The Convention on Biological Diversity’s objectives include conservation of biological diversity at a global level, but has it become another victim of extinction as a result of its text and strategic plan?

This thesis uses a socio-legal approach to explore the nature of the UN 1992’s Convention of Biological Diversity’s (CBD) Aichi targets (ATs). It uses different theories to grasp how international legal obligations such as the ATs can be viewed and how these theoretical underpinnings of legal obligation relate to theories of compliance. It uses doctrinal analysis, interview data and a ‘micro-ethnography’ of CBD COP13 to critically assess the decision-making process and the CBDs compliance mechanisms in light of the theory of interactional law. Finally, it looks at processes that internalise the ATs into domestic law and policy in the UK, specifically AT2 on biodiversity values and AT9 on Invasive Alien Species. The CBD has gone far in forming a legal regime to address the global biodiversity crisis, but most of the ATs will not be reached by 2020. The thesis concludes that the failure of the current strategic plan can be understood from an interactional perspective in part due to the lack of fulfilment of internal criteria of legal obligation (e.g. clarity), and also due to failures of the CBD COP to attract broader participation of actors and to create true shared understandings and shape actor identity. Whilst AT2 and AT9 have been internalised in the UK in laws and policies, these are not interactional and do not elicit compliance because they also lack certain criteria of interactional legal obligation. The internalised legal obligations have the potential to form interactional law if they fulfil the relevant criteria. More attention needs to be given in legal and policy making fora to the internal criteria of interactional legal obligation, and to pushing shared understandings in relation to biodiversity conservation through interactions and encouraging broad participation of actors at all levels of governance

Actions on sustainable food production and consumption for the post-2020 global biodiversity framework

Current food production and consumption trends are inconsistent with the Convention on Biological Diversity’s 2050 vision of living in harmony with nature. Here, we examine how, and under what conditions, the post-2020 biodiversity framework can support transformative change in food systems. Our analysis of actions proposed in four science-policy fora reveals that subsidy reform, valuation, food waste reduction, sustainability standards, life cycle assessments, sustainable diets, mainstreaming biodiversity, and strengthening governance can support more sustainable food production and consumption. By considering barriers and opportunities of implementing these actions in Peru and the United Kingdom, we derive potential targets and indicators for the post-2020 biodiversity framework. For targets to support transformation, genuine political commitment, accountability and compliance, and wider enabling conditions and actions by diverse agents are needed to shift food systems onto a sustainable path

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Magma plumbing systems: a geophysical perspective

Over the last few decades, significant advances in using geophysical techniques to image the structure of magma plumbing systems have enabled the identification of zones of melt accumulation, crystal mush development, and magma migration. Combining advanced geophysical observations with petrological and geochemical data has arguably revolutionised our understanding of, and afforded exciting new insights into, the development of entire magma plumbing systems. However, divisions between the scales and physical settings over which these geophysical, petrological, and geochemical methods are applied still remain. To characterise some of these differences and promote the benefits of further integration between these methodologies, we provide a review of geophysical techniques and discuss how they can be utilised to provide a structural context for and place physical limits on the chemical evolution of magma plumbing systems. For example, we examine how Interferometric Synthetic Aperture Radar (InSAR), coupled with Global Positioning System (GPS) and Global Navigation Satellite System (GNSS) data, and seismicity may be used to track magma migration in near real-time. We also discuss how seismic imaging, gravimetry and electromagnetic data can identify contemporary melt zones, magma reservoirs and/or crystal mushes. These techniques complement seismic reflection data and rock magnetic analyses that delimit the structure and emplacement of ancient magma plumbing systems. For each of these techniques, with the addition of full-waveform inversion (FWI), the use of Unmanned Aerial Vehicles (UAVs) and the integration of geophysics with numerical modelling, we discuss potential future directions. We show that approaching problems concerning magma plumbing systems from an integrated petrological, geochemical, and geophysical perspective will undoubtedly yield important scientific advances, providing exciting future opportunities for the volcanological community

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Global Biodiversity Governance: What Needs to Be Transformed?

The chapter firstly introduces the key global biodiversity treaty, the 1992 UN Convention on Biological Diversity, and its principal institutional body, the Conference of the Parties (COP) (Section 3.2). The evolution of the CBD is analyzed along with its procedural mechanisms, including its decision-making and review mechanisms. Secondly, the chapter presents the other relevant international institutions in what constitutes the “regime complex” for global biodiversity governance (Section 3.3). Within this complex, biodiversity governance takes place at multiple levels, from global to local, and in different sectors, including some of those most responsible for biodiversity loss such as agriculture, trade and development. The evolution of biodiversity governance beyond the CBD is also explored by analyzing the role of private actors, including business and civil society, in global biodiversity governance. Thirdly, the implementation of global biodiversity laws and policies is examined through global and national governance processes (Section 3.4). The final section draws upon the analyses to propose ways to transform and strengthen global biodiversity governance (Section 3.5), before concluding. The chapter is mainly based on legal analyses, while also drawing on more generic biodiversity governance literature

Global Biodiversity Governance: What Needs to Be Transformed?

The Post-2020 Global Biodiversity Framework (GBF) of the Convention on Biological Diversity (CBD) (the Post-2020 Framework) is expected to embody transformative change through the adoption of the framework’s “Theory of Change” (CBD, 2020). Its implementation must recognize that the global biodiversity governance architecture needs to transform to lead the required personal and social transformations, including shifts in values, beliefs and patterns of social behaviors (Chaffin et al., 2016), necessary to successfully tackle biodiversity loss. Against this backdrop, the overarching goal of this chapter is to analyze what needs to be transformed in global biodiversity governance, including institutional structures that shape values, beliefs and behavioral change. The chapter examines obstacles and opportunities for transformation, with the indirect objective of informing implementation of the Post-2020 Framework; at the time of writing, the CBD is expected to adopt the Post-2020 GBF in 2022