Building an Archives for Butte, America

In 1981 only a few residents and scholars knew about the Butte-Silver Bow Public Archives and even fewer used its services, but by 2006 the archives was providing research assistance to more than 4,000 people each year. In 2007, Butte’s voters, proud of the archives and its role in the preservation of their heritage, approved a $7.5 million bond to support it. This case study outlines how almost twenty years of advocacy by the archives staff, Friends, and board increased access to collections, improved community awareness, and ultimately resulted in a state-of-the-art facility for Butte’s records of enduring value

Work-Family Conflict, Family-Supportive Supervisor Behaviors (FSSB), and Sleep Outcomes

Although critical to health and well-being, relatively little research has been conducted in the organizational literature on linkages between the work-family interface and sleep. Drawing on Conservation of Resources theory, we use a sample of 623 information technology workers to examine the relationships between work-family conflict, family-supportive supervisor behaviors (FSSB), and sleep quality and quantity. Validated wrist actigraphy methods were used to collect objective sleep quality and quantity data over a one week period of time, and survey methods were used to collect information on self-reported work-family conflict, FSSB, and sleep quality and quantity. Results demonstrated that the combination of predictors (i.e., work-to-family conflict, family-to-work conflict, FSSB) was significantly related to both objective and self-report measures of sleep quantity and quality. Future research should further examine the work-family interface to sleep link and make use of interventions targeting the work-family interface as a means for improving sleep health

Intervention Effects on Safety Compliance and Citizenship Behaviors: Evidence From the Work, Family, and Health Study

We tested the effects of a work–family intervention on employee reports of safety compliance and organizational citizenship behaviors in 30 health care facilities using a group-randomized trial. Based on conservation of resources theory and the work–home resources model, we hypothesized that implementing a work–family intervention aimed at increasing contextual resources via supervisor support for work and family, and employee control over work time, would lead to improved personal resources and increased employee performance on the job in the form of self-reported safety compliance and organizational citizenship behaviors. Multilevel analyses used survey data from 1,524 employees at baseline and at 6-month and 12-month postintervention follow-ups. Significant intervention effects were observed for safety compliance at the 6-month, and organizational citizenship behaviors at the 12-month, follow-ups. More specifically, results demonstrate that the intervention protected against declines in employee self-reported safety compliance and organizational citizenship behaviors compared with employees in the control facilities. The hypothesized mediators of perceptions of family-supportive supervisor behaviors, control over work time, and work–family conflict (work-to-family conflict, family-to-work conflict) were not significantly improved by the intervention. However, baseline perceptions of family-supportive supervisor behaviors, control over work time, and work–family climate were significant moderators of the intervention effect on the self-reported safety compliance and organizational citizenship behavior outcomes.Keywords: group-randomized trial, family supportive supervisor behavior, organizational citizenship behavior, work-family conflict, safety complianceKeywords: group-randomized trial, family supportive supervisor behavior, organizational citizenship behavior, work-family conflict, safety complianc

The Ambulatory Pediatric Association Fellowship in Pediatric Environmental Health: A 5-Year Assessment

Background: Evidence is mounting that environmental exposures contribute to causation of disease in children. Yet few pediatricians are trained to diagnose, treat, or prevent disease of environmental origin. Objectives: To develop a cadre of future leaders in pediatric environmental health (PEH), the Ambulatory Pediatric Association (APA) launched a new 3-year fellowship in 2001—the world’s first formal training program in PEH. Sites were established at Boston Children’s Hospital, Mount Sinai School of Medicine, George Washington University, University of Cincinnati, and University of Washington. Fellows are trained in epidemiology, biostatistics, toxicology, risk assessment, and preventive medicine. They gain clinical experience in environmental pediatrics and mentored training in clinical research, policy development, and evidence-based advocacy. Thirteen fellows have graduated. Two sites have secured follow-on federal funding to enable them to continue PEH training. Discussion: To assess objectively the program’s success in preparing fellows for leadership careers in PEH, we conducted a mailed survey in 2006 with follow-up in 2007. Conclusions: Fifteen (88%) of 17 fellows and graduates participated; program directors provided information on the remaining two. Nine graduates are pursuing full-time academic careers, and two have leadership positions in governmental and environmental organizations. Ten have published one or more first-authored papers. Seven graduates are principal investigators on federal or foundation grants. The strongest predictors of academic success are remaining affiliated with the fellowship training site and devoting <20% of fellowship time to clinical practice. Conclusion: The APA fellowship program is proving successful in preparing pediatricians for leadership careers in PEH

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies