bluuebunny/crossref_metadata_2025 huggingface dataset:
Blockchain and insurance: a review for operations and regulation
Authors: Brophy Richard
Published: November 2019

Purpose

The purpose of this paper is to examine the operational and regulatory positions of the employment of Blockchain in the insurance industry. Blockchain technology has attracted wide interest from various stakeholders. Many theorists are predicting that this technology will disrupt financial services, including insurance. As stated that the development of blockchain is dependent on regulatory acceptance of this technology, it is essential to establish the current state of play with regard to the application and use of blockchain from a commercial and regulatory standpoints.

Design/methodology/approach

This review encompasses a number of approaches to view the current status of Blockchain applications. From a commercial approach, this research lists the current applications of blockchain within the insurance industry. From a regulatory point of view, the current positions of the EU and national regulatory bodies are enquired upon to establish how they are examining FinTech and Blockchain technologies within their regulatory processes.

Findings

This review illustrates a number of Blockchain applications in situ from a commercial point of view. From a regulatory setting and following a call from international and EU levels, it appears that various regulatory bodies have begun the process of formulating testing processes for FinTech applications. There are two predominant types in operation, while others are forming points of contact for advice for FinTechs and a small amount who have not begun the process at all.

Research limitations/implications

This review illustrates the current state of play of blockchain in insurance from a commercial and regulatory point of view. While this has been observational, this review pulls together information from various sources to encapsulate the regulatory positioning of evaluating FinTech and Blockchain technologies for academia, regulatory and industry audiences.

Originality/value

This review offers a central resource of information with regard to the current state of blockchain technologies in operation and regulatory approaches to this and other FinTech developments.
Industrie 4.0 process transformation: findings from a case study in automotive logistics
Authors: Hermann Mario , Bücker Isabel , Otto Boris
Published: November 2019

Purpose

The purpose of this paper is to explore the transformation of logistics processes to meet requirements of Industrie 4.0.

Design/methodology/approach

The authors follow the principles of action design research to conduct a single-case study investigating four logistics processes at a leading German car manufacturer. For the development of artifacts, the authors used Method Engineering.

Findings

The case study reveals a set of Industrie 4.0 process design principles, providing guidelines for the design and management of Industrie 4.0 compliant processes. In the second step, the authors use these process design principles for the development of a first version of a method for Industrie 4.0 process transformation.

Research limitations/implications

In the light of limited scientific knowledge about Industrie 4.0 process transformation, the paper uses a single-case study design. This is adequate considering the research goal at hand and the richness of empirical insight the authors had access to. However, a single-case design is limited regarding generalizability and demand for future qualitative and quantitative research.

Practical implications

The Industrie 4.0 process design principles support practitioners in the design and management of Industrie 4.0 compliant processes. In addition, the method developed by the authors supports enterprises in the transformation of their current processes toward Industrie 4.0.

Originality/value

The paper describes the first attempt – as far as the authors are aware – to derive guidelines for the design and management of Industrie 4.0 processes from the analysis of a real-world industrial setting. Likewise, the method for Industrie 4.0 process transformation presented in this paper is presumed to be the first such method developed in full accordance with the principles of Method Engineering.
Moving beyond one-off procurement innovation; an ambidexterity perspective
Authors: Plantinga Henrico , Voordijk Hans , Dorée André
Published: November 2019

Purpose

The development of innovative procurement instruments can be costly and risky. To capitalize on successful innovative instruments, it is essential that these are reused. However, reuse can be problematic in project-based public client organizations. This paper aims to apply the ambidexterity concept of integration mechanisms to examine how such reuse can be facilitated.

Design/methodology/approach

An initial framework is developed to conceptualize and contextualize the ambidexterity integration mechanism for the procurement function of a multi-project public client. Concluding that, in this situation, an organizational procedure is an appropriate interpretation of the integration mechanism, a design science project is carried out to develop and implement a procedure in a real-life setting.

Findings

Reconstructed reuse patterns confirm the need to have an actionable integration mechanism implemented. Integration, in the sense of drawing benefits from successful one-off innovative procurement instruments, may fail unnoticed if not organized and deliberately managed. The procedure developed in the design science project demonstrates how such integration can be achieved.

Originality/value

Although research on ambidexterity has grown exponentially in the past decade, it is yet to be applied in the field of public procurement. Furthermore, the application of design science research is novel in this field of literature. The paper illustrates how both can help solve a relevant organizational problem.
Strategic outsourcing in SMEs
Authors: Edvardsson Ingi Runar , Durst Susanne , Oskarsson Gudmundur Kristjan
Published: November 2019

Purpose

So far, there are very few empirical research studies available on the outsourcing pattern among small- and medium-sized enterprises (SMEs). The purpose of this paper is to examine strategic outsourcing among Icelandic SME service firms, from 2009 to 2018.

Design/methodology/approach

The data presented in this paper cover responses from 802 small service firms, which were collected through telephone and online questionnaires. In order to have sufficient data on strategic outsourcing and to ensure a decent analysis, three surveys were combined.

Findings

The main finding of the present paper is that SMEs that have a developed strategy on outsourcing seem to perform better than those who do not have. The former are more likely to have achieved cost reduction, especially in housing and finance, and they use outsourcing to increase core businesses. They select vendor firms more on the bases of cost and services, rather than personal contacts. Also, these firms have improved service quality, by focusing on their core competences.

