bluuebunny/crossref_metadata_2025 huggingface dataset:
A chaotic particle-swarm krill herd algorithm for global numerical optimization
Authors: Wang Gai-Ge , Hossein Gandomi Amir , Hossein Alavi Amir
Published: September 2013

Purpose

– To improve the performance of the krill herd (KH) algorithm, in this paper, a series of chaotic particle-swarm krill herd (CPKH) algorithms are proposed for solving optimization tasks within limited time requirements. The paper aims to discuss these issues.

Design/methodology/approach

– In CPKH, chaos sequence is introduced into the KH algorithm so as to further enhance its global search ability.

Findings

– This new method can accelerate the global convergence speed while preserving the strong robustness of the basic KH.

Originality/value

– Here, 32 different benchmarks and a gear train design problem are applied to tune the three main movements of the krill in CPKH method. It has been demonstrated that, in most cases, CPKH with an appropriate chaotic map performs superiorly to, or at least highly competitively with, the standard KH and other population-based optimization methods.
The development of an institutional repository at the Aquaculture Department of the Southeast Asian Fisheries Development Center, Philippines
Authors: Biaco Alayon Stephen , Santillan Nemiz Elvi , Lustracion Superio Daryl , Garvilles de la Peña Jesserylle , Gadot Pacino Luisa
Published: September 2013

Purpose

– This paper aims to present the experiences of SEAFDEC/AQD library staff in digitizing institutional publications and developing an institutional repository (IR).

Design/methodology/approach

– SEAFDEC/AQD IR or SAIR provides a reliable means for its researchers to store, preserve, share their research outputs, enable easy access to and increase the visibility of its scientific publications. The repository uses DSpace customized with some add-ons. Details on the digitization hardware and software, layout, delivery format, and persistent identifier used are provided.

Findings

– As of March 2012, the repository contains 771 items with 541 downloadable PDFs. SAIR had 88,287 item views, 69,249 PDF downloads and 271,978 searches. SAIR is registered to and indexed by OpenDOAR, ROAR, Google Scholar and WorldCat. It is harvested by AVANO Ifremer, BASE, Sciencegate.ch and OAIster. Initial impact based on indicators in webometrics ranking web of world repositories and research centers was presented. Reluctance to contribute to IR has been observed by the library staff among SEAFDEC/AQD researchers.

Research limitations/implications

– The IR can be an effective tool to promote institutional publications and those written by researchers in peer-reviewed journals and to generate higher citations through increased visibility. IR submission policy and procedures are being drafted by the library staff.

Practical implications

– SAIR provides free access to all in-house publications of SEAFDEC/AQD. Full-text digitized copies of fish farmer-friendly materials like books, handbooks, policy guidebooks, extension manuals, institutional reports, and newsletters can be downloaded.

Originality/value

– SAIR is one of only three open access institutional repositories registered in the Philippines. The paper discusses the lessons learned and issues to be addressed in developing an IR of value to other institutions considering similar projects. Future plans and further development are also presented.
The construct validity of a measure of the benchmarks of educational practices
Authors: El Hassan Karma
Published: September 2013

Purpose

– The American University of Beruit has generated a model for student success that builds on Kuh's five benchmarks of academic practice. The purpose of this study is to investigate the psychometric properties of the measures used to assess effectiveness of the benchmarks.

Design/methodology/approach

– Using a database of student responses to the College Outcomes Survey, scalelets representing each of the five benchmarks were constructed. Confirmatory factor analysis, correlations, and structural equation modeling were used to test the measurement model and overall fit of the data, assess the extent the constructs are interdependent, and investigate influence of benchmarks on valued student outcomes.

Findings

– Results provided evidence of reliability and construct validity of the measures. The university needs studies addressing the psychometric properties of the measures used to answer fundamental questions about its institutional effectiveness and needs to know whether these findings represent true relationships or measurement error. Without psychometric information, the university cannot monitor its institutional effectiveness in meeting its goals nor the impact of new policies and practices on student outcomes.

Originality/value

– The study provides insight on meaning and components of various benchmarks and their impact on desired outcomes that the university has for its students, and thus provides more useful representations that meet its needs.
Older people and home care in Wales: findings from a survey of service users
Authors: Llewellyn Mark , Longley Marcus , Jarvis Paul , Garthwaite Tony
Published: September 2013

Purpose

– The purpose of this paper is to provide an account of a comprehensive and independent study of 1,029 older people who receive home care in Wales. The study aims to expand knowledge on the views of older people, a group who traditionally have struggled to make their voices heard. It asked older people about six specific components of home care: being listened to; having trained, knowledgeable and skilled care workers; having enough time to be cared for; receiving care from as few different workers as possible; receiving quality care; and being signposted to other sources of information.

Design/methodology/approach

– After an initial literature review and period of analysis, a thematic framework for home care was developed which contained the six components described above. A questionnaire was subsequently designed and distributed via the post to all home care services over 65 years old in four local authorities across Wales. A sample response rate of 26.7 per cent was achieved.

Findings

– The paper provides evidence on the levels of satisfaction (or otherwise) with the home care received by older people in Wales. Overall, nearly 85 per cent of older people are either “satisfied” or “very satisfied”, and given the sample size these data are significant (within appropriate confidence intervals) for the whole of the 25,000 people who receive home care in Wales. However, it is difficult to contextualise these findings given that there are no effective comparator data.

