An investigation of sliced inverse regression with censored data.

The complexity of high-dimensional data creates a number of concerns when trying to analyze it. This data often consists of a response or survival time and potentially thousands of predictors. These predictors can be highly correlated, and the sample size is often very small and right censored. Sliced inverse regression (SIR) is a method of reducing the dimension of the data, while preserving all the regression information. Sliced inverse regression with regularizations was developed to work when the number of predictors exceeds the sample size, and to deal with highly correlated predictors as well. In this study we investigated the performance of Sliced inverse regression with regularizations using three different approaches for handling right censored data. The methods of reweighting, mean imputation, and multiple imputation were analyzed. Based on the simulation scenarios, the mean imputation method performs the best in regards to fitting the data as well as prediction. The method of reweighting appears inadequate when combined with SIR

Ecological differences in the associations between air pollution, greenness, and risk of stroke: The REGARDS study.

The adverse health effects of air pollution have long been recognized, with the majority of morbidity and mortality due to its effects on the cardiovascular system. Alternatively, living in areas with higher greenness has been found to be beneficial to a wide range of health outcomes. However, few studies have considered that these relationships may vary depending on the surrounding ecosystem. The purpose of this dissertation was to examine the effects of long-term exposure to air pollution and greenness on incidence of stroke, and how these relationships vary with the major ecological regions of the United States. We utilized the Reasons for Geographic and Racial Differences in Stroke study (REGARDS), a prospective cohort study of 30,239 participants recruited between 2003 and 2007. One-year and 3-year exposure to PM2.5, PM10, O3, NO2, SO2, and CO were assigned to participants’ census block group. Residential greenspace was estimated by the Normalized Difference Vegetation Index (NDVI) and Enhance Vegetation Index (EVI). The risk of incident stroke associated with baseline pollutants and greenness was assessed using adjusted Cox proportional hazards models. Models were stratified by EPA created ecoregions to determine how associations varied by geographic areas with similar environmental features. The hazard ratio (95% CI) for a 2.9 µg/m3 (interquartile range) increase in 1-year PM10 was 1.07 (1.003, 1.15) for risk of stroke in the full study population. We did not find evidence of positive associations for PM2.5, O3, NO2, SO2, and CO in the full population. In our ecoregion specific analysis, we found positive associations for PM2.5 in the Great Plains ecoregion, while associations for PM10 were strongest in the Eastern Temperate Forests region. There was suggestive evidence of a negative association between greenness and stroke incidence (hazard ratio: 0.989; 95% CI: 0.946, 1.033) for a 0.1 increase in NDVI within 250-m. In our analysis by ecoregions, we found negative associations between greenness and stroke incidence in the Eastern Temperate Forests region, but positive associations in the Great Plains and Mediterranean California regions. The associations between exposure to air pollution, greenness and stroke incidence varied by ecoregion, highlighting the importance of considering the complexities of the natural environment

Thyroxine-Induced Changes in the Development of Neutral Α-Amino Acid Transport Systems of Rat Brain

Transport of representative neutral Α-amino acids was measured in brain slices after injecting thy-roxine into donor rats of various ages from 1 to 23 days old. The hormone did not alter uptake in slices from 1-day-old rats even when treatment was begun on pregnant rats as much as 10 days before delivery. Injecting thy-roxine until age 6 days, however, decreased the activity of transport system A (the major sodium-dependent system in most mammalian cells) and caused appearance of a new transport system used by the model amino acids, 2-aminoisobutyric acid and 2-(methylamino)isobutyric acid. Uptake at 6 days was similar to that found in slices from older, untreated rats (e.g., those 14 days old). These results strongly suggest that one action of thyroxine is to accelerate the development of neutral Α-amino acid transport systems of brain over the first six days after birth. Thyroxine treatment of rats from birth to age 14 days also appears to increase the activities of both system A and the second transport system used by the two model amino acids in brains from 14-day-old rats.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66252/1/j.1471-4159.1984.tb02781.x.pd

Developmental Changes in the Neutral Α-Amino Acid Transport Systems of Rat Brain Over the First Three Weeks After Birth

