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https://www.readbyqxmd.com/read/29452210/computer-simulations-for-bioequivalence-trials-selection-of-analyte-in-bcs-class-ii-and-iv-drugs-with-first-pass-metabolism-two-metabolic-pathways-and-intestinal-efflux-transporter
#1
V Mangas-Sanjuan, C Navarro-Fontestad, A García-Arieta, I F Trocóniz, M Bermejo
A semi-physiological two compartment pharmacokinetic model with two active metabolites (primary (PM) and secondary metabolites (SM)) with saturable and non-saturable pre-systemic efflux transporter, intestinal and hepatic metabolism has been developed. The aim of this work is to explore in several scenarios which analyte (parent drug or any of the metabolites) is the most sensitive to changes in drug product performance (i.e. differences in in vivo dissolution) and to make recommendations based on the simulations outcome...
February 13, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29452133/some-properties-of-the-conditioned-reconstructed-process-with-bernoulli-sampling
#2
Carsten Wiuf
In many areas of genetics it is of relevance to consider a population of individuals that is founded by a single individual in the past. One model for such a scenario is the conditioned reconstructed process with Bernoulli sampling that describes the evolution of a population of individuals that originates from a single individual. Several aspects of this reconstructed process are studied, in particular the Markov structure of the process. It is shown that at any given time in the past, the conditioned reconstructed process behaves as the original conditioned reconstructed process after a suitable time-dependent change of the sampling probability...
February 13, 2018: Theoretical Population Biology
https://www.readbyqxmd.com/read/29452132/effect-of-the-gstm1-gene-deletion-on-glycemic-variability-sympatho-vagal-balance-and-arterial-stiffness-in-patients-with-metabolic-syndrome-but-without-diabetes
#3
Andrea Iorio, Dorina Ylli, Renato Polimanti, Fabiana Picconi, Paola Maggio, Davide Francomano, Antonio Aversa, Dario Manfellotto, Maria Fuciarelli, Simona Frontoni
AIMS: An increased rate of cerebrovascular complications in patients with metabolic syndrome (MetS) has been reported. Previous studies demonstrated an association between glycemic variability (GV) and cerebrovascular reactivity (CRV) in MetS, thus suggesting a putative role of GV on cerebrovascular events. Although the pathophysiological mechanism linking GV to damage is still to be elucidated, evidence suggests oxidative stress plays a crucial role. Since functional variants in glutathione S-transferases (GST) genes modulate the cellular detoxification processes, the aim of this study was to elucidate the involvement of GSTs in MetS and investigating the correlation with GV, arterial stiffness, and sympatho-vagal (SV) balance...
February 13, 2018: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/29452031/prehospital-cervical-spine-motion-immobilization-versus-spine-motion-restriction
#4
Erik E Swartz, W Steven Tucker, Matthew Nowak, Jason Roberto, Amy Hollingworth, Laura C Decoster, Thomas W Trimarco, Jason P Mihalik
OBJECTIVE: This study aims to evaluate the efficacy of two different spinal immobilization techniques on cervical spine movement in a simulated prehospital ground transport setting. METHODS: A counterbalanced crossover design was used to evaluate two different spinal immobilization techniques in a standardized environment. Twenty healthy male volunteers (age = 20.9 ± 2.2 yr) underwent ambulance transport from a simulated scene to a simulated emergency department setting in two separate conditions: utilizing traditional spinal immobilization (TSI) and spinal motion restriction (SMR)...
February 16, 2018: Prehospital Emergency Care
https://www.readbyqxmd.com/read/29451985/a-comparison-of-barriers-to-accessing-services-for-mental-and-physical-health-conditions-in-a-sample-of-rural-australian-adults
#5
Kate Fennell, Melissa Hull, Martin Jones, James Dollman
INTRODUCTION: The prevalence of chronic disease, mortality and suicide rates is higher in rural Australia than in urban centres. Understanding rural Australians' barriers to accessing health services requires urgent attention. The purpose of this study was to compare barriers to help-seeking for physical and mental health issues among rural South Australian adults. METHODS: A total of 409 people from three rural and remote regions in South Australia completed a computer-assisted telephone interview...
February 2018: Rural and Remote Health
https://www.readbyqxmd.com/read/29451884/a-damped-oscillator-imposes-temporal-order-on-posterior-gap-gene-expression-in-drosophila
#6
Berta Verd, Erik Clark, Karl R Wotton, Hilde Janssens, Eva Jiménez-Guri, Anton Crombach, Johannes Jaeger
Insects determine their body segments in two different ways. Short-germband insects, such as the flour beetle Tribolium castaneum, use a molecular clock to establish segments sequentially. In contrast, long-germband insects, such as the vinegar fly Drosophila melanogaster, determine all segments simultaneously through a hierarchical cascade of gene regulation. Gap genes constitute the first layer of the Drosophila segmentation gene hierarchy, downstream of maternal gradients such as that of Caudal (Cad). We use data-driven mathematical modelling and phase space analysis to show that shifting gap domains in the posterior half of the Drosophila embryo are an emergent property of a robust damped oscillator mechanism, suggesting that the regulatory dynamics underlying long- and short-germband segmentation are much more similar than previously thought...
February 16, 2018: PLoS Biology
https://www.readbyqxmd.com/read/29451667/approach-to-concurrent-coronary-and-carotid-artery-disease-epidemiology-screening-and-treatment
#7
Patrícia Feitosa Frota Dos Reis, Pedro Vieira Linhares, Fábio Grunspun Pitta, Eduardo Gomes Lima
The concomitance between coronary artery disease and carotid artery disease is known and well documented. However, it is a fact that, despite the screening methods for these conditions and the advances in surgical treatment, little has been achieved in terms of reducing the risk of complications in the perioperative period. Publications are scarce, being mostly composed of reports or case series. There is little agreement on the best initial therapeutic approach (myocardial versus carotid revascularization) or the best technique to be used (surgery with or without extracorporeal circulation, hybrid treatments, etc...
November 2017: Revista da Associação Médica Brasileira
https://www.readbyqxmd.com/read/29451586/virtual-reality-exposure-therapy-for-fear-of-driving-analysis-of-clinical-characteristics-physiological-response-and-sense-of-presence
#8
Rafael T da Costa, Marcele R de Carvalho, Pedro Ribeiro, Antonio E Nardi
OBJECTIVE: To investigate the reactions of women with driving phobia to a therapeutic program of scheduled virtual reality exposure treatment (VRET) sessions. METHODS: The study intervention consisted of a computer game with car-driving scenarios that included several traffic situations. We investigated the participants' sense of presence, subjective distress, and physiological responses during eight virtual-reality exposures. We also evaluated clinical characteristics, driving cognitions, and quality of life in the participants...
February 15, 2018: Revista Brasileira de Psiquiatria
https://www.readbyqxmd.com/read/29451518/-access-to-hepatitis-c-treatment-a-lesson-for-the-future
#9
Lucia Craxì
The new generation of direct acting antivirals (DAA) for the treatment of chronic hepatitis C virus infection has revolutionized the previous scenario and has put the institutions under test because of the high cost of therapies. An analysis of what has happened over the last three years, especially in Italy, helps us understand how price negotiation has been managed, and what criteria were chosen at first to allow limited access on the basis of the need of patient care. This allows to focus on some important issues and to identify the challenges ahead in the near future...
January 2018: Recenti Progressi in Medicina
https://www.readbyqxmd.com/read/29451473/uremia-a-historical-reappraisal-of-what-happened
#10
Rajeev Raghavan, Garabed Eknoyan
Urea was identified as a urinary salt in 1662 and was the first organic bodily product to be synthesized in vitro in 1828. This heralded the end of an era that defined disease as an imbalance between vital life forces, and catalyzed the merging of organic chemical sciences into clinical medicine. The term urée (urea) was introduced in 1803, its accumulation in blood was dubbed urémie (uremia) in 1847, and the procedure for its removal from urine across semi-permeable membranes designated dialysis in 1861...
February 16, 2018: Clinical Nephrology
https://www.readbyqxmd.com/read/29451414/comparing-methods-of-misclassification-correction-for-studies-of-adolescent-alcohol-use
#11
Melvin D Livingston, Brad Cannell, Keith Muller, Kelli A Komro
BACKGROUND: Despite concerns over measurement error, self-report continues to be the most common measure of adolescent alcohol use used by researchers. Objective measures of adolescent alcohol use continue to advance; however, they tend to be cost prohibitive for larger studies. By combining appropriate statistical techniques and validation subsamples, the benefits of objective alcohol measures can be made more accessible to a greater number of researchers. OBJECTIVES: To compare three easily implemented methods to correct for measurement error when objective measures of alcohol use are available for a subsample of participants, regression calibration, multiple imputation for measurement error (MIME), and probabilistic sensitivity analysis (PSA), and provide guidance regarding the use of each method in scenarios likely to occur in practice...
2018: American Journal of Drug and Alcohol Abuse
https://www.readbyqxmd.com/read/29451371/young-s-modulus-and-load-complexity-modeling-their-effects-on-proximal-femur-strain
#12
Adam D Sylvester, Patricia A Kramer
Finite element analysis (FEA) is a powerful tool for evaluating questions of functional morphology, but the application of FEA to extant or extinct creatures is a non-trivial task. Three categories of input data are needed to appropriately implement FEA: geometry, material properties, and boundary conditions. Geometric data are relatively easily obtained from imaging techniques, but often material properties and boundary conditions must be estimated. Here we conduct sensitivity analyses of the effect of the choice of Young's Modulus for elements representing trabecular bone and muscle loading complexity on the proximal femur using a finite element mesh of a modern human femur...
February 16, 2018: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
https://www.readbyqxmd.com/read/29451322/intuitive-probabilities-and-the-limitation-of-moral-imagination
#13
Arseny A Ryazanov, Jonathan Knutzen, Samuel C Rickless, Nicholas J S Christenfeld, Dana Kay Nelkin
There is a vast literature that seeks to uncover features underlying moral judgment by eliciting reactions to hypothetical scenarios such as trolley problems. These thought experiments assume that participants accept the outcomes stipulated in the scenarios. Across seven studies (N = 968), we demonstrate that intuition overrides stipulated outcomes even when participants are explicitly told that an action will result in a particular outcome. Participants instead substitute their own estimates of the probability of outcomes for stipulated outcomes, and these probability estimates in turn influence moral judgments...
February 16, 2018: Cognitive Science
https://www.readbyqxmd.com/read/29451293/the-role-of-near-wall-drag-effects-in-the-dynamics-of-tethered-dna-under-shear-flow
#14
Guy Nir, Einat Chetrit, Anat Vivante, Yuval Garini, Ronen Berkovich
We utilized single-molecule tethered particle motion (TPM) tracking, optimized for studying the behavior of short (0.922 μm) dsDNA molecules under shear flow conditions, in the proximity of a wall (surface). These experiments track the individual trajectories through a gold nanobead (40 nm in radius), attached to the loose end of the DNA molecules. Under such circumstances, local interactions with the wall become more pronounced, manifested through hydrodynamic interactions. To elucidate the mechanical mechanism that affects the statistics of the molecular trajectories of the tethered molecules, we estimate the resting diffusion coefficient of our system...
February 16, 2018: Soft Matter
https://www.readbyqxmd.com/read/29451169/patient-perception-and-preference-of-eus-guided-drainage-over-percutaneous-drainage-when-endoscopic-transpapillary-biliary-drainage-fails-an-international-multicenter-survey
#15
Kwangwoo Nam, Dong Uk Kim, Tae Hoon Lee, Takuji Iwashita, Yousuke Nakai, Ahmed Bolkhir, Lara Aguilera Castro, Enrique Vazquez-Sequeiros, Carlos de la Serna, Manuel Perez-Miranda, John G Lee, Sang Soo Lee, Dong-Wan Seo, Sung Koo Lee, Myung-Hwan Kim, Do Hyun Park
Background and Objectives: EUS-guided biliary drainage (EUS-BD) is a feasible procedure when ERCP fails, as is percutaneous transhepatic BD (PTBD). However, little is known about patient perception and preference of EUS-BD and PTBD. Patients and Methods: An international multicenter survey was conducted in seven tertiary referral centers. In total, 327 patients, scheduled to undergo ERCP for suspected malignant biliary obstruction, were enrolled in the study. Patients received decision aids with visual representation regarding the techniques, benefits, and adverse events (AEs) of EUS-BD and PTBD...
