bluuebunny/crossref_metadata_2025 huggingface dataset:
Lean manufacturing implementation: leadership styles and contextual variables
Authors: Tortorella Guilherme Luz , de Castro Fettermann Diego , Frank Alejandro , Marodin Giuliano
Published: March 2018

Purpose

The purpose of this paper is to understand how the association between leadership styles (task or relation orientation) and lean manufacturing (LM) implementation changes due to two contextual variables, team size and the leader’s age.

Design/methodology/approach

The authors carried out a survey with 225 leaders from different Brazilian companies that are implementing LM. Research constructs were validated through rigorous procedures using confirmatory factor analysis. Hypotheses were tested using ordinary linear least squares regression.

Findings

The results suggest that larger teams and more senior managers were negatively associated with LM implementation. Task-orientation style makes leaders more likely to achieve higher levels of LM than relation-orientation style leaders. Finally, the influence of relation-oriented leaders on LM implementation is contingent upon the size of the team.

Research limitations/implications

Regarding study’s limitations, sample size and respondents’ location restrict results to this contextual condition, indicating that increasing the sample would help provide wider and more generalizable results. It is also worth noting that results are based on respondents’ (leaders) perspective. Hence, future studies may collect data from multiple perspectives, such as leaders and their followers, in order to compare results so as to verify the convergence or divergence among different respondents.

Practical implications

The results suggest that leaders should have different behaviors according to the context in which they are inserted. Therefore, such behavioral prescriptions are useful for managers since they are pressured to achieve high operational performance in short time periods and with few resources. Further, companies undergoing lean implementation may also be able to stimulate proper leadership behaviors and promote development programs accordingly, which is extremely relevant since behavioral changes usually take time.

Originality/value

The evolutionary process for achieving a successful lean enterprise requires different leadership styles according to the context in which leaders are inserted. This research provides arguments to help better understand the recommended leadership behaviors for lean implementation, complementing existing roadmaps by considering the proper leadership style as a contingency issue during lean implementation. Moreover, identifying the effect of contextual variables helps specify the contexts in which lean practices are more likely to be implemented.
A call for co-working – users’ expectations regarding learning spaces in higher education
Authors: Sankari Inka , Peltokorpi Antti , Nenonen Suvi
Published: March 2018

Purpose

Today, academic work includes increasingly informal and collaborative activities. This research attempts to determine whether stakeholders in the development of learning spaces in higher education could benefit from the principles of co-working space. This paper aims to determine whether a need exists for co-working space as a learning space solution from the viewpoint of academic space users. This determination will be made by examining the following research question: How does the co-working space concept meet user expectations regarding academic space?

Design/methodology/approach

The research question is answered by investigating users’ experiences of existing learning spaces in higher education in light of future workplace needs. Users’ requirements are examined by analysing user experience survey and interviews. The results are confirmed by focus group interviews and examined in the light of co-working space characteristics that are identified in the literature from the viewpoint of workplace management by searching for similarities between descriptions in the literature and the empirical data.

Findings

This research suggests that academic space users would appreciate it if the spaces they use would reflect some of the co-working space characteristics. These characteristics are community, multipurpose office, high accessibility and attractive workplace. A less applicable co-working space characteristic is space as service.

Research limitations/implications

The results of this study are based on one case, which limits the generalisability of the results.

Practical implications

The results provide suggestions for corporate real estate management and stakeholders in academic institutions to consider when renovating outdated spaces.

Originality/value

The paper expands the literature on learning spaces in higher education and related practices by linking it with co-working spaces, thereby contributing to a field that has not yet been explored in depth.
The entrepreneurial ecosystem and born globals: the Estonian context
Authors: Velt Hannes , Torkkeli Lasse , Saarenketo Sami
Published: March 2018

Purpose

The purpose of this study is to develop a framework of the elements of the entrepreneurial ecosystem in the context of born global start-ups. The study also applies this framework to uncover the ecosystem elements that impact start-ups during their initial phases of discovery and validation.

Design/methodology/approach

The authors used an online survey questionnaire sent out to several Estonian start-ups. Based on the responses, a dataset was developed and analysed using STATA and t-test methodology.

Findings

The analysis resulted in the identification of seven systemic ecosystem elements as the main factors impacting the launch and ten elements impacting the growth of born global start-ups. The systemic elements that comprise the ecosystem’s strengths and weaknesses were also identified.

Research limitations/implications

The cross-sectional nature of the survey method and the single-country context are noted as limitations of the study and offer future research potential for longitudinal settings, for mixed method studies and for comparative country data.

Practical implications

The study suggests that start-ups should function in a more collective manner to create platforms, promote one another’s products and services where possible and launch collective initiatives to enhance their visibility in the global context. Born globals should engage with their local entrepreneurial ecosystem, while remaining aware of its relative strengths and weaknesses for supporting internationalisation.

Social implications

Although the local ecosystem involves many stakeholders, this study helps identify key stakeholders that should be focused on by the government. Doing so will help create an increasingly comprehensive ecosystem at the national level – one that functions efficiently in supporting growth-seeking enterprises such as born globals.