Originality/value

To the authors‘ knowledge, the present study is one of the few empirical studies that have examined outsourcing in SMEs from a strategic perspective. The findings are valuable for managerial practice and could be a base for outsourcing strategies in SMEs.
Pakistani students’ perceptions about their learning experience through video games
Authors: Khalid Tooba , Batool Syeda Hina , Khalid Ayesha , Saeed Henna , Zaidi Syed Waqas Hussain
Published: November 2019

Purpose

The emergence of digital technological advances pushes educators for understanding and utilizing these technologies for classroom use. The current generation of teenagers has grown up in a networked world where everyone is immersed in technology-based gadgets in everyday life. Therefore, the purpose of this paper is to investigate video game-based academic and information literacy (IL) learning of teenagers of private schools of Lahore city. Lahore is the capital city of the province of Punjab. Literary works highlighted the importance of video games in developing academic and IL skills; therefore, the current research aims to reveal this fact in local context.

Design/methodology/approach

The present study adopted qualitative research design and utilized phenomenological research method to achieve study’s objectives. The data were collected through face-to-face interviews. The study participants were teenagers (aged 13‒19 years) of elite economic class of private schools where students normally owned latest video game gadgets.

Findings

Based on the study findings, it is elucidated that playing video games has a positive impact on teenagers’ learning, and it promotes quick thinking. The participants exert effort to achieve goals, take up challenges for completing different points at various stages of games and interact with online competitors. It enhanced their social communication, problem-solving and IL (searching/locating and evaluating) skills.

Research limitations/implications

The present study has some limitations. First, sample is limited to elite economic private schools of Lahore. Second, the lack of availability of regular video game players has limited the sample size, as Pakistan is a developing country and limited numbers of teenagers use and can afford gaming gadgets. Lastly, the results of this study are based on students’ perceptions, so there is a need to measure actual learning with assessments.

Originality/value

The results of the study are beneficial for the game developers, teachers, librarians and parents. The education sector may support video games usability as learning tools.
Audit committee attributes and cosmetic accounting in Nigeria
Authors: Bala Hussaini , Amran Noor Afza , Shaari Hasnah
Published: November 2019

Purpose

The literature on the influence of audit committees (ACs) and cosmetic accounting (CSA) is scarce. This paper aims to examine the influence of AC attributes on CSA and how this relationship is moderated by the audit price (AUPR).

Design/methodology/approach

The study used pooled logistic regressions to analyse 624 firm-year observations of listed companies in Nigeria from 2008 to 2016.

Findings

The results show that AC financial accounting expertise, AC legal expertise and female AC membership were negatively related to CSA. The negative relationship is highly pronounced when a firm incurs higher audit fees. Results for the robustness checks were similar, even with changes to the measurements of dependent and independent variables and alternative estimation.

Practical implications

This study can benefit policymakers and regulators, enabling them to better appreciate the importance of AC attributes and AUPR in curtailing artificial manipulation and enhancing financial reporting quality.

Social implications

This study can benefit policymakers and regulators, enabling them to better appreciate the importance of AC attributes and AUPR in curtailing artificial manipulation and enhancing financial reporting quality.

Originality/value

The findings provide an initial insight into the moderating effect of AUPR on the relationship between AC attributes and CSA.
Life cycle assessment of anaerobic digestion systems
Authors: Gopal Gahana , Dhanorkar Manikprabhu , Kale Sharad , Patil Yogesh B.
Published: November 2019

Purpose

It is well known that sustainability is the ideal driving path of the entire world and renewable energy is the backbone of the ongoing initiatives. The current topic of argument among the sustainability research community is on the wise selection of processes that will maximize yield and minimize emissions. The purpose of this paper is to outline different parameters and processes that impact the performance of biogas production plants through an extensive literature review. These include: comparison of biogas plant efficiency based on the use of a diverse range of feedstock; comparison of environmental impacts and its reasons during biogas production based on different feedstock and the processes followed in the management of digestate; analysis of the root cause of inefficiencies in the process of biogas production; factors affecting the energy efficiency of biogas plants based on the processes followed; and the best practices and the future research directions based on the existing life cycle assessment (LCA) studies.

Design/methodology/approach

The authors adopted a systematic literature review of research articles pertaining to LCA to understand in depth the current research and gaps, and to suggest future research directions.

Findings

Findings include the impact of the type of feedstock used on the efficiency of the biogas plants and the level of environmental emissions. Based on the analysis of literature pertaining to LCA, diverse factors causing emissions from biogas plants are enlisted. Similarly, the root causes of inefficiencies of biogas plants were also analyzed, which will further help researchers/professionals resolve such issues. Findings also include the limitations of existing research body and factors affecting the energy efficiency of biogas plants.

Research limitations/implications

This review is focused on articles published from 2006 to 2019 and is limited to the performance of biogas plants using LCA methodology.

