Access to Opportunity Project: Final Report

This project’s goal is to lift up promising approaches, suggest new strategies and encourage honest conversations that result in public policy solutions to income and racial segregation and poverty. The overarching question that motivates this work is: What are effective policies and strategies that promote access to high-opportunity amenities for low-income families? As a first step, the researchers surveyed efforts on the ground in the metropolitan areas encompassing Seattle, Washington; Portland, Oregon; and San Diego, California, to determine whether there were any candidates for deeper study. We selected these three metropolitan areas for several reasons. First, prior interaction revealed that attention had been given to this question and that parties in each had embarked on purposeful efforts to make progress. Second, they represent a diverse array of communities that vary in significant ways, including along key economic, demographic, and social dimensions, and in some regards are bellwethers for changes beginning to take place in many parts of the country. As a consequence, experiences and successes in these places could potentially be applied to a diverse set of other urban areas across the United States. The three regions are among the largest in the United States, with Seattle and Portland being the largest in their respective states and San Diego third in California (behind Los Angeles and the Bay Area). Despite their size, they differ in important ways that result in different social and political dynamics prevailing in each location. In considering access to opportunity, one must understand the opportunities that are available in order to tailor skill-building efforts and investments in “connective infrastructure,” such as mass transit and suburban affordable housing, so that they are maximally effective. From an economic perspective, the three regions are quite different, which means that the approaches observed across the regions will potentially vary in measurable ways. In each metropolitan area, we sought the counsel of key governmental, practitioner, academic, and philanthropic players. During the course of our initial visits to each region, we met with and interviewed almost 80 people—28 in Seattle, 26 in Portland, and 24 in San Diego. Through these conversations, we identified 27 projects—nine in each metropolitan area—as being promising examples of cases where lower-income families may have achieved increased access to high-opportunity amenities. Given time, available funding, and the presence of partners willing to support our research effort by providing access to program data and program participants, we chose three projects for examination: • The San Diego Housing Commission’s Achievement Academy • Seattle/King County’s A Regional Coalition for Housing (ARCH) • Humboldt Gardens in Northeast Portlan

The role of temperate bacteriophages in bacterial infection

Bacteriophages are viruses that infect bacteria. There are an estimated 1031 phage on the planet, making them the most abundant form of life. We are rapidly approaching the centenary of their identification, and yet still have only a limited understanding of their role in the ecology and evolution of bacterial populations. Temperate prophage carriage is often associated with increased bacterial virulence. The rise in use of technologies, such as genome sequencing and transcriptomics, has highlighted more subtle ways in which prophages contribute to pathogenicity. This review discusses the current knowledge of the multifaceted effects that phage can exert on their hosts and how this may contribute to bacterial adaptation during infection

A Unifying Gravity Framework for Dispersal

Most organisms disperse at some life-history stage, but different research traditions to study dispersal have evolved in botany, zoology, and epidemiology. In this paper, we synthesize concepts, principles, patterns, and processes in dispersal across organisms. We suggest a consistent conceptual framework for dispersal, which utilizes generalized gravity models. This framework will facilitate communication among research traditions, guide the development of dispersal models for theoretical and applied ecology, and enable common representation across taxonomic groups, encapsulating processes at the source and destination of movement, as well as during the intervening relocation process, while allowing each of these stages in the dispersal process to be addressed separately and in relevant detail. For different research traditions, certain parts of the dispersal process are less studied than others (e.g., seed release processes in plants and termination of dispersal in terrestrial and aquatic animals). The generalized gravity model can serve as a unifying framework for such processes, because it captures the general conceptual and formal components of any dispersal process, no matter what the relevant biological timescale involved. We illustrate the use of the framework with examples of passive (a plant), active (an animal), and vectored (a fungus) dispersal, and point out promising applications, including studies of dispersal mechanisms, total dispersal kernels, and spatial population dynamics

A Unifying Gravity Framework for Dispersal

Most organisms disperse at some life-history stage, but different research traditions to study dispersal have evolved in botany, zoology, and epidemiology. In this paper, we synthesize concepts, principles, patterns, and processes in dispersal across organisms. We suggest a consistent conceptual framework for dispersal, which utilizes generalized gravity models. This framework will facilitate communication among research traditions, guide the development of dispersal models for theoretical and applied ecology, and enable common representation across taxonomic groups, encapsulating processes at the source and destination of movement, as well as during the intervening relocation process, while allowing each of these stages in the dispersal process to be addressed separately and in relevant detail. For different research traditions, certain parts of the dispersal process are less studied than others (e.g., seed release processes in plants and termination of dispersal in terrestrial and aquatic animals). The generalized gravity model can serve as a unifying framework for such processes, because it captures the general conceptual and formal components of any dispersal process, no matter what the relevant biological timescale involved. We illustrate the use of the framework with examples of passive (a plant), active (an animal), and vectored (a fungus) dispersal, and point out promising applications, including studies of dispersal mechanisms, total dispersal kernels, and spatial population dynamics

To sleep or not to sleep, that is the question: A systematic review and meta-analysis on the effect of post-trauma sleep on intrusive memories of analog trauma

Distressing intrusive memories of a traumatic event are one of the hallmark symptoms of posttraumatic stress disorder. Thus, it is crucial to identify early interventions that prevent the occurrence of intrusive memories. Both, sleep and sleep deprivation have been discussed as such interventions, yet previous studies yielded contradicting effects. Our systematic review aims at evaluating existing evidence by means of traditional and individual participant data (IPD) meta-analyses to overcome power issues of sleep research. Until May 16th, 2022, six databases were searched for experimental analog studies examining the effect of post-trauma sleep versus wakefulness on intrusive memories. Nine studies were included in our traditional meta-analysis (8 in the IPD meta-analysis). Our analysis provided evidence for a small effect favoring sleep over wakefulness, log-ROM = 0.25, p < .001, suggesting that sleep is associated with a lower number of intrusions but unrelated to the occurrence of any versus no intrusions. We found no evidence for an effect of sleep on intrusion distress. Heterogeneity was low and certainty of evidence for our primary analysis was moderate. Our findings suggest that post-trauma sleep has the potential to be protective by reducing intrusion frequency. More research is needed to determine the impact following real-world trauma and the potential clinical significance

The DNA-encoded nucleosome organization of a eukaryotic genome

Nucleosome organization is critical for gene regulation1. In living cells this organization is determined by multiple factors, including the action of chromatin remodellers2, competition with site-specific DNA-binding proteins3, and the DNA sequence preferences of the nucleosomes themselves4-8. However, it has been difficult to estimate the relative importance of each of these mechanisms in vivo7,9-11, because in vivo nucleosome maps reflect the combined action of all influencing factors. Here we determine the importance of nucleosome DNA sequence preferences experimentally by measuring the genome-wide occupancy of nucleosomes assembled on purified yeast genomic DNA. The resulting map, in which nucleosome occupancy is governed only by the intrinsic sequence preferences of nucleosomes, is similar to in vivo nucleosome maps generated in three different growth conditions. In vitro, nucleosome depletion is evident at many transcription factor binding sites and around gene start and end sites, indicating that nucleosome depletion at these sites in vivo is partly encoded in the genome. We confirm these results with a micrococcal nuclease-independent experiment that measures the relative affinity of nucleosomes for ∼40,000 double-stranded 150-base-pair oligonucleotides. Using our in vitro data, we devise a computational model of nucleosome sequence preferences that is significantly correlated with in vivo nucleosome occupancy in Caenorhabditis elegans. Our results indicate that the intrinsic DNA sequence preferences of nucleosomes have a central role in determining the organization of nucleosomes in vivo

Restricting Dosage Compensation Complex Binding to the X Chromosomes by H2A.Z/HTZ-1

