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1.
BMC Health Serv Res ; 18(1): 161, 2018 03 07.
Article in English | MEDLINE | ID: mdl-29514676

ABSTRACT

BACKGROUND: In the United States, home-based primary care (HBPC) is increasingly proposed as a means of enabling frail elders to remain at home for as long as possible, while still receiving needed medical care. However, there are relatively few studies of either the medical outcome effects or cost benefits of HBPC. In this paper, we examine medical cost and mortality outcomes for enrollees in the HBPC program offered by Spectrum Health/Priority Health (SH/PH), a not-for-profit integrated health care/health insurance system located in Grand Rapids, MI, USA. METHODS: We perform a concurrent matched cohort study. SH/PH HBPC enrollees during 2012-2014 are matched for prior costs, age, sex and comorbidities against controls selected from unenrolled insurance plan members. Twelve and twenty four-month medical costs are compared between HBPC participants and matched controls, overall and conditional on mortality status. Mortality rates of HBPC participants are studied on their own and in comparison to controls. RESULTS: At 12 and 24 months, in comparison to matched controls HBPC participants show higher ($2933) and lower ($8620) costs respectively. Relative costs and savings of HBPC participants are a function of short term increased costs upon entry into the program (enrollees who survive the first year cost $5866 more than controls); substantial savings at end-of-life (approximately $37,037 in savings relative to controls are realized); and the overall mortality of HBPC participants (mean residual lifespan is 37.75 months from the time of enrollment). We project the present value of lifetime medical cost savings due to enrollment in the HBPC program to be at least $14,336. CONCLUSIONS: The SH/PC HBPC program reduces healthcare costs while enabling frail elders to remain at home. Reduction in costs is obtained at end-of-life and is offset with a smaller initial increase in costs upon enrollment.


Subject(s)
Health Care Costs/statistics & numerical data , Home Care Services/economics , Medicare/economics , Primary Health Care/economics , Aged , Cohort Studies , Female , Frail Elderly/statistics & numerical data , Humans , Male , Program Evaluation , United States
2.
PLoS One ; 7(9): e42367, 2012.
Article in English | MEDLINE | ID: mdl-22970116

ABSTRACT

In a two stage genome-wide association study (2S-GWAS), a sample of cases and controls is allocated into two groups, and genetic markers are analyzed sequentially with respect to these groups. For such studies, experimental design considerations have primarily focused on minimizing study cost as a function of the allocation of cases and controls to stages, subject to a constraint on the power to detect an associated marker. However, most treatments of this problem implicitly restrict the set of feasible designs to only those that allocate the same proportions of cases and controls to each stage. In this paper, we demonstrate that removing this restriction can improve the cost advantages demonstrated by previous 2S-GWAS designs by up to 40%. Additionally, we consider designs that maximize study power with respect to a cost constraint, and show that recalculated power maximizing designs can recover a substantial amount of the planned study power that might otherwise be lost if study funding is reduced. We provide open source software for calculating cost minimizing or power maximizing 2S-GWAS designs.


Subject(s)
Genome-Wide Association Study/economics , Genome-Wide Association Study/methods , Case-Control Studies , Costs and Cost Analysis , Humans
3.
Bioinformatics ; 28(11): 1553-4, 2012 Jun 01.
Article in English | MEDLINE | ID: mdl-22522135

ABSTRACT

SUMMARY: Mixed model-based approaches to genome-wide association studies (GWAS) of binary traits in related individuals can account for non-genetic risk factors in an integrated manner. However, they are technically challenging. GLOGS (Genome-wide LOGistic mixed model/Score test) addresses such challenges with efficient statistical procedures and a parallel implementation. GLOGS has high power relative to alternative approaches as risk covariate effects increase, and can complete a GWAS in minutes. AVAILABILITY: Source code and documentation are provided at http://www.bioinformatics.org/~stanhope/GLOGS.


