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This article explores the transformative potential of legal pathways and societal struggles to conserve biodiversity and achieve sustainability transformations toward multi-species justice. Exploring contemporary discourse on sustainability transformations, including emerging attention to relationality and critical perspectives, we analyse a range of legal instruments and measures to assess their transformative potential drawing upon their capacity to overcome rigid Cartesian dichotomies between humans and nature, to challenge capitalist accumulation imperatives and hence to contribute to a new societal sustainability goal of pluriversal, multi-species justice. Ranging from mainstream approaches in existing biodiversity and environmental instruments and supply chain instruments, such as environmental and deforestation due diligence, to newly emerging, more radical propositions of Rights of Nature, Ecocide and Restorative Justice, we review existing literature and empirical cases to interrogate and reflect upon their transformative potential, and to identify potentially effective combinations of socio-legal pathways.

Abstract Background No recent studies have evaluated the association between clinical signs of lower urinary tract disease (LUTD) and positive urine culture in dogs with diabetes mellitus. Objective Determine the prevalence of subclinical bacteriuria (ie, positive urine culture without signs of LUTD) in dogs with diabetes mellitus. Animals One hundred seven dogs with diabetes mellitus were evaluated at a university veterinary hospital. Methods Retrospective study evaluating diabetic dogs with a single sample paired urinalysis and urine culture. Relationship between the presence of signs of LUTD, pyuria, and bacteriuria and urine culture results were compared using Fisher exact testing. Results Fifteen dogs (14%) had a positive urine culture via cystocentesis or free catch, of which 8 (53%) had pyuria, and 4 (27%) had signs of LUTD. Of the 88 dogs (82%) without signs of LUTD, 11 (13%) had a positive culture. A significant association was found between a positive urine culture and pyuria (OR infinity; 95% CI 20.34-infinity, P < .00001) and bacteriuria (OR infinity; 95% CI 164.4-infinity, P < .00001). No association was found between urine culture results and signs of LUTD (OR 1.87; 95% CI 0.59-6.85, P = .46). Conclusion and Clinical Importance Subclinical bacteriuria occurred in this cohort of dogs, and our findings reinforce the recommendation that urine cultures should not be routinely performed in diabetic dogs particularly if pyuria and bacteriuria are absent.

BackgroundResponse rates to single agent immune checkpoint blockade in unselected pretreated HER2−negative metastatic breast cancer (MBC) are low. However, they may be augmented when combined with chemotherapy.MethodsWe conducted a single-arm, phase II study of patients with triple negative (TN) or hormone receptor-positive endocrine-refractory (HR+) MBC who were candidates for capecitabine. Patients were treated with pembrolizumab 200 mg intravenously day 1 and capecitabine 1000 mg/m2 by mouth twice daily on days 1–14 of a 21-day cycle. The primary end point was median progression-free survival (mPFS) compared with historic controls and secondary end points were overall response rate (ORR), safety and tolerability. The study had 80% power to detect a 2-month improvement in mPFS with the addition of pembrolizumab over historic controls treated with capecitabine alone.ResultsThirty patients, 16 TN and 14 HR+ MBC, were enrolled from 2017 to 2018. Patients had a median age of 51 years and received a median of 1 (range 0–6) prior lines of therapy for MBC. Of 29 evaluable patients, the mPFS was 4.0 (95% CI 2.0 to 6.4) months and was not significantly longer than historic controls of 3 months. The median overall survival was 15.4 (95% CI 8.2 to 20.3) months. The ORR was 14% (n=4), stable disease (SD) was 41% (n=12) and clinical benefit rate (CBR=partial response+SD>6 months) was 28% (n=8). The ORR and CBR were not significantly different between disease subtypes (ORR 13% and 14%, CBR 25% and 29% for TN and HR+, respectively). The 1-year PFS rate was 20.7% and three patients have ongoing responses. The most common adverse events were low grade and consistent with those seen in MBC patients receiving capecitabine, including hand-foot syndrome, gastrointestinal symptoms, fatigue and cytopenias. Toxicities at least possibly from pembrolizumab included grade 3 or 4 liver test abnormalities (7%), rash (7%) and diarrhea (3%), as well as grade 5 hepatic failure in a patient with liver metastases.ConclusionsCompared with historical controls, pembrolizumab with capecitabine did not improve PFS in this biomarker unselected, pretreated cohort. However, some patients had prolonged disease control.Trial registration number NCT03044730.

Tropical forests are rapidly disappearing due to the expansion of cash crops to meet demands from distant markets. Pressing concerns on deforestation impacts resulting from the global trade of tropical commodities have led some high-income countries’ governments to consider diverse regulatory and trade levers to tackle the problem. These include proposals for new supply chain due diligence legislation concerning imports of forest-risk products and the inclusion of environmental measures in trade deals. To contribute to this debate, we conducted a comprehensive analysis of existing data on global trade and consumption patterns of tropical commodities, attribution of commodity production to deforestation, trade agreements, and progress in the implementation of crop sustainability standards. We used global data on key tropical commodities of oil palm, cocoa, and coffee. Our study shows that high-income countries have the highest per capita consumption for the three commodities evaluated and that consumption rates have dramatically increased in the last two decades. We discuss a range of measures that can potentially be required to tackle deforestation in global supply chains, which are currently being considered by policymakers, before discussing the kinds of post-growth, convivial approaches that are often excluded by the framing. Given the inherent expansionary nature of global market dynamics, we show that market-based initiatives are inadequate to tackle continuing deforestation and socio-ecological degradation. More transformative solutions amplify commoning and post-growth approaches are required to lead to some uncoupling of trade and territorialising of economic activity to fit within planetary boundaries and allow for plural values.