Research limitations/implications

– Given the chosen research approach, the results may lack a certain depth of understanding. That said, the size of the sample does provide commissioners and providers of services with certainty about the general population view.

Originality/value

– This paper offers a unique independent analysis of home care in Wales, and provides the reader with detailed insights into the views of older people who rarely get a chance to be heard.
Independent living in care homes for older people
Authors: Moore John
Published: September 2013

Purpose

– The purpose of this paper is to investigate how care homes can be de-institutionalised and what factors are key in independence for residents?

Design/methodology/approach

– This paper takes the form of a review of the current life of residents in care homes with insight from My Home Life Cymru.

Findings

– This research identifies eight best practice themes which together form a vision for care homes in the twenty-first century.

Originality/value

– Care homes play an important role in social care, providing services to some of our most vulnerable citizens. By focusing on the quality of life in care homes for older people, we can play a part in delivering services that people want, in the way that they want them.
Absolutely fabulous!
Authors: Daniel Hjorth
Published: September 2013

Purpose

– This paper seeks to apply a processual thinking of subjectivity in the study of “becoming entrepreneur”.

Design/methodology/approach

– Through analysing Foucault's idea of subjectification, by the help of Deleuze's comments and elaborations, the paper seeks to clarify one opacity in entrepreneurship research – the “vanishing presence” of the entrepreneur in processual studies of entrepreneurship. To avoid performative contradiction, the paper seeks to contextualise this attempt in guiding principles provided by process philosophy.

Findings

– Without a process view, “the subject” as entity and self-constitutiveres cogitans(thinking thing or mind) will take priority over subjectification, and the paper will loose the possibility to think and study the process of becoming-subject in its own terms.

Originality/value

– Understanding entrepreneurship as organisation-creation, the paper here adds a processual conceptualisation to the study of such processes by focusing on the arrangements (agancements as Deleuze called this, or dispositifs as Foucault preferred to use) in which subjectification into “entrepreneur” happens.
Molecular Tagging Velocimetry and Its Application to In-Cylinder Flow Measurements
Authors: Vedula Ravi , Mittal Mayank , Schock Harold J.
Published: September 2013

This review article provides an overview of the experimental studies of in-cylinder flows using various flow measurement techniques with a focus on molecular tagging velocimetry. It is necessary to understand the evolution of large-scale and small-scale turbulence as prepared during the intake stroke with a cycle resolved quantitative description. Due to the difficulty in obtaining these descriptions, either by modeling or experimentally, they are often characterized with somewhat ambiguous notions of bulk swirl and tumble measurement methods. During the intake stroke, in-cylinder flows are formed in such a manner as to provide advantageous spatial and temporal behavior for mixture formation later during the compression stroke. Understanding the details of how these flows influence fuel-air mixing, the initiation of ignition, combustion, and subsequent flame propagation processes is the primary motivation for the development of the methods described in this paper. The authors provide an introduction to fundamental flow motion inside the engine cylinder and measurement techniques, e.g., hot-wire anemometry, laser Doppler anemometry, and particle image velocimetry. Furthermore, molecular tagging velocimetry is discussed in detail in terms of (i) different mechanisms, (ii) procedure and data reduction methods to obtain the desired flow properties such as velocity, vorticity, and turbulent intensities, and (iii) applications to flow studies in internal combustion engines. Finally, the significance of experimental investigations of in-cylinder flows is discussed along with possible future applications.
Bridging the Gap Between Continuum Mechanical Microrotation Viscosity and Lagrangian Point-Particles
Authors: Andersson Helge I. , Zhao Lihao
Published: September 2013

The microrotation viscosity is an essential fluid property in micropolar fluid dynamics. By considering a dilute suspension of inertial spherical point-particles in an otherwise Newtonian fluid, an explicit analytical expression for the microrotation viscosity is derived. This non-Newtonian continuum mechanical fluid property is seen to be proportional with the viscosity of the carrier fluid and the local particle loading. A number of assumptions were made in order to arrive at this simple relation, which implies that the microrotation viscosity should be considered as a flow variable rather than as a constant fluid property.
Micro and Nanofluidics: Historical Perspectives and Challenges
Authors: Conlisk A. T.
Published: September 2013

In this paper, we discuss the fundamentals of micro and nanofluidics and the interdisciplinary nature of the field. The study of fluid flows at micro and nanoscales inevitably requires expertise in and an understanding of surface chemistry, electrostatics and electrokinetics, electrochemistry, molecular biology, heat and mass transfer, and macroscale fluid mechanics simultaneously. To design devices having micro and nanoscale features requires a team approach involving chemists, biologists, medical researchers and practitioners, engineers, and systems analysts. Significant advances have been made in the last 20 years in developing the capability of designing devices with microscale and nanoscale features. However, challenges remain in each of the three pillars of micro and nanofluidics: modeling, experimentation, and fabrication. Several challenges are discussed; those falling within the areas of modeling and experiment are described in some detail. It is clear in the present research environment that understanding the micro/nanofluidic environment is crucial to achieving the efficient and cost-effective design of biomedical devices.
Impact of Marine Locomotion Constraints on a Bio-inspired Aerial-Aquatic Wing: Experimental Performance Verification
Authors: Lock Richard J. , Vaidyanathan Ravi , Burgess Stuart C.
Published: September 2013