Transport of seven different amino acids into brain slices increased as donor rats aged from 1 to 6 days. Uptakes of 2-aminoisobutyric acid, 2-(methyl-amino)isobutyric acid, and L-alanine then decreased by day 14, while uptakes of other amino acids continued to increase or remained fairly constant. Neutral Α-amino acid transport systems were characterized by measuring inhibition of uptakes and kinetics for representative amino acids at different ages. Results indicate that 2-ami-noisobutyrate and 2-(methylamino)isobutyrate used only one (and the same) system in brain slices from 6-day-old rats, with characteristics of system A (the major sodium-dependent system in most mammalian cells). They used at least two systems at ages 1, 14, and 23 days, but, of these, only at 1 day did they use the same systems in the same proportions. Alanine and leucine used more than one system at all four ages, and somewhat different combinations than used by each other or by 2-aminoisobu-tyrate or 2-(methylamino)isobutyrate. Their transport characteristics showed they used mostly system ASC (a sodium-dependent system distinguished from A) and/or system L (sodium-independent). We conclude that system A increases as the brain ages from 1 to 6 days and declines thereafter. System L probably increases with aging from 1 to 23 days.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66235/1/j.1471-4159.1984.tb02780.x.pd

Residential Proximity to Major Roadways Is Associated With Increased Levels of AC133+ Circulating Angiogenic Cells

Objectives: Previous studies have shown that residential proximity to a roadway is associated with increased cardiovascular disease risk. Yet, the nature of this association remains unclear, and its effect on individual cardiovascular disease risk factors has not been assessed. The objective of this study was to determine whether residential proximity to roadways influences systemic inflammation and the levels of circulating angiogenic cells. Approach and Results: In a cross-sectional study, cardiovascular disease risk factors, blood levels of C-reactive protein, and 15 antigenically defined circulating angiogenic cell populations were measured in participants (n=316) with moderate-to-high cardiovascular disease risk. Attributes of roadways surrounding residential locations were assessed using geographic information systems. Associations between road proximity and cardiovascular indices were analyzed using generalized linear models. Close proximity (\u3c50 m) to a major roadway was associated with lower income and higher rates of smoking but not C-reactive protein levels. After adjustment for potential confounders, the levels of circulating angiogenic cells in peripheral blood were significantly elevated in people living in close proximity to a major roadway (CD31+/AC133+, AC133+, CD34+/AC133+, and CD34+/45dim/AC133+ cells) and positively associated with road segment distance (CD31+/AC133+, AC133+, and CD34+/AC133+ cells), traffic intensity (CD31+/AC133+ and AC133+ cells), and distance-weighted traffic intensity (CD31+/34+/45+/AC133+ cells). Conclusions: Living close to a major roadway is associated with elevated levels of circulating cells positive for the early stem marker AC133+. This may reflect an increased need for vascular repair. Levels of these cells in peripheral blood may be a sensitive index of cardiovascular injury because of residential proximity to roadways

Residential Proximity to Major Roadways Is Associated With Increased Levels of AC133+ Circulating Angiogenic Cells

OBJECTIVES: Previous studies have shown that residential proximity to a roadway is associated with increased cardiovascular disease risk. Yet, the nature of this association remains unclear, and its effect on individual cardiovascular disease risk factors has not been assessed. The objective of this study was to determine whether residential proximity to roadways influences systemic inflammation and the levels of circulating angiogenic cells. APPROACH AND RESULTS: In a cross-sectional study, cardiovascular disease risk factors, blood levels of C-reactive protein, and 15 antigenically defined circulating angiogenic cell populations were measured in participants (n=316) with moderate-to-high cardiovascular disease risk. Attributes of roadways surrounding residential locations were assessed using geographic information systems. Associations between road proximity and cardiovascular indices were analyzed using generalized linear models. Close proximity (\u3c50 \u3em) to a major roadway was associated with lower income and higher rates of smoking but not C-reactive protein levels. After adjustment for potential confounders, the levels of circulating angiogenic cells in peripheral blood were significantly elevated in people living in close proximity to a major roadway (CD31+/AC133+, AC133+, CD34+/AC133+, and CD34+/45dim/AC133+ cells) and positively associated with road segment distance (CD31+/AC133+, AC133+, and CD34+/AC133+ cells), traffic intensity (CD31+/AC133+ and AC133+ cells), and distance-weighted traffic intensity (CD31+/34+/45+/AC133+ cells). CONCLUSIONS: Living close to a major roadway is associated with elevated levels of circulating cells positive for the early stem marker AC133+. This may reflect an increased need for vascular repair. Levels of these cells in peripheral blood may be a sensitive index of cardiovascular injury because of residential proximity to roadways

