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

Coregulated human globin genes are frequently in spatial proximity when active

The organization of genes within the nucleus may influence transcription. We have analyzed the nuclear positioning of the coordinately regulated α- and β-globin genes and show that the gene-dense chromatin surrounding the human α-globin genes is frequently decondensed, independent of transcription. Against this background, we show the frequent juxtaposition of active α- and β-globin genes and of homologous α-globin loci that occurs at nuclear speckles and correlates with transcription. However, we did not see increased colocalization of signals, which would be expected with direct physical interaction. The same degree of proximity does not occur between human β-globin genes or between murine globin genes, which are more constrained to their chromosome territories. Our findings suggest that the distribution of globin genes within erythroblast nuclei is the result of a self-organizing process, involving transcriptional status, diffusional ability of chromatin, and physical interactions with nuclear proteins, rather than a directed form of higher-order control

Do sustainability measures constrain urban design creativity?

Planners, architects, urban designers and other built environment professionals engage with a myriad of checkboxes, guidelines, requirements and specifications, all of which potentially compromise creativity and innovation in urban design. Approaches that measure performance are accused of belying the nature of places as messy, plural, organic, accidental and emotive; trying to find a formula that works may tick boxes, but it risks creating soulless spaces, oppressing innovation and incorporation of inappropriate design elements. This paper argues that sustainability assessment methods do have something to contribute to creativity and innovation in urban design precisely because they encourage engagement with challenging and often complex societal priorities. Through interviews with built environment professionals and a critical examination of sustainability assessment methods, the authors suggest that such methods can promote creativity and innovation if they engage competently with sustainability, work at a scale that allows for both breadth and depth (typically greater than the building scale) and incorporate in their design a set of eight key characteristics designed to promote creativity and innovation. </jats:p

Indigenous knowledges and development: a postcolonial caution

As a result of the failure of formal top-down development, there has recently been increased interest in the possibilities of drawing upon the indigenous knowledges of those in the communities involved, in an attempt to produce more effective development strategies. The concept of indigenous knowledge calls for the inclusion of local voices and priorities, and promises empowerment through ownership of the process. However, there has been little critical examination of the ways in which indigenous knowledges have been included in the development process. Drawing upon postcolonial theory, this article suggests that indigenous knowledges are often drawn into development by both theorists and development institutions in a very limited way, failing to engage with other ways of perceiving development, and thus missing the possibility of devising more challenging alternatives

A mixed-method investigation of patient monitoring and enhanced feedback in routine practice: Barriers and facilitators

Objective: To investigate the barriers and facilitators of an effective implementation of an outcome monitoring and feedback system in a UK National Health Service psychological therapy service. Method: An outcome monitoring system was introduced in two services. Enhanced feedback was given to therapists after session 4. Qualitative and quantitative methods were used, including questionnaires for therapists and patients. Thematic analysis was carried out on written and verbal feedback from therapists. Analysis of patient outcomes for 202 episodes of therapy was compared with benchmark data of 136 episodes of therapy for which feedback was not given to therapists. Results: Themes influencing the feasibility and acceptability of the feedback system were the extent to which therapists integrated the measures and feedback into the therapy, availability of administrative support, information technology, and complexity of the service. There were low levels of therapist actions resulting from the feedback, including discussing the feedback in supervision and with patients. Conclusions: The findings support the feasibility and acceptability of setting up a routine system in a complex service, but a number of challenges and barriers have to be overcome and therapist differences are apparent. More research on implementation and effectiveness is needed in diverse clinical settings

RUNX1 is a driver of renal cell carcinoma correlating with clinical outcome

The recurring association of specific genetic lesions with particular types of cancer is a fascinating, and largely unexplained area of cancer biology. This is particularly true of clear cell renal cell carcinoma (ccRCC) where although key mutations such as loss of VHL is an almost ubiquitous finding, there remains a conspicuous lack of targetable genetic drivers. In this study, we have identified a previously unknown pro-tumorigenic role for the RUNX genes in this disease setting. Analysis of patient tumor biopsies together with loss of function studies in preclinical models established the importance of RUNX1 and RUNX2 in ccRCC. Patients with high RUNX1 (and RUNX2) expression exhibited significantly poorer clinical survival compared to patients with low expression. This was functionally relevant as deletion of RUNX1 in ccRCC cell lines reduced tumor cell growth and viability in vitro and in vivo. Transcriptional profiling of RUNX1-CRISPR-deleted cells revealed a gene signature dominated by extracellular matrix remodelling, notably affecting STMN3, SERPINH1, and EPHRIN signaling. Finally, RUNX1 deletion in a genetic mouse model of kidney cancer improved overall survival and reduced tumor cell proliferation. In summary, these data attest to the validity of targeting a RUNX1-transcriptional program in ccRCC. [Abstract copyright: Copyright ©2020, American Association for Cancer Research.

