Communications-Inspired Projection Design with Application to Compressive Sensing

We consider the recovery of an underlying signal x \in C^m based on projection measurements of the form y=Mx+w, where y \in C^l and w is measurement noise; we are interested in the case l < m. It is assumed that the signal model p(x) is known, and w CN(w;0,S_w), for known S_W. The objective is to design a projection matrix M \in C^(l x m) to maximize key information-theoretic quantities with operational significance, including the mutual information between the signal and the projections I(x;y) or the Renyi entropy of the projections h_a(y) (Shannon entropy is a special case). By capitalizing on explicit characterizations of the gradients of the information measures with respect to the projections matrix, where we also partially extend the well-known results of Palomar and Verdu from the mutual information to the Renyi entropy domain, we unveil the key operations carried out by the optimal projections designs: mode exposure and mode alignment. Experiments are considered for the case of compressive sensing (CS) applied to imagery. In this context, we provide a demonstration of the performance improvement possible through the application of the novel projection designs in relation to conventional ones, as well as justification for a fast online projections design method with which state-of-the-art adaptive CS signal recovery is achieved.Comment: 25 pages, 7 figures, parts of material published in IEEE ICASSP 2012, submitted to SIIM

Brain Age from the Electroencephalogram of Sleep

The human electroencephalogram (EEG) of sleep undergoes profound changes with age. These changes can be conceptualized as "brain age", which can be compared to an age norm to reflect the deviation from normal aging process. Here, we develop an interpretable machine learning model to predict brain age based on two large sleep EEG datasets: the Massachusetts General Hospital sleep lab dataset (MGH, N = 2,621) covering age 18 to 80; and the Sleep Hearth Health Study (SHHS, N = 3,520) covering age 40 to 80. The model obtains a mean absolute deviation of 8.1 years between brain age and chronological age in the healthy participants in the MGH dataset. As validation, we analyze a subset of SHHS containing longitudinal EEGs 5 years apart, which shows a 5.5 years difference in brain age. Participants with neurological and psychiatric diseases, as well as diabetes and hypertension medications show an older brain age compared to chronological age. The findings raise the prospect of using sleep EEG as a biomarker for healthy brain aging

Shutting off the fuel supply to target metabolic vulnerabilities in multiple myeloma

Pathways that govern cellular bioenergetics are deregulated in tumor cells and represent a hallmark of cancer. Tumor cells have the capacity to reprogram pathways that control nutrient acquisition, anabolism and catabolism to enhance their growth and survival. Tumorigenesis requires the autonomous reprogramming of key metabolic pathways that obtain, generate and produce metabolites from a nutrient-deprived tumor microenvironment to meet the increased bioenergetic demands of cancer cells. Intra- and extracellular factors also have a profound effect on gene expression to drive metabolic pathway reprogramming in not only cancer cells but also surrounding cell types that contribute to anti-tumor immunity. Despite a vast amount of genetic and histologic heterogeneity within and between cancer types, a finite set of pathways are commonly deregulated to support anabolism, catabolism and redox balance. Multiple myeloma (MM) is the second most common hematologic malignancy in adults and remains incurable in the vast majority of patients. Genetic events and the hypoxic bone marrow milieu deregulate glycolysis, glutaminolysis and fatty acid synthesis in MM cells to promote their proliferation, survival, metastasis, drug resistance and evasion of immunosurveillance. Here, we discuss mechanisms that disrupt metabolic pathways in MM cells to support the development of therapeutic resistance and thwart the effects of anti-myeloma immunity. A better understanding of the events that reprogram metabolism in myeloma and immune cells may reveal unforeseen vulnerabilities and advance the rational design of drug cocktails that improve patient survival

Lipid phosphate phosphatase-1 regulates lysophosphatidic acid- and platelet-derived-growth-factor-induced cell migration

