Editorial : environmental governance of urban and regional development – scales and sectors, conflict and cooperation

Recent years have continued to see a concern for the detrimental environmental impacts of human economic activities particularly in the form of enhanced global warming, sea level rise, land degradation and deforestation. Although it can be argued that economic development and growth remain the priority for governments at a variety of spatial scales or levels, these same governments also express a desire through a growing number of policy initiatives to make such development more sustainable and environmentally-friendly. A growing interest amongst policy makers has been in identifying the ways in which environmental protection measures can be made complementary to economic development aims. Rather than seeing the environment and the economy in opposition, there has been a focus on the growth potential from developing a green or low-carbon economy (OECD, 2011). At the urban and regional scale governments have increasingly begun to try and position themselves as destinations for new forms of green economy investments as a source of a new round of capital accumulation (GIBBS and O’NEILL, 2014). In total then, questions around the environment, climate change and sustainability look set to grow in importance for decision makers in cities and regions

Fibroblast-like synoviocytes orchestrate daily rhythmic inflammation in arthritis

Rheumatoid arthritis is a chronic inflammatory disease that shows characteristic diurnal variation in symptom severity, where joint resident fibroblast-like synoviocytes (FLS) act as important mediators of arthritis pathology. We investigate the role of FLS circadian clock function in directing rhythmic joint inflammation in a murine model of inflammatory arthritis. We demonstrate FLS time-of-day-dependent gene expression is attenuated in arthritic joints, except for a subset of disease-modifying genes. The deletion of essential clock gene Bmal1 in FLS reduced susceptibility to collagen-induced arthritis but did not impact symptomatic severity in affected mice. Notably, FLS Bmal1 deletion resulted in loss of diurnal expression of disease-modulating genes across the joint, and elevated production of MMP3, a prognostic marker of joint damage in inflammatory arthritis. This work identifies the FLS circadian clock as an influential driver of daily oscillations in joint inflammation, and a potential regulator of destructive pathology in chronic inflammatory arthritis

Epistasis between 5-HTTLPR and ADRA2B polymorphisms influences attentional bias for emotional information in healthy volunteers

Individual differences in emotional processing are likely to contribute to vulnerability and resilience to emotional disorders such as depression and anxiety. Genetic variation is known to contribute to these differences but they remain incompletely understood. The serotonin transporter (5-HTTLPR) and alpha(2B)-adrenergic autoreceptor (ADRA2B) insertion/deletion polymorphisms impact on two separate but interacting monaminergic signalling mechanisms that have been implicated in both emotional processing and emotional disorders. Recent studies suggest that the 5-HTTLPR s allele is associated with a negative attentional bias and an increased risk of emotional disorders. However, such complex behavioural traits are likely to exhibit polygenicity, including epistasis. This study examined the contribution of the 5-HTTLPR and ADRA2B insertion/deletion polymorphisms to attentional biases for aversive information in 94 healthy male volunteers and found evidence of a significant epistatic effect (p < 0.001). Specifically, in the presence of the 5-HTTLPR s allele, the attentional bias for aversive information was attenuated by possession of the ADRA2B deletion variant whereas in the absence of the s allele, the bias was enhanced. These data identify a cognitive mechanism linking genotype-dependent serotonergic and noradrenergic signalling that is likely to have implications for the development of cognitive markers for depression/anxiety as well as therapeutic drug effects and personalized approaches to treatment

Prevalence of liver fluke (Fasciola hepatica) in wild Red Deer (Cervus elaphus): coproantigen ELISA is a practicable alternative to faecal egg counting for surveillance in remote populations