Originality/value

This study combines the two research streams of the entrepreneurial ecosystem and born globals by directly connecting them with systemic elements. This study is, to our knowledge, the first to combine the two, thus making an added contribution by highlighting macro- and micro-viewpoints, with the former lacking in research on born globals and the latter in research on ecosystems. Thus, the present study helps in bringing venture creation and local ecosystem development research closer to each other.
Socially creative activities in Psychologically Informed Planned Environments: engaging and relating in the Offender Personality Disorder Pathway
Authors: Ryan Sue , Benefield Nick , Baker Vikki
Published: March 2018

Purpose

Major developments in the management of and intervention for people with significant personality difficulties who have offended are continuing, most recently with the implementation of the Offender Personality Disorder (Department of Health/National Offender Management Service (DoH/NOMS), 2011) Pathway. Included in this, is the Psychologically Informed Planned Environment model, currently being implemented in Prisons and Probation Approved Premises. This model includes the provision of “socially creative activities” (Benefield et al., 2018), opportunities for social learning and relationship building. The purpose of this paper is to explore the rationale for and examples of the implementation of these.

Design/methodology/approach

The paper offers a narrative review of research around child development, personality, social learning and the policy context around the OPD Pathway. An overview of the socially creative sessions and a rationale for them is provided.

Findings

A conceptual understanding of the rationale for socially creative sessions is provided with a description of the sessions that focussed upon development of imagination, narrative/story making, social expression and relational experiences, i.e. singing, drama and reading with others. It is argued that the activities offered opportunities to engage in a different medium for expression, learning and relating, that may provide a catalyst for change in individuals with entrenched motivational and interpersonal difficulties.

Research limitations/implications

This is a conceptual paper that provides a rationale for socially creative sessions and describes the sessions. This paper does not feature outcome data which are outside the remit of this paper; however, future research into the impact of this approach to aid relational development and assist in emotional and behavioural stability is essential.

Practical implications

The complex needs of this client group emphasise the need for services to offer holistic ways to engage people who can have a positive impact upon relationships.

Originality/value

The work presented in this paper is valuable for professionals working within the personality disorder and criminal justice field, also for policy makers and commissioners.
An evaluation of the reablement service programme on physical ability, care needs and care plan packages
Authors: Slater Paul , Hasson Felicity
Published: March 2018

Purpose

In response to an aging population and rising prevalence of disability, reablement initiatives have been introduced yet the evidence base concerning the long-term effects remains inconclusive. The purpose of this paper is to examine the impact of reablement on physical independence, care plans and care packages post-discharge for older adults.

Design/methodology/approach

A retrospective cohort design was used to examine patient records who had completed a reablement programme. Measures on internationally renowned and psychometrically strong tools, completed by trained healthcare professionals, were examined pre-and post-intervention with a consecutive sample (n=416) of participants since the introduction of the reablement programme.

Findings

Reablement had a significant impact on physical independence living scores and a corresponding reduction in care needs and care plans post-discharge enabling the person to stay at home.

Originality/value

The study’s findings present empirical evidence on the value of reablement health service programme developed to promote independent living at home following a short illness, for older people. While no examination of financial data was recorded in this study, the increase in physical ability and corresponding reduction in care needs and care plans post-discharge indicates a reduction in costs and a better standard of living.
Shipbuilding and economic cycles: a non-linear econometric approach
Authors: Ferrari Claudio , Marchese Malvina , Tei Alessio
Published: March 2018

Purpose

Economic studies have always underlined the cyclical trends of many industries and their different relations to the macro-economic cycles. Shipping is one of those industries and it has been often characterised by peaks that have influenced both the trade patterns and industry investment structure (e.g. fleet, shipyard activity, freight rates). One of the main issues related with the cycles is the effect on overcapacity and prices for newbuilding and how the understanding of these patterns can help in preventing short-hand strategies. The purpose of this paper is to evaluate different effects of business elements on shipbuilding activity, in relation to different economic-cycle phases.

Design/methodology/approach

This paper proposes a non-linear econometric model to identify the relations between shipbuilding and economic cycles over the past 30 years. The research focuses on identifying the cycle characteristics and understanding the asymmetrical effect of economic- and business-related variables on its development.

Findings

The study underlines the presence of an asymmetric effect of several business variables on the shipbuilding productions, depending on the cyclical phases (i.e. market expansion or economic slowdown). Moreover, lagged effects seem to be stronger than contemporaneous variables.

Originality/value

The paper is a first attempt of using non-linear modelling to shipbuilding cycles, giving indications that could be included in relevant investment policies.
Growth and job creation at the firm level: Swedish SME data
Authors: Yazdanfar Darush , Öhman Peter
Published: March 2018

Purpose

The purpose of this study is to investigate the association between firm sales growth and employment level as a proxy for job creation among small and medium-sized enterprises (SMEs).

Design/methodology/approach

The hypotheses were empirically examined by performing several univariate and multivariate regressions to investigate a large panel data set of 13,548 Swedish SMEs in four industry sectors in the four-year period from 2009 to 2012.

Findings

The results indicate that growth, in terms of sales, as a competitive advantage is positively related to the number of employees hired by the sampled firms. In addition, the size and age variables are also positively associated with the number of employees hired. The results support the suitability of implementing the resource-based view to explain job creation by SMEs.