This paper describes the design, fabrication, experimental testing and performance optimization of the morphology of a flapping wing for use on a robot capable of aerial and aquatic modes of locomotion. The focus of the optimization studies is that of wing design for aquatic propulsion. Inspiration for the research stems from numerous avian species which use a flapping wing for the dual purpose of locomotion (propulsion) in both air and water. The main aim of this research is to determine optimal kinematic parameters for marine locomotion that maximize nondimensionalized performance measures (e.g., propulsive efficiency), derived from analysis of avian wing morphing mechanisms that balance competing demands of both aerial and aquatic movement. Optimization of the kinematic parameters enables the direct comparison between outstretched (aerial) and retracted (aquatic) wing morphologies and permits trade-off studies in the design space for future robotic vehicles. Static foils representing the wing in both an extended and retracted orientation have been manufactured and subsequently subjected to testing over a range of kinematics. Details of the purpose built 2 degree-of-freedom (dof) flapping mechanism are presented. The gathered results enable validation of previously developed numerical models as well as quantifying achievable performance measures. This research focuses on the mechanical propulsive efficiencies and thrust coefficients as key performance measures whilst simultaneously considering the required mechanical input torques and the associated thrust produced.
Nonlinear System Modeling and Application Based on System Equilibrium Manifold and Expansion Model
Authors: Liu Xiaofeng , Yuan Ye
Published: September 2013

A new modeling method for a nonlinear system by using equilibrium manifold (EM) and its expansion model (EME model) was presented. The property of the EME model was discussed, and the effect of mapping design to the model has been discussed. This paper also has researched the adaptivity analysis to the EME model. Then an approximate nonlinear model for an aircraft engine is applied, followed by an identification procedure for an aircraft engine. Simulations showed good precision of this model in capturing the nonlinear behavior of nonlinearities and had the simpler structure.
Aircraft Engine Gas Path Diagnostic Methods: Public Benchmarking Results
Authors: Simon Donald L. , Borguet Sébastien , Léonard Olivier , Zhang Xiaodong (Frank)
Published: September 2013

Recent technology reviews have identified the need for objective assessments of aircraft engine health management (EHM) technologies. To help address this issue, a gas path diagnostic benchmark problem has been created and made publicly available. This software tool, referred to as the Propulsion Diagnostic Method Evaluation Strategy (ProDiMES), has been constructed based on feedback provided by the aircraft EHM community. It provides a standard benchmark problem enabling users to develop, evaluate, and compare diagnostic methods. This paper will present an overview of ProDiMES along with a description of four gas path diagnostic methods developed and applied to the problem. These methods, which include analytical and empirical diagnostic techniques, will be described and associated blind-test-case metric results will be presented and compared. Lessons learned along with recommendations for improving the public benchmarking processes will also be presented and discussed.
Energy Release of the 2013
M
w
8.3 Sea of Okhotsk Earthquake and Deep Slab Stress Heterogeneity
Authors: Ye Lingling , Lay Thorne , Kanamori Hiroo , Koper Keith D.
Published: September 2013

Delineating Deep Faults

Most large, damaging earthquakes initiate in Earth's crust where friction and brittle fracture control the release of energy. Strong earthquakes can occur in the mantle too, but their rupture dynamics are difficult to determine because higher temperatures and pressures play a more important role.

Ye
et al.

(p.
1380
) analyzed seismic
P
waves generated by the 2013
M
w
8.3 Sea of Okhotsk earthquake—the largest deep earthquake recorded to date—and its associated aftershocks. The earthquake ruptured along a fault over 180-kilometer-long and structural heterogeneity resulted in a massive release of stress from the subducting slab. In a set of complementary laboratory deformation experiments,

Schubnel
et al.

(p.
1377
) simulated the nucleation of acoustic emission events that resemble deep earthquakes. These events are caused by an instantaneous phase transition from olivine to spinel, which would occur at the same depth and result in large stress releases observed for other deep earthquakes.
Evaluation of the Nanosphere Verigene Gram-Positive Blood Culture Assay with the VersaTREK Blood Culture System and Assessment of Possible Impact on Selected Patients
Authors: Beal Stacy G. , Ciurca Jane , Smith Geremy , John Jeffrey , Lee Francesca , Doern Christopher D. , Gander Rita M.
Published: September 2013