Originality/value

Literature review showed that a majority of articles focused mainly on the efficiency of biogas plants. The novel and the original aspect of this review paper is that the authors, alongside efficiency, have considered other critical parameters such as environmental emission, energy usage, processes followed during anaerobic digestion and the impact of co-digestion of feed as well. The authors also provide solid scientific reasoning to the emission and inefficiencies of the biogas plants, which were rarely analyzed in the past.
Theory and practice: from Delphi-study to pedagogical training
Authors: Andronie Melina , Krzyzek Sebastian , Bien-Miller Lena , Wildemann Anja
Published: November 2019

Purpose

The purpose of this paper is to focus on the combination of Delphi and focus group techniques and on the utilization of qualitative content analysis in this context. Moreover, it illustrates the potential of this hybridized methodology for gathering information from experts on multilingual practices in the primary school context in Germany in order to conceptualize a teacher training.

Design/methodology/approach

Based on a structured guideline, two group discussions with experts from the scientific community, schools and educational institutions (n=13;n=12) focused on language diversity in the school context, multilingualism, the heritage languages of children as well as on the role of language reflection and metalinguistic awareness in (second) language acquisition and development in primary school. Both group discussions were qualitatively analyzed, and inductive categories were framed.

Findings

The main aspects derived from the data were: teaching actors, their language awareness, their knowledge about multilingualism and attitudes toward it, characteristics of the materials and methods used in language lessons as well as students’ own experiences with both heritage and second language(s).

Practical implications

Following these domains derived from the analyses of the data, the authors developed a teacher training, systematically considering multilingual teaching practices and implications resulting from the modified Delphi-study.

Originality/value

Due to the fact that knowledge and experience of experts from research and school context had been taken into account, the teacher training measure achieved higher acceptance and efficacy.
Modeling dermatophytosis: Guinea pig skin explants represent a highly suitable model to study Trichophyton benhamiae infections
Authors: Baumbach Christina‐Marie , Schrödl Wieland , Nenoff Pietro , Uhrlaß Silke , Mülling Christoph K. W. , Michler Jule Kristin
Published: November 2019

Dermatophyte infections are a growing health concern worldwide with increasing patient numbers, especially in children. However, detailed knowledge about infection mechanisms and virulence factors are scarce. This study aimed to establish an infection model based on guinea pig skin explants mimicking the in vivo situation as closely as possible to survey the pathogenesis of dermatophytoses. A fundamental prerequisite was the detailed description of native guinea pig skin and its morphological changes during tissue culture because comprehensive data on guinea pig skin characteristics were not available. Skin explants were harvested from healthy, adult guinea pigs and transferred to cell culture inserts. One group was inoculated with defined suspensions of colony‐forming units of zoonotic Trichophyton benhamiae isolates; others served as controls to assess the tissue viability during the 10‐day culture. Samples were taken on days 3, 5, 7 and 10 and processed for histological and immunohistochemical analysis. Standard tissue culture conditions provoked acantholysis and regional orthokeratotic alterations. The reduced desquamation caused hyperkeratosis paralleled by hypogranulosis or regional hyperplasia. During T. benhamiae infection, keratinocyte proliferation came to a complete halt on day 5 whereas the number of terminal deoxynucleotidyl transferase dUTP nick end labeling assay‐positive cells increased moderately up to day 7. Hyphae grew massively into the skin explants causing strong keratinolysis and tricholysis. By the end of the culture, complete disintegration of the basement membrane and dermal tissue was observed. A realistic and reliable skin infection model was established to study dermatophytoses in general and cutaneous T. benhamiae infections in particular.
Taurine Suppression of Central Amygdala GABAergic Inhibitory Signaling via Glycine Receptors Is Disrupted in Alcohol Dependence
Authors: Kirson Dean , Oleata Christopher S. , Roberto Marisa
Published: November 2019

Background

Alcohol use disorder (AUD) increases brain stress systems while suppressing reward system functioning. One expression of stress system recruitment is elevated GABAergic activity in the central amygdala (CeA), which is involved in the excessive drinking seen with AUD. The sulfonic amino acid taurine, a glycine receptor partial agonist, modulates GABAergic activity in the rewarding effects of alcohol. Despite taurine abundance in the amygdala, its role in the dysregulation of GABAergic activity associated with AUD has not been studied. Thus, here, we evaluated the effects of taurine on locally stimulated GABAergic neurotransmission in the CeA of naïve‐ and alcohol‐dependent rats.

Methods

We recorded intracellularly from CeA neurons of naïve‐ and alcohol‐dependent rats, quantifying locally evoked GABAA receptor‐mediated inhibitory postsynaptic potentials (eIPSP). We examined the effects of taurine and alcohol on CeA eIPSP to characterize potential alcohol dependence‐induced changes in the effects of taurine.

Results

We found that taurine decreased amplitudes of eIPSP in CeA neurons of naïve rats, without affecting the acute alcohol‐induced facilitation of GABAergic responses. In CeA neurons from dependent rats, taurine no longer had an effect on eIPSP, but now blocked the ethanol (EtOH)‐induced increase in eIPSP amplitude normally seen. Additionally, preapplication of the glycine receptor‐specific antagonist strychnine blocked the EtOH‐induced increase in eIPSP amplitude in neurons from naïve rats.

Conclusions

These data suggest taurine may act to oppose the effects of acute alcohol via the glycine receptor in the CeA of naïve rats, and this modulatory system is altered in the CeA of dependent rats.
A randomized clinical trial of mobile phone motivational interviewing for alcohol use problems in Kenya
Authors: Harder Valerie S. , Musau Abednego M. , Musyimi Christine W. , Ndetei David M. , Mutiso Victoria N.
Published: November 2019

Aim

To test the effectiveness of a motivational interviewing (MI) intervention using the mobile phone among adults with alcohol use problems.

Design

A randomized clinical trial of mobile MI and standard in‐person MI with 1‐ and 6‐month follow‐up, including a 1‐month waitlist control followed by mobile MI.

Setting

A primary health center in rural Kenya.

Participants

Three hundred adults screening positive for alcohol use problems were randomized and received immediate mobile MI (n = 89), in‐person MI (n = 65) or delayed mobile MI (n = 76) for waiting‐list controls 1 month after no treatment, with 70 unable to be reached for intervention.

Intervention and comparator

One MI session was provided either immediately by mobile phone, in‐person at the health center or delayed by 1 month and then provided by mobile phone.

Measurements

Alcohol use problems were repeatedly assessed using the Alcohol Use Disorder Identification Test (AUDIT) and the shorter AUDIT‐C. The primary outcome was difference in alcohol score 1 month after no intervention for waiting‐list control versus 1 month after MI for mobile MI. The secondary outcomes were difference in alcohol score for in‐person MI versus mobile MI one and 6 months after MI.

Findings

For our primary outcome, average AUDIT‐C scores were nearly three points higher (difference = 2.88, 95% confidence interval = 2.11, 3.66) for waiting‐list controls after 1 month of no intervention versus mobile MI 1 month after intervention. Results for secondary outcomes supported the null hypothesis of no difference between in‐person and mobile MI at 1 month (Bayes factor = 0.22), but were inconclusive at 6 months (Bayes factor = 0.41).

Conclusion

Mobile phone‐based motivational interviewing may be an effective treatment for alcohol use problems among adults visiting primary care in Kenya. Providing mobile motivational interviewing may help clinicians in rural areas to reach patients needing treatment for alcohol use problems.
Understanding registered nurse decision‐making, communication and care delivery between emergency departments and residential aged care facilities: A research protocol
Authors: Gurung Apil , Broadbent Marc , Bakon Shannon , Hocking Julia , Glenwright Amanda , Shaw Christine , Tweddell Sheryl , Clark Sean
Published: November 2019

Objectives

Nursing staff in residential aged care facilities (RACF)s often make decisions about the transfer of residents to the emergency department (ED). This paper describes the protocol of a study that aims to understand decision‐making process utilised by RACF registered nurses (RNs) and to explore the perceptions of RNs about the decision and communication process between RACF and ED.

Methods

The proposed mixed‐method study will survey and interview RACF RNs to understand their decision to transfer a resident and collect information about older people referred to the ED. Data collection will involve telephone survey, ED information system (EDIS) data and semistructured interviews.

Results

The project outcomes will provide an understanding of existing ED service provision, communication between facilities and the reasons for transfer of older person to ED. This may inform redesign in communication processes between the ED and local RACFs and outreach care from the ED to RACFs.
Therapeutic and prophylactic deletion of IL‐4Ra‐signaling ameliorates established ovalbumin induced allergic asthma
Authors: Khumalo Jermaine , Kirstein Frank , Scibiorek Martyna , Hadebe Sabelo , Brombacher Frank
Published: November 2019

Background

Allergic asthma is a chronic inflammatory airway disease driven predominantly by a TH2 immune response to environmental allergens. IL‐4Rα‐signaling is essential for driving TH2‐type immunity to allergens. Anti‐TH2 therapies have the potential to effectively reduce airway obstruction and inflammation in allergic asthma.

Objective

We investigated potential therapeutic effects of selective inhibition of this pathway in mice with established allergic airway disease. We further investigated whether IL‐4Rα disruption in systemically sensitized mice can prevent the onset of the disease.

Methods

We used RosacreERT2IL‐4Rα−/lox mice, a tamoxifen (TAM)‐inducible IL‐4Rα knockdown model to investigate the role of IL‐4/IL‐13 signaling prior to the onset of the disease and during the effector phase in the ovalbumin‐induced allergic airway disease.

Results

Inducible deletion of IL‐4Rα demonstrated therapeutic effects, on established allergic airway disease, and prevented the development of ovalbumin‐induced airway hyperreactivity, eosinophilia, and goblet cell metaplasia in allergen‐sensitized mice. Interestingly, IL‐4Rα knockdown after allergic sensitization did not induce TH17, a neutrophilic inflammatory response as observed in global IL‐4Rα‐deficient mice after intranasal allergen challenge.

Conclusion

Abrogation of IL‐4Rα signaling after allergic sensitization would have significant therapeutic benefit for TH2‐type allergic asthma.
The impact of modifiable risk factors on the long‐term outcomes of non‐alcoholic fatty liver disease
Authors: Paik James M. , Deshpande Rati , Golabi Pegah , Younossi Issah , Henry Linda , Younossi Zobair M.
Published: November 2019

Background

Cardiovascular (CV) disease is the leading cause of mortality in patients with non‐alcoholic fatty liver disease (NAFLD). The American Heart Association (AHA) developed 7 CV health metrics (poor, intermediate and ideal health) to improve CV health.

Aim

To assess population‐attributable fractions (PAFs) of CV health metrics to all‐cause and CV mortality among NAFLD patients

Methods

We included adult participants from National Health and Nutrition Examination Survey (NHANES 1988‐1994) with clinical and mortality data. NAFLD was defined as the presence of hepatic steatosis on ultrasonography in the absence of other chronic liver diseases and excessive alcohol use.

