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1.
Am J Surg ; 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31421893

RESUMO

BACKGROUND: We hypothesized that long-term quality of life (QoL) is improved among patients with ventral hernias (VHs) and comorbid conditions managed operatively than with non-operative management. METHODS: This was the 3-year follow-up to a prospective observational study of patients with comorbid conditions and VHs. Primary outcome was change in QoL measured utilizing the modified Activities Assessment Scale (AAS), a validated, hernia-specific survey. Outcomes were compared using: (1)paired t-test on matched subset and (2)multivariable linear regression on the overall cohort. RESULTS: In the matched cohort (n = 80; 40/group), the operative group experienced a significantly greater improvement in QoL compared to the non-operative group (28.4 ±â€¯27.1 vs. 11.8 ±â€¯23.8,p = 0.005). The operative group, had 10 (25.0%) reported recurrences while the non-operative group, reported 4/15 (26.7%) recurrences among the 15 (37.5%) patients that underwent repair. On multivariable analysis of the whole cohort (n = 137), operative management was associated with a 19.5 (95% CI7.0-31.9) point greater improvement in QoL compared to non-operative management. CONCLUSIONS: This is the first long term prospective study showing the benefits of operative as opposed to non-operative management of patients with comorbid conditions and VHs.

2.
PLoS Genet ; 15(7): e1008203, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31269027

RESUMO

Polymorphic inversions contribute to adaptation and phenotypic variation. However, large multi-centric association studies of inversions remain challenging. We present scoreInvHap, a method to genotype inversions from SNP data for genome-wide association studies (GWASs), overcoming important limitations of current methods and outperforming them in accuracy and applicability. scoreInvHap calls individual inversion-genotypes from a similarity score to the SNPs of experimentally validated references. It can be used on different sources of SNP data, including those with low SNP coverage such as exome sequencing, and is easily adaptable to genotype new inversions, either in humans or in other species. We present 20 human inversions that can be reliably and easily genotyped with scoreInvHap to discover their role in complex human traits, and illustrate a first genome-wide association study of experimentally-validated human inversions. scoreInvHap is implemented in R and it is freely available from Bioconductor.

3.
Bioinformatics ; 2019 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-31243429

RESUMO

SUMMARY: Genomics has dramatically improved our understanding of the molecular origins of certain human diseases. Nonetheless, our health is also influenced by the cumulative impact of exposures experienced across the life course (termed "exposome"). The study of the high-dimensional exposome offers a new paradigm for investigating environmental contributions to disease etiology. However, there is a lack of bioinformatics tools for managing, visualizing and analyzing the exposome. The analysis data should include both association with health outcomes and integration with omic layers. We provide a generic framework called rexposome project, developed in the R/Bioconductor architecture that includes object-oriented classes and methods to leverage high-dimensional exposome data in disease association studies including its integration with a variety of high-throughput data types. The usefulness of the package is illustrated by analyzing a real dataset including exposome data, three health outcomes realted to respiratory diseases and its integration with the transcriptome and methylome. AVAILABILITY: rexposome project is available at https://isglobal-brge.github.io/rexposome/.

4.
Neuroinformatics ; 17(4): 583-592, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30903541

RESUMO

Multivariate methods have the potential to better capture complex relationships that may exist between different biological levels. Multiple Factor Analysis (MFA) is one of the most popular methods to obtain factor scores and measures of discrepancy between data sets. However, singular value decomposition in MFA is based on PCA, which is adequate only if the data is normally distributed, linear or stationary. In addition, including strongly correlated variables can overemphasize the contribution of the estimated components. In this work, we introduced a novel method referred as Independent Multifactorial Analysis (ICA-MFA) to derive relevant features from multiscale data. This method is an extended implementation of MFA, where the component value decomposition is based on Independent Component Analysis. In addition, ICA-MFA incorporates a predictive step based on an Independent Component Regression. We evaluated and compared the performance of ICA-MFA with both, the MFA method and traditional univariate analyses, in a simulation study. We showed how ICA-MFA explained up to 10-fold more variance than MFA and univariate methods. We applied the proposed algorithm in a study of 4057 individuals belonging to the population-based Rotterdam Study with available genetic and neuroimaging data, as well as information about executive cognitive functioning. Specifically, we used ICA-MFA to detect relevant genetic features related to structural brain regions, which in turn were involved, in the mechanisms of executive cognitive function. The proposed strategy makes it possible to determine the degree to which the whole set of genetic and/or neuroimaging markers contribute to the variability of the symptomatology jointly, rather than individually. While univariate results and MFA combinations only explained a limited proportion of variance (less than 2%), our method increased the explained variance (10%) and allowed the identification of significant components that maximize the variance explained in the model. The potential application of the ICA-MFA algorithm constitutes an important aspect of integrating multivariate multiscale data, specifically in the field of Neurogenetics.

