bluuebunny/crossref_metadata_2025 huggingface dataset:
RBF-trained POD-accelerated CFD analysis of wind loads on PV systems
Authors: Huayamave Victor , Ceballos Andres , Barriento Carolina , Seigneur Hubert , Barkaszi Stephen , Divo Eduardo , Kassab Alain
Published: April 2017

Purpose

Wind loading calculations are currently performed according to the ASCE 7 standard. Values in this standard were estimated from simplified models that do not necessarily take into account relevant flow characteristics. Thus, the standard does not have provisions to handle the majority of rooftop photovoltaic (PV) systems. Accurate solutions for this problem can be produced using a full-fledged three-dimensional computational fluid dynamics (CFD) analysis. Unfortunately, CFD requires enormous computation times, and its use would be unsuitable for this application which requires real-time solutions. To this end, a real-time response framework based on the proper orthogonal decomposition (POD) method is proposed.

Design/methodology/approach

A real-time response framework based on the POD method was used. This framework used beforehand and off-line CFD solutions from an extensive data set developed using a predefined design space. Solutions were organized to form the basis snapshots of a POD matrix. The interpolation network using a radial-basis function (RBF) was used to predict the solution from the POD method given a set of values of the design variables. The results presented assume varying design variables for wind speed and direction on typical PV roof installations.

Findings

The trained POD–RBF interpolation network was tested and validated by performing the fast-algebraic interpolation to obtain the pressure distribution on the PV system surface and they were compared to actual grid-converged fully turbulent 3D CFD solutions at the specified values of the design variables. The POD network was validated and proved that large-scale CFD problems can be parametrized and simplified by using this framework.

Originality/value

The solar power industry, engineering design firms and the society as a whole could realize significant savings with the availability of a real-time in situ wind-load calculator that can prove essential for plug-and-play installation of PV systems. Additionally, this technology allows for automated parametric design optimization to arrive at the best fit for a set of given operating conditions. All these tasks are currently prohibited because of the massive computational resources and time required to address large-scale CFD analysis problems, all made possible by a simple but robust technology that can yield massive savings for the solar industry.
Estimation of the local heat transfer coefficient in coiled tubes
Authors: Bozzoli Fabio , Cattani Luca , Rainieri Sara , Bazán Fermín S.V. , Borges Leonardo S.
Published: April 2017

Purpose

Most of the passive techniques for enhancing heat transfer inside pipes (e.g. rough surfaces, swirl-flow devices and coiled tubes) give origin to an irregular distribution of the heat transfer coefficient at the fluid–wall interface along the wall perimeter. This irregular distribution could be critical in some industrial applications, but most of the available research papers, mainly due to the practical difficulty of local measuring heat flux on the internal wall surface of a pipe, present the results only in terms of Nusselt number averaged along the wall circumference. This paper aims to study the application of inverse problem solution techniques, which could overcome this limitation.

Design/methodology/approach

With regard to the estimation of the local convective heat transfer coefficient in coiled tubes, two different inverse heat conduction problem solution techniques were considered and compared both by synthetic and experimental data.

Findings

The paper shows the success of two inverse problem solution techniques in the estimation of the local convective heat transfer coefficient in coiled tubes.

Originality/value

This paper fulfills an identified need because most of the available research papers present the results only in terms of average thermal performance, neglecting local behavior.
Inverse problems in identification and modeling of thermal processes: Russian contributions
Authors: Alifanov Oleg M.
Published: April 2017

Purpose

The main purpose of this study, reflecting mainly the content of the authors’ plenary lecture, is to make a brief overview of several approaches developed by the author and his colleagues to the solution to ill-posed inverse heat transfer problems (IHTPs) with their possible extension to a wider class of inverse problems of mathematical physics and, most importantly, to show the wide possibilities of this methodology by examples of aerospace applications. In this regard, this study can be seen as a continuation of those applications that were discussed in the lecture.

Design/methodology/approach

The application of the inverse method was pre-tested with experimental investigations on a special test equipment in laboratory conditions. In these studies, the author used the solution to the nonlinear inverse problem in the conjugate (conductive and convective) statement. The corresponding iterative algorithm has been developed and tested by a numerical and experimental way.

Findings

It can be stated that the theory and methodology of solving IHTPs combined with experimental simulation of thermal conditions is an effective tool for various fundamental and applied research and development in the field of heat and mass transfer.

Originality/value

With the help of the developed methods of inverse problems, the investigation was conducted for a porous cooling with a gaseous coolant for heat protection of the re-entry vehicle in the natural environment of hypersonic flight. Moreover, the analysis showed that the inverse methods can make a useful contribution to the study of heat transfer at the surface of a solid body under the influence of the hypersonic heterogeneous (dusty) gas stream and in many other aerospace applications.
Inverse problem solution for a laser flash studies of a thin layer coatings
Authors: Stryczniewicz Wit , Zmywaczyk Janusz , Panas Andrzej Jaroslaw
Published: April 2017

Purpose

The paper aims to discuss the inverse heat conduction methodology in solution of a certain parameter identification problem. The problem itself concerns determination of the thermophysical properties of a thin layer coating by applying the laser flash apparatus.

