bluuebunny/crossref_metadata_2025 huggingface dataset:
Consequences of New Product Development Speed: A Meta‐Analysis
Authors: Cankurtaran Pinar , Langerak Fred , Griffin Abbie
Published: April 2013

Five meta‐analyses previously have been published on the topic of new product development involving the concept of new product development speed. Three of these studies have investigated antecedents to new product development success, of which just one was new product development speed. The other two studies used new product development speed as the dependent variable, and analyzed antecedents to achieving speed. This article extends previous empirical generalizations in this domain by using a meta‐analytic methodology to understand the link between new product development speed and new product success at a more granular level. Specifically, it considers the relationship with different dimensions of success as measured overall or compositely, operationally (i.e., the process measures of decreasing development costs and proficiently managing market entry timing and the product measures of technical product performance and product competitive advantage), and relative to external success outcomes (i.e., customer based and financial success). While the results indicate that, in general, new product development speed is associated with improving success outcomes, those relationships may diminish or even disappear depending upon a number of methodological design decisions and research contexts. A subsequent meta‐analysis of the antecedents of development speed provides a more holistic picture of development speed. These results are broadly consistent with those produced by another recent meta‐analytic investigation of the issue. Together, these findings have important implications for academics pursuing further research in this domain, as well as for managers considering implementing a program to increase new product development speed.
Complements or Substitutes? Internal Technological Strength, Competitor Alliance Participation, and Innovation Development
Authors: Xu Shichun , Wu Fang , Cavusgil Erin
Published: April 2013

While a firm can choose to develop an innovation internally or externally, the internal knowledge development and external knowledge acquisition tend to interact with each other in the innovation process. The present study examines whether internal technological strength and external competitor alliance participation serve as complements or substitutes in innovation development. Built on the knowledge‐based view, this study offers a contingency perspective on the nature of knowledge integration between internal technological strength and external alliance relationships, and how they jointly influence radical and incremental innovation differently. Adopting a random effect negative binomial model specification, a panel data set of 64 pharmaceutical firms over a 15‐year period were used to test the hypothesized effects. The findings indicate that internal technological knowledge strength has an inverted U‐shaped relationship with radical and incremental innovation. More importantly, the findings also demonstrate that the combined effect of internal and external sources of innovation can have differential effects on radical and incremental innovation development. Specifically, competitor alliance participation strengthens the effect of internal technological strength on incremental product innovation while it weakens the above effect on radical product innovation. This suggests that internal and external sources of innovation may complement each other for incremental innovation while they may represent trade‐offs for radical innovation development. The above findings provide empirical evidence for the complexity of pursuing organizational ambidexterity in innovation generation and highlight the importance of balancing the internal and external knowledge sources in pursuing innovation.
A Stage‐Wise Approach to Exploring Performance Effects of Cycle Time Reduction
Authors: Eling Katrin , Langerak Fred , Griffin Abbie
Published: April 2013

Research on reducing new product development (NPD) cycle time has shown that firms tend to adopt different cycle time reduction mechanisms for different process stages. However, the vast majority of previous studies investigating the relationship between new product performance and NPD cycle time have adopted a monolithic process perspective rather than looking at cycle time for the distinct stages of the NPD process (i.e., fuzzy front end, development, and commercialization). As a result, little is known about the specific effect of the cycle times of the different stages on new product performance or how they interact to influence new product performance. This study uses a stage‐wise approach to NPD cycle time to test the main and interacting effects of fuzzy front end, development, and commercialization cycle times on new product performance using objective data for 399 NPD projects developed following a Stage‐Gate® type of process in one firm. The results reveal that at least in this firm, new product performance only increases if all three stages of the NPD process are consistently accelerated. This finding, combined with the previous research showing that firms use different mechanisms to accelerate different stages of the process, emphasizes the need to conduct performance effect studies of NPD cycle time at the stage level rather than at the monolithic process level.
I spy with my little eye something beginning with O: looking at what the myth of ‘doing the observations’ means in mental health nursing culture
Authors: Holyoake D.‐D.
Published: April 2013

Accessible summary

This paper uses ethnographic research conducted in psychiatric in‐patient settings to explore the phenomenon of observation.

The discussion uses a post‐structural frame to offer an alternative analysis and rethinking about what the performance of observing could and might mean in psychiatric nursing culture.

The traditional aim of viewing observation as a task to keep clients safe is juxtaposed against the possibility that it is the psychiatric culture (which subjects both the carer and the cared for) that is actually doing the observing.

The justification of observation beyond the analysis of keeping clients safe is negotiated by the way nurses observe one another and are themselves observed by psychiatric culture to ensure validated representation and performance.

Those who are familiar with psychiatric inpatient settings will be aware of the expressions ‘doing the obs’, ‘being on checks’ and ‘special observations’. That is because the task of observing patients is seen as being pivotal to the mental health nursing role. This paper describes an ethnographic research project that offers a rethinking of psychiatric observation. The author uses data from an ethnographic research project to provide an examination of the structure, process and outcome of this seemingly straightforward nursing task and explores how ‘doing the obs’ has additional symbolic and cultural meaning similar to what Barthes terms myth. The symbolic connotations are numerous and wide‐ranging and expose a practice that could be said to punctuate daily activities and an ordering of relationships between nurses and services users. The classic sociological issues of status, power and containment are all relevant, yet rethought. The use of ethnographic research allowed the author to focus on the more symbolic cultural dynamics and develop five initial ethnographic themes concerning the constituting experience of watching and being watched.
Clinical parameters predictive of outcomes in sorafenib‐treated patients with advanced hepatocellular carcinoma
Authors: Cho Ju‐Yeon , Paik Yong‐Han , Lim Ho Yeong , Kim Young Gon , Lim Hyo Keun , Min Yang Won , Gwak Geum‐Youn , Choi Moon Seok , Lee Joon Hyeok , Koh Kwang Cheol , Paik Seung Woon , Yoo Byung Chul
Published: April 2013

Background

Sorafenib is an orally active multikinase inhibitor approved for the treatment of advanced hepatocellular carcinoma (HCC). However, clinical parameters that may predict the treatment outcomes in sorafenib‐treated advanced HCC patients remains unknown.

