bluuebunny/crossref_metadata_2025 huggingface dataset:
Pressure‐stabilized maximum‐entropy methods for incompressible Stokes
Authors: Nissen K. , Wall W. A.
Published: November 2015

We present a parameter‐free stable maximum‐entropy method for incompressible Stokes flow. Derived from a least‐biased optimization inspired by information theory, the meshfree maximum‐entropy method appears as an interesting alternative to classical approximation schemes like the finite element method. Especially compared with other meshfree methods, e.g. the moving least‐squares method, it allows for a straightforward imposition of boundary conditions. However, no Eulerian approach has yet been presented for real incompressible flow, encountering the convective and pressure instabilities. In this paper, we exclusively address the pressure instabilities caused by the mixed velocity‐pressure formulation of incompressible Stokes flow. In a preparatory discussion, existing stable and stabilized methods are investigated and evaluated. This is used to develop different approaches towards a stable maximum‐entropy formulation. We show results for two analytical tests, including a presentation of the convergence behavior. As a typical benchmark problem, results are also shown for the leaky lid‐driven cavity. The already presented information‐flux method for convection‐dominated problems in mind, we see this as the last step towards a maximum‐entropy method capable of simulating full incompressible flow problems. Copyright © 2015 John Wiley & Sons, Ltd.
The Effect of Nonlinearity between Credit Conditions and Economic Activity on Density Forecasts
Authors: Franta Michal
Published: November 2015

This paper examines the effect of nonlinearities on density forecasting. It focuses on the relationship between credit markets and the rest of the economy. The possible nonlinearity of this relationship is captured by a threshold vector autoregressive model estimated on US data using Bayesian methods. Density forecasts thus account for the uncertainty in all model parameters and possible future regime changes. It is shown that considering nonlinearity can improve the probabilistic assessment of the economic outlook. Moreover, three illustrative examples are discussed to shed some light on the possible practical applicability of density forecasts derived from non‐linear models. Copyright © 2015 John Wiley & Sons, Ltd.
International long‐term trends and recent patterns in the incidence of leukemias and lymphomas among children and adolescents ages 0–19 years
Authors: Linet Martha S. , Brown Linda M. , Mbulaiteye Sam M. , Check David , Ostroumova Evgenia , Landgren Annelie , Devesa Susan S.
Published: November 2015

To enhance understanding of etiology, we examined international population‐based cancer incidence data for lymphoid leukemia, non‐Hodgkin lymphoma, Hodgkin lymphoma and myeloid leukemia among children aged 0–19. Based on temporal trends during 1978–2007 in 24 populations, lymphoid leukemia and myeloid leukemia incidence rates generally have not changed greatly and differences in rates for non‐Hodgkin and for Hodgkin lymphoma have diminished in some regions. Lymphoid leukemia rates during 2003–2007 in 54 populations varied about 10‐fold, with rates highest in US white Hispanics (50.2 per million person‐years) and Ecuador (48.3) and lowest in US blacks (20.4), Tunisia (17.7) and Uganda (6.9). Non‐Hodgkin lymphoma rates varied 30‐fold, with very high rates in sub‐Saharan Africa (146.0 in Malawi and 54.3 in Uganda) and low rates (≤10) in some Asian populations (China, Japan, India, the Philippines and Thailand) and U.S. Asian‐Pacific Islanders, eastern and northern European populations and Puerto Rico. Hodgkin lymphoma rates varied 15‐fold, with rates highest in Italy (21.3) and lowest in China (1.7) . Myeloid leukemia rates varied only about fivefold, with rates highest in the Philippines and Korea (exceeding 14.0) and lowest in Eastern Europe (5.9 in Serbia and 5.3 in the Czech Republic) and Uganda (2.7). The boy/girl average incidence rate ratios were 2.00 or lower. Age‐specific patterns differed among the four hematopoietic malignancies, but were generally consistent within major categories world‐wide, except for non‐Hodgkin lymphoma. A systematic world‐wide approach comparing postulated etiologic factors in low‐ versus high‐risk populations may help clarify the etiology of these childhood malignancies.
DIRECT‐ID: An automated method to identify and quantify conformational variations—application to β2‐adrenergic GPCR
Authors: Lakkaraju Sirish Kaushik , Lemkul Justin A. , Huang Jing , MacKerell Alexander D.
Published: November 2015

