Local Propensity Research Articles

Covariate balance-related propensity score weighting in estimating overall hazard ratio with distributed survival data

BackgroundWhen data is distributed across multiple sites, sharing information at the individual level among sites may be difficult. In these multi-site studies, propensity score model can be fitted with data within each site or data from all sites when using inverse probability-weighted Cox regression to estimate overall hazard ratio. However, when there is unknown heterogeneity of covariates in different sites, either approach may lead to potential bias or reduced efficiency. In this study, we proposed a method to estimate propensity score based on covariate balance-related criterion and estimate the overall hazard ratio while overcoming data sharing constraints across sites.MethodsThe proposed propensity score was generated by choosing between global and local propensity score based on covariate balance-related criterion, combining the global propensity score fitted in the entire population and the local propensity score fitted within each site. We used this proposed propensity score to estimate overall hazard ratio of distributed survival data with multiple sites, while requiring only the summary-level information across sites. We conducted simulation studies to evaluate the performance of the proposed method. Besides, we applied the proposed method to real-world data to examine the effect of radiation therapy on time to death among breast cancer patients.ResultsThe simulation studies showed that the proposed method improved the performance in estimating overall hazard ratio comparing with global and local propensity score method, regardless of the number of sites and sample size in each site. Similar results were observed under both homogeneous and heterogeneous settings. Besides, the proposed method yielded identical results to the pooled individual-level data analysis. The real-world data analysis indicated that the proposed method was more likely to find a significant effect of radiation therapy on mortality compared to the global propensity score method and local propensity score method.ConclusionsThe proposed covariate balance-related propensity score in multi-site distributed survival data outperformed the global propensity score estimated using data from the entire population or the local propensity score estimated within each site in estimating the overall hazard ratio. The proposed approach can be performed without individual-level data transfer between sites and would yield the same results as the corresponding pooled individual-level data analysis.

The association between local brain structure and disgust propensity

Research has discovered structural differences in the brains of people with different personality types. In the present voxel-based morphometry study we focused on the association between disgust propensity (DP: the temporally stable tendency to experience disgust across different situations) and grey matter volume (GMV) in regions of interest [insula, orbitofrontal cortex (OFC), basal ganglia]. We collected structural brain scans from 498 healthy individuals (352 females, 146 males; mean age = 27 years). Regression analyses were performed to test the association between three domains of DP (core, animal-reminder, contamination) and GMV. We observed negative correlations between animal-reminder DP and the volume of the insula, and contamination DP and OFC volume. Animal-reminder DP correlated positively with GMV in the basal ganglia (putamen). This study identified weak correlations between local brain volume and disgust propensity. The association between DP and insula volume concerned the posterior insula and was in the opposite of the expected direction. The findings of this study are inconsistent with the concept of the anterior insula as a region that specifically mediates DP.

Breaking Ties: Regression Discontinuity Design Meets Market Design

Many schools in large urban districts have more applicants than seats. Centralized school assignment algorithms ration seats at over‐subscribed schools using randomly assigned lottery numbers, non‐lottery tie‐breakers like test scores, or both. The New York City public high school match illustrates the latter, using test scores and other criteria to rank applicants at the city's screened schools, combined with lottery tie‐breaking at the rest. We show how to identify causal effects of school attendance in such settings. Our approach generalizes regression discontinuity methods to allow for multiple treatments and multiple running variables, some of which are randomly assigned. The key to this generalization is a local propensity score that quantifies the school assignment probabilities induced by lottery and non‐lottery tie‐breakers. The utility of the local propensity score is demonstrated in an assessment of the predictive value of New York City's school report cards. Schools that earn the highest report card grade indeed improve SAT math scores and increase graduation rates, though by much less than OLS estimates suggest. Selection bias in OLS estimates of grade effects is egregious for screened schools.

Assessing the low complexity of protein sequences via the low complexity triangle.

