bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and determinants of end-user intention: usage of expert systems
Authors: Alshare Khaled A. , Alomari Mohammad Kamel , Lane Peggy L. , Freeze Ronald D.
Published: June 2019

Purpose

Expert systems (ES) design emulates expertise with the intention that the ES be used by non-experts. This study aims to predict end-user intention and use of ES by proposing a research model that extends the basic components of the unified theory of acceptance and use of technology (UTAUT) by including additional relevant factors to ES, including the expert domain, perceived relevance, reliability, quality of ES and management support, which directly and indirectly influence the end-user intention to use an expert system.

Design/methodology/approach

A structural equation model (SEM), using LISREL, was used to test the measurement and structural models using a sample of 205 end-users of expert systems in the USA. These users of expert systems come from a variety of domains. The factors include both internal and external factors for the individual level of analysis design of this study.

Findings

The results showed behavioral intention had the strongest effect on usage, followed by perceived relevance. With respect to the factors that impact intention, perceived relevance had the strongest total effect, followed by attitude. For attitude, effort expectancy had the strongest total effect, followed by management support and perceived relevance.

Research limitations/implications

The results of this study should assist decision-makers in planning training and communications about the use of expert systems so that the expert systems will be used as intended.

Originality/value

The originality of this work resides in the addition of external factors to the UTAUT model that helps provide advice to practitioners in the support needed to insure expert system implementation success.
Integrating wearable technology products and big data analytics in business strategy
Authors: Nayak Bishwajit , Bhattacharyya Som Sekhar , Krishnamoorthy Bala
Published: June 2019

Purpose

This study aims to explore the impact of the adoption of wearable technology products for Indian health insurance firms. It identifies the key dynamic capabilities that health insurance firms should build to manage big data generated by wearable technology so as to attain a competitive advantage.

Design/methodology/approach

A qualitative exploratory study using in-depth personal interviews with 53 Indian health insurance experts was conducted with a semi-structured questionnaire. The data were coded using holistic and pattern codes and then analyzed using the content analysis technique. The findings were based on the thematic and relational intensity analysis of the codes.

Findings

An empirical model was established where all the propositions were strongly established except for the moderate relationship between wearable technology adoption and product innovation. The study established the nature of the interaction of variables on technology policy, organizational culture, strategic philosophy, product innovation, knowledge management and customer service quality with wearable technology adoption and also ascertained its influence on firm performance and competitive advantage.

Research limitations/implications

From a dynamic capabilities perspective, this study deliberates on wearable technology adoption in the health insurance context. It also explicates the relationship between the variables on technology policy, organizational culture, strategic philosophy, product innovation, knowledge management and customer service quality with wearable technology adoption on firm performance.

Originality/value

This study is one of the first studies to add the context of wearable technology and health insurance to the existing body of knowledge on dynamic capabilities and sustainable competitive advantage for the service sector. It would help existing and prospective players in adopting or setting up appropriate business models.
A microcredit evaluation model for non-bank financial institutions
Authors: Leon Ramona Diana , Treapăt Laurențiu Mihai , Gheorghiu Anda , Stan Sergiu Octavian
Published: June 2019

Purpose

The paper aims to develop a microcredit evaluation model (MEM) which could serve as a useful tool for banks and NBFIs when SMEs’ economic and financial risks are evaluated.

Design/methodology/approach

Based on the literature review, a set of 17 qualitative and quantitative prudential indicators is selected. Further, a calculation system is developed which relies on the multiple criteria analysis model elaborated by Altman (1968); starting from this, a matrix is developed and a rating system is built. The model is tested among six NBFIs which operate on the Romanian market; three of them are labeled by the Romanian Central Bank as the worst performers, while the other ones are qualified as the best performers. Data are collected from companies’ annual reports and also from the Ministry of Finance.

Findings

It proves that the MEM can serve as a useful tool for the national and international NBFIs’ risk assessment. It can anticipate NBFIs’ success or fall. Furthermore, its results can be guaranteed with a probability of 95 per cent, calculated through the VaR method. Last but not least, it can also be used by the international NBFIs which intend to enter in the Romanian market.

Originality/value

The present paper proposes an original model based on both quantitative and qualitative indicators organized in an integrative equation. The MEM helps both parties involved in the financial grant awarding process – NBFIs are able to better assess requests from SMEs, enabling them to increase the volume of granting, whereas SMEs are able to access money for development projects more easily.
Human resource allocation in an emergency department
Authors: Yousefi Milad , Yousefi Moslem
Published: June 2019

Purpose

The complexity and interdisciplinarity of healthcare industry problems make this industry one of the attention centers of computer-based simulation studies to provide a proper tool for interaction between decision-makers and experts. The purpose of this study is to present a metamodel-based simulation optimization in an emergency department (ED) to allocate human resources in the best way to minimize door to doctor time subject to the problem constraints which are capacity and budget.