The conformational dynamics of a macromolecule can be modulated by a number of factors, including changes in environment, ligand binding, and interactions with other macromolecules, among others. We present a method that quantifies the differences in macromolecular conformational dynamics and automatically extracts the structural features responsible for these changes. Given a set of molecular dynamics (MD) simulations of a macromolecule, the norms of the differences in covariance matrices are calculated for each pair of trajectories. A matrix of these norms thus quantifies the differences in conformational dynamics across the set of simulations. For each pair of trajectories, covariance difference matrices are parsed to extract structural elements that undergo changes in conformational properties. As a demonstration of its applicability to biomacromolecular systems, the method, referred to as DIRECT‐ID, was used to identify relevant ligand‐modulated structural variations in the β2‐adrenergic (β2AR) G‐protein coupled receptor. Micro‐second MD simulations of the β2AR in an explicit lipid bilayer were run in the apo state and complexed with the ligands: BI‐167107 (agonist), epinephrine (agonist), salbutamol (long‐acting partial agonist), or carazolol (inverse agonist). Each ligand modulated the conformational dynamics of β2AR differently and DIRECT‐ID analysis of the inverse‐agonist vs. agonist‐modulated β2AR identified residues known through previous studies to selectively propagate deactivation/activation information, along with some previously unidentified ligand‐specific microswitches across the GPCR. This study demonstrates the utility of DIRECT‐ID to rapidly extract functionally relevant conformational dynamics information from extended MD simulations of large and complex macromolecular systems. © 2015 Wiley Periodicals, Inc.
Moment expansion of the linear density‐density response function
Authors: Scherrer Arne , Sebastiani Daniel
Published: November 2015

We present a low rank moment expansion of the linear density‐density response function. The general interacting (fully nonlocal) density‐density response function is calculated by means of its spectral decomposition via an iterative Lanczos diagonalization technique within linear density functional perturbation theory. We derive a unitary transformation in the space of the eigenfunctions yielding subspaces with well‐defined moments. This transformation generates the irreducible representations of the density‐density response function with respect to rotations within SO(3). This allows to separate the contributions to the electronic response density from different multipole moments of the perturbation. Our representation maximally condenses the physically relevant information of the density‐density response function required for intermolecular interactions, yielding a considerable reduction in dimensionality. We illustrate the performance and accuracy of our scheme by computing the electronic response density of a water molecule to a complex interaction potential. © 2015 Wiley Periodicals, Inc.
Attracting cavities for docking. Replacing the rough energy landscape of the protein by a smooth attracting landscape
Authors: Zoete Vincent , Schuepbach Thierry , Bovigny Christophe , Chaskar Prasad , Daina Antoine , Röhrig Ute F. , Michielin Olivier
Published: November 2015

Molecular docking is a computational approach for predicting the most probable position of ligands in the binding sites of macromolecules and constitutes the cornerstone of structure‐based computer‐aided drug design. Here, we present a new algorithm called Attracting Cavities that allows molecular docking to be performed by simple energy minimizations only. The approach consists in transiently replacing the rough potential energy hypersurface of the protein by a smooth attracting potential driving the ligands into protein cavities. The actual protein energy landscape is reintroduced in a second step to refine the ligand position. The scoring function of Attracting Cavities is based on the CHARMM force field and the FACTS solvation model. The approach was tested on the 85 experimental ligand–protein structures included in the Astex diverse set and achieved a success rate of 80% in reproducing the experimental binding mode starting from a completely randomized ligand conformer. The algorithm thus compares favorably with current state‐of‐the‐art docking programs. © 2015 The Authors. Journal of Computational Chemistry Published by Wiley Periodicals, Inc.
As‐needed intravenous antihypertensive therapy and blood pressure control
Authors: Lipari Melissa , Moser Lynette R. , Petrovitch Elizabeth A. , Farber Margo , Flack John M.
Published: November 2015

BACKGROUND

Hospitalized patients with elevated blood pressure (BP) in most cases should be treated with intensification of oral regimens, but are often given intravenous (IV) antihypertensives.

OBJECTIVE

To determine frequency of prescribing and administering episodic IV antihypertensives and outcomes.

DESIGN

Retrospective review.

SETTING

Urban academic hospital.

PATIENTS

Non–critically ill, hospitalized patients with an IV antihypertensive order for enalaprilat, labetalol, hydralazine, or metoprolol.

MEASUREMENTS

We analyzed BP thresholds for ordering and administering IV antihypertensives, the types and frequencies of IV antihypertensives administered, and the effect of IV antihypertensive use on short‐term BP and adverse outcomes. The BP change during hospitalization was contrasted in those receiving IV antihypertensives between those who did and did not receive subsequent intensification of chronic oral antihypertensive regimens.

RESULTS

Two hundred forty‐six patients had an episodic IV antihypertensive order. One hundred seventy‐two patients received 458 doses, with 48% receiving a single dose. Over 98% of episodic IV antihypertensive doses were administered for systolic blood pressure (SBP) <200 mm Hg and 84.5% for SBP <180 mm Hg. Within 6 hours of administration, there was a statistically significant decline in average SBP and diastolic BP in patients receiving IV hydralazine and labetolol. After administration of IV antihypertensives, the oral inpatient medication regimen was adjusted in 52% of patients; these patients had a greater reduction in SBP from admission to discharge than patients with no change to their oral regimens. A total of 32.6% of patients receiving treatment experienced a BP reduction of more than 25% within 6 hours.

CONCLUSIONS

IV antihypertensive drugs are ordered and administered in patients with asymptomatic, uncontrolled BP for levels unassociated with substantive immediate cardiovascular risk, which may cause adverse effects. Journal of Hospital Medicine 2016;11:193–198. © 2015 Society of Hospital Medicine
Development of antimicrobial active packaging materials based on gluten proteins
Authors: Gómez‐Heincke Diana , Martínez Inmaculada , Partal Pedro , Guerrero Antonio , Gallegos Críspulo
Published: November 2015

BACKGROUND

The incorporation of natural biocide agents into protein‐based bioplastics, a source of biodegradable polymeric materials, manufactured by a thermo‐mechanical method is a way to contribute to a sustainable food packaging industry. This study assesses the antimicrobial activity of 10 different biocides incorporated into wheat gluten‐based bioplastics. The effect that formulation, processing, and further thermal treatments exert on the thermo‐mechanical properties, water absorption characteristics and rheological behaviour of these materials is also studied.

