Contributors: Saribekyan, Hayk, Giakkoupis, George, Mallmann-Trenn, Frederik
... We study the problem of randomized information dissemination in networks. We compare the now standard push-pull protocol, with agent-based alternatives where information is disseminated by a collection of agents performing independent random walks. In the visit-exchange protocol, both nodes and agents store information, and each time an agent visits a node, the two exchange all the information they have. In the meet-exchange protocol, only the agents store information, and exchange their information with each agent they meet. We consider the broadcast time of a single piece of information in an n-node graph for the above three protocols, assuming a linear number of agents that start from the stationary distribution. We observe that there are graphs on which the agent-based protocols are significantly faster than push-pull, and graphs where the converse is true. We attribute the good performance of agent-based algorithms to their inherently fair bandwidth utilization, and conclude that, in certain settings, agent-based information dissemination, separately or in combination with push-pull, can significantly improve the broadcast time. The graphs considered above are highly non-regular. Our main technical result is that on any regular graph of at least logarithmic degree, push-pull and visit-exchange have the same asymptotic broadcast time. The proof uses a novel coupling argument which relates the random choices of vertices in push-pull with the random walks in visit-exchange. Further, we show that the broadcast time of meet-exchange is asymptotically at least as large as the other two's on all regular graphs, and strictly larger on some regular graphs. As far as we know, this is the first systematic and thorough comparison of the running times of these very natural information dissemination protocols.
Contributors: Orr, John, Darby, Antony, Ibell, Timothy, Evernden, Mark
... By replacing conventional concrete moulds with flexible sheets of permeable fabric the construction of optimised concrete elements that provide material savings of up to 40% when compared to an equivalent strength prismatic member is possible. This paper details the results of recent tests undertaken at the Building Research Establishment Centre for Innovative Construction Materials at the University of Bath (BRE CICM) that demonstrate significant additional durability advantages for fabric cast concrete.Using accelerated test methods 50% average reductions in both the non-steady state chloride diffusion coefficient and carbonation coefficients were found when comparing concrete samples cast against permeable and impermeable surfaces. Sorptivity, surface hardness, and scanning electron microscopy tests demonstrate further beneficial changes in the fabric cast concrete. The combined results demonstrate that fabric formwork may be used to create structures optimised for strength and durability.
Logistic early warning scores to predict death, cardiac arrest or unplanned intensive care unit re‐admission after cardiac surgery
Contributors: Chiu, YD, Villar, SS, Brand, JW, Patteril, MV, Morrice, DJ, Clayton, J, Mackay, JH
Contributors: Nik-Zainal Abidin, Nik
... Ductal carcinoma in situ (DCIS) now represents 20–25% of all ‘breast cancers’ consequent upon detection by population-based breast cancer screening programs. Currently, all DCIS lesions are treated, and treatment comprises either mastectomy or breast-conserving surgery supplemented with radiotherapy. However, most DCIS lesions remain indolent; difficulty in discerning harmless lesions from potentially invasive ones can lead to overtreatment of this condition in many patients. To counter overtreatment and to transform clinical practice, a global, comprehensive, and multidisciplinary collaboration is required. Here, we review the incidence of DCIS, the perception of risk for developing invasive breast cancer, the current treatment options and the known molecular aspects of progression. Further research is needed to gain new insights for improved diagnosis and management of DCIS, and this is integrated in the PRECISION ('Prevent ductal Carcinoma In Situ Overtreatment Now') initiative. This international effort will seek to determine which DCIS requires treatment and prevent the consequences of overtreatment on the lives of many women affected by DCIS.
ERβ-mediated induction of cystatins results in suppression of TGFβ signaling and inhibition of triple-negative breast cancer metastasis.
Contributors: Reese, Jordan M, Bruinsma, Elizabeth S, Nelson, Adam W, Chernukhin, Igor, Carroll, Jason, Li, Ying, Subramaniam, Malayannan, Suman, Vera J, Negron, Vivian, Monroe, David G
... Triple-negative breast cancer (TNBC) accounts for a disproportionately high number of deaths due to a lack of targeted therapies and an increased likelihood of distant recurrence. Estrogen receptor beta (ERβ), a well-characterized tumor suppressor, is expressed in 30% of TNBCs, and its expression is associated with improved patient outcomes. We demonstrate that therapeutic activation of ERβ elicits potent anticancer effects in TNBC through the induction of a family of secreted proteins known as the cystatins, which function to inhibit canonical TGFβ signaling and suppress metastatic phenotypes both in vitro and in vivo. These data reveal the involvement of cystatins in suppressing breast cancer progression and highlight the value of ERβ-targeted therapies for the treatment of TNBC patients.