Design/methodology/approach

The modelled laser flash diffusivity data from the three-layer sample investigation are used as input for the following parameter estimation procedure. Assuming known middle layer, i.e. substrate properties, the thermal diffusivity (TD) of the side layers’ material is determined. The estimation technique utilises the finite element method for numerical solution of the direct, 2D axisymmetric heat conduction problem.

Findings

The paper presents methodology developed for a three-layer sample studies and results of the estimation technique testing and evaluation based on simulated data. The multi-parametrical identification procedure results in identification of the out of plane thin layer material diffusivity from the inverse problem solution.

Research limitations/implications

The presentation itself is limited to numerical simulation data, but it should be underlined that the flake graphite thermophysical parameters have been utilised in numerical tests.

Practical implications

The developed methodology is planned to be applied in detailed experimental studies of flake graphite.

Originality/value

In the course of a present study, a methodology of the thin-coating layer TD determination was developed. In spite of the fact that it has been developed for the graphite coating investigation, it was planned to be universal in application to any thin–thick composite structure study.
State estimation in bioheat transfer: a comparison of particle filter algorithms
Authors: Lamien Bernard , Varon Leonardo A.B. , Orlande Helcio R.B. , Elicabe Guillermo E.
Published: April 2017

Purpose

The purpose of this paper is to focus on applications related to the hyperthermia treatment of cancer, with heating imposed either by a laser in the near-infrared range or by radiofrequency waves. The particle filter algorithms are compared in terms of computational time and solution accuracy.

Design/methodology/approach

The authors extend the analyses performed in their previous works to compare three different algorithms of the particle filter, as applied to the hyperthermia treatment of cancer. The particle filters examined here are the sampling importance resampling (SIR) algorithm, the auxiliary sampling importance resampling (ASIR) algorithm and Liu & West’s algorithm.

Findings

Liu & West’s algorithm resulted in the largest computational times. On the other hand, this filter was shown to be capable of dealing with very large uncertainties. In fact, besides the uncertainties in the model parameters, Gaussian noises, similar to those used for the SIR and ASIR filters, were added to the evolution models for the application of Liu & West’s filter. For the three filters, the estimated temperatures were in excellent agreement with the exact ones.

Practical implications

This work may help medical doctors in the future to prescribe treatment protocols and also opens the possibility of devising control strategies for the hyperthermia treatment of cancer.

Originality/value

The natural solution to couple the uncertain results from numerical simulations with the measurements that contain uncertainties, aiming at the better prediction of the temperature field of the tissues inside the body, is to formulate the problem in terms of state estimation, as performed in this work.
Retrieving thermal conductivity of the solid sample using reduced order model inverse approach
Authors: Adamczyk Wojciech Piotr , Ostrowski Ziemowit
Published: April 2017

Purpose

Prompted by the reliability and robustness of the previously proposed method of non-destructive measurement of thermal conductivity (TC) for anisotropic materials, the enhanced approach is presented in this study. The main improvement lies in the substitution of the analytic solution of direct problem solver with a numerical one. This solver, used during the inverse procedure that fits measurement data into simulated ones, is proposed to be a numerical one (finite volume method). Moreover, the purpose of this study is to show the applicability of the reduce order model for retrieving thermal conductivity of solid body.

Design/methodology/approach

In the proposed methodology, both the laser heat source and temperature measurements are performed on the same side of the sample material, which is the main difference with respect to the classic Parker flash method. To speed up the computational time, the full numerical model used in the course of inverse solution is replaced by the proper orthogonal decomposition (POD)-radial basis function (RBF) reduced order model, which is fast and accurate.

Findings

The TCs measured using the proposed methodology are in good agreement with the well established (but destructive) measurement methods. The advantage of the proposed approach lies in the optimal approximation properties of the POD approximation basis used in reduced order model, as well as in its regularization properties.

Practical implications

The proposed technique has high application potential in the design of novel apparatus for non-destructive measurement of TCs for both isotropic and anisotropic materials.

Originality/value

This is the first time when the POD-RBF reduced order model is used in the procedure of non-destructive TC measurement for anisotropic bodies.
The need for a long-term mindset when measuring the effects of lean on health-related quality management values
Authors: Ingelsson Pernilla , Bäckström Ingela
Published: April 2017

Purpose

The purpose of this paper is to investigate the effects a lean initiative has on the health-related quality management (QM) values, “Leadership Commitment” and “Participation of Everybody,” as well as on perceived co-worker health in the public sector.

Design/methodology/approach

A case study was carried out at a municipal division that had been working with lean for approximately 18 months. A questionnaire was used to measure the effect on health-related QM values both before and after the initial 18 month period. Documents from the intended lean implementation were studied at the starting point and after 18 months; this was followed up by examining new documents. The results from the questionnaires were analyzed using SPSS and the documents were analyzed by means of document comparisons and consensus discussion in the research group.