RESULTS

Bioplastics containing six of the 10 examined bioactive agents have demonstrated suitable antimicrobial activity at 37 °C after their incorporation into the bioplastic. Moreover, the essential oils are able to create an antimicrobial atmosphere within a Petri dish.

CONCLUSION

Depending on the selected biocide, its addition may alter the bioplastics protein network in a different extent, which leads to materials exhibiting less water uptake and different rheological and thermo‐mechanical behaviours. © 2015 Society of Chemical Industry
In situ calibration of meteorological sensor in Himalayan high mountain environment
Authors: Merlone Andrea , Roggero Guido , Verza Gian Pietro
Published: November 2015

A dedicated facility for in situ calibration of weather stations has been installed in the Everest Pyramid Laboratory/Observatory at an altitude of 5050 m in the Khumbu Valley, on the Nepalese side of Mount Everest. This highest metrology laboratory in the world represents a fruitful collaboration between metrological and environmental sciences. The common goal is the improvement of data quality and the reliability of climate monitoring. High altitude extreme environmental observations are of high scientific relevancy, underlining the advantages of performing in situ instrument calibration to make measurements fully traceable to standards. In establishing such a laboratory in extreme conditions, the involved staff had to face several challenges: weight of the system components for the eventual transport by human porters, modification to ‘off the shelf equipment’, special procedures and optimization of power request, reduced room available, properties of fluids at high altitude and many more.

The work and the mission reported are tasks of the MeteoMet project, which are presented here together with the organizations involved. The calibration chamber, the calibration procedure and the results of the first calibration campaign are then presented with full uncertainty analysis.

The capabilities achieved, together with the trained staff and dedicated procedures, now allow calibration and checking of the instruments positioned all along the Khumbu Valley, up to the Everest South Col at 8000 m, more frequently, with less difficulties and with reduced loss of time. Future plans include the extension of the calibration capabilities to soil, ice, permafrost and lake water temperature sensors.
Measuring Social Enterprise Value Creation
Authors: Mook Laurie , Chan Andrea , Kershaw Dan
Published: November 2015

This article presents a case study that explores the creation of value by a social enterprise, Furniture Bank, for its stakeholders. The study is undertaken using the social return on investment framework. The case highlights insights and caveats that resulted from undertaking this type of analysis. This article calls for an integrated approach to social return on investment processes, incorporating both conventional accounting and social accounting.
Social Return on Investment for Good Foot Delivery
Authors: Vieta Marcelo , Schatz Naomi , Kasparian Greg
Published: November 2015

This article provides reflections on a social return on investment (SROI) research process with Good Foot Delivery, a work integration social enterprise in Toronto, Canada, engaged in package delivery and employing people with developmental challenges. The article has three aims: (1) to assess Good Foot's key business inputs, activities, and outputs, and the social impact that these have had on its key stakeholders for the 2013 calendar year; (2) to critically reflect on how the research team arrived at the SROI’s inputs, outputs, outcomes, proxies, and other findings; and (3) to discuss some of the strengths and challenges of the SROI process in practice.
Ensure veterans' success on campus by starting before enrollment
Authors: Sutton Halley
Published: November 2015

SAN DIEGO — Given the wide differences among student‐veterans in college preparedness, life experience and academic background, having a college campus fully equipped to service student‐veterans after active duty may mean enlisting the help of outside organizations. In a session at the recent National Association for College Admission Counseling annual conference, representatives from Yale University as well as the nonprofits Service to School and the Warrior‐Scholar Project focused on best practices for preparing and helping veterans enter higher education post‐service.
How do you control the amount of time you spend in meetings?
Authors: Hope Joan
Published: November 2015

Sometimes at the end of the day, you look back and think that all you did was go to meetings. Some of them were productive. And you know it's important to collaborate, keep communication open, and get buy‐in for important initiatives. But some of those meetings were a waste of time. What would you do?
Reports provide snapshot of national trends for tuition, awarded degrees
Authors: Sutton Halley
Published: November 2015

The National Center for Education Statistics released three different reports of interest to officials engaged in educating adults.
Inline quality rating of multi‐crystalline wafers based on photoluminescence images
Authors: Demant Matthias , Rein Stefan , Haunschild Jonas , Strauch Theresa , Höffler Hannes , Broisch Juliane , Wasmer Sven , Sunder Kirsten , Anspach Oliver , Brox Thomas
Published: November 2015