Design/methodology/approach

To obtain the objective of this research, first the data are collected from a public hospital ED in Brazil, and then an agent-based simulation is designed and constructed. Afterwards, three machine-learning approaches, namely, adaptive neuro-fuzzy inference system (ANFIS), feed forward neural network (FNN) and recurrent neural network (RNN), are used to build an ensemble metamodel through adaptive boosting. Finally, the results from the metamodel are applied in a discrete imperialist competitive algorithm (ICA) for optimization.

Findings

Analyzing the results shows that the yellow zone section is considered as a potential bottleneck of the ED. After 100 executions of the algorithm, the results show a reduction of 24.82 per cent in the door to doctor time with a success rate of 59 per cent.

Originality/value

This study fulfils an identified need to optimize human resources in an ED with less computational time.
Improving healthcare service quality through performance management
Authors: Kennedy Denise M. , Anastos Christopher T. , Genau Michael C.
Published: June 2019

Purpose

Healthcare service quality in the USA has gained importance under value-based payment models. Providing feedback to front-line staff is a vital component of managing service performance, but complex organizational dynamics can prevent effective communication. This work explored the performance management of appointment desk staff at Mayo Clinic Arizona, identified barriers to effective management and sought to standardize the process for monitoring service performance.

Design/methodology/approach

Multiple data sources, including qualitative inquiry with 31 employees from the primary care and surgery departments, were used. The research was conducted in two phases – facilitated roundtable discussions with supervisors and semi-structured interviews with supervisors and staff six months after implementation of service standards. Participants were probed for attitudes about the service standards and supervisor feedback after implementation.

Findings

While all staff indicated a positive work environment, there was an unexpected and pervasive negative stigma surrounding individual feedback from one’s supervisor. Half the participants indicated there had been no individual feedback regarding the service standards from the supervisor. Presenting service standards in a simple, one-page format, signed by both supervisor and the patient service representative (PSR), was well received.

Originality/value

Combining rapid-cycle quality improvement methodology with qualitative inquiry allowed efficient development of role-specific service standards and quick evaluation of their implementation. This unique approach for improving healthcare service quality and identifying barriers to providing individual feedback may be useful to organizations navigating a more value- and consumer-driven healthcare market.
Education for tourism: a perspective article
Authors: Airey David
Published: June 2019

Purpose

This paper aims to provide a short scholarly review on the development of tourism education that contributes to the celebration of 75 years of the Tourism Review.

Design/methodology/approach

The paper is based on selective literature on the topic.

Findings

Tourism education has developed into a major field of study in the period since the Second World War, but after a long period of growth, it now faces some important challenges.

Research limitations/implications

The paper is based on selective literature.

Practical implications

The review provides a brief overview of the development and challenges for tourism education.

Social implications

The review provides a brief overview of the development and challenges for tourism education.

Originality/value

The paper provides a brief overview of developments.
Vertical seismic profiling using distributed acoustic sensing with scatter‐enhanced fibre‐optic cable at the Cu–Au New Afton porphyry deposit, British Columbia, Canada
Authors: Bellefleur Gilles , Schetselaar Ernst , Wade Devin , White Don , Enkin Randolph , Schmitt Doug R.
Published: June 2019

Wireline logs and vertical seismic profile data were acquired in two boreholes intersecting the main mineralized zone at the Cu–Au New Afton porphyry deposit, Canada, with the objectives of imaging lithological contacts, fault zones that may have acted as conduits that channelled the mineralization, and alteration zones. Log data provide physical rock properties for the main lithologies and alteration zones. Calliper logs reveal many faults and caved‐in zones generally indicating rocks with low integrity at the borehole wall. The preponderance of these zones, as indicated by the logs, suggests that their response may dominate the seismic‐reflection wavefield. Outside fault zones, compressional and shear‐wave velocities exhibit significant variability due to porosity, the heterogeneity of volcanic fragmental rocks and alteration. Distributed acoustic sensing was used to acquire vertical seismic profiling data in the two boreholes surveyed with wireline logs. Straight and helically wound fibre‐optic cables housed standard fibres and a fibre engineered to increase the intensity of backscattering at the distributed acoustic sensing interrogator. Standard and engineered optical fibres placed in the two boreholes were daisy‐chained together to form two 5‐km‐long continuous fibres that were interrogated at once with two interrogators. A new generation of interrogator connected to the engineered fibres provided field data with lower noise level and higher signal‐to‐noise ratio. These data with higher signal‐to‐noise ratio from straight fibre‐optic cable were processed and used for depth imaging. Depth images benefitted from new migration weights that account for the directional sensitivity of the straight fibre‐optic cable and limit the extent of migration artefacts. Migration results show several reflectors with shallow dips to the northwest, some explained by faults intersecting the surveyed boreholes. The main sub‐vertical lithological and alteration contacts at New Afton generated downgoing reflections that were not considered in the migration.
The impact of different clay minerals on the anisotropy of clay matrix in shale
Authors: Sayers Colin M. , den Boer Lennert D.
Published: June 2019