Findings

The effects on the health-related QM values; “Leadership Commitment” and “Participation of everybody” in this study showed that the values still permeated the organization to a relatively high extent after 18 months but that no statistical differences can be shown between the two measurement points. When measuring what effects a lean initiative has on values, a period of 18 months might be too short, if significance changes are expected. None the less, the results can be a way of monitoring the development of these softer values. Something that is equally important is to see if there have been any major changes, as a way of keeping the work with building a new culture alive and in focus. The results strengthen the assumption that a long-term mindset is needed when QM initiatives such as lean are applied within an organization especially when changes to values and workplaces are expected.

Originality/value

This study has further explored the QM in relation to lean in the respect of how the QM values “Leadership commitment” and “Participation of Everybody” are effected by a lean initiative.
Stock prices, exchange rate and interest rate: evidence beyond symmetry
Authors: Ajaz Taufeeq , Nain Md Zulquar , Kamaiah Bandi , Sharma Naresh Kumar
Published: April 2017

Purpose

This paper aims to examine the dynamic interactions between monetary and financial variables in the Indian context.

Design/methodology/approach

In this paper, the authors have applied a recently developed asymmetric autoregressive distributed lag (ARDL) model by Shinet al.(2014), for detecting nonlinearities focusing on the long-run and short-run asymmetries among economic variables.

Findings

The results point toward the presence of asymmetric reaction of stock prices to changes in interest rate and exchange rate in full sample, as well as in pre-crisis. However, no asymmetry was found in the post-crisis period. The results further suggest that tight monetary policies appear to retard the stock prices, more than easy monetary policies that stimulate them.

Practical implications

The findings of the study can be helpful in understanding the policy transmission mechanism through asset price channel.

Originality/value

To the best of the authors’ knowledge, this is the first study that examines the interactions between monetary and financial variables in the Indian context in an asymmetric framework. The findings of this study are quite interesting and are different from several existing studies in the literature.
Does public investment crowd-out private investment in India
Authors: Muthu Shanmugam
Published: April 2017

Purpose

The purpose of this paper is to examine the crowding-in or crowding-out relationship between public and private investment in India.

Design/methodology/approach

The autoregressive distributed lag (ARDL) bounds testing approach is used to estimate the long run relationship between public and private investment using annual data from 1971-1972 to 2009-2010.

Findings

Based on the empirical findings, it is observed that aggregate public investment has a positive effect on private investment both in the long run and the short run. In contrast to the findings of previous studies, no significant impact of public infrastructure investment on private investments is found in the long run, while non-infrastructure investment has a positive impact on private investment in the short run. Among the various categories of infrastructure sector, a positive and significant impact in the case of electricity, gas and water supply is observed. Similarly, the result indicates that public investment in machinery and equipment and construction have substantially influenced the private sector machinery and equipment in the long run and the short run. In the case of the role of macroeconomic uncertainty, the results find a negative and significant impact on private investment and the impact is higher in the short run than in the long run.

Originality/value

The present study extends the literature in three important ways: First, the study attempts to capture heterogeneity of public investment as well as disaggregate effects of two different categories of public infrastructure on private investment. The extent to which two different types of public assets impact the private investment in machinery and equipment investment is also examined. Second, ARDL model is used to examine the long-run relationship between public and private investment. Third, the study incorporates macroeconomic uncertainty into the empirical analysis to examine the role of macroeconomic volatility in determining private investment decision.
Size does matter – span of control in hospitals
Authors: Holm-Petersen Christina , Østergaard Sussanne , Andersen Per Bo Noergaard
Published: April 2017

Purpose

Centralization, mergers and cost reductions have generally led to increasing levels of span of control (SOC), and thus potentially to lower leadership capacity. The purpose of this paper is to explore how a large SOC impacts hospital staff and their leaders.

Design/methodology/approach

The study is based on a qualitative explorative case study of three large inpatient wards.

Findings

The study finds that the nursing staff and their frontline leaders experience challenges in regard to visibility and role of the leader, e.g., in creating overview, coordination, setting-up clear goals, following up and being in touch. However, large wards also provide flexibility and development possibilities.

Practical implications

The authors discuss the implications of these findings for decision makers in deciding future SOC and for future SOC research.

Originality/value

Only few studies have qualitatively explored the consequences of large SOC in hospitals.
Leadership quality: a factor important for social capital in healthcare organizations
Authors: Strömgren Marcus , Eriksson Andrea , Ahlstrom Linda , Bergman David Kristofer , Dellve Lotta
Published: April 2017

Purpose

The purpose of this paper is to investigate the relation between leadership and social capital and what qualities of leadership are important for social capital among employees in hospital settings over time.

Design/methodology/approach

A cohort of employees in hospitals answered a questionnaire at three occasions. Five small (approx. 100-bed) or mid-sized (approx. 500-bed) hospitals were included. The response rate was 54 percent at baseline (n=865), 59 percent at one-year follow-up (n=908) and 67 percent at two-year follow-up (n=632).

Findings

Repeated measures over time showed differences between groups in levels of social capital with respect to levels of leadership quality. Relation-oriented leadership had the strongest association with social capital. There was evidence that leadership was associated with social capital over time and that different kinds of leadership qualities were associated with social capital.

Research limitations/implications

This study conducted and analyzed quantitative data, and therefore, there is no knowledge of managers’ or employees’ own perceptions in this study. However, it would be interesting to compare managers’ decreased and increased leadership quality and how such differences affect social capital over time.

Practical implications

The findings feature the possibility for healthcare leaders to build high quality leadership as an important resource for social capital, by using different leadership orientations under different circumstances.

Originality/value

The paper showed that leadership was an important factor for building social capital and that different leadership qualities have different importance with respect to certain circumstances.
The effect of marketing communication on business relationship loyalty
Authors: Hänninen Nora , Karjaluoto Heikki
Published: April 2017

Purpose

The purpose of this paper is to create a new understanding of industrial business-to-business (B2B) relationships by connecting the theoretical streams of marketing communications and relationship marketing. This study tests how various marketing communication channels and communication quality increase the transformation of customer-perceived value into customer loyalty.

Design/methodology/approach

The theoretical framework consists of links between customer-perceived value, marketing communication quality, channel effectiveness, and customer loyalty. The age of the business relationship is also taken into consideration. Empirical testing is based on global survey data (n=121) collected from customers of Finnish manufacturing companies operating in the paper, mineral, and metal-processing industries.

Findings

The effects of customer-perceived value on customer loyalty are both direct and indirect, as marketing communications partially mediate this relationship. The customer-perceived effectiveness of various marketing communication channels adds more to loyalty formation than the perceived quality of marketing communications.

Practical implications

Of special interest for marketing practitioners is the channel-specific approach to the effectiveness of marketing communications. Results suggest that personalized channels would be the most important mediators of the effects of perceived value on loyalty and also bring up the possibility of combining personalized direct communication with new cost-effective digital channels.

Originality/value

Relatively little research has examined the mediating role of marketing communications in the relationship between perceived value and loyalty in the B2B context.
Investigating consumer advocacy, community usefulness, and brand avoidance
Authors: Jayasimha K.R. , Chaudhary Harish , Chauhan Anurag
Published: April 2017

Purpose

The purpose of this paper is to examine the behavioral outcomes and effectiveness of organizational response to open complaints by consumers following a dissatisfactory service experience.

Design/methodology/approach

Three natural communities (WhatsApp groups) were used with reference to online food and grocery retailing. The respondents comprised community members sharing negative experiences on the group. A scenario implanted in a survey was used as the research approach.

Findings

Consumer advocacy, a form of complaining, is a way to help other community members. The relationship between consumer advocacy and community usefulness strengthens the argument of consumers’ collective concern as one of the motivational frames for consumer advocacy. Consumer advocates show stronger reactions, resulting in brand avoidance following voice complaining. An effective organizational response can mitigate brand avoidance.

Practical implications

Finding ways to restrict and alleviate brand avoidance is an area that is of major interest to practitioners. The study finds that prospective explanations could be a very effective antidote to brand avoidance.

Originality/value

The social side of complaining is a relatively under-researched area. This study examines the relationship between consumer advocacy, community usefulness and brand avoidance. To the best of the authors’ knowledge, this is the first study to examine the moderating effect of organizational response on consumer advocacy and its outcomes in the virtual context.
Examining the dilution of the consumer-brand relationship on Facebook: the saturation issue
Authors: Ramadan Zahy
Published: April 2017

Purpose

Brands have been progressively using social networking sites, namely, Facebook, as part of their strategy to engage their consumers and ultimately build long-term relationships with them. Nonetheless, with the overuse of “engagement ads” by brands, saturation related to information overload is expected to be reached leading to the dilution of the consumer–brand relationship. The purpose of this paper is to fill a gap in the literature which has predominantly focused on the positive side of social networking sites, and hence still lacks a thorough understanding of the potential risks brands face when using Facebook. Accordingly, this research examines the different risks brands would be facing from saturated consumers on social networking sites such as Facebook.

Design/methodology/approach

A qualitative study was conducted, with a total of 40 respondents using face-to-face semi-structured interviews over two stages. While the first stage of the study focused on examining the saturation risk and its potential negative effects, the second one explored these risks specifically on the consumer–brand relationship on Facebook. The interviews were recorded, transcribed and then coded for analysis using NVivo 8.

Findings

Brands are overloading their followers with passively endorsed brand messages, which are negatively affecting consumers’ experience on Facebook, as well as the relationship with these brands. This overall dilution of the consumer–brand relationship on Facebook was hence found to be affecting interaction, similarity with friends, the system quality of the social networking site, as well as information quality. Furthermore, this dilution was found to be affecting brand likability, brand trust and brand association.

