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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/28636311/insights-into-integrated-lead-generation-and-target-identification-in-malaria-and-tuberculosis-drug-discovery
#2
John Okombo, Kelly Chibale
New, safe and effective drugs are urgently needed to treat and control malaria and tuberculosis, which affect millions of people annually. However, financial return on investment in the poor settings where these diseases are mostly prevalent is very minimal to support market-driven drug discovery and development. Moreover, the imminent loss of therapeutic lifespan of existing therapies due to evolution and spread of drug resistance further compounds the urgency to identify novel effective drugs. However, the advent of new public-private partnerships focused on tropical diseases and the recent release of large data sets by pharmaceutical companies on antimalarial and antituberculosis compounds derived from phenotypic whole cell high throughput screening have spurred renewed interest and opened new frontiers in malaria and tuberculosis drug discovery...
June 21, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28633460/guidelines-for-composing-and-assessing-a-paper-on-treatment-of-pain
#3
Nikolai Bogduk, David J Kennedy, Yakov Vorobeychik, Andrew Engel
Authors, readers, and editors share a common focus. Authors want to publish their work. Readers want to see high-quality, new information. Referees and editors serve to ensure that authors provide valid conclusions based on the quality of information that readers want. Common to each of these roles are instructions to authors. However, these are typically written in an uninspiring, legalistic style, as if they are a set of rules that authors must obey if they expect to get published. This renders the instructions boring and oppressive, if not forbidding...
June 17, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/28630156/apoptotic-foci-at-mitochondria-in-and-around-bax-pores
#4
REVIEW
Begoña Ugarte-Uribe, Ana J García-Sáez
The permeabilization of the mitochondrial outer membrane by Bax and Bak during apoptosis is considered a key step and a point of no return in the signalling pathway. It is always closely related to the reorganization of mitochondrial cristae that frees cytochrome c to the intermembrane space and to massive mitochondrial fragmentation mediated by the dynamin-like protein Drp1. Despite multiple evidence in favour of a functional link between these processes, the molecular mechanisms that connect them and their relevance for efficient apoptosis signalling remain obscure...
August 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28628860/in-silico-modeling-on-adme-properties-of-natural-products-classification-models-for-blood-brain-barrier-permeability-its-application-to-traditional-chinese-medicine-and-in-vitro-experimental-validation
#5
Xiuqing Zhang, Ting Liu, Xiaohui Fan, Ni Ai
In silico modeling of blood-brain barrier (BBB) permeability plays an important role in early discovery of central nervous system (CNS) drugs due to its high-throughput and cost-effectiveness. Natural products (NP) have demonstrated considerable therapeutic efficacy against several CNS diseases. However, BBB permeation property of NP is scarcely evaluated both experimentally and computationally. It is well accepted that significant difference in chemical spaces exists between NP and synthetic drugs, which calls into doubt on suitability of available synthetic chemical based BBB permeability models for the evaluation of NP...
June 7, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28626962/three-dimensional-motion-corrected-sensitivity-encoding-reconstruction-for-multi-shot-multi-slice-mri-application-to-neonatal-brain-imaging
#6
Lucilio Cordero-Grande, Emer J Hughes, Jana Hutter, Anthony N Price, Joseph V Hajnal
PURPOSE: To introduce a methodology for the reconstruction of multi-shot, multi-slice magnetic resonance imaging able to cope with both within-plane and through-plane rigid motion and to describe its application in structural brain imaging. THEORY AND METHODS: The method alternates between motion estimation and reconstruction using a common objective function for both. Estimates of three-dimensional motion states for each shot and slice are gradually refined by improving on the fit of current reconstructions to the partial k-space information from multiple coils...
June 19, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/28622010/-are-you-in-or-are-you-out-moral-appeals-to-the-public-in-organ-donation-poster-campaigns-a-multimodal-and-ethical-analysis
#7
Solveig L Hansen, Marthe I Eisner, Larissa Pfaller, Silke Schicktanz
Organ transplantation is a well-established practice in modern medicine. However, many countries, especially those with an opt-in regulation, face the problem of low donation numbers. Respective public campaigns attempt to increase the number of donors by swaying public opinion with the use of carefully selected bits of information. Germany serves as a case study for an opt-in country investing approximately €7.5 million/year in the distribution of respective campaigns. To address diverse populations, large-scale posters in various public spaces still display a multitude of moral messages for organ donation...