January 2018: Endoscopic Ultrasound
https://www.readbyqxmd.com/read/29451093/adjustment-for-time-invariant-and-time-varying-confounders-in-unexplained-residuals-models-for-longitudinal-data-within-a-causal-framework-and-associated-challenges
#16
K F Arnold, Gth Ellison, S C Gadd, J Textor, Pwg Tennant, A Heppenstall, M S Gilthorpe
'Unexplained residuals' models have been used within lifecourse epidemiology to model an exposure measured longitudinally at several time points in relation to a distal outcome. It has been claimed that these models have several advantages, including: the ability to estimate multiple total causal effects in a single model, and additional insight into the effect on the outcome of greater-than-expected increases in the exposure compared to traditional regression methods. We evaluate these properties and prove mathematically how adjustment for confounding variables must be made within this modelling framework...
January 1, 2018: Statistical Methods in Medical Research
https://www.readbyqxmd.com/read/29451021/the-uva-padova-type-1-diabetes-simulator-goes-from-single-meal-to-single-day
#17
Roberto Visentin, Enrique Campos-Náñez, Michele Schiavon, Dayu Lv, Martina Vettoretti, Marc Breton, Boris P Kovatchev, Chiara Dalla Man, Claudio Cobelli
BACKGROUND: A new version of the UVA/Padova Type 1 Diabetes (T1D) Simulator is presented which provides a more realistic testing scenario. The upgrades to the previous simulator, which was accepted by the Food and Drug Administration in 2013, are described. METHOD: Intraday variability of insulin sensitivity (S I ) has been modeled, based on clinical T1D data, accounting for both intra- and intersubject variability of daily S I . Thus, time-varying distributions of both subject's basal insulin infusion and insulin-to-carbohydrate ratio were calculated and made available to the user...
February 1, 2018: Journal of Diabetes Science and Technology
https://www.readbyqxmd.com/read/29451004/simulating-localised-cellular-inflammation-and-substrate-properties-in-a-strain-energy-density-based-bone-remodelling-algorithm-for-use-in-modelling-trauma
#18
Naomi Rosenberg, Anthony M J Bull
Bone responds to mechanical stimulus and a range of pre-existing finite element models have been suggested to reproduce the internal physiological structure of bone. Inflammation effects are not included in these models, yet inflammation is a key component of bone repair in trauma. Therefore, a model is proposed and tested here that extends these methods to include parameters that could be considered to represent the behaviour of bone remodelling when influenced by inflammation. The proposed model regulates remodelling based on findings from recent studies into the nature of heterotopic ossification, the formation of heterotopic bone, which have revealed information about the nature of bone after high levels of trauma...
February 16, 2018: Computer Methods in Biomechanics and Biomedical Engineering
https://www.readbyqxmd.com/read/29450968/knowledge-about-traumatic-dental-injuries-in-the-permanent-dentition-a-survey-of-lithuanian-dentists
#19
Vaida Zaleckienė, Vytautė Pečiulienė, Vilma Brukienė, Audronė Jakaitienė, Jolanta Aleksejūnienė, Linas Zaleckas
BACKGROUND/AIMS: In Lithuania, dental trauma cases are also treated by general dentists but it is unknown whether their age, self-evaluation of trauma knowledge and practice location can predict their actual knowledge and management of trauma cases. The aim of this study was to evaluate whether these factors can be used to predict the actual knowledge and management of trauma cases. METHODS: A two-part questionnaire included 17 multiple-choice questions about practitioners' demographics, their self-evaluated knowledge, and how frequently they treated traumatized permanent teeth as well as 13 clinical scenarios reflecting a variety of clinical trauma cases and their complications...
February 16, 2018: Dental Traumatology: Official Publication of International Association for Dental Traumatology
https://www.readbyqxmd.com/read/29450770/how-can-water-quality-be-improved-when-the-urban-waste-water-directive-has-been-fulfilled-a-case-study-of-the-lot-river-france
#20
Josette Garnier, Antsiva Ramarson, Vincent Thieu, Julien Némery, Sylvain Théry, Gilles Billen, Alexandra Coynel
The Lot river, a major tributary of the downstream Garonne river, the largest river on the Northern side of the Pyrenees Mountains, was intensively studied in the 1970s. A pioneering program called "Lot Rivière Claire" provided a diagnosis of water quality at the scale of the whole watershed and proposed an ambitious program to manage nutrient pollution and eutrophication largely caused by urban wastewater releases. Later on, the implementation of European directives from 1991 to 2000 resulted in the nearly complete treatment of point sources of pollution in spite of a doubling of the basin's population...
February 15, 2018: Environmental Science and Pollution Research International
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