bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling Cu2+-Aβ complexes from computational approaches
Authors: Alí-Torres Jorge , Mirats Andrea , Maréchal Jean-Didier , Rodríguez-Santiago Luis , Sodupe Mariona
Published: May 2015

Amyloid plaques formation and oxidative stress are two key events in the pathology of the Alzheimer disease (AD), in which metal cations have been shown to play an important role. In particular, the interaction of the redox active Cu2+ metal cation with Aβ has been found to interfere in amyloid aggregation and to lead to reactive oxygen species (ROS). A detailed knowledge of the electronic and molecular structure of Cu2+-Aβ complexes is thus important to get a better understanding of the role of these complexes in the development and progression of the AD disease. The computational treatment of these systems requires a combination of several available computational methodologies, because two fundamental aspects have to be addressed: the metal coordination sphere and the conformation adopted by the peptide upon copper binding. In this paper we review the main computational strategies used to deal with the Cu2+-Aβ coordination and build plausible Cu2+-Aβ models that will afterwards allow determining physicochemical properties of interest, such as their redox potential.
Fibrillar dimer formation of islet amyloid polypeptides
Authors: Chiu Chi-cheng , de Pablo Juan J.
Published: May 2015

Amyloid deposits of human islet amyloid polypeptide (hIAPP), a 37-residue hormone co-produced with insulin, have been implicated in the development of type 2 diabetes. Residues 20 – 29 of hIAPP have been proposed to constitute the amyloidogenic core for the aggregation process, yet the segment is mostly unstructured in the mature fibril, according to solid-state NMR data. Here we use molecular simulations combined with bias-exchange metadynamics to characterize the conformational free energies of hIAPP fibrillar dimer and its derivative, pramlintide. We show that residues 20 – 29 are involved in an intermediate that exhibits transient β-sheets, consistent with recent experimental and simulation results. By comparing the aggregation of hIAPP and pramlintide, we illustrate the effects of proline residues on inhibition of the dimerization of IAPP. The mechanistic insights presented here could be useful for development of therapeutic inhibitors of hIAPP amyloid formation.
Optogenetic and pharmacological suppression of spatial clusters of face neurons reveal their causal role in face gender discrimination
Authors: Afraz Arash , Boyden Edward S. , DiCarlo James J.
Published: May 2015

Significance

There exist subregions of the primate brain that contain neurons that respond more to images of faces over other objects. These subregions are thought to support face-detection and discrimination behaviors. Although the role of these areas in telling faces from other objects is supported by direct evidence, their causal role in distinguishing faces from each other lacks direct experimental evidence. Using optogenetics, here we reveal their causal role in face-discrimination behavior and provide a mechanistic explanation for the process. This study is the first documentation of behavioral effects of optogenetic intervention in primate object-recognition behavior. The methods developed here facilitate the usage of the technical advantages of optogenetics for future studies of high-level vision.
Explaining the Chechen schism in Georgia’s Pankisi valley
Authors: Jasutis Grazvydas
Published: May 2015

This article explores the dynamics within the Pankisi Chechen community, which is divided between radicals and traditionalists, identifying the main obstacles thwarting their cohabitation and offering some ideas that would consolidate and reconcile the communities. It employs intercultural miscommunication theory, emphasising that when the parties are not especially aware of their differences, or of how members of different communities understand particular behaviours, tensions begin to mount. This article hypothesises that the feud within the Chechen community in Pankisi is caused by intercultural miscommunication and unwillingness to share and communicate what they have in common. This article analyses the development and genesis of the Chechen community in Pankisi, unravels internal frictions with regard to religion, customs and traditions, and concludes that tensions arise from misinterpretations of traditions and customs and a radicalised form of Islam, which brings different values. It suggests that a cultural Chechenisation process, with introduction of the Chechen language and the Chechen history in the schools’ curriculum would work towards the preservation of the Vainakh traditions, customs and history, and improve the intra-community communication process.
Time series analysis of the impact of an intervention in Tayside, Scotland to reduce primary care broad-spectrum antimicrobial use
Authors: Hernandez-Santiago Virginia , Marwick Charis A. , Patton Andrea , Davey Peter G. , Donnan Peter T. , Guthrie Bruce
Published: May 2015

Objectives

Concern about Clostridium difficile infection (CDI) and resistance has driven interventions internationally to reduce broad-spectrum antimicrobial use. An intervention combining guidelines, education and feedback was implemented in Tayside, Scotland in 2009 aiming to reduce primary care prescribing of co-amoxiclav, cephalosporins, fluoroquinolones and clindamycin (‘4C antimicrobials’). Our aim was to assess the impact of this real-world intervention on antimicrobial prescribing rates.

Methods

We used interrupted time series with segmented regression analysis to examine associations between the intervention and changes in antimicrobial prescribing (quarterly rates of patients exposed to 4C antimicrobials, non-4C antimicrobials and any antimicrobial in 2005–12).

Results

The intervention was associated with a highly significant and sustained decrease in 4C antimicrobial prescribing, by 33.5% (95% CI –26.1 to –40.9), 42.2% (95% CI –34.2 to –50.2) and 55.5% (95% CI –45.9 to –65.1) at 6, 12 and 24 months after intervention, respectively. The effect was seen across all age groups, with the largest reductions in people aged 65 years and over (58.4% reduction at 24 months, 95% CI –46.7 to –70.1) and care home residents (65.6% reduction at 24 months, 95% CI –51.8 to –79.4). There were balancing increases in doxycycline, nitrofurantoin and trimethoprim prescribing as well as a reduction in macrolide prescribing. Total antimicrobial exposure did not change.