Proteins with low complexity regions (LCRs) have atypical sequence and structural features. Their amino acid composition varies from the expected, determined proteome-wise, and they do not follow the rules of structural folding that prevail in globular regions. One way to characterize these regions is by assessing the repeatability of a sequence, that is, calculating the local propensity of a region to be part of a repeat. We combine two local measures of low complexity, repeatability (using the RES algorithm) and fraction of the most frequent amino acid, to evaluate different proteomes, datasets of protein regions with specific features, and individual cases of proteins with extreme compositions. We apply a representation called 'low complexity triangle' as a proof-of-concept to represent the low complexity measured values. Results show that proteomes have distinct signatures in the low complexity triangle, and that these signatures are associated to complexity features of the sequences. We developed a web tool called LCT (http://cbdm-01.zdv.uni-mainz.de/~munoz/lct/) to allow users to calculate the low complexity triangle of a given protein or region of interest. The low complexity triangle proves to be a suitable procedure to represent the general low complexity of a sequence or protein dataset. Homorepeats, direpeats, compositionally biased regions and globular regions occupy characteristic positions in the triangle. The described pipeline can be used to characterize LCRs and may help in quantifying the content of degenerated tandem repeats in proteins and proteomes.

The evolutionary background and functional consequences of the rs2071307 polymorphism in human tropoelastin.

Elastin is a major polymeric protein of the extracellular matrix, providing critical properties of extensibility and elastic recoil. The rs2071307 genomic polymorphism, resulting in the substitution of a serine for a glycine residue in a VPG motif in tropoelastin, has an unusually high minor allele frequency in humans. A consequence of such allelic heterozygosity would be the presence of a heterogeneous elastin polymer in up to 50% of the population, a situation which appears to be unique to Homo sapiens. VPG motifs are extremely common in hydrophobic domains of tropoelastins and are the sites of transient β-turns that are essential for maintaining the conformational flexibility required for its function as an entropic elastomer. Earlier data demonstrated that single amino acid substitutions in tropoelastin can have functional consequences for polymeric elastin, particularly when present in mixed polymers. Here, using NMR and molecular dynamics approaches, we show the rs2071307 polymorphism reduces local propensity for β-turn formation, with a consequent increase in polypeptide hydration and an expansion of the conformational ensemble manifested as an increased hydrodynamic radius, radius of gyration and asphericity. Furthermore, this substitution affects functional properties of polymeric elastin, particularly in heterogeneous polymers mimicking allelic heterozygosity. We discuss whether such effects, together with the unusually high minor allele frequency of the polymorphism, could imply some some evolutionary advantage for the heterozygous state.

Family-managed firms and local export spillovers: evidence from Spanish manufacturing firms

ABSTRACT By combining arguments from regional economics and family business research, the aim of this article is to test the relationships among local export spillovers, management characteristics, and export propensity on a large sample of Spanish manufacturing firms over the 2003–2015 period. We find that family-managed firms, compared to their non-family counterparts, benefit more from being located in regions with a high density of exporters. Because of their firm-specific social capital and strong embeddedness in local networks, family-managed firms are better positioned to leverage the spatially bounded flow of knowledge and information in these regions, resulting in a higher likelihood to export than non-family firms. Additionally, our results show that the knowledge spillover effect is stronger for small and low-tech family firms’ export propensity.

Quantitative Characterization of Binding Pockets and Binding Complementarity by Means of Zernike Descriptors.

In this work, we describe the application of the Zernike formalism to quantitatively characterize the binding pockets of two sets of biologically relevant systems. Such an approach, when applied to molecular dynamics trajectories, is able to pinpoint the subtle differences between very similar molecular regions and their impact on the local propensity to ligand binding, allowing us to quantify such differences. The statistical robustness of our procedure suggests that it is very suitable to describe protein binding sites and protein–ligand interactions within a rigorous and well-defined framework.

Breaking Ties: Regression Discontinuity Design Meets Market Design

Many schools in large urban districts have more applicants than seats. Centralized school assignment algorithms ration seats at over-subscribed schools using randomly assigned lottery numbers, non-lottery tie-breakers like test scores, or both. The New York City public high school match illustrates the latter, using test scores and other criteria to rank applicants at ``screened'' schools, combined with lottery tie-breaking at unscreened ``lottery'' schools. We show how to identify causal effects of school attendance in such settings. Our approach generalizes regression discontinuity methods to allow for multiple treatments and multiple running variables, some of which are randomly assigned. The key to this generalization is a local propensity score that quantifies the school assignment probabilities induced by lottery and non-lottery tie-breakers. The local propensity score is applied in an empirical assessment of the predictive value of New York City's school report cards. Schools that receive a high grade indeed improve SAT math scores and increase graduation rates, though by much less than OLS estimates suggest. Selection bias in OLS estimates is egregious for screened schools.

Local Creative Culture and Dividend Policy

This paper examines the role of local risk-taking propensity on dividend demand and corporate payout by using a novel measure. We empirically investigate geographically varying dividend demand and corporate dividend policies by using local creative culture as a measure of local risk-taking tendency. We find that firms located in areas with a strong creative culture are less likely to pay and initiate dividends. These firms also have lower levels of dividend yield. The empirical findings also remain robust after addressing endogeneity and a series of robustness checks.. In addition, our paper highlights the local component of corporate dividend policies and supports the notion that firms cater to investors’ dividend preferences determined by investors’ risk-taking characteristics through dividend policies. Our results underscore the importance of cultural determinants of investors’ risk-taking for the financial industry participants.

Short-term memory effects on visual global/local processing in tufted capuchin monkeys (Sapajus spp.).

Nonhuman primates, differently from humans, are less proficient at processing global properties of visual compound stimuli. It has been suggested that humans preferentially process stimuli globally because this enables a more economical encoding of the stimuli. In this study we assessed the role of short-term memory (STM) in global/local processing by presenting tufted capuchin monkeys with Navon-type hierarchical figures in both simultaneous and delayed matching-to-sample tasks. Capuchins' ability to discriminate hierarchical stimuli was evaluated as a function of increasing delay intervals (0.0, 0.5, 1.0, 2.0 and 3.0 sec) between the disappearance of the sample and the presentation of the comparison stimuli. The results showed that recognition accuracy for local features was above chance level with delays of up to 3.0 sec, as previously reported when capuchins were faced with nonhierarchical stimuli. By contrast, the recognition of global configurations was above chance level in simultaneous, 0.0 and 0.5 sec delay conditions but not at delay intervals of 1.0 sec or longer. These findings indicate that capuchins' propensity to process the local properties of visual stimuli can be observed when a delay is interposed between the presentation of sample and comparison stimuli and was not reversed by increasing the delay. Moreover, our results show that capuchins' local propensity was not reversed by increasing stimulus size. Overall, our study confirms crucial differences between human and nonhuman primates and adds new insights into the comparative research on visual grouping functions of these species. (PsycINFO Database Record

Extenuating Circumstances: Salvaged Landscape

AbstractBuilt outside legislative guidelines and established construction procedures in the derelict and feral environment of Detroit, Salvaged Landscapes is a true product of transgression. As Catie Newell, founding principal of *Alibi Studio, explains, its making and unmaking was as dependent on the intentions of the designers as the local propensity for arson.

