bluuebunny/crossref_metadata_2025 huggingface dataset:
Creating excellent and competitive motels services
Authors: Cheng Ching-Chan , Chen Cheng-Ta
Published: January 2018

Purpose

The motel industry in Taiwan is a highly competitive industry, which requires considerable investment and demands innovative services. This paper aims to identify the competitive qualities that urgently require improvement to enhance the service quality of motels using the two-phase method of importance-performance and gap analysis (IPGA) and the Kano model, and develops specific improvement strategies.

Design/methodology/approach

By questionnaire survey, this study collects 562 valid questionnaires from motels in Taipei City. The IPGA and Kano model are used to identify the service attributes of market competitiveness that urgently require improvement.

Findings

The results show there are 14 attributes that should be urgently improved, of which four are the attractive qualities of market competitiveness (competitive qualities). This study develops ten improvement strategies, as based on the four competitive qualities, for the reference of the motel industry.

Practical implications

The results can identify the competitive qualities that require urgent improvement to address the development of improvement strategies for motels. The managers of motels can refer to the ten improvement strategies to create excellent and competitive motel services.

Originality/value

The results combine “customers’ needs” with “the competitive meanings of quality attributes in the market” under limited resources, to upgrade motel service quality, customers’ willingness to purchase and motel competitiveness.
Influence of specialized hotels on employees’ perception of abuse in the selective tourism destination
Authors: Vučetić Aleksa Š.
Published: January 2018

Purpose

This paper aims to determine to what extent there is a difference in employees’ perception of abuse in the selective tourism destination in various types of specialized hotels.

Design/methodology/approach

A survey of employees in specialized hotels in the selective tourism destination has the sample of 1,796 cases. Multivariate analysis of variance is used for testing the level of perception’s differences.

Findings

There is a statistically significant difference in the perception of abuse among employees in various types of specialized hotels such as wellness hotels, sport hotels, business hotels and congress hotels.

Research limitations/implications

The results offer employees’ perception of differences about abuse in various types of specialized hotels in the selective tourism destination. There is a possibility of practical usage of methodology for identification of the most often types of abuse in specialized hotels. The identification of abuse is to protect specific social structures such as employees in specialized hotels in the selective tourism destination.

Originality/value

Research could serve as a good example for future practical and theoretical research in the field of abuse and specialized hotels. The paper can be used as a methodological tool to show how to identify the most often types of abuse in specialized hotels in a concrete selective tourism destination.
Gender and age preferences of hotel room design
Authors: Bogicevic Vanja , Bujisic Milos , Cobanoglu Cihan , Feinstein Andrew Hale
Published: January 2018

Purpose

The purpose of this study is to investigate what people with different demographic characteristics such as age and gender expect from hotel room design and examine how design preferences affect purchase intent and desire to stay and word-of-mouth behavior.

Design/methodology/approach

The study was based on a quasi-experimental design conducted on 762 participants. The manipulations of room color and design style were prepared using the 3D modeling software, while age and gender were self-reported variables.

Findings

The results indicated that age and gender moderate the relationship between hotel guest satisfaction and room design style. Younger guests prefer contemporary design style, while older guests show equal satisfaction with traditional and contemporary styles. Male guests prefer rooms decorated in masculine colors, while women are equally satisfied with masculine or feminine color schemes.

Research limitations/implications

This study was conducted as a hypothetical, computer-aided experimental scenario. A field experiment captured guests’ satisfaction with an experimental hotel room. A substantive cause–effect relationship between hotel room visual servicescape stimuli and satisfaction was established.

Practical implications

Identifying design style and color preferences of a hotel target market is paramount for investment payoff and further supports the customization of hotel services.

Originality/value

This is the first experimental study to manipulate color scheme and type of design in a hotel room and capture their effects on satisfaction and behavior of guests with different demographic characteristics.
Vacation co-creation: the case of Chinese family travelers
Authors: Fu Xiaoxiao , Lehto Xinran
Published: January 2018

Purpose

The purpose of this study is to provide a nuanced understanding of Chinese family tourists’ value co-creation by examining three important aspects of family vacation: What do families do during vacation? How do they make meaning of what they do? Do travelers’ role identities within their families play a role in the value creation process?

Design/methodology/approach

Upon reviewing related theoretical work, the authors undertook a mixed-method study consisting of both survey data and in-depth interviews.

Findings

The analysis revealed three clusters of family interactional content, including We open and share our worlds, We build knowledge and skills and We co-create and co-evaluate, and five clusters of family travelers, including Outdoor enthusiasts, Socializers, Nature lovers, Culture admirers and Relaxation seekers. Family roles, life situations and destination environments also interfaced with family activity participation and family conversations. A family vacation value co-creation process framework with four propositions was, thus, proposed.

Research limitations/implications

Further exploration and validation of the proposed framework and propositions which emerged from the findings of this study are needed. Impacts of various family types and relational dynamics also warrant future investigation.

Practical implications

The results of family interactional and relational well-being facilitated by family vacation are pertinent to academia, industry and public policy-making.