Originality/value

While previous studies have mostly ignored the impact of these firm-level variables on job creation, the current study highlights the effect of firm-specific characteristics such as sales growth, size, age and industry. The authors use a combination of models to analyse a large cross-sectoral data set regarding the association, in SMEs, between the firms’ sales growth and job creation.
Semantic Disclosure Control: semantics meets data privacy
Authors: Batet Montserrat , Sánchez David
Published: March 2018

Purpose

To overcome the limitations of purely statistical approaches to data protection, the purpose of this paper is to propose Semantic Disclosure Control (SeDC): an inherently semantic privacy protection paradigm that, by relying on state of the art semantic technologies, rethinks privacy and data protection in terms of the meaning of the data.

Design/methodology/approach

The need for data protection mechanisms able to manage data from a semantic perspective is discussed and the limitations of statistical approaches are highlighted. Then, SeDC is presented by detailing how it can be enforced to detect and protect sensitive data.

Findings

So far, data privacy has been tackled from a statistical perspective; that is, available solutions focus just on the distribution of the data values. This contrasts with the semantic way by which humans understand and manage (sensitive) data. As a result, current solutions present limitations both in preventing disclosure risks and in preserving the semantics (utility) of the protected data.

Practical implications

SeDC captures more general, realistic and intuitive notions of privacy and information disclosure than purely statistical methods. As a result, it is better suited to protect heterogenous and unstructured data, which are the most common in current data release scenarios. Moreover, SeDC preserves the semantics of the protected data better than statistical approaches, which is crucial when using protected data for research.

Social implications

Individuals are increasingly aware of the privacy threats that the uncontrolled collection and exploitation of their personal data may produce. In this respect, SeDC offers an intuitive notion of privacy protection that users can easily understand. It also naturally captures the (non-quantitative) privacy notions stated in current legislations on personal data protection.

Originality/value

On the contrary to statistical approaches to data protection, SeDC assesses disclosure risks and enforces data protection from a semantic perspective. As a result, it offers more general, intuitive, robust and utility-preserving protection of data, regardless their type and structure.
How do social network sites support product users’ knowledge construction? A study of LinkedIn
Authors: Li Xuguang , Cox Andrew , Wang Zefeng
Published: March 2018

Purpose

Social network sites are emerging as a popular communication tool for knowledge sharing and construction. LinkedIn, which concentrates on professional networking, is reported to generate great informational benefits to its users. The purpose of this paper is to explore product users’ knowledge construction in solving technical problems on LinkedIn, which was chosen as a case example.

Design/methodology/approach

Discussion threads with rich knowledge elements were selected from an interest group about solving technical problems with laptops. Adopting a qualitative content analysis method, selected threads were analysed with a prior analysis framework built in the context of traditional IT company sponsored peer user support forums.

Findings

The analysis revealed that the iterative and progressive knowledge construction process and associated trial-and-error strategy used on LinkedIn are similar to those found in peer support forums. However, LinkedIn members are more engaged in knowledge construction episodes. Meanwhile, the sub-category “proposing a new idea” accounts for a larger portion of discussions reflecting the high-level of expertise. One-to-one direct interaction is quite salient. Therefore, LinkedIn can support knowledge construction in a more efficient way due to the character of its social capital, including trust, sense of belonging, norms of cooperation, visible identity, knowledge articulation skills, one-to-one direct interaction and suitable strength of ties.

Originality/value

This research is novel in empirically revealing how LinkedIn attributes and its social capital attributes interact with each other and together facilitate an efficient knowledge construction process.
Cost‐effectiveness of hydromorphone for severe opioid use disorder: findings from the SALOME randomized clinical trial
Authors: Bansback Nick , Guh Daphne , Oviedo‐Joekes Eugenia , Brissette Suzanne , Harrison Scott , Janmohamed Amin , Krausz Michael , MacDonald Scott , Marsh David C. , Schechter Martin T. , Anis Aslam H.
Published: March 2018

Background and aims

Previous research has found diacetylmorphine, delivered under supervision, to be cost‐effective in the treatment of severe opioid use disorder, but diacetylmorphine is not available in many settings. The Study to Assess Long‐term Opioid Maintenance Effectiveness (SALOME) randomized controlled trial provided evidence that injectable hydromorphone is non‐inferior to diacetylmorphine. The current study aimed to compare the cost‐effectiveness of hydromorphone directly with diacetylmorphine and indirectly with methadone maintenance treatment.

Design

A within‐trial analysis was conducted using the patient level data from the 6‐month, double‐blind, non‐inferiority SALOME trial. A life‐time analysis extrapolated costs and outcomes using a decision analytical cohort model. The model incorporated data from a previous trial to include an indirect comparison to methadone maintenance.

Setting

A supervised clinic in Vancouver, British Columbia, Canada.

Participants

A total of 202 long‐term street opioid injectors who had at least two attempts at treatment, including one with methadone (or other substitution), were randomized to hydromorphone (n = 100) or diacetylmorphine (n = 102).