The Verigene Gram-positive blood culture (BC-GP) assay (Nanosphere, Northbrook, IL) is a molecular method for the rapid identification of Gram-positive organisms and resistance markers directly from blood culture bottles. A total of 148 VersaTREK REDOX 1 40-ml aerobic bottles demonstrating Gram-positive bacteria were tested. Results were compared with those from conventional biochemical and matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) identifications. We obtained isolates of methicillin-resistant
Staphylococcus aureus
(MRSA) (24), methicillin-susceptible
Staphylococcus aureus
(MSSA) (14), methicillin-resistant
Staphylococcus epidermidis
(MRSE) (17), methicillin-susceptible
Staphylococcus epidermidis
(MSSE) (9), other coagulase-negative staphylococci (19),
Streptococcus salivarius
(5),
Streptococcus parasanguinis
(2),
Streptococcus sanguinis
(1),
Streptococcus cristatus
(1), the
Streptococcus bovis
group (5),
Streptococcus agalactiae
(9), the
Streptococcus anginosus
group (1),
Streptococcus pneumoniae
(6), vancomycin-resistant
Enterococcus faecium
(VRE FCM) (16), vancomycin-susceptible
Enterococcus faecalis
(3),
Aerococcus viridans
(2),
Bacillus
(6),
Corynebacterium
(8),
Lactobacillus
(2),
Micrococcus
(2),
Neisseria mucosa
(1),
Escherichia coli
(3),
Candida tropicalis
(1),
Propionibacterium
(1), and
Rothia
(1). Overall agreement with the culture results was 95%. A total of 137 of 138 (99%) monomicrobial cultures were concordant. We tested 9 polymicrobial samples and found 33% agreement. A chart review of 31 patients with MRSA, MSSA, or VRE demonstrated that the Nanosphere BC-GP assay might have led to more appropriate antibiotic selection for these patients an average of 42 h earlier. Additionally, contact isolation could have been initiated an average of 37 h earlier for patients with MRSA or VRE. The BC-GP assay may have a positive impact on patient care, health care costs, and antibiotic stewardship.
Precise Dissection of an Escherichia coli O157:H7 Outbreak by Single Nucleotide Polymorphism Analysis
Authors: Turabelidze George , Lawrence Steven J. , Gao Hongyu , Sodergren Erica , Weinstock George M. , Abubucker Sahar , Wylie Todd , Mitreva Makedonka , Shaikh Nurmohammad , Gautom Romesh , Tarr Phillip I.
Published: September 2013

The current pathogen-typing methods have suboptimal sensitivities and specificities. DNA sequencing offers an opportunity to type pathogens with greater degrees of discrimination using single nucleotide polymorphisms (SNPs) than with pulsed-field gel electrophoresis (PFGE) and other methodologies. In a recent cluster ofEscherichia coliO157:H7 infections attributed to salad bar exposures and romaine lettuce, a subset of cases denied exposure to either source, although PFGE and multiple-locus variable-number tandem-repeat analysis (MLVA) suggested that all isolates had the same recent progenitor. Interrogation of a preselected set of 3,442,673 nucleotides in backbone open reading frames (ORFs) identified only 1 or 2 single nucleotide differences in 3 of 12 isolates from the cases who denied exposure. The backbone DNAs of 9 of 9 and 3 of 3 cases who reported or were unsure about exposure, respectively, were isogenic. Backbone ORF SNP set sequencing offers pathogen differentiation capabilities that exceed those of PFGE and MLVA.
Identification of Alpha Interferon-Induced Envelope Mutations of Hepatitis C Virus
In Vitro
Associated with Increased Viral Fitness and Interferon Resistance
Authors: Serre Stéphanie B. N. , Krarup Henrik B. , Bukh Jens , Gottwein Judith M.
Published: September 2013

Alpha interferon (IFN-α) is an essential component of innate antiviral immunity and of treatment regimens for chronic hepatitis C virus (HCV) infection. Resistance to IFN might be important for HCV persistence and failure of IFN-based therapies. Evidence for HCV genetic correlates of IFN resistance is limited. Experimental studies were hampered by lack of HCV culture systems. Using genotype (strain) 1a(H77) and 3a(S52) Core-NS2 JFH1-based recombinants, we aimed at identifying viral correlates of IFN-α resistance
in vitro
. Long-term culture with IFN-α2b in Huh7.5 cells resulted in viral spread with acquisition of putative escape mutations in HCV structural and nonstructural proteins. Reverse genetic studies showed that primarily amino acid changes I348T in 1a(H77) E1 and F345V/V414A in 3a(S52) E1/E2 increased viral fitness. Single-cycle assays revealed that I348T and F345V/V414A enhanced viral entry and release, respectively. In assays allowing viral spread, these mutations conferred a level of IFN-α resistance exceeding the observed fitness effect. The identified mutations acted in a subtype-specific manner but were not found in genotype 1a and 3a patients, who failed IFN-α therapy. Studies with HCV recombinants with different degrees of culture adaptation confirmed the correlation between viral fitness and IFN-α resistance. In conclusion,
in vitro
escape experiments led to identification of HCV envelope mutations resulting in increased viral fitness and conferring IFN-α resistance. While we established a close link between viral fitness and IFN-α resistance, identified mutations acted via different mechanisms and appeared to be relatively specific to the infecting virus, possibly explaining difficulties in identifying signature mutations for IFN resistance.
Determining the Cellular Diversity of Hepatitis C Virus Quasispecies by Single-Cell Viral Sequencing
Authors: McWilliam Leitch E. Carol , McLauchlan John
Published: September 2013