Measurement of extravascular lung water to diagnose severe reperfusion lung injury following pulmonary endarterectomy: a prospective cohort clinical validation study
Contributors: Butchart, AG, Zochios, V, Villar, SS, Jones, NL, Curry, S, Agrawal, B, Jenkins, DP, Klein, AA
... The measurement of extravascular lung water is a relatively new technology which has not yet been well validated as a clinically useful tool. We studied its utility in patients undergoing pulmonary endarterectomy as they frequently suffer reperfusion lung injury and associated oedematous lungs. Such patients are therefore ideal for evaluating this new monitor. We performed a prospective observational cohort study during which extravascular lung water index measurements were taken before and immediately after surgery and postoperatively in intensive care. Data were analysed for 57 patients; 21 patients (37%) experienced severe reperfusion lung injury. The first extravascular lung water index measurement after cardiopulmonary bypass failed to predict severe reperfusion lung injury, area under the receiver operating characteristic curve 0.59 (95%CI 0.44–0.74). On intensive care, extravascular lung water index correlated most strongly at 36 h, area under the receiver operating characteristic curve 0.90 (95%CI 0.80–1.00). Peri‐operative extravascular lung water index is not a useful measure to predict severe reperfusion lung injury after pulmonary endarterectomy, however, it does allow monitoring and measurement during the postoperative period. This study implies that extravascular lung water index can be used to directly assess pulmonary fluid overload and that monitoring patients by measuring extravascular lung water index during their intensive care stay is useful and correlates with their clinical course. This may allow directed, pre‐empted therapy to attenuate the effects and improve patient outcomes and should prompt further studies.
Macrocyclisation and functionalisation of unprotected peptides via divinyltriazine cysteine stapling
Contributors: Robertson, Naomi, Walsh, Stephen J, Fowler, Elaine, Yoshida, Masao, Rowe, Sam, Wu, Yuteng, Sore, Hannah, Parker, Jeremy, Spring, David R
... We report a novel divinyltriazine (DVT) linker for the stapling of two cysteine residues to form macrocyclic peptides from their unprotected linear counterparts. The stapling reaction occurred rapidly under mild...
Self-assembly of embryonic and two extra-embryonic stem cell types into gastrulating embryo-like structures.
Contributors: Sozen, Berna, Amadei, Gianluca, Cox, Andy, Wang, Ran, Na, Ellen, Czukiewska, Sylwia, Chappell, Lia, Voet, Thierry, Michel, Geert, Jing, Naihe
... Embryonic stem (ES) cells can be incorporated into the developing embryo and its germ line but when cultured alone, their ability to generate embryonic structures is restricted. They can interact with trophoblast stem (TS) cells to generate structures that break symmetry and specify mesoderm, but their development is limited as the epithelial-mesenchymal-transition (EMT) of gastrulation cannot occur. Here we describe a system that, for the first time, allows assembly of mouse ES, TS and extra-embryonic-endoderm (XEN) cells into structures that acquire the embryo’s architecture with all distinct embryonic and extra-embryonic compartments. Strikingly, such embryo structures develop to undertake EMT, leading to mesoderm and then definitive endoderm specification. Spatial transcriptomic analyses demonstrate that these morphological transformations are underpinned by gene-expression patterns characteristic of gastrulating embryos. This demonstrates the remarkable ability of three stem cell types to self-assemble in vitro into gastrulating embryo structures undertaking spatio-temporal events of the gastrulating mammalian embryo.
Contributors: McKie, Mikel, Villar Moreschi, Sofia
... Because the mortality rate is very low in thoracic surgery, its use as a quality discriminator is limited. Acute kidney injury (AKI) is a candidate measure because it is associated with increased rates of morbidity and mortality and is partly preventable. The incidence of AKI after thoracic surgery is not well documented. We conducted an audit to determine the incidence and outcomes of AKI. This audit became a pilot project, and the results indicate the feasibility of a larger study.
Contributors: Tennyson, Elizabeth, Doherty, Tiarnan AS, Stranks, Samuel
... Materials with highly crystalline lattice structures and low defect concentrations have classically been considered essential for high-performance optoelectronic devices. However, the emergence of high-efficiency devices based on halide perovskites is provoking researchers to rethink this traditional picture, as the heterogeneity in several properties within these materials occurs on a series of length scales. Perovskites are typically fabricated crudely through simple processing techniques, which leads to large local fluctuations in defect density, lattice structure, chemistry and bandgap that appear on short length scales (10 μm). Despite these variable and complex non-uniformities, perovskites maintain exceptional device efficiencies, and are, as of 2018, the best-performing polycrystalline thin-film solar cell material. In this Review, we highlight the multiple layers of heterogeneity ascertained using high-spatial-resolution methods that provide access to the required length scales. We discuss the impact that the optoelectronic variations have on halide perovskite devices, including the prospect that it is this very disorder that leads to their remarkable power-conversion efficiencies.