PolyMatch: Novel Libraries, Algorithms, and Visualizations for Discovering Polymers and Chemical Series.

Polymers are integral components of everyday products, ranging from plastics and emulsifiers to lubricants and detergents. Characterization of these materials at the molecular level is essential to understanding their physicochemical properties and potential health impacts, considering factors such as the number of repeating units, chemical moieties, functional groups, and degree of unsaturation. This study introduces a free open-source vendor neutral software, PolyMatch, designed to annotate polysorbates, polysorbides, polyethylene glycols (PEGs), fatty acid esterified species, and related chemical species based on mass spectral and chromatographic patterns inherent in the repeating nature of chemical moieties. PolyMatch facilitates the generation of MS/MS libraries for polymeric chemical species characterization (with over 800 000 structures with associated fragment masses already built in) and covers the entire liquid chromatography-high-resolution mass spectrometry (LC-HRMS/MS) data-processing workflow. PolyMatch covers peak picking, blank filtering, annotation, data visualization, and sharing of interactive data sets via an HTML link to the community. The software was applied to a Tween 80 mixture, using LC-HRMS/MS on an Agilent 6546 Q-TOF instrument with iterative exclusion for comprehensive fragmentation coverage. PolyMatch automatically assigned 86 features with high confidence at the species level, 362 based on PEG containing fragments and accurate mass matching to a simulated polymer database, and over 10 000 based on being a member of a homologous series (three or more) with CH2CH2O repeating units. The ease of use of PolyMatch and comprehensive coverage with species level assignment is expected to contribute to the advancement of materials science, health research, and product development.

Use of Both Fluoro-Jade B and Hematoxylin and Eosin to Detect Cell Death in the Juvenile Rat Brain Exposed to NMDA-Receptor Antagonists or GABA-Receptor Agonists in Safety Assessment.

Administration of pediatric anesthetics with N-methyl D-aspartate (NMDA)-receptor antagonist and/or γ-aminobutyric acid (GABA) agonist activities may result in neuronal degeneration and/or neuronal cell death in neonatal rats. Evaluating pediatric drug candidates for this potential neurotoxicity is often part of overall preclinical new drug development strategy. This specialized assessment may require dosing neonatal rats at postnatal day 7 at the peak of the brain growth spurt and evaluating brain tissue 24 to 48 hours following dosing. The need to identify methods to aid in the accurate and reproducible detection of lesions associated with this type of neurotoxic profile is paramount for meeting the changing needs of neuropathology assessment and addressing emerging challenges in the neuroscience field. We document the use of Fluoro-Jade B (FJB) staining, to be used in conjunction with standard hematoxylin and eosin staining, to detect acute neurodegeneration and neuronal cell death that can be caused by some NMDA-receptor antagonists and/or GABA agonists in the neonatal rat brain. The FJB staining is simple, specific, and sensitive and can be performed on brain specimens from the same cohort of animals utilized for standard neurotoxicity assessment, thus satisfying animal welfare recommendations with no effect on achievement of scientific and regulatory goals.

Malaria and Early African Development: Evidence from the Sickle Cell Trait.

We examine the effect of malaria on economic development in Africa over the very long run. Using data on the prevalence of the mutation that causes sickle cell disease, we measure the impact of malaria on mortality in Africa prior to the period in which formal data were collected. Our estimate is that in the more afflicted regions, malaria lowered the probability of surviving to adulthood by about ten percentage points, which is twice the current burden of the disease. The reduction in malaria mortality has been roughly equal to the reduction in other causes of mortality. We then ask whether the estimated burden of malaria had an effect on economic development in the period before European contact. Using data at the ethnic group level, we find little evidence of a negative relationship between malaria burden and population density or other measures of development.

THE GLOBAL DISTRIBUTION OF ECONOMIC ACTIVITY: NATURE, HISTORY, AND THE ROLE OF TRADE.