Subject(s)
Genome-Wide Association Study/methods , Logistic Models , Models, Genetic , Humans , Phenotype , Risk
4.
PLoS One ; 5(7): e11652, 2010 Jul 29.
Article in English | MEDLINE | ID: mdl-20686599

ABSTRACT

Mathematical aspects of coverage and gaps in genome assembly have received substantial attention by bioinformaticians. Typical problems under consideration suppose that reads can be experimentally obtained from a single genome and that the number of reads will be set to cover a large percentage of that genome at a desired depth. In metagenomics experiments genomes from multiple species are simultaneously analyzed and obtaining large numbers of reads per genome is unlikely. We propose the probability of obtaining at least one contig of a desired minimum size from each novel genome in the pool without restriction based on depth of coverage as a metric for metagenomic experimental design. We derive an approximation to the distribution of maximum contig size for single genome assemblies using relatively few reads. This approximation is verified in simulation studies and applied to a number of different metagenomic experimental design problems, ranging in difficulty from detecting a single novel genome in a pool of known species to detecting each of a random number of novel genomes collectively sized and with abundances corresponding to given distributions in a single pool.


Subject(s)
Computational Biology/methods , Metagenomics/methods , Models, Theoretical
5.
Blood ; 115(1): 133-9, 2010 Jan 07.
Article in English | MEDLINE | ID: mdl-19880500

ABSTRACT

Recently, messenger RNAs in eukaryotes have shown to associate with antisense (AS) transcript partners that are often referred to as long noncoding RNAs (lncRNAs) whose function is largely unknown. Here, we have identified a natural AS transcript for tyrosine kinase containing immunoglobulin and epidermal growth factor homology domain-1 (tie-1), tie-1AS lncRNA in zebrafish, mouse, and humans. In embryonic zebrafish, tie-1AS lncRNA transcript is expressed temporally and spatially in vivo with its native target, the tie-1 coding transcript and in additional locations (ear and brain). The tie-1AS lncRNA selectively binds tie-1 mRNA in vivo and regulates tie-1 transcript levels, resulting in specific defects in endothelial cell contact junctions in vivo and in vitro. The ratio of tie-1 versus tie-1AS lncRNA is altered in human vascular anomaly samples. These results directly implicate noncoding RNA-mediated transcriptional regulation of gene expression as a fundamental control mechanism for physiologic processes, such as vascular development.


Subject(s)
Genetic Loci/genetics , RNA, Antisense/genetics , RNA, Untranslated/genetics , Zebrafish Proteins/metabolism , Zebrafish/genetics , Animals , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Endothelial Cells/pathology , Endothelium/drug effects , Endothelium/metabolism , Endothelium/pathology , Gene Expression Profiling , Gene Expression Regulation/drug effects , Humans , Intercellular Junctions/drug effects , Intercellular Junctions/metabolism , Intercellular Junctions/pathology , Mice , Neovascularization, Physiologic/drug effects , Phenotype , RNA, Antisense/metabolism , RNA, Untranslated/metabolism , Receptor, TIE-1/genetics , Receptor, TIE-1/metabolism , Species Specificity , Vascular Diseases/genetics , Vascular Diseases/pathology , Vascular Endothelial Growth Factor A/pharmacology , Zebrafish Proteins/genetics
6.
PLoS Comput Biol ; 5(9): e1000516, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19779550

ABSTRACT

MicroRNAs (miRNAs) posttranscriptionally regulate targeted messenger RNAs (mRNAs) by inducing cleavage or otherwise repressing their translation. We address the problem of detecting m/miRNA targeting relationships in homo sapiens from microarray data by developing statistical models that are motivated by the biological mechanisms used by miRNAs. The focus of our modeling is the construction, activity, and mediation of RNA-induced silencing complexes (RISCs) competent for targeted mRNA cleavage. We demonstrate that regression models accommodating RISC abundance and controlling for other mediating factors fit the expression profiles of known target pairs substantially better than models based on m/miRNA expressions alone, and lead to verifications of computational target pair predictions that are more sensitive than those based on marginal expression levels. Because our models are fully independent of exogenous results from sequence-based computational methods, they are appropriate for use as either a primary or secondary source of information regarding m/miRNA target pair relationships, especially in conjunction with high-throughput expression studies.


