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https://www.readbyqxmd.com/read/28636403/applying-precision-medicine-to-trial-design-using-physiology-extracorporeal-co2-removal-for-ards
#1
Ewan C Goligher, Marcelo B P Amato, Arthur S Slutsky
In clinical trials of therapies for ARDS, the average treatment effect in the study population may be attenuated because individual patient responses vary widely. This inflates sample size requirements and increases the cost and difficulty of conducting successful clinical trials. One solution is to enrich the study population with patients most likely to benefit based on predicted patient response to treatment (predictive enrichment). In this perspective, we apply the precision medicine paradigm to the emerging use of extracorporeal CO2 removal (ECCO2R) for ultra-protective ventilation in ARDS...
June 21, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28633724/change-in-end-expiratory-lung-volume-during-sleep-in-patients-at-risk-for-obstructive-sleep-apnea
#2
Patrick Koo, Eric J Gartman, Jigme M Sethi, Eyad Kawar, F Dennis McCool
STUDY OBJECTIVES: As lung volume decreases radial traction on the upper airway is reduced, making it more collapsible. The purpose of this study was to measure change in end-expiratory lung volume (EELV) following sleep onset and to evaluate the relationship between change in EELV and sleep-disordered breathing. METHODS: Twenty subjects underwent overnight polysomnography, of whom 14 (70%) had obstructive sleep apnea (OSA). Change in EELV was measured throughout the night using magnetometry...
June 16, 2017: Journal of Clinical Sleep Medicine: JCSM: Official Publication of the American Academy of Sleep Medicine
https://www.readbyqxmd.com/read/28617226/contextualization-of-drug-mediator-relations-using-evidence-networks
#3
Hai Joey Tran, Gil Speyer, Jeff Kiefer, Seungchan Kim
BACKGROUND: Genomic analysis of drug response can provide unique insights into therapies that can be used to match the "right drug to the right patient." However, the process of discovering such therapeutic insights using genomic data is not straightforward and represents an area of active investigation. EDDY (Evaluation of Differential DependencY), a statistical test to detect differential statistical dependencies, is one method that leverages genomic data to identify differential genetic dependencies...
May 31, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28605458/prioritizing-tests-of-epistasis-through-hierarchical-representation-of-genomic-redundancies
#4
Tyler Cowman, Mehmet Koyutürk
Epistasis is defined as a statistical interaction between two or more genomic loci in terms of their association with a phenotype of interest. Epistatic loci that are identified using data from Genome-Wide Association Studies (GWAS) provide insights into the interplay among multiple genetic factors, with applications including assessment of susceptibility to complex diseases, decision making in precision medicine, and gaining insights into disease mechanisms. Since the number of genomic loci assayed by GWAS is extremely large (usually in the order of millions), identification of epistatic loci is a statistically difficult and computationally intensive problem...
June 9, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28598966/joint-modeling-of-genetically-correlated-diseases-and-functional-annotations-increases-accuracy-of-polygenic-risk-prediction
#5
Yiming Hu, Qiongshi Lu, Wei Liu, Yuhua Zhang, Mo Li, Hongyu Zhao
Accurate prediction of disease risk based on genetic factors is an important goal in human genetics research and precision medicine. Advanced prediction models will lead to more effective disease prevention and treatment strategies. Despite the identification of thousands of disease-associated genetic variants through genome-wide association studies (GWAS) in the past decade, accuracy of genetic risk prediction remains moderate for most diseases, which is largely due to the challenges in both identifying all the functionally relevant variants and accurately estimating their effect sizes...
June 9, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28596117/disrupted-white-matter-structural-networks-in-healthy-older-adults-apoe-%C3%AE%C2%B54-carriers-an-international-multicenter-dti-study
#6
Enrica Cavedo, Simone Lista, Katrine Rojkova, Patrizia Andrea Chiesa, Marion Houot, Katharina Brueggen, Janusch Blautzik, Arun L W Bokde, Bruno Dubois, Frederik Barkhof, Petra J W Pouwels, Stefan Teipel, Harald Hampel
The ε4 allelic variant of the Apolipoprotein E gene (APOE ε4) is the best-established genetic risk factor for late-onset Alzheimer's disease (AD). White matter (WM) microstructural damages measured with Diffusion Tensor Imaging (DTI) represent an early sign of fiber tract disconnection in AD. We examined the impact of APOEε4 on WM microstructure in elderly individuals from the multicenter European DTI Study on Dementia. Voxelwise statistical analysis of Fractional anisotropy (FA), mean diffusivity, radial and axial diffusivity (MD, radD and axD respectively) was carried out using Tract-Based Spatial Statistics...
