Delivering sustainable, resilient and liveable cities via transformed governance

In the context of steadily declining Natural Capital and universal recognition of the imperative to reverse this trend before we get to the point that nature is not able to restore itself, cities have a crucial role to play. The UK Government commissioned a comprehensive study into the value of biodiversity, and by extension nature, reinforcing “why we should change our ways”—yet what is missing is the “how?”. This paper uniquely describes both the “how?” and a conclusive demonstration of the remarkable benefits of implementing it in a city. Critical to this process, it took a UK Parliamentary Inquiry to reveal that nature has become invisible within the economy, yet the ecological ecosystem services nature provides have enormous benefits to both people and the economy. Therefore integration—or seamless weaving—of urban greenspace and nature into people's lives and the places where they live, work, and spend their leisure time is vital. Moreover, what nature does not provide must be provided by engineered systems, and these have an economic cost; put another way, there are enormous cost savings to be made by taking advantage of what nature provides. In addressing these issues, this paper is the definitive paper from a 20-year portfolio of research on how to bring about transformative change in the complex system-of-systems that make up our cities, providing as it does the crucial in-depth research into the many diverse strands of governance—the last link in a chain of the creation, testing and proof of efficacy of methodologies underpinning a theory and practice of change for infrastructure and cities. The impact of this portfolio of research on Birmingham is two-fold: the Star Framework that placed natural environment considerations at the heart of all decision-making in the city, and the successful bid for the largest of the UK Future Parks Accelerator awards. While both are transformative in their different ways, yet mutually supportive, the latter enabled the design of a suite of system interventions from which the value of Birmingham's greenspaces is estimated to rise from £11.0 billion to £14.4 billion—a remarkable return on investment from the research's conceptualization of Birmingham's urban greenspace as a “business” (with its associated business models). In achieving this, the necessary enablers of thinking and practicing systemically, seamlessly working across disciplinary boundaries, an unusually strong focus on both the aspirations of all stakeholders and the context in question to define “the problem,” and the testing of proposed system intervention(s) both now and in the future have been iteratively combined. However, it is the critical enabling steps of identifying the complete range of value-generating opportunities that the interventions offer, formulating them into alternative business models to underpin the case for change and ensuring that they are synergistic with all the dimensions of governance that yielded the profound outcomes sought

The Australia Telescope 20 GHz (AT20G) Survey: The Bright Source Sample

The Australia Telescope 20 GHz (AT20G) Survey is a blind survey of the whole Southern sky at 20 GHz (with follow-up observations at 4.8 and 8.6 GHz) carried out with the Australia Telescope Compact Array (ATCA) from 2004 to 2007. The Bright Source Sample (BSS) is a complete flux-limited subsample of the AT20G Survey catalogue comprising 320 extragalactic (|b|>1.5 deg) radio sources south of dec = -15 deg with S(20 GHz) > 0.50 Jy. Of these, 218 have near simultaneous observations at 8 and 5 GHz. In this paper we present an analysis of radio spectral properties in total intensity and polarisation, size, optical identifications and redshift distribution of the BSS sources. The analysis of the spectral behaviour shows spectral curvature in most sources with spectral steepening that increases at higher frequencies (the median spectral index \alpha, assuming S\propto \nu^\alpha, decreases from \alpha_{4.8}^{8.6}=0.11 between 4.8 and 8.6 GHz to \alpha_{8.6}^{20}=-0.16 between 8.6 and 20 GHz), even if the sample is dominated by flat spectra sources (85 per cent of the sample has \alpha_{8.6}^{20}>-0.5). The almost simultaneous spectra in total intensity and polarisation allowed us a comparison of the polarised and total intensity spectra: polarised fraction slightly increases with frequency, but the shapes of the spectra have little correlation. Optical identifications provided an estimation of redshift for 186 sources with a median value of 1.20 and 0.13 respectively for QSO and galaxies.Comment: 34 pages, 19 figures, tables of data included, replaced with version published in MNRA

Development of a mechanism to facilitate the safety stock planning configuration in ERP

Safety stock planning in ERP in general is dependent upon the planner having the experience to simulate planning scenarios. This paper focuses on the development of a mechanism to calculate adequate safety stocks in accordance with required service levels while enabling efficient configuration of the ERP safety stock parameters. The proposed mechanism could be of great benefit to industrial firms as it offers the ability to classify demand patterns, proposes replenishment strategies that are consistent with the demand profile, calculates key parameters and identifies the changes required to the ERP master data. The associated real world application is able to identify potential to save approximately £1.2 M in stock reductions and, more importantly, allows targeted actions to be implemented at material level. These results demonstrated that the proposed mechanism can be considered as a valuable new development for manufacturing industry to gain the competitive advantage