Association Between Residential Greenness and Cardiovascular Disease Risk

Background Exposure to green vegetation has been linked to positive health, but the pathophysiological processes affected by exposure to vegetation remain unclear. To study the relationship between greenness and cardiovascular disease, we examined the association between residential greenness and biomarkers of cardiovascular injury and disease risk in susceptible individuals. Methods and Results In this cross-sectional study of 408 individuals recruited from a preventive cardiology clinic, we measured biomarkers of cardiovascular injury and risk in participant blood and urine. We estimated greenness from satellite-derived normalized difference vegetation index ( NDVI ) in zones with radii of 250 m and 1 km surrounding the participants' residences. We used generalized estimating equations to examine associations between greenness and cardiovascular disease biomarkers. We adjusted for residential clustering, demographic, clinical, and environmental variables. In fully adjusted models, contemporaneous NDVI within 250 m of participant residence was inversely associated with urinary levels of epinephrine (-6.9%; 95% confidence interval, -11.5, -2.0/0.1 NDVI ) and F2-isoprostane (-9.0%; 95% confidence interval, -15.1, -2.5/0.1 NDVI ). We found stronger associations between NDVI and urinary epinephrine in women, those not on β-blockers, and those who had not previously experienced a myocardial infarction. Of the 15 subtypes of circulating angiogenic cells examined, 11 were inversely associated (8.0-15.6% decrease/0.1 NDVI ), whereas 2 were positively associated (37.6-45.8% increase/0.1 NDVI ) with contemporaneous NDVI . Conclusions Independent of age, sex, race, smoking status, neighborhood deprivation, statin use, and roadway exposure, residential greenness is associated with lower levels of sympathetic activation, reduced oxidative stress, and higher angiogenic capacity

Belowground biomass response to nutrient enrichment depends on light limitation across globally distributed grasslands

Anthropogenic activities are increasing nutrient inputs to ecosystems worldwide, with consequences for global carbon and nutrient cycles. Recent meta-analyses show that aboveground primary production is often co-limited by multiple nutrients; however, little is known about how root production responds to changes in nutrient availability. At twenty-nine grassland sites on four continents, we quantified shallow root biomass responses to nitrogen (N), phosphorus (P) and potassium plus micronutrient enrichment and compared below- and aboveground responses. We hypothesized that optimal allocation theory would predict context dependence in root biomass responses to nutrient enrichment, given variation among sites in the resources limiting to plant growth (specifically light versus nutrients). Consistent with the predictions of optimal allocation theory, the proportion of total biomass belowground declined with N or P addition, due to increased biomass aboveground (for N and P) and decreased biomass belowground (N, particularly in sites with low canopy light penetration). Absolute root biomass increased with N addition where light was abundant at the soil surface, but declined in sites where the grassland canopy intercepted a large proportion of incoming light. These results demonstrate that belowground responses to changes in resource supply can differ strongly from aboveground responses, which could significantly modify predictions of future rates of nutrient cycling and carbon sequestration. Our results also highlight how optimal allocation theory developed for individual plants may help predict belowground biomass responses to nutrient enrichment at the ecosystem scale across wide climatic and environmental gradients

A multi-disciplinary perspective on emergent and future innovations in peer review [version 2; referees: 2 approved]

Peer review of research articles is a core part of our scholarly communication system. In spite of its importance, the status and purpose of peer review is often contested. What is its role in our modern digital research and communications infrastructure? Does it perform to the high standards with which it is generally regarded? Studies of peer review have shown that it is prone to bias and abuse in numerous dimensions, frequently unreliable, and can fail to detect even fraudulent research. With the advent of web technologies, we are now witnessing a phase of innovation and experimentation in our approaches to peer review. These developments prompted us to examine emerging models of peer review from a range of disciplines and venues, and to ask how they might address some of the issues with our current systems of peer review. We examine the functionality of a range of social Web platforms, and compare these with the traits underlying a viable peer review system: quality control, quantified performance metrics as engagement incentives, and certification and reputation. Ideally, any new systems will demonstrate that they out-perform and reduce the biases of existing models as much as possible. We conclude that there is considerable scope for new peer review initiatives to be developed, each with their own potential issues and advantages. We also propose a novel hybrid platform model that could, at least partially, resolve many of the socio-technical issues associated with peer review, and potentially disrupt the entire scholarly communication system. Success for any such development relies on reaching a critical threshold of research community engagement with both the process and the platform, and therefore cannot be achieved without a significant change of incentives in research environments

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure