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https://www.readbyqxmd.com/read/28646641/do-large-mergers-increase-or-decrease-the-productivity-of-pharmaceutical-r-d
#1
Michael S Ringel, Michael K Choy
There is current uncertainty regarding the effects of mergers on pharmaceutical R&D productivity, with various mechanisms reported by which mergers could either help or harm R&D, and mixed empirical findings in prior analyses. Here, we present an analysis that is novel in several ways: we use downstream measures of R&D productivity, account for both inputs and outputs in our calculations, and use a self-controlled design. We find that recent large pharmaceutical mergers are associated with statistically significant increases in R&D productivity...
June 21, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28646611/prediction-in-ecology-a-first-principles-framework
#2
Michael C Dietze
Quantitative predictions are ubiquitous in ecology, yet there is limited discussion on the nature of prediction in this field. Herein I derive a general quantitative framework for analyzing and partitioning the sources of uncertainty that control predictability. The implications of this framework are assessed conceptually and linked to classic questions in ecology, such as the relative importance of endogenous (density dependent) versus exogenous factors, stability versus drift, and the spatial scaling of processes...
June 24, 2017: Ecological Applications: a Publication of the Ecological Society of America
https://www.readbyqxmd.com/read/28646258/selective-survival-advantage-associated-with-primary-tumor-resection-for-metastatic-gastric-cancer-in-a-western-population
#3
René Warschkow, Matthias Baechtold, Kenneth Leung, Bruno M Schmied, Daniel P Nussbaum, Beat Gloor, Dan G Blazer Iii, Mathias Worni
BACKGROUND: The prognosis of metastatic gastric cancer (GC) remains dismal, with a median survival of 10 months. Historically, primary tumor resection was not thought to confer any survival benefit. Although high-level data exist guiding treatment of metastatic GC for patients in the East, no such data exist for Western patients despite inherent ethnic differences in GC biology. METHODS: The 2006-2012 National Cancer Database was queried for adult patients with metastatic gastric adenocarcinoma...
June 23, 2017: Gastric Cancer
https://www.readbyqxmd.com/read/28646140/effect-of-dietary-advanced-glycation-end-products-on-inflammation-and-cardiovascular-risks-in-healthy-overweight-adults-a-randomised-crossover-trial
#4
Estifanos Baye, Maximilian Pj de Courten, Karen Walker, Sanjeeva Ranasinha, Arul Earnest, Josephine M Forbes, Barbora de Courten
Diets high in advanced glycation end products (AGEs) are thought to be detrimental to cardiovascular health. However, there remains uncertainty about the beneficial effect of a low AGE diet on cardiovascular risk factors and inflammatory markers in overweight individuals. We thus performed a randomised, double blind, crossover trial to determine whether consumption of low AGE diets reduce inflammation and cardiovascular risks in overweight and obese otherwise healthy adults. All participants (n = 20) consumed low and high AGE diets alternately for two weeks and separated by a four week washout period...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646132/global-rainfall-erosivity-assessment-based-on-high-temporal-resolution-rainfall-records
#5
Panos Panagos, Pasquale Borrelli, Katrin Meusburger, Bofu Yu, Andreas Klik, Kyoung Jae Lim, Jae E Yang, Jinren Ni, Chiyuan Miao, Nabansu Chattopadhyay, Seyed Hamidreza Sadeghi, Zeinab Hazbavi, Mohsen Zabihi, Gennady A Larionov, Sergey F Krasnov, Andrey V Gorobets, Yoav Levi, Gunay Erpul, Christian Birkel, Natalia Hoyos, Victoria Naipal, Paulo Tarso S Oliveira, Carlos A Bonilla, Mohamed Meddi, Werner Nel, Hassan Al Dashti, Martino Boni, Nazzareno Diodato, Kristof Van Oost, Mark Nearing, Cristiano Ballabio
The exposure of the Earth's surface to the energetic input of rainfall is one of the key factors controlling water erosion. While water erosion is identified as the most serious cause of soil degradation globally, global patterns of rainfall erosivity remain poorly quantified and estimates have large uncertainties. This hampers the implementation of effective soil degradation mitigation and restoration strategies. Quantifying rainfall erosivity is challenging as it requires high temporal resolution(<30 min) and high fidelity rainfall recordings...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646078/stereospecific-metabolism-of-r-and-s-warfarin-by-human-hepatic-cytosolic-reductases