June 16, 2017: Health Communication
https://www.readbyqxmd.com/read/28621602/resolution-of-nonurine-transudative-pleural-effusion-in-a-cat-after-removal-of-a-hydronephrotic-kidney
#8
Maura E Duffy, Andrew J Specht, Ahmira R Torres, May-Li Cuypers
CASE DESCRIPTION A 3-year-old spayed female Bengal cat was evaluated because of a history of bilateral pleural effusion and hydronephrosis of the right kidney. CLINICAL FINDINGS Cytologic analysis of a pleural fluid sample revealed characteristics of a pure transudate with a high percentage of lymphocytes. Results of fluid biochemical testing were not consistent with urine or chyle. Serum biochemical analysis and echocardiography yielded no evidence of hypoalbuminemia or high hydrostatic pressure secondary to cardiac disease...
July 1, 2017: Journal of the American Veterinary Medical Association
https://www.readbyqxmd.com/read/28619593/on-the-halt-of-spontaneous-capillary-flows-in-diverging-open-channels
#9
J Berthier, K A Brakke, D Gosselin, F Navarro, N Belgacem, D Chaussy, E Berthier
Due to their compactness and independence of exterior energy sources, capillary microsystems are increasingly used in many different scientific domains, from biotechnology to medicine and biology, chemistry, energy and space. Obtaining a capillary flow depends on channel geometry and contact angle. A general condition for the establishment of a spontaneous capillary flow in a uniform cross section channel has already been derived from Gibbs free energy. In this work, we consider spontaneous capillary flows (SCF) in diverging open rectangular channels and suspended channels, and we show that they do not flow indefinitely but stop at some location in the channel...
June 12, 2017: Medical Engineering & Physics
https://www.readbyqxmd.com/read/28617993/rigid-body-motion-correction-of-the-liver-in-image-reconstruction-for-golden-angle-stack-of-stars-dce-mri
#10
Adam Johansson, James Balter, Yue Cao
PURPOSE: Respiratory motion can affect pharmacokinetic perfusion parameters quantified from liver dynamic contrast-enhanced MRI. Image registration can be used to align dynamic images after reconstruction. However, intra-image motion blur remains after alignment and can alter the shape of contrast-agent uptake curves. We introduce a method to correct for inter- and intra-image motion during image reconstruction. METHODS: Sixteen liver dynamic contrast-enhanced MRI examinations of nine subjects were performed using a golden-angle stack-of-stars sequence...
June 15, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/28611985/adaptation-through-collaboration-developing-novel-platforms-to-advance-the-delivery-of-advanced-therapies-to-patients
#11
REVIEW
Magdalini Papadaki
For the nascent field of advanced therapies, collaboration will be a game-changer, turning scientific progress that was once unimaginable into transformative medical practice. Despite promise for lifelong management and even cure of disease, skepticism remains about the feasibility of their delivery to patients, fueling investment risks. With the potential for long-term effectiveness in need of frequent reassessment, current approaches to predict real-life drug performance bear little relevance, necessitating novel and iterative schemes to monitoring the benefit-risk profiles throughout the life span of advanced therapies...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28608411/interleaved-epi-diffusion-imaging-using-spirit-based-reconstruction-with-virtual-coil-compression
#12
Zijing Dong, Fuyixue Wang, Xiaodong Ma, Zhe Zhang, Erpeng Dai, Chun Yuan, Hua Guo
PURPOSE: To develop a novel diffusion imaging reconstruction framework based on iterative self-consistent parallel imaging reconstruction (SPIRiT) for multishot interleaved echo planar imaging (iEPI), with computation acceleration by virtual coil compression. METHODS: As a general approach for autocalibrating parallel imaging, SPIRiT improves the performance of traditional generalized autocalibrating partially parallel acquisitions (GRAPPA) methods in that the formulation with self-consistency is better conditioned, suggesting SPIRiT to be a better candidate in k-space-based reconstruction...
June 12, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/28606207/utilizing-a-pediatric-disaster-coalition-model-to-increase-pediatric-critical-care-surge-capacity-in-new-york-city
#13
Michael Frogel, Avram Flamm, Mayer Sagy, Katharine Uraneck, Edward Conway, Michael Ushay, Bruce M Greenwald, Louisdon Pierre, Vikas Shah, Mohamed Gaffoor, Arthur Cooper, George Foltin
A mass casualty event can result in an overwhelming number of critically injured pediatric victims that exceeds the available capacity of pediatric critical care (PCC) units, both locally and regionally. To address these gaps, the New York City (NYC) Pediatric Disaster Coalition (PDC) was established. The PDC includes experts in emergency preparedness, critical care, surgery, and emergency medicine from 18 of 25 major NYC PCC-capable hospitals. A PCC surge committee created recommendations for making additional PCC beds available with an emphasis on space, staff, stuff (equipment), and systems...