Social implications

Family vacation can be a positive intervention for the creation of family value and a means of meaning-making. Programs that integrate multiple family roles and address family-level value propositions would be collectively enriching.

Originality/value

The current study initiated a pioneering investigation by providing a depiction of how family travelers experience and make sense of a shared tourism experience, along with their value perceptions in such a co-created consumptive scenario.
The impact of restaurant patrons’ flow experience on SNS satisfaction and offline purchase intentions
Authors: Kang Jee-Won , Lee Hyesung , Namkung Young
Published: January 2018

Purpose

It is important for restaurants’ social networking sites (SNSs) to provide a flow experience because it encourages positive brand responses and attracts consumers. However, there is a paucity of research on SNS flow experience in the restaurant industry, and more importantly, most of the research is focused only on online behavior. Therefore, this study aims to investigate how SNS flow antecedents (skill, challenge, telepresence and time distortion) influence overall flow, SNS satisfaction and offline restaurant purchase intentions. In addition, this study examined the mediating role of SNS satisfaction between flow and offline purchase intentions.

Design/methodology/approach

An online survey was carried out to examine the patron’s flow experiences. 517 valid responses were analyzed to test hypotheses using structural equation model.

Findings

The results indicated that four antecedents of SNS flow positively influenced overall flow. Specifically, time distortion was the most influential antecedent. Overall flow positively influenced SNS satisfaction and offline purchase intentions. Furthermore, SNS satisfaction acted as a mediator between overall flow and offline purchase intentions.

Practical implications

The findings provide not only new insights for restaurant managers to implement SNS marketing but also several strategies to encourage consumer’s flow on restaurant SNS.

Originality/value

This study investigated the theoretical framework of flow experience more in depth than previous research as dealing with four dimensions of SNS flow antecedents: skill, challenge, telepresence and time distortion.
Payout and firm’s catering
Authors: Neves Maria Elisabete Duarte
Published: January 2018

Purpose

The purpose of this paper is to investigate whether investor sentiments exert significant influence on corporate dividend policy. Additionally it provides further evidence on the moderating role of certain firm’s characteristics on the relation between dividends and investor sentiment.

Design/methodology/approach

A sample of 635 firms from 12 Eurozone countries for the period of 1986-2003 has been used. A dividend model has been suggested which incorporates a variable at the firm level that proxies for the catering effect, as a measure of investor sentiments. The estimation model of dividends is based on the Generalized Method of Moments (Arellano and Bond, 1991).

Findings

It can be concluded that psychological factors influence the decision to pay. Furthermore, other relevant findings show an interaction effect between catering and firm’s characteristics, particularly high liquid assets, valuable investment opportunities, and higher levels of free cash flow.

Research limitations/implications

Given the subjectivity inherent in creating a variable that captures the sentiment of investors, the author admits that there are other variables to consider. Also, corporate governance factors could have been introduced as well as other countries with different institutional environments.

Originality/value

To the best of the author’s knowledge, this is a novel approach that incorporates a variable capturing investor’s sentiment at the firm level. With the approach suggested it has been shown that investors’ sentiments impact dividends payout, highlighting its usefulness for managers who are expected to pay dividends according to investors’ expectations. Moreover, this work also demonstrated that firm’s characteristics could affect the investor sentiments for dividends also conveying a valuable contribution for investors.
Determinants of viewer attention in concurrent event sponsorship
Authors: Boronczyk Felix , Rumpf Christopher , Breuer Christoph
Published: January 2018

Purpose

The purpose of this paper is to examine the impact of exposure-related and consumer-related factors on the return of sponsorship investment through their influence on viewers’ attention for sponsor signage.

Design/methodology/approach

Data were collected through an experimental study (n=92) involving eye-tracking and a questionnaire, and were analyzed using regression analysis.

Findings

The results show that viewers’ attention for sponsor signage is affected by the signage color of concurrent sponsors, as well as viewers’ brand familiarity, and sport involvement. In particular, the findings reveal that viewers’ attention for sponsor signage increases with greater color contrast between concurrently visible sponsor signage. Further, signage receives more attention if viewers are familiar with the brand and less involved with the sponsored event. Given that attention is an important prerequisite for further processing of sponsorship information, these findings have important implications for managers seeking to evaluate the return on their sponsorship investment.

Practical implications

When assessing the return on a sponsorship investment, marketers should consider the characteristics of surrounding sponsor signage and the audience with regard to their impact on viewers’ attention for their own signage. Ideally, marketers should attempt to create a greater color contrast between their own signage and its surroundings in order to maximize viewer attention.

Originality/value

This paper provides valuable information on the importance of concurrently visible sponsor signage and audience characteristics for the return on investment of sponsorships through their impact on viewers’ attention.
Assessing the effectiveness of sponsorship messaging
Authors: Alonso Dos Santos Manuel , Calabuig Moreno Ferran
Published: January 2018

Purpose

The purpose of this paper is to represent a pilot study which aims to explore the attention to sponsorship variable by assessing the level of congruence linked to both the sponsor and the sponsored entity (sponsee).

