Development of plasmacytoid and conventional dendritic cell subtypes from single precursor cells derived in vitro and in vivo

Naik, Shalin H,Sathe, Priyanka,Park, Hae-Young,Metcalf, Donald,Proietto, Anna I,Dakic, Aleksander,Carotta, Sebastian,O'Keeffe, Meredith,Bahlo, Melanie,Papenfuss, Anthony,Kwak, Jong-Young,Wu, Li,Shortm NATURE AMERICA INC 2007 NATURE IMMUNOLOGY Vol.8 No.11

The development of functionally specialized subtypes of dendritic cells (DCs) can be modeled through the culture of bone marrow with the ligand for the cytokine receptor Flt3. Such cultures produce DCs resembling spleen plasmacytoid DCs (pDCs), CD8<SUP>+</SUP> conventional DCs (cDCs) and CD8<SUP>−</SUP> cDCs. Here we isolated two sequential DC-committed precursor cells from such cultures: dividing 'pro-DCs', which gave rise to transitional 'pre-DCs' en route to differentiating into the three distinct DC subtypes (pDCs, CD8<SUP>+</SUP> cDCs and CD8<SUP>−</SUP> cDCs). We also isolated an in vivo equivalent of the DC-committed pro-DC precursor cell, which also gave rise to the three DC subtypes. Clonal analysis of the progeny of individual pro-DC precursors demonstrated that some pro-DC precursors gave rise to all three DC subtypes, some produced cDCs but not pDCs, and some were fully committed to a single DC subtype. Thus, commitment to particular DC subtypes begins mainly at this pro-DC stage.

Development of integrated waste management options for irradiated graphite

Alan Wareing,Liam Abrahamsen-Mills,Linda Fowler,Michael Grave,Richard Jarvis,Martin Metcalfe,Simon Norris,Anthony William Banford 한국원자력학회 2017 Nuclear Engineering and Technology Vol.49 No.5

The European Treatment and Disposal of Irradiated Graphite and other Carbonaceous Waste projectsought to develop best practices in the retrieval, treatment, and disposal of irradiated graphite includingother irradiated carbonaceous waste such as structural material made of graphite, nongraphitized carbonbricks, and fuel coatings. Emphasis was given on legacy irradiated graphite, as this represents a significantinventory in respective national waste management programs. This paper provides an overview ofthe characteristics of graphite irradiated during its use, primarily as a moderator material, within nuclearreactors. It describes the potential techniques applicable to the retrieval, treatment, recycling/reuse, anddisposal of these graphite wastes. Considering the lifecycle of nuclear graphite, from manufacture to finaldisposal, a number of waste management options have been developed. These options consider thetechniques and technologies required to address each stage of the lifecycle, such as segregation, treatment,recycle, and ultimate disposal in a radioactive waste repository, providing a toolbox to aid operatorsand regulators to determine the most appropriate management strategy. It is noted that nationalwaste management programs currently have, or are in the process of developing, respective approachesto irradiated graphite management. The output of the Treatment and Disposal of Irradiated Graphite andother Carbonaceous Waste project is intended to aid these considerations, rather than dictate them.

A 6-Point TACS Score Predicts In-Hospital Mortality Following Total Anterior Circulation Stroke

Adrian D Wood,Nicholas D Gollop,Joao H Bettencourt-Silva,Allan B Clark,Anthony K Metcalf,Kristian M Bowles,Marcus D Flather,John F Potter,Phyo Kyaw Myinta 대한신경과학회 2016 Journal of Clinical Neurology Vol.12 No.4

Background and Purpose Little is known about the factors associated with in-hospital mortality following total anterior circulation stroke (TACS). We examined the characteristics and comorbidity data for TACS patients in relation to in-hospital mortality with the aim of developing a simple clinical rule for predicting the acute mortality outcome in TACS. Methods A routine data registry of one regional hospital in the UK was analyzed. The sub¬jects were 2,971 stroke patients with TACS (82% ischemic; median age=81 years, interquar¬tile age range=74–86 years) admitted between 1996 and 2012. Uni- and multivariate regres¬sion models were used to estimate in-hospital mortality odds ratios for the study covariates. A 6-point TACS scoring system was developed from regression analyses to predict in-hospi¬tal mortality as the outcome. Results Factors associated with in-hospital mortality of TACS were male sex [adjusted odds ratio (AOR)=1.19], age (AOR=4.96 for ≥85 years vs. <65 years), hemorrhagic subtype (AOR=1.70), nonlateralization (AOR=1.75), prestroke disability (AOR=1.73 for moderate disability vs. no symptoms), and congestive heart failure (CHF) (AOR=1.61). Risk stratifica¬tion using the 6-point TACS Score [T=type (hemorrhage=1 point) and territory (nonlateral¬ization=1 point), A=age (65–84 years=1 point, ≥85 years=2 points), C=CHF (if present=1 point), S=status before stroke (prestroke modified Rankin Scale score of 4 or 5=1 point)] reli-ably predicted a mortality outcome: score=0, 29.4% mortality; score=1, 46.2% mortality [negative predictive value (NPV)=70.6%, positive predictive value (PPV)=46.2%]; score=2, 64.1% mortality (NPV=70.6, PPV=64.1%); score=3, 73.7% mortality (NPV=70.6%, PPV=73.7%); and score=4 or 5, 81.2% mortality (NPV=70.6%, PPV=81.2%). Conclusions We have identified the key determinants of in-hospital mortality following TACS and derived a 6-point TACS Score that can be used to predict the prognosis of particular patients.