June 5, 2017: Neuroscience
https://www.readbyqxmd.com/read/28595259/molecular-profiling-of-signet-ring-cell-colorectal-cancer-provides-a-strong-rationale-for-genomic-targeted-and-immune-checkpoint-inhibitor-therapies
#7
Muhammad A Alvi, Maurice B Loughrey, Philip Dunne, Stephen McQuaid, Richard Turkington, Marc-Aurel Fuchs, Claire McGready, Victoria Bingham, Brendan Pang, Wendy Moore, Perry Maxwell, Mark Lawler, Jacqueline A James, Graeme I Murray, Richard H Wilson, Manuel Salto-Tellez
BACKGROUND: Signet ring cell colorectal cancer (SRCCa) has a bleak prognosis. Employing molecular pathology techniques we investigated the potential of precision medicine in this disease. METHODS: Using test (n=26) and validation (n=18) cohorts, analysis of mutations, DNA methylation and transcriptome was carried out. Microsatellite instability (MSI) status was established and immunohistochemistry (IHC) was used to test for adaptive immunity (CD3) and the immune checkpoint PDL1...
June 8, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28594818/leveraging-functional-annotations-in-genetic-risk-prediction-for-human-complex-diseases
#8
Yiming Hu, Qiongshi Lu, Ryan Powles, Xinwei Yao, Can Yang, Fang Fang, Xinran Xu, Hongyu Zhao
Genetic risk prediction is an important goal in human genetics research and precision medicine. Accurate prediction models will have great impacts on both disease prevention and early treatment strategies. Despite the identification of thousands of disease-associated genetic variants through genome wide association studies (GWAS), genetic risk prediction accuracy remains moderate for most diseases, which is largely due to the challenges in both identifying all the functionally relevant variants and accurately estimating their effect sizes in the presence of linkage disequilibrium...
June 8, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28559747/structure-leveraged-methods-in-breast-cancer-risk-prediction
#9
Jun Fan, Yirong Wu, Ming Yuan, David Page, Jie Liu, Irene M Ong, Peggy Peissig, Elizabeth Burnside
Predicting breast cancer risk has long been a goal of medical research in the pursuit of precision medicine. The goal of this study is to develop novel penalized methods to improve breast cancer risk prediction by leveraging structure information in electronic health records. We conducted a retrospective case-control study, garnering 49 mammography descriptors and 77 high-frequency/low-penetrance single-nucleotide polymorphisms (SNPs) from an existing personalized medicine data repository. Structured mammography reports and breast imaging features have long been part of a standard electronic health record (EHR), and genetic markers likely will be in the near future...
December 2016: Journal of Machine Learning Research: JMLR
https://www.readbyqxmd.com/read/28552011/testing-for-differentially-expressed-genetic-pathways-with-single-subject-n-of-1-data-in-the-presence-of-inter-gene-correlation
#10
A Grant Schissler, Walter W Piegorsch, Yves A Lussier
Modern precision medicine increasingly relies on molecular data analytics, wherein development of interpretable single-subject ("N-of-1") signals is a challenging goal. A previously developed global framework, N-of-1- pathways, employs single-subject gene expression data to identify differentially expressed gene set pathways in an individual patient. Unfortunately, the limited amount of data within the single-subject, N-of-1 setting makes construction of suitable statistical inferences for identifying differentially expressed gene set pathways difficult, especially when non-trivial inter-gene correlation is present...
January 1, 2017: Statistical Methods in Medical Research
https://www.readbyqxmd.com/read/28546520/-omic-approach-in-non-smoker-female-with-lung-squamous-cell-carcinoma-pinpoints-to-germline-susceptibility-and-personalized-medicine
#11
Margherita Baldassarri, Chiara Fallerini, Francesco Cetta, Marco Ghisalberti, Cristiana Bellan, Simone Furini, Ottavia Spiga, Sergio Crispino, Giuseppe Gotti, Francesca Ariani, Piero Paladini, Alessandra Renieri, Elisa Frullanti
Purpose: Lung cancer is strongly associated to tobacco smoking. However, global statistics estimate that in females the proportion of lung cancer cases that is unrelated to tobacco smoking reaches fifty percent, making questionable the etiology of the disease. Materials and Methods: A never-smoker female with primary EGFR/KRAS/ALK-negative squamous cell carcinoma of the lung and their normal sibs were subjected to a novel integrative "omic" approach using a pedigree-based model for discovering genetic factors leading to cancer in the absence of well-known environmental trigger...
