Placebo-controlled study in neuromyelitis optica : ethical and design considerations

BACKGROUND: To date, no treatment for neuromyelitis optica (NMO) has been granted regulatory approval, and no controlled clinical studies have been reported. OBJECTIVE: To design a placebo-controlled study in NMO that appropriately balances patient safety and clinical-scientific integrity. METHODS: We assessed the "standard of care" for NMO to establish the ethical framework for a placebo-controlled trial. We implemented measures that balance the need for scientific robustness while mitigating the risks associated with a placebo-controlled study. The medical or scientific community, patient organizations, and regulatory authorities were engaged early in discussions on this placebo-controlled study, and their input contributed to the final study design. RESULTS: The N-MOmentum study (NCT02200770) is a clinical trial that randomizes NMO patients to receive MEDI-551, a monoclonal antibody that depletes CD19+ B-cells, or placebo. The study design has received regulatory, ethical, clinical, and patient approval in over 100 clinical sites in more than 20 countries worldwide. CONCLUSION: The approach we took in the design of the N-MOmentum trial might serve as a roadmap for other rare severe diseases when there is no proven therapy and no established clinical development path

The Code large-scale meteorological, sea surface temperature, and coastal sea level data set, 1980-84

Meteorological, sea surface temperature, and coastal sea level data were collected along the west coast of North America from northern Baja California to the Alaska/British Columbia border from 1980 to mid-1984 for the large-scale component of the Coastal Ocean Dynamics Experiment (CODE). This report presents statistical summaries and plots of selected meteorological variables, sea surface temperature, and coastal sea level from this data set

Protected areas and freshwater biodiversity: a novel systematic review distils eight lessons for effective conservation

Protected areas are a global cornerstone of biodiversity conservation and restoration. Yet freshwater biodiversity is continuing to decline rapidly. To date there has been no formal review of the effectiveness of protected areas for conserving or restoring biodiversity in rivers, lakes, and wetlands. We present the first assessment using a systematic review of the published scientific evidence of the effectiveness of freshwater protected areas. Systematic searches returned 2,586 separate publications, of which 44 provided quantitative evidence comprising 75 case studies. Of these, 38 reported positive, 25 neutral, and 12 negative outcomes for freshwater biodiversity conservation. Analysis revealed variable relationships between conservation effectiveness and factors such as taxa assessed, protected area size and characteristics, International Union for Conservation of Nature (IUCN) protected area category, and ecoregion. Lack of effectiveness was attributed to many anthropogenic factors, including fishing (often with a lack of law enforcement), water management (abstraction, dams, and flow regulation), habitat degradation, and invasive non‐native species. Drawing on the review and wider literature we distil eight lessons to enhance the effectiveness of protected areas for freshwater biodiversity conservation. We urge policymakers, protected area managers, and those who fund them to invest in well‐designed research and monitoring programs and publication of evidence of protected area effectiveness

Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients

BACKGROUND: The diagnostic and pathophysiological relevance of antibodies to aquaporin-4 (AQP4-Ab) in patients with neuromyelitis optica spectrum disorders (NMOSD) has been intensively studied. However, little is known so far about the clinical impact of AQP4-Ab seropositivity. OBJECTIVE: To analyse systematically the clinical and paraclinical features associated with NMO spectrum disorders in Caucasians in a stratified fashion according to the patients' AQP4-Ab serostatus. METHODS: Retrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3%). RESULTS: Seropositive patients were found to be predominantly female (p 1 myelitis attacks in the first year were identified as possible predictors of a worse outcome. CONCLUSION: This study provides an overview of the clinical and paraclinical features of NMOSD in Caucasians and demonstrates a number of distinct disease characteristics in seropositive and seronegative patients

Irrigators’ willingness to pay for the adoption of soil moisture monitoring tools in South-Eastern Africa

Contingent valuation is used to elicit irrigators’ willingness to pay for soil moisture tools in irrigation schemes in Africa, with various econometric methods employed to mitigate potential bias. Key results include that there is a neighbourhood effect influencing adoption, and that being located downstream and spending more on irrigation water positively and statistically significantly influenced willingness to pay for tools. The result suggests that although focusing on economic incentives and promoting farmer learning by those using the tools may promote greater adoption, there is likely to still be a need for co-investment by other bodies

Neuromyelitis optica MOG-IgG causes reversible lesions in mouse brain.

INTRODUCTION: Antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) are present in some neuromyelitis optica patients who lack antibodies against aquaporin-4 (AQP4-IgG). The effects of neuromyelitis optica MOG-IgG in the central nervous system have not been investigated in vivo. We microinjected MOG-IgG, obtained from patients with neuromyelitis optica, into mouse brains and compared the results with AQP4-IgG. RESULTS: MOG-IgG caused myelin changes and altered the expression of axonal proteins that are essential for action potential firing, but did not produce inflammation, axonal loss, neuronal or astrocyte death. These changes were independent of complement and recovered within two weeks. By contrast, AQP4-IgG produced complement-mediated myelin loss, neuronal and astrocyte death with limited recovery at two weeks. CONCLUSIONS: These differences mirror the better outcomes for MOG-IgG compared with AQP4-IgG patients and raise the possibility that MOG-IgG contributes to pathology in some neuromyelitis optica patients

Neuromyelitis optica MOG-IgG causes reversible lesions in mouse brain.

INTRODUCTION: Antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) are present in some neuromyelitis optica patients who lack antibodies against aquaporin-4 (AQP4-IgG). The effects of neuromyelitis optica MOG-IgG in the central nervous system have not been investigated in vivo. We microinjected MOG-IgG, obtained from patients with neuromyelitis optica, into mouse brains and compared the results with AQP4-IgG. RESULTS: MOG-IgG caused myelin changes and altered the expression of axonal proteins that are essential for action potential firing, but did not produce inflammation, axonal loss, neuronal or astrocyte death. These changes were independent of complement and recovered within two weeks. By contrast, AQP4-IgG produced complement-mediated myelin loss, neuronal and astrocyte death with limited recovery at two weeks. CONCLUSIONS: These differences mirror the better outcomes for MOG-IgG compared with AQP4-IgG patients and raise the possibility that MOG-IgG contributes to pathology in some neuromyelitis optica patients