HST NIR Snapshot Survey of 3CR Radio Source Counterparts II: An Atlas and Inventory of the Host Galaxies, Mergers and Companions

We present the second part of an H-band (1.6 microns) atlas of z<0.3 3CR radio galaxies, using the Hubble Space Telescope Near Infrared Camera and Multi-Object Spectrometer (HST NICMOS2). We present new imaging for 21 recently acquired sources, and host galaxy modeling for the full sample of 101 (including 11 archival) -- an 87% completion rate. Two different modeling techniques are applied, following those adopted by the galaxy morphology and the quasar host galaxy communities. Results are compared, and found to be in excellent agreement, although the former breaks down in the case of strongly nucleated sources. Companion sources are tabulated, and the presence of mergers, tidal features, dust disks and jets are catalogued. The tables form a catalogue for those interested in the structural and morphological dust-free host galaxy properties of the 3CR sample, and for comparison with morphological studies of quiescent galaxies and quasar host galaxies. Host galaxy masses are estimated, and found to typically lie at around 2*10^11 solar masses. In general, the population is found to be consistent with the local population of quiescent elliptical galaxies, but with a longer tail to low Sersic index, mainly consisting of low-redshift (z<0.1) and low-radio-power (FR I) sources. A few unusually disky FR II host galaxies are picked out for further discussion. Nearby external sources are identified in the majority of our images, many of which we argue are likely to be companion galaxies or merger remnants. The reduced NICMOS data are now publicly available from our website (http://archive.stsci.edu/prepds/3cr/)Comment: ApJS, 177, 148: Final version; includes revised figures 1, 15b, and section 7.5 (and other minor changes from editing process. 65 pages, inc. 17 figure

A facilitated home-based cardiac rehabilitation intervention for people with heart failure and their caregivers:a research programme including the REACH-HF RCT