May 26, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28545640/artificial-intelligence-in-precision%C3%A2-cardiovascular-medicine
#12
REVIEW
Chayakrit Krittanawong, HongJu Zhang, Zhen Wang, Mehmet Aydar, Takeshi Kitai
Artificial intelligence (AI) is a field of computer science that aims to mimic human thought processes, learning capacity, and knowledge storage. AI techniques have been applied in cardiovascular medicine to explore novel genotypes and phenotypes in existing diseases, improve the quality of patient care, enable cost-effectiveness, and reduce readmission and mortality rates. Over the past decade, several machine-learning techniques have been used for cardiovascular disease diagnosis and prediction. Each problem requires some degree of understanding of the problem, in terms of cardiovascular medicine and statistics, to apply the optimal machine-learning algorithm...
May 30, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28541380/a-fully-bayesian-latent-variable-model-for-integrative-clustering-analysis-of-multi-type-omics-data
#13
Qianxing Mo, Ronglai Shen, Cui Guo, Marina Vannucci, Keith S Chan, Susan G Hilsenbeck
Identification of clinically relevant tumor subtypes and omics signatures is an important task in cancer translational research for precision medicine. Large-scale genomic profiling studies such as The Cancer Genome Atlas (TCGA) Research Network have generated vast amounts of genomic, transcriptomic, epigenomic, and proteomic data. While these studies have provided great resources for researchers to discover clinically relevant tumor subtypes and driver molecular alterations, there are few computationally efficient methods and tools for integrative clustering analysis of these multi-type omics data...
May 24, 2017: Biostatistics
https://www.readbyqxmd.com/read/28533813/rapid-identification-of-growth-years-and-profiling-of-bioactive-ingredients-in-astragalus-membranaceus-var-mongholicus-huangqi-roots-from-hunyuan-shanxi
#14
Hua-Sheng Peng, Jun Wang, He-Ting Zhang, Hai-Yan Duan, Xiao-Mei Xie, Ling Zhang, Ming-En Cheng, Dai-Yin Peng
BACKGROUND: The content of medicinal bioactive constituents in huangqi is affected by plant age. In this study, we devised a quick and convenient method for determining the age of huangqi, which was cultivated in Hunyuan County (Shanxi Province). METHODS: 1, 2, 3, 4, 5, 8, 10 growth years huangqi had 38 samples, all samples were collected separately. The growth rings in these samples were observed after making paraffin section and freehand-section. The relationship between growth rings and its growth years was analyzed by SPSS 19...
2017: Chinese Medicine
https://www.readbyqxmd.com/read/28503676/learning-optimal-individualized-treatment-rules-from-electronic-health-record-data
#15
Yuanjia Wang, Peng Wu, Ying Liu, Chunhua Weng, Donglin Zeng
Medical research is experiencing a paradigm shift from "one-size-fits-all" strategy to a precision medicine approach where the right therapy, for the right patient, and at the right time, will be prescribed. We propose a statistical method to estimate the optimal individualized treatment rules (ITRs) that are tailored according to subject-specific features using electronic health records (EHR) data. Our approach merges statistical modeling and medical domain knowledge with machine learning algorithms to assist personalized medical decision making using EHR...
October 2016: IEEE International Conference on Healthcare Informatics IEEE International Conference on Healthcare Informatics
https://www.readbyqxmd.com/read/28488287/design-for-the-transfer-of-a-validated-liquid-chromatography-tandem-mass-spectrometry-analytical-method-for-the-determination-of-antimicrobial-residues-in-honey-from-low-resolution-to-high-resolution-mass-spectrometry
#16
Khaled El Hawari, Mohamad Al Iskandarani, Sophie Mompelat, Dominique Hurtaud-Pessel, Eric Verdon
RATIONALE: This paper investigates the validity of the transfer of a liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for the determination of veterinary medicinal products in honey and compares it with an LC/linear ion trap/Orbitrap mass spectrometry method. A descriptive statistical approach was used in order to assess whether such a transfer would succeed or fail. This approach is based on the simultaneous evaluation of the trueness and of the intermediate precision for each compound at a 95% interval of confidence of both analytical techniques...