Methods

A total of 99 advanced (BCLC C) HCC patients treated with sorafenib as an initial treatment modality from January 2007 to December 2011 were retrospectively reviewed. Overall survival was the primary endpoint for the analysis. Various clinical parameters including tumour stage and adverse effects to sorafenib were analysed. Univariate and multivariate analysis were carried out to identify clinical parameters predictive of the effect of sorafenib.

Results

There were 86 males and 13 females included in this study, with a median age of 53 years. The median overall survival was 91 days. Sixty‐nine patients had Child‐Pugh class A cirrhosis and 30 patients had Child‐Pugh class B cirrhosis. Hepatitis B virus was the predominant cause of HCC (75.8%). Noted adverse effects were hand‐foot syndrome, diarrhoea, fatigue, abdominal pain, nausea and stomatitis. The presence of hand‐foot syndrome and diarrhoea and the absence of portal vein thrombosis and lymph node metastasis predicted a better overall survival in the multivariate analysis. Excluding the absence of lymph node metastasis, the same parameters were associated with a longer radiological time to progression.

Conclusion

Advanced HCC patients treated with sorafenib who experienced hand‐foot syndrome and diarrhoea showed better overall survival than patients without these side effects. These side effects may be used as clinical parameters predictive of sorafenib response in patients with HCC.
The evolutionary history of Xiphophorus fish and their sexually selected sword: a genome‐wide approach using restriction site‐associated DNA sequencing
Authors: Jones Julia C. , Fan Shaohua , Franchini Paolo , Schartl Manfred , Meyer Axel
Published: April 2013

Next‐generation sequencing (NGS) techniques are now key tools in the detection of population genomic and gene expression differences in a large array of organisms. However, so far few studies have utilized such data for phylogenetic estimations. Here, we use NGS data obtained from genome‐wide restriction site‐associated DNA (RAD) (∼66000 SNPs) to estimate the phylogenetic relationships among all 26 species of swordtail and platyfish (genus Xiphophorus) from Central America. Past studies, both sequence and morphology‐based, have differed in their inferences of the evolutionary relationships within this genus, particularly at the species‐level and among monophyletic groupings. We show that using a large number of markers throughout the genome, we are able to infer the phylogenetic relationships with unparalleled resolution for this genus. The relationships among all three major clades and species within each of them are highly resolved and consistent under maximum likelihood, Bayesian inference and maximum parsimony. However, we also highlight the current cautions with this data type and analyses. This genus exhibits a particularly interesting evolutionary history where at least two species may have arisen through hybridization events. Here, we are able to infer the paternal lineages of these putative hybrid species. Using the RAD‐marker‐based tree we reconstruct the evolutionary history of the sexually selected sword trait and show that it may have been present in the common ancestor of the genus. Together our results highlight the outstanding capacity that RAD sequencing data has for resolving previously problematic phylogenetic relationships, particularly among relatively closely related species.
Prolonged stimuli alter the bacterial chemosensory clusters
Authors: Frank Vered , Vaknin Ady
Published: April 2013

The clustering of membrane‐bound receptors plays an essential role in various biological systems. A notable model system for studying this phenomenon is the bacterial chemosensory cluster that allows motile bacteria to navigate along chemical gradients in their environment. While the basic structure of these chemosensory clusters is becoming clear, their dynamic nature and operation are not yet understood. By measuring the fluorescence polarization of tagged receptor clusters in live Escherichia coli cells, we provide evidence for stimulus‐induced dynamics in these sensory clusters. We find that when a stimulus is applied, the packing of the receptors slowly decreases and that the process reverses when the stimulus is removed. Consistent with these physical changes we find that the effective cooperativity of the kinase response slowly evolves in the presence of a stimulus. Time‐lapse fluorescence imaging indicates that, despite these changes, the receptor clusters do not generally dissociate upon ligand binding. These data reveal stimulus‐dependent plasticity in chemoreceptor clusters.
Comparative in vitro fungicidal activity of echinocandins against Candida albicans in peritoneal dialysis fluids
Authors: Tobudic Selma , Forstner Christina , Schranz Heidelinde , Poeppl Wolfgang , Vychytil Andreas , Burgmann Heinz
Published: April 2013