A History of Falls is Associated with a Significant Increase in Acute Mortality in Women after Stroke

Emma J. Foster,Raphae S. Barlas,Adrian D Wood,Joao H. Bettencourt-Silva,Allan B Clark,Anthony K Metcalf,Kristian M Bowles,John F Potter,Phyo K. Myint 대한신경과학회 2017 Journal of Clinical Neurology Vol.13 No.4

Background and Purpose The risks of falls and fractures increase after stroke. Little is known about the prognostic significance of previous falls and fractures after stroke. This study examined whether having a history of either event is associated with poststroke mortality. Methods We analyzed stroke register data collected prospectively between 2003 and 2015. Eight sex-specific models were analyzed, to which the following variables were incrementally added to examine their potential confounding effects: age, type of stroke, Oxfordshire Community Stroke Project classification, previous comorbidities, frailty as indicated by the prestroke modified Rankin Scale score, and acute illness parameters. Logistic regression was applied to investigate in-hospital and 30-day mortality, and Cox proportional-hazards models were applied to investigate longer-term outcomes of mortality. Results In total, 10,477 patients with stroke (86.1% ischemic) were included in the analysis. They were aged 77.7±11.9 years (mean±SD), and 52.2% were women. A history of falls was present in 8.6% of the men (n=430) and 20.2% of the women (n=1,105), while 3.8% (n=189) of the men and 12.9% of the women (n=706) had a history of both falls and fractures. Of the outcomes examined, a history of falls alone was associated with increased in-hospital mortality [odds ratio (OR)=1.33, 95% confidence interval (CI)=1.03–1.71] and 30-day mortality (OR=1.34, 95% CI=1.03–1.73) in women in the fully adjusted models. The Cox proportional-hazards models for longer-term outcomes and the history of falls and fractures combined showed no significant results. Conclusions The history of falls is an important factor for acute stroke mortality in women. A previous history of falls may therefore be an important factor to consider in the short-term stroke prognosis, particularly in women.

Bioactive glasses and electrospun composites that release cobalt to stimulate the HIF pathway for wound healing applications

Anu K. Solanki,Ferdinand V. Lali,Hélène Autefage,Shweta Agarwal,Amy Nommeots-Nomm,Anthony D. Metcalfe,Molly M. Stevens,Julian R. Jones 한국생체재료학회 2021 생체재료학회지 Vol.25 No.1

Background: Bioactive glasses are traditionally associated with bonding to bone through a hydroxycarbonate apatite (HCA) surface layer but the release of active ions is more important for bone regeneration. They are now being used to deliver ions for soft tissue applications, particularly wound healing. Cobalt is known to simulate hypoxia and provoke angiogenesis. The aim here was to develop new bioactive glass compositions designed to be scaffold materials to locally deliver pro-angiogenic cobalt ions, at a controlled rate, without forming an HCA layer, for wound healing applications. Methods: New melt-derived bioactive glass compositions were designed that had the same network connectivity (mean number of bridging covalent bonds between silica tetrahedra), and therefore similar biodegradation rate, as the original 45S5 Bioglass. The amount of magnesium and cobalt in the glass was varied, with the aim of reducing or removing calcium and phosphate from the compositions. Electrospun poly(ε-caprolactone)/bioactive glass composites were also produced. Glasses were tested for ion release in dissolution studies and their influence on Hypoxia-Inducible Factor 1-alpha (HIF-1α) and expression of Vascular Endothelial Growth Factor (VEGF) from fibroblast cells was investigated. Results: Dissolution tests showed the silica rich layer differed depending on the amount of MgO in the glass, which influenced the delivery of cobalt. The electrospun composites delivered a more sustained ion release relative to glass particles alone. Exposing fibroblasts to conditioned media from these composites did not cause a detrimental effect on metabolic activity but glasses containing cobalt did stabilise HIF-1α and provoked a significantly higher expression of VEGF (not seen in Co-free controls). Conclusions: The composite fibres containing new bioactive glass compositions delivered cobalt ions at a sustained rate, which could be mediated by the magnesium content of the glass. The dissolution products stabilised HIF-1α and provoked a significantly higher expression of VEGF, suggesting the composites activated the HIF pathway to stimulate angiogenesis.