June 13, 2017: Disaster Medicine and Public Health Preparedness
https://www.readbyqxmd.com/read/28605458/prioritizing-tests-of-epistasis-through-hierarchical-representation-of-genomic-redundancies
#14
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/28603644/neighbours-of-cancer-related-proteins-have-key-influence-on-pathogenesis-and-could-increase-the-drug-target-space-for-anticancer-therapies
#15
Dezső Módos, Krishna C Bulusu, Dávid Fazekas, János Kubisch, Johanne Brooks, István Marczell, Péter M Szabó, Tibor Vellai, Péter Csermely, Katalin Lenti, Andreas Bender, Tamás Korcsmáros
Even targeted chemotherapies against solid cancers show a moderate success increasing the need to novel targeting strategies. To address this problem, we designed a systems-level approach investigating the neighbourhood of mutated or differentially expressed cancer-related proteins in four major solid cancers (colon, breast, liver and lung). Using signalling and protein-protein interaction network resources integrated with mutational and expression datasets, we analysed the properties of the direct and indirect interactors (first and second neighbours) of cancer-related proteins, not found previously related to the given cancer type...
January 24, 2017: NPJ Systems Biology and Applications
https://www.readbyqxmd.com/read/28598606/4s-hydroxylation-of-insulin-at-prob28-accelerates-hexamer-dissociation-and-delays-fibrillation
#16
Seth A Lieblich, Katharine Y Fang, Jackson K B Cahn, Jeffrey Rawson, Jeanne LeBon, H Teresa Ku, David A Tirrell
Daily injections of insulin provide lifesaving benefits to millions of diabetics. But currently available prandial insulins are suboptimal: The onset of action is delayed by slow dissociation of the insulin hexamer in the subcutaneous space, and insulin forms amyloid fibrils upon storage in solution. Here we show, through the use of noncanonical amino acid mutagenesis, that replacement of the proline residue at position 28 of the insulin B-chain (ProB28) by (4S)-hydroxyproline (Hzp) yields an active form of insulin that dissociates more rapidly, and fibrillates more slowly, than the wild-type protein...
June 20, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28593635/multichannel-compressed-sensing-mr-image-reconstruction-using-statistically-optimized-nonlinear-diffusion
#17
Ajin Joy, Joseph Suresh Paul
PURPOSE: Eliminate the need for parametric tuning in total variation (TV) based multichannel compressed-sensing image reconstruction using statistically optimized nonlinear diffusion without compromising image quality. THEORY AND METHODS: Nonlinear diffusion controls the denoising process using a contrast parameter that separates the gradients corresponding to noise and true edges in the image. This parameter is statistically estimated from the variance of combined image gradient to yield minimum steady-state reconstruction error...
June 7, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/28590562/robust-epi-nyquist-ghost-removal-by-incorporating-phase-error-correction-with-sensitivity-encoding-pec-sense
#18
Victor B Xie, Mengye Lyu, Yilong Liu, Yanqiu Feng, Ed X Wu
PURPOSE: The existing approach of Nyquist ghost correction by parallel imaging in echo planar imaging (EPI) can suffer from image noise amplification. We propose a method that estimates a phase error map from multi-channel data itself and incorporates it into the sensitivity encoding (SENSE) reconstruction for Nyquist ghost correction without compromising the image SNR. METHODS: This method first reconstructs two ghost-free images from positive and negative echoes using SENSE, respectively, from which the phase error map is computed...
June 7, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/28588970/modifying-the-interagency-emergency-health-kit-to-include-treatment-for-non-communicable-diseases-in-natural-disasters-and-complex-emergencies
#19
Marcello Tonelli, Natasha Wiebe, Brian Nadler, Ara Darzi, Shahnawaz Rasheed
The Interagency Emergency Health Kit (IEHK) provides a standard package of medicines and simple medical devices for aid agencies to use in emergencies such as disasters and armed conflicts. Despite the increasing burden of non-communicable diseases (NCDs) in such settings, the IEHK includes few drugs and devices for management of NCDs. Using published data to model the population burden of acute and chronic presentations of NCDs in emergency-prone regions, we estimated the quantity of medications and devices that should be included in the IEHK...
November 2016: BMJ Global Health
https://www.readbyqxmd.com/read/28588896/promoting-transparency-accountability-and-access-through-a-multi-stakeholder-initiative-lessons-from-the-medicines-transparency-alliance
#20
Taryn Vian, Jillian C Kohler, Gilles Forte, Deirdre Dimancesco
BACKGROUND: Barriers to expanding access to medicines include weak pharmaceutical sector governance, lack of transparency and accountability, inadequate attention to social services on the political agenda, and financing challenges. Multi-stakeholder initiatives such as the Medicines Transparency Alliance (MeTA) may help overcome these barriers. Between 2008 and 2015, MeTA engaged stakeholders in the pharmaceutical sectors of seven countries (Ghana, Jordan, Kyrgyzstan, Peru, Philippines, Uganda, and Zambia) to promote access goals through greater transparency...
2017: Journal of Pharmaceutical Policy and Practice
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