bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interdisciplinary pharmacometrics linking oseltamivir pharmacology, influenza epidemiology and health economics to inform antiviral use in pandemics
Authors: Kamal Mohamed A. , Smith Patrick F. , Chaiyakunapruk Nathorn , Wu David B. C. , Pratoomsoot Chayanin , Lee Kenneth K. C. , Chong Huey Yi , Nelson Richard E. , Nieforth Keith , Dall Georgina , Toovey Stephen , Kong David C. M. , Kamauu Aaron , Kirkpatrick Carl M. , Rayner Craig R. 
Published: February 2017

AimsA modular interdisciplinary platform was developed to investigate the economic impact of oseltamivir treatment by dosage regimen under simulated influenza pandemic scenarios.MethodsThe pharmacology module consisted of a pharmacokinetic distribution of oseltamivir carboxylate daily area under the concentration–time curve at steady state (simulated for 75 mg and 150 mg twice daily regimens for 5 days) and a pharmacodynamic distribution of viral shedding duration obtained from phase II influenza inoculation data. The epidemiological module comprised a susceptible, exposed, infected, recovered (SEIR) model to which drug effect on the basic reproductive number (R0), a measure of transmissibility, was linked by reduction of viral shedding duration. The number of infected patients per population of 100 000 susceptible individuals was simulated for a series of pandemic scenarios, varying oseltamivir dose, R0 (1.9 vs. 2.7), and drug uptake (25%, 50%, and 80%). The number of infected patients for each scenario was entered into the health economics module, a decision analytic model populated with branch probabilities, disease utility, costs of hospitalized patients developing complications, and case‐fatality rates. Change in quality‐adjusted life years was determined relative to base case.ResultsOseltamivir 75 mg relative to no treatment reduced the median number of infected patients, increased change in quality‐adjusted life years by deaths averted, and was cost‐saving under all scenarios; 150 mg relative to 75 mg was not cost effective in low transmissibility scenarios but was cost saving in high transmissibility scenarios.ConclusionThis methodological study demonstrates proof of concept that the disciplines of pharmacology, disease epidemiology and health economics can be linked in a single quantitative framework.
Hypoalbuminaemia and decreased midazolam clearance in terminally ill adult patients, an inflammatory effect?
Authors: Franken Linda G. , Masman Anniek D. , de Winter Brenda C. M. , Baar Frans P. M. , Tibboel Dick , van Gelder Teun , Koch Birgit C. P. , Mathot Ron A. A. 
Published: February 2017

AimsMidazolam is the drug of choice for palliative sedation and is titrated to achieve the desired level of sedation. Because of large inter‐individual variability (IIV), however, the time it takes to achieve adequate sedation varies widely. It would therefore greatly improve clinical care if an individualized dose could be determined beforehand. To find clinically relevant parameters for dose individualization, we performed a pharmacokinetic study on midazolam, 1OH‐midazolam (1‐OH‐M) and 1OH‐midazolam‐glucuronide (1‐OH‐MG) in terminally ill patients.MethodsUsing nonlinear mixed effects modelling (NONMEM 7.2), a population pharmacokinetic analysis was conducted with 192 samples from 45 terminally ill patients who received midazolam either orally or subcutaneously. The covariates analysed were patient characteristics, co‐medication and blood chemistry levels.ResultsThe data were accurately described by a one compartment model for midazolam, 1‐OH‐M and 1‐OH‐MG. The population mean estimates for midazolam, 1‐OH‐M and 1‐OH‐MG clearance were 8.4 l h−1 (RSE 9%, IIV 49%), 45.4 l h−1 (RSE 12%, IIV 60.5%) and 5.1 l h−1 (RSE 11%, IIV 49.9%), respectively. 1‐OH‐MG clearance was correlated with the estimated glomular filtration rate (eGFR) explaining 28.4% of the IIV in 1‐OH‐MG clearance. In addition, low albumin levels were associated with decreased midazolam clearance, explaining 18.2% of the IIV.ConclusionOur study indicates albumin levels and eGFR as relevant clinical parameters to optimize midazolam dosing in terminally ill patients. The correlation between low albumin levels and decreased midazolam clearance is probably a result of inflammatory response as high CRP levels were correlated in a similar way.
The Impact of Acquiring EU Status on the Earnings of East European Migrants in the UK: Evidence from a Quasi‐Natural Experiment
Authors: Ruhs Martin 
Published: February 2017

AbstractOn 1 May 2004, 10 new states — including the ‘A8’ countries in Central and Eastern Europe — joined the European Union (EU). This article explores the impact of EU enlargement on A8 workers who were already working in the UK before 1 May 2004 — legally or illegally. More specifically, the article analyses the impact of the change in the legal (immigration) status that A8 workers experienced on 1 May 2004 on their earnings in the UK. The empirical analysis employs difference‐in‐difference estimation using data obtained from a relatively small but unique survey of migrant workers from four of the A8 countries (Poland, Czech Republic, Slovakia and Lithuania) and two other East European countries (Ukraine and Bulgaria), carried out one month before and six to eight months after EU enlargement in May 2004. The results of this exploratory analysis suggest a statistically significant and positive impact of acquiring EU status on earnings. The data further indicate that, in part, this effect was brought about by A8 workers gaining the right to freely change jobs after EU enlargement. There is no evidence of a ‘legalization effect’ on earnings.
Broad spectrum efficacy with LY2969822, an oral prodrug of metabotropic glutamate 2/3 receptor agonist LY2934747, in rodent pain models
Authors: Johnson Michael P , Muhlhauser Mark A , Nisenbaum Eric S , Simmons Rosa M A , Forster Beth M , Knopp Kelly L , Yang Lijuan , Morrow Denise , Li Dominic L , Kennedy Jeffrey D , Swanson Steven , Monn James A 
Published: February 2017

Background and PurposeA body of evidence suggests activation of metabotropic glutamate 2/3 (mGlu2/3) receptors would be an effective analgesic in chronic pain conditions. Thus, the analgesic properties of a novel mGlu2/3 receptor agonist prodrug were investigated.Experimental ApproachAfter oral absorption, the prodrug LY2969822 rapidly converts to the brain penetrant, potent and subtype‐selective mGlu2/3 receptor agonist LY2934747. Behavioural assessments of allodynia, hyperalgesia and nocifensive behaviours were determined in preclinical pain models after administration of LY2969822 0.3–10 mg·kg−1. In addition, the ability of i.v. LY2934747 to modulate dorsal horn spinal cord wide dynamic range (WDR) neurons in spinal nerve ligated (SNL) rats was assessed.Key ResultsFollowing treatment with LY2934747, the spontaneous activity and electrically‐evoked wind‐up of WDR neurons in rats that had undergone spinal nerve ligation and developed mechanical allodynia were suppressed. In a model of sensitization, orally administered LY2969822 prevented the nociceptive behaviours induced by an intraplantar injection of formalin. The on‐target nature of this effect was confirmed by blockade with an mGlu2/3 receptor antagonist. LY2969822 prevented capsaicin‐induced tactile hypersensitivity, reversed the SNL‐induced tactile hypersensitivity and reversed complete Freund's adjuvant – induced mechanical hyperalgesia. The mGlu2/3 receptor agonist prodrug demonstrated efficacy in visceral pain models, including a colorectal distension model and partially prevented the nocifensive behaviours in the mouse acetic acid writhing model.Conclusions and implicationsFollowing oral administration of the prodrug LY2969822, the mGlu2/3 receptor agonist LY2934747 was formed and this attenuated pain behaviours across a broad range of preclinical pain models.
Gender Differences in the Developmental Cascade From Harsh Parenting to Educational Attainment: An Evolutionary Perspective
Authors: Hentges Rochelle F. , Wang Ming‐Te 
Published: February 2017

This study utilized life history theory to test a developmental cascade model linking harsh parenting to low educational attainment. Multigroup models were examined to test for potential gender differences. The sample consisted of 1,482 adolescents followed up for 9 years starting in seventh grade (Mage = 12.74). Results supported indirect links between harsh parenting and low educational attainment through the development of extreme peer orientations, early sexual behavior, and delinquency. Among male adolescents, harsh parenting was related to the development of an extreme peer orientation, which further led to increased delinquency, and subsequently lower educational attainment. Among female adolescents, harsh parenting predicted extreme peer orientations, which increased both delinquency and early sexual behavior. Early sexual behavior further predicted lower educational attainment in female adolescents.
A Sustainability Agenda for Tropical Marine Science
Authors: Partelow Stefan , Schlüter Achim , von Wehrden Henrik , Jänig Manuel , Senff Paula 
Published: February 2017

AbstractTropical coasts face unprecedented sustainability challenges for advancing human welfare and maintaining ecosystem functioning and diversity. These coupled social–ecological processes exist within interdependent relationships across multiple levels and scales. Reflection is needed on the knowledge tropical marine science generates to advance a research agenda for sustainability. In this article we systematically review 753 social and natural science articles conducted within the tropical coastal marine sector. Our results are organized in five themes. (1) The spatial distribution and disciplinary composition of research is not homogeneous across regions. (2) A third of all research lacks a stated problem orientation and coral reefs dominate the ecosystem focus. (3) Research is primarily conducted on selected subgroups of levels and scales. (4) The social and natural sciences focus on a varying diversity of system processes that indicate different degrees of inter‐ and intradisciplinary research. (5) Statistically clustered terminology usage across all articles indicates that distinct research communities exist across a social to natural science gradient. The social and natural sciences generate different types of knowledge associated with terminology at different scales. This analysis attempts to provide a guidepost for discussing the challenges and pathways forward to progress a sustainability agenda in tropical marine science.
Acute physiological effects of glucocorticoids on fuel metabolism in humans are permissive but not direct
Authors: Stimson Roland H. , Anderson Anna J. , Ramage Lynne E. , Macfarlane David P. , de Beaux Andrew C. , Mole Damian J. , Andrew Ruth , Walker Brian R. 
Published: February 2017

Background and aimsThe effects of glucocorticoids on fuel metabolism are complex. Acute glucocorticoid excess promotes lipolysis but chronic glucocorticoid excess causes visceral fat accumulation. We hypothesized that interactions between cortisol and insulin and adrenaline account for these conflicting results. We tested the effect of cortisol on lipolysis and glucose production with and without insulin and adrenaline in humans both in vivo and in vitro.Materials and methodsA total of 20 healthy men were randomized to low and high insulin groups (both n = 10). Subjects attended on 3 occasions and received low (c. 150 nM), medium (c. 400 nM) or high (c. 1400 nM) cortisol infusion in a randomized crossover design. Deuterated glucose and glycerol were infused intravenously along with a pancreatic clamp (somatostatin with replacement of glucagon, insulin and growth hormone) and adrenaline. Subcutaneous adipose tissue was obtained for analysis. In parallel, the effect of cortisol on lipolysis was tested in paired primary cultures of human subcutaneous and visceral adipocytes.ResultsIn vivo, high cortisol increased lipolysis only in the presence of high insulin and/or adrenaline but did not alter glucose kinetics. High cortisol increased adipose mRNA levels of ATGL, HSL and CGI‐58 and suppressed
G0S2. In vitro, high cortisol increased lipolysis in the presence of insulin in subcutaneous, but not visceral, adipocytes.ConclusionsThe acute lipolytic effects of cortisol require supraphysiological concentrations, are dependent on insulin and adrenaline and are observed only in subcutaneous adipose tissue. The resistance of visceral adipose tissue to cortisol's lipolytic effects may contribute to the central fat accumulation observed with chronic glucocorticoid excess.
Steering the Poverty‐Environment Nexus in Central Asia: A metagovernance analysis of the Poverty‐Environment Initiative (PEI)
Authors: Challe Sarah , Christopoulos Stamatios , Kull Michael , Meuleman Louis 
Published: February 2017