Single-cell genomics is emerging as an important tool in cellular biology. We describe for the first time a system to investigate RNA virus quasispecies diversity at the cellular level utilizing hepatitis C virus (HCV) replicons. A high-fidelity nested reverse transcription (RT)-PCR assay was developed, and validation using control transcripts of known copy number indicated a detection limit of 3 copies of viral RNA/reaction. This system was used to determine the cellular diversity of subgenomic JFH-1 HCV replicons constitutively expressed in Huh7 cells. Each cell contained a unique quasispecies that was much less diverse than the quasispecies of the bulk cell population from which the single cells were derived, suggesting the occurrence of independent evolution at the cellular level. An assessment of the replicative fitness of the predominant single-cell quasispecies variants indicated a modest reduction in fitness compared to the wild type. Real-time RT-PCR methods capable of determining single-cell viral loads were developed and indicated an average of 113 copies of replicon RNA per cell, correlating with calculated RNA copy numbers in the bulk cell population. This study introduces a single-cell RNA viral-sequencing method with numerous potential applications to explore host-virus interactions during infection. HCV quasispecies diversity varied greatly between cells
in vitro
, suggesting different within-cell evolutionary pathways. Such divergent trajectories
in vivo
could have implications for the evolution and establishment of antiviral-resistant variants and host immune escape mutants.
Prohibitin Interacts with Envelope Proteins of White Spot Syndrome Virus and Prevents Infection in the Red Swamp Crayfish, Procambarus clarkii
Authors: Lan Jiang-Feng , Li Xin-Cang , Sun Jie-Jie , Gong Jing , Wang Xian-Wei , Shi Xiu-Zhen , Shi Li-Jie , Weng Yu-Ding , Zhao Xiao-Fan , Wang Jin-Xing
Published: September 2013

Prohibitins (PHBs) are ubiquitously expressed conserved proteins in eukaryotes that are associated with apoptosis, cancer formation, aging, stress responses, cell proliferation, and immune regulation. However, the function of PHBs in crustacean immunity remains largely unknown. In the present study, we identified a PHB in
Procambarus clarkii
red swamp crayfish, which was designated
Pc
PHB1.
Pc
PHB1 was widely distributed in several tissues, and its expression was significantly upregulated by white spot syndrome virus (WSSV) challenge at the mRNA level and the protein level. These observations prompted us to investigate the role of
Pc
PHB1 in the crayfish antiviral response. Recombinant
Pc
PHB1 (r
Pc
PHB1) significantly reduced the amount of WSSV in crayfish and the mortality of WSSV-infected crayfish. The quantity of WSSV in
Pc
PHB1 knockdown crayfish was increased compared with that in the controls. The effects of RNA silencing were rescued by r
Pc
PHB1 reinjection. We further confirmed the interaction of
Pc
PHB1 with the WSSV envelope proteins VP28, VP26, and VP24 using pulldown and far-Western overlay assays. Finally, we observed that the colloidal gold-labeled
Pc
PHB1 was located on the outer surface of the WSSV, which suggests that
Pc
PHB1 specifically binds to the envelope proteins of WSSV. VP28, VP26, and VP24 are structural envelope proteins and are essential for attachment and entry into crayfish cells. Therefore,
Pc
PHB1 exerts its anti-WSSV effect by binding to VP28, VP26, and VP24, preventing viral infection. This study is the first report on the antiviral function of PHB in the innate immune system of crustaceans.
Subdural effusions and lack of early pontocerebellar hypoplasia in siblings with RARS2 mutations
Authors: Kastrissianakis Katherina , Anand Geetha , Quaghebeur Gerardine , Price Sue , Prabhakar Prab , Marinova Jasmina , Brown Garry , McShane Tony
Published: September 2013

Mutations in the recently describedRARS2gene encoding for mitochondrial arginyl-transfer RNA synthetase give rise to a disorder characterised by early onset seizures, progressive microcephaly and developmental delay. The disorder was named pontocerebellar hypoplasia type 6 (PCH6) based on the corresponding radiological findings observed in the original cases. We report two siblings with theRARS2mutation who displayed typical clinical features of PCH6, but who had distinct neuroimaging features. Early scans showed marked supratentorial, rather than infratentorial, atrophy, and the pons remained preserved throughout. One sibling also had bilateral subdural effusions at presentation. The deceleration in head growth pointed to an evolving genetic/metabolic process giving rise to cerebral atrophy and secondary subdural effusions.RARS2mutations should be considered in infants presenting with seizures, subdural effusions, decelerating head growth and evidence of cerebral atrophy even in the absence of pontocerebellar hypoplasia on imaging.
Phase I trial of concurrent sunitinib and radiation therapy as preoperative treatment for soft tissue sarcoma
Authors: Jakob Jens , Rauch Geraldine , Wenz Frederik , Hohenberger Peter
Published: September 2013

Introduction

Although the introduction of multimodal treatment of soft tissue sarcoma improved local tumour control, local failure still occurs in a good number of patients. Therefore, further improvement of current treatment strategies is necessary. The proposed study treatment will combine standard external beam radiation and the orally administered receptor tyrosine kinase inhibitor sunitinib.

