bluuebunny/crossref_metadata_2025 huggingface dataset:
Collusion or Competition? Interfirm Relationships in the Chinese Auto Industry
Authors: Hu Wei‐Min , Xiao Junji , Zhou Xiaolan
Published: March 2014

The Chinese passenger‐vehicle industry contains a large number of manufacturers. Some of them are members of big corporate groups centered around state owned enterprises. These corporate relationships may facilitate collusion. This paper applies the non‐nested hypothesis test methodology to data on passenger vehicles to identify whether price collusion exists within corporate groups or across groups. Our empirical results support the assumption of Bertrand Nash competition in the Chinese passenger‐vehicle industry: We find no evidence for within or cross‐group price collusion. Our policy experiments show that indigenous brands will gain market shares and profits if within‐group companies merge.
On Welfare Losses Due to Imperfect Competition
Authors: Ritz Robert A.
Published: March 2014

Corporate managers and executive compensation in many industries place significant emphasis on measures of firm size, such as sales revenue or market share. Such objectives have an important—yet thus far unquantified—impact on market performance. With n symmetric firms, equilibrium welfare losses are of order 1/n4, and thus vanish extremely quickly. Welfare losses are less than 5% for many empirically relevant market structures, despite significant firm asymmetry and industry concentration. They can be estimated using only basic information on market shares. These results also apply to oligopsonistic competition (e.g., for retail bank deposits) and strategic forward trading (e.g., in restructured electricity markets).
Information Unraveling Revisited: Disclosure of Horizontal Attributes
Authors: Celik Levent
Published: March 2014

This paper analyzes in a spatial framework how much information a seller discloses about the variety he sells when he faces a buyer with a privately known taste for variety. I identify an equilibrium in which, for each possible variety, the seller's optimal strategy consists of either fully disclosing the variety or disclosing how far it is from the buyer's expected taste. The set of varieties the seller fully discloses monotonically expands as the buyer's taste for variety becomes stronger. I show that this is the unique undefeated equilibrium. From a policy perspective, mandating full disclosure is socially harmful.
Naked Exclusion in the Lab: The Case of Sequential Contracting
Authors: Boone Jan , Müller Wieland , Suetens Sigrid
Published: March 2014

In the context of the naked exclusion model of Rasmusen, Ramseyer and Wiley [1991] and Segal and Whinston [2009b], we examine whether sequential contracting is more conducive to exclusion in the lab, and whether it is cheaper for the incumbent than simultaneous contracting. We find that an incumbent who proposes contracts to buyers sequentially, excludes significantly more often than an incumbent who proposes contracts simultaneously. In contrast to theory, this comes at a substantial cost for the incumbent. Accounting for the observation that buyers are more likely to accept an exclusive contract the higher the payment, substantially improves the fit between theoretical predictions and observed behavior.
Application of routine electronic health record databases for pharmacogenetic research
Authors: Yasmina A. , Deneer V. H. M. , Maitland‐van der Zee A. H. , van Staa T. P. , de Boer A. , Klungel O.H.
Published: March 2014

Inter‐individual variability in drug responses is a common problem in pharmacotherapy. Several factors (non‐genetic and genetic) influence drug responses in patients. When aiming to obtain an optimal benefit–risk ratio of medicines and with the emergence of genotyping technology, pharmacogenetic studies are important for providing recommendations on drug treatments. Advances in electronic healthcare information systems can contribute to increasing the quality and efficiency of such studies. This review describes the definition of pharmacogenetics, gene selection and study design for pharmacogenetic research. It also summarizes the potential of linking pharmacoepidemiology and pharmacogenetics (along with its strengths and limitations) and provides examples of pharmacogenetic studies utilizing electronic health record databases.
The collagen cross‐linking enzyme lysyl oxidase is associated with the healing of human atherosclerotic lesions
Authors: Ovchinnikova O. A. , Folkersen L. , Persson J. , Lindeman J. H. N. , Ueland T. , Aukrust P. , Gavrisheva N. , Shlyakhto E. , Paulsson‐Berne G. , Hedin U. , Olofsson P. S. , Hansson G. K.
Published: March 2014

Background

Acute clinical complications of atherosclerosis such as myocardial infarction (MI) and ischaemic stroke are usually caused by thrombus formation on the ruptured plaque surface. Collagen, the main structural protein of the fibrous cap, provides mechanical strength to the atherosclerotic plaque. The integrity of the fibrous cap depends on collagen fibre cross‐linking, a process controlled by the enzyme lysyl oxidase (LOX).

Methods and results

We studied atherosclerotic plaques from human carotid endarterectomies. LOX was strongly expressed in atherosclerotic lesions and detected in the regions with ongoing fibrogenesis. Higher LOX levels were associated with a more stable phenotype of the plaque. In the studied population, LOX mRNA levels in carotid plaques predicted the risk for future MI. Within the lesion, LOX mRNA levels correlated positively with levels of osteoprotegerin (OPG) and negatively with markers of immune activation. The amount of LOX‐mediated collagen cross‐links in plaques correlated positively also with serum levels of OPG.

Conclusions

Lysyl oxidase may contribute to the healing of atherosclerotic lesions and to the prevention of its lethal complications. Mediators of inflammation may control LOX expression in plaques and hence plaque stability.
DO FLOODS HAVE PERMANENT EFFECTS? EVIDENCE FROM THE NETHERLANDS
Authors: Husby Trond G. , de Groot Henri L.F. , Hofkes Marjan W. , Dröes Martijn I.
Published: March 2014

This study investigates the short‐ and long‐run impact on population dynamics of the major flood in the Netherlands in 1953. A dynamic difference‐in‐differences analysis reveals that the flood had an immediate negative impact on population growth, but limited long‐term effects. In contrast, the resulting flood protection program (Deltaworks), had a persisting positive effect on population growth. As a result, there has been an increase in population in flood‐prone areas. Our results suggest a moral hazard effect of flood mitigation leading to more people locating in flood‐prone areas, increasing potential disaster costs.
THE PUBLIC FINANCING OF AMERICA'S LARGEST CITIES: A STUDY OF CITY FINANCIAL RECORDS IN THE WAKE OF THE GREAT RECESSION
Authors: Ross Justin , Yan Wenli , Johnson Craig
Published: March 2014

This paper employs Comprehensive Annual Financial Reports of the 35 largest population American cities from 2005 to 2011 to examine how these cities managed the Great Recession, which was a global macroeconomic shock particularly damaging to the housing sector. While broader surveys of local government suggest that the Great Recession has been associated with substantive revenue declines, particularly via the property tax, the Comprehensive Annual Financial Reports data indicate that large cities remained relatively stable in revenue by using higher property taxes to compensate for other revenue declines. Furthermore, these cities were able to rely on their net assets to engage in deficit spending. These findings indicate that cities are relying on traditional strengths of local governments, but are also able to engage in the deficit spending that is typically characteristic of national governments. It also seems to be the case that grants for capital projects were largely transferred into highly liquid and spendable assets.
Enhanced response using a multicomponent urine alarm treatment for nocturnal enuresis
Authors: Axelrod Michael I. , Tornehl Christopher , Fontanini‐Axelrod Angela
Published: March 2014

Purpose

The current study investigated the effects of using the combination of a urine alarm and simple reward system to treat nocturnal enuresis (NE) for three children who failed to fully respond to the urine alarm alone.

Design and Methods

A withdrawal design (i.e., ABACA) embedded within a delayed multiple baseline design across participants was used to evaluate the effects of the urine alarm alone and in combination with a reward system on participants' frequency of wet nights per week. Results were analyzed through visual and descriptive methods.

Results

The urine alarm in combination with a reward system resulted in improvements in all three participants' NE. These results are contrasted with the urine alarm alone, which produced less frequent dry nights.

Practice Implications

Nursing professionals in primary care settings are positioned to provide evidence‐based treatment recommendations to families with children with NE. Findings from the current study provide a promising approach to the treatment of NE for those children who fail to respond fully to the urine alarm.
Pathways Involving Beta‐3 Adrenergic Receptors Modulate Cold Stress‐Induced Detrusor Overactivity in Conscious Rats
Authors: IMAMURA Tetsuya , ISHIZUKA Osamu , OGAWA Teruyuki , YAMAGISHI Takahiro , YOKOYAMA Hitoshi , MINAGAWA Tomonori , NAKAZAWA Masaki , NISHIZAWA Osamu
Published: March 2014

Objective

To investigate pathways involving beta‐3 adrenergic receptors (ARs) in detrusor overactivity induced by cold stress, we determined if the beta‐3 AR agonist CL316243 could modulate the cold stress‐induced detrusor overactivity in normal rats.

Methods

Two days prior to cystometric investigations, the bladders of 10‐week‐old female Sprague–Dawley rats were cannulated. Cystometric measurements of the unanesthetized, unrestricted rats were taken to estimate baseline values at room temperature (RT, 27 ± 2 °C) for 20 min. They were then intravenously administered vehicle, 0.1, or 1.0 mg/kg CL316243 (n = 6 in each group). Five minutes after the treatments, they were gently and quickly transferred to the low temperature (LT, 4 ± 2 °C) room for 40 min where the cystometric measurements were again made. Afterward, the rats were returned to RT for final cystometric measurements. The cystometric effects of CL316243 were also measured at RT (n = 6 in each group).

Results

At RT, both low and high dose of CL316243 decreased basal and micturition pressure while the high dose (1.0 mg/kg) significantly increased voiding interval and bladder capacity. During LT exposure, the high dose of CL316243 partially reduced cold stress‐induced detrusor overactivity characterized by increased basal pressure and urinary frequency. The high drug dose also significantly inhibited the decreases of both voiding interval and bladder capacity compared to the vehicle‐ and low dose (0.1 mg/kg)‐treated rats.

Conclusion

A high dose of the beta‐3 agonist CL316243 could modulate cold stress‐induced detrusor overactivity. Therefore, one of the mechanisms in cold stress‐induced detrusor overactivity includes a pathway involving beta‐3 ARs.
Petrogenesis of anomalous Queen Alexandra Range enstatite meteorites and their relation to enstatite chondrites, primitive enstatite achondrites, and aubrites
Authors: van Niekerk Deon , Keil Klaus , Humayun Munir
Published: March 2014