The peritoneal dialysis (PD)‐associated peritonitis caused by fungi is a relatively rare, but very serious disease. PD fluids (PDFs) affect inhibitory efficacy on the microorganisms' growth, which may compromise the affectivity of some antimicrobials. The purpose of this study was to investigate in vitro the fungicidal effectiveness of echinocandins in diverse PDFs. The fungicidal efficacy of caspofungin (CAS), anidulafungin (ANA), micafungin (MYC) against five clinical isolates of Candida albicans was studied in the different PDFs using time‐kill curves. As control substance amphotericin B was used. Echinocandins showed slower and reduced killing of C. albicans in PDFs when compared with the time‐kill curves in control bouillon. At concentration of 8 × minimal inhibitory concentration (MIC) the greatest reduction in the growth of C. albicans was seen by ANA in lactate‐buffered Nutrineal PD4® with 1.1% amino acid (2.33 ± 0.52 log10 CFU ml−1), and by CAS and MYC in lactate‐buffered Dianeal PD4® with 1.36% glucose (2.36 ± 0.89 log10 CFU ml−1 and 2.36 ± 0.99 log10 CFU ml−1 respectively). Using high concentration of 128 × MIC echinocandins achieved fungicidal effect in all PDFs. PDFs may significantly impair the activities of echinocandins, but fungicidal activity of drugs can be achieved at high concentration of 128 × MIC.
Brain malformation with loss of normal FGFR3 expression in thanatophoric dysplasia type I
Authors: Itoh Kyoko , Pooh Ritsuko , Kanemura Yonehiro , Yamasaki Mami , Fushiki Shinji
Published: April 2013

Thanatophoric dysplasia is a lethal form of chondrodysplastic dwarfism in which the cerebral cortex displays a unique and complex malformation. We report a female case of thanatophoric dysplasia type I (TD1) with FGFR3 mutation. In this case, fetal ultrasonography at the 18th week of gestation led to a prenatal diagnosis of TD1 with characteristic bone features. The subject was stillborn at the 21st week of gestation, showing marked shortening of the long bones, small thorax and curved short femurs, but without a cloverleaf skull. The temporal lobe was enlarged and hyperconvoluted, appearing as broad gyri and deep sulci, which were composed of focal polymicrogyria‐like shallow sulci and heterotopic neuroblastic nests in the intermediate zone and marginal zone. Abundant precursor cells, immunoreactive for nestin and Ki‐67 were observed with scattered mitoses in the thickened inner intermediate and subventricular zones of the temporal and occipital lobes. The cytoarchitecture from the entorhinal cortex to Ammon's horn was disorganized with leptomeningeal glioneuronal heterotopia, immunoreactive for doublecortin and nestin. The expression of FGFR3 was virtually not discernible in the temporal and occipital lobes or in the hippocampus. Genetic analysis revealed a point mutation at C8526T (R248C) in the exon 7 of FGFR3. This is the first report that demonstrates that overproduction of intermediate progenitor cells might be induced by FGFR3 mutation in a human TD1 case.
A population‐based study of associations between functional gastrointestinal disorders and psychosocial characteristics in Xi'an, China
Authors: Xu J.‐R. , Shang L. , Si W.‐L. , Song Y. , Wang Y. , Ma J.‐L. , Liu J.
Published: April 2013

Background

Functional gastrointestinal disorders (FGIDs) are disorders with chronic and recurring gastrointestinal symptoms. This study investigated the prevalence of FGIDs, assessed the association between FGIDs and psychosocial factors, and identified potential risk factors for FGIDs in a population in Xi'an, China.

Methods

Of 752 recruited residents in Xi'an, 720 were selected for an epidemiological survey using a cluster sampling method. All subjects were interviewed face‐to‐face to complete the Chinese version of ROME III FGIDs questionnaire, the Symptom Check‐List‐90, the Eysenck Personality Questionnaire, a Life Event Scale, and a questionnaire regarding personal childhood adversity. The prevalence of FGIDs and associations between FGIDs and psychosocial factors were determined using EpiData Software. Logistic regression analysis was performed to identify the potential risk factors for FGIDs.

Key Results

The prevalence of FGIDs in this sample population was 14.3% (103/720). There were 13 (1.8%) cases of overlap of different FGIDs. No significant difference in the prevalence of FGIDs was observed between men and women. Alcohol intake and smoking habits were significantly associated with the presence of FGIDs. The presence of FGIDs was significantly associated with psychological factors and influences such as personality type, life events, childhood adversity, and psychopathology. The potential risk factors for contracting FGIDs were certain life events, childhood adversity, somatization, and a hostile affect (P < 0.001).

Conclusions & Inferences

The prevalence of FGIDs and overlap syndrome in Xi'an, China was lower than that reported in other countries. There was a strong correlation between specific lifestyle habits and psychosocial characteristics and the presence of FGIDs.
A Potential Autocrine Role for Interferon Tau in Ovine Trophectoderm
Authors: Wang X‐L , Wang K , Han G‐C , Zeng S‐M
Published: April 2013

Contents

Interferon tau (IFNT), a type I IFN produced by the conceptus trophectoderm, is the signal for maternal pregnancy recognition in ruminants. The purpose of this study was to investigate whether IFNT effected on the proliferation of ovine trophectoderm cells in an autocrine manner. Elongated ovine conceptuses (Days 15, Day 0 = day of mating) were collected for isolation of mononuclear ovine trophectoderm (oTr‐1) cells, and conceptuses (Days 15 and 20, n = 4 and 3, respectively) were collected for RNA extraction. We demonstrated that the IFNT receptor, IFNAR1, was expressed in trophectoderm of day 15 and 20 conceptuses. Interestingly, the ovine trophectoderm cell line oTr‐1 cultured in the presence of recombinant bovine IFNT (rbIFNT) displayed increased expressions of IFN‐stimulated genes (ISGs), such as IFN‐stimulated gene 15 (ISG15), 2‐5‐oligoadenylate synthetase 1 (OAS1) and bone marrow stromal cell antigen 2 (BST2). Meanwhile, the presence of rbIFNT in the culture media could promote the cell proliferation in a dose‐dependent manner. Furthermore, the connective tissue growth factor, which has diverse functions in cell proliferation and is involved in conceptus elongation, was upregulated in oTr‐1 cell by rbIFNT treatment in vitro. These data indicated that IFNT could act as an autocrine factor to regulate trophectoderm cell proliferation.
Constructing Emotional and Relational Understanding: The Role of Mother–Child Reminiscing about Negatively Valenced Events
Authors: Laible Deborah , Panfile Murphy Tia , Augustine Mairin
Published: April 2013

