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https://www.readbyqxmd.com/read/28088842/unbiased-split-variable-selection-for-random-survival-forests-using-maximally-selected-rank-statistics
#1
Marvin N Wright, Theresa Dankowski, Andreas Ziegler
The most popular approach for analyzing survival data is the Cox regression model. The Cox model may, however, be misspecified, and its proportionality assumption may not always be fulfilled. An alternative approach for survival prediction is random forests for survival outcomes. The standard split criterion for random survival forests is the log-rank test statistic, which favors splitting variables with many possible split points. Conditional inference forests avoid this split variable selection bias. However, linear rank statistics are utilized by default in conditional inference forests to select the optimal splitting variable, which cannot detect non-linear effects in the independent variables...
January 15, 2017: Statistics in Medicine
https://www.readbyqxmd.com/read/28088839/pharmacokinetic-pharmacodynamic-modeling-of-the-pde4-inhibitor-tak-648-in-type-2-diabetes-early-translational-approaches-for-human-dose-prediction
#2
N Plock, S Vollert, M Mayer, G Hanauer, G Lahu
TAK-648 is a PDE4 inhibitor with demonstrated preclinical antidiabetic properties. Our objective was to develop a translational pharmacokinetic/pharmacodynamic (PK/PD) model for human type 2 diabetes (T2D) dose prediction using HbA1c results from a db/db mouse study. Estimated parameters in combination with tPDE4i values calculated for the clinical roflumilast dose of 500 μg were used to translate preclinical effects of TAK-648 to required exposure in humans. A first-in-human study with single TAK-648 doses of 0...
January 15, 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/28088837/disease-severity-classification-using-quantitative-magnetic-resonance-imaging-data-of-cartilage-in-femoroacetabular-impingement
#3
Lisa L Henn, John Hughes, Eleena Iisakka, Jutta Ellermann, Shabnam Mortazavi, Connor Ziegler, Mikko J Nissi, Patrick Morgan
Femoroacetabular impingement (FAI) is a condition in which subtle deformities of the femoral head and acetabulum (hip socket) result in pathological abutment during hip motion. FAI is a common cause of hip pain and can lead to acetabular cartilage damage and osteoarthritis. For some patients with FAI, surgical intervention is indicated, and it can improve quality of life and potentially delay the onset of osteoarthritis. For other patients, however, surgery is contraindicated because significant cartilage damage has already occurred...
January 15, 2017: Statistics in Medicine
https://www.readbyqxmd.com/read/28088759/how-accurate-are-accurate-force-fields-for-b-dna
#4
Pablo D Dans, Ivan Ivani, Adam Hospital, Guillem Portella, Carlos González, Modesto Orozco
Last generation of force-fields are raising expectations on the quality of molecular dynamics (MD) simulations of DNA, as well as to the belief that theoretical models can substitute experimental ones in several cases. However these claims are based on limited benchmarks, where MD simulations have shown the ability to reproduce already existing 'experimental models', which in turn, have an unclear accuracy to represent DNA conformation in solution. In this work we explore the ability of different force-fields to predict the structure of two new B-DNA dodecamers, determined herein by means of (1)H nuclear magnetic resonance (NMR)...
January 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28088694/metabolic-network-modeling-with-model-organisms
#5
REVIEW
L Safak Yilmaz, Albertha Jm Walhout
Flux balance analysis (FBA) with genome-scale metabolic network models (GSMNM) allows systems level predictions of metabolism in a variety of organisms. Different types of predictions with different accuracy levels can be made depending on the applied experimental constraints ranging from measurement of exchange fluxes to the integration of gene expression data. Metabolic network modeling with model organisms has pioneered method development in this field. In addition, model organism GSMNMs are useful for basic understanding of metabolism, and in the case of animal models, for the study of metabolic human diseases...
January 12, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28088645/towards-solving-the-hard-problem-of-consciousness-the-varieties-of-brain-resonances-and-the-conscious-experiences-that-they-support
#6
Stephen Grossberg
The hard problem of consciousness is the problem of explaining how we experience qualia or phenomenal experiences, such as seeing, hearing, and feeling, and knowing what they are. To solve this problem, a theory of consciousness needs to link brain to mind by modeling how emergent properties of several brain mechanisms interacting together embody detailed properties of individual conscious psychological experiences. This article summarizes evidence that Adaptive Resonance Theory, or ART, accomplishes this goal...