Queen Alexandra Range (QUE) meteorite 94204 is an anomalous enstatite meteorite whose petrogenesis has been ascribed to either partial melting or impact melting. We studied the meteorite pairs QUE 94204, 97289/97348, 99059/99122/99157/99158/99387, and Yamato (Y)‐793225; these were previously suggested to represent a new grouplet. We present new data for mineral abundances, mineral chemistries, and siderophile trace element compositions (of Fe,Ni metal) in these meteorites. We find that the texture and composition of Y‐793225 are related to EL6, and that this meteorite is unrelated to the QUEs. The mineralogy and siderophile element compositions of the QUEs are consistent with petrogenesis from an enstatite chondrite precursor. We caution that potential re‐equilibration during melting and recrystallization of enstatite chondrite melt‐rocks make it unreliable to use mineral chemistries to assign a specific parent body affinity (i.e., EH or EL). The QUEs have similar mineral chemistries among themselves, while slight variations in texture and modal abundances exist between them. They are dominated by inclusion‐bearing millimeter‐sized enstatite (average En99.1–99.5) with interstitial spaces filled predominantly by oligoclase feldspar (sometimes zoned), kamacite (Si approximately 2.4 wt%), troilite (≤2.4 wt% Ti), and cristobalite. Siderophile elements that partition compatibly between solid metal and liquid metal are not enriched like in partial melt residues Itqiy and Northwest Africa (NWA) 2526. We find that the modal compositions of the QUEs are broadly unfractionated with respect to enstatite chondrites. We conclude that a petrogenesis by impact melting, not partial melting, is most consistent with our observations.
Soluble organic compounds in the Tagish Lake meteorite
Authors: Hilts Robert W. , Herd Christopher D. K. , Simkus Danielle N. , Slater Greg F.
Published: March 2014

The C2 ungrouped Tagish Lake meteorite preserves a range of lithologies, reflecting variable degrees of parent‐body aqueous alteration. Here, we report on soluble organic compounds, including aliphatic and aromatic hydrocarbons, monocarboxylic acids, and amino acids, found within specimens representative of the range of aqueous alteration. We find that differences in soluble organic compounds among the lithologies may be explained by oxidative, fluid‐assisted alteration, primarily involving the derivation of soluble organic compounds from macromolecular material. In contrast, amino acids probably evolved from precursor molecules, albeit in parallel with other soluble organic compounds. Our results demonstrate the role of parent‐body alteration in the modification of organic matter and generation of prebiotic compounds in the early solar system, and have implications for interpretation of the complement of soluble organic compounds in carbonaceous chondrites.
Calreticulin Protects Rat Microvascular Endothelial Cells against Microwave Radiation‐induced Injury by Attenuating Endoplasmic Reticulum Stress
Authors: Li Wei‐Hong , Li Yu‐Zhen , Song Dan‐Dan , Wang Xiao‐Reng , Liu Mi , Wu Xu‐Dong , Liu Xiu‐Hua
Published: March 2014

Objective

This study was designed to evaluate whether exogenous CRT was beneficial for alleviating MR‐induced injury by suppressing ER stress in rat MMECs.

Methods

MMECs were pretreated with CRT (25 pg/mL) for 12 hours, followed by the exposure to 2.856 GHz radiation at a mean power density of 30 mW/cm2 for six minutes. MR‐induced injury in MMECs was evaluated by LDH leakage, apoptosis, and cell viability analysis. The expression of GRP78, CRT, CHOP, Bcl‐2, and Bax were examined by Western blot analysis to reflect ER stress response and ER stress‐related apoptosis.

Results

MR induced marked MMECs injury, as shown by increased LDH leakage and apoptosis rate and decreased cell viability. MR also induced excessive ER stress, characterized by increased expression of GRP78 and CRT, and ER stress‐related apoptotic signaling as well, as shown by the upregulation of CHOP and Bax and the downregulation of Bcl‐2. Exogenous CRT pretreatment remarkably attenuated MR‐induced cell apoptosis and LDH leakage, ER stress, and activation of the ER stress‐related apoptotic signaling.

Conclusions

Exogenous CRT attenuates MR‐induced ER stress‐related apoptosis by suppressing CHOP‐mediated apoptotic signaling pathways in MMECs.
Rhodotorula glutinis meningitis: a case report and review of literature
Authors: Menon Sarala , Gupta H. R. , Sequeira R. , Chavan Shazia , Gholape D. , Amandeep S. , Bhilave N. , Chowdhary A. S.
Published: March 2014

Rhodotorula is ubiquitous saprophytic yeast belonging to phylum Basidiomycota. These encapsulated basidiomycetes are being increasingly recognised as important emerging human pathogens. There are scanty reports of meningitis caused by Rhodurorula spp in HIV infected patients. We present one such case of meningitis by Rhodutorula glutinis in HIV‐infected patient. The patient also had a past history of abdominal tuberculosis. The diagnosis of Rhodotorula was confirmed by Gram staining and culture of the cerebrospinal fluid (CSF). Contamination was ruled out by repeated culturing of CSF from the same patient. Therapy with Amphotericin B showed good results. Patient was discharged from the hospital. However, in the seventh month of follow‐up patient was readmitted with complaints of fever, breathlessness, altered sensorium, vomiting and succumbed to his illness. This time the CSF cultures remained negative for Rhodotorula, acid fast bacilli and other pyogenic organisms. Our last 11‐year retrospective analysis of 8197 specimens received for mycological work‐up showed that this is the first report of R. glutinis isolation from our institute.
Root jasmonic acid synthesis and perception regulate folivore‐induced shoot metabolites and increase Nicotiana attenuata resistance
Authors: Fragoso Variluska , Rothe Eva , Baldwin Ian T. , Kim Sang‐Gyu
Published: March 2014

While jasmonic acid (JA) signaling is widely accepted as mediating plant resistance to herbivores, and the importance of the roots in plant defenses is recently being recognized, the role of root JA in the defense of above‐ground parts remains unstudied.

To restrict JA impairment to the roots, we micrografted wildtype Nicotiana attenuata shoots to the roots of transgenic plants impaired in JA signaling and evaluated ecologically relevant traits in the glasshouse and in nature.