Conclusions

A real-world intervention to reduce primary care prescribing of antimicrobials associated with CDI led to large, sustained reductions in the targeted prescribing, largely due to substitution with guideline-recommended antimicrobials rather than by avoiding antimicrobial use altogether. Further research is needed to examine the impact on antimicrobial resistance.
Can therapeutic drug monitoring optimize exposure to piperacillin in febrile neutropenic patients with haematological malignancies? A randomized controlled trial
Authors: Sime Fekade Bruck , Roberts Michael S. , Tiong Ing Soo , Gardner Julia H. , Lehman Sheila , Peake Sandra L. , Hahn Uwe , Warner Morgyn S. , Roberts Jason A.
Published: May 2015

Objectives

The objectives of this study were to describe piperacillin exposure in febrile neutropenia patients and determine whether therapeutic drug monitoring (TDM) can be used to increase the achievement of pharmacokinetic (PK)/pharmacodynamic (PD) targets.

Methods

In a prospective randomized controlled study (Australian New Zealand Registry, ACTRN12615000086561), patients were subjected to TDM for 3 consecutive days. Dose was adjusted in the intervention group to achieve a free drug concentration above the MIC for 100% of the dose interval (100% fT>MIC), which was also the primary outcome measure. The secondary PK/PD target was 50% fT>MIC. Duration of fever and days to recovery from neutropenia were recorded.

Results

Thirty-two patients were enrolled. Initially, patients received 4.5 g of piperacillin/tazobactam every 8 h or every 6 h along with gentamicin co-therapy in 30/32 (94%) patients. At the first TDM, 7/32 (22%) patients achieved 100% fT>MIC and 12/32 (38%) patients achieved 50% fT>MIC. Following dose adjustment, 11/16 (69%) of intervention patients versus 3/16 (19%) of control patients (P = 0.012) attained 100% fT>MIC, and 15/16 (94%) of intervention patients versus 5/16 (31%) of control patients (P = 0.001) achieved 50% fT>MIC. After the third TDM, the proportion of patients attaining 100% fT>MIC improved from a baseline 3/16 (19%) to 11/15 (73%) in the intervention group, while it declined from 4/16 (25%) to 1/15 (7%) in the control group. No difference was noted in the duration of fever and days to recovery from neutropenia.

Conclusions

Conventional doses of piperacillin/tazobactam may not offer adequate piperacillin exposure in febrile neutropenic patients. TDM provides useful feedback of dosing adequacy to guide dose optimization.
Complementary therapy and survival in glioblastoma
Authors: Mulpur Bhageeradh H. , Nabors L. Burt , Thompson Reid C. , Olson Jeffrey J. , LaRocca Renato V. , Thompson Zachary , Egan Kathleen M.
Published: May 2015

Background

Complementary therapy (CAM) is common in cancer patients. We undertook this study to assess the association of complementary therapy usage with mortality in glioblastoma (GBM) patients.

Methods

The analysis was based on 470 patients. Information on current use of CAM was collected in structured interviews conducted a median of 6 weeks following GBM diagnosis. Proportional hazards regression was used to estimate hazard ratios (HRs) for GBM-related death according to the use of individual supplements with multivariate adjustment for known prognostic factors including age, KPS, and extent of tumor resection (ESR).

Results

Use of CAM agents was common, with 77% of the cohort reporting CAM usage. No mortality association was observed with the use of multivitamins (HR = 0.91; P = .40) or omega-3 fatty acids (HR = 1.07; P = .69). Patients taking vitamin D as an individual supplement (containing higher dosages than in a multivitamin) had reduced mortality when compared with nonusers (age-adjusted HR = 0.68; P = .02). However, the association was diminished after adjustment for KPS and ESR (HR = 0.74; P = .09). Use of herbal supplements was also associated with reduced mortality (HR = 0.58; P = .04). Vitamin E users had a nonsignificantly higher mortality when compared with nonusers (HR = 1.54; P = .09).

Conclusions

Use of CAM is common in GBM patients. These exploratory analyses suggest no mortality association with the use of multivitamins or omega-3 fatty acids. Associations observed with vitamins D and E merit further investigation.
Kibdelosporangium lantanae sp. nov., isolated from the rhizosphere soil of an ornamental plant, Lantana camara L.
Authors: Li Dan , Huang Yaojian , Song Siyang , Xue Ci , Wu Yingying , Deng Xianming
Published: May 2015

Strain XMU 506T, isolated from the rhizosphere soil of an ornamental plant,Lantana camaraL., collected from Xiamen City, China, was identified using a polyphasic approach to clarify its taxonomic position. The aerial mycelium of this organism formed long straight or curved chains of spores and sporangium-like structures. The optimum growth occurred at 28–30 °C, pH 7.0 with 0–1 % NaCl. Strain XMU 506Tshowed the highest 16S rRNA gene sequence similarity (96.5  %) toKibdelosporangium philippinenseDSM 44226T, and formed a monophyletic clade in the 16S rRNA gene phylogenetic tree together with the type strains of the genusKibdelosporangium. The chemotaxonomic properties further supported the assignment of strain XMU 506Tto the genusKibdelosporangium:meso-diaminopimelic acid was the diagnostic amino acid in the cell wall peptidoglycan; mycolic acids were not present in the cell wall; the whole-cell hydrolysates contained arabinose, galactose, glucose and ribose. The major menaquinone was MK-9(H4); the phospholipids of the isolate comprised phosphatidylethanolamine, OH-phosphatidylethanolamine, diphosphatidylglycerol and unidentified amino-, glyco- and phospholipids; the major fatty acids of the strain were iso-C16 : 0, C17 : 1ω6cand iso-C16 : 1H. The G+C content of genomic DNA was 67.3 mol%. Based on the results of phylogenetic analysis, phenotypic and genotypic characterization, strain XMU 506Trepresents a novel species in the genusKibdelosporangium, for which the nameKibdelosporangium lantanaesp. nov. is proposed. The type strain is XMU 506T( = KCTC 29675T = MCCC 1K00430T).
A Vision for Ubiquitous Sequencing
Authors: Erlich Yaniv
Published: May 2015

Genomics has recently celebrated reaching the $1000 genome milestone, making affordable DNA sequencing a reality. With this goal successfully completed, the next goal of the sequencing revolution can be sequencing sensors miniaturized sequencing devices that are manufactured for real time applications and deployed in large quantities at low costs. The first part of this manuscript envisions applications that will benefit from moving the sequencers to the samples in a range of domains. In the second part, the manuscript outlines the critical barriers that need to be addressed in order to reach the goal of ubiquitous sequencing sensors.
Perspectives on Quorum sensing in Fungi
Authors: Majumdar Sarangam , Mondal Subhoshmita
Published: May 2015

Keeping a pace with Quorum sensing, analyzing communication shows the close co-evolution of fungi with organisms present in their environment giving insights into multispecies communication. Subsequently, many examples of cell density dependent regulation by extracellular factors have been found in diverse microorganisms. The widespread incidence of diverse quorum-sensing systems strongly suggests that regulation in accordance with cell density is important for the success of microbes in many environments. The paper includes the basic autoregulatory quorum sensing molecules that has been perceived. Although fungal quorum sensing research is still in its infancy, its discovery has changed our views about the fungal kingdom and could eventually lead to the development of new antifungal therapeutics.
Ab initio simulation of diffractometer instrumental function for high-resolution X-ray diffraction
Authors: Mikhalychev Alexander , Benediktovitch Andrei , Ulyanenkova Tatjana , Ulyanenkov Alex
Published: May 2015

Modeling of the X-ray diffractometer instrumental function for a given optics configuration is important both for planning experiments and for the analysis of measured data. A fast and universal method for instrumental function simulation, suitable for fully automated computer realization and describing both coplanar and noncoplanar measurement geometries for any combination of X-ray optical elements, is proposed. The method can be identified as semi-analytical backward ray tracing and is based on the calculation of a detected signal as an integral of X-ray intensities for all the rays reaching the detector. The high speed of calculation is provided by the expressions for analytical integration over the spatial coordinates that describe the detection point. Consideration of the three-dimensional propagation of rays without restriction to the diffraction plane provides the applicability of the method for noncoplanar geometry and the accuracy for characterization of the signal from a two-dimensional detector. The correctness of the simulation algorithm is checked in the following two ways: by verifying the consistency of the calculated data with the patterns expected for certain simple limiting cases and by comparing measured reciprocal-space maps with the corresponding maps simulated by the proposed method for the same diffractometer configurations. Both kinds of tests demonstrate the agreement of the simulated instrumental function shape with the measured data.
X-ray pulse wavefront metrology using speckle tracking
Authors: Berujon Sebastien , Ziegler Eric , Cloetens Peter
Published: May 2015

An instrument allowing the quantitative analysis of X-ray pulsed wavefronts is presented and its processing method explained. The system relies on the X-ray speckle tracking principle to accurately measure the phase gradient of the X-ray beam from which beam optical aberrations can be deduced. The key component of this instrument, a semi-transparent scintillator emitting visible light while transmitting X-rays, allows simultaneous recording of two speckle images at two different propagation distances from the X-ray source. The speckle tracking procedure for a reference-less metrology mode is described with a detailed account on the advanced processing schemes used. A method to characterize and compensate for the imaging detector distortion, whose principle is also based on speckle, is included. The presented instrument is expected to find interest at synchrotrons and at the new X-ray free-electron laser sources under development worldwide where successful exploitation of beams relies on the availability of an accurate wavefront metrology.
Crystal structure of (E)-N-{2-[2-(3-chlorobenzylidene)hydrazinyl]-2-oxoethyl}-4-methylbenzenesulfonamide monohydrate
Authors: Purandara H. , Foro Sabine , Gowda B. Thimme
Published: May 2015