AbstractThe close and reciprocal ties between poverty and environmental degradation present significant potential for simultaneous improvement of the livelihood of the poorest along with increased opportunities and enhanced resilience of the environment and natural resources. By supporting governments and other stakeholders in designing and implementing development plans that tackle environmental and poverty concerns in a joint manner, the globally operatingUNDP‐UNEPPoverty‐Environment Initiative (PEI) addresses a major governance challenge for sustainable development (SD) and the Sustainable Development Goals (SDGs) in particular. Focusing on Central Asia, and specifically Tajikistan, a country outside the spotlight of studies concerned withSDgovernance mechanisms, and through the analysis ofPEIprogramme documents and stakeholders’ interviews, this article probes into the governance and governance co‐ordination (metagovernance) settings forSD. The article closes by presenting a set of recommendations to improve governance co‐ordination, while achieving more inclusive decision‐making and ultimately increasing the impact ofPEIon the society and the environment. Specifically, it argues for improved information policy and enhanced integration of endogenous knowledge. Furthermore, national and local development planning and private initiatives should be better linked, and the different levels of governance for poverty‐environment mainstreaming should be more coherent. The solutions discussed are of relevance for wider Central Asia and the global community engaged in moving theSDGs into the mainstream of governance and policy frameworks.
Correlation of platelet‐to‐lymphocyte ratio and neutrophil‐to‐lymphocyte ratio with thrombolysis in myocardial infarction frame count in ST‐segment elevation myocardial infarction
Authors: Vakili Hossein , Shirazi Mahin , Charkhkar Mahsa , Khaheshi Isa , Memaryan Mehdi , Naderian Mohammadreza 
Published: February 2017

AbstractBackgroundImpaired coronary artery reflow after primary percutaneous coronary intervention (PPCI) in patients with ST‐segment elevation myocardial infarction has been associated with postintervention adverse effects. Thus, finding an easily achievable index would be of great value to predict no‐reflow phenomenon. In this regard, platelet‐to‐lymphocyte ratio (PLR) and neutrophil‐to‐lymphocyte ratio (NLR) have been introduced. In this study, we aimed to investigate correlation of PLR and NLR with thrombolysis in myocardial infarction (TIMI) frame count.Materials and methodsA total of 215 consecutive patients with ST‐segment elevation myocardial infarction (STEMI) were recruited. Pre‐intervention laboratory tests were performed. Moreover, PLR and NLR were calculated for each patient. Ultimately, TIMI frame count was assessed subsequent to primary PCI for each patient.ResultsWe found that both PLR and NLR are correlated with TIMI frame count (R: 0·372, P < 0·001 and R: 0·301, P < 0·001, respectively). Furthermore, it was revealed that both PLR and NLR are positively correlated with corrected TIMI frame count (R: 0·388, P < 0·001 and R: 0·290, P < 0·001, respectively).ConclusionsPLR and NLR are two easily calculated and efficient indexes for predicting the no‐reflow phenomenon in patients with STEMI undergoing PPCI. Therefore, they might be employed in accurate risk stratification when a patient is a candidate for PPCI and in accurately referring patients who would benefit greatly from PPCI.
Physiological responses of Eucalyptus spp. hybrids to infection by Ceratocystis fimbriata
Authors: Pimenta L. , Ferreira M. A. , Ribeiro P. M. , Zacaroni L. M. , Mafia R. G. , Resende M. L. V. 
Published: February 2017

SummaryIn Brazil, the selection and planting of eucalyptus clones resistant to Ceratocystis fimbriata is the pre‐eminent control strategy for the wilt pathogen. However, little is known about host defence responses associated with resistance of eucalyptus to C. fimbriata infection. In this work, enzymatic activity, sugars, lignin, total phenols and phenolic compounds involved in the defence response of eucalyptus clones resistant (RC) and susceptible (SC) to the Ceratocystis wilt were evaluated. Changes were detected in the sugars produced by RC clones, with higher concentrations occurring compared with SC. A similar response occurred with lignin content at 28 days after inoculation (dai) in RC plants. SC plants had an increase in polyphenol oxidase and peroxidase activities at 7 dai. In contrast, RC plants demonstrated high activity of the same enzymes at 2 and 4 dai, decreasing afterwards. There was no difference in phenylalanine ammonia‐lyase activity between resistant and susceptible clones. Hydroxycinnamic acid concentration was higher in RC than in SC; however, there was no difference between RC and SC in flavonoid concentrations. RC had high concentrations catechin, chlorogenic acid and caffeic acid. Histochemical tests demonstrated the presence of phenolic compounds and lignin, at higher intensities, in xylem of RC plants. Inoculation with C. fimbriata induced defence responses in both resistant and susceptible eucalyptus clones, but both the intensity and speed of the responses were higher in RC. Alterations in the concentrations of sugars and lignin, as well as certain enzymes and phenolic compounds, could be used to predict the relative susceptibilities to Ceratocystis wilt of different phenotypes of eucalyptus clones.
Development of an implementation guide to facilitate the roll‐out of early intervention services for psychosis
Authors: Hetrick Sarah E. , O'Connor Denise A , Stavely Heather , Hughes Frank , Pennell Kerryn , Killackey Eoin , McGorry Patrick D. 
Published: February 2017