5.
J Gen Intern Med ; 34(3): 429-434, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30604124

RESUMO

BACKGROUND: Financial interactions between industry and healthcare providers are reportable. Substantial discrepancies have been detected between industry and self-report of these conflicts of interest (COIs). OBJECTIVE: Our aim was to determine if authors who fail to disclose reportable COI are more likely to publish findings that are favorable to industry than authors with no COI. DESIGN: In this blinded, observational study of medical and surgical primary research articles in PubMed, 590 articles were reviewed. MAIN MEASURES: Reportable financial relationships between authors and industry were evaluated. COIs were considered to have relevance if they were associated with the product(s) mentioned by an article. Primary outcome was favorability, defined as an impression favorable to the product(s) discussed by an article and determined by 3 independent, blinded clinicians for each article. Primary analysis compared Incomplete Self-Disclosure to No COI. Two-level multivariable mixed-effects ordered logistic regression was used to assess factors associated with favorability. KEY RESULTS: A 69% discordance rate existed between industry and self-report in COI disclosure. When authors failed to disclose COI, their conclusions were more likely to favor industry partners than authors without COI (favorable ratings 73% versus 62%, RR 1.18, p = < 0.001). On univariate (any COI 74% versus no COI 62%, RR 1.11, p = < 0.001) and multivariable analyses, any COI was associated with favorability. CONCLUSIONS: All financial COIs (disclosed or undisclosed, relevant or not relevant, research or non-research) influence whether studies report findings favorable to industry sponsors.

6.
Nat Genet ; 51(2): 245-257, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30643258

RESUMO

Humans vary substantially in their willingness to take risks. In a combined sample of over 1 million individuals, we conducted genome-wide association studies (GWAS) of general risk tolerance, adventurousness, and risky behaviors in the driving, drinking, smoking, and sexual domains. Across all GWAS, we identified hundreds of associated loci, including 99 loci associated with general risk tolerance. We report evidence of substantial shared genetic influences across risk tolerance and the risky behaviors: 46 of the 99 general risk tolerance loci contain a lead SNP for at least one of our other GWAS, and general risk tolerance is genetically correlated ([Formula: see text] ~ 0.25 to 0.50) with a range of risky behaviors. Bioinformatics analyses imply that genes near SNPs associated with general risk tolerance are highly expressed in brain tissues and point to a role for glutamatergic and GABAergic neurotransmission. We found no evidence of enrichment for genes previously hypothesized to relate to risk tolerance.


Assuntos
Comportamento/fisiologia , Loci Gênicos/genética , Predisposição Genética para Doença/genética , Estudos de Casos e Controles , Feminino , Genética Comportamental/métodos , Estudo de Associação Genômica Ampla/métodos , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genética
7.
BMC Genomics ; 20(1): 26, 2019 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-30626339

RESUMO

BACKGROUND: There is great interest to study how gene pathways change their structure across different tissues. The assessment of inter-study reliability of pathway changes across tissues can inform on the fraction of tissues with specific functional changes in network structure. However, there is a lack of agreement measures among studies that independently observe how a group of observations change across conditions. We, therefore, propose λ, a new inter-study reliability measure that determines the consistency to distinguish observations by condition. RESULTS: We derived λ's distributional characteristics, determine its reliability properties and compared it with Cohen's κ. We studied the co-expression structure of 287 gene pathways across four brain regions in two transcriptomic studies and applied λ to assess the inter-study reliability of the pathways' brain-regional changes. Brain-related pathways showed highest λ; the top value was for the nicotine addiction pathway whose structure was reliably distinguishable among regions with dopaminergic projections. CONCLUSION: Our results offer novel substantial evidence that changes in network structure across tissues can be inferred independently of samples, algorithms and experiments (RNA-sequencing or microarrays). Reliability measures, such as λ, can inform on the tissues where changes in a network's structure are likely functional. An R package is available at https://github.com/isglobal-brge/lambda .