The molecule of the title compound, C16H16ClN3O3S·H2O, is L-shaped being bent at the S atom; the S—N—C—C torsion angle is 132.0 (3)°. The central part of the molecule, C—C—N—N=C, is almost linear, with the C—C—N—N and C—N—N=C torsion angles being −174.1 (2) and 176.0 (2)°, respectively. The dihedral angle between thep-toluenesulfonyl ring and the S—N—C—C(=O) segment is 67.5 (4)°, while that between the two aromatic rings is 52.17 (11)°. In the crystal, the water H atom is involved in O—H...O hydrogen bonds with a sulfonamide O atom and the carbonyl O atom. The water O atom is itself hydrogen bonded to both NH hydrogen atoms. These four hydrogen bonds lead to the formation of corrugated sheets lying parallel to (100). There are also weak C—H...O contacts present within the sheets.
Crystal structure of 2-(4-chloro-3-fluorophenyl)-1H-benzimidazole
Authors: Krishnamurthy M. S. , Begum Noor Shahina
Published: May 2015

In the title compound, C13H8ClFN2, the dihedral angle between the plane of the benzimidazole ring system (r.m.s. deviation = 0.022 Å) and the benzene ring is 26.90 (8)°. The F atom at themetaposition of the benzene ring is disordered over two sites in a 0.843 (4):0.157 (4) ratio. In the crystal, molecules are linked by N—H...N hydrogen bonds, forming infiniteC(4) chains propagating along [010]. In addition, weak C—H...π and π–π interactions [shortest centroid–centroid separation = 3.6838 (12) Å] are observed, which link the chains into a three-dimensional network.
Synthèse et étude structrale de lyonsite-type (Na0,4,Li0,6)(Fe,Li2)(MoO4)3
Authors: Souilem Amira , Zid Mohamed Faouzi , Driss Ahmed
Published: May 2015

The new compound (Na0.4,Li0.6)(Fe,Li2)(MoO4)3was synthesized by cooling from the melt. Its anionic framework is built up from two distinctMO6octahedra, each containing disordered Li+and Fe3+ions in 0.6:0.4 and 0.7:0.3 ratios, and two MoO4tetrahedra, which link by vertex-sharing of their O atoms. These tetrameric units are further linked by sharing edges between octahedra and by formation ofM—O—Mo (M= Fe/Li) bridges, forming ribbons propagating in the [100] direction. The ribbons are cross-linked in both theb- andc-axis directions, giving rise to a three-dimensional framework having [100] tunnels in which the monovalent Na+/Li+cations (0.4:0.6 ratio) lie. Bond-valence calculations are consistent with the disorder model for the cations. The structure of the title compound, which is isotypic with Li3Fe(MoO4)3and Li3Ga(MoO4)3, is compared briefly with those of LiFeMo2O8and Li1.6Mn2.2(MoO4)3.
Comparison of parallel solvers for Moving Particle Semi-Implicit method
Authors: Duan Guangtao , Chen Bin
Published: May 2015

Purpose

– The purpose of this paper is to find the best solver for parallelizing particle methods based on solving Pressure Poisson Equation (PPE) by taking Moving Particle Semi-Implicit (MPS) method as an example because the solution for PPE is usually the most time-consuming part difficult to parallelize.

Design/methodology/approach

– To find the best solver, the authors compare six Krylov solvers, namely, Conjugate Gradient method (CG), Scaled Conjugate Gradient method (SCG), Bi-Conjugate Gradient Stabilized (BiCGStab) method, Conjugate Gradient Squared (CGS) method with Symmetric Lanczos Algorithm (SLA) method and Incomplete Cholesky Conjugate Gradient method (ICCG) in terms of convergence, time consumption, parallel efficiency and memory consumption for the semi-implicit particle method. The MPS method is parallelized by the hybrid Open Multi-Processing (OpenMP)/Message Passing Interface (MPI) model. The dam-break flow and channel flow simulations are used to evaluate the performance of different solvers.

Findings

– It is found that CG converges stably, runs fastest in the serial way, uses the least memory and has highest OpenMP parallel efficiency, but its MPI parallel efficiency is lower than SLA because SLA requires less synchronization than CG.

Originality/value

– With all these criteria considered and weighed, the recommended parallel solver for the MPS method is CG.
A generalized XFEM procedure for analyzing intersecting joints in rock masses with excavation
Authors: Deb Debasis , Pramanik Ranjan , Das Kamal Ch
Published: May 2015

Purpose

– The purpose of this paper is to analyse of structures made in rock mass with multiple intersecting discrete discontinuities such as joint, fault, shear plane.

Design/methodology/approach

– In this study, a numerical method is proposed for analyzing multiple intersecting joints with varying dip angles, spacing and roughness in eXtended Finite Element Method platform. A procedure is also outlined to treat excavated enhanced (jointed) elements for analysing the effect of excavation sequences.

Findings

– The proposed method is compared with the existing interface element methods (Phase-2 model) by considering the stress and displacement distributions of a multiple intersecting jointed rock sample under uniaxial loading conditions. A circular tunnel in rock mass having intersecting joints is also analyzed for the distribution of mobilised friction angle of joints and results are compared with a derived analytical solution.

Research limitations/implications

– Nucleation and propagation of cracks should be incorporated into the proposed framework in future studies.

Practical implications

– The proposed method is a useful tool for rock mechanics and geotechnical engineering problems to analyse strength and deformability of jointed rock masses.