Although clay is composed of disconnected anisotropic clay platelets, many rock physics models treat the clay platelets in shale as interconnected. However, the clay matrix in shales can be modelled as anisotropic clay platelets embedded within a soft isotropic interplatelet region, allowing the influence of disconnected clay platelets on the elastic properties of the clay matrix to be analysed. In this model, properties of the interplatelet region are governed by its effective bulk and shear moduli, whereas the effective properties of the clay platelets are governed by their volume fraction, aspect ratio and elastic stiffness tensor. Together, these parameters implicitly account for variations in clay and fluid properties, as well as fluid saturation. Elastic stiffnesses of clay platelets are obtained from the literature, including both experimental measurements and first‐principles calculations of the full anisotropic (monoclinic or triclinic) elastic stiffness tensors of layered silicates. These published elastic stiffness tensors are used to compile a database of equivalent transverse isotropic elastic stiffness tensors, and other physical properties, for eight common varieties of layered silicates. Clay matrix anisotropy is then investigated by examining the influence of these different elastic stiffnesses, and of varying model parameters, upon the effective transverse isotropic elastic stiffness tensor of the clay matrix. The relationship between the different clay minerals and their associated anisotropy parameters is studied, and their impact on the resulting anisotropy of the clay matrix is analysed.
Gender destinies: assigning gender in Disorders of Sex Development‐Intersex clinics
Authors: Timmermans Stefan , Yang Ashelee , Gardner Melissa , Keegan Catherine E. , Yashar Beverly M. , Fechner Patricia Y. , Shnorhavorian Margarett , Vilain Eric , Siminoff Laura A. , Sandberg David E.
Published: June 2019

Based on audio recordings of consultations in three U.S. paediatric multidisciplinary Disorders of Sex Development‐Intersex clinics, we examine the process of gender assignment of children with “atypical” genitalia. Rather than fully determined by the presence of biological sex traits, the gender assignment discussion hinges on how clinician and parent collaboratively imagine different aspects of what constitutes being a gendered person. They orient towards the potential for sexual intimacy, fertility, gender dysphoria, stigma, and gonadal cancer risk. While these futures remain inherently uncertain, clinicians and parents plan to mobilise gender socialisation and medical interventions to render their choice of gender a self‐fulfilling prophecy. Gender destinies capture that the child always had a specific, innate gender awaiting discovery, and presumes a project for medical and social monitoring, intervention, correction, and optimisation.
BmSd gene regulates the silkworm wing size by affecting the Hippo pathway
Authors: Yin Jin , Zhang Jing , Li Tao , Sun Xia , Qin Sheng , Hou Cheng‐Xiang , Zhang Guo‐Zheng , Li Mu‐Wang
Published: June 2019

Insect wings are developed from the wing disc during metamorphosis. Bombyx mori, a model lepidopteran insect, loses flight ability after long‐term domestication from the wild silkworm, Bombyx mandarina. The mw mutant (u11 strain) shows minute wings compared to wild type (e.g., p50 strain) wings. RNA sequencing analysis previously revealed differential Hippo‐pathway‐related gene expression between the u11 and p50 strains. The Hippo pathway is an evolutionarily conserved signaling cascade that controls organ size during development in animals. In this study, the function of BmSd which has been characterized as one of the Hippo‐pathway‐related genes was analyzed for silkworm wing development. We found that mats, warts, and hippo expression levels were higher in u11 compared to p50 wing discs. BmSd (scalloped) expression, which encodes a prominent transcriptional partner to Yorkie (Yki), gradually decreased during the wandering stage in u11, but exhibited the opposite expression pattern in p50. When BmSd was knocked down by small interfering RNA during the wandering stage in the p50 strain, 57.9% of the individuals showed minute wings. Additionally, ex, kibra, and wingless expression levels decreased in the BmSd knockdown mutant. Further, BmSd deletion mediated by clustered regularly interspaced short palindromic repeats (CRISPR) / CRISPR‐associated protein 9 induced 50% of individuals with minute wings, a phenotype similar to the mw mutant. This result demonstrates that BmSd plays pivotal roles in silkworm wing development. Our results show that the Hippo signaling pathway participates and plays crucial roles in the regulation of silkworm wing development, and our findings provide a basis for further research on B. mori wing development.
Temporary employment and voice behavior: the role of self‐efficacy and political savvy
Authors: Qian Xiaoye , Li Qian , Song Yijia , Wang Jue
Published: June 2019

