Using multiple lines of evidence to assess the risk of ecosystem collapse

Effective ecosystem risk assessment relies on a conceptual understanding of ecosystem dynamics and the synthesis of multiple lines of evidence. Risk assessment protocols and ecosystem models integrate limited observational data with threat scenarios, making them valuable tools for monitoring ecosystem status and diagnosing key mechanisms of decline to be addressed by management. We applied the IUCN Red List of Ecosystems criteria to quantify the risk of collapse of the Meso-American Reef, a unique ecosystem containing the second longest barrier reef in the world. We collated a wide array of empirical data (field and remotely sensed), and used a stochastic ecosystem model to backcast past ecosystem dynamics, as well as forecast future ecosystem dynamics under 11 scenarios of threat. The ecosystem is at high risk from mass bleaching in the coming decades, with compounding effects of ocean acidification, hurricanes, pollution and fishing. The overall status of the ecosystem is Critically Endangered (plausibly Vulnerable to Critically Endangered), with notable differences among Red List criteria and data types in detecting the most severe symptoms of risk. Our case study provides a template for assessing risks to coral reefs and for further application of ecosystem models in risk assessment

Using multiple lines of evidence to assess the risk of ecosystem collapse

Effective ecosystem risk assessment relies on a conceptual understanding of ecosystem dynamics and the synthesis of multiple lines of evidence. Risk assessment protocols and ecosystem models integrate limited observational data with threat scenarios, making them valuable tools for monitoring ecosystem status and diagnosing key mechanisms of decline to be addressed by management. We applied the IUCN Red List of Ecosystems criteria to quantify the risk of collapse of the Meso-American Reef, a unique ecosystem containing the second longest barrier reef in the world. We collated a wide array of empirical data (field and remotely sensed), and used a stochastic ecosystem model to backcast past ecosystem dynamics, as well as forecast future ecosystem dynamics under 11 scenarios of threat. The ecosystem is at high risk from mass bleaching in the coming decades, with compounding effects of ocean acidification, hurricanes, pollution and fishing. The overall status of the ecosystem is Critically Endangered (plausibly Vulnerable to Critically Endangered), with notable differences among Red List criteria and data types in detecting the most severe symptoms of risk. Our case study provides a template for assessing risks to coral reefs and for further application of ecosystem models in risk assessment.This work was supported by the Australian Research Council LP 130100435 and a Veski Inspiring Women Fellowship to E.N

A critical realist evaluation of a music therapy intervention in palliative care

BACKGROUND: Music therapy is increasingly used as an adjunct therapy to support symptom management in palliative care. However, studies to date have paid little attention to the processes that lead to changes in patient outcomes. To fill this gap, we examined the processes and experiences involved in the introduction of music therapy as an adjunct complementary therapy to palliative care in a hospice setting in the United Kingdom (UK). METHODS: Using a realistic evaluation approach, we conducted a qualitative study using a variety of approaches. These consisted of open text answers from patients (n = 16) on how music therapy helped meet their needs within one hospice in Northern Ireland, UK. We also conducted three focus groups with a range of palliative care practitioners (seven physicians, seven nursing staff, two social workers and three allied health professionals) to help understand their perspectives on music therapy's impact on their work setting, and what influences its successful implementation. This was supplemented with an interview with the music therapist delivering the intervention. RESULTS: Music therapy contains multiple mechanisms that can provide physical, psychological, emotional, expressive, existential and social support. There is also evidence that the hospice context, animated by a holistic approach to healthcare, is an important facilitator of the effects of music therapy. Examination of patients' responses helped identify specific benefits for different types of patients. CONCLUSIONS: There is a synergy between the therapeutic aims of music therapy and those of palliative care, which appealed to a significant proportion of participants, who perceived it as effective

How many bird and mammal extinctions has recent conservation action prevented?

Aichi Target 12 of the Convention on Biological Diversity (CBD) aims to ‘prevent extinctions of known threatened species’. To measure its success, we used a Delphi expert elicitation method to estimate the number of bird and mammal species whose extinctions were prevented by conservation action in 1993 - 2020 (the lifetime of the CBD) and 2010 - 2020 (the timing of Aichi Target 12). We found that conservation prevented 21–32 bird and 7–16 mammal extinctions since 1993, and 9–18 bird and 2–7 mammal extinctions since 2010. Many remain highly threatened, and may still become extinct in the near future. Nonetheless, given that ten bird and five mammal species did go extinct (or are strongly suspected to) since 1993, extinction rates would have been 2.9–4.2 times greater without conservation action. While policy commitments have fostered significant conservation achievements, future biodiversity action needs to be scaled up to avert additional extinctions

A randomised controlled pilot and feasibility study of music therapy for improving the quality of life of hospice inpatients.

