Best practices for assessing ocean health inmultiple contexts using tailorable frameworks

Marine policy is increasingly calling for maintaining or restoring healthy oceans while human activities continue to intensify. Thus, successful prioritization and management of competing objectives requires a comprehensive assessment of the current state of the ocean. Unfortunately, assessment frameworks to define and quantify current ocean state are often site-specific, limited to a few ocean components, and difficult to reproduce in different geographies or even through time, limiting spatial or temporal comparisons as well as the potential for shared learning. Ideally, frameworks should be tailorable to accommodate use in disparate locations and contexts, removing the need to develop frameworks de novo and allowing efforts to focus on the assessments themselves to advise action. Here, we present some of our experiences using the Ocean Health Index (OHI) framework, a tailorable and repeatable approach that measures health of coupled human-ocean ecosystems in different contexts by accommodating differences in local environmental characteristics, cultural priorities, and information availability and quality. Since its development in 2012, eleven assessments using the OHI framework have been completed at global, national, and regional scales, four of which have been led by independent academic or government groups. We have found the following to be best practices for conducting assessments: Incorporate key characteristics and priorities into the assessment framework design before gathering information; Strategically define spatial boundaries to balance information availability and decision-making scales; Maintain the key characteristics and priorities of the assessment framework regardless of information limitations; and Document and share the assessment process, methods, and tools. These best practices are relevant to most ecosystem assessment processes, but also provide tangible guidance for assessments using the OHI framework. These recommendations also promote transparency around which decisions were made and why, reproducibility through access to detailed methods and computational code, repeatability via the ability to modify methods and computational code, and ease of communication to wide audiences, all of which are critical for any robust assessment process

Patterns and emerging trends in global ocean health.

International and regional policies aimed at managing ocean ecosystem health need quantitative and comprehensive indices to synthesize information from a variety of sources, consistently measure progress, and communicate with key constituencies and the public. Here we present the second annual global assessment of the Ocean Health Index, reporting current scores and annual changes since 2012, recalculated using updated methods and data based on the best available science, for 221 coastal countries and territories. The Index measures performance of ten societal goals for healthy oceans on a quantitative scale of increasing health from 0 to 100, and combines these scores into a single Index score, for each country and globally. The global Index score improved one point (from 67 to 68), while many country-level Index and goal scores had larger changes. Per-country Index scores ranged from 41-95 and, on average, improved by 0.06 points (range -8 to +12). Globally, average scores increased for individual goals by as much as 6.5 points (coastal economies) and decreased by as much as 1.2 points (natural products). Annual updates of the Index, even when not all input data have been updated, provide valuable information to scientists, policy makers, and resource managers because patterns and trends can emerge from the data that have been updated. Changes of even a few points indicate potential successes (when scores increase) that merit recognition, or concerns (when scores decrease) that may require mitigative action, with changes of more than 10-20 points representing large shifts that deserve greater attention. Goal scores showed remarkably little covariance across regions, indicating low redundancy in the Index, such that each goal delivers information about a different facet of ocean health. Together these scores provide a snapshot of global ocean health and suggest where countries have made progress and where a need for further improvement exists

Reduced Physiological Complexity in Robust Elderly Adults with the APOE ε4 Allele

BACKGROUND:It is unclear whether the loss of physiological complexity during the aging process is due to genetic variations. The APOE gene has been studied extensively in regard to its relationship with aging-associated medical illness. We hypothesize that diminished physiological complexity, as measured by heart rate variability, is influenced by polymorphisms in the APOE allele among elderly individuals. METHODOLOGY/PRINCIPAL FINDINGS:A total of 102 robust, non-demented, elderly subjects with normal functions of daily activities participated in this study (97 males and 5 females, aged 79.2+/-4.4 years, range 72-92 years). Among these individuals, the following two APOE genotypes were represented: epsilon4 non-carriers (n = 87, 85.3%) and epsilon4 carriers (n = 15, 14.7%). Multi-scale entropy (MSE), an analysis used in quantifying complexity for nonlinear time series, was employed to analyze heart-rate dynamics. Reduced physiological complexity, as measured by MSE, was significantly associated with the presence of the APOE epsilon4 allele in healthy elderly subjects, as compared to APOE epsilon4 allele non-carriers (24.6+/-5.5 versus 28.9+/-5.2, F = 9.429, p = 0.003, respectively). CONCLUSIONS/SIGNIFICANCE:This finding suggests a role for the APOE gene in the diminished physiological complexity seen in elderly populations

Natural and Vaccine-Mediated Immunity to Salmonella Typhimurium is Impaired by the Helminth Nippostrongylus brasiliensis

The impact of exposure to multiple pathogens concurrently or consecutively on immune function is unclear. Here, immune responses induced by combinations of the bacterium Salmonella Typhimurium (STm) and the helminth Nippostrongylus brasiliensis (Nb), which causes a murine hookworm infection and an experimental porin protein vaccine against STm, were examined. Mice infected with both STm and Nb induced similar numbers of Th1 and Th2 lymphocytes compared with singly infected mice, as determined by flow cytometry, although lower levels of secreted Th2, but not Th1 cytokines were detected by ELISA after re-stimulation of splenocytes. Furthermore, the density of FoxP3+ T cells in the T zone of co-infected mice was lower compared to mice that only received Nb, but was greater than those that received STm. This reflected the intermediate levels of IL-10 detected from splenocytes. Co-infection compromised clearance of both pathogens, with worms still detectable in mice weeks after they were cleared in the control group. Despite altered control of bacterial and helminth colonization in co-infected mice, robust extrafollicular Th1 and Th2-reflecting immunoglobulin-switching profiles were detected, with IgG2a, IgG1 and IgE plasma cells all detected in parallel. Whilst extrafollicular antibody responses were maintained in the first weeks after co-infection, the GC response was less than that in mice infected with Nb only. Nb infection resulted in some abrogation of the longer-term development of anti-STm IgG responses. This suggested that prior Nb infection may modulate the induction of protective antibody responses to vaccination. To assess this we immunized mice with porins, which confer protection in an antibody-dependent manner, before challenging with STm. Mice that had resolved a Nb infection prior to immunization induced less anti-porin IgG and had compromised protection against infection. These findings demonstrate that co-infection can radically alter the development of protective immunity during natural infection and in response to immunization

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

The molecular logic of endocannabinoid signalling

The endocannabinoids are a family of lipid messengers that engage the cell surface receptors that are targeted by Δ9-tetrahydrocannabinol, the active principle in marijuana (Cannabis). They are made on demand through cleavage of membrane precursors and are involved in various short-range signalling processes. In the brain, they combine with CB1 cannabinoid receptors on axon terminals to regulate ion channel activity and neurotransmitter release. Their ability to modulate synaptic efficacy has a wide range of functional consequences and provides unique therapeutic possibilities. © 2003, Nature Publishing Group. All rights reserved

A neuroscientist's guide to lipidomics

Nerve cells mould the lipid fabric of their membranes to ease vesicle fusion, regulate ion fluxes and create specialized microenvironments that contribute to cellular communication. The chemical diversity of membrane lipids controls protein traffic, facilitates recognition between cells and leads to the production of hundreds of molecules that carry information both within and across cells. With so many roles, it is no wonder that lipids make up half of the human brain in dry weight. The objective of neural lipidomics is to understand how these molecules work together; this difficult task will greatly benefit from technical advances that might enable the testing of emerging hypotheses

Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes.

Abstract BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo. (Funded by Amylin Pharmaceuticals; EXSCEL ClinicalTrials.gov number, NCT01144338 .)