Carnosine Inhibits Aβ42 Aggregation by Perturbing the H‐Bond Network in and around the Central Hydrophobic Cluster

Aggregation of the amyloid-β peptide (Aβ) into fibrillar structures is a hallmark of Alzheimer's disease. Thus, preventing self-assembly of the Aβ peptide is an attractive therapeutic strategy. Here, we used experimental techniques and atomistic simulations to investigate the influence of carnosine, a dipeptide naturally occurring in the brain, on Aβ aggregation. Scanning force microscopy, circular dichroism and thioflavin T fluorescence experiments showed that carnosine does not modify the conformational features of Aβ42 but nonetheless inhibits amyloid growth. Molecular dynamics (MD) simulations indicated that carnosine interacts transiently with monomeric Aβ42 by salt bridges with charged side chains, and van der Waals contacts with residues in and around the central hydrophobic cluster ((17)LVFFA(21)). NMR experiments on the nonaggregative fragment Aβ12-28 did not evidence specific intermolecular interactions between the peptide and carnosine, in agreement with MD simulations. However, a close inspection of the spectra revealed that carnosine interferes with the local propensity of the peptide to form backbone hydrogen bonds close to the central hydrophobic cluster (residues E22, S26 and N27). Finally, MD simulations of aggregation-prone Aβ heptapeptide segments show that carnosine reduces the propensity to form intermolecular backbone hydrogen bonds in the region 18-24. Taken together, the experimental and simulation results (cumulative MD sampling of 0.2 ms) suggest that, despite the inability of carnosine to form stable contacts with Aβ, it might block the pathway toward toxic aggregates by perturbing the hydrogen bond network near residues with key roles in fibrillogenesis.

76 Protein–DNA binding and breathing dynamics of DNA

In the living cell, the double-stranded DNA molecule experiences thermal motions that induce spontaneous openings and re-closings of the double helix known as “DNA breathing,” or “DNA transient bubbles” (Englander et al., 1980). The propensity for breathing is interconnected with DNA local stability and flexibility (Vafabakhsh & Ha, 2012), which play a key role in DNA biological function (Bishop et al., 2012). Here, we investigate the relationship between the DNA local propensity for breathing and binding of two transcription factors (TFs): (i) the human TF YY1, (see e.g. Usheva & Shenk, 1996), and (ii) the nucleoid-associated protein Fis in Escherichia coli (see e.g. Finkel & Johnson, 1992). Using a mesoscopic nonlinear model of double-stranded DNA (Peyrard & Bishop, 1989) that can be augmented for rational design of DNA breathing (Alexandrov et al., 2010), we have simulated the dynamics of known Fis- and YY1-binding sites, analyzed published in vitro and genomic data-sets, and conducted targeted experimental tests of our predictions (Alexandrov et al., 2012; Nowak-Lovato et al., in press). We found a strong correlation between the propensity for breathing (at the binding sites) and YY1/Fis binding. We identified a breathing profile that is characteristic for a strong Fis-binding site that is significantly enriched among the identified in vivo E. coli Fis-binding sites. To test our understanding of how Fis binding is influenced by the breathing, we designed base-pair substitutions, mismatch, and O6-Guanine methylation modifications of nucleotides, in sequences that are known to interact (or not interact) with Fis, seeking to make the breathing either closer to or farther from the breathing profile of a strong Fis-binding site. For the modified DNA segments, we found that Fis-DNA binding, as assessed by EMSA, changed in accordance with our expectations. Further, by using site-specific chromatin immunopecipitations, BIOBASE data, and simulations, we also found a specific breathing profile at the binding cites of YY1 in vivo. Our finding suggests that the genomic-flanking sequence variations and SNPs presence may exert long-range effects on DNA breathing and predetermine YY1 binding in cells.

Evaluation of local control strategies in patients with localized Ewing sarcoma of bone: A report from the Children’s Oncology Group.