The quality assessment of multi‐crystalline and high‐performance multi‐crystalline silicon wafers during incoming inspection of solar cell production requires a reproducible description of the relevant material defects and a classification scheme that is capable to rate as‐cut wafers from unknown manufacturers. Both needs are addressed in this work. We introduce an image processing framework that allows the various types of crystallization‐related defects visible in photoluminescence images to be detected quantitatively and thus enables a complete wafer description in terms of defects. The importance of different features within this defect characteristic is weighted by predicting the open‐circuit voltage of solar cells with aluminum back‐surface field as well as passivated emitter and rear cells with a stepwise extension of the model. The resulting robust classification scheme is successfully evaluated on a set of 7500 wafers, which represents the whole spectrum of material types and qualities that are currently available at the market. A comparison of defect signatures in high‐performance multi‐crystalline and standard multi‐crystalline silicon materials underlines the relevance of additional features. As a result of this paper, we show that a regularized version of multi‐linear regression models for quality prediction can optimize simpler linear models by adding selected features to the defect characteristic leading to mean absolute prediction errors of 2.2 mV for solar cells with aluminum back‐surface field and 2.9 mV for passivated emitter and rear cells solar cells in a true blind test. Copyright © 2015 John Wiley & Sons, Ltd.
Aminothiazonaphthalic anhydride derivatives as photoinitiators for violet/blue LED‐Induced cationic and radical photopolymerizations and 3D‐Printing resins
Authors: Zhang Jing , Dumur Frédéric , Xiao Pu , Graff Bernadette , Gigmes Didier , Pierre Fouassier Jean , Lalevée Jacques
Published: November 2015

The cations and radicals produced in aminothiazonaphthalic anhydride derivatives (ATNAs) combined with an iodonium salt, N‐vinylcarbazole, amine, or chloro triazine initiate the ring‐opening cationic polymerization of epoxides and the free radical polymerization of acrylates under LEDs at 405 or 455 nm. The photoinitiating ability of these novel photoinitiating systems is higher than that of the well‐known camphorquinone‐based systems. An example of the high reactivity of the new proposed photoinitiator is also provided in resins for 3D‐printing using a LED projector@405 nm. The chemical mechanisms are investigated by steady‐state photolysis, cyclic voltammetry, fluorescence, laser flash photolysis, and electron spin resonance spin‐trapping techniques. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 1189–1196
Blue to light gray electrochromic polymers from dodecyl‐derivatized thiophene Bis‐substituted dibenzothiophene/dibenzofuran
Authors: Lin Kaiwen , Zhao Yao , Ming Shouli , Liu Hongtao , Zhen Shijie , Xu Jingkun , Lu Baoyang
Published: November 2015

3‐Dodecylthiophene end‐capped two monomers: 2,8‐bis‐(4‐dodecyl‐thiophen‐2‐yl)‐dibenzothiophene (DBT‐3DTh) and 2,8‐bis‐(4‐dodecyl‐thiophen‐2‐yl)‐dibenzofuran (DBF‐3DTh) were synthesized via Stille coupling reaction. Both monomers exhibited emission peaks at about 400 nm with fluorescence quantum yields ranging from 0.16 to 0.21. The corresponding electroactive polymers poly(2,8‐bis‐(4‐dodecyl‐thiophen‐2‐yl)‐dibenzothiophene) (PDBT‐3DTh) and poly(2,8‐bis‐(4‐dodecyl‐thiophen‐2‐yl)‐dibenzofuran) (PDBF‐3DTh) were obtained by electropolymerization method and displayed good electrochemical stability. Both polymers switched between light gray in the neutral state and blue in the oxidized state. Kinetic investigations showed that PDBT‐3DTh exhibited a maximum optical contrast (ΔT %) of 25.23% at 575 nm with the coloration efficiency (CE) of 196 cm2 C−1. However, the electrochromic properties of PDBF‐3DTh were inferior to PDBT‐3DTh. Further detailed discussions with EDOT and 3‐alkylthiophenes end‐capped DBT/DBF hybrid electrochromic polymers were comparatively studied. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 1468–1478
A low cost, large area light soaking and testing station
Authors: Ogulgonen Guvenc , Kincal Serkan
Published: November 2015

Test stations for accelerated aging tests are crucial in the development of commercial solar panel manufacturing technologies. Such test‐beds must provide a reasonably uniform flux whose spectral distribution is an acceptable match to the solar spectrum. This work outlines the detailed design on a low cost test system based on metal‐ halide lamps that can deliver a simulated solar flux of up to 3 suns on a 100 cm by 100 cm square area with an intensity variation of around 15%. A total of 9 metal‐halide lamps, each rated at 1000 W, is placed on top an enclosure which has a sample holding table whose distance to the lamps can be adjusted anywhere between 10 cm and 70 cm. A series of fans, blow ambient air over the panels being tested in order to maintain surface temperatures. The system is complemented by the necessary instrumentation to capture IV curves simultaneously for up to 8 solar devices. A model based design strategy is adopted during the construction of the test station in order to predict and optimize the light distribution as well as the thermal behaviour. Sample IV data from commercial thin film Si solar cells are reported to demonstrate the stability of operation. The cost of the entire system is below $ 20,000, with most of the budget going towards the data acquisition hardware. (© 2015 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
A Multi‐functional Biofilm Used as an Active Insert in Modified Atmosphere Packaging for Fresh Produce
Authors: Wang Hong Jiang , An Duck Soon , Rhim Jong‐Whan , Lee Dong Sun
Published: November 2015

