their potential impacts on sustaining existing systems or developing alternatives. We posit that for sustainable transitions and wider systemic changes to be accomplished by design, a new approach is necessary. Engaging with emerging and diverse matters of concern, such as more-than-human design, design futures and speculation, design for policy and design activism informed by the decolonial lens, we propose ways that practice-based design education can be informed. In our view, for systemic change to emerge, we need to shift from an industrial, mass production-inspired model of education to a pluriversal one that fosters the emergence of systemic changers. This paper examines different roles and issues facing design for systemic change as discussed at a public event hosted by the Design Products MA programme at the Royal College of Art. Leading thinkers based in the UK, Finland, France, and Brazil shared perspectives on design for environmental and social sustainability based on their expertise in sustainable transitions, systemic contradictions, ecological restoration, and multi-species design. Through thematic analysis of the presentations and discussion that followed, we identify four key questions in the context of systemic change: how can designers situate themselves and work with others? What are the most critical considerations? At what scale is design most effective? What does design work for systemic change look like? We map relevant debates, theories and exemplars presented by the speakers, supported by additional references used in teaching and research in the Design Products programme. From our position as design educators and researchers, we reflect on what systemic change could mean for ‘Design Products’ and the design field more broadly. The paper provides an overview of current discussions and issues in design for systemic change, offering insights to help designers visualise and navigate this journey towards viable futures

Material-led thinking as a practice of care: a strategy from art and design education

In this paper, we present an online workshop that uses making as a strategy to reveal new insights and facilitate interdisciplinary collaboration. The paper is intended to start conversations about different forms of material engagement in learning environments, and how artists and designers can use material approaches to respond to complex challenges, such as care. Our aim for this material-led workshop was to encourage students to engage with care as a topic of critical analysis by adopting making as a way to think about this abstract concept. As educators, we also experimented with making as a strategy to create a caring learning environment. Our analysis identified that the workshop fostered inclusive collaboration, sparked stimulating conversations, connected theory and practice, and created experiences and spaces of care. We discuss our findings based on three categories: care as a subject of art and design education, care through teaching and care through making. We also consider how the workshop might be different in physical spaces and propose aspects that we can incorporate in future iterations, such as having more time to learn about the objects created. The workshop can serve as a model and be applied to explore other abstract concepts in various contexts and is relevant to professionals interested in making and applying similar approaches in their practice

Long‐term clinical and socioeconomic outcomes of children with biliary atresia

Abstract Background Biliary atresia (BA) is rare liver disease of unknown etiology, and is a major indication for liver transplant (LT). Previous data indicate improved outcomes with early referral for Kasai portoenterostomy (KPE). Objective Evaluate the long‐term outcomes in BA, with particular focus on those transitioned to adult care with native livers. Subjects and Methods Patients with BA treated between1980 and 2012 were identified. Data were collected from the time of referral, transition to adult care, and the most recent clinic notes, from which patient and native liver survival were calculated. Results Four hundred and fifty‐four patients with BA were identified, who were followed up for median of 16.4 years from birth; 74 died (41 of whom had a LT), giving a 20‐year survival rate of 83.6%. Two hundred and seventy‐two patients received an LT, with the median native liver survival being 35 months. Of patients who transitioned to adult care, 54 of 180 (30.0%) retained their native liver. Of these, 72% (39 of 54) had evidence of chronic liver disease at transition, of whom 8 were subsequently lost to follow‐up, 9 were transplanted, and 22 remained stable with compensated liver disease. Of the 15 of 54 patients (28%) with no evidence of chronic disease in their native liver disease at transition, 3 were subsequently lost to follow‐up; none received transplants, although 3 patients developed new‐onset liver disease. All patients transitioned to adult care completed secondary school education (N = 180), with 49% having attended college/university and 87% being in employment or education at the last follow‐up. Of female patients, 34% had at least one pregnancy (27 children in 21 women), while 22% of males had fathered a child. Conclusion Long‐term outcomes in BA are good, with patients surviving into adult life. Progression of chronic liver disease and associated morbidity is common in those who retained their native livers, suggesting that these patients require monitoring of liver disease throughout adult life, and early recognition of the need for LT

Children with developmental coordination disorder are less able to fine-tune muscle activity in anticipation of postural perturbations than typically developing counterparts

The majority of children with developmental coordination disorder (DCD) struggle with static and dynamic balance, yet there is limited understanding of the underlying neuromechanical mechanisms that underpin poor balance control in these children. Eighteen children with DCD and seven typically developing (TD) children aged 7–10 years stood with eyes open on a moveable platform progressively translated antero-posteriorly through three frequencies (0.1, 0.25 and 0.5 Hz). Myoelectric activity of eight leg muscles, whole-body 3D kinematics and centre of pressure were recorded. At each frequency, postural data were divided into transition-state and steady-state cycles. Data were analyzed using a linear mixed model with follow-up Tukey’s pairwise comparisons. At the slowest frequency, children with DCD behaved like age-matched TD controls. At the fastest frequency, children with DCD took a greater number of steps, had a greater centre of mass variability, had a greater centre of pressure area, and tended to activate their muscles earlier and for longer than TD children. Children with DCD did not alter their postural response following prolonged exposure to platform movement, however they made more, non-structured postural adjustments in the medio-lateral direction as task difficulty increased. At the faster oscillation frequencies, children with DCD adopted a different muscle recruitment strategy to TD children. Activating their muscles earlier and for longer may suggest that children with DCD attempt to predict and react to postural disturbances, however the resulting anticipatory muscle excitation patterns do not seem as finely tuned to the perturbation as those demonstrated by TD children. Future work should examine the impact of balance training interventions on the muscle recruitment strategies of children with DCD, to ensure optimal interventions can be prescribed