#6
Dustyn A Barnette, Bryce Johnson, Dakota L Pouncey, Robert Nshimiyimana, Linda Desrochers, Thomas E Goodwin, Grover Paul Miller
Coumadin (rac-warfarin) is the most commonly used anticoagulant in the world, yet its clinical use is often challenging due to a narrow therapeutic range and inter-individual variations in response. A critical contributor to the uncertainty is variability in warfarin metabolism, which includes mostly oxidative but also reductive pathways. Reduction of each warfarin enantiomer yields two warfarin alcohol isomers, and the corresponding four alcohols retain varying levels of anticoagulant activity. Studies on the kinetics of warfarin reduction have often lacked resolution of parent drug enantiomers and suffered from co-elution of pairs of alcohol metabolites; thus, those studies fail to establish the importance of individual, stereospecific reductive pathways...
June 23, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28645902/the-cause-of-the-stroke-a-diagnostic-uncertainty
#7
Abhishek Dattani, Ava Jackson
A 39-year-old man with a history of sickle cell disease (SCD) presented with left leg weakness. He had a normal CT head and CT angiogram, but MRI head showed multiple acute bilateral cortical infarcts including in the right precentral gyrus. The MRI findings were more in keeping with an embolic source rather than stroke related to SCD, although it could not be ruled out. He also had an echocardiogram which revealed a patent foramen ovale. He was treated with antiplatelet therapy and also had red blood cell exchange transfusion...
June 23, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28645838/sensitivity-analysis-and-uncertainty-quantification-in-pulmonary-drug-delivery-of-orally-inhaled-pharmaceuticals
#8
Jun Lu, Jinxiang Xi, Joseph E Langenderfer
In spite of widespread use of modeling tools in inhalation dosimetry, it remains difficult to quantify the output uncertainties when subjected to various sources of input variability. This study aimed to develop a computational model that can quantify the input sensitivity and output uncertainty in pulmonary drug delivery by coupling probabilistic analysis package NESSUS with ANSYS Fluent. An image-based mouth-lung model was used to simulate the transport and deposition of drug particles and variability in particle size, density, and inhalation speed were considered...
June 20, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28645585/thrombocytopenia-and-neurosurgery-a-literature-review
#9
REVIEW
Daphne Li, Taylor Glor, G Alexander Jones
The absence of evidence-based guidelines for platelet transfusion surrounding invasive neurosurgical procedures leads to uncertainty in management. Multiple studies have illuminated this lack of high quality data, and subsequent reliance on expert opinion. The generally accepted threshold for platelet transfusion has hovered around 100,000/μl. We have conducted a review of available clinical literature, in order to identify any evidence that may support or refute these general guidelines, in an attempt to clarify the need for platelet transfusion in the patient requiring neurosurgical intervention...
June 20, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28645137/-to-take-or-not-to-take-the-association-between-perceived-addiction-risk-expected-analgesic-response-and-likelihood-of-trying-novel-pain-relievers-in-self-identified-chronic-pain-patients
#10
D Andrew Tompkins, Andrew S Huhn, Patrick S Johnson, Michael T Smith, Eric C Strain, Robert R Edwards, Matthew W Johnson
BACKGROUND AND AIMS: Probability discounting refers to the effect of outcome uncertainty on decision making. Using probability discounting, we examined the degree to which self-identified chronic pain patients (CPP) were likely to try a novel analgesic medication given increasing addiction risk. We postulated that propensity for opioid misuse, trait impulsivity, and previous opioid experience would be positively associated with likelihood of risky medication use. DESIGN: This cross-sectional online study determined state/trait associations with addiction-related medication decisions in CPP...