We developed a multi‐functional agar‐based biofilm for fresh produce packaging by modulating its CO2 absorption and water vapour absorption functions. The film was prepared from solutions containing agar as a matrix and a water vapour absorbent, glycerol as a plasticizer, and sodium carbonate (SC) and/or sodium glycinate (SG) as a CO2 absorbent. The optical, mechanical, and CO2 and water vapour absorption properties of SC, SG, and SC/SG films were investigated. Multi‐functional films tended to show poor mechanical properties, with a hard texture and an opaque and yellowish colour. The three films had different CO2 absorption capacities and coefficients, with SC film showing the highest absorption, followed by SC/SG and SG films. The water absorption coefficients were much higher than those of CO2, with the opposite dependence on the absorbent compound. The multi‐functional benefits of the developed film were shown by using the film for modified atmosphere packaging (MAP) of shiitake mushrooms as an insert label. A tailored MAP design for shiitake mushrooms was produced based on mass transfer mathematical models. The package attached with SC film label was capable of generating the desired internal atmosphere and thus showed the best quality preservation in terms of colour, firmness, flavour score, and bacterial growth after 5‐day storage. A tailored MAP system with our multi‐functional film can provide an optimal modified atmosphere for CO2‐sensitive fresh commodities, preserve their quality, and extend their shelf life. Copyright © 2015 John Wiley & Sons, Ltd.
Box Compression Strength: A Crippling Approach
Authors: Linvill Eric
Published: November 2015

A crippling analysis method has been utilized to estimate the compression strength paperboard boxes. Crippling analysis is typically utilized in the aerospace industry to predict the compressive failure strength of thin, slender structures with complex cross‐sectional geometry. This type of analysis is investigated, because crippling is a simple, predictive method that can provide very good estimates of the compressive failure strength of thin, slender structures. This preliminary study investigates the possibility of applying crippling analysis to estimate paperboard box compression strength by comparing experimental and theoretical results for box compression tests of milk and cigarette boxes in various loading scenarios and with various materials. This preliminary study shows that the crippling method provides results which are almost as accurate as pre‐existing methods, although significant work remains to verify the validity and applicability of the crippling approach for paper‐based boxes. Copyright © 2015 John Wiley & Sons, Ltd.
The different paths for renewable energies in Latin American Countries: the relevance of the enabling frameworks and the design of instruments
Authors: Recalde Marina Yesica
Published: November 2015

The promotion of renewable energy is a priority for the majority of the regions of the world. The key motivation for the promotion of these sources varies according to the countries; in some cases, the aim is to mitigate climate change, in some others is to address the growing energy demand, or to reduce the dependence on imported fossil fuels. To this purpose, governments implement different energy policies, based on a combination of primary and secondary instruments. Nevertheless, the performance of the policy will depend on the policy design and the enabling environment of the policy, e.g., macroeconomic conditions, political and regulatory risk, and financial sources. During the last decades, many Latin American and Caribbean countries have implemented energy policies to promote renewable electricity. Many of these countries have used a similar combination of support instruments (feed‐in laws, targets, auctions, investment subsidies, etc.). However, the results are very dissimilar. In some cases, similar policies, and even the same instruments led to significant increases in renewable energies, while in other cases the impact has been very small. The aim of this study is to review the recent application of energy policies to renewable energies in a group of South American countries and to analyze whether the performance of the policy is due to policy incentives or enabling environment. WIREs Energy Environ 2016, 5:305–326. doi: 10.1002/wene.190

This article is categorized under:

Energy and Climate > Economics and Policy

Energy Policy and Planning > Economics and Policy

Energy and Development > Climate and Environment
Modeling calcium regulation of contraction, energetics, signaling, and transcription in the cardiac myocyte
Authors: Winslow Raimond L. , Walker Mark A. , Greenstein Joseph L.
Published: November 2015

Calcium (Ca2+) plays many important regulatory roles in cardiac muscle cells. In the initial phase of the action potential, influx of Ca2+ through sarcolemmal voltage‐gated L‐type Ca2+ channels (LCCs) acts as a feed‐forward signal that triggers a large release of Ca2+ from the junctional sarcoplasmic reticulum (SR). This Ca2+ drives heart muscle contraction and pumping of blood in a process known as excitation–contraction coupling (ECC). Triggered and released Ca2+ also feed back to inactivate LCCs, attenuating the triggered Ca2+ signal once release has been achieved. The process of ECC consumes large amounts of ATP. It is now clear that in a process known as excitation–energetics coupling, Ca2+ signals exert beat‐to‐beat regulation of mitochondrial ATP production that closely couples energy production with demand. This occurs through transport of Ca2+ into mitochondria, where it regulates enzymes of the tricarboxylic acid cycle. In excitation–signaling coupling, Ca2+ activates a number of signaling pathways in a feed‐forward manner. Through effects on their target proteins, these interconnected pathways regulate Ca2+ signals in complex ways to control electrical excitability and contractility of heart muscle. In a process known as excitation–transcription coupling, Ca2+ acting primarily through signal transduction pathways also regulates the process of gene transcription. Because of these diverse and complex roles, experimentally based mechanistic computational models are proving to be very useful for understanding Ca2+ signaling in the cardiac myocyte. WIREs Syst Biol Med 2016, 8:37–67. doi: 10.1002/wsbm.1322