Root JA synthesis and perception are involved in regulating nicotine production in roots. Strikingly, systemic root JA regulated local leaf JA and abscisic acid (ABA) concentrations, which were associated with differences in nicotine transport from roots to leaves via the transpiration stream. Root JA signaling also regulated the accumulation of other shoot metabolites; together these account for differences in resistance against a generalist, Spodoptera littoralis, and a specialist herbivore, Manduca sexta. In N. attenuata's native habitat, silencing root JA synthesis increased the shoot damage inflicted by Empoasca leafhoppers, which are able to select natural jasmonate mutants. Silencing JA perception in roots also increased damage by Tupiocoris notatus.

We conclude that attack from above‐ground herbivores recruits root JA signaling to launch the full complement of plant defense responses.
Alternative Sites for Right Ventricular Pacing in Chagas Disease: A Comparative Study of the Mid‐Septum and Inflow Tract
Authors: da SILVA JÚNIOR OTAVIANO , BORGES MARIA CÂNDIDA CALZADA , de MELO CELSO SALGADO , NASCENTE GABRIEL ANTONIO NOGUEIRA , CORREIA DALMO
Published: March 2014

Background

The right ventricular mid‐septum and inflow tract are alternative pacing sites that are potentially less harmful to cardiac function.

Objective

This study aimed to analyze the influence of these two alternative pacing sites on the clinical course of patients with chronic Chagas disease, who underwent definitive pacemaker implantation.

Methods

A total of 80 patients with Chagas disease and classical indications for definitive pacemaker implantation were randomized into two groups between October 2008 and August 2010: 40 received inflow tract implantation and 40 patients received mid‐septum implantation. The analyzed parameters included: (1) progression stage of chronic chagasic cardiomyopathy (CCC), (2) electrocardiographic analysis, (3) left ventricular remodeling, and (4) electromechanical dyssynchrony. The assessment was performed 24–48 hours after implantation and a follow‐up period of 18 months.

Results

Compared with inflow tract implantation, mid‐septum implantation was associated with slower CCC progression and the generation of narrower QRS complexes (131.8 ± 8.4 milliseconds vs 150.5 ± 10.5 milliseconds; P < 0.01). No left ventricular remodeling was detected. Intraventricular dyssynchrony was more frequent in the inflow tract group than in the mid‐septum group (85% vs 32.5%, respectively; odds ratio [OR], 9.15; P = 0.02) as was interventricular dyssynchrony (37.5% vs 17.5%, respectively; OR, 2.83; P < 0.01).

Conclusions

Mid‐septum implantation was associated with slower CCC progression, generation of narrower QRS complexes, and lower electromechanical dyssynchrony, suggesting that this pacing site could be less harmful to cardiac function than the inflow tract site in patients with CCC.
No Simples, No Gunk, No Nothing
Authors: Cowling Sam
Published: March 2014

Mereological realism holds that the world has a mereological structure – i.e. a distribution of mereological properties and relations. In this article, I defendEleaticism about properties, according to which there are no causally inert non‐logical properties. I then present anEleatic argument for mereological anti‐realism, which denies the existence of both mereological composites and mereological simples. After defendingEleaticism and mereological anti‐realism, I argue that mereological anti‐realism is preferable to mereological nihilism. I then conclude by examining the thesis that composition is identity and noting its consequences for the question of mereological structure.
Water relations of Robinia pseudoacacia L.: do vessels cavitate and refill diurnally or are R‐shaped curves invalid in Robinia?
Authors: WANG RUIQING , ZHANG LINGLING , ZHANG SHUOXIN , CAI JING , TYREE MELVIN T.
Published: March 2014

Since 2005, an unresolved debate has questioned whether R‐shaped vulnerability curves (VCs) might be an artefact of the centrifuge method of measuring VCs. VCs with R‐shape show loss of stem conductivity from approximately zero tension, and if true, this suggests that some plants either refill embolized vessels every night or function well with a high percentage of vessels permanently embolized. The R‐shaped curves occur more in species with vessels greater than half the length of the segments spun in a centrifuge. Many have hypothesized that the embolism is seeded by agents (bubbles or particles) entering the stem end and travelling towards the axis of rotation in long vessels, causing premature cavitation. VCs were measured on Robinia pseudoacacia L. by three different techniques to yield three different VCs; R‐shaped: Cavitron P50 = 0.30 MPa and S‐shaped: air injection P50 = 1.48 MPa and bench top dehydration P50 = 3.57 MPa. Stem conductivity measured in the Cavitron was unstable and is a function of vessel length when measured repeatedly with constant tension, and this observation is discussed in terms of stability of air bubbles drawn into cut‐open vessels during repeated Cavitron measurement of conductivity; hence, R‐shaped curves measured in a Cavitron are probably invalid.
The Effect of Photodynamic Action on Leakage of Ions Through Liposomal Membranes that Contain Oxidatively Modified Lipids
Authors: Ytzhak Shany , Ehrenberg Benjamin
Published: March 2014

Singlet oxygen, created in photosensitization, peroxidizes unsaturated fatty acids of the membrane's lipids. This generates alcoholic or aldehyde groups at double bonds' breakage points. In a previous study, we examined the leakage of a K+‐induced cross‐membrane electric potential of liposomes that undergo photosensitization. The question remains to what extent peroxidized lipids can compromise the stability of the membrane. In this study, we studied the effect of the oxidatively modified lipids PGPC and ALDOPC in the membrane on its stability, by monitoring the membrane electric potential with the potentiometric dye DiSC2(5). As the content of the modified lipids increases the membrane becomes less stable, and even at just 2% of the modified lipids the membrane's integrity is affected, in respect to the leakage of ions through it. When the liposomes that contain the modified lipids undergo photosensitization by hematoporphyrin, the lipid bilayer becomes even more unstable and passage of ions is accelerated. We conclude that the existence of lipids with a shortened fatty acid that is terminated by a carboxylic acid or an aldehyde and more so when photosensitized damage occurs to unsaturated fatty acids in lecithin, add up to a critical alteration of the membrane, which becomes leaky to ions.
Problem gamblers are hyposensitive to wins: An analysis of skin conductance responses during actual gambling on electronic gaming machines
Authors: Lole Lisa , Gonsalvez Craig J. , Barry Robert J. , Blaszczynski Alex
Published: March 2014