Measurements

We measured the utilization of drugs, visits to health professionals, hospitalizations, criminal activity, mortality and quality of life. This enabled us to estimate incremental costs, quality‐adjusted life years (QALYs) and cost‐effectiveness ratios from a societal perspective. Sensitivity analyses considered different sources of evidence, assumptions and perspectives.

Findings

The within‐trial analysis found hydromorphone provided similar QALYs to diacetylmorphine [0.377, 95% confidence interval (CI) = 0.361–0.393 versus 0.375, 95% CI = 0.357–0.391], but accumulated marginally greater costs [$49 830 ($28 401–73 637) versus $34 320 ($21 780–55 998)]. The life‐time analysis suggested that both diacetylmorphine and hydromorphone provide more benefits than methadone [8.4 (7.4–9.5) and 8.3 (7.2–9.5) versus 7.4 (6.5–8.3) QALYs] at lower cost [$1.01 million ($0.6–1.59 million) and $1.02 million ($0.72–1.51 million) versus $1.15 million ($0.71–1.84 million)].

Conclusions

In patients with severe opioid use disorder enrolled into the SALOME trial, injectable hydromorphone provided similar outcomes to injectable diacetylmorphine. Modelling outcomes during a patient's life‐time suggested that injectable hydromorphone might provide greater benefit than methadone alone and may be cost‐saving, with drug costs being offset by costs saved from reduced involvement in criminal activity.
Chronic idiopathic erythroderma of elderly men is an independent entity that has a distinct TARC/IgE profile from adult atopic dermatitis
Authors: Ohga Yasunori , Bayaraa Bolortuya , Imafuku Shinichi
Published: March 2018

Background

Although there are several diseases that cause erythroderma, patients are often encountered with erythroderma of unknown cause which persists for a long time. The aim of this study was to characterize this chronic idiopathic erythroderma (CIE).

Methods

Adult patients with CIE, atopic dermatitis (AD), psoriatic erythroderma (PsE), or generalized drug eruption (DE), who visited Fukuoka University Hospital Dermatology Department from 2010 to 2015, were enrolled. Their clinical and laboratory data were extracted from the patient database. CIE was defined as erythroderma without any apparent cause and lasting more than 3 months.

Results

Twenty‐three CIE, 82 AD, 39 psoriatic erythroderma, and 99 drug eruption cases were enrolled. The mean age of CIE patients was 74.7 ± 8.8, and the male : female ratio was 21 : 2. Laboratory data for CIE and AD were similar, but serum levels of thymus and activation‐regulated chemokine (TARC), a T‐helper (Th) 2 cytokine, in the CIE group were significantly more elevated than in the AD group. Conversely, serum immunoglobulin (Ig) E levels were significantly lower in CIE patients compared with the atopic dermatitis group, and the ROC curve of the TARC/IgE ratio (7.24) provided efficient differentiation of the CIE group from AD patients. About PsE and DE, significant elevation of C‐reactive protein was observed. Aspartate aminotransferase and alanine aminotransferase were also elevated in DE.

Conclusions

Chronic idiopathic erythroderma is an independent condition which is likely to occur in elderly men. Immunity is shifted to the Th2 type in CIE; however, the mechanism may differ from that of atopic dermatitis.
Judging Judicial Foreclosure
Authors: Feinstein Brian D.
Published: March 2018

For the third time in the last several decades, policymakers are contemplating an overhaul of mortgage‐finance regulations. Despite the considerable attention paid to how ex ante regulations affect the availability of credit and the appropriateness of the mortgage products that lenders offer, however, our understanding of how the legal framework governing foreclosures—a form of ex post borrower protection—affects mortgage lending is incomplete. Leveraging data on loan applicants that are geographically proximate and subject to the same federal mortgage‐finance regulations and nearly identical state foreclosure regimes—but for the presence or absence of a judicial foreclosure requirement—this analysis enables the identification of the independent effects of judicial‐foreclosure requirements on loan approval decisions and the share of approved applicants who are offered subprime loans. I find that lenders adopt a more conservative posture in evaluating loan applications in jurisdictions where they must haul delinquent borrowers into court. All else equal, loan applications are less likely to be approved and approved borrowers are less likely to be offered subprime loans in judicial‐foreclosure states. Further, some models indicate that these results may be amplified for borrowers with lower socioeconomic status, suggesting that judicial supervision of foreclosures may have tempered one of the more flagrant practices of the subprime era: providing high‐rate mortgages with a greater likelihood of default to lower‐income and minority borrowers. These results suggest that, in contemplating changes to the regulation of mortgage lenders, policymakers should consider state foreclosure law to be among the tools in their regulatory toolkit.
Energy stored during deformation of crystallizing TPU foams
Authors: Lachhab A. , Robin E. , Le Cam J.‐B. , Mortier F. , Tirel Y. , Canevet F.
Published: March 2018