BACKGROUND: Evidence about the effectiveness of music therapy for improving the quality of life of palliative care patients is positive but weak in terms of risk of bias. METHODS: This study aimed to determine the feasibility of a randomised controlled trial to evaluate the effectiveness of music therapy for improving the quality of life of hospice inpatients, as measured by the McGill Quality of Life questionnaire. Objectives included recruitment of 52 participants over 12 months and provision of data to support the calculation of the required sample size for a definitive randomised trial, taking into account the retention rates of recruited participants; and evaluation of the viability of the intervention and the acceptability of the assessment tool. The design was a single-centre, researcher-blinded randomised pilot and feasibility study involving two parallel groups. Participants were recruited from one inpatient hospice unit in Northern Ireland. Eligibility criteria were an Eastern Cooperative Oncology Group performance status of two or lower and an Abbreviated Mental Test score of seven or more. Consenting patients were randomly allocated to the intervention or control group using a 1:1 allocation ratio. The intervention group received up to six individual music therapy sessions over 3 weeks in addition to usual care. The control group received usual care only. RESULTS: Fifty one participants were recruited over 12 months. Twenty five were allocated to the intervention group and 26 to the control group. Seventy one percent of participants were lost to follow up by week 3, the proposed primary endpoint. The primary endpoint was moved from week 3, when 71% were lost to follow up to week 1, when 33% were lost. The McGill Quality of Life questionnaire was generally acceptable to participants. In order to detect a small to moderate effect size of 0.3, a fully powered study would require the recruitment of 698 participants. CONCLUSIONS: A Phase III randomised controlled trial to evaluate the effectiveness of music therapy in improving the quality of life of hospice inpatients is feasible. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02791048 . Registered 6 June 2016

Symptom-based stratification of patients with primary Sjögren's syndrome: multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials

Background Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjögren's syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response. Methods We did hierarchical cluster analysis using five common symptoms associated with primary Sjögren's syndrome (pain, fatigue, dryness, anxiety, and depression), followed by multinomial logistic regression to identify subgroups in the UK Primary Sjögren's Syndrome Registry (UKPSSR). We assessed clinical and biological differences between these subgroups, including transcriptional differences in peripheral blood. Patients from two independent validation cohorts in Norway and France were used to confirm patient stratification. Data from two phase 3 clinical trials were similarly stratified to assess the differences between subgroups in treatment response to hydroxychloroquine and rituximab. Findings In the UKPSSR cohort (n=608), we identified four subgroups: Low symptom burden (LSB), high symptom burden (HSB), dryness dominant with fatigue (DDF), and pain dominant with fatigue (PDF). Significant differences in peripheral blood lymphocyte counts, anti-SSA and anti-SSB antibody positivity, as well as serum IgG, κ-free light chain, β2-microglobulin, and CXCL13 concentrations were observed between these subgroups, along with differentially expressed transcriptomic modules in peripheral blood. Similar findings were observed in the independent validation cohorts (n=396). Reanalysis of trial data stratifying patients into these subgroups suggested a treatment effect with hydroxychloroquine in the HSB subgroup and with rituximab in the DDF subgroup compared with placebo. Interpretation Stratification on the basis of patient-reported symptoms of patients with primary Sjögren's syndrome revealed distinct pathobiological endotypes with distinct responses to immunomodulatory treatments. Our data have important implications for clinical management, trial design, and therapeutic development. Similar stratification approaches might be useful for patients with other chronic immune-mediated diseases. Funding UK Medical Research Council, British Sjogren's Syndrome Association, French Ministry of Health, Arthritis Research UK, Foundation for Research in Rheumatology

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

How many bird and mammal extinctions has recent conservation action prevented?

Aichi Target 12 of the Convention on Biological Diversity (CBD) contains the aim to ‘prevent extinctions of known threatened species’. To measure the degree to which this was achieved, we used expert elicitation to estimate the number of bird and mammal species whose extinctions were prevented by conservation action in 1993–2020 (the lifetime of the CBD) and 2010–2020 (the timing of Aichi Target 12). We found that conservation action prevented 21–32 bird and 7–16 mammal extinctions since 1993, and 9–18 bird and two to seven mammal extinctions since 2010. Many remain highly threatened and may still become extinct. Considering that 10 bird and five mammal species did go extinct (or are strongly suspected to) since 1993, extinction rates would have been 2.9–4.2 times greater without conservation action. While policy commitments have fostered significant conservation achievements, future biodiversity action needs to be scaled up to avert additional extinctions.https://wileyonlinelibrary.com/journal/conlMammal Research Institut

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders