keyword
MENU ▼
Read by QxMD icon Read
search

clarks rule

keyword
https://www.readbyqxmd.com/read/29337578/physiologically-based-pharmacokinetic-modeling-in-lead-optimization-i-evaluation-and-adaptation-of-gastroplus-to-predict-bioavailability-of-medchem-series
#1
Pankaj R Daga, Michael B Bolger, Ian S Haworth, Robert Daniel Clark, Eric J Martin
When medicinal chemists need to improve bioavailability (%F) within a chemical series during lead optimization, they synthesize new series members with systematically modified properties mainly by following experience and general rules of thumb. More quantitative models that predict %F of proposed compounds from chemical structure alone have proven elusive. Global empirical %F quantitative structure-property (QSPR) models perform poorly and projects have too little data to train local %F QSPR models. Mechanistic oral absorption and physiologically-based pharmacokinetic (PBPK) models simulate the dissolution, absorption, systemic distribution, and clearance of a drug in preclinical species and humans...
January 16, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29337562/physiologically-based-pharmacokinetic-modeling-in-lead-optimization-ii-rational-bioavailability-design-by-global-sensitivity-analysis-to-identify-properties-affecting-bioavailability
#2
Pankaj R Daga, Michael B Bolger, Ian Haworth, Robert Daniel Clark, Eric J Martin
When medicinal chemists need to improve oral bioavailability (%F) during lead optimization, they systematically modify compound properties mainly based on their own experience and general rules of thumb. However, at least a dozen properties can influence %F, and the difficulty of multi-parameter optimization for such complex non-linear processes grows combinatorially with the number of variables. Furthermore, strategies can be in conflict. For example, adding a polar or charged group will generally increase solubility but decrease permeability...
January 16, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29273092/nitrated-nucleosome-levels-and-neuropsychiatric-events-in-systemic-lupus-erythematosus-a-multi-center-retrospective-case-control-study
#3
Isabel Ferreira, Sara Croca, Maria Gabriella Raimondo, Manjit Matharu, Sarah Miller, Ian Giles, David Isenberg, Yiannis Ioannou, John G Hanly, Murray B Urowitz, Nicole Anderson, Cynthia Aranow, Anca Askanase, Sang-Cheol Bae, Sasha Bernatsky, Ian N Bruce, Jill Buyon, Ann E Clarke, Mary Anne Dooley, Paul Fortin, Ellen Ginzler, Dafna Gladman, Caroline Gordon, Murat Inanc, Søren Jacobsen, Kenneth Kalunian, Diane Kamen, Munther Khamashta, Sam Lim, Susan Manzi, Joan Merrill, Ola Nived, Christine Peschken, Michelle Petri, Rosalind Ramsey-Goldman, Guillermo Ruiz-Irastorza, Jorge Sanchez-Guerrero, Kristjan Steinson, Gunnar K Sturfelt, Ronald van Vollenhoven, Daniel J Wallace, Asad Zoma, Anisur Rahman
BACKGROUND: In patients with systemic lupus erythematosus (SLE) there is no serological test that will reliably distinguish neuropsychiatric (NP) events due to active SLE from those due to other causes. Previously we showed that serum levels of nitrated nucleosomes (NN) were elevated in a small number of patients with NPSLE. Here we measured serum NN in samples from a larger population of patients with SLE and NP events to see whether elevated serum NN could be a marker for NPSLE. METHODS: We obtained serum samples from patients in the Systemic Lupus International Collaborative Clinics (SLICC) inception cohort...
December 22, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29186630/music-models-aberrant-rule-decoding-and-reward-valuation-in-dementia
#4
Camilla N Clark, Hannah L Golden, Oliver McCallion, Jennifer M Nicholas, Miriam H Cohen, Catherine F Slattery, Ross W Paterson, Phillip D Fletcher, Catherine J Mummery, Jonathan D Rohrer, Sebastian J Crutch, Jason D Warren
Aberrant rule- and reward-based processes underpin abnormalities of socio-emotional behaviour in major dementias. However, these processes remain poorly characterised. Here we used music to probe rule decoding and reward valuation in patients with frontotemporal dementia syndromes and Alzheimer's disease relative to healthy age-matched individuals. We created short melodies that were either harmonically resolved ('finished') or unresolved ('unfinished'); the task was to classify each melody as finished or unfinished (rule processing) and rate its subjective pleasantness (reward valuation)...
November 24, 2017: Social Cognitive and Affective Neuroscience
https://www.readbyqxmd.com/read/29161113/disseminability-of-computerized-cognitive-training-performance-across-coaches
#5
Ashley S Fournier-Goodnight, Jason M Ashford, Kellie N Clark, Karen Martin-Elbahesh, Kristina K Hardy, Thomas E Merchant, Sima Jeha, Robert J Ogg, Hui Zhang, Lei Wang, Heather M Conklin
Cogmed is a computerized cognitive intervention utilizing coaches who receive standardized instruction in analyzing training indices and tailoring feedback to remotely monitor participant's performance. The goal of this study was to examine adherence, satisfaction, and efficacy of Cogmed across coaches. Survivors of pediatric brain tumors and acute lymphoblastic leukemia (N = 68) were randomized to intervention (Cogmed) or waitlist control. The intervention group was matched with one of two coaches. Cognitive assessments were completed before and after intervention, and participants and caregivers in the intervention group completed satisfaction surveys...
November 21, 2017: Applied Neuropsychology. Child
https://www.readbyqxmd.com/read/29056378/use-of-multi-criteria-decision-analysis-to-identify-potentially-dangerous-glacial-lakes
#6
Ioannis Kougkoulos, Simon J Cook, Vincent Jomelli, Leon Clarke, Elias Symeonakis, Jason M Dortch, Laura A Edwards, Myriam Merad
Glacial Lake Outburst Floods (GLOFs) represent a significant threat in deglaciating environments, necessitating the development of GLOF hazard and risk assessment procedures. Here, we outline a Multi-Criteria Decision Analysis (MCDA) approach that can be used to rapidly identify potentially dangerous lakes in regions without existing tailored GLOF risk assessments, where a range of glacial lake types exist, and where field data are sparse or non-existent. Our MCDA model (1) is desk-based and uses freely and widely available data inputs and software, and (2) allows the relative risk posed by a range of glacial lake types to be assessed simultaneously within any region...
October 19, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/29042060/australian-general-practitioners-initiate-statin-therapy-primarily-on-the-basis-of-lipid-levels-new-zealand-general-practitioners-use-absolute-risk
#7
REVIEW
Chris Schilling, Josh Knight, Duncan Mortimer, Dennis Petrie, Philip Clarke, John Chalmers, Andrew Kerr, Rod Jackson
OBJECTIVES: To compare the determinants of initial statin prescribing between New Zealand and Australia. New Zealand has a system-wide absolute risk-based approach to primary care cardiovascular disease (CVD) management, while Australia has multiple guidelines. METHOD: Classification and Regression Tree (CART) analysis of two observational studies of primary care CVD management from New Zealand (PREDICT-CVD) and Australia (AusHeart). Over 80% of eligible New Zealanders have been screened for CVD risk...
October 10, 2017: Health Policy
https://www.readbyqxmd.com/read/29035718/assessment-of-the-coding-accuracy-of-warfarin-related-bleeding-events
#8
Thomas Delate, Aubrey E Jones, Nathan P Clark, Daniel M Witt
INTRODUCTION: Using International Classification of Diseases, 9th edition (ICD-9) diagnosis codes to identify potential warfarin-related bleeding events from administrative datasets is highly efficient but may be prone to identifying non-events. The objective of this study was to evaluate the ability of bleeding-related ICD-9 codes to identify true bleeding events in patients who were receiving warfarin therapy at the time of hospitalization. METHODS: This was a cross-sectional study conducted in an integrated healthcare delivery system...
October 12, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28990861/qualitative-vs-quantitative-conceptions-of-homogeneity-in-nineteenth-century-dimensional-analysis
#9
Sybil Gertrude De Clark
The emergence of dimensional analysis in the early nineteenth century involved a redefinition of the pre-existing concepts of homogeneity and dimensions, which entailed a shift from a qualitative to a quantitative conception of these notions. Prior to the nineteenth century, these concepts had been used as criteria to assess the soundness of operations and relations between geometrical quantities. Notably, the terms in such relations were required to be homogeneous, which meant that they needed to have the same geometrical dimensions...
October 9, 2017: Annals of Science
https://www.readbyqxmd.com/read/28953896/dynamic-patterning-by-the-drosophila-pair-rule-network-reconciles-long-germ-and-short-germ-segmentation
#10
Erik Clark
Drosophila segmentation is a well-established paradigm for developmental pattern formation. However, the later stages of segment patterning, regulated by the "pair-rule" genes, are still not well understood at the system level. Building on established genetic interactions, I construct a logical model of the Drosophila pair-rule system that takes into account the demonstrated stage-specific architecture of the pair-rule gene network. Simulation of this model can accurately recapitulate the observed spatiotemporal expression of the pair-rule genes, but only when the system is provided with dynamic "gap" inputs...
September 2017: PLoS Biology
https://www.readbyqxmd.com/read/28823079/mechanobiological-model-of-arterial-growth-and-remodeling
#11
Maziyar Keshavarzian, Clark A Meyer, Heather N Hayenga
A coupled agent-based model (ABM) and finite element analysis (FEA) computational framework is developed to study the interplay of bio-chemo-mechanical factors in blood vessels and their role in maintaining homeostasis. The agent-based model implements the power of REPAST Simphony libraries and adapts its environment for biological simulations. Coupling a continuum-level model (FEA) to a cellular-level model (ABM) has enabled this computational framework to capture the response of blood vessels to increased or decreased levels of growth factors, proteases and other signaling molecules (on the micro scale) as well as altered blood pressure...
August 19, 2017: Biomechanics and Modeling in Mechanobiology
https://www.readbyqxmd.com/read/28817775/electronic-structure-and-properties-of-berkelium-iodates
#12
Mark A Silver, Samantha K Cary, Alejandro J Garza, Ryan E Baumbach, Alexandra A Arico, Gregory A Galmin, Kuan-Wen Chen, Jason A Johnson, Jamie C Wang, Ronald J Clark, Alexander Chemey, Teresa M Eaton, Matthew L Marsh, Kevin Seidler, Shane S Galley, Lambertus van de Burgt, Ashley L Gray, David E Hobart, Kenneth Hanson, Shelley M Van Cleve, Frédéric Gendron, Jochen Autschbach, Gustavo E Scuseria, Laurent Maron, Manfred Speldrich, Paul Kögerler, Cristian Celis-Barros, Dayán Páez-Hernández, Ramiro Arratia-Pérez, Michael Ruf, Thomas E Albrecht-Schmitt
The reaction of (249)Bk(OH)4 with iodate under hydrothermal conditions results in the formation of Bk(IO3)3 as the major product with trace amounts of Bk(IO3)4 also crystallizing from the reaction mixture. The structure of Bk(IO3)3 consists of nine-coordinate Bk(III) cations that are bridged by iodate anions to yield layers that are isomorphous with those found for Am(III), Cf(III), and with lanthanides that possess similar ionic radii. Bk(IO3)4 was expected to adopt the same structure as M(IO3)4 (M = Ce, Np, Pu), but instead parallels the structural chemistry of the smaller Zr(IV) cation...
September 14, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28802774/a-rule-based-dose-finding-design-for-use-in-stroke-rehabilitation-research-methodological-development
#13
E Colucci, A Clark, C E Lang, V M Pomeroy
BACKGROUND: Dose-optimisation studies as precursors to clinical trials are rare in stroke rehabilitation. OBJECTIVE: To develop a rule-based, dose-finding design for stroke rehabilitation research. DESIGN: 3+3 rule-based, dose-finding study. Dose escalation/de-escalation was undertaken according to preset rules and a mathematical sequence (modified Fibonacci sequence). The target starting daily dose was 50 repetitions for the first cohort...
January 20, 2017: Physiotherapy
https://www.readbyqxmd.com/read/28670735/six3-deletions-and-incomplete-penetrance-in-families-affected-by-holoprosencephaly
#14
Bethany Stokes, Seth I Berger, Beth A Hall, Karin Weiss, Donald W Hadley, David R Murdock, Subhadra Ramanathan, Robin D Clark, Erich Roessler, Paul Kruszka, Maximilian Muenke
Holoprosencephaly (HPE) is failure of the forebrain to divide completely during embryogenesis. Incomplete penetrance has not been reported previously in SIX3 whole gene deletions, which are known to cause HPE. Both chromosomal microarray and whole exome sequencing (WES) were used to evaluate families with inherited HPE. Two families showed inherited deletions that contain SIX3 and were incompletely penetrant for HPE. Using WES, we ruled out parental mosaicism, a SIX3 hypomorph, and clinically significant variants in genes that are known to interact with SIX3 as causes of incomplete penetrance...
July 2, 2017: Congenital Anomalies
https://www.readbyqxmd.com/read/28631745/achieving-assessor-accuracy-on-the-international-standards-for-neurological-classification-of-spinal-cord-injury
#15
A J Armstrong, J M Clark, D T Ho, C J Payne, S Nolan, L M Goodes, L A Harvey, R Marshall, M P Galea, S A Dunlop
STUDY DESIGN: A retrospective audit of assessor accuracy using the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) in three multicentre randomised controlled trials (SCIPA: Spinal Cord Injury and Physical Activity) spanning 2010-2014 with standards revised in 2011. OBJECTIVES: To investigate assessor accuracy of neurological classification after spinal cord injury. SETTING: Australia and New Zealand...
November 2017: Spinal Cord
https://www.readbyqxmd.com/read/28536093/development-of-trust-in-an-online-breast-cancer-forum-a-qualitative-study
#16
Melanie Lovatt, Peter A Bath, Julie Ellis
BACKGROUND: Online health forums provide peer support for a range of medical conditions including life-threatening and terminal illnesses. Trust is an important component of peer-to-peer support, although relatively little is known about how trust forms within online health forums. OBJECTIVE: The aim of this paper is to examine how trust develops and influences sharing among users of an online breast cancer forum. METHODS: An interpretive qualitative approach was adopted...