This study examines whether and how different employment arrangements (temporary versus regular employment) may affect employees’ voice behaviors (promotive and prohibitive voice). Using a two‐wave panel design, we collected data from a sample of 355 employees from 66 teams in four Chinese organizations. The results show that temporary employees engage in fewer promotive voice behaviors than their regular counterparts, but there is no difference between the two groups when it comes to prohibitive voice. Moreover, self‐efficacy is a mediator between employment status and voice behaviors, and political savvy acts as a moderator. For employees with high political savvy, the negative relationships between temporary employment status and promotive and prohibitive voice is attenuated.
Contextual embeddedness of careers: female “nonsurvivors” and their gendered relational context
Authors: Afiouni Fida , Karam Charlotte M. , Makarem Yasmeen
Published: June 2019

Our aim is to contribute to a better understanding of the contextual embeddedness of women's careers. To do this, we leverage feminist relational theory (a) to understand the relational context of women's careers in Lebanon, with a particular focus on working‐self and career investments, and (b) to trace the gendered power dynamics of career investments in the relational context of work. Through examining the narratives of 24 Lebanese female “nonsurvivors” (i.e., used to work but are not currently engaged in paid work), our findings paint a complex and nuanced picture of different relational contexts. Represented on a continuum ranging from minimally conducive for women's careers to contexts that are incrementally more conducive, the differences between these contexts are unpacked through drawing attention to the gendered power dynamics shaping women's (dis)connection with their working self, the perceived (mis)alignment of others, and the career investments that they make. Our contribution lies in augmenting our understanding of the contextual embeddedness of women's careers by demonstrating the theoretical and practical utility of bringing a deeper feminist analysis to understand the relational context of work.
Castrato Singers as Composers: The Case of Luigi Marchesi's London Sets of Ariette (1788‐9)
Authors: Laterza Marilena
Published: June 2019

As well as being one of the outstanding castrati of the eighteenth century, Luigi Marchesi was also an occasional composer, particularly during his London years (1788‐90). This article examines Marchesi's only published compositions – two sets of ariettas for voice and piano or harp – reconstructing their context and reception, and analysing their texts and music, in order not only to give a more complete picture of the singer but also to investigate both the approach of late eighteenth‐century opera singers to musical creation and the previously neglected subject of vocal chamber music on Italian texts in late eighteenth‐century London.
Indicators of cigarette smoking dependence and relapse in former smokers who vape compared with those who do not: findings from the 2016 International Tobacco Control Four Country Smoking and Vaping Survey
Authors: McNeill Ann , Driezen Pete , Hitchman Sara C. , Cummings K. Michael , Fong Geoffrey T. , Borland Ron
Published: June 2019

Background and Aims

It has been proposed that many smokers switch to vaping because their nicotine addiction makes this their only viable route out of smoking. We compared indicators of prior and current cigarette smoking dependence and of relapse in former smokers who were daily users of nicotine vaping products (‘vapers’) or who were not vaping at the time of survey (‘non‐vapers’).

Design

Cross‐sectional survey‐based comparison between vaping and non‐vaping former smokers, including a weighted logistic regression of vaping status onto predictor variables, adjusting for covariates specified below.

Setting

United States, Canada, Australia and England.

Participants

A total of 1070 people aged 18+ years from the 2016 International Tobacco Control (ITC) Four Country Smoking and Vaping Wave 1 Survey who reported having ever been daily smokers but who stopped less than 2 years ago and who were currently vapers or non‐vapers.

Measurements

Dependent variable was current vaping status. Predictor variables were self‐reported: (1) smoking within 5 minutes of waking and usual daily cigarette consumption, both assessed retrospectively; (2) current perceived addiction to smoking, urges to smoke and confidence in staying quit. Covariates: country, sample sources, sex, age group, ethnicity, income, education, current nicotine replacement therapy use and time since quitting.

