Effectiveness of End-of-Life Strategies to Improve Health Outcomes and Reduce Disparities in Rural Appalachia: An analytic codebook

Appalachia is one of the most medically underserved areas in the nation. The region has provider shortages and limited healthcare infrastructure. Children and adolescents in this area are in poor health and do not receive the needed quality care. Implementation of section 2302 of the 2010 Patient Protection and Affordable Care Act (ACA) enabled children enrolled in Medicaid/Children\u27s Health Insurance Program with a terminal illness to use hospice care while continuing treatment for their terminal illness. In addition to being more comprehensive than standard hospice care, this relatively new type of care is more culturally congruent with the end-of-life values of rural Appalachian families, who often view standard hospice as hastening death. The overall goal of this project was to investigate access to pediatric concurrent hospice care in Appalachia. Our central hypothesis was that concurrent care reduces rural/urban disparities in access to hospice care. Data from the Centers for Medicare and Medicaid Services (CMS) used in this project was used and included 1,788 children who resided in the Appalachian region– from January 1, 2011, to December 31, 2013. Observations with missing birth dates, death dates, and participants older than 21 years were removed from the final sample. Geographic Information Systems (GIS) databases were created to map the boundaries of the Appalachian region, hospice locations, and driving times to them

Extension and approximation of mm-subharmonic functions

Let $\Omega\subset \mathbb C^n$ be a bounded domain, and let $f$ be a real-valued function defined on the whole topological boundary $\partial \Omega$. The aim of this paper is to find a characterization of the functions $f$ which can be extended to the inside to a $m$-subharmonic function under suitable assumptions on $\Omega$. We shall do so by using a function algebraic approach with focus on $m$-subharmonic functions defined on compact sets. We end this note with some remarks on approximation of $m$-subharmonic functions

The Spectrum of Yang Mills on a Sphere

In this note, we determine the representation content of the free, large N, SU(N) Yang Mills theory on a sphere by decomposing its thermal partition function into characters of the irreducible representations of the conformal group SO(4,2). We also discuss the generalization of this procedure to finding the representation content of N=4 Super Yang Mills.Comment: 18 pages v2. references added. typos fixe

C/EBPβ-1 promotes transformation and chemoresistance in Ewing sarcoma cells.

CEBPB copy number gain in Ewing sarcoma was previously shown to be associated with worse clinical outcome compared to tumors with normal CEBPB copy number, although the mechanism was not characterized. We employed gene knockdown and rescue assays to explore the consequences of altered CEBPB gene expression in Ewing sarcoma cell lines. Knockdown of EWS-FLI1 expression led to a decrease in expression of all three C/EBPβ isoforms while re-expression of EWS-FLI1 rescued C/EBPβ expression. Overexpression of C/EBPβ-1, the largest of the three C/EBPβ isoforms, led to a significant increase in colony formation when cells were grown in soft agar compared to empty vector transduced cells. In addition, depletion of C/EBPβ decreased colony formation, and re-expression of either C/EBPβ-1 or C/EBPβ-2 rescued the phenotype. We identified the cancer stem cell marker ALDH1A1 as a target of C/EBPβ in Ewing sarcoma. Furthermore, increased expression of C/EBPβ led to resistance to chemotherapeutic agents. In summary, we have identified CEBPB as an oncogene in Ewing sarcoma. Overexpression of C/EBPβ-1 increases transformation, upregulates expression of the cancer stem cell marker ALDH1A1, and leads to chemoresistance

The function of FGF signaling in the lens placode

AbstractPrevious studies suggested that FGF signaling is important for lens formation. However, the times at which FGFs act to promote lens formation, the FGFs that are involved, the cells that secrete them and the mechanisms by which FGF signaling may promote lens formation are not known. We found that transcripts encoding several FGF ligands and the four classical FGF receptors are detectable in the lens-forming ectoderm at the time of lens induction. Conditional deletion of Fgfr1 and Fgfr2 from this tissue resulted in the formation of small lens rudiments that soon degenerated. Lens placodes lacking Fgfr1 and 2 were thinner than in wild-type embryos. Deletion of Fgfr2 increased cell death from the initiation of placode formation and concurrent deletion of Fgfr1 enhanced this phenotype. Fgfr1/2 conditional knockout placode cells expressed lower levels of proteins known to be regulated by FGF receptor signaling, but proteins known to be important for lens formation were present at normal levels in the remaining placode cells, including the transcription factors Pax6, Sox2 and FoxE3 and the lens-preferred protein αA-crystallin. Previous studies identified a genetic interaction between BMP and FGF signaling in lens formation and conditional deletion of Bmpr1a caused increased cell death in the lens placode, resulting in the formation of smaller lenses. In the present study, conditional deletion of both Bmpr1a and Fgfr2 increased cell death beyond that seen in Fgfr2CKO placodes and prevented lens formation. These results suggest that the primary role of autocrine or paracrine FGF signaling is to provide essential survival signals to lens placode cells. Because apoptosis was already increased at the onset of placode formation in Fgfr1/2 conditional knockout placode cells, FGF signaling was functionally absent during the period of lens induction by the optic vesicle. Since the expression of proteins required for lens formation was not altered in the knockout placode cells, we can conclude that FGF signaling from the optic vesicle is not required for lens induction

Antagonists of Calcium Fluxes and Calmodulin Block Activation of the p21-Activated Protein Kinases in Neutrophils