Originality/value

– The paper enumerates concepts and detail implementation procedures of the proposed method in three-noded triangular elements. The intersection of joints is formulated in such a way that no additional (junction) enrichment is required in model. The method has been improved for inclusion of Dirichlet and Neumann boundary conditions to be applied in the enhanced part of a problem domain.
Effect of boundary condition approximation on convergence and accuracy of a finite volume discretization of the transient heat conduction equation
Authors: Guillot Martin Joseph , McCool Steve C
Published: May 2015

Purpose

– The purpose of this paper is to investigate the effect of numerical boundary condition implementation on local error and convergence in L2-norm of a finite volume discretization of the transient heat conduction equation subject to several boundary conditions, and for cases with volumetric heat generation, using both fully implicit and Crank-Nicolson time discretizations. The goal is to determine which combination of numerical boundary condition implementation and time discretization produces the most accurate solutions with the least computational effort.

Design/methodology/approach

– The paper studies several benchmark cases including constant temperature, convective heating, constant heat flux, time-varying heat flux, and volumetric heating, and compares the convergence rates and local to analytical or semi-analytical solutions.

Findings

– The Crank-Nicolson method coupled with second-order expression for the boundary derivatives produces the most accurate solutions on the coarsest meshes with the least computation times. The Crank-Nicolson method allows up to 16X larger time step for similar accuracy, with nearly negligible additional computational effort compared with the implicit method.

Practical implications

– The findings can be used by researchers writing similar codes for quantitative guidance concerning the effect of various numerical boundary condition approximations for a large class of boundary condition types for two common time discretization methods.

Originality/value

– The paper provides a comprehensive study of accuracy and convergence of the finite volume discretization for a wide range of benchmark cases and common time discretization methods.
Numerical simulation of cavitation shedding flow around a hydrofoil using Partially-Averaged Navier-Stokes model
Authors: Zhang Desheng , Shi Weidong , Pan Dazhi , Zhang Guangjian
Published: May 2015

Purpose

– The purpose of this paper is to predict the unstable cavitation shedding flow around a 2D Clark-y hydrofoil.

Design/methodology/approach

– The paper studies Partially Averaged Navier-Stokes (PANS) model which was employed in the two-phase flow with a homogeneous cavitation model.

Findings

– Maximum density ratio affects the mass transfer rate between the liquid and the vapor significantly. The cavitating flow predicted by PANS model can resolve more turbulent scales by decreasing the parameter fk.

Originality/value

– The accuracy of numerical prediction is improved by increasing the maximum density ratio and decreasing fk.
Oxidation of olive oil fortified with quercetin, caffeic acid, tyrosol and hydroxytyrosol
Authors: Etherton Anne Kristine , Omaye Stanley T.
Published: May 2015

Purpose

– This paper aims to evaluate effects of the fortification of polyphenolic compound mixtures of quercetin, caffeic acid, tryrosol and hydroxytyrosol in olive oil oxidation.

Design/methodology/approach

– The authors measured olive oxidation initiated by copper using thiobarbituric acid reactive substance, as an indicator of lipid peroxidation.

Findings

– Overall, most mixture combinations exhibited oxidation similar to olive oil alone. Some mixture combinations of polyphenolic compounds acted as antioxidants; however, as the concentrations were changed, they became prooxidant in nature.

Research limitations/implications

–In vitrostudies have limitations for extrapolation toin vivoand clinical studies.

Practical implications

– Such information will be useful in determining optimal concentrations and combinations of antioxidants for reducing rancidity and perhaps as models that could be used to modulate various chronic diseases that are associated with oxidative stress.

Originality/value

– Olive oil, along with fruits, vegetables and fish, are important constituents of health promoting diets, such as the Mediterranean diet. Active ingredients include monounsaturated fatty acids, oleic acid and a variety of antioxidants including various polyphenolic compounds.
Stakeholders and corporate environmental decision making: The BP Whiting Refinery controversy
Authors: Stinchfield Bryan T.
Published: May 2015

In 2007, BP sought and received regulatory approval to expand operations at its Whiting Refinery in northwest Indiana. Had the project gone forward as planned, the refinery would have discharged significantly higher levels of pollutants into Lake Michigan, but would have also contributed to economic development in the region. The result of BP seeking and being granted regulatory approval triggered a firestorm of controversy from multiple segments of society. This case study draws from secondary sources to examine the positions of a variety of stakeholders who influenced BP's decision as to whether or not it should expand its Whiting Refinery. Relevant stakeholders included for analysis are citizen and environmental organizations, political groups, trade associations, BP's employees, and stockholders. The intended target audience for this case is upper-level undergraduate business students studying issues related to business and society, such as corporate social responsibility and sustainable development.
Case Writing and Research: Professor Moore Reviews a Case
Authors: Vega Gina , Sherman Herbert , Leach Thomas
Published: May 2015

This is the sixth in a series of articles about case research, writing, teaching, and reviewing. In this article, the protagonist, Prof. Moore, consults experienced case reviewers and learns several different approaches to reviewing cases for journal publication. The article is written as if it were a case; it is fictitious.
Qihoo 360: building a “free” business model
Authors: Li Sun Sunny , Zhang Yanli
Published: May 2015

Synopsis

This case discusses Qihoo 360's free business model, how it used this free model to overpower competitors, and how the model evolved over time. Qihoo 360 is a company that took just six years to become a company listed on the New York Stock Exchange (with a market value of over US$ 2 billion). At Qihoo 360's Initial Public Offering (IPO) at the New York Stock Exchange (NYSE), Qihoo's founder Zhou Hongyi reflected on how Qihoo's free business model had brought its current success and speculates on its future challenges.

