Direct microvascular monitoring of a free autologous jejunal flap using microendoscopy: a case report

BACKGROUND: Early identification of flap failure is an indispensable prerequisite for flap salvage. Although many technical developments of free flap monitoring have now reached clinical application, very few are considered to be reliable and non-invasive for early recognition of flap failure. CASE PRESENTATION: We used microendoscopic technique for microvascular monitoring of free autologous jejunal flap by the direct visualisation of the flow of erythrocytes through the capillary vasculature on both the mucosal and serosal surfaces. Blood flow was seen to be pulsatile, with individual erythrocytes visible in the capillaries. The best view was obtained when the scope was focussed directly on the capillary rather than the graft surface. The view of the unstained mucosal surface was bland apart from the fine capillary loops which were seen to fill with each pulsatile event. The microendoscopic examination of the serosal surface revealed much larger calibre vessels with obvious blood flow. CONCLUSION: The microendoscopic monitoring technique is simple and safe with direct visualisation of blood flow. The technique may also be useful for the monitoring of other free bowel transplants

A Knowledge Distillation Ensemble Framework for Predicting Short and Long-term Hospitalisation Outcomes from Electronic Health Records Data

The ability to perform accurate prognosis of patients is crucial for proactive clinical decision making, informed resource management and personalised care. Existing outcome prediction models suffer from a low recall of infrequent positive outcomes. We present a highly-scalable and robust machine learning framework to automatically predict adversity represented by mortality and ICU admission from time-series vital signs and laboratory results obtained within the first 24 hours of hospital admission. The stacked platform comprises two components: a) an unsupervised LSTM Autoencoder that learns an optimal representation of the time-series, using it to differentiate the less frequent patterns which conclude with an adverse event from the majority patterns that do not, and b) a gradient boosting model, which relies on the constructed representation to refine prediction, incorporating static features of demographics, admission details and clinical summaries. The model is used to assess a patient's risk of adversity over time and provides visual justifications of its prediction based on the patient's static features and dynamic signals. Results of three case studies for predicting mortality and ICU admission show that the model outperforms all existing outcome prediction models, achieving PR-AUC of 0.891 (95$$ CI: 0.878 - 0.969) in predicting mortality in ICU and general ward settings and 0.908 (95$$ CI: 0.870-0.935) in predicting ICU admission.Comment: 14 page

Environmental drivers of Culicoides phenology: how important is species-specific variation when determining disease policy?

Since 2006, arboviruses transmitted by Culicoides biting midges (Diptera: Ceratopogonidae) have caused significant disruption to ruminant production in northern Europe. The most serious incursions involved strains of bluetongue virus (BTV), which cause bluetongue (BT) disease. To control spread of BTV, movement of susceptible livestock is restricted with economic and animal welfare impacts. The timing of BTV transmission in temperate regions is partly determined by the seasonal presence of adult Culicoides females. Legislative measures therefore allow for the relaxation of ruminant movement restrictions during winter, when nightly light-suction trap catches of Culicoides fall below a threshold (the ‘seasonally vector free period’: SVFP). We analysed five years of time-series surveillance data from light-suction trapping in the UK to investigate whether significant inter-specific and yearly variation in adult phenology exists, and whether the SVFP is predictable from environmental factors. Because female vector Culicoides are not easily morphologically separated, inter-specific comparisons in phenology were drawn from male populations. We demonstrate significant inter-specific differences in Culicoides adult phenology with the season of Culicoides scoticus approximately eight weeks shorter than Culicoides obsoletus. Species-specific differences in the length of the SVFP were related to host density and local variation in landscape habitat. When the Avaritia Culicoides females were modelled as a group (as utilised in the SFVP), we were unable to detect links between environmental drivers and phenological metrics. We conclude that the current treatment of Avaritia Culicoides as a single group inhibits understanding of environmentally-driven spatial variation in species phenology and hinders the development of models for predicting the SVFP from environmental factors. Culicoides surveillance methods should be adapted to focus on concentrated assessments of species-specific abundance during the start and end of seasonal activity in temperate regions to facilitate refinement of ruminant movement restrictions thereby reducing the impact of Culicoides-borne arboviruses

Lestaurtinib is a potent inhibitor of anaplastic thyroid cancer cell line models

Anaplastic thyroid cancer (ATC) is a rare and lethal human malignancy with no known effective therapies in the majority of cases. Despite the use of conventional treatments such as chemotherapy, radiation and surgical resection, this disease remains almost universally fatal. In the present study, we identified the JAK2 inhibitor Lestaurtinib as a potent compound when testing against 13 ATC cell lines. Lestaurtinib demonstrated a potent antiproliferative effect in vitro at nanomolar concentrations. Furthermore, Lestaurtinib impeded cell migration and the ability to form colonies from single cells using scratch-wound and colony formation assays, respectively. Flow cytometry was used for cell cycle analysis following drug treatment and demonstrated arrest at the G2/M phase of the cell cycle, indicative of a cytostatic effect. In vivo studies using the chick chorioallantoic membrane xenograft models demonstrated that treatment with Lestaurtinib resulted in a significant decrease in endpoint tumor volume and vascularity using power Doppler ultrasound imaging. Overall, this study provides evidence that Lestaurtinib is a potent antiproliferative agent with potential antiangiogenic activity that warrants further investigation as a targeted therapy for ATC

Human Leukocyte Antigen (HLA) A*1101-restricted Epstein-Barr virus-specific T-cell receptor gene transfer to target Nasopharyngeal carcinoma