The hysteresis loop observed in the mechanical response of elastomers is classically assumed to be due to viscosity. In this study, a complete energy balance is carried out during cyclic deformation of compact and foamed crystallizing thermoplastic polyurethanes. Results show that viscosity is not the only phenomenon involved in the hysteresis loop formation: A significant part of the mechanical energy brought is not dissipated into heat and is stored by the material when the material changes its microstructure, typically when it is crystallizing. Some of this energy is released during unloading, when melting occurs, but with a different rate, which contributes to the hysteresis loop. The part of the mechanical energy stored by the material has been quantified through the γse ratio (Loukil et al. (2018) European Polymer Journal, 98, 448–455) to investigate the effects of the loading rate and the void volume fraction on the energetic response of thermoplastic polyurethane.
A climate-associated multispecies cryptic cline in the northwest Atlantic
Authors: Stanley Ryan R. E. , DiBacco Claudio , Lowen Ben , Beiko Robert G. , Jeffery Nick W. , Van Wyngaarden Mallory , Bentzen Paul , Brickman David , Benestan Laura , Bernatchez Louis , Johnson Catherine , Snelgrove Paul V. R. , Wang Zeliang , Wringe Brendan F. , Bradbury Ian R.
Published: March 2018

Cryptic multispecies genetic structure reflects ocean climate and is associated with response to climate change.
The impact of past vaccination coverage and immunity on pertussis resurgence
Authors: Domenech de Cellès Matthieu , Magpantay Felicia M. G. , King Aaron A. , Rohani Pejman
Published: March 2018

Pertussis reemergence is underpinned by slowly waning immunity to both whole-cell and acellular vaccines together with incomplete past vaccination coverage.
Double safety reins in wayward B cells
Authors: Zeng Hu
Published: March 2018

Two regulatory proteins suppress IRF5 transcription factor in age-associated B cells to prevent systemic autoimmune disorders.
Colocation of the Polymyxin Resistance Gene
mcr-1
and a Variant of
mcr-3
on a Plasmid in an Escherichia coli Isolate from a Chicken Farm
Authors: Xiang Rong , Liu Bi-Hui , Zhang An-Yun , Lei Chang-Wei , Ye Xiao-Lan , Yang Yan-Xian , Chen Yan-Peng , Wang Hong-Ning
Published: March 2018

A colistin-resistant
Escherichia coli
isolate from a commercial poultry farm in China carried two colistin resistance genes,
mcr-1
and variant of
mcr-3
, in an IncP plasmid. The variant of the
mcr-3
gene, named
mcr-3.11
, encoded two amino acid substitutions compared with the
mcr-3
gene. A novel genetic structure, IS
Kpn40-mcr-3-dgkA
-IS
Kpn40
, might be the key element mediating the translocation of
mcr-3
through the formation of a circular form. The
mcr-1
and
mcr-3
genes, which are colocated on a plasmid, might pose a huge threat to public health.
An Antibiotic Stewardship Program Blueprint for Optimizing Verigene BC-GN within an Institution: a Tale of Two Cities
Authors: Pogue Jason M. , Heil Emily L. , Lephart Paul , Johnson J. Kristie , Mynatt Ryan P. , Salimnia Hossein , Claeys Kimberly C.
Published: March 2018

Rapid diagnostic tests (RDTs) have revolutionized the management of Gram-negative bacteremia by allowing antimicrobial stewardship teams the ability to escalate therapy and improve patient outcomes through timely organism identification and detection of certain resistance determinants. However, given the complex nature of Gram-negative resistance, stewardship teams are left without clear direction for how to respond when resistance determinants are absent, as the safety of de-escalation in this setting is unknown. The primary purpose of this analysis was to determine the negative predictive values (NPVs) of resistance marker absence for predicting susceptibility in target bug-drug scenarios at two geographically distinct institutions. A total of 1,046 Gram-negative bloodstream isolates that were analyzed with the Verigene BC-GN platform were assessed. Except for
Pseudomonas aeruginosa
, the absence of resistance determinants as reported by the RDT largely predicted susceptibility to target antibiotics at both institutions. NPVs for ceftriaxone susceptibility in
Escherichia coli
and
Klebsiella pneumoniae
in the absence of either CTX-M or a carbapenemase gene were 98% and 93 to 94%, respectively. Similar results were seen with other target bug-drug scenarios, with NPVs of 94 to 100% demonstrated at both institutions, with the exception of
P. aeruginosa
, for which NPVs were poor, likely due to the more complex nature of resistance in this pathogen. The results of this study show that clinicians at both institutions should have confidence in de-escalation in the absence of resistance determinant detection by Verigene BC-GN testing, and the methodology described within this article can serve as a blueprint for other stewardship programs to employ at their institutions to optimize management of Gram-negative bacteremia.
MEDI3902 Correlates of Protection against Severe Pseudomonas aeruginosa Pneumonia in a Rabbit Acute Pneumonia Model
Authors: Le Hoan N. , Quetz Josiane Silva , Tran Vuvi G. , Le Vien T. M. , Aguiar-Alves Fábio , Pinheiro Marcos G. , Cheng Lily , Yu Li , Sellman Bret R. , Stover Charles K. , DiGiandomenico Antonio , Diep Binh An
Published: March 2018