The discovery of epidermal growth-factor receptor (EGFR)-activating mutations and the introduction of oral EGFR tyrosine kinase inhibitors (EGFR-TKIs) have expanded the treatment options for patients with non-small cell lung cancer. The first two reversible EGFR-TKIs, erlotinib and gefitinib, are approved for use in the first-line setting in patients with known EGFR-activating mutations and in the second- and third-line settings for all NSCLC patients. These first-generation EGFR-TKIs improve progression-free survival when compared to chemotherapy in patients with EGFR-activating mutations in the first-line setting. However, nearly all patients develop resistance to EGFR-directed agents. There is a need for further therapy options for patients with disease progression after treatment with reversible EGFR-TKIs. Afatinib is an irreversible ErbB family blocker that inhibits EGFR, HER2, and HER4. In vitro and in vivo, afatinib have shown increased inhibition of the common EGFR-activating mutations as well as the T790M resistance mutation when compared to erlotinib and gefitinib. Clinically, afatinib has been evaluated in the LUX-Lung series of trials, with improvement in progression-free survival reported in patients with EGFR-activating mutations in both first- and second-/third-line settings when compared to chemotherapy. Further investigation is needed to determine the precise role that afatinib will play in the treatment of patients with non-small cell lung cancer and EGFR-activating mutations.

Achieving just, equitable, and effective sustainability transformations requires diverse social engagement. This paper identifies five key roles played by Indigenous Peoples and local communities as agents of transformative change: embodying sustainable lifeways, resisting harm and defending rights, extending their practices to influence broader systems, and offering foundational models for care-oriented economies and governance. Through illustrative examples, we show how Indigenous Peoples and local communities actively contribute to global transformation. We emphasize the importance of engaging with a wide range of actors in supporting, expanding, and deepening these contributions to realize meaningful, systemic change toward a sustainable and just future. Equitable, just, and effective transformative change for sustainability requires diverse actors and knowledge systems. Indigenous Peoples and local communities play critical roles in advancing strategies and pathways that halt biodiversity loss and reverse nature’s decline.

The rise of private standards, including those involving multi-stakeholder processes, raises questions about whose interests are served and the kind of power that is exerted to maintain these interests. This paper critically examines the battle for ideas—the way competing factions assert their own narratives about value chain relations, the role of standards and related multi-stakeholder processes. Drawing on empirical research on the horticulture and floriculture value chains linking Kenya and the United Kingdom, the analysis explores the framing of sustainability issues, especially around labor issues and good agricultural practice, and the choice of response with respect to private standards and multi-stakeholder initiatives since the late 1990s. We identify four competing narratives currently in play: a dominant global sourcing narrative, a pragmatic development narrative, a broader development narrative and a narrative we term potentially transformative. This last narrative is currently emerging through the unpacking of narratives in relation to the framing of sustainability problems and solutions, and in terms of legislative, executive and judicial governance. The paper contributes to emerging understanding of power in value chains, moving beyond material power to a consideration of how ideational power is exerted and resisted.

Both the addition of neoadjuvant chemoradiation therapy and improvements in surgical techniques have improved local control and overall survival for locally advanced rectal cancer patients over the past few decades. The addition of adjuvant chemotherapy has likely improved outcomes as well, though the contribution has been more difficult to quantify. At present, the majority of resected locally advanced rectal cancer patients receive adjuvant chemotherapy, though there is great variability in this practice based on both patient and institution characteristics. Recently, questions have been raised regarding which sub-groups of patients benefit most from adjuvant chemotherapy. As pathologic complete response (pCR) is increasingly found to be a reasonable surrogate for long-term favorable outcomes, some have questioned the need for adjuvant therapy in this select group of patients. Multiple retrospective analyses have shown minimal to no benefit for adjuvant chemotherapy in this group. Indeed, the patients most consistently shown to benefit from adjuvant therapy both in terms of disease free survival (DFS) and overall survival (OS) are those who achieve an intermediate pathologic response to neoadjuvant treatment. Tumors that have high expression of thymidylate synthetase have also shown to benefit from adjuvant therapy. More study is needed into clinical and molecular features that predict patient benefit from adjuvant therapy.

We are in the midst of an ecological crisis which has been and continues to be provoked by human-led ‘environmental degradation’ (defined for the purposes of this editorial as any harm or adverse impact caused to the environment, including climate change, the contamination of the land and water through the exposure to or dumping of toxic and hazardous substances and wastes, air pollution, the destruction of ecosystems, and the depletion of biodiversity) [...]

Vulnerability to environmental degradation and natural hazards is articulated along social, poverty, and gender lines. Just as gender is not sufficiently mainstreamed in many areas of development policy and practice, so the potential impacts of climate change on gender relations have not been studied, and remain invisible. In this article we outline climate change predictions, and explore the effects of long-term climate change on agriculture, ecological systems, and gender relations, since these could be significant. We identify predicted changes in natural hazard frequency and intensity as a result of climate change, and explore the gendered effects of natural hazards. We highlight the urgent need to integrate gender analyses into public policy-making, and in adaptation responses to climate change.