Results

A total of 4040 adults with NAFLD and 7515 without were included. NAFLD had fewer ideal health metrics than non‐NAFLD (age‐standardised prevalence: 20% vs 10% for ≤1 ideal health metric; 5.1% vs 8.7% for ≥6, all P < .001). Following median follow‐up of 19.2 years (IQR: 17.5‐21.0 years), 1,136 NAFLD subjects (327 CV deaths) and 1600 non‐NAFLD subjects (447 CV deaths) died. Increased number of ideal health metrics (all trend P < .0001) correlated with lower risk for all‐cause and CV mortality. If all NAFLD subjects achieved 7 ideal health metrics, 66% of all‐cause deaths and 83% of CV deaths were preventable. Among NAFLD subjects, lack of glycaemic control (adjusted PAF = 28.3% all‐cause; 38.1% CV) and hypertension (adjusted PAF of 23% all‐cause; 52.8% CV) were the largest mortality contributors. Ideal physical activity level obtainment provided an adjusted PAF = 13.9% all‐cause and 13.8% CV mortality.

Conclusions

Attainment of ideal CV health metrics provides protection against all‐cause and CV deaths in NAFLD.
New prognosis score including absolute lymphocyte/monocyte ratio, red blood cell distribution width and beta‐2 microglobulin in patients with diffuse large B‐cell lymphoma treated with R‐CHOP: Spanish Lymphoma Group Experience (GELTAMO)
Authors: Bento Leyre , Díaz‐López Antonio , Barranco Gilberto , Martín‐Moreno Ana M. , Baile Mónica , Martín Alejandro , Sancho Juan M. , García Olga , Rodríguez Mario , Sánchez‐Pina Jose M. , Novelli Silvana , Salar Antonio , Bastos Mariana , Rodríguez‐Salazar M José , González de Villambrosia Sonia , Córdoba Raul , García‐Recio M. , Martínez‐Serra J. , del Campo Raquel , Luzardo Hugo , García Daniel , Hong Azueg , Abrisqueta Pau , Sastre‐Serra Jorge , Roca Pilar , Rodríguez José , Gutiérrez Antonio ,   the Grupo Español de Linfomas y Trasplante Autólogo (GELTAMO)
Published: November 2019

The International Prognostic Index (IPI) is the most widely used score for non‐Hodgkin lymphoma but lacks the ability to identify a high‐risk population in diffuse large B‐cell lymphoma (DLBCL). Low absolute lymphocyte count and high monocytes have proved to be unfavourable factors. Red‐cell distribution width (RDW) has been associated with inflammation and beta‐2 microglobulin (B2M) with tumour load. The retrospective study included 992 patients with DLBCL treated with R‐CHOP. In the multivariate analysis, age, Eastern Cooperative Oncology Group performance status (ECOG‐PS), stage, bulky mass, B2M, RDW, and lymphocyte/monocyte ratio (LMR) were independently related to progression‐free survival (PFS). A new prognosis score was generated with these variables including age categorized into three groups (0, 1, 2 points); ECOG ≥ 3–4 with two; stage III/IV, bulky mass, high B2M, LMR < 2·25 and RDW > 0·96 with one each; for a maximum of 9. This score could improve the discrimination of a very high‐risk subgroup with five‐year PFS and overall survival (OS) of 19% and 24% versus 45% and 59% of R (revised)‐IPI respectively. This score also showed greater predictive ability than IPI. A new score is presented including complete blood cell count variables and B2M, which are readily available in real‐life practice without additional tests. Compared to R‐IPI, it shows a more precise high‐risk assessment and risk discrimination for both PFS and OS.
Unionization, information asymmetry and the de‐location of firms
Authors: de Pinto Marco , Lingens Jörg
Published: November 2019

We analyze the effects of unionization on the decision of a firm to de‐locate internationally. In a model in which home and foreign workers are perfect substitutes and firms have an informational advantage concerning their productivity, the union offers a menu of wage–employment contracts. Because firms' outside options (producing abroad) depend on productivity, the problem is characterized by countervailing incentives. With the foreign profit sufficiently increasing in productivity, the overstating incentive dominates in equilibrium. Contracts are then characterized by overemployment. The union also affects the extensive margin. High‐productivity firms are excluded because this narrows the possibility to overstate productivity, which saves on information rent. Using a numerical simulation, we show that these effects are quantitatively sizable.
Phase I study of vorinostat with gefitinib in BIM deletion polymorphism/epidermal growth factor receptor mutation double‐positive lung cancer
Authors: Takeuchi Shinji , Hase Tetsunari , Shimizu Shinobu , Ando Masahiko , Hata Akito , Murakami Haruyasu , Kawakami Takahiro , Nagase Katsuhiko , Yoshimura Kenichi , Fujiwara Tadami , Tanimoto Azusa , Nishiyama Akihiro , Arai Sachiko , Fukuda Koji , Katakami Nobuyuki , Takahashi Toshiaki , Hasegawa Yoshinori , Ko Tun Kiat , Ong S. Tiong , Yano Seiji
Published: November 2019