Neutrophils stimulated with fMLP or a variety of other chemoattractants that bind to serpentine receptors coupled to heterotrimeric G proteins exhibit rapid activation of two p21-activated protein kinases (Paks) with molecular masses of ~63 and 69 kDa (y- and a-Pak). Previous studies have shown that products of phosphatidylinositol 3-kinase and tyrosine kinases are required for the activation of Paks. We now report that a variety of structurally distinct compounds which interrupt different stages in calcium/calmodulin (CaM) signaling block activation of the 63- and 69-kDa Paks in fMLP-stimulated neutrophils. These antagonists included selective inhibitors of phospholipase C (1-[6-((17ß-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl]-1H-pyrrole- 2,5-dione), the intracellular Ca^(2+) channel (8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate), CaM (N-(6-aminohexyl)-5- chloro-1-naphthalenesulfonamide; N-(4-aminobutyl)-5-chloro-1-naphthalenesulfonamide; trifluoperazine), and CaM-activated protein kinases (N-[2-(N-(chlorocinnamyl)-N-methylaminomethyl)phenyl]-N-[2-hydroxyethyl]-4-methoxybenzenesulfonamide). This inhibition was dose-dependent with IC50 values very similar to those that interrupt CaM-dependent reactions in vitro. In contrast, less active analogues of these compounds (1-[6-((17ß-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl]-2,5-pyrrolidinedione; N-(6-aminohexyl)-1-naphthalenesulfonamide; N-(4-aminobutyl)-1-naphthalenesulfonamide; promethazine; 2-[N-(4- methoxybenzenesulfonyl)]amino-N-(4-chlorocinnamyl)-N-methylbenzyl-amine]) did not affect activation of Paks in these cells. CaM antagonists (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide; trifluoperazine), but not their less-active analogues (N- (6-aminohexyl)-1-naphthalenesulfonamide; promethazine), were also found to block activation of the small GTPases Ras and Rac in stimulated neutrophils along with the extracellular signal-regulated kinases. These data strongly suggest that the Ca^(2+)/CaM complex plays a major role in the activation of a number of enzyme systems in neutrophils that are regulated by small GTPases

Hierarchical multi-class segmentation of glioma images using networks with multi-level activation function

For many segmentation tasks, especially for the biomedical image, the topological prior is vital information which is useful to exploit. The containment/nesting is a typical inter-class geometric relationship. In the MICCAI Brain tumor segmentation challenge, with its three hierarchically nested classes 'whole tumor', 'tumor core', 'active tumor', the nested classes relationship is introduced into the 3D-residual-Unet architecture. The network comprises a context aggregation pathway and a localization pathway, which encodes increasingly abstract representation of the input as going deeper into the network, and then recombines these representations with shallower features to precisely localize the interest domain via a localization path. The nested-class-prior is combined by proposing the multi-class activation function and its corresponding loss function. The model is trained on the training dataset of Brats2018, and 20% of the dataset is regarded as the validation dataset to determine parameters. When the parameters are fixed, we retrain the model on the whole training dataset. The performance achieved on the validation leaderboard is 86%, 77% and 72% Dice scores for the whole tumor, enhancing tumor and tumor core classes without relying on ensembles or complicated post-processing steps. Based on the same start-of-the-art network architecture, the accuracy of nested-class (enhancing tumor) is reasonably improved from 69% to 72% compared with the traditional Softmax-based method which blind to topological prior.Comment: 12pages first versio

The role of severity perceptions and beliefs in natural infections in Shanghai parents’ vaccine decision-making: a qualitative study

Abstract Background China has reduced incidence of vaccine-preventable diseases through its Expanded Program on Immunization (EPI). Vaccines outside of the EPI are not provided for free by the government, however. This study explored how the stated importance of different disease and vaccine-related attributes interacted with beliefs about the immune system of a child to affect Chinese parents’ decision to obtain a non-EPI vaccine. Methods Mothers and fathers of young children at immunization clinics in Shanghai, China, were interviewed about vaccine decision-making and what attributes of a disease were important when making this decision. An inductive thematic analysis explored their beliefs about disease attributes and how these related to vaccination decisions. Results Among the 34 interviews, severity of the disease—particularly in causing long-term disability—was the most commonly cited factor influencing a parent’s decision to get a vaccine for their child. Many parents believed that natural infection was preferable to vaccination, as long as disease was not severe, and many were concerned that imported vaccines were inadequate for Chinese children’s physical constitutions. All these beliefs could influence the decision to vaccinate. Conclusions Many parents do not appear to understand how and why vaccines can support development of a healthy immune system. Because severity emerged as parents’ overriding concern when making decisions about vaccines, marketing for a childhood vaccine could focus on the severe condition that a vaccine can protect against.https://deepblue.lib.umich.edu/bitstream/2027.42/144525/1/12889_2018_Article_5734.pd

Large non-Gaussianity from two-component hybrid inflation

We study the generation of non-Gaussianity in models of hybrid inflation with two inflaton fields, (2-brid inflation). We analyse the region in the parameter and the initial condition space where a large non-Gaussianity may be generated during slow-roll inflation which is generally characterised by a large f_NL, tau_NL and a small g_NL. For certain parameter values we can satisfy tau_NL>>f_NL^2. The bispectrum is of the local type but may have a significant scale dependence. We show that the loop corrections to the power spectrum and bispectrum are suppressed during inflation, if one assume that the fields follow a classical background trajectory. We also include the effect of the waterfall field, which can lead to a significant change in the observables after the waterfall field is destabilised, depending on the couplings between the waterfall and inflaton fields.Comment: 16 pages, 6 figures; v2: comments and references added, typos corrected, matches published versio

Statistical Multifragmentation in Central Au+Au Collisions at 35 MeV/u

Multifragment disintegrations, measured for central Au + Au collisions at E/A = 35 MeV, are analyzed with the Statistical Multifragmentation Model. Charge distributions, mean fragment energies, and two-fragment correlation functions are well reproduced by the statistical breakup of a large, diluted and thermalized system slightly above the multifragmentation threshold.Comment: Latex file, 8 pages + 4 postscript figures available upon request from [email protected]