Household food insecurity positively associated with increased hospital charges for infants

Objective: To test whether household food insecurity (HFI) was associated with total annual hospitalization charges, annual days hospitalized, and charges per day, among low-income infants (months) with any non-neonatal hospital stays. Methods: Administrative inpatient hospital charge data were matched to survey data from infants\u27 caregivers interviewed 1998-2005 in emergency departments in Boston and Little Rock. All study infants had been hospitalized at least once since birth; infants whose diagnoses were not plausibly related to nutrition were excluded from both groups. Log-transformed hospitalization charges were analyzed, controlling for site fixed effects. Results: 24% of infants from food-insecure households and 16% from food-secure households were hospitalized \u3e2 times (P=0.02). Mean annual inpatient hospital charges ($6,707 vs$5,735; P Conclusion: HFI was positively associated with annual inpatient charges among hospitalized low income infants. Average annual inpatient charges were almost $2,000 higher (inflation adjusted) for infants living in food-insecure households. Reducing or eliminating food insecurity could reduce health services utilization and expenditures for infants in low-income families, most of whom are covered by public health insurance

MYC through miR-17-92 Suppresses Specific Target Genes to Maintain Survival, Autonomous Proliferation, and a Neoplastic State

SummaryThe MYC oncogene regulates gene expression through multiple mechanisms, and its overexpression culminates in tumorigenesis. MYC inactivation reverses turmorigenesis through the loss of distinguishing features of cancer, including autonomous proliferation and survival. Here we report that MYC via miR-17-92 maintains a neoplastic state through the suppression of chromatin regulatory genes Sin3b, Hbp1, Suv420h1, and Btg1, as well as the apoptosis regulator Bim. The enforced expression of miR-17-92 prevents MYC suppression from inducing proliferative arrest, senescence, and apoptosis and abrogates sustained tumor regression. Knockdown of the five miR-17-92 target genes blocks senescence and apoptosis while it modestly delays proliferative arrest, thus partially recapitulating miR-17-92 function. We conclude that MYC, via miR-17-92, maintains a neoplastic state by suppressing specific target genes

Measurement of a Model of Implementation for Health Care: Toward a Testable Theory

Greenhalgh et al. used a considerable evidence-base to develop a comprehensive model of implementation of innovations in healthcare organizations [1]. However, these authors did not fully operationalize their model, making it difficult to test formally. The present paper represents a first step in operationalizing Greenhalgh et al.\u27s model by providing background, rationale, working definitions, and measurement of key constructs.A systematic review of the literature was conducted for key words representing 53 separate sub-constructs from six of the model\u27s broad constructs. Using an iterative process, we reviewed existing measures and utilized or adapted items. Where no one measure was deemed appropriate, we developed other items to measure the constructs through consensus

miQC : An adaptive probabilistic framework for quality control of single-cell RNA-sequencing data

Single-cell RNA-sequencing (scRNA-seq) has made it possible to profile gene expression in tissues at high resolution. An important preprocessing step prior to performing downstream analyses is to identify and remove cells with poor or degraded sample quality using quality control (QC) metrics. Two widely used QC metrics to identify a 'low-quality' cell are (i) if the cell includes a high proportion of reads that map to mitochondrial DNA (mtDNA) encoded genes and (ii) if a small number of genes are detected. Current best practices use these QC metrics independently with either arbitrary, uniform thresholds (e.g. 5%) or biological context-dependent (e.g. species) thresholds, and fail to jointly model these metrics in a data-driven manner. Current practices are often overly stringent and especially untenable on certain types of tissues, such as archived tumor tissues, or tissues associated with mitochondrial function, such as kidney tissue [1]. We propose a data-driven QC metric (miQC) that jointly models both the proportion of reads mapping to mtDNA genes and the number of detected genes with mixture models in a probabilistic framework to predict the low-quality cells in a given dataset. We demonstrate how our QC metric easily adapts to different types of single-cell datasets to remove low-quality cells while preserving high-quality cells that can be used for downstream analyses. Our software package is available at https://bioconductor.org/packages/miQC. Author summary We developed the miQC package to predict the low-quality cells in a given scRNA-seq dataset by jointly modeling both the proportion of reads mapping to mitochondrial DNA (mtDNA) genes and the number of detected genes using mixture models in a probabilistic framework. We demonstrate how our QC metric easily adapts to different types of single-cell datasets to remove low-quality cells while preserving high-quality cells that can be used for downstream analyses.Peer reviewe

Multiple functional risk variants in a SMAD7 enhancer implicate a colorectal cancer risk haplotype

Genome-wide association studies (GWAS) of colorectal cancer (CRC) have led to the identification of a number of common variants associated with modest risk. Several risk variants map within the vicinity of TGFβ/BMP signaling pathway genes, including rs4939827 within an intron of SMAD7 at 18q21.1. A previous study implicated a novel SNP (novel 1 or rs58920878) as a functional variant within an enhancer element in SMAD7 intron 4. In this study, we show that four SNPs including novel 1 (rs6507874, rs6507875, rs8085824, and rs58920878) in linkage disequilibrium (LD) with the index SNP rs4939827 demonstrate allele-specific enhancer effects in a large, multi-component enhancer of SMAD7. All four SNPs demonstrate allele-specific protein binding to nuclear extracts of CRC cell lines. Furthermore, some of the risk-associated alleles correlate with increased expression of SMAD7 in normal colon tissues. Finally, we show that the enhancer is responsive to BMP4 stimulation. Taken together, we propose that the associated CRC risk at 18q21.1 is due to four functional variants that regulate SMAD7 expression and potentially perturb a BMP negative feedback loop in TGFβ/BMP signaling pathways