Originality/value

The negative implications are still scarcely examined in the literature where social media engagement is predominantly discussed through a positive lens. Hence, this study has the peculiarity of discussing the risks that companies would face with Facebook’s engagement model along with their implications on the consumer-brand relationship.
Selecting research approaches and research designs: a reflective essay
Authors: Gaus Nurdiana
Published: April 2017

Purpose

The purpose of this paper is to show the research process which is laid on the interrelated aspects of paradigm-research-based approaches and research designs.

Design/methodology/approach

It draws on my PhD research project experience, where I deployed these interrelated aspects informing my methodological perspective to produce quality research via the generation of legitimate research findings.

Findings

From this practice, my chosen held paradigm, constructionism, has guided me to proceed with my research process, leading to the selection of a research approach (qualitative case study) and research designs (interviews, observation, and document analysis).

Originality/value

This conduct helps valorise the legitimacy of my research findings to produce legitimate knowledge. This reflective account of the research process can become a lesson for others who wish to go through a legitimate process of selecting the research approaches and research designs, particularly, in social sciences.
Ethnographic research with young people: methods and rapport
Authors: Tickle Sarah
Published: April 2017

Purpose

This paper accounts for, and reflects upon, the research design and the methodological approach adopted in ethnographic research with young people. In particular, the purpose of this paper is to reinforce the significance of conducting qualitative participatory and innovative methods with young people, alongside the value of rapport building.

Design/methodology/approach

Qualitative participatory methods are understood as the most appropriate way to empower and respect young people in the research process. Alongside such methods the ethnographic nature of the research is discussed in conveying the importance of rapport building with young people in the field. In doing so the paper examines a number of important considerations when conducting youth research.

Findings

The triangulation of qualitative methods was fundamental in exploring and understanding young people’s lives in each locality and allowed for deep and meaningful explorations of specific themes. The additional and complementary methods employed alongside traditional methods were particularly suited to understanding young people’s everyday lives, as complex experiences are not always conveyed through traditional methods alone. Conducting participatory methods produced narratives around safety, security and governance in public places.

Originality/value

Being reflexive and adapting to a research setting in order to enhance the process of building and maintaining trust with young people is the most important facet when conducting youth research. Giving careful consideration to the impact of a researcher’s presence in the field needs to be carefully navigated.
The role of triangulation in sensitive art-based research with children
Authors: Vanner Catherine , Kimani Mary
Published: April 2017

Purpose

The purpose of this paper is to highlight the critical role of triangulation to create authentic analytical frameworks amidst contradictory participant narratives in sensitive art-based research (ABR) with children.

Design/methodology/approach

Multiple qualitative case study research included three months of participant observation, individual semi-structured teacher interviews and open-ended art-based interviews using the Draw-Write-Narrate method (Ogina and Nieuwenhuis, 2010) with upper primary students in two schools in Kirinyaga County, Kenya.

Findings

The art-based approach to student interviews, combined with participant observation and teacher interviews, provided a child-centred process that illuminated students’ understandings and experiences while minimizing risks to participants. Its application requires researchers to recognize data collection and analysis as subjective processes that strongly benefit from triangulation to interpret a diversity of perspectives that may not easily align.

Originality/value

As ABR with children increases in popularity, it is important to identify challenges in the process of analysis and meaning-making. This paper identifies triangulation as a valuable tool for handling the challenge of diverse perspectives from child participants, particularly in conducting sensitive research that may increase the likelihood of contradictory narratives.
Rapid G0/1 transition and cell cycle progression in CD8+ T cells compared to CD4+ T cells following in vitro stimulation
Authors: Mishima Takuya , Fukaya Shotaro , Toda Shoko , Ando Yoshiaki , Matsunaga Tsukasa , Inobe Manabu
Published: April 2017

T‐cell population consists of two major subsets, CD4+ T cells and CD8+ T cells, which can be distinguished by the expression of CD4 or CD8 molecules, respectively. Although they play quite different roles in the immune system, many of their basic cellular processes such as proliferation following stimulation are presumably common. In this study, we have carefully analyzed time–course of G0/1 transition as well as cell cycle progression in the two subsets of quiescent T‐cell population following in vitro growth stimulation. We found that CD8+ T cells promote G0/1 transition more rapidly and drive their cell cycle progression faster compared to CD4+ T cells. In addition, expression of CD25 and effects of its blockade revealed that IL‐2 is implicated in the rapid progression, but not the earlier G0/1 transition, of CD8+ T cells.
D‐dimer Interval Likelihood Ratios for Pulmonary Embolism
Authors: Kohn Michael A. , Klok Frederikus A. , van Es Nick
Published: April 2017

Objective

The objective was to estimate D‐dimer interval likelihood ratios (iLRs) for diagnosing pulmonary embolism (PE).

Methods

The authors used pooled patient‐level data from five PE diagnostic management studies to estimate iLRs for the eight D‐dimer intervals with boundaries 250, 500, 750, 1,000, 1,500, 2,500, and 5,000 ng/mL. Logistic regression was used to fit the data so that an interval increase corresponds to increasing the likelihood ratio by a constant factor.