Patients with epidermal growth factor receptor (EGFR)‐mutated non‐small cell lung cancer (NSCLC) harboring BIM deletion polymorphism (BIM deletion) have poor responses to EGFR TKI. Mechanistically, the BIM deletion induces preferential splicing of the non‐functional exon 3‐containing isoform over the functional exon 4‐containing isoform, impairing TKI‐induced, BIM‐dependent apoptosis. Histone deacetylase inhibitor, vorinostat, resensitizes BIM deletion‐containing NSCLC cells to EGFR‐TKI. In the present study, we determined the safety of vorinostat‐gefitinib combination and evaluated pharmacodynamic biomarkers of vorinostat activity. Patients with EGFR‐mutated NSCLC with the BIM deletion, pretreated with EGFR‐TKI and chemotherapy, were recruited. Vorinostat (200, 300, 400 mg) was given daily on days 1‐7, and gefitinib 250 mg was given daily on days 1‐14. Vorinostat doses were escalated based on a conventional 3 + 3 design. Pharmacodynamic markers were measured using PBMC collected at baseline and 4 hours after vorinostat dose on day 2 in cycle 1. No dose‐limiting toxicities (DLT) were observed in 12 patients. We determined 400 mg vorinostat as the recommended phase II dose (RP2D). Median progression‐free survival was 5.2 months (95% CI: 1.4‐15.7). Disease control rate at 6 weeks was 83.3% (10/12). Vorinostat preferentially induced BIM mRNA‐containing exon 4 over mRNA‐containing exon 3, acetylated histone H3 protein, and proapoptotic BIMEL protein in 11/11, 10/11, and 5/11 patients, respectively. These data indicate that RP2D was 400 mg vorinostat combined with gefitinib in BIM deletion/EGFR mutation double‐positive NSCLC. BIM mRNA exon 3/exon 4 ratio in PBMC may be a useful pharmacodynamic marker for treatment.
Outcomes research on children with medical complexity: A scoping review of gaps and opportunities
Authors: Looman Wendy S. , Park Young Shin , Gallagher Tiffany T. , Weinfurter Elizabeth V.
Published: November 2019

Background

There has been a recent, rapid increase in the number of studies of children with medical complexity (CMC) and their families. There is a need for attention to gaps and patterns in this emerging field of study.

Objectives

The purpose of this scoping review was to identify patterns and gaps in the evidence related to classification systems, data, and outcomes in studies of CMC.

Data Sources

We searched peer‐reviewed journals for reports of quantitative studies focused on CMC outcomes published between 2008 and 2018. On the basis of a structured screening process, we selected 63 reports that met our inclusion criteria.

Study Appraisal and Synthesis

We used the methodological framework for scoping studies described by Arskey and O'Malley to map relevant literature in the field and the ECHO model to categorize studies according to three health outcome domains (economic, clinical, and humanistic).

Results

The terminology used to describe and classify CMC differed across studies depending on outcome domain. Two thirds of the reports focused on economic outcomes; fewer than a quarter included child or family quality of life as an outcome. A majority of studies used a single source of data, with robust analyses of administrative, payer, and publicly available data.

Conclusions and Implications of Key Findings

Research on CMC and their families would benefit from standardization of terms and classification systems, the use of measurement strategies that map humanistic outcomes as trajectories, and more attention to outcomes identified as most meaningful to CMC and their families.
Psychosocial functioning in children with phenylketonuria: Relationships between quality of life and parenting indicators
Authors: Morawska Alina , Mitchell Amy E. , Etel Evren , Kirby Grace , McGill James , Coman David , Inwood Anita
Published: November 2019

Objective

This study aimed to assess the impact of phenylketonuria (PKU) and its treatment on parent and child health‐related quality of life (HRQoL) and to identify the parenting‐related correlates of parent and child HRQoL, as well as metabolic control.

Methods

Eighteen mothers of 2‐ to 12‐year‐old children with PKU participated and completed a series of self‐report questionnaires including the PKU Impact and Treatment Quality of Life Questionnaire (PKU‐QOL).

Results

Mothers reported that the most significant impact of PKU on HRQoL was in relation to the impact of their child's anxiety during blood tests on their own HRQoL and guilt related to poor adherence to dietary restrictions and supplementation regimens. Higher reported intensity of child emotional and behavioural difficulties and parenting stress were associated with higher scores for PKU symptoms on the PKU‐QOL, higher scores for emotional, social, and overall impact of PKU, and higher scores for the impact of dietary restriction. Where mothers reported greater use of overreactivity as a parenting strategy, children tended to have better lifetime phenylalanine levels; however, the overall impact of PKU and the impact of supplement administration on mothers' HRQoL were worse for these families.

Conclusions

These findings have implications for a holistic family‐centred approach to the care of children with PKU and their families.
Reducing unintentional injuries in under fives: Development and testing of a mobile phone app
Authors: Jones Felicity , Whitehouse Ali , Dopson Amy , Palaghias Niklas , Aldiss Susie , Gibson Faith , Shawe Jill
Published: November 2019

Background

Unintentional injuries are a leading cause of preventable death and a major cause of ill health and disability in children under 5 years of age. A health promotion mobile phone application, “Grow up Safely” (GUS), was developed to support parents and carers in reducing unintentional injuries in this population of children.