Assuntos
Encéfalo/metabolismo , Redes Reguladoras de Genes/genética , Especificidade de Órgãos/genética , Transcriptoma/genética , Regulação da Expressão Gênica/genética , Humanos , Análise em Microsséries , Análise de Sequência de RNA , Transdução de Sinais/genética
8.
BMC Genomics ; 19(1): 926, 2018 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-30545302

RESUMO

BACKGROUND: Genes corregulate their overall transcript volumes to perform their physiological functions. However, it is unknown if they additionally coregulate their transcript diversities. We studied the reliability, consistency and functional associations of co-splicing correlations of genes of interest, across two independent studies, multiple tissues and two statistical methods. We thoroughly investigated the reproducibility of co-splicing correlations of APP, the candidate gene of Azheimer's disease (AD). We then studied how co-splicing correlations in different tissues contributed to predict functional interactions of three other genes and finally computed co-splicing frequency for 17 thousand genes across 52 human tissues. RESULTS: We replicated co-splicing correlations between APP and 5 AD-related genes and reproduced expected enrichment of APP co-splicing in synaptic vesicle cycle and proteosome pathways. We observed novel associations for tissue vulnerability to disease with enrichment in APP co-splicing, co-expression and epistasis in AD. APP co-splicing was the strongest predictor and replicated between studies. We confirmed known gene interactions of PRPF8 and GRIA1 in testis and brain cortex, and observed a novel interaction of FGFR2, in breast and prostate, modulated by cancer risk-variants. We produced a co-splicing map across 52 human tissues to help predict the function of over 17 thousand genes. CONCLUSIONS: We show that coregulation of transcript diversities provides novel biological insights in gene physiology and helps to interpret GWAS results. Co-splicing correlations are reliable and frequent and should be further pursued to help predict gene function. Our results additionally support current AD interventions aiming at the ubiquitin proteosome pathway but unveil the need to consider transcript diversity in addition to volume to assess treatment response and susceptibility to the disease.


Assuntos
Doença de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Processamento Alternativo , Doença de Alzheimer/patologia , Precursor de Proteína beta-Amiloide/metabolismo , Mama/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Feminino , Hipocampo/metabolismo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , RNA/química , RNA/isolamento & purificação , RNA/metabolismo , Proteínas de Ligação a RNA/metabolismo , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Receptores de AMPA/genética , Receptores de AMPA/metabolismo , Receptores Depuradores Classe B/genética , Receptores Depuradores Classe B/metabolismo , Análise de Sequência de RNA , Testículo/metabolismo
9.
Environ Int ; 121(Pt 1): 561-573, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30300814

RESUMO

BACKGROUND: Exposome studies are challenged by exposure misclassification for non-persistent chemicals, whose temporal variability contributes to bias in dose-response functions. OBJECTIVES: We evaluated the variability of urinary concentrations of 24 non-persistent chemicals: 10 phthalate metabolites, 7 phenols, 6 organophosphate (OP) pesticide metabolites, and cotinine, between weeks from different pregnancy trimesters in pregnant women, and between days and between seasons in children. METHODS: 154 pregnant women and 152 children from six European countries were enrolled in 2014-2015. Pregnant women provided three urine samples over a day (morning, midday, and night), for one week in the 2nd and 3rd pregnancy trimesters. Children provided two urines a day (morning and night), over two one-week periods, six months apart. We pooled all samples for a given subject that were collected within a week. In children, we also made four daily pools (combining morning and night voids) during the last four days of the first follow-up week. Pools were analyzed for all 24 metabolites of interest. We calculated intraclass-correlation coefficients (ICC) and estimated the number of pools needed to obtain an ICC above 0.80. RESULTS: All phthalate metabolites and phenols were detected in >90% of pools whereas certain OP pesticide metabolites and cotinine were detected in <43% of pools. We observed fair (ICC = 0.40-0.59) to good (0.60-0.74) between-day reliability of the pools of two samples in children for all chemicals. Reliability was poor (<0.40) to fair between trimesters in pregnant women and between seasons in children. For most chemicals, three daily pools of two urines each (for weekly exposure windows) and four weekly pools of 15-20 urines each would be necessary to obtain an ICC above 0.80. CONCLUSIONS: This quantification of the variability of biomarker measurements of many non-persistent chemicals during several time windows shows that for many of these compounds a few dozen samples are required to accurately assess exposure over periods encompassing several trimesters or months.

10.
Environ Sci Pollut Res Int ; 25(29): 29572-29583, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30141164

RESUMO

The molecular mechanisms that promote pathologic alterations in human physiology mediated by short-term exposure to traffic pollutants remains not well understood. This work was to develop mechanistic networks to determine which specific pathways are activated by real-world exposures of traffic-related air pollution (TRAP) during rest and moderate physical activity (PA). A controlled crossover study to compare whole blood gene expression pre and post short-term exposure to high and low of TRAP was performed together with systems biology analysis. Twenty-eight healthy volunteers aged between 21 and 53 years were recruited. These subjects were exposed during 2 h to different pollution levels (high and low TRAP levels), while either cycling or resting. Global transcriptome profile of each condition was performed from human whole blood samples. Microarrays analysis was performed to obtain differential expressed genes (DEG) to be used as initial input for GeneMANIA software to obtain protein-protein (PPI) networks. Two networks were found reflecting high or low TRAP levels, which shared only 5.6 and 15.5% of its nodes, suggesting specific cell signaling pathways being activated in each environmental condition. However, gene ontology analysis of each PPI network suggests that each level of TRAP regulate common members of NF-κB signaling pathway. Our work provides the first approach describing mechanistic networks to understand TRAP effects on a system level.

11.
Int J Methods Psychiatr Res ; 27(3): e1738, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30105890

RESUMO

OBJECTIVES: We proposed the application of a multivariate cross-sectional framework based on a combination of a variable selection method and a multiple factor analysis (MFA) in order to identify complex meaningful biological signals related to attention-deficit/hyperactivity disorder (ADHD) symptoms and hyperactivity/inattention domains. METHODS: The study included 135 children from the general population with genomic and neuroimaging data. ADHD symptoms were assessed using a questionnaire based on ADHD-DSM-IV criteria. In all analyses, the raw sum scores of the hyperactivity and inattention domains and total ADHD were used. The analytical framework comprised two steps. First, zero-inflated negative binomial linear model via penalized maximum likelihood (LASSO-ZINB) was performed. Second, the most predictive features obtained with LASSO-ZINB were used as input for the MFA. RESULTS: We observed significant relationships between ADHD symptoms and hyperactivity and inattention domains with white matter, gray matter regions, and cerebellum, as well as with loci within chromosome 1. CONCLUSIONS: Multivariate methods can be used to advance the neurobiological characterization of complex diseases, improving the statistical power with respect to univariate methods, allowing the identification of meaningful biological signals in Imaging Genetic studies.