Results

The iLR for the D‐dimer interval 1,000–1,499 ng/mL was essentially 1.0 (0.98 with 95% confidence interval [CI] = 0.82–1.18). In the logistic regression model, the constant between‐interval factor was 2.0 (95% CI = 1.9–2.1). Using these iLR estimates, if the pre–D‐dimer probability of PE is 15%, only a D‐dimer less than 500 ng/mL will result in a posttest probability below 3%; if the pretest probability is 5%, the threshold for a “negative” D‐dimer is 1,000 ng/mL.

Conclusions

A decision strategy based on these approximate iLRs agrees with several published strategies.
Ivabradine: Current and Future Treatment of Heart Failure
Authors: Thorup Lene , Simonsen Ulf , Grimm Daniela , Hedegaard Elise R.
Published: April 2017

In heart failure (HF), the heart cannot pump blood efficiently and is therefore unable to meet the body's demands of oxygen, and/or there is increased end‐diastolic pressure. Current treatments for HF with reduced ejection fraction (HFrEF) include angiotensin‐converting enzyme (ACE) inhibitors, angiotension receptor type 1 (AT1) antagonists, β‐adrenoceptor antagonists, aldosterone receptor antagonists, diuretics, digoxin and a combination drug with AT1 receptor antagonist and neprilysin inhibitor. In HF, the risk of readmission for hospital and mortality is markedly higher with a heart rate (HR) above 70 bpm. Here, we review the evidence regarding the use of ivabradine for lowering HR in HF. Ivabradine is a blocker of an I funny current (I(f)) channel and causes rate‐dependent inhibition of the pacemaker activity in the sinoatrial node. In clinical trials of HFrEF, treatment with ivabradine seems to improve clinical outcome, for example improved ejection fraction (EF) and less readmission for hospital, but the effect appears most pronounced in patients with HRs above 70 bpm, while the effect on cardiovascular death appears less consistent. The adverse effects of ivabradine include bradycardia, atrial fibrillation and visual disturbances, but ivabradine avoids the negative inotrope effects observed with β‐adrenoceptor antagonists. In conclusion, in patients with stable HFrEF with EF<35% and HR above 70 bpm, ivabradine improves the outcome and might be a first choice of therapy, if beta‐adrenoceptor antagonists are not tolerated. Further studies must show whether that can be extended to HF patients with preserved EF.
Targeting Tankyrase to Fight WNT‐dependent Tumours
Authors: Thorvaldsen Tor Espen
Published: April 2017

Aberrant WNT signalling activity is linked to various diseases due to the WNT dependency of fundamental processes during development and in adult tissue homeostasis. Mutations in components of the multi‐protein β‐catenin destruction complex promote excessive amounts of the main transcriptional activator β‐catenin and are particularly common in colorectal cancer (CRC). The tankyrase enzymes were recently implicated as negative regulators of destruction complex activity by mediating degradation of the scaffolding protein AXIN. Indeed, tankyrase inhibitors (TNKSi) have emerged as promising therapeutics by restoring functional signal‐limiting destruction complexes in CRCs. Furthermore, as TNKSi‐induced destruction complexes (so‐called degradasomes) can be visualized by microscopy, they have served as a valuable experimental model system to address unresolved aspects regarding the structure, function and composition of the β‐catenin destruction complex. This MiniReview provides an overview of the current knowledge on the regulatory mechanisms and interactions that govern the β‐catenin destruction complex activity. It further highlights the potential of TNKSi as anticancer drugs and as a novel research tool to dissect the WNT signalling pathway.
The role of interleukin-6 signalling and its therapeutic blockage in skewing the T cell balance in rheumatoid arthritis
Authors: Schinnerling K , Aguillón J C , Catalán D , Soto L
Published: April 2017

Therapeutic blockage of cytokine signalling in autoimmune diseases has improved our understanding of the role of these cytokines in triggering, shaping and perpetuating autoimmune responses. In rheumatoid arthritis (RA), immunopathology is driven by a predominance of arthritogenic T helper cells secreting interferon-γ [T helper type 1 (Th1)] and interleukin (IL)-17 (Th17) over regulatory T cells (Treg). The pleiotropic cytokine IL-6 is crucial to the differentiation of Th17 cells and the balance between pathogenic Th17 and protective Treg. Targeting the IL-6 receptor (IL-6R) by humanized antibodies improves signs and symptoms of RA, and has provided new insights into the mechanisms of inflammation and immune regulation. Here we review current evidence on the role of IL-6 in the pathogenesis of RA and the molecular consequences of IL-6R blockage in disease, with special focus on the Th17/Treg balance and plasticity.
Complement factor 5 (C5) p.A252T mutation is prevalent in, but not restricted to, sub-Saharan Africa: implications for the susceptibility to meningococcal disease
Authors: Franco-Jarava C , Comas D , Orren A , Hernández-González M , Colobran R
Published: April 2017

