Recruitment strategies and rates of a multi-site behavioral intervention for adolescents and young adults with cancer

INTRODUCTION: To provide an overview of factors related to recruitment of adolescents and young adults (AYA) into research and recruitment rates and reasons for refusal from a multicenter study entitled "Stories and Music for Adolescent/Young Adult Resilience during Transplant" (SMART). METHODS: A randomized clinical trial study design was used. The settings included 9 hospitals. The sample included AYAs (aged 11-24 years) who were undergoing a stem cell transplant. Several instruments were used to measure symptom distress, coping, resilience, and quality of life in AYA with cancer. RESULTS: A total of 113 AYA were recruited (50%) for this study. Strategies were refined as the study continued to address challenges related to recruitment. We provide a description of recruitment strategies and an evaluation of our planning, implementing, and monitoring of recruitment rates for the SMART study. DISCUSSION: When designing a study, careful consideration must be given to factors influencing recruitment as well as special considerations for unique populations. Dissemination of strategies specific to unique populations will be helpful to the design of future research studies

African Americans and Land Loss in Texas: Government Duplicity and Discrimination Based on Race and Class

African American Farmers and Land Loss in Texas, surveys the ways that discrimination at the local, state, and national levels constrained minority farmers during the twentieth century. It considers the characteristics of small-scale farming that created liabilities for landowners regardless of race, including state and federal programs that favored commercial and agribusiness interests. In addition to economic challenges African American farmers had to negotiate racism in the Jim Crow South. The Texas Agricultural Extension Service, the state branch of the USDA\u27s Extension Service, segregated in 1915. The Negro division gave black farmers access to information about USDA programs, but it emphasized their subordinate position relative to white farmers. The Civil Rights Act of 1964 did not reverse decades of racial discrimination. Instead, USDA officials relied on federalism, a theory as old as the Constitution, to justify their tolerance of civil rights violations in Texas and elsewhere. Then, special needs legislation passed during the 1970s and 1980s did not realize its potential to serve ethnically diverse and economically disadvantaged rural Texans. Discrimination based on race combined with a bias toward commercial production. This crippled most black farmers and led to their near extinction

Randomized clinical trial of therapeutic music video intervention for resilience outcomes in adolescents/young adults undergoing hematopoietic stem cell transplant: a report from the Children's Oncology Group

BACKGROUND: To reduce the risk of adjustment problems associated with hematopoietic stem cell transplant (HSCT) for adolescents/young adults (AYAs), we examined efficacy of a therapeutic music video (TMV) intervention delivered during the acute phase of HSCT to: 1) increase protective factors of spiritual perspective, social integration, family environment, courageous coping, and hope-derived meaning; 2) decrease risk factors of illness-related distress and defensive coping; and 3) increase outcomes of self-transcendence and resilience. METHODS: This was a multisite randomized, controlled trial (COG-ANUR0631) conducted at 8 Children's Oncology Group sites involving 113 AYAs aged 11-24 years undergoing myeloablative HSCT. Participants, randomized to the TMV or low-dose control (audiobooks) group, completed 6 sessions over 3 weeks with a board-certified music therapist. Variables were based on Haase's Resilience in Illness Model (RIM). Participants completed measures related to latent variables of illness-related distress, social integration, spiritual perspective, family environment, coping, hope-derived meaning, and resilience at baseline (T1), postintervention (T2), and 100 days posttransplant (T3). RESULTS: At T2, the TMV group reported significantly better courageous coping (Effect Size [ES], 0.505; P = .030). At T3, the TMV group reported significantly better social integration (ES, 0.543; P = .028) and family environment (ES, 0.663; P = .008), as well as moderate nonsignificant effect sizes for spiritual perspective (ES, 0.450; P = .071) and self-transcendence (ES, 0.424; P = .088). CONCLUSIONS: The TMV intervention improves positive health outcomes of courageous coping, social integration, and family environment during a high-risk cancer treatment. We recommend the TMV be examined in a broader population of AYAs with high-risk cancers

Autophagy in the eye:from physiology to pathophysology

Autophagy is a catabolic self-degradative pathway that promotes the degradation and recycling of intracellular material through the lysosomal compartment. Although first believed to function in conditions of nutritional stress, autophagy is emerging as a critical cellular pathway, involved in a variety of physiological and pathophysiological processes. Autophagy dysregulation is associated with an increasing number of diseases, including ocular diseases. On one hand, mutations in autophagy-related genes have been linked to cataracts, glaucoma, and corneal dystrophy; on the other hand, alterations in autophagy and lysosomal pathways are a common finding in essentially all diseases of the eye. Moreover, LC3-associated phagocytosis, a form of non-canonical autophagy, is critical in promoting visual cycle function. This review collects the latest understanding of autophagy in the context of the eye. We will review and discuss the respective roles of autophagy in the physiology and/or pathophysiology of each of the ocular tissues, its diurnal/circadian variation, as well as its involvement in diseases of the eye

A case study evaluation of implementation of a care pathway to support normal birth in one English birth centre: anticipated benefits and unintended consequences

Background: The policy drive for the UK National Health Service (NHS) has focused on the need for high quality services informed by evidence of best practice. The introduction of care pathways and protocols to standardise care and support implementation of evidence into practice has taken place across the NHS with limited evaluation of their impact. A multi-site case study evaluation was undertaken to assess the impact of use of care pathways and protocols on clinicians, service users and service delivery. One of the five sites was a midwifery-led Birth Centre, where an adapted version of the All Wales Clinical Pathway for Normal Birth had been implemented. Methods: The overarching framework was realistic evaluation. A case study design enabled the capture of data on use of the pathway in the clinical setting, use of multiple methods of data collection and opportunity to study and understand the experiences of clinicians and service users whose care was informed by the pathway. Women attending the Birth Centre were recruited at their 36 week antenatal visit. Episodes of care during labour were observed, following which the woman and the midwife who cared for her were interviewed about use of the pathway. Interviews were also held with other key stakeholders from the study site. Qualitative data were content analysed. Results: Observations were undertaken of four women during labour. Eighteen interviews were conducted with clinicians and women, including the women whose care was observed and the midwives who cared for them, senior midwifery managers and obstetricians. The implementation of the pathway resulted in a number of anticipated benefits, including increased midwifery confidence in skills to support normal birth and promotion of team working. There were also unintended consequences, including concerns about a lack of documentation of labour care and negative impact on working relationships with obstetric and other midwifery colleagues. Women were unaware their care was informed by a care pathway. Conclusion: Care pathways are complex interventions which generate a number of consequences for practice. Those considering introduction of pathways need to ensure all relevant stakeholders are engaged with this and develop robust evaluation strategies to accompany implementation

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

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

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

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