Red deer (Cervus elaphus) are hosts of liver fluke (Fasciola hepatica); yet, prevalence is rarely quantified in wild populations. Testing fresh samples from remote regions by faecal examination (FE) can be logistically challenging; hence, we appraise frozen storage and the use of a coproantigen ELISA (cELISA) for F. hepatica surveillance. We also present cELISA surveillance data for red deer from the Highlands of Scotland. Diagnoses in faecal samples (207 frozen, 146 fresh) were compared using a cELISA and by FE. For each storage method (frozen or fresh), agreement between the two diagnostics was estimated at individual and population levels, where population prevalence was stratified into cohorts (e.g., by sampling location). To approximate sensitivity and specificity, 65 post-slaughter whole liver examinations were used as a reference. At the individual level, FE and cELISA diagnoses agreed moderately (κfrozen = 0.46; κfresh = 0.51), a likely reflection of their underlying principles. At the population level, FE and cELISA cohort prevalence correlated strongly (Pearson’s R = 0.89, p &lt; 0.0001), reflecting good agreement on relative differences between cohort prevalence. In frozen samples, prevalence by cELISA exceeded FE overall (42.8% vs. 25.8%) and in 9/12 cohorts, alluding to differences in sensitivity; though, in fresh samples, no significant difference was found. In 959 deer tested by cELISA across the Scottish Highlands, infection prevalence ranged from 9.6% to 53% by sampling location. We highlight two key advantages of cELISA over FE: i) the ability to store samples long term (frozen) without apparent loss in diagnostic power; and ii) reduced labour and the ability to process large batches. Further evaluation of cELISA sensitivity in red deer, where a range of fluke burdens can be obtained, is desirable. In the interim, the cELISA is a practicable diagnostic for F. hepatica surveillance in red deer, and its application here has revealed considerable geographic, temporal, sex and age related differences in F. hepatica prevalence in wild Scottish Highland red deer

A multi-label, dual-output deep neural network for automated bug triaging

Bug tracking enables the monitoring and resolution of issues and bugs within organizations. Bug triaging, or assigning bugs to the owner(s) who will resolve them, is a critical component of this process because there are many incorrect assignments that waste developer time and reduce bug resolution throughput. In this work, we explore the use of a novel two-output deep neural network architecture (Dual DNN) for triaging a bug to both an individual team and developer, simultaneously. Dual DNN leverages this simultaneous prediction by exploiting its own guess of the team classes to aid in developer assignment. A multi-label classification approach is used for each of the two outputs to learn from all interim owners, not just the last one who closed the bug. We make use of a heuristic combination of the interim owners (owner-importance-weighted labeling) which is converted into a probability mass function (pmf). We employ a two-stage learning scheme, whereby the team portion of the model is trained first and then held static to train the team--developer and bug--developer relationships. The scheme employed to encode the team--developer relationships is based on an organizational chart (org chart), which renders the model robust to organizational changes as it can adapt to role changes within an organization. There is an observed average lift (with respect to both team and developer assignment) of 13%-points in 11-fold incremental-learning cross-validation (IL-CV) accuracy for Dual DNN utilizing owner-weighted labels compared with the traditional multi-class classification approach. Furthermore, Dual DNN with owner-weighted labels achieves average 11-fold IL-CV accuracies of 76% (team assignment) and 55% (developer assignment), outperforming reference models by 14%- and 25%-points, respectively, on a proprietary dataset with 236,865 entries.Comment: 8 pages, 2 figures, 9 table

A Proposal for Stewardship Support to Private Native Forests in NSW

The Southern Cross Group is proposing a completely new approach to private forest management in NSW based on stewardship support. This means that incentives will be used to encourage landholders to manage their forests in a way that maintains their environmental and other values for the community, without compromising their value as a resource to the farming community. Importantly, the Southern Cross Group system will foster good outcomes through innovation rather than through cumbersome and onerous prescriptions. Private forests in NSW are important as a source of timber as well as for the conservation values they provide to the general community. Landholders should be encouraged to manage them in a way that preserves their productive capacity and their conservation values for the long term. At present, however, neither the current regulatory regime, including the Private Native Forest legislation and proposed code of practice, nor the current market regime encourages sustainable management of the State's private timber resources. The Southern Cross Group has designed an effective and simple way of fostering and rewarding good stewardship of private native forests. Good stewardship may be viewed as a 'duty of care' responsibility that should be enforced by legislation, or as an environmental service that should be recognised and rewarded. The distinction is academic: the reality is that incentives are more effective than punitive regulations. Good environmental outcomes for most forests depend on active management and, especially in the case of private native forests, on incentives for continuing management. The challenge is to devise an equitable scheme that sends the right signals for forest management, is cost-effective to administer, and represents a worthwhile investment in terms of the public good generated. We believe the way forward is with simple, transparent indicators that provide an immediate and ongoing incentive. Under our proposal, landholders will receive an annual cash payment as a reward for progress towards specific outcomes. Rather than complicated targets, we are proposing a simple, two-tiered system that will give enough incentive to landholders to provide the environmental services desired by the community. The first tier rewards and encourages landholders to regenerate more forest, to retain big trees, and to stimulate tree growth on private land. The second tier rewards and encourages stewardship of endangered species and ecological communities. These incentives will be simple to apply and audit, and will encourage landholders to learn about and encourage biodiversity on their land, and to consider it part of their income portfolio. This system will contribute to farmers seeing forests as core business, both as part of their income stream and as part of their environmental stewardship responsibilities. When all farmers view forests in this way, Australia will reap the benefit of forests that are more diverse and productive, and a forest estate that no longer continues to shrink

Experimental Feedback Control of Flow Induced Cavity Tones

Discrete-time, linear quadratic methods were used to design feedback controllers for reducing tones generated by flow over a cavity. The dynamics of a synthetic jet actuator mounted at the leading edge of the cavity as observed by two microphones in the cavity were modeled over a broad frequency range using state space models computed from experimental data. Variations in closed loop performance as a function of model order, control order, control bandwidth, and state estimator design were studied using a cavity in the Probe Calibration Tunnel at NASA Langley. The controller successfully reduced the levels of multiple cavity tones at the tested flow speeds of Mach 0.275, 0.35, and 0.45. In some cases, the closed loop results were limited by excitation of sidebands of the cavity tones, or the creation of new tones at frequencies away from the cavity tones. Nonetheless, the results validate the combination of optimal control and experimentally-generated state space models, and suggest this approach may be useful for other flow control problems. The models were not able to account for non-linear dynamics, such as interactions between tones at different frequencies

Impact of Common Vitamin D-Binding Protein Isoforms on Supplemental Vitamin D3 and/or Calcium Effects on Colorectal Adenoma Recurrence Risk: A Secondary Analysis of a Randomized Clinical Trial

IMPORTANCE: Variants in the vitamin D-binding protein (DBP) gene (GC) encode DBP isoforms that may affect vitamin D metabolism. However, whether these isoforms modify the effects of vitamin D3 and/or calcium supplementation on colorectal adenoma recurrence is unclear. We hypothesized that supplementation effects may be stronger among those with the DBP2 isoform (encoded by the rs4588*A allele), which is associated with vitamin D deficiency and modified the associations of circulating vitamin D with risk for colorectal neoplasms in observational studies. OBJECTIVE: To estimate supplemental vitamin D3 and/or calcium effects on colorectal adenoma recurrence according to 3 common DBP isoforms (DBP1s, DBP1f, DBP2) encoded by 2 missense variants: rs7041 (NG_012837.3:g.57904T\u3eG NP_001191235.1:p.Asp432Glu) and rs4588 (NG_012837.3:g.57915C\u3eA NP_001191235.1:p.Thr436Lys). DESIGN, SETTING, AND PARTICIPANTS: Secondary analysis of a randomized, double-blind, placebo-controlled clinical trial of 2259 participants with a recently diagnosed adenoma and no remaining polyps after complete colonoscopy in the US from July 1, 2004, to August 31, 2013. The current analyses were performed from August 12, 2019, to July 16, 2022. INTERVENTIONS: Daily vitamin D3 (1000 IU), calcium (1200 mg), both, or placebo. MAIN OUTCOMES AND MEASURES: One or more adenomas diagnosed during 3 to 5 years of follow-up. Treatment effects were estimated according to DBP isoform as risk ratios (RRs) and 95% CIs using Poisson regression analysis. RESULTS: Of the 2259 participants randomized (mean [SD] age, 58 [6.8] years; 1033 [64%] men), 1604 non-Hispanic White participants (chosen to avoid population stratification bias) were included in the analysis. Among those with the DBP2 isoform (rs4588*AC or AA), the RRs (95% CI) for adenoma recurrence were 0.84 (0.72-1.00) with vitamin D3 relative to no vitamin D3, 0.83 (95% CI, 0.70-0.99) with calcium relative to no calcium, and 0.76 (95% CI, 0.59-0.98) with both agents relative to neither agent. Conversely, among those without DBP2 (rs4588*CC), the corresponding values were 1.08 (95% CI, 0.93-1.26; P = .03 for interaction) with vitamin D3 relative to no vitamin D3, 0.98 (95% CI, 0.84-1.14; P = .37 for interaction) with calcium relative to no calcium, and 1.09 (0.88-1.36; P = .03 for interaction) with both agents relative to neither agent. Among DBP2 homozygotes (rs4588*AA), the RR for adenoma recurrence was 0.57 (95% CI, 0.31-1.08) with both agents relative to neither agent. CONCLUSIONS AND RELEVANCE: The findings of this secondary analysis of a randomized clinical trial suggest that individuals with the DBP2 isoform-encoding rs4588*A allele may particularly benefit from vitamin D3 and/or calcium supplementation for colorectal adenoma prevention. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00153816