Dosage compensation ensures similar levels of X-linked gene products in males (XY or XO) and females (XX), despite their different numbers of X chromosomes. In mammals, flies, and worms, dosage compensation is mediated by a specialized machinery that localizes to one or both of the X chromosomes in one sex resulting in a change in gene expression from the affected X chromosome(s). In mammals and flies, dosage compensation is associated with specific histone posttranslational modifications and replacement with variant histones. Until now, no specific histone modifications or histone variants have been implicated in Caenorhabditis elegans dosage compensation. Taking a candidate approach, we have looked at specific histone modifications and variants on the C. elegans dosage compensated X chromosomes. Using RNAi-based assays, we show that reducing levels of the histone H2A variant, H2A.Z (HTZ-1 in C. elegans), leads to partial disruption of dosage compensation. By immunofluorescence, we have observed that HTZ-1 is under-represented on the dosage compensated X chromosomes, but not on the non-dosage compensated male X chromosome. We find that reduction of HTZ-1 levels by RNA interference (RNAi) and mutation results in only a very modest change in dosage compensation complex protein levels. However, in these animals, the X chromosome–specific localization of the complex is partially disrupted, with some nuclei displaying DCC localization beyond the X chromosome territory. We propose a model in which HTZ-1, directly or indirectly, serves to restrict the dosage compensation complex to the X chromosome by acting as or regulating the activity of an autosomal repellant

Baseline Features and Reasons for Nonparticipation in the Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) Study, a Colorectal Cancer Screening Trial.

IMPORTANCE: The Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) randomized clinical trial sought to recruit 50 000 adults into a study comparing colorectal cancer (CRC) mortality outcomes after randomization to either an annual fecal immunochemical test (FIT) or colonoscopy. OBJECTIVE: To (1) describe study participant characteristics and (2) examine who declined participation because of a preference for colonoscopy or stool testing (ie, fecal occult blood test [FOBT]/FIT) and assess that preference\u27s association with geographic and temporal factors. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study within CONFIRM, which completed enrollment through 46 Department of Veterans Affairs medical centers between May 22, 2012, and December 1, 2017, with follow-up planned through 2028, comprised veterans aged 50 to 75 years with an average CRC risk and due for screening. Data were analyzed between March 7 and December 5, 2022. EXPOSURE: Case report forms were used to capture enrolled participant data and reasons for declining participation among otherwise eligible individuals. MAIN OUTCOMES AND MEASURES: Descriptive statistics were used to characterize the cohort overall and by intervention. Among individuals declining participation, logistic regression was used to compare preference for FOBT/FIT or colonoscopy by recruitment region and year. RESULTS: A total of 50 126 participants were recruited (mean [SD] age, 59.1 [6.9] years; 46 618 [93.0%] male and 3508 [7.0%] female). The cohort was racially and ethnically diverse, with 748 (1.5%) identifying as Asian, 12 021 (24.0%) as Black, 415 (0.8%) as Native American or Alaska Native, 34 629 (69.1%) as White, and 1877 (3.7%) as other race, including multiracial; and 5734 (11.4%) as having Hispanic ethnicity. Of the 11 109 eligible individuals who declined participation (18.0%), 4824 (43.4%) declined due to a stated preference for a specific screening test, with FOBT/FIT being the most preferred method (2820 [58.5%]) vs colonoscopy (1958 [40.6%]; P \u3c .001) or other screening tests (46 [1.0%] P \u3c .001). Preference for FOBT/FIT was strongest in the West (963 of 1472 [65.4%]) and modest elsewhere, ranging from 199 of 371 (53.6%) in the Northeast to 884 of 1543 (57.3%) in the Midwest (P = .001). Adjusting for region, the preference for FOBT/FIT increased by 19% per recruitment year (odds ratio, 1.19; 95% CI, 1.14-1.25). CONCLUSIONS AND RELEVANCE: In this cross-sectional analysis of veterans choosing nonenrollment in the CONFIRM study, those who declined participation more often preferred FOBT or FIT over colonoscopy. This preference increased over time and was strongest in the western US and may provide insight into trends in CRC screening preferences

Novel Common Genetic Susceptibility Loci for Colorectal Cancer

BACKGROUND: Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk. METHODS: We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided. RESULTS: The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0. CONCLUSIONS: This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screenin