Sacrificial layer process with laser-driven release for batch assembly operations

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Scoping an interdisciplinary model of student dental therapists in maxillofacial trauma.

Introduction This paper outlines a short pilot programme to assess the feasibility of an interdisciplinary model of involving student dental therapists in the management of maxillofacial trauma patients. It involved dental therapy students attending an oral and maxillofacial surgery trauma review clinic at a major trauma hospital in London, UK.Approach The small cohort of 15 second-year dental hygiene and therapy (BSc in Oral Health) students attended the trauma clinic once a week in pairs, over a period of six weeks, after which they completed a survey questionnaire.Findings No students had previous experience of dealing with trauma patients. The majority (81.8%) had learnt something by attending the clinic. Almost all (91.7%) had not thought previously about the importance of oral hygiene in maxillofacial trauma patients. By the end of the pilot programme, ten students (83.3%) felt that they had a role to play in the care of these trauma patients and they felt valued as members of the wider team.Conclusion These initial findings suggest that the scheme has potential for incorporation of maxillofacial trauma experience within the formal dental therapy curriculum. This would prepare them for future involvement in the management of maxillofacial trauma patients to promote oral health benefits and more widely, to work as a team member in interprofessional health care

Human kin detection

Natural selection has favored the evolution of behaviors that benefit not only one's genes, but also their copies in genetically related individuals. These behaviors include optimal outbreeding (choosing a mate that is neither too closely related, nor too distant), nepotism (helping kin), and spite (hurting non-kin at a personal cost), and all require some form of kin detection or kin recognition. Yet, kinship cannot be assessed directly; human kin detection relies on heuristic cues that take into account individuals' context (whether they were reared by our mother, or grew up in our home, or were given birth by our spouse), appearance (whether they smell or look like us), and ability to arouse certain feelings (whether we feel emotionally close to them). The uncertainties of kin detection, along with its dependence on social information, create ample opportunities for the evolution of deception and self-deception. For example, babies carry no unequivocal stamp of their biological father, but across cultures they are passionately claimed to resemble their mother's spouse; to the same effect, neutral' observers are greatly influenced by belief in relatedness when judging resemblance between strangers. Still, paternity uncertainty profoundly shapes human relationships, reducing not only the investment contributed by paternal versus maternal kin, but also prosocial behavior between individuals who are related through one or more males rather than females alone. Because of its relevance to racial discrimination and political preferences, the evolutionary pressure to prefer kin to non-kin has a manifold influence on society at large

NRF2 metagene signature is a novel prognostic biomarker in colorectal cancer

We hypothesise that the NRF2 transcription factor would act a biomarker of poor prognosis in colorectal cancer. We derived and validated an mRNA based metagene signature of NRF2 signalling and validated it in 1360 patients from 4 different datasets as an independent biomarker of poor prognosis. This is a novel insight into the molecular signalling of colorectal cancer. Background: NRF2 over activity confers poor prognosis in some cancers but its prognostic role in colorectal cancer (CRC) is unknown. As a transcription factor, we hypothesise a signature of NRF2 regulated genes could act as a prognostic biomarker in CRC and reveal novel biological insights. Methods: Using known NRF2 regulated genes, differentially expressed in CRC, we defined a signature of NRF2 pathway activity using principal component analysis and Cox proportional hazard models and tested it in four independent mRNA datasets, profiled on three different mRNA platforms. Results: 36 genes comprised the final NRF2 signature. 1360 patients were included in the validation. High NRF2 was associated with worse disease free survival (DFS) and/or overall survival (OS) in all datasets: (GSE14333 HR=1.55, 95% C.I 1.2–2.004, p = 0.0008; GSE39582 HR=1.24, 95% C.I 1.086–1.416, p = 0.001; GSE87211 HR=1.431, 95% C.I 1.06–1.93, p = 0.056; MRC FOCUS trial HR=1.14, 95% C.I 1.04–1.26, p = 0.008). In multivariate analyses, NRF2 remained significant when adjusted for stage and adjuvant chemotherapy in stage I-III disease, and BRAF V600E mutation and sidedness in stage IV disease. NRF2 activity was particularly enriched in Consensus Molecular Subtype (CMS) 4. Conclusion: For the first time, NRF2 is shown to be a consistent, robust prognostic biomarker across all stages of colorectal cancer with additional clinical value to current known prognostic biomarkers. High NRF2 signalling in CMS 4 further refines the molecular taxonomy of CRC, a new biological insight, suggesting avenues of further study

Age and Microenvironment Outweigh Genetic Influence on the Zucker Rat Microbiome

Animal models are invaluable tools which allow us to investigate the microbiome-host dialogue. However, experimental design introduces biases in the data that we collect, also potentially leading to biased conclusions. With obesity at pandemic levels animal models of this disease have been developed; we investigated the role of experimental design on one such rodent model. We used 454 pyrosequencing to profile the faecal bacteria of obese (n = 6) and lean (homozygous n = 6; heterozygous n = 6) Zucker rats over a 10 week period, maintained in mixed-genotype cages, to further understand the relationships between the composition of the intestinal bacteria and age, obesity progression, genetic background and cage environment. Phylogenetic and taxon-based univariate and multivariate analyses (non-metric multidimensional scaling, principal component analysis) showed that age was the most significant source of variation in the composition of the faecal microbiota. Second to this, cage environment was found to clearly impact the composition of the faecal microbiota, with samples from animals from within the same cage showing high community structure concordance, but large differences seen between cages. Importantly, the genetically induced obese phenotype was not found to impact the faecal bacterial profiles. These findings demonstrate that the age and local environmental cage variables were driving the composition of the faecal bacteria and were more deterministically important than the host genotype. These findings have major implications for understanding the significance of functional metagenomic data in experimental studies and beg the question; what is being measured in animal experiments in which different strains are housed separately, nature or nurture