Pseudomonas aeruginosa
is among the most formidable antibiotic-resistant pathogens and is a leading cause of hospital-associated infections. With dwindling options for antibiotic-resistant infections, a new paradigm for treatment and disease resolution is required. MEDI3902, a bispecific antibody targeting the
P. aeruginosa
type III secretion (T3S) protein PcrV and Psl exopolysaccharide, was previously shown to mediate potent protective activity in murine infection models. With the current challenges associated with the clinical development of narrow-spectrum agents, robust preclinical efficacy data in multiple animal species are desirable. Here, we sought to develop a rabbit
P. aeruginosa
acute pneumonia model to further evaluate the activity of MEDI3902 intervention. In the rabbit model of acute pneumonia, prophylaxis with MEDI3902 exhibited potent dose-dependent protection, whereas those receiving control IgG developed fatal hemorrhagic necrotizing pneumonia between 12 and 54 h after infection. Blood biomarkers (e.g., partial pressure of oxygen [pO
2
], partial pressure of carbon dioxide [pCO
2
], base excess, lactate, and creatinine) were grossly deranged for the vast majority of control IgG-treated animals but remained within normal limits for MEDI3902-treated animals. In addition, MEDI3902-treated animals exhibited a profound reduction in
P. aeruginosa
organ burden and a marked reduction in the expression of proinflammatory mediators from lung tissue, which correlated with reduced lung histopathology. These results confirm that targeting PcrV and Psl via MEDI3902 is a promising candidate for immunotherapy against
P. aeruginosa
pneumonia.
The Combination of Daptomycin and Fosfomycin Has Synergistic, Potent, and Rapid Bactericidal Activity against Methicillin-Resistant Staphylococcus aureus in a Rabbit Model of Experimental Endocarditis
Authors: García-de-la-Mària Cristina , Gasch Oriol , García-Gonzalez Javier , Soy Dolors , Shaw Evelyn , Ambrosioni Juan , Almela Manel , Pericàs Juan M. , Tellez Adrián , Falces Carlos , Hernandez-Meneses Marta , Sandoval Elena , Quintana Eduard , Vidal Barbara , Tolosana Jose M. , Fuster David , Llopis Jaume , Pujol Miquel , Moreno Asuncion , Marco Francesc , Miró Jose M. , Miró Jose M. , Ambrosioni Juan , Téllez Adrian , Pericàs Juan M. , Hernández-Meneses Marta , Moreno Asuncion , García de la Mària Cristina , Armero Yolanda , García-González Javier , Almela Manel , Casals Climent , Marco Francesc , Vila Jordi , Quintana Eduard , Sandoval Elena , Paré Juan C. , Falces Carlos , Pereda Daniel , Cartañá Ramon , Ninot Salvador , Azqueta Manel , Sitges Marta , Vidal Barbara , Pomar José L. , Castella Manuel , Tolosana José M. , Ortiz José , Fita Guillermina , Rovira Irene , Fuster David , Ramírez Jose , Brunet Mercè , Soy Dolors , Castro Pedro , Llopis Jaume
Published: March 2018

We investigated whether the addition of fosfomycin or cloxacillin to daptomycin provides better outcomes in the treatment of methicillin-resistant
Staphylococcus aureus
(MRSA) experimental aortic endocarditis in rabbits. Five MRSA strains were used to perform
in vitro
time-kill studies using standard (10
6
) and high (10
8
) inocula. Combined therapy was compared to daptomycin monotherapy treatment in the MRSA experimental endocarditis model. A human-like pharmacokinetics model was applied, and the equivalents of cloxacillin at 2 g/4 h, fosfomycin at 2 g/6 h, and daptomycin at 6 to 10 mg/kg/day were administered intravenously. A combination of daptomycin and either fosfomycin or cloxacillin was synergistic in the five strains tested at both inocula. A bactericidal effect was detected in four of five strains tested with both combinations. The MRSA-277 strain (vancomycin MIC, 2 μg/ml) was used for the experimental endocarditis model. Daptomycin plus fosfomycin significantly improved the efficacy of daptomycin monotherapy at 6 mg/kg/day in terms of both the proportion of sterile vegetations (100% versus 72%,
P
= 0.046) and the decrease in the density of bacteria within the vegetations (
P
= 0.025). Daptomycin plus fosfomycin was as effective as daptomycin monotherapy at 10 mg/kg/day (100% versus 93%,
P
= 1.00) and had activity similar to that of daptomycin plus cloxacillin when daptomycin was administered at 6 mg/kg/day (100% versus 88%,
P
= 0.48). Daptomycin nonsusceptibility was not detected in any of the isolates recovered from vegetations. In conclusion, for the treatment of MRSA experimental endocarditis, the combination of daptomycin plus fosfomycin showed synergistic and bactericidal activity.
Draft Genome Sequences of Two Epidemic OXA-48-Producing Klebsiella pneumoniae Clinical Strains Isolated during a Large Outbreak in Spain
Authors: Gato E. , Álvarez-Fraga L. , Vallejo J. A. , Rumbo-Feal S. , Martínez-Guitián M. , Beceiro A. , Poza M. , Bou G. , Pérez A.
Published: March 2018