Although there is some evidence from cross‐sectional studies that reminiscing is an important context in which children construct socioemotional understanding, longitudinal evidence is lacking. The goal of this study was to examine longitudinally the links between the quality of reminiscing at 42 months and children's subsequent socioemotional development at 48 months. At 42 months, mothers and children reminisced about a past negatively‐valenced emotional event. These conversations were coded for maternal elaboration, the children's contribution and engagement, and the degree to which meaning was co‐constructed by the dyad. At 42 and 48 months, children took part in laboratory measures of socioemotional development. Whereas there were few links between concurrent reminiscing quality and sociomoral development, aspects of reminiscing quality at 42 months (including children's engagement and the dyad's co‐construction of meaning) were related to children's emotional understanding, empathy, representations of relationships, and moral‐self at 48 months. This study provides some of the first longitudinal evidence that reminiscing conversations are linked with children's subsequent sociomoral understanding.
How much is it going to cost me to complete a collection of football trading cards?
Authors: Gerke Oke
Published: April 2013

Trading cards for various sports and a range of other subjects such as architecture, animals, hobbies, and war have been in existence since the late nineteenth century and still enjoy great popularity. Two of the most prominent examples are baseball cards in the U.S. and football cards in Europe. Three strategies for collecting European football trading cards were investigated for two different groups: either a single collector or two collectors joining forces. An activity is proposed in which students use a simulation to compute the factor by which the number of trading cards bought exceeds the number to be collected. This enables them to estimate the expected costs of completing a collection of trading cards. The overall expected costs vary considerably, depending on the strategy used. Savings for a team of two collectors as opposed to a single collector are indicated.
Visceral varicella zoster virus infection after allogeneic stem cell transplantation
Authors: Doki N. , Miyawaki S. , Tanaka M. , Kudo D. , Wake A. , Oshima K. , Fujita H. , Uehara T. , Hyo R. , Mori T. , Takahashi S. , Okamoto S. , Sakamaki H. ,   The Kanto Study Group for Cell Therapy
Published: April 2013

Introduction

Varicella zoster virus (VZV) disease is one of the major infectious complications that can occur after allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Many reports have shown visceral VZV infection, a special type of VZV disease, to be rare. However, few studies so far have included a large number of patients.

Findings

Visceral VZV infection was found in 20 (0.8%) of 2411 patients who underwent allo‐HSCT at our hospitals. Seventeen (85%) patients were taking immunosuppressive agents at the time of presentation with zoster. The presenting symptom was abdominal pain in 16 patients (80%), unconsciousness in 3 patients (15%), and no symptoms in 1 patient. The mean time interval from allo‐HSCT to symptomatic visceral VZV infection was 273 days (103–800 days). The eruptions appeared within 3 days (0–13) after the first symptoms. Treatment with intravenous acyclovir was initiated before the appearance of eruptions in 3 of 18 patients (all 3 survived) with vesicular eruptions, the same day in 12 patients (11 survived, 1 died), and after the appearance in 3 patients (1 survived, 2 died). The overall mortality was 20%.

Conclusion

In conclusion, these data confirm that the incidence of visceral VZV infection is infrequent, but this disease is serious. When patients being treated with immunosuppressive agents demonstrate abdominal pain or unconsciousness, the possibility of visceral VZV infection should be considered as well as earlier therapeutic intervention.
Sequence type 398 meticillin‐resistant Staphylococcus aureus infection in a pet rabbit
Authors: Loncaric Igor , Künzel Frank
Published: April 2013

Background

Meticillin‐resistant Staphylococcus aureus (MRSA) is a frequent pathogen of humans and many animal species, and has become established as a veterinary pathogen.

Case report

In this case report we describe an MRSA infection in a dwarf rabbit, treatment of the infection and, subsequently, the genetic analysis of the isolated strain. The pet rabbit was presented to an animal hospital due to recurrent swellings on the head and on the neck. Bacteriological examination yielded Staphylococcus aureus, which was resistant to β‐lactam antibiotics. The isolate was confirmed as an MRSA by mecA PCR, Panton‐Valentine leukocidin (PVL) negative, and typed as multilocus sequence type (ST)398/staphylococcal protein A (spa) type t011/staphylococcal cassette chromosome mec (SCCmec) type SCCmecIVa. The rabbit was treated with rifampicin for 2 weeks. After 2.5 weeks the rabbit was clinically normal and control swabs were negative for MRSA.

Conclusions and clinical importance

This study is the first to report MRSA in a rabbit in Austria. This study contributes to the growing evidence that MRSA ST398 could be isolated from a variety of animals.
Study to assessin vitroantimicrobial activity of nine ear cleaners against 50Malassezia pachydermatisisolates
Authors: Mason Carly L. , Steen Stephen I. , Paterson Susan , Cripps Peter J.
Published: April 2013

Background

Ear cleaning is an important part of the successful therapy of otitis externa.