12.
Front Microbiol ; 9: 1271, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29988527

RESUMO

Exosomes are extracellular vesicles of endocytic origin containing molecular signatures implying the cell of origin; thus, they offer a unique opportunity to discover biomarkers of disease. Plasmodium vivax, responsible for more than half of all malaria cases outside Africa, is a major obstacle in the goal of malaria elimination due to the presence of dormant liver stages (hypnozoites), which after the initial infection may reactivate to cause disease. Hypnozoite infection is asymptomatic and there are currently no diagnostic tools to detect their presence. The human liver-chimeric (FRG huHep) mouse is a robust P. vivax infection model for exo-erythrocytic development of liver stages, including hypnozoites. We studied the proteome of plasma-derived exosomes isolated from P. vivax infected FRG huHep mice with the objective of identifying liver-stage expressed parasite proteins indicative of infection. Proteomic analysis of these exosomes showed the presence of 290 and 234 proteins from mouse and human origin, respectively, including canonical exosomal markers. Human proteins include proteins previously detected in liver-derived exosomes, highlighting the potential of this chimeric mouse model to study plasma exosomes derived unequivocally from human hepatocytes. Noticeably, we identified 17 parasite proteins including enzymes, surface proteins, components of the endocytic pathway and translation machinery, as well as uncharacterized proteins. Western blot analysis validated the presence of human arginase-I and an uncharacterized P. vivax protein in plasma-derived exosomes. This study represents a proof-of-principle that plasma-derived exosomes from P. vivax infected FRG-huHep mice contain human hepatocyte and P. vivax proteins with the potential to unveil biological features of liver infection and identify biomarkers of hypnozoite infection.

13.
Neurosci Biobehav Rev ; 93: 57-70, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29944960

RESUMO

Imaging Genetics (IG) integrates neuroimaging and genomic data from the same individual, deepening our knowledge of the biological mechanisms behind neurodevelopmental domains and neurological disorders. Although the literature on IG has exponentially grown over the past years, the majority of studies have mainly analyzed associations between candidate brain regions and individual genetic variants. However, this strategy is not designed to deal with the complexity of neurobiological mechanisms underlying behavioral and neurodevelopmental domains. Moreover, larger sample sizes and increased multidimensionality of this type of data represents a challenge for standardizing modeling procedures in IG research. This review provides a systematic update of the methods and strategies currently used in IG studies, and serves as an analytical framework for researchers working in this field. To complement the functionalities of the Neuroconductor framework, we also describe existing R packages that implement these methodologies. In addition, we present an overview of how these methodological approaches are applied in integrating neuroimaging and genetic data.

14.
Nat Commun ; 9(1): 2162, 2018 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-29849136

RESUMO

In the originally published version of this Article, the affiliation details for Santi González, Jian'an Luan and Claudia Langenberg were inadvertently omitted. Santi González should have been affiliated with 'Barcelona Supercomputing Center (BSC), Joint BSC-CRG-IRB Research Program in Computational Biology, 08034 Barcelona, Spain', and Jian'an Luan and Claudia Langenberg should have been affiliated with 'MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK'. Furthermore, the abstract contained an error in the SNP ID for the rare variant in chromosome Xq23, which was incorrectly given as rs146662057 and should have been rs146662075. These errors have now been corrected in both the PDF and HTML versions of the Article.

15.
Bioinformatics ; 34(18): 3235-3237, 2018 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-29688259

RESUMO

Summary: Biomedical studies currently include a large volume of genomic and environmental factors for studying the etiology of human diseases. R/Bioconductor projects provide several tools for performing enrichment analysis at gene-pathway level, allowing researchers to develop novel hypotheses. However, there is a need to perform similar analyses at the chemicals-genes or chemicals-diseases levels to provide complementary knowledge of the causal path between chemicals and diseases. While the Comparative Toxicogenomics DatabaseTM (CTD) provides information about these relationships, there is no software for integrating it into R/Bioconductor analysis pipelines. CTDquerier helps users to easily download CTD data and integrate it in the R/Bioconductor framework. The package also contains functions for visualizing CTD data and performing enrichment analyses. We illustrate how to use the package with a real data analysis of asthma-related genes. CTDquerier is a flexible and easy-to-use Bioconductor package that provides novel hypothesis about the relationships between chemicals and diseases. Availability and implementation: CTDquerier R package is available through Bioconductor and its development version at https://github.com/isglobal-brge/CTDquerier. Supplementary information: Supplementary data are available at Bioinformatics online.

