What Works: Transforming Conditions and Health Outcomes for Boys and Men of Color

What Works is a guide to best practices and movement-building lessons learned from the surge of efforts to improve life conditions and health outcomes for boys and men of color in California. The report lifts up effective on-the-ground efforts to place the practices in a broader context in a way that can be applicable not only to work in California, but across the nation

Changing the Rules of the Game: Youth Development & Structural Racism

With support of the Ford Foundation, the Philanthropic Initiative for Racial Equity (PRE) and mosaic consulting embarked on an 18-month study into the ways select community organizations engage youth in confronting structural racism. For this report we use the definition of structural racism developed by the Aspen Institute Roundtable on Community Change1 : "The history, public policies, institutional practices, and cultural stereotypes and norms that together maintain racial hierarchies and inequitable racial group outcomes." Four primary research questions animated this project: 1. How do youth development organizations conceptualize and approach structural racism in their work? 2. Are there commonalities across these definitions and approaches? 3. What challenges do they face? 4. What can we learn from them

ReGeneration: Young People Shaping the Environmental Justice Movement

ReGeneration examines the powerful visions and strategies of young people in the U.S. environmental justice movement. The Movement Strategy Center interviewed groups across the country, and found that youth organizers in the environmental justice movement are creating new ways to expand leadership, build intergenerational alliances, work sustainably and bridge issue areas and communities. The groups profiled in this report offer models and strategies to reinvigorate every sector of the national progressive movement

Initial investigation of test-retest reliability of home-to-home teleneuropsychological assessment in healthy, English-speaking adults

Prior teleneuropsychological research has assessed the reliability between in-person and remote administration of cognitive assessments. Few, if any, studies have examined the test-retest reliability of cognitive assessments conducted in sequential clinic-to-home or home-to-home teleneuropsychological evaluations - a critical issue given the state of clinical practice during the COVID-19 pandemic. This study examined this key psychometric question for several cognitive tests administered over repeated videoconferencing visits 4-6 months apart in a sample of healthy English-speaking adults. A total of 44 participants (ages 18-75) completed baseline and follow-up cognitive testing 4-6 months apart. Testing was conducted in a home-to-home setting over HIPAA-compliant videoconferencing meetings on participants' audio-visual enabled laptop or desktop computers. The following measures were repeated at both virtual visits: the Controlled Oral Word Association Test (FAS), Category Fluency (Animals), and Digit Span Forward and Backward from the Wechsler Adult Intelligence Scale, Fourth Edition. Intraclass correlation coefficients (ICC), Pearson correlations, root mean square difference (RMSD), and concordance correlation coefficients (CCC) were calculated as test-retest reliability metrics, and practice effects were assessed using paired-samples t-tests. Some tests exhibited small practice effects, and test-retest reliability was marginal or worse for all measures except FAS, which had adequate reliability (based on ICC and r). Reliability estimates with RMSD suggested that change within +/- 1 SD on these measures may reflect typical test-retest variability. The included cognitive measures exhibited questionable reliability over repeated home-to-home videoconferencing evaluations. Future teleneuropsychology test-retest reliability research is needed with larger, more diverse samples and in clinical populations.F31 AG062158 - NIA NIH HHS; R01 AG054671 - NIA NIH HHS; R01 AG066823 - NIA NIH HHSAccepted manuscrip

Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe.

BACKGROUND: The replication-competent recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing a Zaire ebolavirus (ZEBOV) glycoprotein was selected for rapid safety and immunogenicity testing before its use in West Africa. METHODS: We performed three open-label, dose-escalation phase 1 trials and one randomized, double-blind, controlled phase 1 trial to assess the safety, side-effect profile, and immunogenicity of rVSV-ZEBOV at various doses in 158 healthy adults in Europe and Africa. All participants were injected with doses of vaccine ranging from 300,000 to 50 million plaque-forming units (PFU) or placebo. RESULTS: No serious vaccine-related adverse events were reported. Mild-to-moderate early-onset reactogenicity was frequent but transient (median, 1 day). Fever was observed in up to 30% of vaccinees. Vaccine viremia was detected within 3 days in 123 of the 130 participants (95%) receiving 3 million PFU or more; rVSV was not detected in saliva or urine. In the second week after injection, arthritis affecting one to four joints developed in 11 of 51 participants (22%) in Geneva, with pain lasting a median of 8 days (interquartile range, 4 to 87); 2 self-limited cases occurred in 60 participants (3%) in Hamburg, Germany, and Kilifi, Kenya. The virus was identified in one synovial-fluid aspirate and in skin vesicles of 2 other vaccinees, showing peripheral viral replication in the second week after immunization. ZEBOV-glycoprotein-specific antibody responses were detected in all the participants, with similar glycoprotein-binding antibody titers but significantly higher neutralizing antibody titers at higher doses. Glycoprotein-binding antibody titers were sustained through 180 days in all participants. CONCLUSIONS: In these studies, rVSV-ZEBOV was reactogenic but immunogenic after a single dose and warrants further evaluation for safety and efficacy. (Funded by the Wellcome Trust and others; ClinicalTrials.gov numbers, NCT02283099, NCT02287480, and NCT02296983; Pan African Clinical Trials Registry number, PACTR201411000919191.)

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Exceptionally low likelihood of Alzheimer's dementia in APOE2 homozygotes from a 5,000-person neuropathological study.

Each additional copy of the apolipoprotein E4 (APOE4) allele is associated with a higher risk of Alzheimer's dementia, while the APOE2 allele is associated with a lower risk of Alzheimer's dementia, it is not yet known whether APOE2 homozygotes have a particularly low risk. We generated Alzheimer's dementia odds ratios and other findings in more than 5,000 clinically characterized and neuropathologically characterized Alzheimer's dementia cases and controls. APOE2/2 was associated with a low Alzheimer's dementia odds ratios compared to APOE2/3 and 3/3, and an exceptionally low odds ratio compared to APOE4/4, and the impact of APOE2 and APOE4 gene dose was significantly greater in the neuropathologically confirmed group than in more than 24,000 neuropathologically unconfirmed cases and controls. Finding and targeting the factors by which APOE and its variants influence Alzheimer's disease could have a major impact on the understanding, treatment and prevention of the disease