Threshold‐free estimation of functional antibody titers of a group B streptococcus opsonophagocytic killing assay

Opsonophagocytic killing assays (OPKA) are routinely used for the quantification of bactericidal antibodies in blood serum samples. Quantification of the OPKA readout, the titer, provides the basis for the statistical analysis of vaccine clinical trials having functional immune response endpoints. Traditional OPKA titers are defined as the maximum serum dilution yielding a predefined bacterial killing threshold value, and they are estimated by fitting a dose‐response model to the dilution‐killing curve. This paper illustrates a novel definition of titer, the threshold‐free titer, which preserves biological interpretability while not depending on any killing threshold or on a postulated shape of the dose‐response curve. These titers are shown to be more precise than the traditional threshold‐based titers when using simulated and experimental group B streptococcus OPKA experimental data. Also, titer linearity is shown to be not measurable when using threshold‐based titers, whereas it becomes measurable using threshold‐free titers. The biological interpretability and operational characteristics demonstrated here indicate that threshold‐free titers are an appropriate tool for the routine analysis of OPKA data. Copyright © 2015 John Wiley & Sons, Ltd.     

Spouses’ earnings association and inequality: A non-linear perspective

We analyze the association between spouses’ earnings taking account of non-linearities along both spouses’ distribution of earnings. We also document the non-linearity of the relationships between earnings and labor force participation, earnings and couple formation, and earnings and number of children. Using simulations, we then analyze how changes in spouses’ rank-dependence structure, labor force participation and couple formation contribute to the upsurge in inequality in the U.S between 1967 and 2018. We find that an increased tendency towards positive sorting contributed substantially to the rise in inequality only among dual-earner couples, while it contributed little to overall inequality across households. Temporal and distributional heterogeneity are important, as earnings association had a more substantial role in the bottom of the earnings distribution and in recent years. The decline in couple formation contributed substantially to the rise in inequality, while the increase in female labor force participation and the fertility decline had equalizing effects.

     

Endogenous fertility,endogenous lifetime and economic growth: the role of child policies

We examine the effects of child policies on both transitional dynamics and long-term demo-economic outcomes in an overlapping-generations neoclassical growth model à la Chakraborty (J Econ Theory 116(1):119–137, 2004) extended with endogenous fertility under the assumption of weak altruism towards children. The government invests in public health, and an individual’s survival probability at the end of youth depends on health expenditure. We show that multiple development regimes can exist. However, poverty or prosperity does not necessarily depend on the initial conditions, since they are the result of how a child policy is designed. A child tax, for example, can be used effectively to enable those economies that were entrapped in poverty to prosper. There is also a long-term welfare-maximising level of the child tax. We show that a child tax can be used to increase capital accumulation, escape from poverty and maximise long-term welfare also when (a) a public pay-as-you-go pension system is in place and (b) the government issues an amount of public debt. Interestingly, there also exists a couple child tax–health tax that can be used to find the second-best optimum optimorum. In addition, we show that results are robust to the inclusion of decisions regarding the child quantity–quality trade-off under the assumption of impure altruism. In particular, there exists a threshold value of the child tax below (resp. above) which child quality spending is unaffordable (resp. affordable) and different scenarios are in existence.     

Education and Life Satisfaction in Relation to the Probability of Social Trust: a Conceptual Framework and Empirical Analysis

We employ cross-sectional microdata from 2010 through 2012 collected by the Italian National Institute of Statistics to investigate the proposed conceptual framework regarding the joint relationship between education, life satisfaction and the probability of social trust. The analysis has been carried out using two alternative specifications of the logit model: parametric and semiparametric. Our findings suggest that (a) both modelling methods that we utilise yield consistent results in terms of the positive effects of education and life satisfaction on social trust; (b) for unsatisfied individuals, social trust is generally low and largely unresponsive to the individual’s education level, whereas for ‘sufficiently satisfied’ individuals, social trust increases strongly with education; (c) there are some gender differences in the joint relationship between education, life satisfaction and social trust and (d) the parametric approach tends to mask some interesting patterns that are captured by the semiparametric specification. This finding implies that the parametric approach leads to a biased interpretation of the results, with an apparent failure of some of the assumptions made in the conceptual framework.     

Testing for Serial Independence: Beyond the Portmanteau Approach

Portmanteau tests are typically used to test serial independence even if, by construction, they are generally powerful only in presence of pairwise dependence between lagged variables. In this article, we present a simple statistic defining a new serial independence test, which is able to detect more general forms of dependence. In particular, differently from the Portmanteau tests, the resulting test is powerful also under a dependent process characterized by pairwise independence. A diagram, based on p-values from the proposed test, is introduced to investigate serial dependence. Finally, the effectiveness of the proposal is evaluated in a simulation study and with an application on financial data. Both show that the new test, used in synergy with the existing ones, helps in the identification of the true data-generating process. Supplementary materials for this article are available online.     

