A modified false discovery rate multiple-comparisons procedure for discrete data, applied to human immunodeficiency virus genetics

Summary.  To help to design vaccines for acquired immune deficiency syndrome that protect broadly against many genetic variants of the human immunodeficiency virus, the mutation rates at 118 positions in HIV amino-acid sequences of subtype C versus those of subtype B were compared. The false discovery rate (FDR) multiple-comparisons procedure can be used to determine statistical significance. When the test statistics have discrete distributions, the FDR procedure can be made more powerful by a simple modification. The paper develops a modified FDR procedure for discrete data and applies it to the human immunodeficiency virus data. The new procedure detects 15 positions with significantly different mutation rates compared with 11 that are detected by the original FDR method. Simulations delineate conditions under which the modified FDR procedure confers large gains in power over the original technique. In general FDR adjustment methods can be improved for discrete data by incorporating the modification proposed.     

Significance of the Dermal Route of Exposure to Risk Assessment

The skin is a route of exposure that needs to be considered when conducting a risk assessment. It is necessary to identify the potential for dermal penetration by a chemical as well as to determine the overall importance of the dermal route of exposure as compared with inhalation or oral routes of exposure. The physical state of the chemical, vapor or liquid, the concentration, neat or dilute, and the vehicle, lipid or aqueous, is also important. Dermal risk is related to the product of the amounts of penetration and toxicity. Toxicity involves local effects on the skin itself and the potential for systemic effects. Dermal penetration is described in large part by the permeability constant. When permeability constants are not known, partition coefficients can be used to estimate a chemical's potential to permeate the skin. With these concepts in mind, a tiered approach is proposed for dermal risk assessment. A key first step is the determination of a skin-to-air or skin-to-medium partition coefficient to estimate a potential for dermal absorption. Building a physiologically-based pharmacokinetic (PBPK) model is another step in the tiered approach and is useful prior to classical in vivo toxicity tests. A PBPK model can be used to determine a permeability constant for a chemical as well as to show the distribution of the chemical systemically. A detailed understanding of species differences in the structure and function of the skin and how they relate to differences in penetration rates is necessary in order to extrapolate animal data from PBPK models to the human. A study is in progress to examine anatomical differences for four species.     

EVALUATING CHANGES IN THE DISTRIBUTION OF CAPITAL WEALTH

A small-scale general equilibrium model in which the distribution of capital wealth is a key parameter is employed to examine the potential economic consequences of greater capital wealth equality. Every performance indicator examined – aggregate income, consumption equality, social welfare in the sum-of-utilities sense, and aggregate saving –is improved by greater capital wealth equality. However, the bottom-line social welfare gain, relative to the present high-inequality situation – even from the maximum achievable level of complete equality in capital wealth distribution – would be numerically rather modest.     

Reducing U.S. carbon dioxide emissions: an assessment of different instruments

The possibility that carbon dioxide emissions from fossil fuel use might lead to global warming has become a leading environmental concern. Many scientific and environmental organizations have called for immediate action to limit carbon dioxide production. For the most part, however, public debate has focused on a single policy instrument: a carbon tax applied to fossil fuels in proportion to their carbon content. We present a detailed model of the U.S. economy and use it to compare carbon taxes with two other instruments that could achieve the same reduction in carbon dioxide emissions: a tax on the energy content of fossil fuels (a BTU tax) and an ad valorem tax on fuel use. We find that carbon taxes can achieve a given reduction with the least overall effect on the economy, but with a large effect on coal mining. Energy taxes are fairly similar to carbon taxes but have slightly less impact on coal mining and slightly greater overall cost. In contrast, ad valorem taxes fall much more lightly on coal mining but have a much greater effect on the economy as a whole.     

Lumpers and Splitters: The Public Opinion Information that Politicians Collect and Use

Are the decisions of American policymakers informed by generaltrends in the public’s ideology or by the public’spolicy-specific preferences? In this article we discuss twoexplanations for the types of public opinion information thatpoliticians collect and use. Using a unique data set of privatepolls from the White House of Richard Nixon, we find that whenopinion data on specific policies were available, the presidentrelied on them and not on general ideology data. On less importantissues, however, we find that the president often chose notto collect policy-specific data and instead relied on generalideology data. The differential collection and use of informationby policymakers reflect varying strategic calculations. Theyalso have profound implications for representative democracyand the demands placed on citizens and governors.     

TEACHING TOOLS: ON JOURNALISTS' USE OF MACROECONOMIC CONCEPTS

Five macroeconomic concepts are presented which are prominent in the business sections of newspapers, but which are not given equivalent prominence in macroeconomic textbooks. These are the discouraged worker phenomenon, the use of inventories in forecasting, the effect of changes in the money supply on the bond market, and the effects of inflation and nominal interest rates in the foreign exchange market. These concepts are presented via news clips illustrating the way they typically appear in the press. Instructors are urged to place extra emphasis on these concepts.     

Influence of behavioural tactics on recruitment and reproductive trajectory in the kittiwake

Many studies have provided evidence that, in birds, inexperienced breeders have a lower probability of breeding successfully. This is often explained by lack of skills and knowledge, and sometimes late laying dates in the first breeding attempt. There is growing evidence that in many species with deferred reproduction, some prebreeders attend breeding places, acquire territories and form pairs. Several behavioural tactics assumed to be associated with territory acquisition have been described in different species. These tactics may influence the probability of recruiting in the breeding segment of the population, age of first breeding, and reproductive success in the first breeding attempt. Here we addressed the influence of behaviour ('squatting') during the prebreeding period on demographic parameters (survival and recruitment probability) in a long-lived colonial seabird species: the kittiwake. We also investigated the influence of behaviour on reproductive trajectory. Squatters have a higher survival and recruitment probability, and a higher probability of breeding successfully in the first breeding attempt in all age-classes where this category is represented. The influence of behaviour is mainly expressed in the first reproduction. However, there is a relationship between breeding success in the first occasion and subsequent occasions. The influence of breeding success in the first breeding attempt on the rest of the trajectory may indirectly reflect the influence of behaviour on breeding success in the first occasion. The shape of the reproductive trajectory is influenced by behaviour and age of first breeding. There is substantial individual variation from the mean reproductive trajectory, which is accounted for by heterogeneity in performance among individuals in the first attempt, but there is no evidence of individual heterogeneity in the rate of change over time in performance in subsequent breeding occasions