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Moded and Continuous Abstract State Machines
No full textIn view of the increasing importance of cyber-physical systems, and of their correct design, the Abstract State Machine (ASM) framework is extended to include continuously varying quantities as well as the conventional discretely changing ones. This opens the door to the more faithful modelling of many scenarios where digital systems have to interact with the continuously varying physical world. Transitions in the extended framework are thus either moded (catering for discontinuously changing quantities), or pliant (catering for smoothly changing quantities). An operational semantics is provided, first for monolithic systems, and this is then extended to give a semantics for systems consisting of several distinct subsystems. This allows each subsystem to undergo its own subsystem-specific mode and pliant transitions. Refinement is elaborated in the extended context for both monolithic and composed systems. The formalism is illustrated using an example of a bouncing tennis ball
Diagnosing pulmonary aspergillosis is much easier than it used to be: A new diagnostic landscape
No full textSignificant innovations in the past decade have resulted in more sensitive and faster diagnosis of allergic, chronic and invasive pulmonary aspergillosis, as well as Aspergillus bronchitis and Aspergillus nodules. This new diagnostic landscape has revealed that the incidence and prevalence of aspergillosis is substantially higher than previously understood. Oral and intravenous antifungal therapy offers good clinical response rates for affected patients. Yet, missed diagnosis leaves patients over-treated with antibacterial agents, corticosteroids and anti-tuberculous drugs resulting in continuing illness and often death. The clinical introduction of several high performing diagnostic tests is helping to redefine patient management. Assuredly, Aspergillus antigen can be detected in 70-95% of bronchoscopy samples in patients with invasive and chronic aspergillosis in less than 1 hour. Aspergillus IgG (precipitins) is >90% sensitive and 98% specific for chronic and allergic aspergillosis. High volume respiratory fungal culture and Aspergillus PCR have 3-5 fold much higher sensitivity than routine bacterial culture. Aspergillus IgE (or skin prick testing) diagnoses Aspergillus sensitisation in asthma, cystic fibrosis, COPD and after TB, and correlates well with poorer lung function and/or exacerbations. Across the world, clinicians and laboratorians need to mainstream these excellent new tools to improve clinical outcomes by delivering results in a more timely and accurate fashion
Excess deaths from COVID-19 and other causes by region, neighbourhood deprivation level and place of death during the first 30 weeks of the pandemic in England and Wales
No full textBackgroundExcess deaths during the COVID-19 pandemic compared with those expected from historical trends have been unequally distributed, both geographically and socioeconomically. Not all excess deaths have been directly related to COVID-19 infection. We investigated geographical and socioeconomic patterns in excess deaths for major groups of underlying causes during the pandemic. MethodsWeekly mortality data from 27/12/2014 to 2/10/2020 for England and Wales were obtained from the Office of National Statistics. Negative binomial regressions were used to model death counts based on pre-pandemic trends for deaths caused directly by COVID-19 (and other respiratory causes) and those caused indirectly by it (cardiovascular disease or diabetes, cancers, and all other indirect causes) over the first 30 weeks of the pandemic (7/3/2020 –2/10/2020).FindingsThere were 62,321 (95% CI: 58,849 to 65,793) excess deaths in England and Wales in the first 30 weeks of the pandemic. Of these, 46,221 (95% CI: 45,439 to 47,003) were attributable to respiratory causes, including COVID-19, and 16,100 (95% CI: 13,410 to 18,790) to other causes. Rates of all-cause excess mortality ranged from 78 per 100,000 in the South West of England and in Wales to 130 per 100,000 in the West Midlands; and from 93 per 100,000 in the most affluent fifth of areas to 124 per 100,000 in the most deprived. The most deprived areas had the highest rates of death attributable to COVID-19 and other indirect deaths, but there was no socioeconomic gradient for excess deaths from cardiovascular disease/diabetes and cancer.InterpretationDuring the first 30 weeks of the COVID-19 pandemic there was significant geographic and socioeconomic variation in excess deaths for respiratory causes, but not for cardiovascular disease, diabetes and cancer. Pandemic recovery plans, including vaccination programmes, should take account of individual characteristics including health, socioeconomic status and place of residence.<br/
Towards a Tuwün Wariache? Place-making and creative acts of traversing in the Mapuche city
No full textThis article addresses experiences of belonging and place-making of indigenousMapuche youths in Santiago, Chile. Moving from a collaborative ethnography, it elaborates on the emplacement of the tuwün (place of origin) – usually linked to ancestral territories – within the city, and the meanings this shift entails. Furthering knowledge on indigenous spatiality by addressing migration, the analysis focuses on the ambivalent ways in which memory, affect andpower relations are embedded in urban materialities, and are negotiated through ‘acts of traversing’. The significant relationship between persons and places is conceived as mediated by movement, expanding on the creative possibilities of routing. Moreover, drawing on practice based methods, the article argues for a shared engagement with research participants in order to gain a deeper understanding of the ways in which place and self-making in contexts of migration encompass both rupture and creative re-appropriation, contributing to current debates on displacement and the sense of place
Neighbourhoods and dementia: An updated realist review of the qualitative literature to inform contemporary practice and policy understanding
No full textThis realist review of the literature provided a contemporary understanding of neighbourhoods and dementia and described how people living with dementia and their neighbourhood interacted via ongoing place-making and remaking processes. Drawing on 44 articles, neighbourhoods were revealed to have fluid and dynamic qualities where people with dementia used their strength and resources to connect to significant people and places. The review also indicated that the person with dementia-neighbourhood relationship was underpinned by four themes: 'home', 'social interactions', 'activities' and 'transportation'. Further research is encouraged to use innovative, participatory methods to explore the neighbourhood-dementia nexus in depth whilst paying close attention to social inclusion and diversity
How do gender-diverse young people experience high school? A systematic literature review
No full textAims: The current review provides an overview of the international research relating to the lived high school (ages 11-16) experiences of gender-diverse young people. Method: Web and database searches were conducted between October 2019 and January 2020 to identify 12 studies which included direct, first-hand testimonial experiences relating to high school. Data were analysed using thematic synthesis. Findings: The findings indicate that gender-diverse youth experience a range of both negative and affirming experiences throughout high school linked to key themes including cisnormativity, language, identity, relationships and transphobia. Limitations: Not all database searches proved productive, therefore hand searches, reference harvesting and grey literature searches were also conducted. However, given the variability in terminology within this field, there is the possibility that not all relevant literature may have been captured through this process.Conclusions: Findings are discussed in relation to inclusive practices which schools may adopt to support their gender-diverse students. Strategies include: the avoidance of accommodating approaches to inclusion; adopting rights respecting principles; embedding safe and supportive spaces for self-determination; and providing further training for educators. The paper also discusses implications for professional practice
A crystal growth cell incorporating automated image analysis enables measurement of facet specific crystal growth rates.
No full textWe present an automated method for measuring facet specific growth rates by combining a crystal growth flow cell with image processing. This paper details the design of the growth cell and its advantages over previous models. The method of image processing utilizes a Hough transform to identify crystal facets, ultimately leading to facet specific growth rate measurements. Finally, experimental results are presented for facet specific growth rates of αglycine crystals and compared to previous data
Influence of emulsified plant oil composition on growth and biopolymer production of Cupriavidus necator DSM 545
No full textCupriavidus necator DSM 545 was cultivated on a range of crude and emulsified plant oils (olive, rapeseed, sesame seed, spent coffee grounds (SCGs) and sunflower) of varying fatty acid (FA) composition to assess their influence on the organism’s growth and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [P(3HB-co-3HV)] biopolymer production. Initially five different surfactants (gum arabic, dimethyl sulfoxide (DSMO), Tween 80, Triton X-100, and sodium dodecyl sulfate) were screened for their influence on cell growth and ability to form stable oil-in-water emulsions. The highest total biomass (11.3 ± 0.2 g L−1) and P(3HB-co-3HV) (10.0 ± 0.6 g L−1) concentrations were achieved with SCGs oil emulsified with DMSO. At 88.9 ± 5.2 %, the corresponding polymer fraction of the total biomass is among the highest values reported in the literature. During the initial growth phase (0 – 24 h), the organism consumed all fatty acids in broadly the same proportion, but preference was then displayed in the subsequent P(3HB-co-3HV) production phase (24 – 120 h) for saturated FAs (particularly palmitic acid) over unsaturated FAs. SCG oil was an ideal substrate in comparison to the other plant oils due to its high acid value (17.9 ± 0.1 mgKOH goil−1) and palmitic acid content (31.4 ± 0.5 %, w/w). Emulsifying the plant oil cultures initially increased substrate bioavailability, but the influence diminished as the fermentations progressed. Overall, the use of SCGs as a feedstock for PHA production will help reduce the manufacturing costs of the biopolymer and generate a valorisation strategy for an otherwise highly unutilised resource.KeywordsCupriavidus necator; Polyhydroxyalkanoates; Plant oils; Fatty acids; Surfactants; Waste valorisation<br/
Automation and Expansion of EMMA Assembly for Fast-Tracking Mammalian System Engineering
No full textWith applications from functional genomics to the production of therapeutic biologics, libraries of mammalian expression vectors have become a cornerstone of modern biological investigation and engineering. Multiple modular vector platforms facilitate the rapid design and assembly of vectors. However, such systems approach a technical bottleneck when a library of bespoke vectors is required. Utilising the flexibility and robustness of the Extensible Mammalian Modular Assembly toolkit (EMMA), we present an automated work flow for the library-scale design, assembly and verification of mammalian expression vectors. Vector design is simplified using our EMMA computer-aided design tool (EMMA-CAD), whilst the precision and speed of acoustic droplet ejection technology are applied in vector assembly. Our pipeline facilitates significant reductions in both reagent usage and researcher hands-on time when compared with manual assembly, as shown by system Q-metrics. To demonstrate automated EMMA performance, we compiled a library of 48 distinct plasmid vectors, encoding either CRISPR interference or activation modalities. Characterization of work flow parameters shows that high assembly efficiency is maintained across vectors of various sizes and design complexities. Our system also performs strongly when compared to manual assembly efficiency benchmarks. Alongside our automated pipeline, we present a straightforward strategy for integrating gRNA and Cas9 modules into the EMMA platform, enabling the design and manufacture of valuable genome editing resources
Everolimus-induced pneumonitis in patients with neuroendocrine neoplasms: real-world study on risk factors and outcomes
No full textBackground: Everolimus-induced pneumonitis (EiP) has been poorly studied in patients with neuroendocrine neoplasms (NEN) outside clinical trials. The aim of this study was to evaluate the incidence, risk factors, and outcomes of EiP in patients with NENs using real-world data. Methods: Retrospective study of everolimus-treated patients with advanced NENs. Imaging reports were systematically reviewed for the presence of pneumonitis. Clinical features and treatment profiles for EiP were summarized. Overall survival (OS) was calculated from the initiation of everolimus to the date of death or last follow-up using the Kaplan-Meier method. Results: A total of 122 patients were included. Median age at start of everolimus was 62 (19-86) years, 62% (76/122) were male, and half were from pancreatic origin (62, 51%). Twenty-eight patients (23%) developed EiP: 82% grade (G)1 or G2, 14% G3 and 4% G4. The median time to EiP was 3.6 (0.8-51) months. Primary tumor site, concurrent lung disease, smoking history and prior therapies were not associated with the onset of EiP. Patients who developed EiP had longer time on everolimus treatment (median 18 months vs 6 months; p = .0018) and OS (77 months vs 52 months; p = .093). EiP was a predictor of improved OS by multivariable analysis (HR 0.39, 95% CI 0.19-0.82; p = .013). Conclusion: EiP in the real-world clinical setting is present in one quarter of patients with NENs receiving everolimus and often occurs early. While risk factors for EiP were not identified, patients with EiP had improved survival.<br/