Background: Rates of participation in centre (hospital)-cardiac rehabilitation by patients with heart failure are suboptimal. Heart failure has two main phenotypes differing in underlying pathophysiology: Heart failure with reduced ejection fraction is characterised by depressed left ventricular systolic function (‘reduced ejection fraction’), whereas heart failure with preserved ejection fraction is diagnosed after excluding other causes of dyspnoea with normal ejection fraction. This programme aimed to develop and evaluate a facilitated home-based cardiac rehabilitation intervention that could increase the uptake of cardiac rehabilitation while delivering the clinical benefits of centre-based cardiac rehabilitation. Objectives: To develop an evidence-informed, home-based, self-care cardiac rehabilitation programme for patients with heart failure and their caregivers [the REACH-HF (Rehabilitation Enablement in Chronic Heart Failure) intervention]. To conduct a pilot randomised controlled trial to assess the feasibility of a full trial of the clinical effectiveness and cost-effectiveness of the REACH-HF intervention in addition to usual care in patients with heart failure with preserved ejection fraction. To assess the short- and long-term clinical effectiveness and cost-effectiveness of the REACH-HF intervention in addition to usual care in patients with heart failure with reduced ejection fraction and their caregivers. Design: Intervention mapping to develop the REACH-HF intervention; uncontrolled feasibility study; pilot randomised controlled trial in those with heart failure with preserved ejection fraction; randomised controlled trial with a trial-based cost-effectiveness analysis in those with heart failure with reduced ejection fraction; qualitative studies including process evaluation; systematic review of cardiac rehabilitation in heart failure; and modelling to assess long-term cost-effectiveness (in those with heart failure with reduced ejection fraction). Setting: Four centres in England and Wales (Birmingham, Cornwall, Gwent and York); one centre in Scotland (Dundee) for a pilot randomised controlled trial. Participants: Adults aged ≥ 18 years with heart failure with reduced ejection fraction (left ventricular ejection fraction &lt; 45%) for the main randomised controlled trial (n = 216), and those with heart failure with preserved ejection fraction (left ventricular ejection fraction ≥ 45%) for the pilot randomised controlled trial (n = 50). Intervention: A self-care, facilitated cardiac rehabilitation manual was offered to patients (and participating caregivers) at home over 12 weeks by trained health-care professionals in addition to usual care or usual care alone. Main outcome measures: The primary outcome was disease-specific health-related quality of life measured using the Minnesota Living with Heart Failure Questionnaire at 12 months. Secondary outcomes included deaths and hospitalisations. Results: The main randomised controlled trial recruited 216 participants with heart failure with reduced ejection fraction and 97 caregivers. A significant and clinically meaningful between-group difference in the Minnesota Living with Heart Failure Questionnaire score (primary outcome) at 12 months (–5.7 points, 95% confidence interval –10.6 to –0.7 points) favoured the REACH-HF intervention (p = 0.025). Eight (4%) patients (four in each group) had died at 12 months. There was no significant difference in hospital admissions, at 12 months, with 19 participants in the REACH-HF intervention group having at least one hospital admission, compared with 24 participants in the control group (odds ratio 0.72, 95% confidence interval 0.35 to 1.51; p = 0.386). The mean cost of the intervention was £418 per participant with heart failure with reduced ejection fraction. The costs at 12 months were, on average, £401 higher in the intervention group than in the usual care alone group. Model-based economic evaluation, extrapolating from the main randomised controlled trial in those with heart failure with reduced ejection fraction over 4 years, found that adding the REACH-HF intervention to usual care had an estimated mean cost per participant of £15,452 (95% confidence interval £14,240 to £16,780) and a mean quality-adjusted lifeyear gain of 4.47 (95% confidence interval 3.83 to 4.91) years, compared with £15,051 (95% confidence interval £13,844 to £16,289) and 4.24 (95% confidence interval 4.05 to 4.43) years, respectively, for usual care alone. This gave an incremental cost per quality-adjusted life-year of £1721. The probabilistic sensitivity analysis indicated 78% probability that the intervention plus usual care versus usual care alone has a cost-effectiveness below the willingness-to-pay threshold of £20,000 per quality-adjusted life-year gained. The intervention was well received by participants with heart failure with reduced ejection fraction and those with heart failure with preserved ejection fraction, as well as their caregivers. Both randomised controlled trials recruited to target, with &gt; 85% retention at follow-up. Limitations: Key limitations included (1) lack of blinding – given the nature of the intervention and the control we could not mask participants to treatments, so our results may reflect participant expectation bias; (2) that we were not able to capture consistent participant-level data on level of intervention adherence; (3) that there may be an impact on the generalisability of findings due to the demographics of the trial patients, as most were male (78%) and we recruited only seven people from ethnic minorities. Conclusions: Evaluation of the comprehensive, facilitated, home-based REACH-HF intervention for participants with heart failure with reduced ejection fraction and caregivers indicated clinical effectiveness in terms of health-related quality of life and patient self-care but no other secondary outcomes. Although the economic analysis conducted alongside the full randomised controlled trial did not produce significant differences on the EuroQol-5 Dimensions or in quality-adjusted life-years, economic modelling suggested greater cost-effectiveness of the intervention than usual care. Our REACH-HF intervention offers a new evidence-based cardiac rehabilitation option that could increase uptake of cardiac rehabilitation in patients with heart failure not attracted to or able to access hospital-based programmes. Future work: Systematic collection of real-world data would track future changes in uptake of and adherence to alternative cardiac rehabilitation interventions in heart failure with reduced ejection fraction and increase understanding of how changes in service delivery might affect clinical and health economic outcomes. The findings of our pilot randomised controlled trial in patients with heart failure with preserved ejection fraction support progression to a full multicentre randomised controlled trial. </p

A facilitated home-based cardiac rehabilitation intervention for people with heart failure and their caregivers:a research programme including the REACH-HF RCT

Background: Rates of participation in centre (hospital)-cardiac rehabilitation by patients with heart failure are suboptimal. Heart failure has two main phenotypes differing in underlying pathophysiology: Heart failure with reduced ejection fraction is characterised by depressed left ventricular systolic function (‘reduced ejection fraction’), whereas heart failure with preserved ejection fraction is diagnosed after excluding other causes of dyspnoea with normal ejection fraction. This programme aimed to develop and evaluate a facilitated home-based cardiac rehabilitation intervention that could increase the uptake of cardiac rehabilitation while delivering the clinical benefits of centre-based cardiac rehabilitation. Objectives: To develop an evidence-informed, home-based, self-care cardiac rehabilitation programme for patients with heart failure and their caregivers [the REACH-HF (Rehabilitation Enablement in Chronic Heart Failure) intervention]. To conduct a pilot randomised controlled trial to assess the feasibility of a full trial of the clinical effectiveness and cost-effectiveness of the REACH-HF intervention in addition to usual care in patients with heart failure with preserved ejection fraction. To assess the short- and long-term clinical effectiveness and cost-effectiveness of the REACH-HF intervention in addition to usual care in patients with heart failure with reduced ejection fraction and their caregivers. Design: Intervention mapping to develop the REACH-HF intervention; uncontrolled feasibility study; pilot randomised controlled trial in those with heart failure with preserved ejection fraction; randomised controlled trial with a trial-based cost-effectiveness analysis in those with heart failure with reduced ejection fraction; qualitative studies including process evaluation; systematic review of cardiac rehabilitation in heart failure; and modelling to assess long-term cost-effectiveness (in those with heart failure with reduced ejection fraction). Setting: Four centres in England and Wales (Birmingham, Cornwall, Gwent and York); one centre in Scotland (Dundee) for a pilot randomised controlled trial. Participants: Adults aged ≥ 18 years with heart failure with reduced ejection fraction (left ventricular ejection fraction &lt; 45%) for the main randomised controlled trial (n = 216), and those with heart failure with preserved ejection fraction (left ventricular ejection fraction ≥ 45%) for the pilot randomised controlled trial (n = 50). Intervention: A self-care, facilitated cardiac rehabilitation manual was offered to patients (and participating caregivers) at home over 12 weeks by trained health-care professionals in addition to usual care or usual care alone. Main outcome measures: The primary outcome was disease-specific health-related quality of life measured using the Minnesota Living with Heart Failure Questionnaire at 12 months. Secondary outcomes included deaths and hospitalisations. Results: The main randomised controlled trial recruited 216 participants with heart failure with reduced ejection fraction and 97 caregivers. A significant and clinically meaningful between-group difference in the Minnesota Living with Heart Failure Questionnaire score (primary outcome) at 12 months (–5.7 points, 95% confidence interval –10.6 to –0.7 points) favoured the REACH-HF intervention (p = 0.025). Eight (4%) patients (four in each group) had died at 12 months. There was no significant difference in hospital admissions, at 12 months, with 19 participants in the REACH-HF intervention group having at least one hospital admission, compared with 24 participants in the control group (odds ratio 0.72, 95% confidence interval 0.35 to 1.51; p = 0.386). The mean cost of the intervention was £418 per participant with heart failure with reduced ejection fraction. The costs at 12 months were, on average, £401 higher in the intervention group than in the usual care alone group. Model-based economic evaluation, extrapolating from the main randomised controlled trial in those with heart failure with reduced ejection fraction over 4 years, found that adding the REACH-HF intervention to usual care had an estimated mean cost per participant of £15,452 (95% confidence interval £14,240 to £16,780) and a mean quality-adjusted lifeyear gain of 4.47 (95% confidence interval 3.83 to 4.91) years, compared with £15,051 (95% confidence interval £13,844 to £16,289) and 4.24 (95% confidence interval 4.05 to 4.43) years, respectively, for usual care alone. This gave an incremental cost per quality-adjusted life-year of £1721. The probabilistic sensitivity analysis indicated 78% probability that the intervention plus usual care versus usual care alone has a cost-effectiveness below the willingness-to-pay threshold of £20,000 per quality-adjusted life-year gained. The intervention was well received by participants with heart failure with reduced ejection fraction and those with heart failure with preserved ejection fraction, as well as their caregivers. Both randomised controlled trials recruited to target, with &gt; 85% retention at follow-up. Limitations: Key limitations included (1) lack of blinding – given the nature of the intervention and the control we could not mask participants to treatments, so our results may reflect participant expectation bias; (2) that we were not able to capture consistent participant-level data on level of intervention adherence; (3) that there may be an impact on the generalisability of findings due to the demographics of the trial patients, as most were male (78%) and we recruited only seven people from ethnic minorities. Conclusions: Evaluation of the comprehensive, facilitated, home-based REACH-HF intervention for participants with heart failure with reduced ejection fraction and caregivers indicated clinical effectiveness in terms of health-related quality of life and patient self-care but no other secondary outcomes. Although the economic analysis conducted alongside the full randomised controlled trial did not produce significant differences on the EuroQol-5 Dimensions or in quality-adjusted life-years, economic modelling suggested greater cost-effectiveness of the intervention than usual care. Our REACH-HF intervention offers a new evidence-based cardiac rehabilitation option that could increase uptake of cardiac rehabilitation in patients with heart failure not attracted to or able to access hospital-based programmes. Future work: Systematic collection of real-world data would track future changes in uptake of and adherence to alternative cardiac rehabilitation interventions in heart failure with reduced ejection fraction and increase understanding of how changes in service delivery might affect clinical and health economic outcomes. The findings of our pilot randomised controlled trial in patients with heart failure with preserved ejection fraction support progression to a full multicentre randomised controlled trial. </p

Correction: Metal complexes as a promising source for new antibiotics

Correction for ‘Metal complexes as a promising source for new antibiotics’ by Angelo Frei et al., Chem. Sci., 2020, 11, 2627–2639

A Randomised Controlled Trial of a Facilitated Home-Based Rehabilitation Intervention in Patients with Heart Failure with Preserved Ejection Fraction and their Caregivers:The REACH-HFpEF Pilot Study

Abstract Introduction Home-based cardiac rehabilitation may overcome suboptimal rates of participation. The overarching aim of this study was to assess the feasibility and acceptability of the novel Rehabilitation EnAblement in CHronic Hear Failure (REACH-HF) rehabilitation intervention for patients with heart failure with preserved ejection fraction (HFpEF) and their caregivers. Methods and results Patients were randomised 1:1 to REACH-HF intervention plus usual care (intervention group) or usual care alone (control group). REACH-HF is a home-based comprehensive self-management rehabilitation programme that comprises patient and carer manuals with supplementary tools, delivered by trained healthcare facilitators over a 12 week period. Patient outcomes were collected by blinded assessors at baseline, 3 months and 6 months postrandomisation and included health-related quality of life (primary) and psychological well-being, exercise capacity, physical activity and HF-related hospitalisation (secondary). Outcomes were also collected in caregivers. We enrolled 50 symptomatic patients with HF from Tayside, Scotland with a left ventricular ejection fraction ≥45% (mean age 73.9 years, 54% female, 100% white British) and 21 caregivers. Study retention (90%) and intervention uptake (92%) were excellent. At 6 months, data from 45 patients showed a potential direction of effect in favour of the intervention group, including the primary outcome of Minnesota Living with Heart Failure Questionnaire total score (between-group mean difference −11.5, 95% CI −22.8 to 0.3). A total of 11 (4 intervention, 7 control) patients experienced a hospital admission over the 6 months of follow-up with 4 (control patients) of these admissions being HF-related. Improvements were seen in a number intervention caregivers' mental health and burden compared with control. Conclusions Our findings support the feasibility and rationale for delivering the REACH-HF facilitated home-based rehabilitation intervention for patients with HFpEF and their caregivers and progression to a full multicentre randomised clinical trial to test its clinical effectiveness and cost-effectiveness

Metal complexes as a promising source for new antibiotics

There is a dire need for new antimicrobial compounds to combat the growing threat of widespread antibiotic resistance. With a currently very scarce drug pipeline, consisting mostly of derivatives of known antibiotics, new classes of antibiotics are urgently required. Metal complexes are currently in clinical development for the treatment of cancer, malaria and neurodegenerative diseases. However, only little attention has been paid to their application as potential antimicrobial compounds. We report the evaluation of 906 metal-containing compounds that have been screened by the Community for Open Antimicrobial Drug Discovery (CO-ADD) for antimicrobial activity. Metal-bearing compounds display a significantly higher hit-rate (9.9%) when compared to the purely organic molecules (0.87%) in the CO-ADD database. Out of 906 compounds, 88 show activity against at least one of the tested strains, including fungi, while not displaying any cytotoxicity against mammalian cell lines or haemolytic properties. Herein, we highlight the structures of the 30 compounds with activity against Gram-positive and/or Gram-negative bacteria containing Mn, Co, Zn, Ru, Ag, Eu, Ir and Pt, with activities down to the nanomolar range against methicillin resistant S. aureus (MRSA). 23 of these complexes have not been reported for their antimicrobial properties before. This work reveals the vast diversity that metal-containing compounds can bring to antimicrobial research. It is important to raise awareness of these types of compounds for the design of truly novel antibiotics with potential for combatting antimicrobial resistance