June 23, 2017: Addiction
https://www.readbyqxmd.com/read/28644791/culture-and-moral-distress-what-s-the-connection-and-why-does-it-matter
#11
Nancy Berlinger, Annalise Berlinger
Culture is learned behavior shared among members of a group and from generation to generation within that group. In health care work, references to "culture" may also function as code for ethical uncertainty or moral distress concerning patients, families, or populations. This paper analyzes how culture can be a factor in patient-care situations that produce moral distress. It discusses three common, problematic situations in which assumptions about culture may mask more complex problems concerning family dynamics, structural barriers to health care access, or implicit bias...
June 1, 2017: AMA Journal of Ethics
https://www.readbyqxmd.com/read/28644787/who-is-experiencing-what-kind-of-moral-distress-distinctions-for-moving-from-a-narrow-to-a-broad-definition-of-moral-distress
#12
Carina Fourie
Moral distress, according to Andrew Jameton's highly influential definition, occurs when a nurse knows the morally correct action to take but is constrained in some way from taking this action. The definition of moral distress has been broadened, first, to include morally challenging situations that give rise to distress but which are not necessarily linked to nurses feeling constrained, such as those associated with moral uncertainty. Second, moral distress has been broadened so that it is not confined to the experiences of nurses...
June 1, 2017: AMA Journal of Ethics
https://www.readbyqxmd.com/read/28644778/impact-of-economic-hardship-and-financial-threat-on-suicide-ideation-and-confusion
#13
Lisa Fiksenbaum, Zdravko Marjanovic, Esther Greenglass, Francisco Garcia-Santos
The present study tested the extent to which perceived economic hardship is associated with psychological distress (suicide ideation and confusion) after controlling for personal characteristics. It also explored whether perceived financial threat (i.e., fearful anxious-uncertainty about the stability and security of one's personal financial situation) mediates the relationship between economic hardship and psychological distress outcomes. The theoretical model was tested in a sample of Canadian students (n = 211) and was validated in a community sample of employed Portuguese adults (n = 161)...
July 4, 2017: Journal of Psychology
https://www.readbyqxmd.com/read/28644724/modeling-long-term-effects-attributed-to-nitrogen-dioxide-no2-and-sulfur-dioxide-so2-exposure-on-asthma-morbidity-in-a-nationwide-cohort-in-israel
#14
N Greenberg, R S Carel, E Derazne, A Tiktinsky, D Tzur, B A Portnov
Studies have provided extensive documentation that acutely elevated environmental exposures contribute to chronic health problems. However, only attention has been paid to the effects of modificate of exposure assessment methods in environmental health investigations, leading to uncertainty and gaps in our understanding of exposure- and dose-response relationships. The goal of the present study was to evaluate whether average or peak concentration exerts a greater influence on asthma outcome, and which of the exposure models may better explain various physiological responses generated by nitrogen dioxide (NO2) or sulfur dioxide (SO2) air pollutants...
June 23, 2017: Journal of Toxicology and Environmental Health. Part A
https://www.readbyqxmd.com/read/28644643/first-demonstration-of-a-scintillating-xenon-bubble-chamber-for-detecting-dark-matter-and-coherent-elastic-neutrino-nucleus-scattering
#15
D Baxter, C J Chen, M Crisler, T Cwiok, C E Dahl, A Grimsted, J Gupta, M Jin, R Puig, D Temples, J Zhang
A 30-g xenon bubble chamber, operated at Northwestern University in June and November 2016, has for the first time observed simultaneous bubble nucleation and scintillation by nuclear recoils in a superheated liquid. This chamber is instrumented with a CCD camera for near-IR bubble imaging, a solar-blind photomultiplier tube to detect 175-nm xenon scintillation light, and a piezoelectric acoustic transducer to detect the ultrasonic emission from a growing bubble. The time of nucleation determined from the acoustic signal is used to correlate specific scintillation pulses with bubble-nucleating events...