Physiological arousal is purportedly a key determinant in the development and maintenance of gambling behaviors, with problem gambling conceptualized in terms of abnormal autonomic responses. Theoretical conceptualizations of problem gambling are discordant regarding the nature of deficit in this disorder; some accounts posit that problem gamblers are hypersensitive to reward, and others that they are hyposensitive to reward and/or punishment. Previous research examining phasic electrodermal responses in gamblers has been limited to laboratory settings, and reactions to real gaming situations need to be examined. Skin conductance responses (SCRs) to losses, wins, and losses disguised as wins (LDWs) were recorded from 15 problem gamblers (PGs) and 15 nonproblem gamblers (NPGs) while they wagered their own money during electronic gaming machine play.PGsdemonstrated significantly reducedSCRsto reward.SCRsto losses andLDWsdid not differ for eitherPGsorNPGs. This hyposensitivity to wins may reflect abnormalities in incentive processing, and may represent a potential biological marker for problem gambling.
The antecedents of open business models: an exploratory study of incumbent firms
Authors: Frankenberger Karolin , Weiblen Tobias , Gassmann Oliver
Published: March 2014

Firms engage increasingly in open business models. While most research has previously focused on typologies or challenges of open business models, their specific antecedents have not been studied so far. We use data from eight open business model cases to explore this question and identify five main antecedents of open business models: (1) business model inconsistency, (2) need to create and capture new value, (3) previous experience with collaboration, (4) open business model patterns, and (5) industry convergence. Based on openness characteristics from the existing literature, we differentiate four basic types of open business models and develop an initial understanding of the relevance of the identified antecedents for each of them. We thereby provide first guidelines for practitioners in choosing the right form of business model openness for their company.
Innovation without me: why employees do (not) participate in organizational innovation communities
Authors: Wendelken Anke , Danzinger Frank , Rau Christiane , Moeslein Kathrin M.
Published: March 2014

A key issue in community research is the set of motivations stimulating individuals to participate and contribute voluntarily to communities. This article examines the motivations of employees, who are traditionally not involved in the innovation process, to (not) participate in organizational innovation communities. Building on an in‐depth single case study, we aim to answer the following research questions: (1) What motivates participants of organizational innovation communities to participate? and (2) What motivates nonparticipants of organizational innovation communities to not participate? We find and categorize multiple factors that motivate non‐research and development employees to participate and to not participate. Moreover, we find an overlap as well as differences in the set of motivations of participants and nonparticipants. With nonparticipants normally being a large but barely explicitly recognized group, we argue that the found deviations contribute to the understanding of motivations in the context of organizational innovation communities and allow for direct design implications for innovation managers.
Dealing with the devil of deviation: managing uncertainty during product development execution
Authors: Munthe Caroline Ingvarsson , Uppvall Lars , Engwall Mats , Dahlén Lars
Published: March 2014

This paper examines deviations in complex product development. Based on an extensive case study, using participant observations, interviews, and data from deviation reports, it illustrates the causes, procedures, management challenges of deviations, and organizational roles devoted to deviation management. Based on the rich data material, it furthermore proposes a typology of deviations developed for a better understanding of this significant empirical phenomenon.
Vague Objects with Sharp Boundaries
Authors: Benovsky Jiri
Published: March 2014

In this article I shall consider two seemingly contradictory claims: first, the claim that everybody who thinks that there are ordinary objects has to accept that they are vague, and second, the claim that everybody has to accept the existence of sharp boundaries to ordinary objects. The purpose of this article is of course not to defend a contradiction. Indeed, there is no contradiction because the two claims do not concern the same ‘everybody’. The first claim, that all ordinary objects are vague, is a claim that stems both from common sense intuitions as well as from various types of ontologies of ordinary objects. This puts then pressure on theories of vagueness to account for the vague nature of ordinary objects – but, as we shall see, all theories of vagueness have to accept the existence of sharp thresholds. This is obvious in the case of epistemicism, and it is a well‐known defect of supervaluationism, but as we will see friends of metaphysical vagueness do have to endorse the existence of sharp thresholds in their theory as well. Consequently, there are reasons for dissatisfaction with these accounts, since they do not seem to be able to do the job we asked them to do.
Parameter Estimation for Hidden Markov Models with Intractable Likelihoods
Authors: Dean Thomas A. , Singh Sumeetpal S. , Jasra Ajay , Peters Gareth W.
Published: March 2014

Approximate Bayesian computation (ABC) is a popular technique for analysing data for complex models where the likelihood function is intractable. It involves using simulation from the model to approximate the likelihood, with this approximate likelihood then being used to construct an approximate posterior. In this paper, we consider methods that estimate the parameters by maximizing the approximate likelihood used in ABC. We give a theoretical analysis of the asymptotic properties of the resulting estimator. In particular, we derive results analogous to those of consistency and asymptotic normality for standard maximum likelihood estimation. We also discuss how sequential Monte Carlo methods provide a natural method for implementing our likelihood‐based ABC procedures.
Using Structured Telephone Follow‐up Assessments to Improve Suicide‐Related Adverse Event Detection
Authors: Arias Sarah A. , Zhang Zi , Hillerns Carla , Sullivan Ashley F. , Boudreaux Edwin D. , Miller Ivan , Camargo Carlos A.
Published: March 2014