Complement C5 deficiency (C5D) is a rare primary immunodeficiency associated with recurrent infections, particularly meningitis, by Neisseria species. To date, studies to elucidate the molecular basis of hereditary C5D have included fewer than 40 families, and most C5 mutations (13 of 17) have been found in single families. However, the recently described C5 p.A252T mutation is reported to be associated with approximately 7% of meningococcal disease cases in South Africa. This finding raises the question of whether the mutation may be prevalent in other parts of Africa or other continental regions. The aim of this study was to investigate the prevalence of C5 p.A252T in Africa and other regions and discuss the implications for prophylaxis against meningococcal disease. In total, 2710 samples from healthy donors within various populations worldwide were analysed by quantitative polymerase chain reaction (qPCR) assay to detect the C5 p.A252T mutation. Eleven samples were found to be heterozygous for p.A252T, and nine of these samples were from sub-Saharan African populations (allele frequency 0·94%). Interestingly, two other heterozygous samples were from individuals in populations outside Africa (Israel and Pakistan). These findings, together with data from genomic variation databases, indicate a 0·5–2% prevalence of the C5 p.A252T mutation in heterozygosity in sub-Saharan Africa. Therefore, this mutation may have a relevant role in meningococcal disease susceptibility in this geographical area.
Hearing optimisation in neurofibromatosis type 2: A systematic review
Authors: Lloyd S.K.W. , King A.T. , Rutherford S.A. , Hammerbeck‐Ward C.L. , Freeman S.R.M. , Mawman D.J. , O'Driscoll M. , Evans D.G.
Published: April 2017

Background

It is common for patients with neurofibromatosis type 2 to develop bilateral profound hearing loss hearing loss, and this is one of the main determinants of quality of life in this patient group.

Objectives

The aim of this systematic review was to review the current literature regarding hearing outcomes of treatments for vestibular schwannomas in neurofibromatosis type 2 including conservative and medical management, radiotherapy, hearing preservation surgery and auditory implantation in order to determine the most effective way of preserving or rehabilitating hearing.

Search strategy

A MESH search in PubMed using search terms ((‘Neurofibromatosis 2’ [Mesh]) AND ‘Neuroma, Acoustic’[Mesh]) AND ‘Hearing Loss’ [Mesh] was performed. A search using keywords was also performed. Studies with adequate hearing outcome data were included. With the exception of the cochlear implant studies (cohort size was very small), case studies were excluded.

Evaluation method

The GRADE system was used to assess quality of publication. Formal statistical analysis of data was not performed because of very heterogenous data reporting.

Results

Conservative management offers the best chance of hearing preservation in stable tumours. The use of bevacizumab probably improves the likelihood of hearing preservation in growing tumours in the short term and is probably more effective than hearing preservation surgery and radiotherapy in preserving hearing. Of the hearing preservation interventions, hearing preservation surgery probably offers better hearing preservation rates than radiotherapy for small tumours but recurrence rates for hearing preservation surgery were high. For patients with profound hearing loss, cochlear implantation provides significantly better auditory outcomes than auditory brainstem implantation. Patients with untreated stable tumours are likely to achieve the best outcomes from cochlear implantation. Those who have had their tumours treated with surgery or radiotherapy do not gain as much benefit from cochlear implantation than those with untreated tumours.

Conclusions

This review summarises the current literature related to hearing preservation/rehabilitation in patients with NF2. Whilst it provides indicative data, the quality of the data was low and should be interpreted with care. It is also important to consider that the management of vestibular schwannomas in NF2 is complex and decision‐making is determined by many factors, not just the need to preserve hearing.
Comparing characteristics and clinical and echocardiographic outcomes in low‐flow vs normal‐flow severe aortic stenosis with preserved ejection fraction in an Asian population
Authors: Ngiam Jinghao Nicholas , Tan Benjamin Yong‐Qiang , Sia Ching‐Hui , Lee Glenn K.M. , Kong William K.F. , Chan Yiong‐Huak , Poh Kian‐Keong
Published: April 2017

Background/Objectives

In severe aortic stenosis (AS), deterioration of left ventricular ejection fraction (LVEF) to <50% is an AHA/ACC class I indication for valve replacement, regardless of symptoms. Controversy surrounds prognosis of low‐flow AS compared to normal‐flow, and no study has examined LVEF deterioration. We compared factors associated with LVEF deterioration (to <50%) and clinical outcomes.

Methods

Consecutive subjects with low‐flow (stroke volume index <35 mL/m2, n=56) and normal‐flow (n=72) severe AS (aortic valve area <1 cm2) with preserved LVEF (>50%) and with paired echocardiography were studied. Univariate and multivariate analyses identified factors associated with LVEF deterioration. Clinical outcomes were determined on follow‐up for more than 5 years.