Research methodology

The authors used both secondary data and field interviews when preparing this case. After reading through various company reports, competitor information, and financial filings, the authors interviewed five top manager team (TMT) members of Qihoo 360, three TMT members of its competitors, and two partners of venture capital investors who have invested in these companies in Beijing or Shenzhen during the last three years. The authors collected 347 media reports related to these companies in Chinese covering seven years of history. This long span of data collection improves the interpretation of the company and helps construct the storyline of the case.

Relevant courses and levels

This case is suitable for an MBA course or an advanced undergraduate course in strategic management or a technology-oriented entrepreneurship course, focussing on the topic of the free business model, business model innovation, disruptive innovation, and evolution of the business model during the entrepreneurial process.
Financing company growth at MRV Engenharia e Participacoes SA
Authors: Shahriar Khaksari , Stefan Platikanov
Published: May 2015

Case description

The case presents a financing dilemma at a fast growing, Brazilian construction company. The growing demand for residential and commercial real estate in Brazil, coupled with the capital intensive nature of the industry generates the need for a considerable external financing. The students are invited to take the perspective of the financial manager and evaluate three financing alternatives – an issue of debentures, a seasoned equity offering, and a capital-raising ADR offering. In their evaluation and final recommendation students need to consider the implications of each of the financing alternatives on firm value, equity risk, cost of capital, financial leverage, issuance costs, and ownership structure. The case also presents a valuable opportunity to discuss the interdependence between the institutional development of an economy and the development of its capital markets.
The Impact of Children on Australian Couples’ Wealth Accumulation
Authors: Dockery Alfred Michael , Bawa Sherry
Published: May 2015

Existing estimates of the cost of children focus on what parents spend on their children, which has limited relevance to parents’ financial capacity to meet those costs. An alternative indicator of the affordability of children, their impact upon couples’ wealth accumulation, is estimated using the lifecycle model and Australian household panel data. The results suggest children have a very small impact upon wealth accumulation, seemingly at odds with the large ‘costs’ implied from expenditure‐based estimates. In reconciling these highly divergent estimates we argue that the net‐wealth approach is an intuitively more appealing indicator of the financial impost of children.
Prevalence of celiac disease in Indian patients with irritable bowel syndrome and uninvestigated dyspepsia
Authors: Sharma Hanish , Verma Anil K , Das Prasenjit , Dattagupta Siddhartha , Ahuja Vineet , Makharia Govind K
Published: May 2015

Objective

The clinical spectrum of celiac disease (CeD) is wide and its symptoms overlap with those of functional bowel diseases. This study aimed to investigate the relationship among gluten‐related disorders, irritable bowel syndrome (IBS) and uninvestigated dyspepsia in Indian patients.

Methods

Patients with IBS and uninvestigated dyspepsia (using Rome III criteria) were tested for immunoglobulin A (IgA) anti‐tissue transglutaminase (anti‐tTG) antibody and anti‐gliadin antibody (AGA). Those with positive anti‐tTG antibody were evaluated for the presence of villous abnormalities. Patients who were only IgA AGA‐positive were considered to have gluten sensitivity and those with positive anti‐tTG antibody and villous atrophy were considered to have CeD.

Results

Of 362 patients with IBS, 22 (6.1%) had positive anti‐tTG antibody, among whom 3 (0.8%) had CeD and 19 had potential CeD. Of 358 patients with uninvestigated dyspepsia, 18 (5.0%) were anti‐tTG antibody‐positive and among them 4 (1.1%) had CeD and 14 had potential CeD. AGA was positive in 104 (28.7%) patients with IBS and 68 (19.0%) with uninvestigated dyspepsia, suggesting the presence of gluten sensitivity.

Conclusion

This study highlights the relationship between IBS or dyspepsia and CeD or gluten sensitivity.
Joint associations of insomnia and sleep duration with prevalent diabetes: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
Authors: Cespedes Elizabeth M. , Dudley Katherine A. , Sotres‐Alvarez Daniela , Zee Phyllis C. , Daviglus Martha L. , Shah Neomi A. , Talavera Gregory A. , Gallo Linda C. , Mattei Josiemer , Qi Qibin , Ramos Alberto R. , Schneiderman Neil , Espinoza‐Giacinto Rebeca A. , Patel Sanjay R.
Published: May 2015

Background

Inadequate sleep quantity and quality are associated with a higher risk of type 2 diabetes. This relationship is not well‐examined in US Hispanics/Latinos, and prior analyses may be confounded by sleep apnea. This cross‐sectional study examined joint associations of sleep duration and insomnia with diabetes among diverse US Hispanic/Latinos.

Methods

Baseline data on sleep quantity and quality were obtained from 15227 participants (mean age 41; range 18–74 years) from the Hispanic Community Health Study/Study of Latinos. Complex survey multinomial logistic regression was used to examine associations between prevalent diabetes and six phenotypes defined by cross‐classifying sleep duration (short ≤6 h, average >6–9 h, long >9 h) and insomnia, adjusting for sex, age, site and Hispanic/Latino background interaction, education, physical activity, diet quality, and sleep apnea.

Results

In the weighted population, 14% had diabetes, 28% had insomnia, 9% were short sleepers, and 19% were long sleepers. Compared with those with average sleep and no insomnia, those with short sleep and insomnia were more likely to have diabetes (odds ratio [OR] 1.46; 95% confidence interval [CI] 1.02, 2.11). Average sleepers with insomnia (1.28; 95% CI 1.02, 1.61) and long sleepers without insomnia (1.33; 95% CI 1.07, 1.65) also had elevated odds of diabetes. Further adjustment for body mass index attenuated associations, except with long sleep without insomnia.

Conclusions

Both decreased quantity and quality of sleep are associated with diabetes in Hispanic/Latinos, with the greatest odds among those with short sleep duration and insomnia. The association is largely explained by obesity.
Sequence types of Staphylococcus epidermidis associated with prosthetic joint infections are not present in the laminar airflow during prosthetic joint surgery
Authors: Månsson Emeli , Hellmark Bengt , Sundqvist Martin , Söderquist Bo
Published: May 2015

Molecular characterization of Staphylococcus epidermidis isolates from prosthetic joint infections (PJIs) has demonstrated a predominance of healthcare‐associated multi‐drug resistant sequence types (ST2 and ST215). How, and when, patients acquire these nosocomial STs is not known. The aim was to investigate if sequence types of S. epidermidis associated with PJIs are found in the air during prosthetic joint surgery. Air sampling was undertaken during 17 hip/knee arthroplasties performed in operating theaters equipped with mobile laminar airflow units in a 500‐bed hospital in central Sweden. Species identification was performed using MALDI‐TOF MS and 16S rRNA gene analysis. Isolates identified as S. epidermidis were further characterized by MLST and antibiotic susceptibility testing. Seven hundred and thirty‐five isolates were available for species identification. Micrococcus spp. (n = 303) and coagulase‐negative staphylococci (n = 217) constituted the majority of the isolates. Thirty‐two isolates of S. epidermidis were found. S. epidermidis isolates demonstrated a high level of allelic diversity with 18 different sequence types, but neither ST2 nor ST215 was found. Commensals with low pathogenic potential dominated among the airborne microorganisms in the operating field during prosthetic joint surgery. Nosocomial sequence types of S. epidermidis associated with PJIs were not found, and other routes of inoculation are therefore of interest in future studies.
Prognostic model for mantle cell lymphoma in the rituximab era: a nationwide study in Japan
Authors: Chihara Dai , Asano Naoko , Ohmachi Ken , Kinoshita Tomohiro , Okamoto Masataka , Maeda Yoshinobu , Mizuno Ishikazu , Matsue Kosei , Uchida Toshiki , Nagai Hirokazu , Nishikori Momoko , Nakamura Shigeo , Ogura Michinori , Suzuki Ritsuro
Published: May 2015

Mantle cell lymphoma (MCL) is essentially incurable with conventional chemotherapy. The MCL International Prognostic Index (MIPI) is a validated specific prognostic index, but was derived from patients with advanced‐stage disease primarily in the pre‐rituximab era. We analysed 501 MCL patients (median age, 67 years; range 22–90) treated with rituximab‐containing chemotherapy, and evaluated the prognostic factors adjusted by the treatment. Five‐year overall survival (OS) in the low, intermediate and high MIPI groups was 74%, 70% and 35%, respectively. Additional to MIPI risk factors, multivariate analysis revealed that low serum albumin and bone‐marrow involvement were also significantly associated with a poor outcome. The revised‐MIPI (R‐MIPI) was constructed using six factors, namely age, performance status, white blood cell count, serum lactate dehydrogenase, bone‐marrow involvement and serum albumin, which is divided into four prognostic groups. Five‐year OS in low, low‐intermediate (L‐I), high‐intermediate (H‐I) and high R‐MIPI groups was 92%, 75%, 61% and 19%, respectively. Hazard ratio for OS of L‐I, H‐I and high risk to low risk patients were 5·4, 8·3 and 33·0, respectively. R‐MIPI, a new prognostic index with easy application to the general patient population, shows promise for identifying low‐ and high‐risk MCL patients in the rituximab era.
Activation of M3 cholinoceptors attenuates vascular injury after ischaemia/reperfusion by inhibiting the Ca2+/calmodulin‐dependent protein kinase II pathway
Authors: Lu Xing‐Zhu , Bi Xue‐Yuan , He Xi , Zhao Ming , Xu Man , Yu Xiao‐Jiang , Zhao Zheng‐Hang , Zang Wei‐Jin
Published: May 2015

Background and Purpose

The activation of M3 cholinoceptors (M3 receptors) by choline reduces cardiovascular risk, but it is unclear whether these receptors can regulate ischaemia/reperfusion (I/R)‐induced vascular injury. Thus, the primary goal of the present study was to explore the effects of choline on the function of mesenteric arteries following I/R, with a major focus on Ca2+/calmodulin‐dependent protein kinase II (CaMKII) regulation.

Experimental Approach

Rats were given choline (10 mg·kg−1, i.v.) and then the superior mesenteric artery was occluded for 60 min (ischaemia), followed by 90 min of reperfusion. The M3 receptor antagonist, 4‐diphenylacetoxy‐N‐methylpiperidine methiodide (4‐DAMP), was injected (0.12 μg·kg−1, i.v.) 5 min prior to choline treatment. Vascular function was examined in rings of mesenteric arteries isolated after the reperfusion procedure. Vascular superoxide anion production, CaMKII and the levels of Ca2+‐cycling proteins were also assessed.