We explore the role of natural characteristics in determining the worldwide spatial distribution of economic activity, as proxied by lights at night, observed across 240,000 grid cells. A parsimonious set of 24 physical geography attributes explains 47% of worldwide variation and 35% of within-country variation in lights. We divide geographic characteristics into two groups, those primarily important for agriculture and those primarily important for trade, and confront a puzzle. In examining within-country variation in lights, among countries that developed early, agricultural variables incrementally explain over 6 times as much variation in lights as do trade variables, while among late developing countries the ratio is only about 1.5, even though the latter group is far more dependent on agriculture. Correspondingly, the marginal effects of agricultural variables as a group on lights are larger in absolute value, and those for trade smaller, for early developers than for late developers. We show that this apparent puzzle is explained by persistence and the differential timing of technological shocks in the two sets of countries. For early developers, structural transformation due to rising agricultural productivity began when transport costs were still high, so cities were localized in agricultural regions. When transport costs fell, these agglomerations persisted. In late-developing countries, transport costs fell before structural transformation. To exploit urban scale economies, manufacturing agglomerated in relatively few, often coastal, locations. Consistent with this explanation, countries that developed earlier are more spatially equal in their distribution of education and economic activity than late developers.

Gyrations in African Mortality and their Effect on Economic Growth.

I examine recent changes in African mortality and discuss their potential economic and demographic effects. Growth in life expectancy sharply departed from its trend after 1990, and then experienced a sharp acceleration after 2005. This latter acceleration was due overwhelmingly to improvements in HIV and malaria. Economists differ in their estimates of how large the structural effect of health on income is, with many estimates being relatively small. Taking seriously the delays built into many plausible causal channels would lead one to expect that any economic effects of these mortality changes, if they are detectable at all, will not appear for several decades. By contrast, the effect of declining mortality, especially from malaria, should soon be visible in data on population age structure in some countries.

HOW THE GROWING GAP IN LIFE EXPECTANCY MAY AFFECT RETIREMENT BENEFITS AND REFORMS.

Older Americans have experienced dramatic gains in life expectancy in recent decades, but an emerging literature reveals that these gains are accumulating mostly to those at the top of the income distribution. We explore how growing inequality in life expectancy affects lifetime benefits from Social Security, Medicare, and other programs and how this phenomenon interacts with possible program reforms. We first project that life expectancy at age 50 for males in the two highest income quintiles will rise by 7 to 8 years between the 1930 and 1960 birth cohorts, but that the two lowest income quintiles will experience little to no increase over that time period. This divergence in life expectancy will cause the gap between average lifetime program benefits received by men in the highest and lowest quintiles to widen by $130,000 (in $2009) over this period. Finally we simulate the effect of Social Security reforms such as raising the normal retirement age and changing the benefit formula to see whether they mitigate or enhance the reduced progressivity resulting from the widening gap in life expectancy.

The Cognitive Effects of Micronutrient Deficiency: Evidence from Salt Iodization in the United States.

Iodine deficiency is the leading cause of preventable mental retardation in the world today. The condition, which was common in the developed world until the introduction of iodized salt in the 1920s, is connected to low iodine levels in the soil and water. We examine the impact of salt iodization on cognitive outcomes in the US by taking advantage of this natural geographic variation. Salt was iodized over a short period of time beginning in 1924. We use military data collected during WWI and WWII to compare outcomes of cohorts born before and after iodization in localities that were naturally poor and rich in iodine. We find that for the one quarter of the population most deficient in iodine this intervention raised IQ by approximately one standard deviation. Our results can explain roughly one decade's worth of the upward trend in IQ in the US (the Flynn Effect). We also document a large increase in thyroid-related deaths following the countrywide adoption of iodized salt, which affected mostly older individuals in localities with high prevalence of iodine deficiency.

The Effect of Fertility Reduction on Economic Growth.

We assess quantitatively the effect of exogenous reductions in fertility on output per capita. Our simulation model allows for effects that run through schooling, the size and age structure of the population, capital accumulation, parental time input into child-rearing, and crowding of fixed natural resources. The model is parameterized using a combination of microeconomic estimates, data on demographics and natural resource income in developing countries, and standard components of quantitative macroeconomic theory. We apply the model to examine the effect of a change in fertility from the UN medium-variant to the UN low-variant projection, using Nigerian vital rates as a baseline. For a base case set of parameters, we find that such a change would raise output per capita by 5.6 percent at a horizon of 20 years, and by 11.9 percent at a horizon of 50 years.

MEASURING ECONOMIC GROWTH FROM OUTER SPACE.