Design/methodology/approach

This research performed an experiment involving three different sporting activities where the level of congruence was perceived in a different way according to the different attributes of sponsorship message. Electroencephalograms were employed in order to measure reaction times when recognizing and identifying the level of congruence of sponsorship messages. The rate of successful understanding and identification of these sponsorship messages was also measured with this tool.

Findings

Incongruent, misfit messages are processed and encoded with a higher level of attention as opposed to the information which is reliable and consistent with prior expectations (congruent pairings). This means that subjects find fit, congruent messages more difficult to identify; in this case the information is poorly encoded and often misunderstood. In relation to attention congruity, this research found no differences across the different sporting activities which were examined.

Practical implications

This research proves that neuroscientific methods can be useful to assess the performance of sponsorship as an alternative to traditional techniques. In addition, this research contributes to the existing debate in the literature regarding the disagreeing results on the actual effectiveness of sponsoring congruent perceived events involving congruent perceived sports teams.

Originality/value

This paper is pioneering in the measurement of sponsorship performance through the use of electroencephalograms. Also, the level of attention is considered as a performance indicator.
Merging and expanding existing ontologies to cover the Built Cultural Heritage domain
Authors: Zalamea Patino Olga Piedad , Van Orshoven Jos , Steenberghen Thérèse
Published: January 2018

Purpose

The purpose of this paper is to present the development of an ontological model consisting of terms and relationships between these terms, creating a conceptual information model for the Built Cultural Heritage (BCH) domain, more specifically for preventive conservation.

Design/methodology/approach

The On-To-Knowledge methodology was applied in the ontology development process. Terms related to preventive conservation were identified by means of a taxonomy which was used later to identify related existing ontologies. Three ontologies were identified and merged, i.e. Geneva City Geographic Markup Language (Geneva CityGML), Monument Damage ontology (Mondis) and CIDOC Conceptual Reference Model (CIDOC-CRM). Additional classes and properties were defined as to provide a complete semantic framework for management of BCH.

Findings

A BCH-ontology for preventive conservation was created. It consists of 143 classes from which 38 originate from the Mondis ontology, 38 from Geneva CityGML, 37 from CIDOC-CRM and 30 were newly created. The ontology was applied in a use case related to the New cathedral in the city of Cuenca, Ecuador. Advantages over other type of systems and for the BCH-domain were discussed based on this example.

Research limitations/implications

The proposed ontology is in a testing stage through which a number of its aspects are being verified.

Originality/value

This ontological model is the first one to focus on the preventive conservation of BCH.
Sustainable agricultural entrepreneurship in Burundi: drivers and outcomes
Authors: Mupfasoni Bélyse , Kessler Aad , Lans Thomas
Published: January 2018

Purpose

The purpose of this paper is to contribute to the emerging literature on sustainable entrepreneurship by studying knowledge, motivation and early stage outcomes of sustainable agricultural entrepreneurship in the context of farmer groups in Burundi.

Design/methodology/approach

Quantitative and qualitative data were combined in a multiple-source case study. Data were analyzed using content analysis and basic statistics.

Findings

Results revealed that farmer groups’ prior knowledge (PK) on environmental sustainability is better developed than their social and economic sustainability. This is reflected in the environmental sustainability part of the business plans (BPs), which is generally better than the economic and social sustainability parts. Moreover, the top groups on PK identified opportunities directly related to their PK. Pro-activeness of the group was a more determining factor than risk taking and innovativeness. Furthermore, there seemed to be a positive interplay between the groups’ PK, entrepreneurial orientation and knowledge motivation (KM) and the quality of the sustainable BP. In particular, KM seemed to be important, but other variables also explained the quality of the BP, such as level of education.

Originality/value

This research fills a gap in literature because there are few empirical studies on agricultural entrepreneurship that focus on the earliest phase of opportunity recognition, let alone studies that focus on sustainable opportunity recognition in the context of emerging economies such as Burundi. Furthermore, in this research, the authors studied well-known knowledge, motivations and outcomes of sustainable entrepreneurship.
Research on three-dimensional digital process planning based on MBD
Authors: Zhu Haihua , Li Jing
Published: January 2018

Purpose

Three-dimensional digital design and manufacturing technology are changing the current manufacturing pattern and have become the core of enterprise competition. However, the research and application of three-dimensional digital technology in the present phase have a strong bias toward the design of three-dimensional model and focus little on process planning. It restricts the development of manufacturing industry. Therefore, this paper aims to present a design scheme of three-dimensional digital process planning.

Design/methodology/approach

A three-dimensional digital process design method is developed by combining model-based definition technology and knowledge engineering technology. Model-based definition technology is used to display the process information. And knowledge engineering technology is used for process decision; meanwhile, ontology technology is introduced to describe process knowledge. And taking shaft part as an example, this paper establishes the general ontology of manufacturing process and the special ontology of shaft. This research provides an available method for the three-dimensional digital process planning.