Methods and analysis

Patients with soft tissue sarcoma will receive sunitinib and irradiation as neoadjuvant treatment. Radiotherapy will be administered as intensity modulated radiation therapy with a total dose of 50.4 Gy in 28 fractions (5 1/2 weeks). Patients will receive sunitinib daily for 2 weeks prior to and then concurrently with irradiation. Sunitinib will be given in two dose levels. The first dose level will be 25 mg sunitinib per os daily. The second dose level will be 37.5 mg. A dose modification schedule according to a 3+3 design will be applied. Restaging and tumour resection will be performed 6 weeks after completion of sunitinib and irradiation. Primary outcome measures will be the dose-limiting toxicity and maximal tolerated dose of sunitinib administered concurrently with irradiation. Toxicity of the study treatment will be documented according to Common Terminology Criteria of Adverse Events (CTCAE) 4.0. Secondary outcome measures will be the response to the study treatment and morbidity of the tumour resection. Imaging response will be determined according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria comparing MRI performed prior to and 6 weeks after completion of study treatment. Pathological response will be determined evaluating the fraction of non-viable tumour in the resection specimen. Resection morbidity will be evaluated according to CTCAE 4.0.

Ethics and dissemination

Approval was obtained from the ethics committee II of the University of Heidelberg, Germany (Reference number 2011-064F-MA). Furthermore, the study was approved by the German Federal Institute for Drugs and Medical Devices (Reference number 4037708).

Trial Registration EudraCT

2007-002864-87 Clinicaltrials.gov:NCT01498835
Cordotomy in mesothelioma-related pain: a systematic review
Authors: France Barbara D , Lewis Ruth A , Sharma Manohar L , Poolman Marlise
Published: September 2013

Background

Cordotomy can be effective in relieving pain for patients with mesothelioma, but the evidence to support continued provision is limited. This review forms part of the Invasive Neurodestructive Procedures in Cancer Pain pilot study: The role of cordotomy in mesothelioma-related pain in the UK.

Aim/design

We report on the results of the first comprehensive systematic review of the use of cordotomy in mesothelioma-related pain, with specific reference to effectiveness in relieving pain and safety. The review was conducted according to guidelines reported in the NHS Centre for Reviews and Dissemination and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic reviews and meta-analyses.

Data sources

14 databases from inception to March 2012 were searched, with no limitations on language or publication type.

Results

Nine studies met the inclusion criteria, all of which were case series of percutaneous cervical cordotomy (PCC) involving 160 patients. All studies demonstrated good pain relief in the majority of patients. Initial post-procedure measurements showed the greatest reduction in pain. Some side effects (headache, mirror pain, motor weakness) occurred relatively frequently but were mostly transient. Respiratory dysfunction post-PCC was rare. No deaths were directly ascribed to cordotomy.

Conclusions

The available evidence is significantly limited in quantity and quality. Although it seems to suggest that cordotomy might be safe and effective in this setting, more reliable evidence is needed to aid decision making on continued provision. A national registry for cordotomy would be a valuable first step in this process.
Did the Olympics need more drugs? A doctor's reflection on providing medical care during Op OLYMPICS
Authors: Monteiro de Barros James , Ross D A
Published: September 2013

This paper examines some of the medical problems arising from the successful deployment of Defence Medical Services personnel to Op OLYMPICS (mid-June 2012–September 2012). It does not aim to be all encompassing in its scope, but focuses on the most pressing issues affecting a junior military doctor's ability to work effectively under field conditions. This will entail a discussion about whether in a deployment such as Op OLYMPICS medical care should be based upon offering solely primary healthcare in medical centres or using Role 1 medical treatment facilities, which include primary healthcare and pre-hospital emergency care. The main recommendations arising from the deployment are: clinicians should deploy with a minimum of basic emergency drugs and equipment; a medical facility treating a large population at risk for a prolonged period should have a broad stock of medications available on site; and medical risk assessments must be performed on all Reservists during mobilisation.
Validation of a new radiographic protocol for Asian elephant feet and description of their radiographic anatomy
Authors: Mumby C. , Bouts T. , Sambrook L. , Danika S. , Rees E. , Parry A. , Rendle M. , Masters N. , Weller R.
Published: September 2013

Foot problems are extremely common in elephants and radiography is the only imaging method available but the radiographic anatomy has not been described in detail. The aims of this study were to develop a radiographic protocol for elephant feet using digital radiography, and to describe the normal radiographic anatomy of the Asian elephant front and hind foot. A total of fifteen cadaver foot specimens from captive Asian elephants were radiographed using a range of projections and exposures to determine the best radiographic technique. This was subsequently tested in live elephants in a free‐contact setting. The normal radiographic anatomy of the Asian elephant front and hind foot was described with the use of three‐dimensional models based on CT reconstructions. The projection angles that were found to be most useful were 65–70° for the front limb and 55–60° in the hind limb. The beam was centred 10–15 cm proximal to the cuticle in the front and 10–15 cm dorsal to the plantar edge of the sole in the hind foot depending on the size of the foot. The protocol developed can be used for larger‐scale diagnostic investigations of captive elephant foot disorders, while the normal radiographic anatomy described can improve the diagnostic reliability of elephant feet radiography.
Spectrum of myelinated pulmonary afferents (II)
Authors: Liu Jun , Yu Jerry
Published: September 2013