GDP growth is often measured poorly for countries and rarely measured at all for cities or subnational regions. We propose a readily available proxy: satellite data on lights at night. We develop a statistical framework that uses lights growth to augment existing income growth measures, under the assumption that measurement error in using observed light as an indicator of income is uncorrelated with measurement error in national income accounts. For countries with good national income accounts data, information on growth of lights is of marginal value in estimating the true growth rate of income, while for countries with the worst national income accounts, the optimal estimate of true income growth is a composite with roughly equal weights. Among poor-data countries, our new estimate of average annual growth differs by as much as 3 percentage points from official data. Lights data also allow for measurement of income growth in sub- and supranational regions. As an application, we examine growth in Sub Saharan African regions over the last 17 years. We find that real incomes in non-coastal areas have grown faster by 1/3 of an annual percentage point than coastal areas; non-malarial areas have grown faster than malarial ones by 1/3 to 2/3 annual percent points; and primate city regions have grown no faster than hinterland areas. Such applications point toward a research program in which "empirical growth" need no longer be synonymous with "national income accounts."

On the dynamics of the age structure, dependency, and consumption.

We examine the effects of population aging due to declining fertility and rising elderly life expectancy on consumption possibilities in the presence of intergenerational transfers. Our analysis is based on a highly tractable continuous-time overlapping generations model in which the population is divided into three groups (youth dependents, workers, and elderly dependents) and lifecourse transitions take place in a probabilistic fashion. We show that the consumption-maximizing response to greater longevity in highly developed countries is an increase in fertility. However, with larger transfer payments, the actual fertility response will likely be the opposite, leading to further population aging.

Mortality Change, the Uncertainty Effect, and Retirement.

We examine the role of declining mortality in explaining the rise of retirement over the course of the 20th century. We construct a model in which individuals make labor/leisure choices over their lifetimes subject to uncertainty about their dates of death. In an environment with high mortality, an individual who saves for retirement faces a high risk of dying before he can enjoy his planned leisure. In this case, the optimal plan is for people to work until they die. As mortality falls, however, it becomes optimal to plan, and save for, retirement. We analyze our model using two mathematical formulations of the survival function as well as data on actual changes in the US life table over the last century, and show that this "uncertainty effect" of declining mortality would have more than outweighed the "horizon effect" by which rising life expectancy would have led to later retirement.

Post-1500 Population Flows and the Long Run Determinants of Economic Growth and Inequality.

We construct a matrix showing the share of the year 2000 population in every country that is descended from people in different source countries in the year 1500. Using the matrix to adjust indicators of early development so they reflect the history of a population's ancestors rather than the history of the place they live today greatly improves the ability of those indicators to predict current GDP. The variance of early development history of a country's inhabitants is a good predictor for current inequality, with ethnic groups originating in regions having longer histories of organized states tending to be at the upper end of a country's income distribution.

WHEN DOES IMPROVING HEALTH RAISE GDP?

We assess quantitatively the effect of exogenous health improvements on output per capita. Our simulation model allows for a direct effect of health on worker productivity, as well as indirect effects that run through schooling, the size and age-structure of the population, capital accumulation, and crowding of fixed natural resources. The model is parameterized using a combination of microeconomic estimates, data on demographics, disease burdens, and natural resource income in developing countries, and standard components of quantitative macroeconomic theory. We consider both changes in general health, proxied by improvements in life expectancy, and changes in the prevalence of two particular diseases: malaria and tuberculosis. We find that the effects of health improvements on income per capita are substantially lower than those that are often quoted by policy-makers, and may not emerge at all for three decades or more after the initial improvement in health. The results suggest that proponents of efforts to improve health in developing countries should rely on humanitarian rather than economic arguments.

Manganese and other micronutrient additions to improve yield of Agaricus bisporus.

Previous experiments have demonstrated that significant increases in yield of Agaricus bisporus mushrooms were achieved by adding a micronutrient rich fertilizer, Micromax, to the compost. This study was performed to determine the mineral(s) that are responsible for this yield improvement. An initial experiment determined that manganese was the mineral of primary importance; addition of 184 mg kg-1 Mn increased yield by 10.8%, compared to the control. Subsequent experiments demonstrated that the addition of manganese to the compost has a stimulatory effect on mushroom yields. Significant yield increases, ranging from 9.6% to 11.8% (compared to the control), were observed as a result of manganese additions varying between 50 and 300 mg kg-1. Also, data from the last set of experiments indicated that Micromax additions always resulted in greater yields indicating that micronutrients in Micromax, in addition to manganese, may be responsible for increasing yields.