July 15, 2017: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/28458147/analysis-of-gait-symmetry-during-over-ground-walking-in-children-with-autism-spectrum-disorder
#17
Jeffrey D Eggleston, John R Harry, Robbin A Hickman, Janet S Dufek
Gait symmetry is utilized as an indicator of neurologic function. Healthy gait often exhibits minimal asymmetries, while pathological gait exhibits exaggerated asymmetries. The purpose of this study was to examine symmetry of mechanical gait parameters during over-ground walking in children with Autism Spectrum Disorder (ASD). Kinematic and kinetic data were obtained from 10 children (aged 5-12 years) with ASD. The Model Statistic procedure (α=0.05) was used to compare gait related parameters between limbs...
April 21, 2017: Gait & Posture
https://www.readbyqxmd.com/read/28456503/novel-oxytocin-receptor-variants-in-laboring-women-requiring-high-doses-of-oxytocin
#18
Erin L Reinl, Zane A Goodwin, Nandini Raghuraman, Grace Y Lee, Erin Y Jo, Beakal M Gezahegn, Meghan K Pillai, Alison G Cahill, Cristina De Guzman Strong, Sarah K England
BACKGROUND: Although oxytocin commonly is used to augment or induce labor, it is difficult to predict its effectiveness because oxytocin dose requirements vary significantly among women. One possibility is that women requiring high or low doses of oxytocin have variations in the oxytocin receptor gene. OBJECTIVES: To identify oxytocin receptor gene variants in laboring women with low and high oxytocin dosage requirements. STUDY DESIGN: Term, nulliparous women requiring oxytocin doses of ≤4 mU/min (low-dose requiring, n = 83) or ≥20 mU/min (high-dose requiring, n = 104) for labor augmentation or induction provided consent to a postpartum blood draw as a source of genomic DNA...
April 26, 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28430854/dynamic-modeling-and-network-approaches-for-omics-time-course-data-overview-of-computational-approaches-and-applications
#19
Yulan Liang, Arpad Kelemen
Inferring networks and dynamics of genes, proteins, cells and other biological entities from high-throughput biological omics data is a central and challenging issue in computational and systems biology. This is essential for understanding the complexity of human health, disease susceptibility and pathogenesis for Predictive, Preventive, Personalized and Participatory (P4) system and precision medicine. The delineation of the possible interactions of all genes/proteins in a genome/proteome is a task for which conventional experimental techniques are ill suited...
April 18, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/28430547/enhancing-insights-into-pulmonary-vascular-disease-through-a-precision-medicine-approach-a-joint-nhlbi-cardiovascular-medical-research-and-education-fund-workshop-report
#20
John H Newman, Stuart Rich, Steven H Abman, John H Alexander, John Barnard, Gerald J Beck, Raymond L Benza, Todd M Bull, Stephen Y Chan, Hyung J Chun, Declan Doogan, Jocelyn Dupuis, Serpil C Erzurum, Robert P Frantz, Mark Geraci, Hunter Gillies, Mark Gladwin, Michael P Gray, Anna R Hemnes, Roy S Herbst, Adrian F Hernandez, Nicholas S Hill, Evelyn M Horn, Kendall Hunter, Zhi-Cheng Jing, Roger Johns, Sanjay Kaul, Steven M Kawut, Tim Lahm, Jane A Leopold, Greg D Lewis, Stephen C Mathai, Vallerie V McLaughlin, Evangelos D Michelakis, Steven D Nathan, William Nichols, Grier Page, Marlene Rabinovitch, Jonathan Rich, Franz Rischard, Sharon Rounds, Sanjiv J Shah, Victor F Tapson, Naomi Lowy, Norman Stockbridge, Gail Weinmann, Lei Xiao
The Division of Lung Diseases of the NHLBI and the Cardiovascular Medical Education and Research Fund held a workshop to discuss how to leverage the anticipated scientific output from the recently launched "Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics" (PVDOMICS) program to develop newer approaches to pulmonary vascular disease. PVDOMICS is a collaborative, protocol-driven network to analyze all patient populations with pulmonary hypertension to define novel pulmonary vascular disease (PVD) phenotypes...
June 15, 2017: American Journal of Respiratory and Critical Care Medicine
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