A mathematical model of biofilm growth and spread within plant xylem: Case study of Xylella fastidiosa in olive trees.

Xylem-limited bacterial pathogens cause some of the most destructive plant diseases. Though imposed measures to control these pathogens are generally ineffective, even among susceptible taxa, some hosts can limit bacterial loads and symptom expression. Mechanisms by which this resistance is achieved are poorly understood. In particular, it is still unknown how differences in vascular structure may influence biofilm growth and spread within a host. To address this, we developed a novel theoretical framework to describe biofilm behaviour within xylem vessels, adopting a polymer-based modelling approach. We then parameterised the model to investigate the relevance of xylem vessel diameters on Xylella fastidiosa resistance among olive cultivars. The functionality of all vessels was severely reduced under infection, with hydraulic flow reductions of 2-3 orders of magnitude. However, results suggest wider vessels act as biofilm incubators; allowing biofilms to develop over a long time while still transporting them through the vasculature. By contrast, thinner vessels become blocked much earlier, limiting biofilm spread. Using experimental data on vessel diameter distributions, we were able to determine that a mechanism of resistance in the olive cultivar Leccino is a relatively low abundance of the widest vessels, limiting X. fastidiosa spread.

Principles of environmentally-sustainable anaesthesia: a global consensus statement from the World Federation of Societies of Anaesthesiologists.

The Earth's mean surface temperature is already approximately 1.1°C higher than pre-industrial levels. Exceeding a mean 1.5°C rise by 2050 will make global adaptation to the consequences of climate change less possible. To protect public health, anaesthesia providers need to reduce the contribution their practice makes to global warming. We convened a Working Group of 45 anaesthesia providers with a recognised interest in sustainability, and used a three-stage modified Delphi consensus process to agree on principles of environmentally sustainable anaesthesia that are achievable worldwide. The Working Group agreed on the following three important underlying statements: patient safety should not be compromised by sustainable anaesthetic practices; high-, middle- and low-income countries should support each other appropriately in delivering sustainable healthcare (including anaesthesia); and healthcare systems should be mandated to reduce their contribution to global warming. We set out seven fundamental principles to guide anaesthesia providers in the move to environmentally sustainable practice, including: choice of medications and equipment; minimising waste and overuse of resources; and addressing environmental sustainability in anaesthetists' education, research, quality improvement and local healthcare leadership activities. These changes are achievable with minimal material resource and financial investment, and should undergo re-evaluation and updates as better evidence is published. This paper discusses each principle individually, and directs readers towards further important references.

An overall view of temperature oscillations in the solar chromosphere with ALMA.

By direct measurements of the gas temperature, the Atacama Large Millimeter/submillimeter Array (ALMA) has yielded a new diagnostic tool to study the solar chromosphere. Here, we present an overview of the brightness-temperature fluctuations from several high-quality and high-temporal-resolution (i.e. 1 and 2 s cadence) time series of images obtained during the first 2 years of solar observations with ALMA, in Band 3 and Band 6, centred at around 3 mm (100 GHz) and 1.25 mm (239 GHz), respectively. The various datasets represent solar regions with different levels of magnetic flux. We perform fast Fourier and Lomb-Scargle transforms to measure both the spatial structuring of dominant frequencies and the average global frequency distributions of the oscillations (i.e. averaged over the entire field of view). We find that the observed frequencies significantly vary from one dataset to another, which is discussed in terms of the solar regions captured by the observations (i.e. linked to their underlying magnetic topology). While the presence of enhanced power within the frequency range 3-5 mHz is found for the most magnetically quiescent datasets, lower frequencies dominate when there is significant influence from strong underlying magnetic field concentrations (present inside and/or in the immediate vicinity of the observed field of view). We discuss here a number of reasons which could possibly contribute to the power suppression at around 5.5 mHz in the ALMA observations. However, it remains unclear how other chromospheric diagnostics (with an exception of Hα line-core intensity) are unaffected by similar effects, i.e. they show very pronounced 3-min oscillations dominating the dynamics of the chromosphere, whereas only a very small fraction of all the pixels in the 10 ALMA datasets analysed here show peak power near 5.5 mHz. This article is part of the Theo Murphy meeting issue 'High-resolution wave dynamics in the lower solar atmosphere'.

A bibliometric analysis of the conversion and reporting of pilot studies published in six anaesthesia journals.

