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The flexibility and wide applicability of the Fisher randomization test (FRT) make it an attractive tool for assessment of causal effects of interventions from modern-day randomized experiments that are increasing in size and complexity. This paper provides a theoretical inferential framework for FRT by establishing its connection with confidence distributions. Such a connection leads to development’s of (i) an unambiguous procedure for inversion of FRTs to generate confidence intervals with guaranteed coverage, (ii) new insights on the effect of size of the Monte Carlo sample on the estimation of a p-value curve and (iii) generic and specific methods to combine FRTs from multiple independent experiments with theoretical guarantees. Our developments pertain to finite sample settings but have direct extensions to large samples. Simulations and a case example demonstrate the benefit of these new developments.

 

The U.S. has merely 4% of the world population, but contains 25% of the world’s COVID-19 cases. Since the COVID-19 outbreak in the U.S., Massachusetts has been leading other states in the total number of COVID-19 cases. Racial residential segregation is a fundamental cause of racial disparities in health. Moreover, disparities of access to health care have a large impact on COVID-19 cases. Thus, this study estimates racial segregation and disparities in testing site access and employs economic, demographic, and transportation variables at the city/town level in Massachusetts. Spatial regression models are applied to evaluate the relationships between COVID-19 incidence rate and related variables. This is the first study to apply spatial analysis methods across neighborhoods in the U.S. to examine the COVID-19 incidence rate. The findings are: (1) Residential segregations of Hispanic and Non-Hispanic Black/African Americans have a significantly positive association with COVID-19 incidence rate, indicating the higher susceptibility of COVID-19 infections among minority groups. (2) Non-Hispanic Black/African Americans have the shortest drive time to testing sites, followed by Hispanic, Non-Hispanic Asians, and Non-Hispanic Whites. The drive time to testing sites is significantly negatively associated with the COVID-19 incidence rate, implying the importance of the accessibility of testing sites by all populations. (3) Poverty rate and road density are significant explanatory variables. Importantly, overcrowding represented by more than one person per room is a significant variable found to be positively associated with COVID-19 incidence rate, suggesting the effectiveness of social distancing for reducing infection. (4) Different from the findings of previous studies, the elderly population rate is not statistically significantly correlated with the incidence rate because the elderly population in Massachusetts is less distributed in the hotspot regions of COVID-19 infections. The findings in this study provide useful insights for policymakers to propose new strategies to contain the COVID-19 transmissions in Massachusetts. 

Abstract Aldehyde dehydrogenases (ALDHs) catalyze the conversion of various aliphatic and aromatic aldehydes into corresponding carboxylic acids. Traditionally considered as housekeeping enzymes, new biochemical roles are being identified for members of ALDH family. Recent work showed that AldA from the plant pathogen Pseudomonas syringae strain PtoDC3000 (PtoDC3000) functions as an indole-3-acetaldehyde dehydrogenase for the synthesis of indole-3-acetic acid (IAA). IAA produced by AldA allows the pathogen to suppress salicylic acid-mediated defenses in the model plant Arabidopsis thaliana. Here we present a biochemical and structural analysis of the AldA indole-3-acetaldehyde dehydrogenase from PtoDC3000. Site-directed mutants targeting the catalytic residues Cys302 and Glu267 resulted in a loss of enzymatic activity. The X-ray crystal structure of the catalytically inactive AldA C302A mutant in complex with IAA and NAD+ showed the cofactor adopting a conformation that differs from the previously reported structure of AldA. These structures suggest that NAD+ undergoes a conformational change during the AldA reaction mechanism similar to that reported for human ALDH. Site-directed mutagenesis of the IAA binding site indicates that changes in the active site surface reduces AldA activity; however, substitution of Phe169 with a tryptophan altered the substrate selectivity of the mutant to prefer octanal. The present study highlights the inherent biochemical versatility of members of the ALDH enzyme superfamily in P. syringae.