Modified chain sampling plans for lot inspection by variables and attributes

The purpose of acceptance sampling is to develop decision rules to accept or reject production lots based on sample data. When testing is destructive or expensive, dependent sampling procedures cumulate results from several preceding lots. This chaining of past lot results reduces the required size of the samples. A large part of these procedures only chain past lot results when defects are found in the current sample. However, such selective use of past lot results only achieves a limited reduction of sample sizes. In this article, a modified approach for chaining past lot results is proposed that is less selective in its use of quality history and, as a result, requires a smaller sample size than the one required for commonly used dependent sampling procedures, such as multiple dependent sampling plans and chain sampling plans of Dodge. The proposed plans are applicable for inspection by attributes and inspection by variables. Several properties of their operating characteristic-curves are derived, and search procedures are given to select such modified chain sampling plans by using the two-point method.     

Re-randomization tests as sensitivity analyses to confirm immunological noninferiority of an investigational vaccine: Case study

Here we present as case study how re-randomization tests were performed in two randomized, controlled clinical trials as sensitivity analyses, as recommended by the United States Food and Drug Administration in the context of adaptive randomization. This was done to confirm primary conclusions on immunological noninferiority of an investigational new fully liquid presentation of a quadrivalent cross-reacting material conjugate meningococcal vaccine (MenACWY-CRM), over its licensed lyophilized/liquid presentation. In two phase 2b studies (Study #1: NCT03652610; Study #2: NCT03433482), noninferiority of the fully liquid presentation of MenACWY-CRM to the licensed presentation was assessed and demonstrated for immune responses against meningococcal serogroup A (MenA), the only vaccine component modified from lyophilized to liquid in the new presentation. The original vaccine assignment algorithm, with a minimization procedure accounting for center or center within age strata, was used to re-randomize participants belonging to the fully liquid and licensed vaccine groups while keeping antibody responses, covariates and entry order as observed. Test statistics under re-randomization were generated according to the ANCOVA model used in the primary analysis. To confirm immunological noninferiority following re-randomization, the corresponding p-values had to be <0.025. For both studies and all primary objective evaluations, the re-randomization p-values were well below 0.025 (0.0004 for Study #1; 0.0001 for the two co-primary endpoints in Study #2). Re-randomization tests performed to comply with a regulatory request confirmed the primary conclusions of immunological noninferiority for the MenA of the fully liquid compared to the licensed vaccine presentation.     

The Place of Construction in Sociological Realism

In the contemporary epistemological debate on social reality, characterized by the crisis of post‐modern theories and the emergence of new forms of realism, are there any approaches not acknowledging some specific ontological character to the construction of social objects? The question is apparently rhetorical, but the implication of this problem are not obvious. In the sociological literature the opposition between reality and construction is not clearly defined. Sometimes it is considered a dichotomy, in other situations the synthesis of alternative theses in a dialectical horizon. The more systematic attempt considers reality and construction as analytical macro‐dimensions where the relation between social ontology and epistemology operates. From this stance, the acknowledgement of the role of social construction in a wider realist horizon is the true overtaking of postmodern philosophy. If it is true that facts exist beyond representations, it is also true that representations themselves have a specific effect on reality, who continually re‐structures itself around specific relations of emergent power. Stating that reality is socially constructed is an evident limit of postmodern theories. On the other hand, stating that only facts exist constitute an impoverishment of realism and its replacement in neo‐positivism. Social phenomena are real because they are based on specific properties of the inter‐subjective construction of social reality. This thesis represents the revitalization of an advanced, anti‐positivistic realism and the definition of the specificity of social objects. The aim of this essay is to search for a specific place of construction within the development of realist social ontology.     

BIG DATA AND BIG CITIES: THE PROMISES AND LIMITATIONS OF IMPROVED MEASURES OF URBAN LIFE

New, “big data” sources allow measurement of city characteristics and outcome variables at higher collection frequencies and more granular geographic scales than ever before. However, big data will not solve large urban social science questions on its own. Big urban data has the most value for the study of cities when it allows measurement of the previously opaque, or when it can be coupled with exogenous shocks to people or place. We describe a number of new urban data sources and illustrate how they can be used to improve the study and function of cities. We first show how Google Street View images can be used to predict income in New York City, suggesting that similar imagery data can be used to map wealth and poverty in previously unmeasured areas of the developing world. We then discuss how survey techniques can be improved to better measure willingness to pay for urban amenities. Finally, we explain how Internet data is being used to improve the quality of city services. (JEL R1, C8, C18)     

A comparison of approaches for estimating the effect of women's education on the probability of using modern contraceptive methods in Malawi

The aim of this study is to estimate the effect of education on the probability of married Malawian women using modern contraceptive methods by accounting for both observed and unobserved confounders. We conduct a sensitivity analysis and compare the results of naive models with instrumental variable models to account for the potential endogeneity of education. Our findings demonstrate conflicting results between the two modelling approaches. The naive models report smaller education effects on the probability of using modern contraceptive methods compared to instrumental variable models. We also find that by relaxing the functional form assumption on the effect of continuous covariates, using a flexible instrumental variable model, the education's effect follows a positive, nonlinear pattern. This finding is not observed with a classic instrumental variable model.