This article is categorized under:

Biological Mechanisms > Cell Signaling

Analytical and Computational Methods > Computational Methods

Models of Systems Properties and Processes > Mechanistic Models
Systems biology approaches for identifying adverse drug reactions and elucidating their underlying biological mechanisms
Authors: Boland Mary Regina , Jacunski Alexandra , Lorberbaum Tal , Romano Joseph D. , Moskovitch Robert , Tatonetti Nicholas P.
Published: November 2015

Small molecules are indispensable to modern medical therapy. However, their use may lead to unintended, negative medical outcomes commonly referred to as adverse drug reactions (ADRs). These effects vary widely in mechanism, severity, and populations affected, making ADR prediction and identification important public health concerns. Current methods rely on clinical trials and postmarket surveillance programs to find novel ADRs; however, clinical trials are limited by small sample size, whereas postmarket surveillance methods may be biased and inherently leave patients at risk until sufficient clinical evidence has been gathered. Systems pharmacology, an emerging interdisciplinary field combining network and chemical biology, provides important tools to uncover and understand ADRs and may mitigate the drawbacks of traditional methods. In particular, network analysis allows researchers to integrate heterogeneous data sources and quantify the interactions between biological and chemical entities. Recent work in this area has combined chemical, biological, and large‐scale observational health data to predict ADRs in both individual patients and global populations. In this review, we explore the rapid expansion of systems pharmacology in the study of ADRs. We enumerate the existing methods and strategies and illustrate progress in the field with a model framework that incorporates crucial data elements, such as diet and comorbidities, known to modulate ADR risk. Using this framework, we highlight avenues of research that may currently be underexplored, representing opportunities for future work. WIREs Syst Biol Med 2016, 8:104–122. doi: 10.1002/wsbm.1323

This article is categorized under:

Biological Mechanisms > Chemical Biology

Analytical and Computational Methods > Computational Methods

Translational, Genomic, and Systems Medicine > Translational Medicine
Ligand‐induced expansion of the S1′ site in the anthrax toxin lethal factor
Authors: Maize Kimberly M. , Kurbanov Elbek K. , Johnson Rodney L. , Amin Elizabeth Ambrose , Finzel Barry C.
Published: November 2015

The Bacillus anthracis lethal factor (LF) is one component of a tripartite exotoxin partly responsible for persistent anthrax cytotoxicity after initial bacterial infection. Inhibitors of the zinc metalloproteinase have been investigated as potential therapeutic agents, but LF is a challenging target because inhibitors lack sufficient selectivity or possess poor pharmaceutical properties. These structural studies reveal an alternate conformation of the enzyme, induced upon binding of specific inhibitors, that opens a previously unobserved deep pocket termed S1′∗ which might afford new opportunities to design selective inhibitors that target this subsite.
Controlling the Midfield: Treating Patients With Chronic Pain Using Alternative Payment Models
Authors: Haig Andrew J.
Published: November 2015

The entire American health care system is turning upside down, except for the parts that aren't— yet. For physiatrists who manage pain problems, the future is complex. The usual challenge of treating these devastating and costly problems that cannot be measured physiologically is compounded by the requirement to do so in a health care system that doesn't know what it wants to be yet. Payment, regulation, and the very structure of practice are changing at a pace that is halting and unpredictable. Nonetheless, knowledge about some structures is necessary, and some themes almost certainly emerge. I propose that the role of the pain physiatrist is best understood through a soccer analogy. Whereas the casual spectator of the past might note the goals scored by surgical colleagues and shots missed by primary care partners, sophisticated health care systems of the future will learn that the pain game is won by creating a strong physiatry midfield. Physiatrists can reach to the backfield to help primary care with tough cases, send accurate referrals to surgeons, and reorganize the team when chronic pain complicates the situation. Current and emerging payment structures include insurance from government, employers, or individuals. Although the rules may change, certain trends appear to occur: Individuals will be making more choices, deductibles will increase, narrow groups of practitioners will work together, pricing will become important, and the burden on primary care colleagues will increase. Implications of each of these trends on pain medicine and specific strategy examples are addressed. A general concept emerges that, although procedure‐ and activity‐based practice is still important, pain physiatrists can best prepare for the future by leading programs that create value for their health care system.
Current Regulations Related to Opioid Prescribing
Authors: Webster Lynn R. , Grabois Martin
Published: November 2015

