Contracts for environmental outcomes: the use of financial contracts in environmental markets

In environmental markets, parties frequently exchange obligations through environmental contracts. These contracts imply a distribution of risk between parties. The main focus of our paper is to identify contracts that enable risk in environmental markets to be reduced, distributed at least cost, or managed efficiently. The risks that we consider are: moral hazard risk, price risk, exogenous environmental risk, measurement risk and production risk. The first section of our paper outlines some of the contracts currently utilised in financial and insurance markets to achieve these objectives. These are: futures and options contracts, spread contracts, weather contracts and catastrophe bonds. We then provide a snapshot of current applications of these contracts both in real markets and in the literature. Finally we discuss some possible applications in the environmental sector and indicate how the use of these contracts may alter the way government manages environmental assets and responsibilities. We also suggest a staged process to the introduction of contracts that recognises the current limitations faced by government. This paper does not propose new or novel contracts for tackling the problems of risk in exchange. Rather it extends the application of existing contractual arrangements to a new type of problem: environmental markets.Environmental Economics and Policy,

Contracts for environmental outcomes: the use of financial contracts in environmental markets

In environmental markets, parties frequently exchange obligations through environmental contracts. These contracts imply a distribution of risk between parties. The main focus of our paper is to identify contracts that enable risk in environmental markets to be reduced, distributed at least cost, or managed efficiently. The risks that we consider are: moral hazard risk, price risk, exogenous environmental risk, measurement risk and production risk. The first section of our paper outlines some of the contracts currently utilised in financial and insurance markets to achieve these objectives. These are: futures and options contracts, spread contracts, weather contracts and catastrophe bonds. We then provide a snapshot of current applications of these contracts both in real markets and in the literature. Finally we discuss some possible applications in the environmental sector and indicate how the use of these contracts may alter the way government manages environmental assets and responsibilities. We also suggest a staged process to the introduction of contracts that recognises the current limitations faced by government. This paper does not propose new or novel contracts for tackling the problems of risk in exchange. Rather it extends the application of existing contractual arrangements to a new type of problem: environmental markets

Metabolic adverse events associated with systemic corticosteroid therapy-a systematic review and meta-analysis.

OBJECTIVES: To assess the risk of new-onset or worsening hyperglycaemia, hypertension, weight gain and hyperlipidaemia with systemic corticosteroid therapy (CST) as reported in published randomised control trial (RCT) studies. DATA SOURCES: Literature search using MEDLINE, EMBASE, Cochrane library, Web of Science and Scopus STUDY ELIGIBILITY CRITERIA: Published articles on results of RCT with a systemic CST arm with numerical data presented on adverse effect (AE). PARTICIPANTS AND INTERVENTIONS: Reports of hyperglycaemia, hypertension, weight gain and hyperlipidaemia associated with systemic CST in patients or healthy volunteer's ≥17 years of age. STUDY APPRAISAL METHODS: Risk of bias tool, assessment at the level of AE and key study characteristics. RESULTS: A total of 5446 articles were screened to include 118 studies with 152 systemic CST arms (total participants=17 113 among which 8569 participants treated with CST). Pooled prevalence of hyperglycaemia in the CST arms within the studies was 10% (95% CI 7% to 14%), with the highest prevalence in respiratory illnesses at 22% (95% CI 9% to 35%). Pooled prevalence of severe hyperglycaemia, hypertension, weight gain and hyperlipidaemia within the corticosteroid arms was 5% (95% CI 2% to 9%), 6% (95% CI 4% to 8%), 13% (95% CI 8% to 18%), 8% (95% CI 4% to 17%), respectively. CST was significantly associated hyperglycaemia, hypertension and weight gain as noted in double-blinded placebo-controlled parallel-arms studies: OR of 2.13 (95% CI 1.66 to 2.72), 1.68 (95% CI 0.96 to 2.95) and 5.20 (95% CI 2.10 to 12.90), respectively. Intravenous therapy posed higher risk than oral therapy: OR of 2.39 (95% CI 1.16 to 4.91). LIMITATIONS: There was significant heterogeneity in the AE definitions and quality of AE reporting in the primary studies and patient populations in the studies. The impact of cumulative dose effect on incidental AE could not be calculated. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Systemic CST use is associated with increased risk of metabolic AEs, which differs for each disease group and route of administration. PROSPERO REGISTRATION NUMBER: CRD42020161270

Age and DNA-methylation subgroup as potential independent risk factors for treatment stratification in children with Atypical Teratoid/Rhabdoid Tumors

BACKGROUND Controversy exists as to what may be defined as standard of care (including markers for stratification) for patients with Atypical Teratoid Rhabdoid Tumors (ATRT). The European Rhabdoid Registry, EU-RHAB, recruits uniformly treated patients and offers standardized genetic and DNA methylation analyses. METHODS Clinical, genetic and treatment data of 143 patients from 13 European countries were analyzed (2009 - 2017). Therapy consisted of surgery, anthracycline-based induction and either radiotherapy or high dose chemotherapy following a consensus among European experts. FISH, MLPA and sequencing were employed for assessment of somatic and germline mutations in SMARCB1. Molecular subgroups (ATRT-SHH, -TYR and -MYC) were determined using DNA-methylation arrays resulting in profiles of 84 tumors. RESULTS Median age at diagnosis of 67 girls and 76 boys was 29.5 months. 5-year overall survival (OS) and event-free survival (EFS) were 34.7±4.5% and 30.5±4.2%. Tumors displayed allelic partial/whole gene deletions (66%; 122/186 alleles) or single nucleotide variants (34%; 64/186 alleles) of SMARCB1. Germline mutations were detected in 26% of ATRT (30/117). The patient cohort consisted of 47% ATRT-SHH (39/84), 33% ATRT-TYR (28/84), and 20% ATRT-MYC 17/84). Age <1 year, non-TYR signature (ATRT-SHH or -MYC), metastatic or synchronous tumors, germline mutation, incomplete remission and omission of radiotherapy were negative prognostic factors in univariate analyses (p<0.05). An adjusted multivariate model identified age <1 year and a non-TYR signature as independent negative predictors of OS: high risk (<1 year + non-TYR; 5-year OS = 0%), intermediate risk (<1 year + ATRT-TYR or ≥1 year + non-TYR; 5-year OS = 32.5±8.7%) and standard risk (≥1 year + ATRT-TYR, 5-year OS = 71.5±12.2%). CONCLUSIONS Age and molecular subgroup status are independent risk factors for survival in children with ATRT. Our model warrants validation within future clinical trials

Age and DNA-methylation subgroup as potential independent risk factors for treatment stratification in children with Atypical Teratoid/Rhabdoid Tumors (ATRT)

Controversy exists as to what may be defined as standard of care (including markers for stratification) for patients with Atypical Teratoid Rhabdoid Tumors (ATRT). The European Rhabdoid Registry, EU-RHAB, recruits uniformly treated patients and offers standardized genetic and DNA methylation analyses.Clinical, genetic and treatment data of 143 patients from 13 European countries were analyzed (2009 - 2017). Therapy consisted of surgery, anthracycline-based induction and either radiotherapy or high dose chemotherapy following a consensus among European experts. FISH, MLPA and sequencing were employed for assessment of somatic and germline mutations in SMARCB1. Molecular subgroups (ATRT-SHH, -TYR and -MYC) were determined using DNA-methylation arrays resulting in profiles of 84 tumors.Median age at diagnosis of 67 girls and 76 boys was 29.5 months. 5-year overall survival (OS) and event-free survival (EFS) were 34.7±4.5% and 30.5±4.2%. Tumors displayed allelic partial/whole gene deletions (66%; 122/186 alleles) or single nucleotide variants (34%; 64/186 alleles) of SMARCB1. Germline mutations were detected in 26% of ATRT (30/117). The patient cohort consisted of 47% ATRT-SHH (39/84), 33% ATRT-TYR (28/84), and 20% ATRT-MYC 17/84). Age <1 year, non-TYR signature (ATRT-SHH or -MYC), metastatic or synchronous tumors, germline mutation, incomplete remission and omission of radiotherapy were negative prognostic factors in univariate analyses (p<0.05). An adjusted multivariate model identified age <1 year and a non-TYR signature as independent negative predictors of OS: high risk (<1 year + non-TYR; 5-year OS = 0%), intermediate risk (<1 year + ATRT-TYR or ≥1 year + non-TYR; 5-year OS = 32.5±8.7%) and standard risk (≥1 year + ATRT-TYR, 5-year OS = 71.5±12.2%).Age and molecular subgroup status are independent risk factors for survival in children with ATRT. Our model warrants validation within future clinical trials