16.
PLoS One ; 13(3): e0193527, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29505615

RESUMO

Circulating small RNAs, including miRNAs but also isomiRs and other RNA species, have the potential to be used as non-invasive biomarkers for communicable and non-communicable diseases. This study aims to characterize and compare small RNA profiles in human biofluids. For this purpose, RNA was extracted from plasma and breast milk samples from 15 healthy postpartum mothers. Small RNA libraries were prepared with the NEBNext® small RNA library preparation kit and sequenced in an Illumina HiSeq2000 platform. miRNAs, isomiRs and clusters of small RNAs were annotated using seqBuster/seqCluster framework in 5 plasma and 10 milk samples that passed the initial quality control. The RNA yield was 81 ng/mL [standard deviation (SD): 41] and 3985 ng/mL (SD: 3767) for plasma and breast milk, respectively. Mean number of good quality reads was 4.04 million (M) (40.01% of the reads) in plasma and 12.5M (89.6%) in breast milk. One thousand one hundred eighty two miRNAs, 12,084 isomiRs and 1,053 small RNA clusters that included piwi-interfering RNAs (piRNAs), tRNAs, small nucleolar RNAs (snoRNA) and small nuclear RNAs (snRNAs) were detected. Samples grouped by biofluid, with 308 miRNAs, 1,790 isomiRs and 778 small RNA clusters differentially detected. In summary, plasma and milk showed a different small RNA profile. In both, miRNAs, piRNAs, tRNAs, snRNAs, and snoRNAs were identified, confirming the presence of non-miRNA species in plasma, and describing them for the first time in milk.


Assuntos
MicroRNAs/sangue , MicroRNAs/metabolismo , Leite Humano/metabolismo , Adulto , Feminino , Voluntários Saudáveis , Humanos , Masculino , Adulto Jovem
17.
Nat Commun ; 9(1): 321, 2018 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-29358691

RESUMO

The reanalysis of existing GWAS data represents a powerful and cost-effective opportunity to gain insights into the genetics of complex diseases. By reanalyzing publicly available type 2 diabetes (T2D) genome-wide association studies (GWAS) data for 70,127 subjects, we identify seven novel associated regions, five driven by common variants (LYPLAL1, NEUROG3, CAMKK2, ABO, and GIP genes), one by a low-frequency (EHMT2), and one driven by a rare variant in chromosome Xq23, rs146662057, associated with a twofold increased risk for T2D in males. rs146662057 is located within an active enhancer associated with the expression of Angiotensin II Receptor type 2 gene (AGTR2), a modulator of insulin sensitivity, and exhibits allelic specific activity in muscle cells. Beyond providing insights into the genetics and pathophysiology of T2D, these results also underscore the value of reanalyzing publicly available data using novel genetic resources and analytical approaches.


Assuntos
Cromossomos Humanos X/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Alelos , Redes Reguladoras de Genes/genética , Genótipo , Humanos , Resistência à Insulina/genética , Masculino , Modelos Genéticos , Fatores de Risco
18.
Am J Health Promot ; 32(6): 1425-1430, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29129109

RESUMO

PURPOSE: To determine whether increasing the proportion of healthier options in vending machines decreases the amount of calories, fat, sugar, and sodium vended, while maintaining total sales revenue. DESIGN: This study evaluated the impact of altering nutritious options to vending machines throughout the Banner Health organization by comparing vended items' sales and nutrition information over 6 months compared to the same 6 months of the previous year. SETTING: Twenty-three locations including corporate and patient-care centers. INTERVENTION: Changing vending machine composition toward more nutritious options. MEASURES: Comparisons of monthly aggregates of sales, units vended, calories, fat, sodium, and sugar vended by site. ANALYSIS: A pre-post analysis using paired t tests comparing 6 months before implementation to the equivalent 6 months postimplementation. RESULTS: Significant average monthly decreases were seen for calories (16.7%, P = .002), fat (27.4%, P ≤ .0001), sodium (25.9%, P ≤ .0001), and sugar (11.8%, P = .045) vended from 2014 to 2015. Changes in revenue and units vended did not change from 2014 to 2015 ( P = .58 and P = .45, respectively). CONCLUSION: Increasing the proportion of healthier options in vending machines from 20% to 80% significantly lowered the amount of calories, sodium, fat, and sugar vended, while not reducing units vended or having a negative financial impact.