Hypothesis/Objectives

To evaluate thein vitroactivity of nine commercially available ear cleaners (Cerumaural®,CleanAuralDog®,Epi‐Otic®,MalAceticAural®,Otoclean®,Otodine®,Sancerum®,Surosolve®andTrizUltra™ + Keto) against 50Malassezia pachydermatisisolates from clinical cases of canine otitis externa. To the authors' knowledge, this is the first study to analyse thein vitrosusceptibility of a large number ofM. pachydermatisisolates to a variety of ear cleaner products.

Animals

Forty‐nine hospital population dogs diagnosed with otitis externa withMalasseziaspp. present on cytological examination of ear swabs and culture.

Methods

The antimicrobial activity of nine ear cleaners was tested against 50M. pachydermatisisolates from 49 clinical cases of canine otitis externa using anin vitroagar diffusion test.

Results

There were statistically significant differences in activity between ear cleaners, with five showing excellentin vitroanti‐Malasseziaactivity (CleanAuralDog®,Epi‐Otic®,MalAceticAural®,Sancerum®andTrizUltra™ + Keto), two moderate activity (Otodine®andSurosolve®), one variable activity (Otoclean®) and one no activity (Cerumaural®). There was a significant overall difference in susceptibility betweenM. pachydermatisisolates tested (P < 0.001).

Conclusions and clinical importance

Ear cleaners with activity againstMalasseziamay help to reduce the unnecessary use of antibiotic‐containing polypharmaceutical ear medications. This study shows that the use of a large number of isolates may provide a more accurate account of thein vitroactivity of a product.
Aeromechanical Control of High-Speed Axial Compressor Stall and Engine Performance—Part II: Assessments of Methodology
Authors: Coleman K. L. , McGee, III O. G.
Published: April 2013

A theoretical assessment was made explaining how aeromechanical feedback control can be implemented to stabilize rotating stall inception in high-speed axial compression systems. Ten aeromechanical control strategies were quantitatively evaluated based on the control-theoretic formulations and dimensionless performance analysis outlined in the Part I companion paper (McGee and Coleman, 2013, “Aeromechanical Control of High-Speed Axial Compressor Stall and Engine Performance—Part I: Control-Theoretic Models,” ASME J. Fluids Eng., 135(3), p. 031101). The maximum operating range for each aeromechanical control scheme was predicted for optimized structural parameters. Predictability and changeability in the hydrodynamic pressure, temperature, density, operability, and aeromechanical performance of dynamically-compensated, high-speed compressor maps of corrected pressure, corrected mass flow, corrected speeds, temperature ratios, and optimum efficiency were compared for the various aeromechanical control strategies. Compared with dynamically-compensated, low-speed compressor maps of pressure rise and flow coefficient (Gysling and Greitzer, 1995, “Dynamic Control of Rotating Stall in Axial Flow Compressors Using Aeromechanical Feedback,” ASME J. Turbomach., 117(3), pp. 307–319; McGee et al., 2004, “Tailored Structural Design and Aeromechanical Control of Axial Compressor Stall—Part I: Development of Models and Metrics, ASME J. Turbomach, 126(1), pp. 52–62; Fréchette et al., 2004, “Tailored Structural Design and Aeromechanical Control of Axial Compressor Stall—Part II: Evaluation of Approaches,” ASME J. Turbomach., 126(1), pp. 63–72), the present study shows that the most promising aeromechanical designs and controls for a class of high-speed compressors were the use of dynamic fluid injection. Dynamic compensations involving variable duct geometries and dynamically-re-staggered IGV and rotor blades were predicted to yield less controllability under high-speed flow environments. The aeromechanical interaction of a flexible casing wall was predicted to be destabilizing, and thus should be avoided in high-speed compression systems as in low-speed ones by designing sufficiently rigid structures to prevent casing ovalization or other structurally-induced variations in tip clearance.
The switches.ELM Resource: A Compendium of Conditional Regulatory Interaction Interfaces
Authors: Van Roey Kim , Dinkel Holger , Weatheritt Robert J. , Gibson Toby J. , Davey Norman E.
Published: April 2013

A resource centered on short linear motifs provides a repository and exploratory tool for conditional protein interactions.
Making the Final Cut
Authors: Hurtley Stella M.
Published: April 2013

When a daughter cell lets go, the mother cell cuts it loose.
Use of Rifamycin Drugs and Development of Infection by Rifamycin-Resistant Strains of Clostridium difficile
Authors: Huang Jamie S. , Jiang Zhi-Dong , Garey Kevin W. , Lasco Todd , DuPont Herbert L.
Published: April 2013