Recently, it has been recognized that a single airway sensory unit may contain multiple receptive fields and that each field houses at least one encoder. Since some units respond to both lung inflation and deflation, we hypothesized that these units contain heterogeneous encoders for sensing inflation and deflation, respectively. Single unit activities were recorded from the cervical vagus nerve in anesthetized, open chest, and mechanically ventilated rabbits. Fifty-two airway sensory units with multiple receptive fields that responded to both lung inflation and deflation were identified. Among them, 13 units had separate receptive fields for inflation and deflation, where one of the fields could be blocked by local injection of 2% lidocaine (10 μl). In 8 of the 13 units, the deflation response was blocked without affecting the unit's response to inflation, whereas in the remaining five units, the inflation response was blocked without affecting the deflation response. Our results support the hypothesis that a single mechanosensory unit may contain heterogeneous encoders that can respond to either inflation or deflation.
Sexually dimorphic urethral activity in response to pharmacological activation of 5-HT1A receptors in the rat
Authors: Fan Wen-Jia , Li Yu-Ting , Chen Jia-Jin Jason , Chen Shih-Ching , Lin You Shuei , Kou Yu Ru , Peng Chih-Wei
Published: September 2013

In this study, we examined the possibility that 5-HT1A receptors may underlie sexually dimorphic mechanisms affecting the regulation of urethral functions in anesthetized rats. Simultaneous recordings of intravesical pressure under isovolumetric conditions, external urethral sphincter-electromyography, and urethral perfusion pressure were used to examine the effects of a 5-HT1A receptor agonist [8-hydroxy-2-(di- n-propylamino)tetralin (8-OH-DPAT)] and antagonist (WAY-100635) on bladder and urethral functions. This research also evaluated the effects of 8-OH-DPAT and α-bungarotoxin (a neuromuscular blockade agent) on urethral continence using leak point pressure testing, and the distribution of 5-HT1A receptors in the lower urinary tract was assessed by immunohistochemistry. The serotonergic mechanism that controls the urinary bladder and external urethral sphincter-electromyography activity showed no significant sexual differences, but urethral activity in urethral perfusion pressure and leak point pressure values exhibited some sexual differences. 8-OH-DPAT enhanced urethral pressure during continence in rats of both sexes, but the drug elevated the pressure during voiding in male rats and reduced it in female rats. The distribution of 5-HT1A receptors in the spinal cord also showed some sexual differences. The present study contributes to our understanding of the role of 5-HT1A receptors in physiological and immunohistochemical properties of urethral smooth muscle in rats of different sexes. These findings may be a basis for the future development of pharmacotherapies for stress urinary incontinence in men.
Effects of high-fat diet and losartan on renal cortical blood flow using contrast ultrasound imaging
Authors: Declèves Anne-Emilie , Rychak Joshua J. , Smith Dan J. , Sharma Kumar
Published: September 2013

Obesity-related kidney disease occurs as a result of complex interactions between metabolic and hemodynamic effects. Changes in microvascular perfusion may play a major role in kidney disease; however, these changes are difficult to assess in vivo. Here, we used perfusion ultrasound imaging to evaluate cortical blood flow in a mouse model of high-fat diet-induced kidney disease. C57BL/6J mice were randomized to a standard diet (STD) or a high-fat diet (HFD) for 30 wk and then treated either with losartan or a placebo for an additional 6 wk. Noninvasive ultrasound perfusion imaging of the kidney was performed during infusion of a microbubble contrast agent. Blood flow within the microvasculature of the renal cortex and medulla was derived from imaging data. An increase in the time required to achieve full cortical perfusion was observed for HFD mice relative to STD. This was reversed following treatment with losartan. These data were concurrent with an increased glomerular filtration rate in HFD mice compared with STD- or HFD-losartan-treated mice. Losartan treatment also abrogated fibro-inflammatory disease, assessed by markers at the protein and messenger level. Finally, a reduction in capillary density was found in HFD mice, and this was reversed upon losartan treatment. This suggests that alterations in vascular density may be responsible for the elevated perfusion time observed by imaging. These data demonstrate that ultrasound contrast imaging is a robust and sensitive method for evaluating changes in renal microvascular perfusion and that cortical perfusion time may be a useful parameter for evaluating obesity-related renal disease.
Body posture modulates imagined arm movements and responds to them
Authors: Boulton Hayley , Mitra Suvobrata
Published: September 2013

Imagined movements are thought to simulate physical ones, with similar behavioral constraints and neurophysiological activation patterns and with an inhibition mechanism that suppresses movement execution. When upper body movements such as reaching with the arm are made from an upright stance, lower body and trunk muscles are also activated to maintain body posture. It is not clear to what extent parameters of imagined manual movements are sensitive to the postural adjustments their execution would necessitate, nor whether such postural responses are as effectively inhibited as the imagined movements themselves. We asked healthy young participants to imagine reaching movements of the arm while in upright stance, and we measured their self-reported movement times and postural sway during imagined movements. We manipulated mediolateral stance stability and the direction of arm movement (mediolateral or anteroposterior). Imagined arm movements were reportedly slower when subjects were standing in a mediolaterally less stable stance, and the body swayed more when arm movements were imagined in the direction of postural vulnerability. The results suggest that the postural state of the whole body, not just the involved limbs, informs trajectory planning during motor imagery and that measurable adjustments to body posture accompany imagined manual actions. It has been suggested that movement is suppressed during motor imagery by a premotor inhibitory mechanism operating at brain stem or spinal level. Any such inhibition must be incomplete because, for example, it does not eliminate autonomic arousal. Our results suggest that it also does not effectively suppress postural adjustments planned in support of imagined movements.
microRNA Portraits in Human Vulvar Carcinoma
Authors: de Melo Maia Beatriz , Lavorato-Rocha André Mourão , Rodrigues Lara Sant'Ana , Coutinho-Camillo Cláudia Malheiros , Baiocchi Glauco , Stiepcich Monica Maria , Puga Renato , de A. Lima Leandro , Soares Fernando Augusto , Rocha Rafael Malagoli
Published: September 2013

