Iodine-123 metaiodobenzylguanidine scintigraphic assessment of the transplanted human heart: Evidence for late reinnervation

Objectives.This study attempted to determine whether cardiac sympathetic reinnervation occurs late after orthotopic heart transplantation.Background.Metaiodobenzylguanidine (MIBG) is taken up by myocardial sympathetic nerves. Iodine-123 (I-123) MIBG cardiac uptake reflects intact myocardial sympathetic innervation of the heart. Cardiac transplant recipients do not demonstrate I-123 MIBG cardiac uptake when studied <6 months from transplantation. However, physiologic and biochemical studies suggest that sympathetic reinnervation of the heart can occur >1 year after transplantation.Methods.We performed serial cardiac I-123 MIBG imaging in 23 cardiac transplant recipients early (<-1 year) and late (>1 year) after operation. In 16 subjects transmyocardial norepinephrine release was measured late after transplantation.Results.No subject had visible I-123 MIBG uptake on imaging <1 year after transplantation. However, 11 (48%) of 23 subjects developed visible cardiac I-123 MIBG uptake 1 to 2 years after transplantation. Only 3 (25%) of 12 subjects with a pretransplantation diagnosis of idiopathic cardiomyopathy demonstrated I-123 MIBG uptake compared with 8 (73%) of 11 with a pretransplantation diagnosis of ischemic or rheumatic heart disease (p = 0.04). All 10 subjects with a net myocardial release of norepinephrine had cardiac I-123 MIBG uptake; all 6 subjects without a net release of norepinephrine had no cardiac I-123 MIBG uptake.Conclusions.Sympathetic reinnervation of the transplanted human heart can occur >1 year after operation, as assessed by I-123 MIBG imaging and the transmyocardial release of norepinephrine. Reinnervation is less likely to occur in patients with a pretransplantation diagnosis of idiopathic cardiomyopathy than in those with other etiologies of congestive heart failure

Calgary Thrives: Data sharing and linkage in the not-for-profit sector.

Introduction Compared to the public sector, not-for-profits are less focused on cross-agency data linkage. Technical capacity is often secondary to addressing caseloads and protecting clients. Clients’ privacy is paramount and can be perceived as a barrier to collaboration between agencies. However, collaboration could streamline referrals and better assist vulnerable populations. Objectives and Approach Six not-for-profit agencies in Calgary, Canada participated in a data sharing project to measure various aspects of poverty and link data to determine cross-agency service usage. With this goal in mind, agencies examined their consent and data sharing practices to assess barriers to data sharing. There was a thorough exploration of client consent and how a client’s context can enable or limit data sharing. Cross-agency program usage was assessed among participating agencies using a privacy-preserving record linkage (PPRL) methodology. Results Amongst the six participating agencies, four were deemed to have adequate technical capacity to share data. A contributing factor to the willingness of agencies to share data was the development of LinkWise: a PPRL software created and developed by PolicyWise. Linkage rates amongst three agencies were compared. Rates ranged from 47.8% to 0.23%. A higher linkage rate between two agencies indicated a small community based agency which provided many referrals to a larger agency, such as a food bank. Lower linkage rates on client intake may indicate an agency with many clients. It may also indicate differing socio-economic brackets for their clients’ catchment area. Conclusion/Implications While capacity, caseloads, and privacy protection restrict data sharing, not-for-profit agencies would benefit from a data sharing strategy. Linking data represent opportunities for collaboration within a significantly resource constrained sector. Moreover, it could more effectively address issues of vulnerable populations, streamline referrals for services, and facilitate quality improvement

Conference on Best Practices for Managing \u3cem\u3eDaubert\u3c/em\u3e Questions

This article is a transcript of the Philip D. Reed Lecture Series Conference on Best Practices for Managing Daubert Questions, held on October 25, 2019, at Vanderbilt Law School under the sponsorship of the Judicial Conference Advisory Committee on Evidence Rules. The transcript has been lightly edited and represents the panelists’ individual views only and in no way reflects those of their affiliated firms, organizations, law schools, or the judiciary

Children’s and adults’ understanding of death: Cognitive, parental, and experiential influences

This study explored the development of understanding of death in a sample of 4- to 11-year-old British children and adults (N = 136). It also investigated four sets of possible influences on this development: parents’ religion and spiritual beliefs, cognitive ability, socioeconomic status, and experience of illness and death. Participants were interviewed using the “death concept” interview that explores understanding of the subcomponents of inevitability, universality, irreversibility, cessation, and causality of death. Children understood key aspects of death from as early as 4 or 5 years, and with age their explanations of inevitability, universality, and causality became increasingly biological. Understanding of irreversibility and the cessation of mental and physical processes also emerged during early childhood, but by 10 years many children’s explanations reflected not an improved biological understanding but rather the coexistence of apparently contradictory biological and supernatural ideas—religious, spiritual, or metaphysical. Evidence for these coexistent beliefs was more prevalent in older children than in younger children and was associated with their parents’ religious and spiritual beliefs. Socioeconomic status was partly related to children’s biological ideas, whereas cognitive ability and experience of illness and death played less important roles. There was no evidence for coexistent thinking among adults, only a clear distinction between biological explanations about death and supernatural explanations about the afterlife

Perineal Assessment and Repair Longitudinal Study (PEARLS): a matched-pair cluster randomized trial.

Perineal trauma during childbirth affects millions of women worldwide every year. The aim of the Perineal Assessment and Repair Longitudinal Study (PEARLS) was to improve maternal clinical outcomes following childbirth through an enhanced cascaded multiprofessional training program to support implementation of evidence-based perineal management

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