The relationship between rifamycin drug use and the development of resistant strains of
Clostridium difficile
was studied at a large university hospital in Houston, TX, between May 2007 and September 2011. In 49 of 283 (17.3%) patients with
C. difficile
infection (CDI), a rifamycin-resistant strain of
C. difficile
was identified that compares to a rate of 8% using the same definitions in 2006-2007 (
P
= 0.59). The 49 patients infected by a resistant organism were matched by date of admission to 98 control patients with CDI from whom a rifamycin-susceptible
C. difficile
strain was isolated. Cases and controls did not differ according to demographic and clinical characteristics and showed similar but low rates of prior rifamycin use. Similar rates of rifamycin resistance were seen in cases of hospital-acquired CDI (38/112 [34%]) versus community-acquired CDI (7/20 [35%]). At a university hospital in which rifaximin was commonly used, infection by rifamycin-resistant strains of
C. difficile
was not shown to relate to prior use of a rifamycin drug or to acquiring the infection in the hospital, although the rate of overall resistance appeared to be rising.
Human Organic Cation Transporters 1 (
SLC22A1
), 2 (
SLC22A2
), and 3 (
SLC22A3
) as Disposition Pathways for Fluoroquinolone Antimicrobials
Authors: Mulgaonkar Aditi , Venitz Jürgen , Gründemann Dirk , Sweet Douglas H.
Published: April 2013

Fluoroquinolones (FQs) are important antimicrobials that exhibit activity against a wide range of bacterial pathogens and excellent tissue permeation. They exist as charged molecules in biological fluids, and thus, their disposition depends heavily on active transport and facilitative diffusion. A recent review of the clinical literature indicated that tubular secretion and reabsorption are major determinants of their half-life in plasma, efficacy, and drug-drug interactions. In particular, reported
in vivo
interactions between FQs and cationic drugs affecting renal clearance implicated organic cation transporters (OCTs). In this study, 13 FQs, ciprofloxacin, enoxacin, fleroxacin, gatifloxacin, levofloxacin, lomefloxacin, moxifloxacin, norfloxacin, ofloxacin, pefloxacin, prulifloxacin, rufloxacin, and sparfloxacin, were screened for their ability to inhibit transport activity of human OCT1 (hOCT1) (SLC22A1), hOCT2 (SLC22A2), and hOCT3 (SLC22A3). All, with the exception of enoxacin, significantly inhibited hOCT1-mediated uptake under initial test conditions. None of the FQs inhibited hOCT2, and only moxifloxacin inhibited hOCT3 (∼30%), even at a 1,000-fold excess. Gatifloxacin, moxifloxacin, prulifloxacin, and sparfloxacin were determined to be competitive inhibitors of hOCT1. Inhibition constants (

K
i

) were estimated to be 250 ± 18 μM, 161 ± 19 μM, 136 ± 33 μM, and 94 ± 8 μM, respectively. Moxifloxacin competitively inhibited hOCT3-mediated uptake, with a

K
i

value of 1,598 ± 146 μM. Despite expression in enterocytes (luminal), hepatocytes (sinusoidal), and proximal tubule cells (basolateral), hOCT3 does not appear to contribute significantly to FQ disposition. However, hOCT1 in the sinusoidal membrane of hepatocytes, and potentially the basolateral membrane of proximal tubule cells, is likely to play a role in the disposition of these antimicrobial agents.
Evaluation of Ceftaroline Activity against Heteroresistant Vancomycin-Intermediate Staphylococcus aureus and Vancomycin-Intermediate Methicillin-Resistant S. aureus Strains in an
In Vitro
Pharmacokinetic/Pharmacodynamic Model: Exploring the “Seesaw Effect”
Authors: Werth Brian J. , Steed Molly E. , Kaatz Glenn W. , Rybak Michael J.
Published: April 2013

A “seesaw effect” in methicillin-resistant
Staphylococcus aureus
(MRSA) has been demonstrated, whereby susceptibility to β-lactam antimicrobials increases as glyco- and lipopeptide susceptibility decreases. We investigated this effect by evaluating the activity of the anti-MRSA cephalosporin ceftaroline against isogenic pairs of MRSA strains with various susceptibilities to vancomycin in an
in vitro
pharmacokinetic/pharmacodynamic (PK/PD) model. The activities of ceftaroline at 600 mg every 12 h (q12h) (targeted free maximum concentration of drug in serum [
fC
max
], 15.2 μg/ml; half-life [
t
1/2
], 2.3 h) and vancomycin at 1 g q12h (targeted
fC
max
, 18 μg/ml;
t
1/2
, 6 h) were evaluated against 3 pairs of isogenic clinical strains of MRSA that developed increased MICs to vancomycin in patients while on therapy using a two-compartment hollow-fiber PK/PD model with a starting inoculum of ∼10
7
CFU/ml over a 96-h period. Bacterial killing and development of resistance were evaluated. Expression of penicillin-binding proteins (PBPs) 2 and 4 was evaluated by reverse transcription (RT)-PCR. The achieved pharmacokinetic parameters were 98 to 119% of the targeted values. Ceftaroline and vancomycin were bactericidal against 5/6 and 1/6 strains, respectively, at 96 h. Ceftaroline was more active against the mutant strains than the parent strains, with this difference being statistically significant for 2/3 strain pairs at 96 h. The level of PBP2 expression was 4.4× higher in the vancomycin-intermediate
S. aureus
(VISA) strain in 1/3 pairs. The levels of PBP2 and PBP4 expression were otherwise similar between the parent and mutant strains. These data support the seesaw hypothesis that ceftaroline, like traditional β-lactams, is more active against strains that are less susceptible to vancomycin even when the ceftaroline MICs are identical. Further research to explore these unique findings is warranted.
Localization of Phosphatidylinositol 4,5-Bisphosphate to Lipid Rafts and Uroids in the Human Protozoan Parasite Entamoeba histolytica
Authors: Koushik Amrita B. , Powell Rhonda R. , Temesvari Lesly A.
Published: April 2013