We report here the draft genome sequences of
Klebsiella pneumoniae
strains Kp1803 and Kp3380 isolated during a large outbreak at A Coruña Hospital in Spain. The final genome assemblies for Kp1803 and Kp3380 comprise approximately 6.6 and 6.1 Mb, respectively, and both strains have G+C contents of 57.2%.
Draft Genome Sequence of Bacillus paralicheniformis F47, Isolated from an Algerian Salty Lake
Authors: Daas Mohamed Seghir , Rosana Albert Remus R. , Acedo Jeella Z. , Douzane Malika , Nateche Farida , Kebbouche-Gana Salima , Vederas John C.
Published: March 2018

Bacillus paralicheniformis
F47 was isolated from a salty lake in Ain Baida-Ouargla, southern Algeria. The genome contains genes for the production of several bioactive secondary metabolites, including the siderophore bacillibactin, the lipopeptides fengycin, surfactin, and lichenysin, the antibiotics bacitracin and kanosamine, and a putative circular bacteriocin.
Randomised controlled trial of rhinothermy for treatment of the common cold: a feasibility study
Authors: Hei Susanne van de , McKinstry Steven , Bardsley George , Weatherall Mark , Beasley Richard , Fingleton James
Published: March 2018

Objective

To determine the feasibility of a randomised controlled trial (RCT) of rhinothermy for the common cold.

Design

Open label, randomised, controlled feasibility study.

Setting

Single-centre research institute in New Zealand recruiting participants from the community.

Participants

30 adult participants with symptoms of a common cold, presenting within 48 hours of the onset of symptoms.

Interventions

Participants were randomly assigned 2:1 to receive either 35 L/min of 100% humidified air at 41°C via high flow nasal cannulae, 2 hours per day for up to 5 days (rhinothermy), or vitamin C 250 mg daily for 5 days (control).

Primary and secondary outcome measures

The primary outcome was the proportion of screened candidates who were randomised. Secondary outcomes included: proportion of randomised participants who completed the study; modified Jackson scores from randomisation to 10 days after initiation of randomised regimen; time until feeling ‘a lot better’ compared with study entry; time until resolution of symptoms or symptom score at 10 days postrandomisation; proportion of organisms identified by PCR analysis of nasal swabs taken at baseline; the patterns of use of the rhinothermy device; estimated adherence of the control group; and rhinothermy device tolerability.

Results

In all 30/79 (38%, 95% CI 27% to 50%) of potential participants screened for eligibility were randomised. Rhinothermy was well tolerated, and all randomised participants completed the study (100%, 95% CI 88% to 100%). The reduction from baseline in the modified Jackson score was greater with rhinothermy compared with control at days 2, 3, 4, 5 and 6, with the maximum difference at day 4 (−6.4, 95% CI −9.4 to −3.3). The substantial clinical benefit threshold for modified Jackson score was a 5-unit change.

Conclusions

This study shows that an RCT of rhinothermy compared with low-dose vitamin C in the treatment of the common cold is feasible.

Trial registration number

ACTRN12616000470493; Results.
Lessons from a broad view of science: a response to Dr Robergs’ article
Authors: Pires Flavio Oliveira
Published: March 2018

Dr Robergs suggested that the central governor model (CGM) is not a well-worded theory, as it deviated from the tenant of falsification criteria. According to his view of science, exercise researches with the intent to prove rather than disprove the theory contribute little to new knowledge and condemn the theory to the label of pseudoscience. However, exercise scientists should be aware of limitations of the falsification criteria. First, the number of potential falsifiers for a given hypothesis is always infinite so that there is no mean to ensure asymmetric comparison between theories. Thus, assuming a competition between CGM and dichotomised central versus peripheral fatigue theories, scientists guided by the falsification principle should know, a priori, all possible falsifiers between these two theories in order to choose the finest one, thereby leading to an oversimplification of the theories. Second, the failure to formulate refutable hypothesis may be a simple consequence of the lack of instruments to make crucial measurements. The use of refutation principles to test the CGM theory requires capable technology for online feedback and feedforward measures integrated in the central nervous system, in a real-time exercise. Consequently, falsification principle is currently impracticable to test CGM theory. The falsification principle must be applied with equilibrium, as we should do with positive induction process, otherwise Popperian philosophy will be incompatible with the actual practice in science. Rather than driving the scientific debate on a biased single view of science, researchers in the field of exercise sciences may benefit more from different views of science.
Selective screening for atrial fibrillation using multivariable risk models
Authors: Linker David T , Murphy Tasha B , Mokdad Ali H
Published: March 2018

Objective

Atrial fibrillation can lead to stroke if untreated, and identifying those at higher risk is necessary for cost-effective screening for asymptomatic, paroxysmal atrial fibrillation. Age has been proposed to identify those at risk, but risk models may provide better discrimination. This study compares atrial fibrillation risk models with age for screening for atrial fibrillation.

Methods

Nine atrial fibrillation risk models were compared using the Atherosclerosis Risk in Communities study (11 373 subjects, 60.0±5.7 years old). A new risk model (Screening for Asymptomatic Atrial Fibrillation Events—SAAFE) was created using data collected in the Monitoring Disparities in Chronic Conditions study (3790 subjects, 58.9±15.3 years old). The primary measure was the fraction of incident atrial fibrillation subjects who should receive treatment due to a high CHA2DS2-VASc score identified when screening a fixed number equivalent to the age criterion. Secondary measures were the C statistic and net benefit.