Findings

Traditional process planning mainly is based on two-dimensional engineering drawing, which leads to the low efficiency and quality of process planning. Moreover, it cannot achieve effective mining and management of knowledge. Thus, applying an effective knowledge management technology into a three-dimensional process system is necessary.

Research limitations/implications

This paper contributes to an available method for three-dimensional digital process planning.

Originality/value

The introduction of model-based definition technology makes process information display in three-dimensional environment. And ontology technology achieves sematic reference and efficient management of process knowledge.
Key success factors for logistics provider enterprises: an empirical investigation in Iran
Authors: Ahmad Alinejad Ensieh , Pishvaee Mir Saman , Bonyadi Naeini Ali
Published: January 2018

Purpose

This study aims to determine the key success factors of logistics provider enterprises in Iran, a country which has a significant potential for logistics activities among the Middle East countries, and connects the Asian, European and African logistics networks.

Design/methodology/approach

This study is an applied one in terms of goal and descriptive according to the data collection method. Survey analysis is conducted with 130 Iranian logistics provider firms. The 119 responses to the questionnaire are evaluated statistically, and thereafter, analytic hierarchy process and decision-making trial and evaluation laboratory (DEMATEL) methods are used to prioritize the obtained key success factors.

Findings

A comprehensive list of logistics provider firms’ key success factors are provided according to literature and opinion of experts. Among the aforementioned list, the authors found that management and leadership, internationalization and the competence of employees are the most important key success factors of logistics provider firms in Iran.

Originality/value

This is the first research that studies the key success factors of logistics provider firms in Iran. As Iran is an important intermediate country in the Middle East logistics corridor, it is worthy for practitioners and investors to know about success factors of logistics provider companies in Iran. In fact, focusing on the key success factors determined in this research assures the competitiveness of logistics provider firms in Iran. Moreover, the results can be also useful for some other countries in the Middle East such as Turkey and Emirates and can be used to enhance the logistical performance of the Middle East logistics network.
Deconstructing quality in South African higher education
Authors: Fomunyam Kehdinga George
Published: January 2018

Purpose

This study aims to examine six South African universities with a particular focus on the quality of teaching and learning.

Design/methodology/approach

A qualitative case study approach was adopted and data were mainly generated by means of open-ended questionnaires. The questionnaire was circulated to approximately 1,800 students and 746 completed it. The data were categorized and analysed thematically, using both national and international benchmarks for quality teaching and learning.

Findings

The findings reveal that teaching and learning in South African universities is marred by a plethora of challenges. Lecturers lack basic skills and essential resources to effectively facilitate teaching and learning. Furthermore, quality benchmarks set by the Council on Higher Education are only met on paper and little or nothing is done to translate this into practice.

Originality/value

The study proposes among others that clearer policies on funding are recommended to ensure proper allocation of resources, staff development and institutional comeliness. Finally, to enhance transformation, universities should prioritize teaching and learning and take steps to ensure that those teaching in the classroom are qualified to do so.
The legitimacy of offender management programmes in a post-TR landscape
Authors: Rowe Michael , Irving Adele , Soppitt Sarah
Published: January 2018

Purpose

The purpose of this paper is to explore the under-considered perspectives of service users engaged in various community sentences based on a “strengths-based” approach to desistance. Further to recent changes in the sector, the paper considers service user views for programmes delivered by combinations of agencies from private, public and third sectors.

Design/methodology/approach

The paper is based on analysis of 64 semi-structured interviews with users of four programmes, accompanied with informal fieldwork observations by the researchers as they carried out the research at the premises of service providers.

Findings

The research finds that service user perceptions of the legitimacy of programmes are closely related to their understanding of three key dimensions: first, the “authenticity” of those delivering the service; second, the instrumental (in broad terms) gains they expect from engagement; and third, their understanding of the identity and ethos of the programme.

Originality/value

The paper adds important understanding based on service user perceptions in a period when service provision is being diversified. Further directions for other research are identified and it is recognised that a limitation of the current study is that it incorporates a sample drawn from one area.
Electromagnetic based acoustic energy harvester for low power wireless autonomous sensor applications
Authors: Izhar  , Khan Farid Ullah
Published: January 2018

Purpose

The purpose of this paper is to develop a novel electromagnetic-based acoustic energy harvester (EH) for the application of wireless autonomous sensors.

Design/methodology/approach

The developed acoustic EH comprises a Helmholtz resonator (HR), a suspension system that consists of a flexible membrane and a permanent magnet, a couple of coils and a coil holder. Furthermore, the HR, used in the harvester, is designed for a specific resonant frequency based on simulation carried out in COMSOL Multiphysics®.

Findings

The developed harvester is tested both in lab under harmonic sound pressure levels (SPLs) and in real environment under random SPLs. In lab, when exposed to 100 dB SPL, the harvester generated a peak power of 212 µW. Furthermore, in real environment in vicinity of electric generator, the harvester produced an output voltage of about 110 mV collectively from its both coils.