9537 Background: Patients (pts) with Ewing sarcoma (EWS) require local control, either with surgery alone (S), radiation alone (R), or a combination of surgery + radiation (S+R). Optimal choice of local control for disease control remains unclear. Our primary aim was to determine the mode of local control associated with the highest event-free survival (EFS). Methods: Pts with localized EWS of bone treated on INT0091, INT0154, or AEWS0031 phase III trials were included if they had complete local control data, did not have cranial tumors, received local control starting 2-6 months after enrollment, and were randomized to receive standard dose 5-drug chemotherapy every 3 weeks. We used propensity scores to control for differences in age, tumor site, and year of diagnosis between local control groups. We constructed Cox models controlling for local control propensity scores to assess the impact of local control type on EFS and overall survival (OS) from the start of local control. Results: 465 pts were included. Pts selected for S were treated more recently (p < 0.001), more likely to have appendicular tumors (p < 0.001), and younger (p = 0.02). Pts treated with R, compared to S, had higher unadjusted risk of any event (HR 1.70; 95% CI 1.18 - 2.44; p = 0.004) or death (HR 1.84; 95% CI 1.18 – 2.85; p = 0.006). Pts treated with S+R, compared to S, had higher unadjusted risk of death (HR 1.75; 95% CI 1.10 – 2.76; p = 0.02). After adjusting for propensity scores, there was a trend of higher risk of any event for pts treated with R (HR 1.42; 95% CI 0.94 – 2.14; p = 0.10) compared to S, though this was not statistically significant. No other differences in adjusted risk of event or death between local control groups were statistically significant. We confirmed these results with standard Cox models using age, tumor site, and year of diagnosis as covariates. Conclusions: In this large group of uniformly treated pts, investigator choice of local control approach was not significantly related to EFS. These data support current practice of surgical resection when feasible, while validating radiotherapy as a reasonable alternative in selected pts.

IN HIGH SCHOOL AND PREGNANT: THE IMPORTANCE OF EDUCATIONAL AND FERTILITY EXPECTATIONS FOR SUBSEQUENT OUTCOMES

This study uses the High School and Beyond data (1980–1992) to examine the importance of educational and fertility expectations in explaining the achievement gap of adolescent mothers for over 5,500 young women from different socioeconomic backgrounds. Using a non-parametric local propensity score regression, the study finds that the economic disadvantage associated with having a child in high school is particularly large in poor socioeconomic environments; however, this disadvantage is a result of preexisting differences in the educational and fertility expectations and is not because of a diminished capacity of the socioeconomic environment to mediate the effect of an unplanned childbirth. The findings suggest that childcare assistance and other policies designed to alleviate the burden of child rearing for young mothers of low means may not produce the desired improvement in their subsequent educational and labor market outcomes. A much earlier policy intervention with a focus on fostering young women's outlook for the future is needed.

In High School and Pregnant: The Importance of Educational and Fertility Expectations for Subsequent Outcomes

This study uses the High School and Beyond data (1980-1992) to examine the importance of educational and fertility expectations in explaining the achievement gap of adolescent mothers for over 5500 young women from different socioeconomic backgrounds. Using a non-parametric local propensity score regression, the study finds that the economic disadvantage associated with bearing a child in high school is particularly large in poor socioeconomic environments; however, this disadvantage is a result of pre-existing differences in the educational and fertility expectations and is not due to a diminished capacity of the socioeconomic environment to mediate the effect of an unplanned childbirth. The findings suggest that childcare assistance and other policies designed to alleviate the burden of childrearing for young mothers of low means may not produce the desired improvement in their subsequent educational and labor market outcomes. A much earlier policy intervention with a focus on fostering young women’s outlook for the future is needed.

CFP: a web-server for constructing sequence-based protein conformational flexibility profiles.

Many proteins contain conformationally flexible segments that undergo significant changes in the backbone conformation or completely lack a well-defined conformation. Previously, we have developed the generalized local propensity (GLP), a quantitative sequence-based measure of the protein backbone flexibility. In this paper, we present the CFP (Conformational Flexibility Profile) web-server that constructs the GLP flexibility profile for a user-submitted sequence and uses this profile to identify segments with high backbone flexibility. The statistical significance of a flexible sequence segment is assessed using the discrete scan statistics based on the density of flexible residues observed in this segment. CFP is publicly available at http://cfp.rit.albany.edu.