Results

Five risk models were significantly better than age. Age identified 71 (61%) of the subjects at risk for stroke who subsequently developed atrial fibrillation, while the best risk model identified 96 (82%). The newly developed SAAFE model identified 95 (81%), primarily based on age, congestive heart failure and coronary artery disease.

Conclusions

Use of a risk model increases identification of subjects at risk for atrial fibrillation. One of the best performing models (SAAFE) does not require an ECG for its application, so that it could be used instead of age as a screening criterion without adding to the cost.
Aortic elongation part I: the normal aortic ageing process
Authors: Adriaans Bouke P , Heuts Samuel , Gerretsen Suzanne , Cheriex Emile C , Vos Rein , Natour Ehsan , Maessen Jos G , Sardari Nia Peyman , Crijns Harry J G M , Wildberger Joachim E , Schalla Simon
Published: March 2018

Objectives

Differentiation between normal and abnormal features of vascular ageing is crucial, as the latter is associated with adverse outcomes. The normal aortic ageing process is accompanied by gradual luminal dilatation and reduction of vessel compliance. However, the influence of age on longitudinal aortic dimensions and geometry has not been well studied. This study aims to describe the normal evolution of aortic length and shape throughout life.

Methods

A total of 210 consecutive patients were prospectively enrolled in this cross-sectional single-centre study. All subjects underwent CT on a third-generation dual-source CT scanner. Morphometric measurements, including measurements of segmental length and tortuosity, were performed on three-dimensional models of the thoracic aorta.

Results

The length of the thoracic aorta was significantly related to age (r=0.54) and increased by 59 mm (males) or 66 mm (females) between the ages of 20 and 80 years. Elongation was most pronounced in the proximal descending aorta, which showed an almost 2.5-fold length increase during life. The lengthening of the thoracic aorta was accompanied by a marked change of its geometry: whereas the aortic apex was located between the branch vessels in younger patients, it shifted to a more distalward position in the elderly.

Conclusions

The normal ageing process is accompanied by gradual aortic elongation and a notable change of aortic geometry. Part II of this two-part article investigates the hypothesis that excessive elongation could play a role in the occurrence of acute aortic dissection.
Electrical cardioversion in a dog with atrial fibrillation and hypothyroidism
Authors: Seo Joonbum , Singh Manreet K
Published: March 2018

A three‐year‐old male neutered Bullmastiff cross was assessed for lethargy. The dog had recently been diagnosed with atrial fibrillation and hypothyroidism and had been started on thyroid supplementation and cardiac medications. ECG on presentation confirmed atrial fibrillation. Echocardiography showed normal chamber dimensions, making heart failure unlikely. With the lack of structural heart disease, a diagnosis of lone atrial fibrillation was made. After initial medical management of the atrial fibrillation with rate control, the client elected electrical cardioversion. The dog was pretreated with amiodarone and transthoracic electrical cardioversion was performed. Atrial fibrillation was successfully converted to normal sinus rhythm, and the dog was discharged on a maintenance dose of amiodarone. The dog remained in a normal sinus rhythm at the 1‐, 2‐, 4‐, 8‐ and 14‐month revisits. This case report describes management options for atrial fibrillation and the potential association with hypothyroidism.
Assessing the mechanistic target of rapamycin complex-1 pathway in response to resistance exercise and feeding in human skeletal muscle by multiplex assay
Authors: McGlory Chris , Nunes Everson A. , Oikawa Sara Y. , Tsakiridis Evangelia , Phillips Stuart M.
Published: March 2018

The mechanistic target of rapamycin complex-1 (mTORC-1) is a key nutrient and contraction-sensitive protein that regulates a pathway leading to skeletal muscle growth. Utilizing a multiplex assay, we aimed to examine the phosphorylation status of key mTORC-1-related signalling molecules in response to protein feeding and resistance exercise. Eight healthy men (age, 22.5 ± 3.1 years; mass, 80 ± 9 kg; 1-repetition maximum leg extension, 87 ± 5 kg) performed 4 sets of unilateral leg extensions until volitional failure. Immediately following the final set, all participants consumed a protein-enriched beverage. A single skeletal muscle biopsy was obtained from the vastus lateralis before (Pre) with further bilateral biopsies at 1 h (1 h exercised legs (FEDEX) and 1 h nonexercised legs (FED)) and 3 h (3 h FEDEX and 3 h FED) after drink ingestion. Phosphorylated AktSer473was significantly elevated from Pre at 1 h FEDEX. Phosphorylated p70S6K1Thr412was significantly increased above Pre at 1 h FEDEX and 1 h FED and was still significantly elevated at 3 h FEDEX but not 3 h FED. Phosphorylated rpS6Ser235/236was also significantly increased above Pre at 1 h FEDEX and 1 h FED with 1 h FEDEX greater than 1 h FED. Our data highlight the utility of a multiplex assay to assess anabolic signalling molecules in response to protein feeding and resistance exercise in humans. Importantly, these changes are comparable with those as previously reported using standard immunoblotting and protein activity assays.