Subject(s)
E2F1 Transcription Factor/genetics , Gene Expression Regulation , MicroRNAs/genetics , Models, Statistical , RNA-Induced Silencing Complex/genetics , Computational Biology , Databases, Genetic , E2F1 Transcription Factor/metabolism , MicroRNAs/metabolism , Models, Genetic , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA-Induced Silencing Complex/metabolism , Random Allocation , Regression Analysis , Reproducibility of Results
7.
Proc Natl Acad Sci U S A ; 105(15): 5874-8, 2008 Apr 15.
Article in English | MEDLINE | ID: mdl-18390668

ABSTRACT

Using highly sensitive microarray-based procedures, we identified eight microRNAs (miRNAs) showing robust differential expression between 31 laser-capture-microdissected nasopharyngeal carcinomas (NPCs) and 10 normal healthy nasopharyngeal epithelial samples. In particular, miRNA mir-29c was expressed at one-fifth the levels in tumors as in normal epithelium. In NPC tumors, the lower mir-29c levels correlated with higher levels of multiple mRNAs whose 3' UTRs can bind mir-29c at target sequences conserved across many vertebrates. In cultured cells, introduction of mir-29c down-regulated these genes at the level of mRNA and inhibited expression of luciferase encoded by vectors having the 3' UTRs of these genes. Moreover, for each of several genes tested, mutating the mir-29c target sites in the 3' UTR abrogated mir-29c-induced inhibition of luciferase expression. Most of the mir-29c-targeted genes identified encode extracellular matrix proteins, including multiple collagens and laminin gamma1, that are associated with tumor cell invasiveness and metastatic potential, prominent characteristics of NPC. Thus, we identify eight miRNAs differentially expressed in NPC and demonstrate the involvement of one in regulating genes involved in metastasis.


Subject(s)
Extracellular Matrix Proteins/genetics , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Nasopharyngeal Neoplasms/genetics , Case-Control Studies , Down-Regulation , Gene Expression Profiling , Humans , MicroRNAs/physiology , RNA, Messenger , Up-Regulation
8.
Radiat Environ Biophys ; 46(2): 147-54, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17072633

ABSTRACT

Accurate methods for measuring the biological effects of radiation are critical for estimating an individual's health risk from radiation exposure. We investigated the feasibility of using radiation-induced mutations in repetitive DNA sequences to measure genetic damage caused by radiation exposure. Most repetitive sequences are in non-coding regions of the genome and alterations in these loci are usually not deleterious. Thus, mutations in non-coding repetitive sequences might accumulate, providing a stable molecular record of DNA damage caused by all past exposures. To test this hypothesis, we screened repetitive DNA sequences to identify the loci most sensitive to radiation-induced mutations and then investigated whether these mutations were stable in vivo over time and after multiple exposures. Microsatellite repeat markers were identified that exhibited a linear dose response up to 1 Gy of 1 GeV/nucleon 56Fe ions and 137Cs gamma rays in mouse and human cells. Short tandem repeats on the Y chromosome and mononucleotide repeats on autosomal chromosomes exhibited significant increases in mutations at >or= 0.5 Gy of 56Fe ions with frequencies averaging 4.3-10.3 x 10(-3) mutations/locus/Gy/cell, high enough for direct detection of mutations in irradiated cells. A significant increase in radiation-induced mutations in extended mononucleotide repeats was detectible in vivo in mouse blood and cheek samples 10 and 26 weeks after radiation exposure and these mutations were additive over multiple exposures. This study demonstrates the feasibility of a novel method for biodosimetry that is applicable to humans and other species. This new approach should complement existing methods of biodosimetry and might be useful for measuring radiation exposure in circumstances that are not amenable to current methods.


Subject(s)
Biological Assay/methods , DNA Mutational Analysis/methods , DNA/genetics , DNA/radiation effects , Microsatellite Repeats/radiation effects , Radiometry/methods , Dose-Response Relationship, Radiation , Feasibility Studies , Microsatellite Repeats/genetics , Radiation Dosage , Sequence Analysis, DNA/methods
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