December 6, 2016: Neural Networks: the Official Journal of the International Neural Network Society
https://www.readbyqxmd.com/read/28088633/quantitative-analysis-of-lab-to-lab-variability-in-caco-2-permeability-assays
#7
Jong Bong Lee, Atheer Zgair, Dhiaa A Taha, Xiaowei Zang, Leonid Kagan, Tae Hwan Kim, Min Gi Kim, Hwi-Yeol Yun, Peter M Fischer, Pavel Gershkovich
In this study, Caco-2 permeability results from different laboratories were compared. Six different sets of apparent permeability coefficient (Papp) values reported in the literature were compared to experimental Papp obtained in our laboratory. The differences were assessed by determining the root mean square error (RMSE) values between the datasets, which reached levels as high as 0.581 for the training set compounds, i.e. ten compounds with known effective human permeability (Peff). The consequences of these differences in Papp for prediction of oral drug absorption were demonstrated by introducing the Papp into the absorption and pharmacokinetics simulation software application GastroPlus(TM) for prediction of the fraction absorbed (Fa) in humans using calibrated "user-defined permeability models"...
January 11, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28088600/development-and-validation-of-a-methodology-to-reduce-mortality-using-the-veterans-administration-surgical-quality-improvement-program-risk-calculator
#8
Deborah S Keller, Donald Kroll, Harry T Papaconstantinou, C Neal Ellis
BACKGROUND: To identify patients with a high risk of 30 day mortality after elective surgery that may benefit from referral for tertiary care, an institution-specific process using the Veterans Administration Surgical Quality Improvement Program (VASQIP) Risk Calculator was developed. The goal was to develop and validate the methodology. Our hypothesis was the process could optimize referrals and reduce mortality. STUDY DESIGN: A VASQIP risk score was calculated for all patients undergoing elective non-cardiac surgery at a single Veteran's Administration (VA) facility...
January 11, 2017: Journal of the American College of Surgeons
https://www.readbyqxmd.com/read/28088582/ripk1-protects-hepatocytes-from-kupffer-cells-mediated-tnf-induced-apoptosis-in-mouse-models-of-pamp-induced-hepatitis
#9
Aveline Filliol, Claire Piquet-Pellorce, Céline Raguénès-Nicol, Sarah Dion, Muhammad Farooq, Catherine Lucas-Clerc, Peter Vandenabeele, Mathieu J M Bertrand, Jacques Le Seyec, Michel Samson
BACKGROUND & AIMS: The severity of liver diseases is exacerbated by the death of hepatocytes, which can be induced by the sensing of Pathogen Associated Molecular Patterns (PAMPs) derived from the gut microbiota. The molecular mechanisms regulating these cell death pathways are poorly documented. In this study, we investigated the role of the Receptor Interacting Protein Kinase 1 (RIPK1), a protein known to regulate cell fate decisions, in the death of hepatocytes using two in vivo models of PAMP-induced hepatitis...
January 11, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28088534/the-social-transmission-of-metacontrol-policies-mechanisms-underlying-the-interpersonal-transfer-of-persistence-and-flexibility
#10
REVIEW
Bernhard Hommel, Lorenza S Colzato
Humans often face binary cognitive-control dilemmas, with the choice between persistence and flexibility being a crucial one. Tackling these dilemmas requires metacontrol, i.e., the control of the current cognitive-control policy. As predicted from functional, psychometric, neuroscientific, and modeling approaches, interindividual variability in metacontrol biases towards persistence or flexibility could be demonstrated in metacontrol-sensitive tasks. These biases covary systematically with genetic predispositions regarding mesofrontal and nigrostriatal dopaminergic functioning and the individualistic or collectivistic nature of the cultural background...
January 11, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28088499/initial-uncertainty-impacts-statistical-learning-in-sound-sequence-processing
#11
Juanita Todd, Alexander Provost, Lisa Whitson, Daniel Mullens
This paper features two studies confirming a lasting impact of first learning on how subsequent experience is weighted in early relevance-filtering processes. In both studies participants were exposed to sequences of sound that contained a regular pattern on two different timescales. Regular patterning in sound is readily detected by the auditory system and used to form "prediction models" that define the most likely properties of sound to be encountered in a given context. The presence and strength of these prediction models is inferred from changes in automatically elicited components of auditory evoked potentials...
January 11, 2017: Journal of Physiology, Paris
https://www.readbyqxmd.com/read/28088456/development-of-a-predictive-model-for-the-long-term-stability-assessment-of-drug-in-adhesive-transdermal-films-using-polar-pressure-sensitive-adhesives-as-carrier-matrix
#12
Clémence Chenevas-Paule, Hans-Michael Wolff, Mark Ashton, Martin Schubert, Kalliopi Dodou
Drug crystallization in transdermal drug delivery systems (TDDS) is a critical quality defect. The impact of drug load and hydration on the physical stability of polar (acrylic) drug-in-adhesive (DIA) films was investigated with the objective to identify predictive formulation parameters with respect to drug solubility and long-term stability. Medicated acrylic films were prepared over a range of drug concentrations below and above saturation solubility; and were characterized by FTIR, differential scanning calorimetry (DSC), polarized microscopy and Dynamic Vapor Sorption (DVS) analysis...
January 11, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28088444/feeding-recombinant-e-coli-with-gst-mbmktx-fusion-protein-increases-the-fecundity-and-lifespan-of-caenorhabditis-elegans
#13
Jie Xu, Yajie Jiang, Lu Wan, Qi Wang, Zebo Huang, Yongmei Liu, Yingliang Wu, Zongyun Chen, Xin Liu
Scorpion venom could be a useful treatment for a variety of diseases, such as cancer, epilepsy and analgesia. BmKTX is a polypeptide extracts from scorpion venom (PESV), which have attracted much attention from researchers in recent years. mBmKTX is a mutant polypeptide according to the amino acid sequence of BmKTX. We expressed it with the vector pGEX-4T-1 in Escherichia coli, and Caenorhabditis elegans were used as the animal model and fed with the strains. In this study, the expression of pGEX-mBmKTX was analyzed by SDS-PAGE, and GST-mBmKTX purified from pGEX-mBmKTX as a glutathione S-transferase (GST)-tagged fusion protein is approximately 30kDa...
January 11, 2017: Peptides
https://www.readbyqxmd.com/read/28088412/short-communication-urea-hydrolysis-in-dairy-cattle-manure-under-different-temperature-urea-and-ph-conditions
#14
L E Moraes, S A Burgos, E J DePeters, R Zhang, J G Fadel
The objective of the study was to quantify the rate of urea hydrolysis in dairy cattle manure under different initial urea concentration, temperature, and pH conditions. In particular, by varying all 3 factors simultaneously, the interactions between them could also be determined. Fresh feces and artificial urine solutions were combined into a slurry to characterize the rate of urea hydrolysis under 2 temperatures (15°C and 35°C), 3 urea concentrations in urine solutions (500, 1,000, and 1,500 mg of urea-N/dL), and 3 pH levels (6, 7, and 8)...
January 11, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28088411/standardization-of-milk-infrared-spectra-for-the-retroactive-application-of-calibration-models
#15
V Bonfatti, A Fleming, A Koeck, F Miglior
The objective of this study was to standardize the infrared spectra obtained over time and across 2 milk laboratories of Canada to create a uniform historical database and allow (1) the retroactive application of calibration models for prediction of fine milk composition; and (2) the direct use of spectral information for the development of indicators of animal health and efficiency. Spectral variation across laboratories and over time was inspected by principal components analysis (PCA). Shifts in the PCA scores were detected over time, leading to the definition of different subsets of spectra having homogeneous infrared signal...