Entamoeba histolytica
is an intestinal protozoan parasite and is the causative agent of amoebiasis. During invasive infection, highly motile amoebae destroy the colonic epithelium, enter the blood circulation, and disseminate to other organs such as liver, causing liver abscess. Motility is a key factor in
E. histolytica
pathogenesis, and this process relies on a dynamic actomyosin cytoskeleton. In other systems, phosphatidylinositol 4,5-bisphosphate [PI(4,5)P
2
] is known to regulate a wide variety of cellular functions, including signal transduction, actin remodeling, and cell motility. Little is known about the role of PI(4,5)P
2
in
E. histolytica
pathogenicity. In this study, we demonstrate that PI(4,5)P
2
is localized to cholesterol-rich microdomains, lipid rafts, and the actin-rich fractions of the
E. histolytica
membrane. Microscopy revealed that the trailing edge of polarized trophozoites, uroids, are highly enriched in lipid rafts and their constituent lipid, PI(4,5)P
2
. Polarization and enrichment of uroids and rafts with PI(4,5)P
2
were enhanced upon treatment of
E. histolytica
cells with cholesterol. Exposure to cholesterol also increased intracellular calcium, which is a downstream effector of PI(4,5)P
2
, with a concomitant increase in motility. Together, our data suggest that in
E. histolytica
, PI(4,5)P
2
may signal from lipid rafts and cholesterol may play a role in triggering PI(4,5)P
2
-mediated signaling to enhance the motility of this pathogen.
Toll-Like Receptor 4/Stem Cell Antigen 1 Signaling Promotes Hematopoietic Precursor Cell Commitment to Granulocyte Development during the Granulopoietic Response to Escherichia coli Bacteremia
Authors: Shi Xin , Siggins Robert W. , Stanford William L. , Melvan John N. , Basson Marc D. , Zhang Ping
Published: April 2013

In response to severe bacterial infection, bone marrow hematopoietic activity shifts toward promoting granulopoiesis. The underlying cell signaling mechanisms remain obscure. To study the role of Toll-like receptor 4 (TLR4)/stem cell antigen-1 (Sca-1) signaling in this process, bacteremia was induced in mice by intravenous injection ofEscherichia coli. A subgroup of animals also received intravenous 5-bromo-2-deoxyuridine (BrdU). In a separate set of experiments, bone marrow lineage-negative (lin−) stem cell growth factor receptor-positive (c-kit+) Sca-1−cells containing primarily common myeloid progenitors were culturedin vitrowithout or withE. colilipopolysaccharide (LPS). In genotypic background control mice, bacteremia significantly upregulated Sca-1 expression by lin−c-kit+cells, as reflected by a marked increase in BrdU-negative lin−c-kit+Sca-1+cells in the bone marrow. In mice with the TLR4 gene deletion, this bacteremia-evoked Sca-1 response was blocked.In vitro, LPS induced a dose-dependent increase in Sca-1 expression by cultured marrow lin−c-kit+Sca-1−cells. LPS-induced upregulation of Sca-1 expression was regulated at the transcriptional level. Inhibition of c-Jun N-terminal kinase/stress-activated protein kinase (JNK) activity with the specific inhibitor SP600125 suppressed LPS-induced upregulation of Sca-1 expression by marrow lin−c-kit+Sca-1−cells. Engagement of Sca-1 with anti-Sca-1 antibodies enhanced the expression of Sfpi1 spleen focus-forming virus (SFFV) proviral integration 1 (PU.1) in marrow lin−c-kit+Sca-1−cells cultured with LPS. Sca-1 null mice failed to maintain the marrow pool of granulopoietic cells following bacteremia. These results demonstrate that TLR4/Sca-1 signaling plays an important role in the regulation of hematopoietic precursor cell programming and their enhancement of granulocyte lineage commitment in response toE. colibacteremia.
Community engagement: a seven‐point plan for success
Authors: Boland Zara
Published: April 2013

Practices can no longer just assume that clients will be happy with the services they provide, based purely on their proximity. Zara Boland outlines a seven‐point plan for reaching out and building trust with individual clients through a clearly identified and collaborative unique selling point.
Canine nasal disease: investigation and management
Authors: Moores Alison , Walker David
Published: April 2013

Nasal diseases represent an interesting array of disorders to both diagnose and manage. The challenge is to differentiate between the underlying causes, which have widely different prognoses for response to treatment and survival. This article describes the advantages of different diagnostic tools for investigating nasal disease, in particular the use of rhinoscopy. The diagnosis, management and prognosis of specific nasal diseases are discussed in detail.
Preliminary Evaluation of the Interactions of Panax ginseng and Salvia miltiorrhiza Bunge with 5-Fluorouracil on Pharmacokinetics in Rats and Pharmacodynamics in Human Cells
Authors: Gu Chenxin , Qiao Jinping , Zhu Meilin , Du Jinglei , Shang Weihu , Yin Wei , Wang Wei , Han Mei , Lu Weidong
Published: April 2013

