The Role of Neuroinflammation in Postoperative Cognitive Dysfunction: Moving From Hypothesis to Treatment

Postoperative cognitive dysfunction (POCD) is a common complication of the surgical experience and is common in the elderly and patients with preexisting neurocognitive disorders. Animal and human studies suggest that neuroinflammation from either surgery or anesthesia is a major contributor to the development of POCD. Moreover, a large and growing body of literature has focused on identifying potential risk factors for the development of POCD, as well as identifying candidate treatments based on the neuroinflammatory hypothesis. However, variability in animal models and clinical cohorts makes it difficult to interpret the results of such studies, and represents a barrier for the development of treatment options for POCD. Here, we present a broad topical review of the literature supporting the role of neuroinflammation in POCD. We provide an overview of the cellular and molecular mechanisms underlying the pathogenesis of POCD from pre-clinical and human studies. We offer a brief discussion of the ongoing debate on the root cause of POCD. We conclude with a list of current and hypothesized treatments for POCD, with a focus on recent and current human randomized clinical trials

Ecosystem Services in Decision Making: Time to Deliver

Over the past decade, efforts to value and protect ecosystem services have been promoted by many as the last, best hope for making conservation mainstream – attractive and commonplace worldwide. In theory, if we can help individuals and institutions to recognize the value of nature, then this should greatly increase investments in conservation, while at the same time fostering human well-being. In practice, however, we have not yet developed the scientific basis, nor the policy and finance mechanisms, for incorporating natural capital into resource- and land-use decisions on a large scale. Here, we propose a conceptual framework and sketch out a strategic plan for delivering on the promise of ecosystem services, drawing on emerging examples from Hawai‘i. We describe key advances in the science and practice of accounting for natural capital in the decisions of individuals, communities, corporations, and governments

Ecosystem Services in Decision Making: Time to Deliver

Over the past decade, efforts to value and protect ecosystem services have been promoted by many as the last, best hope for making conservation mainstream – attractive and commonplace worldwide. In theory, if we can help individuals and institutions to recognize the value of nature, then this should greatly increase investments in conservation, while at the same time fostering human well-being. In practice, however, we have not yet developed the scientific basis, nor the policy and finance mechanisms, for incorporating natural capital into resource- and land-use decisions on a large scale. Here, we propose a conceptual framework and sketch out a strategic plan for delivering on the promise of ecosystem services, drawing on emerging examples from Hawai‘i. We describe key advances in the science and practice of accounting for natural capital in the decisions of individuals, communities, corporations, and governments

Foundation of Statistical Mechanics under experimentally realistic conditions

We demonstrate the equilibration of isolated macroscopic quantum systems, prepared in non-equilibrium mixed states with significant population of many energy levels, and observed by instruments with a reasonably bound working range compared to the resolution limit. Both properties are fulfilled under many, if not all, experimentally realistic conditions. At equilibrium, the predictions and limitations of Statistical Mechanics are recovered.Comment: Accepted in Phys. Rev. Let

A common cardiac sodium channel variant associated with sudden infant death in African Americans, SCN5A S1103Y.

Thousands die each year from sudden infant death syndrome (SIDS). Neither the cause nor basis for varied prevalence in different populations is understood. While 2 cases have been associated with mutations in type Valpha, cardiac voltage-gated sodium channels (SCN5A), the "Back to Sleep" campaign has decreased SIDS prevalence, consistent with a role for environmental influences in disease pathogenesis. Here we studied SCN5A in African Americans. Three of 133 SIDS cases were homozygous for the variant S1103Y. Among controls, 120 of 1,056 were carriers of the heterozygous genotype, which was previously associated with increased risk for arrhythmia in adults. This suggests that infants with 2 copies of S1103Y have a 24-fold increased risk for SIDS. Variant Y1103 channels were found to operate normally under baseline conditions in vitro. As risk factors for SIDS include apnea and respiratory acidosis, Y1103 and wild-type channels were subjected to lowered intracellular pH. Only Y1103 channels gained abnormal function, demonstrating late reopenings suppressible by the drug mexiletine. The variant appeared to confer susceptibility to acidosis-induced arrhythmia, a gene-environment interaction. Overall, homozygous and rare heterozygous SCN5A missense variants were found in approximately 5% of cases. If our findings are replicated, prospective genetic testing of SIDS cases and screening with counseling for at-risk families warrant consideration

Precise time delays from strongly gravitationally lensed type Ia supernovae with chromatically microlensed images

Time delays between the multiple images of strongly gravitationally lensed Type Ia supernovae (glSNe Ia) have the potential to deliver precise cosmological constraints, but the effects of microlensing on time delay extraction have not been studied in detail. Here we quantify the effect of microlensing on the glSN Ia yield of the Large Synoptic Survey Telescope (LSST) and the effect of microlensing on the precision and accuracy of time delays that can be extracted from LSST glSNe Ia. Microlensing has a negligible effect on the LSST glSN Ia yield, but it can be increased by a factor of ∼2 over previous predictions to 930 systems using a novel photometric identification technique based on spectral template fitting. Crucially, the microlensing of glSNe Ia is achromatic until three rest-frame weeks after the explosion, making the early-time color curves microlensing-insensitive time delay indicators. By fitting simulated flux and color observations of microlensed glSNe Ia with their underlying, unlensed spectral templates, we forecast the distribution of absolute time delay error due to microlensing for LSST, which is unbiased at the sub-percent level and peaked at 1% for color curve observations in the achromatic phase, while for light-curve observations it is comparable to state-of-the-art mass modeling uncertainties (4%). About 70% of LSST glSN Ia images should be discovered during the achromatic phase, indicating that microlensing time delay uncertainties can be minimized if prompt multicolor follow-up observations are obtained. Accounting for microlensing, the 1-2 day time delay on the recently discovered glSN Ia iPTF16geu can be measured to 40% precision, limiting its cosmological utility

The Impact of Socioeconomic Status on the Neural Substrates Associated with Pleasure

Low socio-economic status (SES) is associated with increased morbidity and premature mortality. Because tonic adversity relates to a diminished ability to experience pleasure, we hypothesized that subjects living in poverty would show diminished neural responsivity to positive stimuli in regions associated with positive experience and reward. Visual images were presented to twenty-two subjects in the context of a EPI-BOLD fMRI paradigm. Significant differences in neural responses between SES groups to poverty vs. neutral images were assessed, examining group, condition, and interaction effects. The data suggest that persons living in low-SES have neural experiences consistent with diminished interest in things generally enjoyed and point toward a possible explanation for the relationship between socioeconomic inequalities and mood disorders, such as depression, by SES