Delivering a multi-functional and resilient urban forest

Tree planting is widely advocated and applied in urban areas, with large-scaleprojects underway in cities globally. Numerous potential benefits are used to justify these planting campaigns. However, reports of poor tree survival raise questions about the ability of such projects to deliver on their promises over the long-term. Each potential benefit requires different supporting conditions—relating not only to the type and placement of the tree, but also to the broader urban system within which it is embedded. This set of supportingconditions may not always be mutually compatible and may not persist for the lifetime of the tree. Here, we demonstrate a systems-based approach that makes these dependencies, synergies, and tensions more explicit, allowing them to be used to test the decadal-scale resilience of urban street trees. Our analysis highlights social, environmental, and economic assumptions that are implicit within planting projects; notably that high levels of maintenance and public support for urban street trees will persist throughout their natural lifespan, andthat the surrounding built form will remain largely unchanged. Whilst the vulnerability of each benefit may be highly context specific, we identify approaches that address some typical weaknesses, making a functional, resilient, urban forest more attainable.

US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report

This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference

Weight-loss and exercise for communities with arthritis in North Carolina (we-can): design and rationale of a pragmatic, assessor-blinded, randomized controlled trial

Background: Recently, we determined that in a rigorously monitored environment an intensive diet-induced weight loss of 10% combined with exercise was significantly more effective at reducing pain in men and women with symptomatic knee osteoarthritis (OA) than either intervention alone. Compared to previous long-term weight loss and exercise trials of knee OA, our intensive diet-induced weight loss and exercise intervention was twice as effective at reducing pain intensity. Whether these results can be generalized to less intensively monitored cohorts is unknown. Thus, the policy relevant and clinically important question is: Can we adapt this successful solution to a pervasive public health problem in real-world clinical and community settings? This study aims to develop a systematic, practical, cost-effective diet-induced weight loss and exercise intervention implemented in community settings and to determine its effectiveness in reducing pain and improving other clinical outcomes in persons with knee OA. Methods/Design: This is a Phase III, pragmatic, assessor-blinded, randomized controlled trial. Participants will include 820 ambulatory, community-dwelling, overweight and obese (BMI ≥ 27 kg/m2) men and women aged ≥ 50 years who meet the American College of Rheumatology clinical criteria for knee OA. The primary aim is to determine whether a community-based 18-month diet-induced weight loss and exercise intervention based on social cognitive theory and implemented in three North Carolina counties with diverse residential (from urban to rural) and socioeconomic composition significantly decreases knee pain in overweight and obese adults with knee OA relative to a nutrition and health attention control group. Secondary aims will determine whether this intervention improves self-reported function, health-related quality of life, mobility, and is cost-effective. Discussion: Many physicians who treat people with knee OA have no practical means to implement weight loss and exercise treatments as recommended by numerous OA treatment guidelines. This study will establish the effectiveness of a community program that will serve as a blueprint and exemplar for clinicians and public health officials in urban and rural communities to implement a diet-induced weight loss and exercise program designed to reduce knee pain and improve other clinical outcomes in overweight and obese adults with knee OA

Intergenic Transcription, Cell-Cycle and the Developmentally Regulated Epigenetic Profile of the Human Beta-Globin Locus

Several lines of evidence have established strong links between transcriptional activity and specific post-translation modifications of histones. Here we show using RNA FISH that in erythroid cells, intergenic transcription in the human β-globin locus occurs over a region of greater than 250 kb including several genes in the nearby olfactory receptor gene cluster. This entire region is transcribed during S phase of the cell cycle. However, within this region there are ∼20 kb sub-domains of high intergenic transcription that occurs outside of S phase. These sub-domains are developmentally regulated and enriched with high levels of active modifications primarily to histone H3. The sub-domains correspond to the β-globin locus control region, which is active at all developmental stages in erythroid cells, and the region flanking the developmentally regulated, active globin genes. These results correlate high levels of non-S phase intergenic transcription with domain-wide active histone modifications to histone H3