Methods

A prototype of the mobile application was developed to deliver health education on unintentional injury prevention linked to stages of child development. In order to explore the usability of the app and refine its content, three focus groups were conducted with 15 mothers. Data were analysed using thematic analysis.

Results

The majority of participants reported previous use of health apps, mainly related to pregnancy and recommended by health professionals. The app was considered user‐friendly and easy to navigate. Participants in two focus groups found the app informative and offered new information, and they would consider using it. Participants in the “young mum's” group considered the advice to be “common sense” but found the language too complex. All participants commented that further development of push‐out notifications and endorsement by a reputable source would increase their engagement with the app.

Conclusion

The GUS mobile phone app, aimed at reducing unintentional injuries in children under five, was supported by mothers as a health promotion app. They would consider downloading it, particularly if recommended by a health professional or endorsed by a reputable organization. Further development is planned with push‐out notifications and wider feasibility testing to engage targeted groups, such as young mothers, fathers, and other carers.
Season of birth, childhood asthma and allergy in a nationwide cohort—Mediation through lower respiratory infections
Authors: Almqvist Catarina , Ekberg Sara , Rhedin Samuel , Fang Fang , Fall Tove , Lundholm Cecilia
Published: November 2019

Background

Previous studies have suggested an association between season of birth and risk of childhood asthma and allergic disease. The association may be modified by birth year and region, or mediated by respiratory tract infections.

Objective

We aimed to estimate the association between season of birth and risk of childhood asthma/wheeze or allergic rhinoconjunctivitis in a population‐based setting, and the mediating effect of lower respiratory infections.

Methods

Two population‐based cohorts were identified from the nationwide Swedish Medical Birth, Patient and Prescribed Drug Registers. The association between birth month/season and asthma/wheeze incidence was analysed using Cox proportional regression in the younger cohort born 2005‐2010 (n = 582 494) and asthma/allergic rhinoconjunctivitis prevalence during the 7th year of life using log‐binomial models in the older cohort born 2001‐2004 (n = 367 583). Interactions were formally tested. Mediation analyses to address the effect of lower respiratory infections were performed in the older cohort using the R package “medflex.”

Results

Children born during fall and winter had an increased risk of asthma/wheeze after 2 years of age in the younger cohort: hazard ratio 1.24 (95% confidence interval, CI 1.17, 1.33) for winter and risk of prevalent asthma during their 7th year of life in the older cohort; prevalence ratio (PR) 1.12 (95% CI 1.08, 1.16) for winter. These estimates were partly mediated by lower respiratory infections; the indirect effect for winter compared with summer was PR 1.03 (95% CI 1.03, 1.04). The association was similar for allergic rhinoconjunctivitis in the 7th year of life, but not mediated by respiratory infections.

Conclusion

We found that the association between season of birth and risk of childhood asthma/wheeze, but not allergic rhinoconjunctivitis, is partly mediated through lower respiratory infections.

Clinical relevance

This has important implications for patient care, such as asthma management programmes to notify timing of seasonality for viral respiratory tract infections.
Unusual subcutaneous dedifferentiated liposarcoma exhibiting coexistence of meningothelial‐like whorls and inflammatory myofibroblastic tumor‐like structures
Authors: Chen Shuai , He Shujin , Huang Haining , Li Lei , Wang Wei , Cui Zhihong , Zhang Renya
Published: November 2019

To explore the clinicopathological features of a rare dedifferentiated liposarcoma (DDLPS) with meningothelial‐like whorls, we retrospectively analyzed 46 reported cases and 1 case that we encountered. Fluorescence in situ hybridization (FISH) analysis of the MDM2 amplification status of our case was also performed. Our case involved a 73‐year‐old male patient who had a mass in the upper part of his left arm for 10 years and was treated by surgical ablation of the tumor because of the mass' recent rapid enlargement. Microscopically, the tumor tissues showed coexistence of well‐differentiated and dedifferentiated components, the latter of which included meningothelial‐like whorls and inflammatory myofibroblastic tumor‐like structures. The dedifferentiated components diffusely expressed vimentin, MDM2, CDK4, p16, and smooth muscle actin. They were also focally positive for desmin but negative for S‐100, CD117, CD34, ALK, EMA, SOX‐10, p53, and β‐catenin. FISH detection showed MDM2 amplification. In conclusion, subcutaneous DDLPS with meningothelial‐like whorls and inflammatory myofibroblastic tumor‐like features is rare. This case broadens the histopathological lineage of DDLPS, and confirms DDLPS with myogenic differentiation. The use of the combination of MDM2, CDK4, p16, and FISH to detect MDM2 amplification is a reliable basis for the diagnosis of DDLPS with meningothelial‐like whorls.
Safe hemostasis method using newly developed hemoclip for post‐endoscopic papillary large balloon dilation with sphincterotomy bleeding
Authors: Shimatani Masaaki , Tokuhara Mitsuo , Okazaki Kazuichi
Published: November 2019

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Potential feedback mediated by soil microbiome response to warming in a glacier forefield
Authors: Wang Yuwan , Ma Anzhou , Liu Guohua , Ma Jianpeng , Wei Jing , Zhou Hanchang , Brandt Kristian Koefoed , Zhuang Guoqiang
Published: November 2019