Originality/value

In this paper, a novel geometric configuration for electromagnetic-based acoustic EH is proposed. In the developed harvester, two coils are placed in it to achieve enhanced electrical output from it for the first time.
A dual-mode proximity sensor with combination of inductive and capacitive sensing units
Authors: Kan Wenqing , Huang Ying , Zeng Xiao , Guo Xiaohui , Liu Ping
Published: January 2018

Purpose

The purpose of this paper is to present a dual-mode proximity sensor composed of inductive and capacitive sensing modes, which can help the robot distinguish different objects and obtain distance information at the same time. A systematic study of sensor response to various objects and the function of cooperation sensing is needed. Furthermore, the application in the field of robotic area needs to be discussed.

Design/methodology/approach

Numerical modeling of each sensing modes and simulations based on finite element analysis method has been carried out to verify the designed dual-mode sensor. A number of objects composed of different materials are used to research the cooperation perception and proximity sensing functions. In addition, the proposed sensor is used on the palm of a mechanical hand as application experiment.

Findings

The characteristics of the sensor are summarized as follows: the sensing range of inductive mode is 0-5.6 mm for detecting a copper block and the perceive range of capacitive mode is 0-5.1 mm for detecting a plastic block. The collaborative perceive tests validated that the non-ferromagnetism metals can be distinguished by inductive mode. Correspondingly, ferromagnetism metals and dielectric objects are differentiated by capacitive mode. Application experiments results reveal that both plastic bottle and steel bottle could be detected and differentiated. The experimental results are in agreement with those of simulations.

Originality value

This paper provides a study of dual-mode proximity sensor in terms of design, experiments and application.
Local current–voltage estimation and characteristization based on field emission image processing of large-area field emitters
Authors: Popov Eugeni O. , Kolosko Anatoly G. , Filippov Sergey V. , Terukov Evgeny I.
Published: January 2018

Local emission characteristics of microscopic emission sites on the surface of large-area field emitters are among the most important factors influencing macroscopic emission properties. This work aimed to evaluate the local field emission characteristics using a computerized field emission projector and a technique involving multichannel recording of current–voltage characteristics. The model field emitter consisted of nanocomposite multiwall carbon nanotubes in a polymer matrix.
Age effects on perceptual restoration of degraded interrupted sentences
Authors: Jaekel Brittany N. , Newman Rochelle S. , Goupell Matthew J.
Published: January 2018

Adult cochlear-implant (CI) users show small or non-existent perceptual restoration effects when listening to interrupted speech. Perceptual restoration is believed to be a top-down mechanism that enhances speech perception in adverse listening conditions, and appears to be particularly utilized by older normal-hearing participants. Whether older normal-hearing participants can derive any restoration benefits from degraded speech (as would be presented through a CI speech processor) is the focus of this study. Two groups of normal-hearing participants (younger: age ≤30 yrs; older: age ≥60 yrs) were tested for perceptual restoration effects in the context of interrupted sentences. Speech signal degradations were controlled by manipulating parameters of a noise vocoder and were used to analyze effects of spectral resolution and noise burst spectral content on perceptual restoration. Older normal-hearing participants generally showed larger and more consistent perceptual restoration benefits for vocoded speech than did younger normal-hearing participants, even in the lowest spectral resolution conditions. Reduced restoration in CI users thus may be caused by factors like noise reduction strategies or small dynamic ranges rather than an interaction of aging effects and low spectral resolution.
Phonological feature-based speech recognition system for pronunciation training in non-native language learning
Authors: Arora Vipul , Lahiri Aditi , Reetz Henning
Published: January 2018

The authors address the question whether phonological features can be used effectively in an automatic speech recognition (ASR) system for pronunciation training in non-native language (L2) learning. Computer-aided pronunciation training consists of two essential tasks—detecting mispronunciations and providing corrective feedback, usually either on the basis of full words or phonemes. Phonemes, however, can be further disassembled into phonological features, which in turn define groups of phonemes. A phonological feature-based ASR system allows the authors to perform a sub-phonemic analysis at feature level, providing a more effective feedback to reach the acoustic goal and perceptual constancy. Furthermore, phonological features provide a structured way for analysing the types of errors a learner makes, and can readily convey which pronunciations need improvement. This paper presents the authors implementation of such an ASR system using deep neural networks as an acoustic model, and its use for detecting mispronunciations, analysing errors, and rendering corrective feedback. Quantitative as well as qualitative evaluations are carried out for German and Italian learners of English. In addition to achieving high accuracy of mispronunciation detection, the system also provides accurate diagnosis of errors.
Riding Into the Future: A Financial Examination of SoulCycle and the Indoor Cycling Studio Trend
Authors: Hambrick Marion E.
Published: January 2018

SoulCycle is a $122 million company offering customers 45-min workouts in its indoor cycling studios. As one of the first boutique fitness firms to emerge in the $28.5 billion fitness industry, SoulCycle grew from one indoor cycling studio in New York City in 2006 to 67 studios across the United States by 2016. SoulCycle executives faced a pivotal moment in May 2016. Chief executive officer Melanie Whelan recognized the company faced increasing competition in the boutique fitness segment, with companies such as Flywheel and Peloton making inroads into this market. In addition, two of SoulCycle’s founders resigned from their leadership positions earlier the same year. These developments led to questions about the long-term viability of SoulCycle within the larger fitness industry. A detailed financial analysis of SoulCycle, including an examination of the company’s financial statements, financial ratios, strategic initiatives, and competitors, could provide insights about its chances for continued success.
Intrapulmonary Pharmacokinetics of Relebactam, a Novel β-Lactamase Inhibitor, Dosed in Combination with Imipenem-Cilastatin in Healthy Subjects
Authors: Rizk Matthew L. , Rhee Elizabeth G. , Jumes Patricia A. , Gotfried Mark H. , Zhao Tian , Mangin Eric , Bi Sheng , Chavez-Eng Cynthia M. , Zhang Zufei , Butterton Joan R.
Published: January 2018

This phase I study assessed the intrapulmonary pharmacokinetic profiles of relebactam (MK-7655), a novel β-lactamase inhibitor, and imipenem. Sixteen healthy subjects received 250 mg relebactam with 500 mg imipenem-cilastatin, given intravenously every 6 h for 5 doses, and were randomized to bronchoscopy/bronchoalveolar lavage at 0.5, 1, 1.5, or 3 h after the last dose (4 subjects per time point). Both drugs penetrated the epithelial lining fluid (ELF) to a similar degree, with the profiles being similar in shape to the corresponding plasma profiles and with the apparent terminal half-lives in plasma and ELF being 1.2 and 1.3 h, respectively, for relebactam and 1.0 h in both compartments for imipenem. The exposure (area under the concentration-time curve from time zero to infinity) in ELF relative to that in plasma was 54% for relebactam and 55% for imipenem, after adjusting for protein binding. ELF penetration for relebactam was further analyzed by fitting the data to a two-compartment pharmacokinetic model to capture its behavior in plasma, with a partitioning coefficient capturing its behavior in the lung compartment. In this model, the time-invariant partition coefficient for relebactam was found to be 55%, based on free drug levels. These results support the clinical evaluation of relebactam with imipenem-cilastatin for the treatment of bacterial pneumonia.
Prospective Clinical Trial Assessing Species-Specific Efficacy of Artemether-Lumefantrine for the Treatment of Plasmodium malariae, Plasmodium ovale, and Mixed Plasmodium Malaria in Gabon
Authors: Groger Mirjam , Veletzky Luzia , Lalremruata Albert , Cattaneo Chiara , Mischlinger Johannes , Zoleko-Manego Rella , Endamne Lilian , Klicpera Anna , Kim Johanna , Nguyen The , Flohr Lena , Remppis Jonathan , Matsiegui Pierre-Blaise , Adegnika Ayôla A. , Agnandji Selidji T. , Kremsner Peter G. , Mordmüller Benjamin , Mombo-Ngoma Ghyslain , Ramharter Michael
Published: January 2018

Treatment recommendations for
Plasmodium malariae
and
Plasmodium ovale
malaria are largely based on anecdotal evidence. The aim of this prospective study, conducted in Gabon, was to systematically assess the efficacy and safety of artemether-lumefantrine for the treatment of patients with uncomplicated
P. malariae
or
P. ovale
species monoinfections or mixed
Plasmodium
infections. Patients with microscopically confirmed
P. malariae
,
P. ovale
, or mixed-species malaria with at least one of these two
Plasmodium
species were treated with an oral, fixed-dose combination of artemether-lumefantrine for 3 consecutive days. The primary endpoints were per-protocol PCR-corrected adequate clinical and parasitological response (ACPR) on days 28 and 42. Tolerability and safety were recorded throughout the follow-up period. Seventy-two participants (42 male and 30 female) were enrolled; 62.5% of them had PCR-corrected mixed
Plasmodium
infections. Per protocol, PCR-corrected ACPR rates were 96.6% (95% confidence interval [CI], 91.9 to 100) on day 28 and 94.2% (95% CI, 87.7 to 100) on day 42. Considering
Plasmodium
species independently from their coinfecting species, day 42 ACPR rates were 95.5% (95% CI, 89.0 to 100) for
P. falciparum
, 100% (exact CI, 84.6 to 100) for
P. malariae
, 100% (exact CI, 76.8 to 100) for
P. ovale curtisi
, and 90.9% (95% CI, 70.7 to 100) for
P. ovale wallikeri
. Study drug-related adverse events were generally mild or moderate. In conclusion, this clinical trial demonstrated satisfying antimalarial activity of artemether-lumefantrine against
P. ovale
wallikeri
,
P. ovale curtisi
,
P. malariae
, and mixed
Plasmodium
infections, with per-protocol efficacies of 90% to 100% and without evident tolerability or safety concerns. (This trial was registered in the clinical study database ClinicalTrials.gov under the identifier NCT02528279.)
G-Quadruplex DNA Motifs in the Malaria Parasite Plasmodium falciparum and Their Potential as Novel Antimalarial Drug Targets
Authors: Harris Lynne M. , Monsell Katelyn R. , Noulin Florian , Famodimu M. Toyin , Smargiasso Nicolas , Damblon Christian , Horrocks Paul , Merrick Catherine J.
Published: January 2018