AimOur aim was to develop an implementation guide that was informed by an analysis of context‐specific barriers and enablers, behaviour change theory, as well as evidence about the effects of implementation interventions, for the establishment and scaling up of an early intervention model for psychosis (called Early Psychosis Prevention and Intervention Centre (EPPIC)).MethodsWe used a systematic approach involving four steps. First, the target behaviours of the EPPIC model for implementation were specified. Second, a consultation was undertaken to explore the barriers and enablers to undertaking these priority minimum standard clinical behaviours. Third, an implementation strategy that included a range of behaviour change techniques tailored to address the identified barriers was developed. Finally, a tool to assess whether those implementing the EPPIC model maintained fidelity to the implementation strategy was designed.ResultsWe identified a range of barriers that could act to dilute the core components of the EPPIC model and compromise its implementation. An implementation strategy using theory and evidence‐based strategies for behaviour change was designed to address these barriers.ConclusionsThe process we used in the development of the implementation strategy provided a unique opportunity to consider the essential areas to cover, how to make information easily understandable and accessible while noting the complexity of issues involved in not only implementation, but also the scaling up of the EPPIC model for services.
From Maxwell's equations to the theory of current‐source density analysis
Authors: Gratiy Sergey L. , Halnes Geir , Denman Daniel , Hawrylycz Michael J. , Koch Christof , Einevoll Gaute T. , Anastassiou Costas A. 
Published: February 2017

AbstractDespite the widespread use of current‐source density (CSD) analysis of extracellular potential recordings in the brain, the physical mechanisms responsible for the generation of the signal are still debated. While the extracellular potential is thought to be exclusively generated by the transmembrane currents, recent studies suggest that extracellular diffusive, advective and displacement currents—traditionally neglected—may also contribute considerably toward extracellular potential recordings. Here, we first justify the application of the electro‐quasistatic approximation of Maxwell's equations to describe the electromagnetic field of physiological origin. Subsequently, we perform spatial averaging of currents in neural tissue to arrive at the notion of the CSD and derive an equation relating it to the extracellular potential. We show that, in general, the extracellular potential is determined by the CSD of membrane currents as well as the gradients of the putative extracellular diffusion current. The diffusion current can contribute significantly to the extracellular potential at frequencies less than a few Hertz; in which case it must be subtracted to obtain correct CSD estimates. We also show that the advective and displacement currents in the extracellular space are negligible for physiological frequencies while, within cellular membrane, displacement current contributes toward the CSD as a capacitive current. Taken together, these findings elucidate the relationship between electric currents and the extracellular potential in brain tissue and form the necessary foundation for the analysis of extracellular recordings.
Changes in diet associated with cancer: An evolutionary perspective
Authors: Thomas Frédéric , Rome Sophie , Mery Frédéric , Dawson Erika , Montagne Jacques , Biro Peter A. , Beckmann Christa , Renaud François , Poulin Robert , Raymond Michel , Ujvari Beata 
Published: February 2017

AbstractChanges in diet are frequently correlated with the occurrence and progression of malignant tumors (i.e., cancer) in both humans and other animals, but an integrated conceptual framework to interpret these changes still needs to be developed. Our aim is to provide a new perspective on dietary changes in tumor‐bearing individuals by adapting concepts from parasitology. Dietary changes may occur alongside tumor progression for several reasons: (i) as a pathological side effect with no adaptive value, (ii) as the result of self‐medication by the host to eradicate the tumor and/or to slow down its progression, (iii) as a result of host manipulation by the tumor that benefits its progression, and finally (iv) as a host tolerance strategy, to alleviate and repair damages caused by tumor progression. Surprisingly, this tolerance strategy can be beneficial for the host even if diet changes are beneficial to tumor progression, provided that cancer‐induced death occurs sufficiently late (i.e., when natural selection is weak). We argue that more data and a unifying evolutionary framework, especially during the early stages of tumorigenesis, are needed to understand the links between changes in diet and tumor progression. We argue that a focus on dietary changes accompanying tumor progression can offer novel preventive and therapeutic strategies against cancer.