Trends in Household and Child Food Insecurity Among Families with Young Children from 2007 to 2013

Background: 2007-2013 spanned an economic downturn with rising food costs. While Supplemental Nutrition Assistance Program (SNAP) benefits increased during those years by 13.6% from the 2009 American Recovery Reinvestment Act (ARRA), the impact of these competing conditions on household food insecurity (HFI, household food insecure but child food secure) and child food insecurity (CFI, household and child food insecure) in households with infants and toddlers has not been investigated. Objective: To describe HFI and CFI in households participating in SNAP vs. households likely eligible but not participating (No SNAP). Design: Repeat cross-sectional Participants/Setting: 19,999 caregivers of childrenChildren’s HealthWatch survey in emergency and primary care departments in 5 US cities. Main Outcome Measures: The 18-item U.S. Household Food Security Survey (HFSS) measured HFI (≥3 affirmative responses on non-child-specific questions) and CFI (≥2 affirmative responses to eight child-specific questions). Statistical analyses performed: The sample was stratified by SNAP/ No SNAP. Multinomial logistic regression analyses examined the association between SNAP receipt and HFI and CFI. Results: Across the study period, controlling for confounders including year, households with SNAP were 17% less likely to experience HFI (AOR 0.83; 95% CI,0 .75, 0.91; p Conclusions: Receipt of SNAP vs. No SNAP was associated with decreased prevalence of HFI and CFI during much of the economic downturn; this impact waned as the buying power of the boost in benefit amounts during the ARRA period eroded

Cancer prevention and therapy through the modulation of the tumor microenvironment

Cancer arises in the context of an in vivo tumor microenvironment. This microenvironment is both a cause and consequence of tumorigenesis. Tumor and host cells co-evolve dynamically through indirect and direct cellular interactions, eliciting multiscale effects on many biological programs, including cellular proliferation, growth, and metabolism, as well as angiogenesis and hypoxia and innate and adaptive immunity. Here we highlight specific biological processes that could be exploited as targets for the prevention and therapy of cancer. Specifically, we describe how inhibition of targets such as cholesterol synthesis and metabolites, reactive oxygen species and hypoxia, macrophage activation and conversion, indoleamine 2,3-dioxygenase regulation of dendritic cells, vascular endothelial growth factor regulation of angiogenesis, fibrosis inhibition, endoglin, and Janus kinase signaling emerge as examples of important potential nexuses in the regulation of tumorigenesis and the tumor microenvironment that can be targeted. We have also identified therapeutic agents as approaches, in particular natural products such as berberine, resveratrol, onionin A, epigallocatechin gallate, genistein, curcumin, naringenin, desoxyrhapontigenin, piperine, and zerumbone, that may warrant further investigation to target the tumor microenvironment for the treatment and/or prevention of cancer

The Accretion History of AGN: A Newly Defined Population of Cold Quasars

Quasars are the most luminous of active galactic nuclei (AGN), and are perhaps responsible for quenching star formation in their hosts. The Stripe 82X catalog covers 31.3 deg$^2$ of the Stripe 82 field, of which the 15.6 deg$^2$ covered with XMM-Newton is also covered by Herschel/SPIRE. We have 2500 X-ray detected sources with multi-wavelength counterparts, and 30% of these are unobscured quasars, with $L_X > 10^{44}\,$erg/s and $M_B < -23$. We define a new population of quasars which are unobscured, have X-ray luminosities in excess of $10^{44}\,$erg/s, have broad emission lines, and yet are also bright in the far-infrared, with a 250$\mu$m flux density of $S_{\rm 250}>30$mJy. We refer to these Herschel-detected, unobscured quasars as "Cold Quasars". A mere 4% (21) of the X-ray- and optically-selected unobscured quasars in Stripe 82X are detected at 250$\mu$m. These Cold Quasars lie at $z\sim1-3$, have $L_{\rm IR}>10^{12}\,L_\odot$, and have star formation rates of $\sim200-1400\,M_\odot$/yr. Cold Quasars are bluer in the mid-IR than the full quasar population, and 72% of our Cold Quasars have WISE W3 $<$ 11.5 [Vega], while only 19% of the full quasar sample meets this criteria. Crucially, Cold Quasars have on average $\sim9\times$ as much star formation as the main sequence of star forming galaxies at similar redshifts. Although dust-rich, unobscured quasars have occasionally been noted in the literature before, we argue that they should be considered as a separate class of quasars due to their high star formation rates. This phase is likely short-lived, as the central engine and immense star formation consume the gas reservoir. Cold Quasars are type-1 blue quasars that reside in starburst galaxies.Comment: Accepted for publication in Ap