G-quadruplexes are DNA or RNA secondary structures that can be formed from guanine-rich nucleic acids. These four-stranded structures, composed of stacked quartets of guanine bases, can be highly stable and have been demonstrated to occur
in vivo
in the DNA of human cells and other systems, where they play important biological roles, influencing processes such as telomere maintenance, DNA replication and transcription, or, in the case of RNA G-quadruplexes, RNA translation and processing. We report for the first time that DNA G-quadruplexes can be detected in the nuclei of the malaria parasite
Plasmodium falciparum
, which has one of the most A/T-biased genomes sequenced and therefore possesses few guanine-rich sequences with the potential to form G-quadruplexes. We show that despite this paucity of putative G-quadruplex-forming sequences,
P. falciparum
parasites are sensitive to several G-quadruplex-stabilizing drugs, including quarfloxin, which previously reached phase 2 clinical trials as an anticancer drug. Quarfloxin has a rapid initial rate of kill and is active against ring stages as well as replicative stages of intraerythrocytic development. We show that several G-quadruplex-stabilizing drugs, including quarfloxin, can suppress the transcription of a G-quadruplex-containing reporter gene in
P. falciparum
but that quarfloxin does not appear to disrupt the transcription of rRNAs, which was proposed as its mode of action in both human cells and trypanosomes. These data suggest that quarfloxin has potential for repositioning as an antimalarial with a novel mode of action. Furthermore, G-quadruplex biology in
P. falciparum
may present a target for development of other new antimalarial drugs.
A Lactobacillus-Deficient Vaginal Microbiota Dominates Postpartum Women in Rural Malawi
Authors: Doyle Ronan , Gondwe Austridia , Fan Yue-Mei , Maleta Kenneth , Ashorn Per , Klein Nigel , Harris Kathryn
Published: January 2018

The bacterial community found in the vagina is an important determinant of a woman's health and disease status. A healthy vaginal microbiota is associated with low species richness and a high proportion of one of a number of different
Lactobacillus
spp. When disrupted, the resulting abnormal vaginal microbiota is associated with a number of disease states and poor pregnancy outcomes. Studies up until now have concentrated on relatively small numbers of American and European populations that may not capture the full complexity of the community or adequately predict what constitutes a healthy microbiota in all populations. In this study, we sampled and characterized the vaginal microbiota found on vaginal swabs taken postpartum from a cohort of 1,107 women in rural Malawi. We found a population dominated by
Gardnerella vaginalis
and devoid of the most common vaginal
Lactobacillus
species, even if the vagina was sampled over a year postpartum. This
Lactobacillus
-deficient anaerobic community, commonly labeled community state type (CST) 4, could be subdivided into four further communities. A
Lactobacillus iners
-dominated vaginal microbiota became more common the longer after delivery the vagina was sampled, but
G. vaginalis
remained the dominant organism. These results outline the difficulty in all-encompassing definitions of what a healthy or abnormal postpartum vaginal microbiota is. Previous identification of community state types and associations among bacterial species, bacterial vaginosis, and adverse birth outcomes may not represent the complex heterogeneity of the microbiota present. (This study has been registered at ClinicalTrials.gov as NCT01239693.)

IMPORTANCE
A bacterial community in the vaginal tract is dominated by a small number of
Lactobacillus
species, and when not present there is an increased incidence of inflammatory conditions and adverse birth outcomes. A switch to a vaginal bacterial community lacking in
Lactobacillus
species is common after pregnancy. In this study, we characterized the postpartum vaginal bacterial community of a large group of women from a resource-poor, undersampled population in rural Malawi. The majority of women were found to have a
Lactobacillus-
deficient community, and even when sampled a year after delivery the majority of women still did not have
Lactobacillus
present in their vaginal microbiota. The effect of becoming pregnant again for those who do not revert to a
Lactobacillus
-dominant community is unknown, and this could suggest that not all
Lactobacillus-
deficient community structures are adverse. A better understanding of this complex community state type is needed.
Deletion of the Major Facilitator Superfamily Transporter
fptB
Alters Host Cell Interactions and Attenuates Virulence of Type A Francisella tularensis
Authors: Balzano Phillip M. , Cunningham Aimee L. , Grassel Christen , Barry Eileen M.
Published: January 2018