Pilot and feasibility studies are preliminary investigations undertaken before a larger study. We hypothesised that only a small proportion of pilot or feasibility studies published in anaesthesia journals were correctly labelled as such. We searched for papers published between 2007 and 2017 in six anaesthesia journals using the text words 'pilot' OR 'feasibility' and included 266 original articles with 26,682 human participants. Only 34 (12.8%) were correctly labelled as a pilot or feasibility study. They were more likely to: have more median (IQR [range]) participants, 73 (40-130 [4-2716]) vs. 27 (15-60 [2-3305], p < 0.001; report feasibility outcomes, 82.4% vs. 4.3%, p < 0.001; and report an intention to convert, 100% vs. 39.7%, p < 0.001. They were less likely to test the efficacy of the primary outcome, 50% vs. 72.8%, p = 0.009; and report firm clinical conclusions 41.2% vs. 67.7%, p = 0.004. Of the studies published more than 5 years ago, correctly labelled pilot or feasibility studies were more likely to precede a published conversion study, 53.8% vs. 16%, p = 0.004. There was no difference between the number of citations 18 (9-44 [2-216]) vs. 20 (7-47 [0-251]), p = 0.865. These results have important consequences for patients, trialists, researchers and funders. We argue that correctly labelled pilot studies enhance the quality of scientific research by encouraging methodological rigour, ensuring scientific validity and reducing research waste. Authors, reviewers, editors and publishers should ensure they adhere to the contents of the 2016 CONSORT extension for pilot and feasibility studies.

Anaesthetic aspects in the treatment of fragility fracture patients.

As longevity increases globally, the number of older, frailer, comorbid patients requiring fragility fracture surgery will increase. Fundamentally, anaesthesia should aim to maintain these patients' pre-fracture cognitive and physiological trajectories and facilitate early (ie day 1) postoperative recovery. This review describes the 10 general principles of anaesthesia for fragility fracture surgery that best achieve these aims: multidisciplinary care, 'getting it right first time', timely surgery, standardisation, sympathetic anaesthesia, avoiding ischaemia, sympathetic analgesia, re-enablement, data collection and training.

Arterial immune protein expression demonstrates the complexity of immune responses in Kawasaki disease arteritis.

A more complete understanding of immune-mediated damage to the coronary arteries in children with Kawasaki disease (KD) is required for improvements in patient treatment and outcomes. We recently reported the transcriptional profile of KD coronary arteritis, and in this study sought to determine protein expression of transcriptionally up-regulated immune genes in KD coronary arteries from the first 2 months after disease onset. We examined the coronary arteries of 12 fatal KD cases and 13 childhood controls for expression of a set of proteins whose genes were highly up-regulated in the KD coronary artery transcriptome: allograft inflammatory factor 1 (AIF1), interleukin 18 (IL-18), CD74, CD1c, CD20 (MS4A1), Toll-like receptor 7 (TLR-7) and Z-DNA binding protein 1 (ZBP1). Immunohistochemistry and immunofluorescence studies were performed to evaluate protein expression and co-localization, respectively. AIF1 was expressed transmurally in KD arteritis and localized to macrophages and myeloid dendritic cells. CD74, which interacts with major histocompatibility complex (MHC) class II on antigen-presenting cells, localized to the intima-media. CD1c, a marker of myeloid dendritic cells, was expressed in a transmural pattern, as were IL-18 and CD20. ZBP1 and TLR-7 were up-regulated compared to controls, but less highly compared to the other proteins. These findings provide evidence of antigen presentation and interferon response in KD arteritis. In combination with prior studies demonstrating T lymphocyte activation, these results demonstrate the complexity of the KD arterial immune response.

Yes-associated protein mediates immune reprogramming in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a high degree of inflammation and profound immune suppression. Here we identify Yes-associated protein (Yap) as a critical regulator of the immunosuppressive microenvironment in both mouse and human PDAC. Within Kras:p53 mutant pancreatic ductal cells, Yap drives the expression and secretion of multiple cytokines/chemokines, which in turn promote the differentiation and accumulation of myeloid-derived suppressor cells (MDSCs) both in vitro and in vivo. Pancreas-specific knockout of Yap or antibody-mediated depletion of MDSCs promoted macrophage reprogramming, reactivation of T cells, apoptosis of Kras mutant neoplastic ductal cells and pancreatic regeneration after acute pancreatitis. In primary human PDAC, YAP expression levels strongly correlate with an MDSC gene signature, and high expression of YAP or MDSC-related genes predicts decreased survival in PDAC patients. These results reveal multifaceted roles of YAP in PDAC pathogenesis and underscore its promise as a therapeutic target for this deadly disease.