Findings

Vapers were more likely than non‐vapers to report: (1) having smoked within 5 minutes of waking [34.3 versus 15.9%, adjusted odds ratio (aOR) = 3.74, 95% confidence interval (CI) = 1.99, 7.03), χ2 = 16.92, P < 0.001]; having smoked > 10 cigarettes/day (74.4 versus 47.2%, aOR = 4.39, 95% CI = 2.22, 8.68), χ2 = 18.18, P < 0.001); (2) perceiving themselves to be still very addicted to smoking (41.3 versus 26.2%, aOR = 2.89, 95% CI = 1.58, 5.30, χ2 = 11.87, P < 0.001) and feeling extremely confident about staying quit (62.1 versus 36.6%, aOR = 3.22, 95% CI = 1.86, 5.59, χ2 = 17.36, P < 0.001). Vapers were not more likely to report any urges to smoke than non‐vapers (27.7 versus 38.8%, aOR = 0.86, 95% CI = 0.44, 1.65, χ2 = 0.21, P = 0.643).

Conclusions

While former smokers who currently vape nicotine daily report higher levels of cigarette smoking dependence pre‐ and post‐cessation compared with former smokers who are current non‐vapers, they report greater confidence in staying quit and similar strength of urges to smoke.
Waste to energy:
Authors: AHMANN CHLOE
Published: June 2019

If it had been built, the Fairfield Renewable Energy Project would have been the largest trash incinerator in the United States, burning 4,000 tons of waste each day in late‐industrial Baltimore. When it was first proposed, two discourses of renewal coalesced around the project. One was propagated by technocrats who argued incineration should be regulated as a renewable technology. Another emerged among working‐class whites who hoped the plant would reinvigorate their ailing economy. Both discourses hinged on comparisons with the past and maneuvers between futures near and far, gaining ground through subjunctive politics. Recast in this light, both technocratic dreams and local narratives of waste, race, and decline betray a deep ambivalence about the sorts of futures that seem plausible within a geography of “undesirables.” [subjunctive politics, waste, race, renewal, future, uncertainty, environment, Baltimore, United States]
Progress towards near‐zero 90‐day mortality: 388 consecutive hepatectomies over a 16‐year period
Authors: Liu Jianliang , Reid Jessica , Leopardi Lisa , Edwards Suzanne , Trochsler Markus , Maddern Guy
Published: June 2019

Background

Hepatectomy has been the gold standard procedure for curative treatment of benign and malignant hepatobiliary lesions for over a century. The aim of this study is to report on the 16‐year experience of a single institution.

Methods

All patients admitted to The Queen Elizabeth Hospital, South Australia, for a hepatectomy between 2001 and 2016 were included in this audit. Data regarding demographics, tumour type and operative outcomes were prospectively collected. To identify trends, patients were divided into four periods, each spanning 4 years (Period 1 = 2001–2004, Period 2 = 2005–2008, Period 3 = 2009–2012 and Period 4 = 2012–2016).

Results

Between 2001 and 2016, 388 consecutive patients (230 men; 158 women; mean age ± SD = 63.7 ± 13.0 years) underwent hepatectomy. From Periods 2 to 4, complex cases increased from 14.4% to 18.9%, and there was an increase in mean duration of operation time from 187.0 ± 60.6 to 217.3 ± 78.7 min. Length of hospitalization decreased from Periods 1 to 4 (12.2 ± 9.2 to 8.1 ± 5.6 days). Intraoperative and 90‐day mortalities were 0.5% and 2.3%, respectively. Length of stay, morbidity and 90‐day mortality were significantly affected by mass of resection.

Conclusion

Hepatectomy can be safely performed in a specialized Western centre with low mortality. Advances in health care have facilitated in shorter duration of hospitalization despite more frequent complex resections, operating on older patients and patients with worse American Society of Anesthesiologists scores, without increasing rates of mortality.
Compositional study of bronze vessels from the Derveni tombs of central Macedonia of the fourth century bce using energy‐dispersive micro‐X‐ray fluorescence (EDμXRF) spectrometry
Authors: Katsifas C. S. , Touloumzidou A. , Zachariadis G. A.
Published: June 2019