LPPs (lipid phosphate phosphatases) are members of a family of enzymes that catalyse the dephosphorylation of lipid phosphates. The only known form of regulation of this family of enzymes is via de novo expression of LPP isoforms in response to growth factors. In this respect, we evaluated the effect of moderate increases in the expression of recombinant LPP1 on signal transduction by both G-protein-coupled receptors and receptor tyrosine kinases. We present evidence for a novel role of LPP1 in reducing PDGF (platelet-derived growth factor)- and lysophosphatidic acid-induced migration of embryonic fibroblasts. We demonstrate that the overexpression of LPP1 inhibits cell migration by reducing the PDGF-induced activation of p42/p44 MAPK (mitogen-activated protein kinase). This appears to occur via a mechanism that involves the LPP1-induced down-regulation of typical PKC (protein kinase C) isoform(s), which are normally required for PDGF-induced activation of p42/p44 MAPK and migration. In this regard, DAG (diacylglycerol) levels are high and sustained in cells overexpressing LPP1, suggesting a dynamic interconversion of phosphatidic acid into DAG by LPP1. This may account for the effects of LPP1 on cell migration, as sustained DAG is known to down-regulate PKC isoforms in cells. Therefore the physiological changes in the expression levels of LPP1 might represent a heterologous desensitization mechanism for attenuating PKC-mediated signalling and regulation of cell migration

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Long-Acting Injectable ART and PrEP Among Women in Six Cities Across the United States: A Qualitative Analysis of Who Would Benefit the Most

Long-acting injectable (LAI) modalities have been developed for ART and PrEP. Women face unique barriers to LAI use yet little research has examined women’s perceptions of potential LAI HIV therapy candidates. We conducted 89 in-depth interviews at six Women’s Interagency HIV Study (WIHS) sites with women living with HIV (n = 59) and HIV-negative women (n = 30) from 2017 to 2018. Interviews were recorded, transcribed, and analyzed using thematic content analysis. Participants identified specific sub-populations who could most benefit from LAI over daily pills: (1) young people; (2) women with childcare responsibilities; (3) people with adherence-related psychological distress; (4) individuals with multiple sex partners; and (5) people facing structural insecurities such as homelessness. Women are underserved by current HIV care options and their perspectives are imperative to ensure a successful scale-up of LAI PrEP and LAI ART that prioritizes equitable access and benefit for all individuals

Brief Report: PrEP Eligibility among At-Risk Women in the Southern United States: Associated Factors, Awareness, and Acceptability

Background:Among women in the United States, non-Latina black women in the South have disproportionately high rates of new HIV infections but low use of pre-exposure prophylaxis (PrEP). Effective strategies to identify factors associated with PrEP eligibility could facilitate improved screening, offering, and uptake of PrEP among US women at risk of HIV.Setting and methods:We applied 2014 CDC criteria for PrEP use to at-risk HIV-negative women enrolled in the Southern US sites (Atlanta, Chapel Hill, Birmingham/Jackson, Miami) of the Women's Interagency HIV Study from 2014 to 2015 to estimate PrEP eligibility and assess PrEP knowledge and acceptability. Factors associated with PrEP eligibility were assessed using multivariable models.Results:Among 225 women, 72 (32%) were PrEP-eligible; the most common PrEP indicator was condomless sex. The majority of PrEP-eligible women (88%) reported willingness to consider PrEP. Only 24 (11%) PrEP-eligible women had previously heard of PrEP, and only 1 reported previous use. Education level less than high school [adjusted odds ratio (aOR) 2.56; 95% confidence interval (CI): 1.22 to 5.37], history of sexual violence (aOR 4.52; 95% CI: 1.52 to 17.76), and medium to high self-perception of HIV risk (aOR 6.76; 95% CI: 3.26 to 14.05) were significantly associated with PrEP eligibility in adjusted models.Conclusions:Extremely low PrEP awareness and use despite a high proportion of eligibility and acceptability signify a critical need to enhance PrEP education and delivery for women in this region. Supplementing CDC eligibility criteria with questions about history of sexual violence and HIV risk self-assessment may enhance PrEP screening and uptake among US women

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