It is the responsibility of medical professionals to do all that is possible to safely alleviate pain. Opioids are frequently prescribed for pain but are associated with the potential for misuse, addiction, diversion, and overdose mortality, and thus they are strictly regulated. To adhere to legitimate practice standards, physicians and other health care providers who prescribe opioids for pain, particularly on a long‐term basis, need current information on federal and state laws, treatment guidelines, and regulatory actions aimed at reducing opioid‐related harm. The number of opioid‐prescribing policies is increasing as federal and state governments increase scrutiny to alleviate opioid‐related problems in society. Failure to adequately comply with opioid‐prescribing laws and policies may put a prescriber at risk for legal or regulatory sanctions. Necessary actions include thorough documentation of prescribing decisions and assessment and follow‐up of patient risk for opioid misuse or addiction. Tools to check for patient adherence to the prescribed regimen include prescription monitoring databases and urine drug screening. This article presents an overview of the legal and regulatory framework surrounding controlled substances law. It further discusses recent actions at the federal and state level to prevent opioid‐related harm.
Assessing and Treating Patients With Neuropathic Pain
Authors: Scholten Paul M. , Harden R. Norman
Published: November 2015

Neuropathic pain (NP) is a significant source of suffering, disability, and impairment, as well as an enormous cost to society. Historically, pharmacologic treatment has been limited to drugs approved for other conditions, including anticonvulsants, antidepressants, antiarrhythmics, and opioids, but in the past 2 decades several drugs have been approved by the Food and Drug Administration specifically for NP. Understanding the underlying pathophysiology and clinical presentation of the various causes of NP states facilitates a rational selection of pharmacologic, interventional, rehabilitative, and psychological options for reducing pain and maximizing function.
How to Maximize Patient Safety When Prescribing Opioids
Authors: Kirpalani Dhiruj
Published: November 2015

Opioid prescribing and deaths in the United States have increased exponentially in the past couple of decades. This increase has occurred amidst growing awareness of the lack of long‐term efficacy of opioids, as well as the significant long‐ and short‐term risks associated with these medications. The scope of the opioid epidemic has led to the development of extensive clinical screening and monitoring tools recommended for health care providers who prescribe opioids to patients for chronic nonmalignant pain. The purpose of this review is to summarize the latest guidelines and evidence that will assist in maximizing patient safety while using chronic opioid therapy as part of pain management.
Managing Chronic Pain in Children and Adolescents: A Clinical Review
Authors: Landry Bradford W. , Fischer Philip R. , Driscoll Sherilyn W. , Koch Krista M. , Harbeck‐Weber Cynthia , Mack Kenneth J. , Wilder Robert T. , Bauer Brent A. , Brandenburg Joline E.
Published: November 2015

Chronic pain in children and adolescents can be difficult for a single provider to manage in a busy clinical setting. Part of this difficulty is that pediatric chronic pain not only impacts the child but also the families of these children. In this review article, we discuss etiology and pathophysiology of chronic pain, along with variables that impact the severity of chronic pain and functional loss. We review diagnosis and management of selected chronic pain conditions in pediatric patients, including headache, low back pain, hypermobility, chronic fatigue, postural orthostatic tachycardia syndrome, abdominal pain, fibromyalgia, and complex regional pain syndrome. For each condition, we create a road map that contains therapy prescriptions, exercise recommendations, and variables that may influence pain severity. Potential medications for these pain conditions and associated symptoms are reviewed. A multidisciplinary approach for managing children with these conditions, including pediatric pain rehabilitation programs, is emphasized. Lastly, we discuss psychological factors and interventions for pediatric chronic pain and potential complementary and alternative natural products and interventions.
Étude des facteurs hospitaliers associés aux départs avant prise en charge médicale à l’urgence d’un centre hospitalier de soins tertiaires
Authors: Elazhary Nicolas , Dolbec Marie-Laure , Boucher Thierry , Deshaies Jean-François , Vanasse Alain , Beaudoin René
Published: November 2015

Objectif

L’objectif de cette étude rétrospective était d’identifier les facteurs associés aux décomptes quotidiens de départs avant prise en charge médicale (DAPCM) dans les deux salles d’urgence du Centre hospitalier universitaire de Sherbrooke, Fleurimont (HF) et Hôtel-Dieu (HD).

Méthode

Des données cliniques et démographiques anonymisées, ainsi que des données hospitalières, ont été extraites de la banque de données du Centre Informatisé de Recherche Évaluative en Services et Soins de Santé pour la période du 1er avril 2011 au 30 juin 2012. Les variables étant corrélées au nombre de DAPCM par jour par site lors des analyses univariées ont été retenues pour l’analyse de régression linéaire multivariée.

Résultats

Les analyses de régression multivariées démontrent que le nombre de DAPCM par jour diminue pour les deux sites lorsque la durée moyenne de séjour des patients non hospitalisés à l’urgence diminue (HF:b=1,17, p<0,001; HD:b=1,41, p<0,001) et lorsqu’un médecin dédié aux patients ambulatoires est présent (HF:b=-4,35, p<0,001; HD:b=-5,48, p<0,001). De plus, des facteurs reliés à l’achalandage des salles d’urgence et la raison primaire de consultation ont également eu un effet sur le nombre de DAPCM par jour.