The chemical composition of 61 copper alloy vessels was studied non‐invasively by energy‐dispersive micro‐X‐ray fluorescence (EDμXRF) spectrometry. The vessels were found in five tombs (A, B, D, Z and H) at Derveni in central Macedonia, Greece, which belong to the cemetery of the ancient city of Lete. The tombs are dated to the last quarter of the fourth century bce. The opulence of the numerous grave offerings denotes the high social status of the deceased within Macedonian society. The material under study was divided into two main groups according to their appearance and use. The first group included 44 vessels with a golden appearance for use in banquets; the second group consisted of 17 dark vessels for domestic use. The aim of this research was to study the vessels' technology according to their chemical composition. Both golden and dark vessels consisted of a binary Cu‐Sn alloy and a slight amount of impurities (Fe, Ni, Zn, Pb, As, Co, Sb, Ag, Ti). It is probable that during construction the ancient metalsmiths were taking into account criteria such as the desired appearance, cost of metals, future use and physical properties such as resistance to corrosion. Banquet vessels had a consistent chemical composition in all their different parts compared with those for domestic use. The only chemical element used systemically for alloying purposes, except Sn, was Pb in order to improve the castability of the bases and handles of the vessels. The study provides additional information about the metalworking of bronzes in central Macedonia in the fourth century bce, as well as about the access Macedonian metalworkers had at the time to the raw materials for such use.
Oxycodone concentrations in the central nervous system and cerebrospinal fluid after epidural administration to the pregnant ewe
Authors: Kinnunen Mari , Kokki Hannu , Hautajärvi Heidi , Lantto Juulia , Räsänen Juha , Voipio Hanna‐Marja , Kokki Merja
Published: June 2019

The main sites of the analgesic action of oxycodone are the brain and spinal cord. The present study describes the concentrations of oxycodone and its metabolites in the brain and spinal cord after epidural administration to the ewe. Twenty pregnant ewes undergoing laparotomy were randomized into two groups to receive epidural oxycodone: infusion group (n = 10, 0.1 mg·kg−1 bolus followed by continuous infusion of 0.05 mg·kg−1·h−1 for five days) or repeated boluses group (n = 10, 0.2 + 2x0.1 mg·kg−1 bolus followed by a 0.2 mg·kg−1 bolus every 12 hours for five days). After five days of oxycodone administration, arterial blood samples were collected, the sheep were killed, and a CSF sample and tissue samples from the cortex, thalamus, cerebellum and spinal cord were obtained for the quantification of oxycodone and its main metabolites. The median plasma and CSF concentrations of oxycodone were 9.0 and 14.2 ng·mL−1 after infusion and 0.4 and 1.1 ng·mL−1 after repeated boluses. In the infusion group, the cortex, thalamus and cerebellum oxycodone concentrations were 4‐8 times higher and in the spinal cord 1310 times higher than in plasma. In the repeated boluses group, brain tissue concentrations were similar in the three areas, and in the spinal cord were 720 times higher than in plasma. Oxymorphone was the main metabolite detected, which accumulated in the brain and spinal cord tissue. In conclusion, first, accumulation of oxycodone and oxymorphone in the CNS was observed, and second, high spinal cord concentrations suggest that epidural oxycodone may provide segmental analgesia.
Cutting red tape to manage public health threats: An ethical dilemma of expediting antibiotic drug innovation
Authors: Munthe Christian , Nijsingh Niels
Published: June 2019

Antibiotic resistance, arising when bacteria develop defences against antibiotics, is creating a public health threat of massive proportions. This raises challenging questions for standard notions in bioethics when suitable policy is to be characterized and justified. We examine the particular proposal of expediting innovation of new antibiotics by cutting various forms of regulatory ‘red tape’ in the standard system for the clinical introduction of new drugs. We find strong principled reasons in favour of such a lowering of the ethical standards of research and the clinical introduction of new antibiotic formulas. However, this support is undermined by pragmatic challenges owing to expected responses from stakeholders, creating uncertainty about which policies could actually be effectively implemented. We describe an underlying dilemma on how to rationally justify compromises between ideal ethical justification and pragmatic risks that needs to be further addressed in this light. We suggest a solution to this dilemma related to proposals of expediting antibiotic drug innovation.
Health ethics and Indigenous ethnocide
Authors: Matthews Richard
Published: June 2019

In colonial societies such as Canada the implications of colonialism and ethnocide (or cultural genocide) for ethical decision‐making are ill‐understood yet have profound implications in health ethics and other spheres. They combine to shape racism in health care in ways, sometimes obvious, more often subtle, that are inadequately understood and often wholly unnoticed. Along with overt experiences of interpersonal racism, Indigenous people with health care needs are confronted by systemic racism in the shaping of institutional structures, hospital policies and in resource allocation decisions. Above all, racism is a function of state law – of the unilateral imposition of the settler society law on Indigenous communities. Indeed, the laws, including health laws, are social determinants of the ill‐health of Indigenous peoples. This article describes the problem of Indigenous ethnocide and explores its ethical implications. It thereby problematizes the role of law in health ethics.
On Null Hypotheses in Survival Analysis
Authors: Stensrud Mats J. , Røysland Kjetil , Ryalen Pål C.
Published: June 2019