June 9, 2017: Physical Review Letters
https://www.readbyqxmd.com/read/28644635/fundamental-transitions-and-ionization-energies-of-the-hydrogen-molecular-ions-with-few-ppt-uncertainty
#16
Vladimir I Korobov, L Hilico, J-Ph Karr
We calculate ionization energies and fundamental vibrational transitions for H_{2}^{+}, D_{2}^{+}, and HD^{+} molecular ions. The nonrelativistic quantum electrodynamics expansion for the energy in terms of the fine structure constant α is used. Previous calculations of orders mα^{6} and mα^{7} are improved by including second-order contributions due to the vibrational motion of nuclei. Furthermore, we evaluate the largest corrections at the order mα^{8}. That allows us to reduce the fractional uncertainty to the level of 7...
June 9, 2017: Physical Review Letters
https://www.readbyqxmd.com/read/28644624/extensive-assessment-of-various-computational-methods-for-aspartate-s-pka-shift
#17
Zhaoxi Sun, Xiaohui Wang, Jianing Song
A series of computational methods for pKa shift prediction are extensively tested on a set of benchmark protein systems, aiming at identifying pitfalls and evaluating their performance on high variants. Including 19 ASP residues in 10 protein systems, the benchmark set consists of both residues with highly shifted pKa values as well as those varying little from the reference value, with an experimental RMS free energy differences of 2.49 kcal/mol with respect to blocked amino acid, namely the RMS pKa shift being 1...
June 23, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28644579/pairing-field-methods-to-improve-inference-in-wildlife-surveys-while-accommodating-detection-covariance
#18
John Clare, Shawn T McKinney, John E DePue, Cynthia S Loftin
It is common to use multiple field sampling methods when implementing wildlife surveys to compare method efficacy or cost-efficiency, integrate distinct pieces of information provided by separate methods, or evaluate method-specific biases and misclassification error. Existing models that combine information from multiple field methods or sampling devices permit rigorous comparison of method-specific detection parameters, enable estimation of additional parameters such as false-positive detection probability, and improve occurrence or abundance estimates, but with the assumption that the separate sampling methods produce detections independently of one another...
June 23, 2017: Ecological Applications: a Publication of the Ecological Society of America
https://www.readbyqxmd.com/read/28644546/-18-f-fluoromisonidazole-uptake-in-advanced-stage-non-small-cell-lung-cancer-a-voxel-by-voxel-pet-kinetics-study
#19
Daniel R McGowan, Ruth E Macpherson, Sara L Hackett, Dan Liu, Fergus V Gleeson, W Gillies McKenna, Geoff S Higgins, John D Fenwick
PURPOSE: To determine the relative abilities of compartment models to describe time-courses of 18F-fluoromisonidazole (FMISO) uptake in tumor voxels of patients with non-small cell lung cancer (NSCLC) imaged using dynamic positron emission tomography. Also to use fits of the best-performing model to investigate changes in fitted rate-constants with distance from the tumor edge. METHODS: Reversible and irreversible two- and three-tissue compartment models were fitted to 24,662 individual voxel time activity curves (TACs) obtained from tumors in 9 patients, each imaged twice...
June 23, 2017: Medical Physics
https://www.readbyqxmd.com/read/28644430/the-clinical-landscape-for-sma-in-a-new-therapeutic-era
#20
REVIEW
K Talbot, E F Tizzano
Despite significant advances in basic research, the treatment of degenerative diseases of the nervous system remains one of the greatest challenges for translational medicine. The childhood onset motor neuron disorder spinal muscular atrophy (SMA) has been viewed as one of the more tractable targets for molecular therapy, due to a detailed understanding of the molecular genetic basis of the disease. In SMA, inactivating mutations in the SMN1 gene can be partially compensated for by limited expression of SMN protein from a variable number of copies of the SMN2 gene, which provides both a molecular explanation for phenotypic severity and a target for therapy...
June 23, 2017: Gene Therapy
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