Conclusion

Des efforts devraient être faits afin de diminuer la durée moyenne de séjour des patients non hospitalisés à l’urgence et d’assurer la présence d’un médecin dédié aux patients ambulatoires pour diminuer le nombre de DAPCM.
Methods of preservation and flotation for the detection of nematode eggs and coccidian oocysts in faeces of the forest musk deer
Authors: Hu X.L. , Liu G. , Wang W.X. , Zhou R. , Liu S.Q. , Li L.H. , Hu D.F.
Published: November 2015

Parasitic infections influence the health of captive forest musk deer (Moschus berezovskii) and affect population increases. Nevertheless, there are few quantitative studies regarding forest musk deer parasites, and there is no common preservation method or flotation solution used for detection of faecal parasites because of the biology of the worms and the host physiological state. The objective of this study was to evaluate preservation and flotation methods for the detection of nematode eggs and coccidian oocysts in faeces of the forest musk deer. The McMaster technique was used to count nematode eggs and coccidian oocysts in 33 samples of faeces. For the nematode eggs, the differences among flotation solutions were significant (P< 0.01), with sodium nitrate being the best flotation solution, and the combination of freezing and sodium nitrate resulted in the greatest number of eggs per gram (EPG = 209.4 ± 67.8). For the coccidian oocysts, the interaction between preservation method and flotation solution was significant (P< 0.01), and the combination of formalin and sodium chloride yielded the greatest number of oocysts per gram (OPG = 1010.7 ± 162.3). The forest musk deer had a high prevalence of parasitic infections, with the parasite load of coccidia (96.4%) significantly greater than that of nematodes (71.9%, P< 0.01). These results confirm that captive forest musk deer suffer from serious parasitic invasions and demonstrate that the novel method described here could be utilized for parasitological diagnosis, detection and prevention in species of Moschidae and Cervidae.
Land Requisitions and State–Village Power Restructuring in Southern China
Authors: Wong Siu Wai
Published: November 2015

Land requisitions for urban development have led to a rapid growth of wealthy, autonomous villages in southern China. However, the underlying causes of this emerging phenomenon and its impact on local governance have been largely unexplored by the existing literature. Through an in-depth analysis of the contestations and negotiations between the local state and villagers when dealing with the various problems arising from land compensation, this study explains how and why land requisitions strengthened the collective power of villagers in defending their rightful interests. This bolstered power has in turn forced the local state constantly to adjust its tactics when addressing the needs of villagers in order to avoid widespread conflicts and potential social unrest. The findings provide new insights into the complexities of land conflicts and their actual impact on state–village power restructuring in southern China.
Quality of life in adolescents and young adults with CHD is not reduced: a systematic review and meta-analysis
Authors: Schrøder Morten , Boisen Kirsten A. , Reimers Jesper , Teilmann Grete , Brok Jesper
Published: November 2015

Purpose

We performed a systematic review and meta-analysis of observational studies assessing quality of life in adolescents and young adults born with CHD compared with age-matched controls.

Methods

We carried out a systematic search of the literature published in Medline, Embase, PsychINFO, and the Cochrane Library’s Database (1990–2013); two authors independently extracted data from the included studies. We used the Newcastle–Ottawa scale for quality assessment of studies. A random effects meta-analysis model was used. Heterogeneity was assessed using the I2-test.

Results

We included 18 studies with 1786 patients. The studies were of acceptable-to-good quality. The meta-analysis of six studies on quality of life showed no significant difference – mean difference: −1.31; 95% confidence intervals: −6.51 to +3.89, I2=90.9% – between adolescents and young adults with CHD and controls. Similar results were found in 10 studies not eligible for the meta-analysis. In subdomains, it seems that patients had reduced physical quality of life; however, social functioning was comparable or better compared with controls.

Conclusion

For the first time in a meta-analysis, we have shown that quality of life in adolescents and young adults with CHD is not reduced when compared with age-matched controls.
Parental perceptions of congenital cardiovascular malformations in their children
Authors: Ezzat Sameera , Saeedi Osamah , Saleh Doa’a A. , Hamzeh Hala , Hamid Mohamed A. , Crowell Nancy , Boostrom Camille , Loffredo Christopher A. , Jillson Irene A.
Published: November 2015

We assessed parental attitudes towards congenital cardiovascular malformations in their children in a cross-sectional study in Egypt. Parents face many problems related to concerns about their child’s prognosis, but these associations with parental stress have never been evaluated in Egypt or examined in relation to religiosity in a predominantly Muslim society. Accordingly, we conducted interviews in Cairo with mothers of 99 sequential infants born with conotruncal heart malformations (cases) and 65 mothers of age-matched controls. The survey assessed healthcare access and usage, knowledge of congenital cardiovascular malformations, religiosity, the Locus of Control Scale, and the Parenting Stress Index. Results showed that 45% of the mothers of cases had correct knowledge about their child’s diagnosis; 85% were satisfied with the clinical care; and 79% reported that the cost of care was burdensome. Compared with parents of cases, parents of controls were more likely to report stress overall and all its subscales. Regarding belief about locus of control over health, God as a determining factor was given the highest endorsement. Mothers in the congenital cardiovascular malformations group reported a higher level of parental locus of control than did those in the control group. The correlations between stress and locus of control were stronger in the control than in the case group. Religiosity was related neither to stress nor to locus of control. Future studies can explore the roles that personal, familial, and societal factors play in exacerbating or reducing stress levels among parents of sick children, particularly in developing countries where economic pressures are acute.