Adverse event (AE) detection and reporting practices were compared during the first phase of the Emergency Department Safety Assessment and Follow‐up Evaluation (ED‐SAFE), a suicide intervention study. Data were collected using a combination of chart reviews and structured telephone follow‐up assessments postenrollment. Beyond chart reviews, structured telephone follow‐up assessments identified 45% of the total AEs in our study. Notably, detection of suicide attempts significantly varied by approach with 53 (18%) detected by chart review, 173 (59%) by structured telephone follow‐up assessments, and 69 (23%) marked as duplicates. Findings provide support for utilizing multiple methods for more robust AE detection in suicide research.
Impact of choice of NRTI in first‐line antiretroviral therapy: a cohort analysis of stavudine vs. tenofovir
Authors: Brennan Alana T. , Shearer Kate , Maskew Mhairi , Long Lawrence , Sanne Ian , Fox Matthew P.
Published: March 2014

Objective

In April 2010, South Africa replaced stavudine with tenofovir in first‐line antiretroviral therapy (ART) despite tenofovir's higher cost. We examined treatment outcomes over 24 months amongst patients initiated on tenofovir‐based vs. stavudine‐based first‐line regimens.

Methods

Prospective cohort analysis of 3940 patients newly initiating either stavudine‐based (April 2009 to March 2010) or tenofovir‐based (April 2010 to March 2011) ART in Johannesburg, South Africa. Cox proportional hazards models and Fine and Gray's competing risk regression accounting for death were used to model mortality and loss to follow‐up, respectively. Linear and log‐binomial regression were used to evaluate associations with immunologic response and unsuppressed virus (≥400 copies/ml), respectively.

Results

About 1878 patients prescribed tenofovir and 2062 patients prescribed stavudine were included. One hundred and sixty‐six (8.8%) tenofovir and 244 (11.8%) stavudine patients died. Three hundred and fifty (18.6%) tenofovir and 379 (18.4%) stavudine patients were lost to follow‐up over 24 months on ART. Adjusted regression models showed tenofovir and stavudine were comparable regarding death, loss to follow‐up, immunologic response and virologic status.

Conclusions

We found no difference in mortality, loss to follow‐up, immunological and virologic outcomes over the first 24‐months on ART associated with tenofovir compared with stavudine.
Thiol‐based redox proteins in abscisic acid and methyl jasmonate signaling in Brassica napus guard cells
Authors: Zhu Mengmeng , Zhu Ning , Song Wen‐yuan , Harmon Alice C. , Assmann Sarah M. , Chen Sixue
Published: March 2014

Reversibly oxidized cysteine sulfhydryl groups serve as redox sensors or targets of redox sensing that are important in various physiological processes. However, little is known about redox‐sensitive proteins in guard cells and how they function in stomatal signaling. In this study, Brassica napus guard‐cell proteins altered by redox in response to abscisic acid (ABA) or methyl jasmonate (MeJA) were identified by complementary proteomics approaches, saturation differential in‐gel electrophoresis and isotope‐coded affinity tagging. In total, 65 and 118 potential redox‐responsive proteins were identified in ABA‐ and MeJA‐treated guard cells, respectively. All the proteins contain at least one cysteine, and over half of them are predicted to form intra‐molecular disulfide bonds. Most of the proteins fall into the functional groups of ‘energy’, ‘stress and defense’ and ‘metabolism’. Based on the peptide sequences identified by mass spectrometry, 30 proteins were common to ABA‐ and MeJA‐treated samples. A total of 44 cysteines were mapped in the identified proteins, and their levels of redox sensitivity were quantified. Two of the proteins, a sucrose non‐fermenting 1‐related protein kinase and an isopropylmalate dehydrogenase, were confirmed to be redox‐regulated and involved in stomatal movement. This study creates an inventory of potential redox switches, and highlights a protein redox regulatory mechanism in ABA and MeJA signal transduction in guard cells.
A homolog of splicing factor SF1 is essential for development and is involved in the alternative splicing of pre‐mRNA in Arabidopsis thaliana
Authors: Jang Yun Hee , Park Hyo‐Young , Lee Keh Chien , Thu May Phyo , Kim Soon‐Kap , Suh Mi Chung , Kang Hunseung , Kim Jeong‐Kook
Published: March 2014

During initial spliceosome assembly, SF1 binds to intron branch points and interacts with U2 snRNP auxiliary factor 65 (U2AF65). Here, we present evidence indicating that AtSF1, the Arabidopsis SF1 homolog, interacts with AtU2AF65a and AtU2AF65b, the Arabidopsis U2AF65 homologs. A mutant allele of AtSF1 (At5g51300) that contains a T–DNA insertion conferred pleiotropic developmental defects, including early flowering and abnormal sensitivity to abscisic acid. An AtSF1 promoter‐driven GUS reporter assay showed that AtSF1 promoter activity was temporally and spatially altered, and that full AtSF1 promoter activity required a significant proportion of the coding region. DNA chip analyses showed that only a small proportion of the transcriptome was altered by more than twofold in either direction in the AtSF1 mutant. Expression of the mRNAs of many heat shock proteins was more than fourfold higher in the mutant strain; these mRNAs were among those whose expression was increased most in the mutant strain. An RT–PCR assay revealed an altered alternative splicing pattern for heat shock transcription factor HsfA2 (At2g26150) in the mutant; this altered splicing is probably responsible for the increased expression of the target genes induced by HsfA2. Altered alternative splicing patterns were also detected for the transcripts of other genes in the mutant strain. These results suggest that AtSF1 has functional similarities to its yeast and metazoan counterparts.
In vitro hypercoagulability on whole blood thromboelastometry associated with in vivo reduction of circulating red cell mass in dogs
Authors: McMichael Maureen A. , Smith Stephanie A. , Galligan Alyssa , Swanson Kelly S.
Published: March 2014