The conventional nonparametric tests in survival analysis, such as the log-rank test, assess the null hypothesis that the hazards are equal at all times. However, hazards are hard to interpret causally, and other null hypotheses are more relevant in many scenarios with survival outcomes. To allow for a wider range of null hypotheses, we present a generic approach to define test statistics. This approach utilizes the fact that a wide range of common parameters in survival analysis can be expressed as solutions of differential equations. Thereby, we can test hypotheses based on survival parameters that solve differential equations driven by cumulative hazards, and it is easy to implement the tests on a computer. We present simulations, suggesting that our tests perform well for several hypotheses in a range of scenarios. As an illustration, we apply our tests to evaluate the effect of adjuvant chemotherapies in patients with colon cancer, using data from a randomized controlled trial.
Model Selection for G-Estimation of Dynamic Treatment Regimes
Authors: Wallace Michael P. , Moodie Erica E. M. , Stephens David A.
Published: June 2019

Dynamic treatment regimes (DTRs) aim to formalize personalized medicine by tailoring treatment decisions to individual patient characteristics. G-estimation for DTR identification targets the parameters of a structural nested mean model, known as the blip function, from which the optimal DTR is derived. Despite its potential, G-estimation has not seen widespread use in the literature, owing in part to its often complex presentation and implementation, but also due to the necessity for correct specification of the blip. Using a quadratic approximation approach inspired by iteratively reweighted least squares, we derive a quasi-likelihood function for G-estimation within the DTR framework, and show how it can be used to form an information criterion for blip model selection. We outline the theoretical properties of this model selection criterion and demonstrate its application in a variety of simulation studies as well as in data from the Sequenced Treatment Alternatives to Relieve Depression study.
Semiparametric mixed‐scale models using shared Bayesian forests
Authors: Linero Antonio R. , Sinha Debajyoti , Lipsitz Stuart R.
Published: June 2019

This paper demonstrates the advantages of sharing information about unknown features of covariates across multiple model components in various nonparametric regression problems including multivariate, heteroscedastic, and semicontinuous responses. In this paper, we present a methodology which allows for information to be shared nonparametrically across various model components using Bayesian sum‐of‐tree models. Our simulation results demonstrate that sharing of information across related model components is often very beneficial, particularly in sparse high‐dimensional problems in which variable selection must be conducted. We illustrate our methodology by analyzing medical expenditure data from the Medical Expenditure Panel Survey (MEPS). To facilitate the Bayesian nonparametric regression analysis, we develop two novel models for analyzing the MEPS data using Bayesian additive regression trees—a heteroskedastic log‐normal hurdle model with a “shrink‐toward‐homoskedasticity” prior and a gamma hurdle model.
Stand‐alone intrathecal central nervous system (CNS) prophylaxis provide unclear benefit in reducing CNS relapse risk in elderly DLBCL patients treated with R‐CHOP and is associated increased infection‐related toxicity
Authors: Eyre Toby A. , Kirkwood Amy A. , Wolf Julia , Hildyard Catherine , Mercer Carolyn , Plaschkes Hannah , Griffith John , Fields Paul , Gunawan Arief , Oliver Rebecca , Booth Stephen , Martinez‐Calle Nicolas , McMillan Andrew , Bishton Mark , Fox Christopher P. , Collins Graham P. , Hatton Chris S. R.
Published: June 2019

Central nervous system (CNS) relapse following R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) occurs in 2–5% of patents with diffuse large B‐cell lymphoma (DLBCL). Many patients aged ≥70 years are unsuitable for high‐dose methotrexate (HDMTX) prophylaxis and therefore often receive stand‐alone intrathecal prophylaxis. The CNS international prognostic index (CNS‐IPI) is a clinical CNS relapse risk score that has not specifically been validated in elderly patients. The value of CNS prophylaxis in patients aged ≥70 years remains uncertain. Data on 690 consecutively R‐CHOP‐treated DLBCL patients aged ≥70 years were collected across 8 UK centres (2009–2018). CNS prophylaxis was administered per physician preference. Median age was 77·2 years and median follow‐up was 2·8 years. CNS‐IPI was 1–3 in 60·1%, 4 in 23·8%, 5 in 13·0% and 6 in 3·3%. Renal and/or adrenal (R/A) involvement occurred in 8·8%. Two‐year overall CNS relapse incidence was 2·6% and according to CNS‐IPI, 1–3:0·8%, 4:3·6%, 5:3·8% and 6:21·8%. Two‐year CNS relapse incidence for R/A was 10·0%. When excluding HDMTX (n = 31) patients, there remained no change in unadjusted/adjusted CNS relapse for intrathecal prophylaxis effect according to CNS‐IPI. CNS‐IPI is valid in elderly R‐CHOP‐treated DLBCL patients, with the highest risk in those with CNS‐IPI 6 and R/A involvement. We observed no clear benefit for stand‐alone intrathecal prophylaxis but observed an independent increased risk of infection‐related admission during R‐CHOP when intrathecal prophylaxis was administered.
Is real per capita state personal income stationary? New nonlinear, asymmetric panel‐data evidence
Authors: Emirmahmutoglu Furkan , Gupta Rangan , Miller Stephen M. , Omay Tolga
Published: June 2019