January 11, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28088404/variation-in-fat-globule-size-in-bovine-milk-and-its-prediction-using-mid-infrared-spectroscopy
#16
A Fleming, F S Schenkel, J Chen, F Malchiodi, R A Ali, B Mallard, M Sargolzaei, M Corredig, F Miglior
The objectives of this study were to investigate the sources of variation in milk fat globule (MFG) size in bovine milk and its prediction using mid-infrared (MIR) spectroscopy. Mean MFG size was measured in 2,076 milk samples from 399 Ayrshire, Brown Swiss, Holstein, and Jersey cows, and expressed as volume moment mean (D[4,3]) and surface moment mean (D[3,2]). The mid-infrared spectra of the samples and milk performance data were also recorded during routine milk recording and testing. The effects of breed, herd nested within breed, days in milk, season, milking period, age at calving, parity, and individual animal on the variation observed in MFG size were investigated...
January 11, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28088357/joint-genome-wide-prediction-in-several-populations-accounting-for-randomness-of-genotypes-a-hierarchical-bayes-approach-ii-multivariate-spike-and-slab-priors-for-marker-effects-and-derivation-of-approximate-bayes-and-fractional-bayes-factors-for-the-complete
#17
Carlos Alberto Martínez, Kshitij Khare, Arunava Banerjee, Mauricio A Elzo
This study corresponds to the second part of a companion paper devoted to the development of Bayesian multiple regression models accounting for randomness of genotypes in across population genome-wide prediction. This family of models considers heterogeneous and correlated marker effects and allelic frequencies across populations, and has the ability of considering records from non-genotyped individuals and individuals with missing genotypes in any subset of loci without the need for previous imputation, taking into account uncertainty about imputed genotypes...
January 11, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28088356/advancing-the-prediction-accuracy-of-protein-protein-interactions-by-utilizing-evolutionary-information-from-position-specific-scoring-matrix-and-ensemble-classifier
#18
Lei Wang, Zhu-Hong You, Shi-Xiong Xia, Feng Liu, Xing Chen, Xin Yan, Yong Zhou
Protein-Protein Interactions (PPIs) are essential to most biological processes and play a critical role in most cellular functions. With the development of high-throughput biological techniques and in silico methods, a large number of PPI data have been generated for various organisms, but many problems remain unsolved. These factors promoted the development of the in silico methods based on machine learning to predict PPIs. In this study, we propose a novel method by combining ensemble Rotation Forest (RF) classifier and Discrete Cosine Transform (DCT) algorithm to predict the interactions among proteins...
January 11, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28088338/relation-between-resting-amygdalar-activity-and-cardiovascular-events-a-longitudinal-and-cohort-study
#19
Ahmed Tawakol, Amorina Ishai, Richard Ap Takx, Amparo L Figueroa, Abdelrahman Ali, Yannick Kaiser, Quynh A Truong, Chloe Je Solomon, Claudia Calcagno, Venkatesh Mani, Cheuk Y Tang, Willem Jm Mulder, James W Murrough, Udo Hoffmann, Matthias Nahrendorf, Lisa M Shin, Zahi A Fayad, Roger K Pitman
BACKGROUND: Emotional stress is associated with increased risk of cardiovascular disease. We imaged the amygdala, a brain region involved in stress, to determine whether its resting metabolic activity predicts risk of subsequent cardiovascular events. METHODS: Individuals aged 30 years or older without known cardiovascular disease or active cancer disorders, who underwent (18)F-fluorodexoyglucose PET/CT at Massachusetts General Hospital (Boston, MA, USA) between Jan 1, 2005, and Dec 31, 2008, were studied longitudinally...
January 12, 2017: Lancet
https://www.readbyqxmd.com/read/28088305/inertial-particle-dynamics-in-large-artery-flows-implications-for-modeling-arterial-embolisms
#20
Debanjan Mukherjee, Shawn C Shadden
The complexity of inertial particle dynamics through swirling chaotic flow structures characteristic of pulsatile large-artery hemodynamics renders significant challenges in predictive understanding of transport of such particles. This is specifically crucial for arterial embolisms, where knowledge of embolus transport to major vascular beds helps in disease diagnosis and surgical planning. Using a computational framework built upon image-based CFD and discrete particle dynamics modeling, a multi-parameter sampling-based study was conducted on embolic particle dynamics and transport...
December 29, 2016: Journal of Biomechanics
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