19.
World J Surg ; 42(1): 19-25, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28828517

RESUMO

BACKGROUND: The modified Activities Assessment Scale (AAS) is a 13-question abdominal wall quality of life (AW-QOL) survey validated in patients undergoing ventral hernia repair (VHR). No studies have assessed AW-QOL among individuals without abdominal wall pathology. The minimal clinically important difference (MCID) of the modified AAS and its implications for the threshold at which VHR should be offered also remain unknown. Our objectives were to (1) establish the AW-QOL of patients with a clinical abdominal wall hernia versus those with no hernia, (2) determine the MCID of the modified AAS, and (3) identify the baseline quality of life (QOL) score at which patients derive little clinical benefit from VHR. METHODS: Patient-centered outcomes data for all patients presenting to General Surgery and Hernia Clinics October-December 2016 at a single safety-net institution were collected via a prospective, cross-sectional observational study design. Primary outcome was QOL measured using the modified AAS. Secondary outcome was the MCID. RESULTS: Patients with no hernia had modified AAS scores of 81.6 (50.4-94.4), while patients with a clinically apparent hernia had lower modified AAS scores of 31.4 (12.6-58.7) (p < 0.001). The MCID threshold was 7.6 for a "slight" change and 14.9 for "definite" change. Above a modified AAS score of 81, the risk of worsening a patient's QOL by surgery is higher than the chances of improvement. CONCLUSIONS: VHR can improve 1-year postsurgical AW-QOL to levels similar to that of the general population. The MCID of the modified AAS is 7.6 points. Patients with high baseline scores should be counseled about the lack of potential benefit in QOL from elective VHR.


Assuntos
Hérnia Ventral/cirurgia , Herniorrafia/reabilitação , Qualidade de Vida , Parede Abdominal/cirurgia , Adulto , Idoso , Estudos Transversais , Procedimentos Cirúrgicos Eletivos/reabilitação , Feminino , Inquéritos Epidemiológicos , Hérnia Ventral/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados da Assistência ao Paciente , Estudos Prospectivos , Psicometria
20.
BMC Bioinformatics ; 18(1): 553, 2017 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-29237399

RESUMO

BACKGROUND: DNA methylation is an epigenetic process that regulates gene expression. Methylation can be modified by environmental exposures and changes in the methylation patterns have been associated with diseases. Methylation microarrays measure methylation levels at more than 450,000 CpGs in a single experiment, and the most common analysis strategy is to perform a single probe analysis to find methylation probes associated with the outcome of interest. However, methylation changes usually occur at the regional level: for example, genomic structural variants can affect methylation patterns in regions up to several megabases in length. Existing DMR methods provide lists of Differentially Methylated Regions (DMRs) of up to only few kilobases in length, and cannot check if a target region is differentially methylated. Therefore, these methods are not suitable to evaluate methylation changes in large regions. To address these limitations, we developed a new DMR approach based on redundancy analysis (RDA) that assesses whether a target region is differentially methylated. RESULTS: Using simulated and real datasets, we compared our approach to three common DMR detection methods (Bumphunter, blockFinder, and DMRcate). We found that Bumphunter underestimated methylation changes and blockFinder showed poor performance. DMRcate showed poor power in the simulated datasets and low specificity in the real data analysis. Our method showed very high performance in all simulation settings, even with small sample sizes and subtle methylation changes, while controlling type I error. Other advantages of our method are: 1) it estimates the degree of association between the DMR and the outcome; 2) it can analyze a targeted or region of interest; and 3) it can evaluate the simultaneous effects of different variables. The proposed methodology is implemented in MEAL, a Bioconductor package designed to facilitate the analysis of methylation data. CONCLUSIONS: We propose a multivariate approach to decipher whether an outcome of interest alters the methylation pattern of a region of interest. The method is designed to analyze large target genomic regions and outperforms the three most popular methods for detecting DMRs. Our method can evaluate factors with more than two levels or the simultaneous effect of more than one continuous variable, which is not possible with the state-of-the-art methods.


Assuntos
Metilação de DNA/genética , Genoma/genética , Genômica/métodos , Neoplasias da Mama/genética , Bases de Dados Genéticas , Epigênese Genética , Feminino , Humanos
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