An increasing number of cancer patients are using herbs in combination with conventional chemotherapeutic treatment. It is therefore important to study the potential consequences of the interactions between herbs and anticancer drugs. The effects of extracts from Panax ginseng (PGS) and Salvia miltiorrhiza Bunge (SMB) on the pharmacokinetics of 5-fluorouracil (5-FU) were performed in vivo and detected by high performance liquid chromatography (HPLC), while, an ATP assay was used to study the pharmacodynamic interactions in vitro. The results of the pharmacokinetic experiments showed a significant increase in the elimination half-life (t1/2(k e )) of 5-FU in the PGS-pretreated group and in the area under the curve (AUC) in the SMB-pretreated group compared with the control group. However, after SMB pretreatment, weight loss was observed in rats. The results of pharmacodynamic experiments showed that neither PGS nor SMB, when used alone, directly inhibited cancer cell growth at 0.1–100 μg/ml. Moreover, PGS had a synergistic cytotoxic effect with 5-FU on human gastric cancer cells but not on normal gastric cells. The results imply that when combined with 5-FU, PGS may be a better candidate for further study. This study might provide insights for the selection of herbal-chemotherapy agent interactions.
GROWTH AND STUDIES OF PROPERTIES OF COPPER SUCCINATE DIHYDRATE SINGLE CRYSTALS
Authors: BINITHA M. P. , PRADYUMNAN P. P.
Published: April 2013

Single crystals of copper succinate dihydrate (CSD) with triclinic structure were grown in silica gel medium. The functional groups in the crystal were analyzed by FT-IR Spectroscopy. Atomic Force Microscopy (AFM) revealed the striations on the surface of grown crystals, which were incorporated during its time of growth. Thermal degradation studies have been carried out by Differential Scanning Calorimetry (DSC). Dielectric constant and AC conductivity have been estimated as a function of frequency at different temperatures.
EVOLUTION OF PRIMORDIAL BLACK HOLE MASS SPECTRUM IN BRANS–DICKE THEORY
Authors: DWIVEDEE D. , NAYAK B. , SINGH L. P.
Published: April 2013

We investigate the evolution of primordial black hole mass spectrum by including both accretion of radiation and Hawking evaporation within Brans–Dicke (BD) cosmology in radiation-, matter- and vacuum-dominated eras. We also consider the effect of evaporation of primordial black holes on the expansion dynamics of the universe. The analytic solutions describing the energy density of the black holes in equilibrium with radiation are presented. We demonstrate that these solutions act as attractors for the system ensuring stability for both linear and nonlinear situations. We show, however, that inclusion of accretion of radiation delays the onset of this equilibrium in all radiation-, matter- and vacuum-dominated eras.
The Moderating Effects of Family Control on the Relation between Managerial Overconfidence and Earnings Management
Authors: Li I-Cheng , Hung Jung-Hua
Published: April 2013

This study investigates the relation between managerial overconfidence and earnings management and whether this relation is moderated by family control. Using a sample of Taiwan-listed firms, we estimate managerial overconfidence from manager dealings and determine the following: First, overconfident managers are more likely to engage in earnings management behaviors; second, family control negatively moderates the positive relation between managerial overconfidence and earnings management; and third, the negative moderating effects of family control primarily result from family chief executive officers.
MULTI-FEATURE-BASED SEGMENTATION OF SONOELASTOGRAPHIC BREAST IMAGES
Authors: SINDHUJA A. , SADASIVAM V.
Published: April 2013

Breast cancer is the leading cause of death in women. Early detection and early treatment can significantly reduce the breast cancer mortality. Texture features are widely used in classification problems, i.e., mainly for diagnostic purposes where the region of interest is delineated manually. It has not yet been considered for sonoelastographic segmentation. This paper proposes a method of segmenting the sonoelastographic breast images with optimum number of features from 32 features extracted from three different extraction methods: Gray Level Co-occurrence Matrix (GLCM), Local Binary Pattern (LBP), and Edge-Based Features. The image undergoes preprocessing by Sticks filter that improves the contrast and enhances the edges and emphasizes the tumor boundary. The features are extracted and then ranked according to the Sequential Forward Floating Selection (SFFS). The optimum number of ranked features is used for segmentation using k-means clustering. The segmented images are subjected to morphological processing that marks the tumor boundary. The overall accuracy is studied to investigate the effect of automated segmentation where the subset of first 10 ranked features provides an accuracy of 79%. The combined metric of overlap, over- and under-segmentation is 90%. The proposed work can also be considered for diagnostic purposes, along with the sonographic breast images.
AN EFFICIENT OBJECT ORIENTED TEXT ANALYSIS (OOTA) APPROACH TO CONSTRUCT STATIC STRUCTURE WITH DYNAMIC BEHAVIOR
Authors: EL-SAID ASMAA M. , ELDESOKY ALI I. , ARAFAT HESHAM A.
Published: April 2013

In many fields of science, IT applications and business environments successfully evolved systems to receive vast amount of electronic data and information. Due to increasing electronic data and information, most recent researches have tried to find a solution to resolve the crisis of information overload. These solutions include a combination of techniques of data mining, machine learning, natural language processing and information retrieval, information extraction, and knowledge management. A great challenge is how to exploit those information and knowledge resources and turn them into useful knowledge available to concerned people. The value of knowledge increases when people can share and capitalize on it. Thus, approaches that can help researchers to benefit from existing hidden knowledge are needed. For this, tools that can analyze, extract and explore relevant and useful information with relations are required. So, the main contribution of this paper is to integrate the technology of XML with text analysis for introducing an efficient concept-based structure model, where this model can represent the text in a form that can be easily understood, shared, managed and mined. This paper describes an efficient object oriented text analysis (OOTA) approach by generating an object oriented model that transforms unstructured text to a specific structured form and stored in XML format. The experimental results show that this approach has a good promotion on results.