Lab-based X-ray micro-computed tomography coupled with machine-learning segmentation to investigate phosphoric acid leaching in high-temperature polymer electrolyte fuel cells

A machine-learning approach is used to segment 14 X-ray computed-tomography datasets acquired by lab-based scanning of laser-milled, high-temperature polymer electrolyte fuel cell samples mounted in a 3D-printed sample holder. Two modes of operation, one with constant current load and the other with current cycling, are explored and their impact on microstructural change is correlated with electrochemical performance degradation. Constant-current testing shows the overall quantity of phosphoric acid in the gas diffusion layers is effectively unchanged between 50 and 100 h of operation but that inter-electrode distribution becomes less uniform. Current-cycling tests reveal similar quantities of phosphoric acid but a different intra-electrode distribution. Membrane swelling appears more pronounced after current-cycling tests and in both cases, significant catalyst layer migration is observed. The present analysis provides a lab-based approach to monitoring microstructural degradation in high-temperature polymer electrolyte fuel cells and provides a more accessible and more statistically robust platform for assessing the impact of phosphoric acid mitigation strategies

Preparation and crystallization of hollow α-Fe<inf>2</inf>O<inf>3</inf> microspheres following the gas-bubble template method

In this work we report the formation of hollow α-Fe2O3 (hematite) microspheres by the gas-bubble template method. This technique is simple and it does not require hard templates, surfactants, special conditions of atmosphere or complex steps. After reacting Fe(NO3)3.9H2O and citric acid in water by sol-gel, the precursor was annealed in air at different temperatures between 180 and 600 ºC. Annealing at 550 and 600 ºC generates bubbles on the melt which crystallize and oxidizes to form hematite hollow spheres after condensation. The morphology and crystal evolution are studied by means of X-ray diffraction and scanning electron microscopy. We found that after annealing at 250-400 ºC, the sample consist of a mixture of magnetite, maghemite and hematite. Single hematite phase in the form of hollow microspheres is obtained after annealing at 500 and 600 ºC. The crystallization and crystal size of the hematite shells increase with annealing temperature. A possible mechanism for hollow sphere formation is presented.This work was supported by the Engineering and Physical Science Research Council (EPSRC No. EP/J003638/1). The work in Peru has been supported by CONCYTEC. The work in Brazil was supported by CNPq (307552/2012-8), CAPES (PNPD- 230.007518/2011-11) and FACEPE (APQ-0589-1.05/08).This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.matchemphys.2015.11.02

A phase 1 trial of the safety, tolerability and biological effects of intravenous Enadenotucirev, a novel oncolytic virus, in combination with chemoradiotherapy in locally advanced rectal cancer (CEDAR)

BACKGROUND: Chemoradiotherapy remains the standard of care for locally advanced rectal cancer. Efforts to intensify treatment and increase response rates have yet to yield practice changing results due to increased toxicity and/or absence of increased radiosensitization. Enadenotucirev (EnAd) is a tumour selective, oncolytic adenovirus which can be given intravenously. Pre-clinical evidence of synergy with radiation warrants further clinical testing and assessment of safety with radiation. METHODS: Eligibility include histology confirmed locally advanced rectal cancer that require chemoradiation. The trial will use a Time-to-Event Continual Reassessment Model-based (TiTE-CRM) approach using toxicity and efficacy as co-primary endpoints to recommend the optimal dose and treatment schedule 30 patients will be recruited. Secondary endpoints include pathological complete response the neoadjuvant rectal score. A translational program will be based on a mandatory biopsy during the second week of treatment for 'proof-of-concept' and exploration of mechanism. The trial opened to recruitment in July 2019, at an expected rate of 1 per month for up to 4 years. DISCUSSION: Chemoradiation with Enadenotucirev as a radiosensitiser in locally Advanced Rectal cancer (CEDAR) is a prospective multicentre study testing a new paradigm in radiosensitization in rectal cancer. The unique ability of EnAd to selectively infect tumour cells following intravenous delivery is an exciting opportunity with a clear translational goal. The novel statistical design will make efficient use of both toxicity and efficacy data to inform subsequent studies. TRIAL REGISTRATION: ClinicalTrial.gov, NCT03916510. Registered 16th April 2019

Welcoming Wolves? Governing the Return of Large Carnivores in Traditional Pastoral Landscapes

Wolf populations are recovering across Europe and readily recolonize most areas where humans allow their presence. Reintegrating wolves in human-dominated landscapes is a major challenge, particularly in places where memories and experience of coexistence have been lost. Despite the observed expansion trends, little has been done to prepare communities for the return of these apex predators, or to understand what fosters and perpetuates coexistence. In this study, we present a theoretical framework for resilient coexistence based on four conditions: Effective institutions, large carnivore persistence, social legitimacy, and low levels of risk and vulnerability, nested within the social-ecological systems (SES) concept. To empirically show how the conditions can be manifested and interconnected, and how this knowledge could be used to improve local coexistence capacities, the framework is applied in a case study of human–wolf relations in Spain. We examined three traditionally pastoral landscapes at different states of cohabitation with wolves: uninterrupted presence, recent recolonization, and imminent return. We found that both the perceptions of wolves and the capacity to coexist with them diverged across these states, and that this was largely determined by a diversity of vulnerabilities that have not been recognized or addressed within current management regimes, such as economic precarity and weak legitimacy for governing institutions. Our results illustrate the importance of working in close contact with communities to understand local needs and enhance adaptive capacities in the face of rural transitions, beyond those directly related to wolves. The framework complements emerging tools for coexistence developed by researchers and practitioners, which offer guidance on the process of situational analysis, planning, and resource allocation needed to balance large carnivore conservation with local livelihoods