Results

Significant LVEF deterioration (to <50%) was seen in 18% of low‐flow (initial LVEF 63±8% to 32±9%) and 18% of normal‐flow AS (61±7% to 31±12%). Independent factors in low‐flow AS were hypertension (OR: 30.7, 95% CI: 2.0–467.6, P=.014) and higher end‐systolic wall stress (OR: 1.086, 95% CI: 1.022–1.153, P=.008), compared to normal‐flow, which were hypertension (OR: 15.9, 95% CI: 3.1–81.9, P=.001), higher septal E/E′ ratio (OR: 1.16, 95% CI: 1.01–1.35, P=.043), lower septal S′ velocity (OR: 0.204, 95% CI: 0.061–0.682, P=.010), and higher end‐systolic wall stress (OR: 1.051, 95% CI: 1.001–1.104, P=.047). Overall, a third of the cohort experienced MACE, regardless of flow (log‐rank 0.048, P=.827). However, aortic valve replacement (AVR) rates were lower in low‐flow AS (20% vs 43%, P=.005).

Conclusions

Low‐flow AS despite normal LVEF appears similar to normal‐flow in terms of LVEF deterioration and clinical outcomes in our Asian population. AVR rate was lower even though low‐flow may not reflect less severe disease.
Regional right ventricular remodeling and function in children with idiopathic pulmonary arterial hypertension vs those with pulmonary valve stenosis: Insights into mechanics of right ventricular dysfunction
Authors: Driessen Mieke M.P. , Meijboom Folkert J. , Hui Wei , Dragulescu Andreea , Mertens Luc , Friedberg Mark K.
Published: April 2017

Background

Right ventricular (RV) pressure overload in the context of pulmonary stenosis (PS) has a much better prognosis than in the context of idiopathic pulmonary arterial hypertension (iPAH), which may be related to differences in global and regional RV remodeling and systolic function. We compared RV mechanics in children with PS to those with iPAH, aiming to identify mechanisms and markers of RV dysfunction.

Methods

Eighteen controls, 18 iPAH and 16 PS patients were retrospectively studied. Age, BSA, and sex distribution were comparable. Two‐dimensional echocardiography, blood flow and tissue Doppler, and longitudinal RV deformation were analyzed. ANCOVA—including RV systolic pressure (RVSP) and length as covariates—was used to compare patient groups.

Results

RV systolic pressure was higher in iPAH vs PS (96.8±25.4 vs 75.4±18.9 mm Hg, P=.011). Compared to controls, PS patients showed mild dilation (P<.01) and decreased longitudinal deformation (P<.001) at the RV apex. Compared to both PS and controls, iPAH patients showed marked spherical RV dilation (P<.001), reduced global, RV free wall and septal longitudinal deformation (iPAH −22.07%±4.35% vs controls −28.18%±1.69%; −9.98%±4.30% vs −17.45%±2.52%; P<.001) and RV postsystolic shortening (P<.001). RV transverse shortening (radial performance) was increased in PS (31.75%±10.35%; P<.001) but reduced in iPAH (−1.62%±11.11% vs controls 12.00%±7.74%; P<.001).

Conclusion

Children with iPAH demonstrate adverse global and regional RV remodeling and mechanics compared to those with PS. Mechanisms of RV systolic dysfunction in iPAH include decreased longitudinal deformation, decreased or absent transverse shortening, and postsystolic shortening. These markers may be useful to identify children at risk of RV failure.
Left atrial function and phenotypes in asymmetric hypertrophic cardiomyopathy
Authors: Kobayashi Yukari , Wheeler Matthew , Finocchiaro Gherardo , Ariyama Miyuki , Kobayashi Yuhei , Perez Marco V. , Liang David , Kuznetsova Tatiana , Schnittger Ingela , Ashley Euan , Haddad Francois
Published: April 2017

Background

Few studies have analyzed changes in left atrial (LA) function associated with different phenotypes of asymmetric hypertrophic cardiomyopathy (HCM). We sought to demonstrate the association of impairments in LA function with disease phenotype in patients with obstructive and nonobstructive HCM.

Methods

From Stanford Cardiomyopathy Registry, we randomly selected 50 age‐/sex‐matched healthy controls, 35 patients with nonobstructive HCM (HCM 1), 35 patients with obstructive HCM (HCM 2), and 35 patients with obstructive HCM requiring septal reduction therapy (HCM 3). Echocardiography was performed to evaluate left ventricular (LV) strain as well as LA function including LA emptying fraction and LA strain.

Results

The mean age was 51±14 years and 57% were male. LA volume index differed among all four predefined groups (25.6±6.7 mL/m2 in controls, 32.2±13.3 mL/m2 in HCM 1, 42.0±12.9 mL/m2 in HCM 2, 52.4±15.2 mL/m2 for HCM 3, and P<.05 all between groups). All measurement of LA function was impaired in patients with HCM than controls. Total and passive LA function was further impaired in HCM 2 or 3 compared with HCM 1, while active LA function was not different among the three groups. Among LV strains, only septal longitudinal strain differed among all groups (−18.5±1.9% in controls, −14.5±1.9% in HCM 1, −13.3±1.8% in HCM 2, −11.6±2.3% in HCM 3, and P<.05 all between groups).

Conclusions

LA function was impaired in patients with HCM even in minimally symptomatic nonobstructive phenotype. Total and passive LA function was further impaired in patients with obstructive HCM.