Retrofit 2050: critical challenges for urban transitions

Scaling up retrofit presents a number of critical challenges for the transition to urban sustainability. Drawing together insights from the EPSRC Retrofit 2050 project this briefing sets out key success factors that need to be in place to deliver sustainable futures for UK cities

Olhares e reflexões contemporâneas sobre o triângulo sociedade-educação-tecnologias e suas influências no ensino das ciências

Quando se combinam termos como sociedade, educação e tecnologias, parece destacar-se a ideia de que as tecnologias têm sido associadas a algumas das mais expressivas mudanças ocorridas na sociedade do século XX e início do século XXI, e têm sido relatadas como capazes de influenciar aspetos diversos e significativos da realidade social, a ponto de alguns autores dizerem que estamos perante uma nova forma de organização da sociedade e do sistema econômico, à qual o sistema educativo deveria procurar corresponder, adequando-se. Neste artigo, apresentam-se algumas perspetivas e olhares que julgamos úteis para alavancar uma reflexão sustentada e projetiva sobre o passado, o presente e o futuro das inter-relações entre as esferas social, educativa e tecnológica e as possíveis influências daí decorrentes para o ensino das ciências. Assim, de forma mais descritiva, importa referir que este artigo é constituído por cinco tópicos que julgamos relevantes para consubstanciar a reflexão sobre a temática em apreço. Começando por apresentar algumas considerações sobre a sociedade da informação, a metáfora da rede e o potencial coletivo, segue-se um enfoque nas tecnologias e na sua relação com as "escolas que aprendem". Na medida em que o letramento digital não se esgota na competência tecnológica, a instituição escolar - e os seus agentes pode assumir um papel de mediação entre os desafios da sociedade do conhecimento e as novas gerações. Nesse contexto de interdependências múltiplas, termina-se o artigo com algumas reflexões sobre a educação em ciência, o ensino das ciências e o letramento científico na sociedade da informação

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Sustainability in a climate of austerity: responses from UK-city-regions Title: Sustainability in a climate of austerity: Responses from UK city-regions

The economic and financial crises experienced in recent years have put pressure on governments around the world to focus their efforts on promoting and implementing structural reforms in strategic areas like education, health, labour and product markets, competition, taxes and innovation. Many governments are already taking some measures to "green" their approaches to economic revival, addressing recovery by supporting sustainable long-term growth. A recent report published by the OECD (2009) argues that the economic and financial down-turn provides both an opportunity and an incentive to promote a greener model of economic growth and development: a green growth that ensures natural assets continue to provide the resources and environmental services on which human health and well-being relies. Urban retrofitting is becoming critical to the achievement of ambitious carbon reduction targets and to purse a green growth agenda. In order to realize the ecological and economic benefits of retrofit, cities are continually searching for a "fix" that allows them to upscale retrofit from a largely ad hoc and piecemeal activity into strategic and systemic programmes that transform existing cities. It is with the issue and purpose of such experimentation and efforts to integrate retrofit and governing that we are concerned in this paper, drawing, from a research study that investigates lessons and practices in sustainable retrofitting 1 in two core UK city-regions (Cardiff -South East Wales and Greater Manchester). National priorities, policies and programmes create possibilities and constraints on those governing city-regions in their construction of retrofit strategies. In the UK since the onset of the financial crisis in 2007 the ways in which retrofit has been promoted across a range of UK national government bodies has varied. Elements of both a low carbon industrial interventionism and seeing retrofit as a market making opportunity were inherent in the last 1 Retrofit is defined for the purpose of the paper as the "directed alteration of the fabric, form or systems which comprise the built environment in order to improve energy, water and waste efficiencies" A narrative for retrofit has recently been developed in response of a complex set of pressures and drivers ranging from climate, energy and fuel poverty, in the two city-regions. This has resulted in a number of key policy objectives and programmes developed to address urban and regional economic development. From a first reading, these responses seem to follow common rhetoric of sustainability and economic growth in both the case study regions. Nevertheless, the two different governance settings and different historical development in the two city regions have generated different responses towards a transition to sustainable retrofit in a climate of austerity. Greater Manchester: Retrofitting ON and IN The governance framework in GM has recently changed from a two-tier governing has created the conditions for an era of austerity within which efforts to constitute the capacity to shape retrofitting strategies needs to be understood. A strategy for retrofitting Greater Manchester housing stock is set out in the low carbon housing retrofit strategy and the wide range of retrofit activities illustrate two emergent and distinct pathways for urban retrofit. On the one hand, there is a dominant national/cityregional policy and business led view of the relationship between Greater Manchester and retrofit which is "top down" and aims at: reducing emissions in relation to Greater Manchester"s carbon reduction emissions targets in a broader national context; as a way of 2 This is a national policy established by the post-2010 coaltiion government and run from the Department of Energy & Climate. The Green Deal establishes "a framework to enable private firms to offer consumer energy efficiency improvements to their homes, community spaces and business at no upfront costs, and recoup payments through a charge in instalments on the energy bill" (Department of Energy & Climate Change, 2010:5). 3 Where the strategic level of Greater Manchester County Council shared power with the 10 metropolitan boroughs that constituted it. 4 Through the Association of Greater Manchester Authorities (AGMA) and associated agencies (see for instance Manchester which is more "bottom up", embedded in local contexts with manifold motivations for retrofit and community engagement. These initiatives emerge primarily fro