Infusing virus-specific T-cells is effective treatment for rare Epstein-Barr virus (EBV)-associated post-transplant lymphomas and more limited success has been reported using this approach to treat a far more common EBV-associated malignancy, Nasopharyngeal carcinoma (NPC). However, current approaches using EBV-transformed lymphoblastoid cell lines to reactivate EBV-specific T-cells for infusion take 2-3 months of in vitro culture and favour outgrowth of T-cells targeting viral antigens expressed within EBV+ lymphomas but not NPC. Here we explore T-cell receptor (TCR) gene transfer to rapidly and reliably generate T-cells specific for the NPC-associated viral protein LMP2. We cloned a HLA A*1101-restricted TCR, which would be widely applicable since 40% of NPC patients carry this HLA allele. Studying both wild-type and modified forms we have optimised expression of the TCR and demonstrated high avidity antigen-specific function (proliferation, cytotoxicity, cytokine release) in both CD8+ and CD4+ T-cells. The engineered T-cells also inhibited LMP2+ epithelial tumour growth in a mouse model. Furthermore, transduced T-cells from patients with advanced NPC lysed LMP2-expressing NPC cell lines. Therefore, using this approach, within a few days large numbers of high avidity LMP2-specific T-cells can be reliably generated to treat NPC, providing an ideal clinical setting to test TCR gene transfer without the risk of autoimmunity through targeting self-antigens

Genome sequence of an Australian kangaroo, Macropus eugenii, provides insight into the evolution of mammalian reproduction and development.

BACKGROUND: We present the genome sequence of the tammar wallaby, Macropus eugenii, which is a member of the kangaroo family and the first representative of the iconic hopping mammals that symbolize Australia to be sequenced. The tammar has many unusual biological characteristics, including the longest period of embryonic diapause of any mammal, extremely synchronized seasonal breeding and prolonged and sophisticated lactation within a well-defined pouch. Like other marsupials, it gives birth to highly altricial young, and has a small number of very large chromosomes, making it a valuable model for genomics, reproduction and development. RESULTS: The genome has been sequenced to 2 × coverage using Sanger sequencing, enhanced with additional next generation sequencing and the integration of extensive physical and linkage maps to build the genome assembly. We also sequenced the tammar transcriptome across many tissues and developmental time points. Our analyses of these data shed light on mammalian reproduction, development and genome evolution: there is innovation in reproductive and lactational genes, rapid evolution of germ cell genes, and incomplete, locus-specific X inactivation. We also observe novel retrotransposons and a highly rearranged major histocompatibility complex, with many class I genes located outside the complex. Novel microRNAs in the tammar HOX clusters uncover new potential mammalian HOX regulatory elements. CONCLUSIONS: Analyses of these resources enhance our understanding of marsupial gene evolution, identify marsupial-specific conserved non-coding elements and critical genes across a range of biological systems, including reproduction, development and immunity, and provide new insight into marsupial and mammalian biology and genome evolution

Community Resilience to Climate Change : Outcomes of the Scottish Borders Climate Resilient Communities Project

Aims and Objectives: This report presents findings from an action research project conducted in the Scottish Borders between May 2015 and September 2016. The project aimed to:1) Support a local process of community change through building partnerships, learning and capacity building; and2) Understand the critical factors involved in facilitating the development of community resilience to climate change to draw out key levers for change nationally.The project was a collaboration between the University of Dundee, the Scottish Borders Council, Tweed Forum, Southern Uplands Partnership, International Futures Forum and the Scottish Association of Marine Sciences. It worked with three communities that had experience of flooding in the Borders council area and involved bringing together diverse organisations and community members in workshops and other activities

Desired Chinese medicine practitioner capabilities and professional development needs: a survey of registered practitioners in Victoria, Australia

Background The State of Victoria in Australia introduced Chinese medicine practitioner registration in 2000 and issued its education guidelines in late 2002 for introduction in 2005. This study obtained practitioners' views on desired capabilities for competent Chinese medicine practice and to identify professional development needs. Methods A questionnaire, consisting of 28 predefined capabilities in four categories with a rating scale of importance from one to five, was developed and sent to all registered Chinese medicine practitioners in the State of Victoria, Australia in October, 2005. Results Two hundreds and twenty eight completed questionnaires were returned which represented a response rate of 32.5%. Of the four categories of capabilities, technical capabilities were considered to be the most important for clinical practice. Specifically, the ability to perform acupuncture treatment and/or dispense an herbal prescription was ranked the highest. In contrast, research and information management capabilities were considered the least important. The educational background of practitioners appeared to be an important factor influencing their rating of capabilities. Significantly, nearly double the number of practitioners with Australian qualifications than practitioners trained overseas valued communication as an important capability. For continuing professional education, clinical skills courses were considered as a priority while research degree studies were not. Conclusion Registered Chinese medicine practitioners viewed skills training as important but did not support the need for research and information management training. This represents a significant hurdle to developing Chinese medicine as a form of evidence-based healthcare

Community Resilience to Climate Change : Summary for policy and practice

The Scottish Borders Climate Resilient Communities Project (SBCRC)1 was a participatory action research project that sought to build community resilience to climate change through working in three communities with a history of flooding in the Scottish Borders. It aimed to:- Understand some of the critical factors that contribute to shaping community resilience in the context of climate disadvantage;- Understand how community resilience to climate change can be developed in different local contexts in practice by supporting and facilitating engagement between members of three local communities and other stakeholders in the Scottish Borders region, and evaluating outcomes;- Draw out lessons for policymakers and practitioners on how to support the development of community resilience in the context of climate change.The project was structured around nine workshops (three per community) that brought together different organisations (e.g. the Scottish Borders Council, local NGOs) to examine issues and develop actions to build community resilience in the context of climate change. A tenth workshop used the outcomes from the work within the communities to examine how a more integrated and synergistic national policy landscape in Scotland could be developed to enhance community resilience to climate change. An evaluation helped to inform project delivery and the overall findings