Background

Previous studies have reported a strong correlation between indicators of red cell mass (RCM) and thromboelastometry results (TEM) in several species, specifically an association of apparent hypercoagulability with decreased RCM.

Objectives

The objectives of the study were to (1) evaluate the effect of decreased circulating RCM on TEM results in dogs, and (2) determine the relative contributions of citrate dilution vs in vivo reduction of RCM to hemostatic potential.

Materials and Methods

Thirteen healthy dogs had one unit of blood removed on day 0. Whole blood, EDTA, and citrated blood samples for evaluation of TEM variables and PT, APTT, platelet count, fibrinogen, thrombin–antithrombin (TAT), and thrombin generation were collected at baseline, and 3 and 21 days after blood removal. Blood samples were also corrected to a PCV of 45% by adding citrate or removing plasma.

Results

On day 3 after blood removal, the PCV was significantly decreased (45 ± 6%) compared with baseline (52 ± 6%) and day 21 (50 ± 4%, P < .001), accompanied by TEM variables indicating hypercoagulability, which returned to baseline values by day 21. Other coagulation variables such as PT, APTT, platelet count, TAT, or plasma thrombin generation remained unchanged, with the exception of fibrinogen that was significantly higher on day 3. No changes were related to citrate dilution.

Conclusions

Transiently decreased RCM in vivo was accompanied by TEM variables indicating hypercoagulability, which was not confirmed by other coagulation variables. This suggests an artifact of TEM, which presents a potential limitation of this technology in patient populations with abnormal RCM.
Evaluation of the impact of tromethamine edetate disodium dihydrate on antimicrobial susceptibility of Pseudomonas aeruginosa in biofilm in vitro
Authors: Pye Charlotte C. , Singh Ameet , Weese J. Scott
Published: March 2014

Background

Biofilm formation by Pseudomonas aeruginosa has been documented in canine otic isolates. An increase in minimal inhibitory concentration (MIC) for specific antibiotics has been noted for biofilm‐embedded bacteria. Tromethamine edetate disodium dihydrate buffered to pH 8 with tromethamine hydrochloride and deionized water (Triz‐EDTA®) has been documented to potentiate bactericidal activity when used in combination with topical antibiotics, but the impact on biofilm‐embedded bacteria is unknown.

Hypothesis/Objectives

The objective of this study was to evaluate the impact of Triz‐EDTA® use on in vitro antimicrobial susceptibility of biofilm‐embedded P. aeruginosa.

Methods

Biofilm formation was documented using a microtitre plate assay. Broth microdilution was used to assess the MIC of neomycin, polymyxin B, enrofloxacin and gentamicin for the biofilm‐embedded bacteria. The microtitre plate assay was again used to assess the MIC of neomycin, polymyxin B, enrofloxacin and gentamicin for biofilm‐embedded bacteria with added Triz‐EDTA®.

Results

Thirty‐one isolates from dogs with otitis were tested. Addition of Triz‐EDTA® significantly reduced MICs for neomycin (P < 0.003) and gentamicin (P < 0.02) but not for polymyxin B (P = 0.3). Enrofloxacin MICs increased in the presence of Triz‐EDTA (P < 0.036).

Conclusions and clinical importance

Triz‐EDTA® may be a useful adjunctive treatment for chronic cases of Pseudomonas otitis where biofilms may have developed, if gentamicin or neomycin is to be used as a topical treatment. In vivo study is required to confirm this effect.
Abdominal wall necrotising fasciitis due to dislodged percutaneous endoscopic gastrostomy tube
Authors: Artul Suheil , Nseir William , Assaf Victor , Abboud Nabil
Published: March 2014

Accessing the stomach via a percutaneous endoscopic gastrostomy (PEG) tube is the preferred (and sometimes the only) method for providing enteral nutritional support in disabled patients. However, it is associated with serious and potentially lethal complications which must be completely recognised by physicians, by nurses and especially by radiologists. Abdominal wall necrotising fasciitis of a dislodged or leaking PEG tube could be a lethal complication. We present a case of a 74-year-old bed bound woman who was admitted to our hospital with fever and abdominal pain. On presentation, the patient’s temperature was 36°C and laboratory tests showed leucocytosis. Physical examination revealed extensive redness of the abdominal wall, diffuse tenderness of the abdomen and yellowish discharge around the gastrostomy.
Spotty skin pigmentation and multiple blue naevi as cutaneous markers for spinal melanotic schwannoma
Authors: Mahesh Inbasekaran , Karthikeyan Vilvapathy Senguttuvan , Malathi Munisamy
Published: March 2014