May 23, 2017: Journal of Medical Internet Research
https://www.readbyqxmd.com/read/28485597/photoaquation-mechanism-of-hexacyanoferrate-ii-ions-ultrafast-2d-uv-and-transient-visible-and-ir-spectroscopies
#17
Marco Reinhard, Gerald Auböck, Nicholas A Besley, Ian P Clark, Gregory M Greetham, Magnus W D Hanson-Heine, Raphael Horvath, Thomas S Murphy, Thomas J Penfold, Michael Towrie, Michael W George, Majed Chergui
Ferrous iron(II) hexacyanide in aqueous solutions is known to undergo photoionization and photoaquation reactions depending on the excitation wavelength. To investigate this wavelength dependence, we implemented ultrafast two-dimensional UV transient absorption spectroscopy, covering a range from 280 to 370 nm in both excitation and probing, along with UV pump/visible probe or time-resolved infrared (TRIR) transient absorption spectroscopy and density functional theory (DFT) calculations. As far as photoaquation is concerned, we find that excitation of the molecule leads to ultrafast intramolecular relaxation to the lowest triplet state of the [Fe(CN)6](4-) complex, followed by its dissociation into CN(-) and [Fe(CN)5](3-) fragments and partial geminate recombination, all within <0...
May 18, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28439809/site-selection-a-case-study-in-the-identification-of-optimal-cysteine-engineered-antibody-drug-conjugates
#18
L Nathan Tumey, Fengping Li, Brian Rago, Xiaogang Han, Frank Loganzo, Sylvia Musto, Edmund I Graziani, Sujiet Puthenveetil, Jeffrey Casavant, Kimberly Marquette, Tracey Clark, Jack Bikker, Eric M Bennett, Frank Barletta, Nicole Piche-Nicholas, Amy Tam, Christopher J O'Donnell, Hans Peter Gerber, Lioudmila Tchistiakova
As the antibody drug conjugate (ADC) community continues to shift towards site-specific conjugation technology, there is a growing need to understand how the site of conjugation impacts the biophysical and biological properties of an ADC. In order to address this need, we prepared a carefully selected series of engineered cysteine ADCs and proceeded to systematically evaluate their potency, stability, and PK exposure. The site of conjugation did not have a significant influence on the thermal stability and in vitro cytotoxicity of the ADCs...
July 2017: AAPS Journal
https://www.readbyqxmd.com/read/28420054/the-prevalence-and-determinants-of-anti-dfs70-autoantibodies-in-an-international-inception-cohort-of-systemic-lupus-erythematosus-patients
#19
M Y Choi, A E Clarke, Y St Pierre, J G Hanly, M B Urowitz, J Romero-Diaz, C Gordon, S-C Bae, S Bernatsky, D J Wallace, J T Merrill, D A Isenberg, A Rahman, E M Ginzler, M Petri, I N Bruce, M A Dooley, P Fortin, D D Gladman, J Sanchez-Guerrero, K Steinsson, R Ramsey-Goldman, M A Khamashta, C Aranow, G S Alarcón, S Manzi, O Nived, A A Zoma, R F van Vollenhoven, M Ramos-Casals, G Ruiz-Irastorza, S S Lim, K C Kalunian, M Inanc, D L Kamen, C A Peschken, S Jacobsen, A Askanase, J Buyon, M Mahler, M J Fritzler
Autoantibodies to dense fine speckles 70 (DFS70) are purported to rule out the diagnosis of SLE when they occur in the absence of other SLE-related autoantibodies. This study is the first to report the prevalence of anti-DFS70 in an early, multinational inception SLE cohort and examine demographic, clinical, and autoantibody associations. Patients were enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort within 15 months of diagnosis. The association between anti-DFS70 and multiple parameters in 1137 patients was assessed using univariate and multivariate logistic regression...
September 2017: Lupus
https://www.readbyqxmd.com/read/28407555/thalamocortical-connectivity-in-major-depressive-disorder
#20
Elliot C Brown, Darren L Clark, Stefanie Hassel, Glenda MacQueen, Rajamannar Ramasubbu
BACKGROUND: Major Depressive Disorder (MDD) is highly prevalent and potentially devastating, with widespread aberrations in brain activity. Thalamocortical networks are a potential candidate marker for psychopathology in MDD, but have not yet been thoroughly investigated. Here we examined functional connectivity between major cortical areas and thalamus. METHOD: Resting-state fMRI from 54 MDD patients and 40 healthy controls were collected. The cortex was segmented into six regions of interest (ROIs) consisting of frontal, temporal, parietal, and occipital lobes and pre-central and post-central gyri...
August 1, 2017: Journal of Affective Disorders
keyword
keyword
57966
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"