The relationship between N‐gram patterns and protein secondary structure

An n-gram pattern (NP{n,m}) in a protein sequence is a set of n residues and m wildcards in a window of size n+m. Each window of n+m amino acids is associated with a collection of NP{n,m} patterns based on the combinatorics of n+m objects taken m at a time. NP{n,m} patterns that are shared between sequences reflect evolutionary relationships. Recently the authors developed an alignment-independent protein classification algorithm based on shared NP{4,2} patterns that compared favorably to PSI-BLAST. Theoretically, NP{4,2} patterns should also reflect secondary structure propensity since they contain all possible n-grams for 1 < or = n < or = 4 and a window of 6 residues is wide enough to capture periodicities in the 2 < or = n < or = 5 range. This sparked interest in differentiating the information content in NP{4,2} patterns related to evolution from the content related to local propensity. The probability of alpha-, beta-, and coil components was determined for every NP{4,2} pattern over all the chains in the Protein Data Bank (PDB). An algorithm exclusively based on the Z-values of these distributions was developed, which accurately predicted 71-76% of alpha-helical segments and 62-67% of beta-sheets in rigorous jackknife tests. This provided evidence for the strong correlation between NP{4,2} patterns and secondary structure. By grouping PDB chains into subsets with increasing levels of sequence identity, it was also possible to separate the evolutionary and local propensity contributions to the classification process. The results showed that information derived from evolutionary relationships was more important for beta-sheet prediction than alpha-helix prediction.

Preferential Solvation in Urea Solutions at Different Concentrations: Properties from Simulation Studies

We performed molecular dynamics simulations of urea solutions at different concentrations with two urea models (OPLS and KBFF) to examine the structures responsible for the thermodynamic solution properties. Our simulation results showed that hydrogen-bonding properties such as the average number of hydrogen bonds and their lifetime distributions were nearly constant at all concentrations between infinite dilution and the solubility limit. This implies that the characterization of urea-water solutions in the molarity concentration scale as nearly ideal is a result of facile local hydrogen bonding rather than a global property. Thus, urea concentration does not influence the local propensity for hydrogen bonds, only how they are satisfied. By comparison, the KBFF model of urea donated fewer hydrogen bonds than OPLS. We found that the KBFF urea model in TIP3P water better reproduced the experimental density and diffusion constant data. Preferential solvation analysis showed that there were weak urea-urea and water-water associations in OPLS solution at short distances, but there were no strong associations. We divided urea molecules into large, medium, and small clusters to examine fluctuation properties and found that any particular urea molecule did not stay in the same cluster for a long time. We found neither persistent nor large clusters.

The High-Low Amputation Ratio: A Deeper Insight into Diabetic Foot Care?

The purpose of this study was to propose and evaluate a high to low (Hi-Lo) amputation ratio as a potential additional quality measure giving further insight into high-risk foot surveillance beyond foot screening examinations. As part of the Dartmouth Atlas of Health Care project, a secondary analysis was performed on Medicare administrative data. Amputation rates were adjusted for age, gender, and race. This included 37,808 minor (foot-level) amputations and 44,599 major amputations from 1996 to 1997. We also calculated the longitudinal national trends in the Hi-Lo ratio with data from the Centers for Disease Control and Prevention from 1992 to 2002. The adjusted mean Hi-Lo ratio was 1.35 (standard deviation, 0.42). The lowest ratio was 0.56, and the highest ratio was 3.43. The correlation coefficient for the Hi-Lo ratio with major amputation rate was 0.48 (P < .0001; R2 = 0.23). Similar correlations were found for the highest and lowest percentiles for major and minor rates. The Centers for Disease Control and Prevention data of the Hi-Lo ratio using the crude and age-adjusted rates suggest stable trends in the ratio over a decade. The Hi-Lo measure demonstrates face validity, yet only a small proportion of the variance is described by local propensity to perform major amputation or by major amputation rates alone. The United States has relied on a foot screening measure alone, perhaps explaining why major amputation rates have not substantively declined. If we are to reduce the amputation burden, we should begin with a straightforward measure that can be implemented at most any center.