Mountain glaciers are retreating at an unprecedented rate due to global warming. Glacier retreat is widely believed to be driven by the physiochemical characteristics of glacier surfaces; however, the current knowledge of such biological drivers remains limited. An estimated 130 Tg of organic carbon (OC) is stored in mountain glaciers globally. As a result of global warming, the accelerated microbial decomposition of OC may further accelerate the melting process of mountain glaciers by heat production with the release of greenhouse gases, such as carbon dioxide (CO2) and methane. Here, using short‐term aerobic incubation data from the forefield of Urumqi Glacier No. 1, we assessed the potential climate feedback mediated by soil microbiomes at temperatures of 5°C (control), 6.2°C (RCP 2.6), 11°C (RCP 8.5), and 15°C (extreme temperature). We observed enhanced CO2‐C release and heat production under warming conditions, which led to an increase in near‐surface (2 m) atmospheric temperatures, ranging from 0.9°C to 3.4°C. Warming significantly changed the structures of the RNA‐derived (active) and DNA‐derived (total) soil microbiomes, and active microbes were more sensitive to increased temperatures than total microbes. Considering the positive effects of temperature and deglaciation age on the CO2‐C release rate, the alterations in the active microbial community structure had a negative impact on the increased CO2‐C release rate. Our results revealed that glacial melting could potentially be significantly accelerated by heat production from increased microbial decomposition of OC. This risk might be true for other high‐altitude glaciers under emerging warming, thus improving the predictions of the effects of potential feedback on global warming.
Effectiveness of a modified comprehensive behavioral intervention for tics for children and adolescents with tourette's syndrome: A randomized controlled trial
Authors: Chen Chia‐Wen , Wang Huei‐Shyong , Chang Hsiu‐Ju , Hsueh Chang‐Wei
Published: November 2019

Aim

To evaluate the effectiveness of a modified four‐session Comprehensive Behavioral Intervention for Tics programme for decreasing tics in children and adolescents with Tourette's syndrome.

Background

Comprehensive Behavioral Intervention for Tics programme has been shown to decrease tic severity. However, the lack of behaviour therapists in countries, such as in Taiwan, may preclude application of the standard eight‐session, 10‐week programme.

Design

Randomized controlled study.

Methods

Participants aged 6–18 years diagnosed with Tourette's syndrome or chronic tic disorder were recruited from February 2015 through September 2016. Participants in the control and intervention groups (N = 23 each) received the routine care (daily pyridoxine [50 mg] and psychoeducation). The intervention group received additional four behavioural intervention sessions over a 3‐month period that included psychoeducation, habit reversal training, relaxation training, and education on tic relapse prevention. The outcome measures, Yale Global Tic Severity Scale scores, were assessed at before and after the completion of programme for both groups and again at 3 months follow‐up for the intervention group. The effect of the intervention on severity scores was assessed using a generalized estimated equation.

Results

Comparison of scores before and after intervention showed that the intervention significantly decreased the severity of total motor tics (B = −3.28, p < .01) and total tics (B = −5.86, p < .01) as compared with control treatment. YGTSS scores for the intervention group were lower at 3‐month follow‐up as compared with before treatment or immediately after treatment completion (total tics, p < .001).

Conclusion

The modified four‐session Comprehensive Behavioral Intervention for Tics programme was more effective than routine care for decreasing tic severity in our cohort of 6‐ to 18‐year olds. This improvement was maintained 3 months after intervention.

Impact

Healthcare providers, including nurses, in countries currently not adopting Comprehensive Behavioral Intervention for Tics programme should be made aware of the positive effects of this modified intervention for Tourette's syndrome.
Up‐regulation of HDACs, a harbinger of uraemic endothelial dysfunction, is prevented by defibrotide
Authors: Palomo Marta , Vera Manel , Martin Susana , Torramadé‐Moix Sergi , Martinez‐Sanchez Julia , Belen Moreno Ana , Carreras Enric , Escolar Ginés , Cases Aleix , Díaz‐Ricart Maribel
Published: November 2019

Endothelial dysfunction is an earlier contributor to the development of atherosclerosis in chronic kidney disease (CKD), in which the role of epigenetic triggers cannot be ruled out. Endothelial protective strategies, such as defibrotide (DF), may be useful in this scenario. We evaluated changes induced by CKD on endothelial cell proteome and explored the effect of DF and the mechanisms involved. Human umbilical cord vein endothelial cells were exposed to sera from healthy donors (n = 20) and patients with end‐stage renal disease on haemodialysis (n = 20). Differential protein expression was investigated by using a proteomic approach, Western blot and immunofluorescence. HDAC1 and HDAC2 overexpression was detected. Increased HDAC1 expression occurred at both cytoplasm and nucleus. These effects were dose‐dependently inhibited by DF. Both the HDACs inhibitor trichostatin A and DF prevented the up‐regulation of the endothelial dysfunction markers induced by the uraemic milieu: intercellular adhesion molecule‐1, surface Toll‐like receptor‐4, von Willebrand Factor and reactive oxygen species. Moreover, DF down‐regulated HDACs expression through the PI3/AKT signalling pathway. HDACs appear as key modulators of the CKD‐induced endothelial dysfunction as specific blockade by trichostatin A or by DF prevents endothelial dysfunction responses to the CKD insult. Moreover, DF exerts its endothelial protective effect by inhibiting HDAC up‐regulation likely through PI3K/AKT.