Spinal melanotic schwannomas are rare spinal tumours with a very poor prognosis in terms of mortality due to difficulty in complete resection and local recurrences. A 67-year-old man presented with acute onset progressive paraparesis for 2 weeks. The patient also had spotty skin pigmentations (blue naevi) in his right lateral thigh. MRI revealed an intradural extramedullary enhancing lesion in the lower thoracic cord level. With a preoperative diagnosis of simple nerve sheath tumour excision was planned. At laminotomy, an infiltrating “en plaque” like lesion reaching up to mid and upper thoracic cord level was identified and excision was carried out. Postoperative histopathology was unique with the identification of melanin and presence of epitheloid cells, with the additional detection of psammoma bodies and adipose-like cells. Melanotic schwannomas though rare and carry poor prognosis must be borne in mind in patients with spotty skin pigmentation and acute onset limb weakness.
Novel therapeutic use of Versajet for intestinal mucormycosis
Authors: Calvert William , Mullassery Dhanya , Shukla Rajeev , Lamont Graham
Published: March 2014

We describe the case of a 17-year-old boy who developed intestinal mucormycosis fromRhizophus oryzae(order Mucorales) following chemotherapy for the management of acute myeloid leukaemia. He underwent a hemicolectomy and further surgery utilising the pressure washing of Versajet to debride colonised fungal collections from the psoas muscle limiting the amount of surgical debridement needed.
Familial bulbar urethral strictures
Authors: Jindal Tarun , Pal Partha , Sinha Rajan Kumar , Karmakar Dilip
Published: March 2014

Strictures are commonly encountered in the urological practice. The most common aetiologies are infection, trauma and iatrogenic events. Familial occurrence of urethral stricture is exceptionally rare. We present a case in which bulbar urethral strictures developed in a father and his two sons.
Generalised weakness in a young patient: a cause for concern?
Authors: Saenz-Abad Daniel , Rivero-Sanz Elena , Lahoz-Perez Maria del Carmen , Martinez-Diez Maria
Published: March 2014

Muscular weakness in young patients is usually due to mild, self-limiting causes. Nonetheless, it is important to remember other, more serious aetiologies which can cause this clinical picture. Thyrotoxic hypokalaemic periodic paralysis (THPP) is a rare disease in Europe and the USA, with fatal cardiovascular and respiratory complications. It is characterised by recurrent episodes of generalised muscular weakness, especially in the legs, with an associated hypokalaemia and hyperthyroidism. Diagnosis is based on clinical history, laboratory tests and an ECG. Early treatment focused on cautious correction blood potassium and non-cardiac selective β-blockers. Additionally, it is imperative to normalise thyroid function to prevent relapses. We present a young, healthy man to the emergency department with episodes of intermittent leg weakness. The history and the ECG findings allowed for the diagnosis of THPP to be reached with early treatment causing remission.
Exploring cyclic dominance of sockeye salmon with a predator–prey model
Authors: Guill Christian , Carmack Eddy , Drossel Barbara
Published: March 2014

We explain in an intuitive and detailed way a predator–prey model that generates cyclic dominance in Fraser River sockeye salmon. In contrast with usual predator–prey models, this model includes four distinct prey lines and thus a combination of continuous and discrete dynamics, reflecting the particular freshwater and marine life cycle features of sockeye salmon (Oncorhynchus nerka) populations. The predator–prey interaction causing the oscillations takes place in the rearing lakes, rather than in the ocean. The values of most parameters of this model can be estimated from empirical data that are available for the large salmon-rearing lakes in the Fraser River basin. The mechanism that produces the oscillations in this model is compared with other mechanisms that can generate population oscillations, and we argue that predator–prey dynamics is the most likely mechanism to produce the observed patterns. We explain why the period of the oscillation is exactly 4 years, and we explore how the dynamical pattern is affected by changes in external conditions or by management decisions.
Effect of atorvastatin on the angiogenic responsiveness of coronary endothelial cells in normal and streptozotocin (STZ) induced diabetic rats
Authors: Chaudagar Kiranj K. , Mehta Anita A.
Published: March 2014

Atorvastatin, a lipid lowering agent, possesses various pleiotropic vasculoprotective effects, but its role in coronary angiogenesis is still controversial. Our objective was to study the effects of atorvastatin on the angiogenic responsiveness of coronary endothelial cells (cEC) from normal and diabetic rats. Male Wistar rats were distributed among 9 groups; (i) normal rats, (ii) 30 day diabetic rats, (iii) 60 day diabetic rats, (iv) normal rats administered a low dose of atorvastatin (1 mg/kg body mass, per oral (p.o.), for 15 days); (v) 30 day diabetic rats administered a low dose of atorvastatin; (vi) 60 day diabetic rats administered a low dose of atorvastatin; (vii) normal rats administered a high dose of atorvastatin (5 mg/kg, p.o., for 15 days); (viii) 30 day diabetic rats administered a high dose of atorvastatin; (ix) 60 day diabetic rats administered a high dose of atorvastatin. Each group was further divided into 2 subgroups, (i) sham ischemia–reperfusion and (ii) rats hearts that underwent ischemia–reperfusion. Angiogenic responsiveness the and nitric oxide (NO) releasing properties of the subgroups of cECs were studied using a chorioallantoic membrane assay and the Griess method, respectively. Atorvastatin treatment significantly increased VEGF-induced angiogenic responsiveness and the NO-releasing properties of cECs from all of the subgroups, compared with their respective non-treated subgroups except for the late-phase diabetic rat hearts that underwent ischemia–reperfusion, and the high dose of atorvastatin treatment groups. These effects of atorvastatin were significantly inhibited by pretreatment of cECs with l-NAME, wortmannin, and chelerythrine. Thus, treatment with a low dose of atorvastatin improves the angiogenic responsiveness of the cECs from normal and diabetic rats, in the presence of VEGF, via activation of eNOS–NO release.