Francisella tularensis
is a Gram-negative, facultative, intracellular coccobacillus that can infect a wide variety of hosts. In humans,
F. tularensis
causes the zoonosis tularemia following insect bites, ingestion, inhalation, and the handling of infected animals. The fact that a very small inoculum delivered by the aerosol route can cause severe disease, coupled with the possibility of its use as an aerosolized bioweapon, has led to the classification of
Francisella tularensis
as a category A select agent and has renewed interest in the formulation of a vaccine. To this end, we engineered a type A strain SchuS4 derivative containing a targeted deletion of the major facilitator superfamily (MFS) transporter
fptB
. Based on the attenuating capacity of this deletion in the
F. tularensis
LVS background, we hypothesized that the deletion of this transporter would alter the intracellular replication and cytokine induction of the type A strain and attenuate virulence in the stringent C57BL/6J mouse model. Here we demonstrate that the deletion of
fptB
significantly alters the intracellular life cycle of
F. tularensis
, attenuating intracellular replication in both cell line-derived and primary macrophages and inducing a novel cytosolic escape delay. Additionally, we observed prominent differences in the
in vitro
cytokine profiles in human macrophage-like cells. The mutant was highly attenuated in the C57BL/6J mouse model and provided partial protection against virulent type A
F. tularensis
challenge. These results indicate a fundamental necessity for this nutrient transporter in the timely progression of
F. tularensis
through its replication cycle and in pathogenesis.
A Robust CRISPR Interference Gene Repression System in Pseudomonas
Authors: Tan Sue Zanne , Reisch Christopher R. , Prather Kristala L. J.
Published: January 2018

Pseudomonas
spp. are widely used model organisms in different areas of research. Despite the relevance of
Pseudomonas
in many applications, the use of protein depletion tools in this host remains limited. Here, we developed the CRISPR interference system for gene repression in
Pseudomonas
spp. using a nuclease-null
Streptococcus pasteurianus
Cas9 variant (dead Cas9, or dCas9). We demonstrate a robust and titratable gene depletion system with up to 100-fold repression in β-galactosidase activity in
P. aeruginosa
and 300-fold repression in pyoverdine production in
Pseudomonas putida
. This inducible system enables the study of essential genes, as shown by
ftsZ
depletions in
P. aeruginosa
,
P. putida
, and
Pseudomonas fluorescens
that led to phenotypic changes consistent with depletion of the targeted gene. Additionally, we performed the first
in vivo
characterization of protospacer adjacent motif (PAM) site preferences of
S. pasteurianus
dCas9 and identified NNGCGA as a functional PAM site that resulted in repression efficiencies comparable to the consensus NNGTGA sequence. This discovery significantly expands the potential genomic targets of
S. pasteurianus
dCas9, especially in GC-rich organisms.

IMPORTANCE
Pseudomonas
spp. are prevalent in a variety of environments, such as the soil, on the surface of plants, and in the human body. Although
Pseudomonas
spp. are widely used as model organisms in different areas of research, existing tools to deplete a protein of interest in these organisms remain limited. We have developed a robust and inducible gene repression tool in
P. aeruginosa
,
P. putida
, and
P. fluorescens
using the
Streptococcus pasteurianus
dCas9. This method of protein depletion is superior to existing methods, such as promoter replacements and addition of degradation tags, because it does not involve genomic modifications of the target protein, is titratable, and is capable of repressing multiple genes simultaneously. This gene repression system now enables easy depletion of specific proteins in
Pseudomonas
, accelerating the study and engineering of this widely used model organism.
Epidemiology, Clinical Characteristics, and Antimicrobial Susceptibility Profiles of Human Clinical Isolates of Staphylococcus intermedius Group
Authors: Yarbrough Melanie L. , Lainhart William , Burnham Carey-Ann D.
Published: January 2018

The veterinary pathogens in the
Staphylococcus intermedius
group (SIG) are increasingly recognized as causes of human infection. Shared features between SIG and
Staphylococcus aureus
may result in the misidentification of SIG in human clinical cultures. This study examined the clinical and microbiological characteristics of isolates recovered at a tertiary-care academic medical center. From 2013 to 2015, 81 SIG isolates were recovered from 62 patients. Patients were commonly ≥50 years old, diabetic, and/or immunocompromised. Documentation of dog exposure in the electronic medical record was not common. Of the 81 SIG isolates, common sites of isolation included 37 (46%) isolates from wound cultures and 17 (21%) isolates from respiratory specimens. Although less common, 10 (12%) bloodstream infections were documented in 7 unique patients. The majority of SIG (65%) isolates were obtained from polymicrobial cultures. In comparison to
S. aureus
isolates from the same time period, significant differences were noted in proportion of SIG isolates that were susceptible to doxycycline (74% versus 97%, respectively;
P
< 0.001), trimethoprim-sulfamethoxazole (65% versus 97%, respectively;
P
< 0.001), and ciprofloxacin (78% versus 59%, respectively;
P
< 0.01). Methicillin resistance (MR) was detected in 12 (15%) of 81 SIG isolates. All MR isolates detected by an oxacillin disk diffusion test would have been misclassified as methicillin susceptible using a cefoxitin disk diffusion test. Thus, SIG is recovered from human clinical specimens, and distinction of SIG from
S. aureus
is critical for the accurate characterization of MR status in these isolates.