Key Results

Choline treatment attenuated I/R‐induced vascular dysfunction, blocked elevations in the levels of reactive oxygen species (ROS) and decreased the up‐regulated expression of oxidised CaMKII and phosphorylated CaMKII. In addition, choline reversed the abnormal expression of Ca2+‐cycling proteins, including Na+/Ca2+ exchanger, inositol 1,4,5‐trisphosphate receptor, sarcoplasmic reticulum Ca2+‐ATPase and phospholamban. All of these cholinergic effects of choline were abolished by 4‐DAMP.

Conclusions and Implications

Our data suggest that inhibition of the ROS‐mediated CaMKII pathway and modulation of Ca2+‐cycling proteins may be novel mechanisms underlying choline‐induced vascular protection. These results represent a significant addition to the understanding of the pharmacological roles of M3 receptors in the vasculature, providing a new therapeutic strategy for I/R‐induced vascular injury.

Linked Articles

This article is part of a themed section on Chinese Innovation in Cardiovascular Drug Discovery. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-23
Standardizing terms, definitions and concepts for describing and interpreting unwanted immunogenicity of biopharmaceuticals: recommendations of the Innovative Medicines Initiative ABIRISK consortium
Authors:   ABIRISK Consortium, Rup B , Pallardy M , Sikkema D , Albert T , Allez M , Broet P , Carini C , Creeke P , Davidson J , De Vries N , Finco D , Fogdell-Hahn A , Havrdova E , Hincelin-Mery A , Holland M C , Jensen P E H , Jury E C , Kirby H , Kramer D , Lacroix-Desmazes S , Legrand J , Maggi E , Maillère B , Mariette X , Mauri C , Mikol V , Mulleman D , Oldenburg J , Paintaud G , Pedersen C R , Ruperto N , Seitz R , Spindeldreher S , Deisenhammer F
Published: May 2015

Biopharmaceuticals (BPs) represent a rapidly growing class of approved and investigational drug therapies that is contributing significantly to advancing treatment in multiple disease areas, including inflammatory and autoimmune diseases, genetic deficiencies and cancer. Unfortunately, unwanted immunogenic responses to BPs, in particular those affecting clinical safety or efficacy, remain among the most common negative effects associated with this important class of drugs. To manage and reduce risk of unwanted immunogenicity, diverse communities of clinicians, pharmaceutical industry and academic scientists are involved in: interpretation and management of clinical and biological outcomes of BP immunogenicity, improvement of methods for describing, predicting and mitigating immunogenicity risk and elucidation of underlying causes. Collaboration and alignment of efforts across these communities is made difficult due to lack of agreement on concepts, practices and standardized terms and definitions related to immunogenicity. The Innovative Medicines Initiative (IMI; www.imi-europe.org), ABIRISK consortium [Anti-Biopharmaceutical (BP) Immunization Prediction and Clinical Relevance to Reduce the Risk; www.abirisk.eu] was formed by leading clinicians, academic scientists and EFPIA (European Federation of Pharmaceutical Industries and Associations) members to elucidate underlying causes, improve methods for immunogenicity prediction and mitigation and establish common definitions around terms and concepts related to immunogenicity. These efforts are expected to facilitate broader collaborations and lead to new guidelines for managing immunogenicity. To support alignment, an overview of concepts behind the set of key terms and definitions adopted to date by ABIRISK is provided herein along with a link to access and download the ABIRISK terms and definitions and provide comments (http://www.abirisk.eu/index_t_and_d.asp).
Endocrine sequelae beyond 10 years in survivors of medulloblastoma
Authors: Uday Suma , Murray Robert D. , Picton Susan , Chumas Paul , Raju Midhu , Chandwani Manju , Alvi Sabah
Published: May 2015

Introduction

Survival following treatment of paediatric medulloblastomas has significantly improved over the past few decades, but as a consequence, late effects, particularly endocrine sequelae, have been recognized. The complete picture of late effects, however, has been limited by short duration of follow‐up.

Aim

To establish the evolution of endocrine sequelae in patients treated for medulloblastoma.

Methods

Single‐centre analysis of medulloblastoma treatment and endocrine sequelae in patients diagnosed between 1982 and 2002.

Results

A total of 109 patients were treated for medulloblastoma, with various treatment modalities involving radio‐ and chemotherapy. Only 45 (41%) patients remained alive, and details of treatment and late effects were available for 35 (25 m). The median age at diagnosis was 8 (range 2–14) years, and the median follow‐up was 18 (range 10–28) years. Growth hormone deficiency (GHD) was the most prevalent hormone deficiency (97%), followed by primary hypothyroidism (60%) and adrenocorticotrophic hormone (ACTH) deficiency (45·5%). The median time from end of treatment to loss of growth hormone was 1·7 (range 0·7–15) years, ACTH deficiency 2·9 (range 0·75–7·5) years and hypothyroidism 4·1 (range 0·7–11·4) years. Twenty‐three percentage developed hypogonadism (17% primary and 6% secondary), whilst precocious puberty was seen in 20%. Endocrinopathies appeared to be more prevalent in those treated with concomitant chemotherapy and radiotherapy.

Conclusions

Prevalence of endocrine sequelae in medulloblastoma survivors is high, and evolution of endocrine dysfunction can occur as late as 15 years from treatment completion; hence, long‐term close monitoring of growth, puberty and gonadal function is essential.