Unregulated expression of microRNAs is well known and has already been demonstrated in many tumor types. However, in vulvar carcinoma this field has been unknown territory. Our study characterizes microRNA in vulvar tumors through an expression profile of 754 miRNAs, relating this with clinical and anatomopathologic data, and presence of HPV infection. Twenty HPV-negative and 20 HPV-positive samples, genotyped for high-risk HPVs (HPV16, 18, 31, 33) and a pool of seven normal vulvar skin samples were used for the identification of differentially expressed miRNAs by TLDA Quantitative Real Time PCR (qRT-PCR). Twenty-five differentially expressed microRNAs between HPV-positive and HPV-negative groups and 79 differentially expressed on the tumor compared with normal samples were obtained. A network between microRNA expression profiles and putative target mRNAs predicted by target prediction algorithms and previously demonstrated as relevant in vulvar carcinomas, such as TP53, RB, PTEN, and EGFR was constructed. Downregulation of both miR-223-5p and miR-19-b1-5p were correlated with the presence of lymph node metastasis; downregulation of miR-100-3p and miR-19-b1-5p were correlated with presence of vascular invasion; overexpression of miR-519b and miR-133a were associated with advanced FIGO staging. In conclusion, our study demonstrates that microRNAs may be clinically important in vulvar carcinomas and our findings may help for further studies on functional implications of miRNA deregulation in this type of cancer. Cancer Prev Res; 6(11); 1231–41. ©2013 AACR.
Increased Permeability of Cutaneous Lymphatic Capillaries and Enhanced Blood Flow in Psoriatic Plaques
Authors: Meier Thomas O. , Kovacicova Ludmila , Huggenberger Reto , Navarini Alexander A. , Gitzelmann Gabriela , Amann-Vesti Beatrice R.
Published: September 2013

Introduction: Morphological abnormalities of microvessels are described in psoriasis. However, there are conflicting data as to whether their function is also altered. Objective: Our aim was to study the morphology and function of the lymphatic capillaries of psoriatic skin. Methods: Morphology and permeability of initial lymphatics were studied by microlymphography and densitometry in 20 patients. Perfusion was studied by laser Doppler fluxmetry. Results: Permeability of lymphatics in plaques was increased by 7.6% compared to unafflicted skin (p < 0.001). Lymphatic vessel density and the extension of dye in lymphatic networks were not significantly different between involved and uninvolved areas. Both sites showed a wide range of diameters of lymphatics. The median laser Doppler flux in plaques was increased by 144% (91-380%) compared to unaffected skin (p < 0.001). Conclusions: Increased permeability of lymphatics and increased blood flow was demonstrated in vivo in psoriatic skin lesions. These findings may reflect the local inflammatory process and may be used as markers when studying new therapeutic approaches for psoriasis.
Class IA Phosphatidylinositol 3-Kinase Inhibition Inhibits Cell Growth and Proliferation in Mantle Cell Lymphoma
Authors: Tabe Yoko , Jin Linhua , Konopleva Marina , Shikami Masato , Kimura Shinya , Andreeff Michael , Raffeld Mark , Miida Takashi
Published: September 2013

Background/Aims: Constitutive activation of the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin signaling pathway preferentially occurs in aggressive blastoid variants of mantle cell lymphoma (MCL) and is implicated in the pathogenesis of this disease. In this study, we investigated the role of PI3K isoforms on proliferation of aggressive MCL cells. Methods: The changes in cell viability, cell cycle distribution and apoptosis induction by the PI3K isoform-selective inhibitors were evaluated. The molecular basis underlying the effects of the specific inhibition of PI3K isoforms was investigated by Western blot analysis. Results: Our results demonstrated that a class IA PI3K isoform is most commonly involved in the constitutive activation of Akt in aggressive MCL. Treatment with a p110α isoform-specific inhibitor induced prominent cell cycle arrest followed by apoptosis through complete abolishment of phosphorylated (p)-Akt and its downstream targets. An inhibitor of isoform p110δ induced moderate cell cycle arrest with downregulation of p-Akt and p-S6K. A dual inhibitor of p110α and p110δ GDC-0941 caused more prominent cell growth inhibition compared to selective p110α or p110δ inhibitors. Inhibition of the class IB PI3K isoform p110γ did not cause cell cycle arrest or induce apoptosis in MCL cells. Conclusion: These findings suggest that the therapeutic ablation of class IA PI3K may be a promising strategy for the treatment of refractory, aggressive MCL.