This paper re‐examines the stochastic properties of U.S. state real per capita personal income, using new panel unit‐root procedures. The new developments incorporate non‐linearity, asymmetry, and cross‐sectional correlation within panel‐data estimation. Including nonlinearity and asymmetry finds that 43 states exhibit stationary real per capita personal income whereas including only nonlinearity produces 42 states that exhibit stationarity. Stated differently, we find that two states exhibit nonstationary real per capita personal income when considering nonlinearity, asymmetry, and cross‐sectional dependence.
The Tajik Basin: A composite record of sedimentary basin evolution in response to tectonics in the Pamir
Authors: Chapman James B. , Carrapa Barbara , DeCelles Peter G. , Worthington James , Mancin Nicoletta , Cobianchi Miriam , Stoica Marius , Wang Xin , Gadoev Mustafo , Oimahmadov Ilhomjon
Published: June 2019

Investigation of a >6‐km‐thick succession of Cretaceous to Cenozoic sedimentary rocks in the Tajik Basin reveals that this depocentre consists of three stacked basin systems that are interpreted to reflect different mechanisms of subsidence associated with tectonics in the Pamir Mountains: a Lower to mid‐Cretaceous succession, an Upper Cretaceous–Lower Eocene succession and an Eocene–Neogene succession. The Lower to mid‐Cretaceous succession consists of fluvial deposits that were primarily derived from the Triassic Karakul–Mazar subduction–accretion complex in the northern Pamir. This succession is characterized by a convex‐up (accelerating) subsidence curve, thickens towards the Pamir and is interpreted as a retroarc foreland basin system associated with northward subduction of Tethyan oceanic lithosphere. The Upper Cretaceous to early Eocene succession consists of fine‐grained, marginal marine and sabkha deposits. The succession is characterized by a concave‐up subsidence curve. Regionally extensive limestone beds in the succession are consistent with late stage thermal relaxation and relative sea‐level rise following lithospheric extension, potentially in response to Tethyan slab rollback/foundering. The Upper Cretaceous–early Eocene succession is capped by a middle Eocene to early Oligocene (ca. 50–30 Ma) disconformity, which is interpreted to record the passage of a flexural forebulge. The disconformity is represented by a depositional hiatus, which is 10–30 Myr younger than estimates for the initiation of India–Asia collision and overlaps in age with the start of prograde metamorphism recorded in the Pamir gneiss domes. Overlying the disconformity, a >4‐km‐thick upper Eocene–Neogene succession displays a classic, coarsening upward unroofing sequence characterized by accelerating subsidence, which is interpreted as a retro‐foreland basin associated with crustal thickening of the Pamir during India–Asia collision. Thus, the Tajik Basin provides an example of a long‐lived composite basin in a retrowedge position that displays a sensitivity to plate margin processes. Subsidence, sediment accumulation and basin‐forming mechanisms are influenced by subduction dynamics, including periods of slab‐shallowing and retreat.
Identification of candidates for driver oncogenes in scirrhous‐type gastric cancer cell lines
Authors: Sai Eirin , Miwa Yoshiyuki , Takeyama Reina , Kojima Shinya , Ueno Toshihide , Yashiro Masakazu , Seto Yasuyuki , Mano Hiroyuki
Published: June 2019

Scirrhous‐type gastric cancer (SGC) is one of the most intractable cancer subtypes in humans, and its therapeutic targets have been rarely identified to date. Exploration of somatic mutations in the SGC genome with the next‐generation sequencers has been hampered by markedly increased fibrous tissues. Thus, SGC cell lines may be useful resources for searching for novel oncogenes. Here we have conducted whole exome sequencing and RNA sequencing on 2 SGC cell lines, OCUM‐8 and OCUM‐9. Interestingly, most of the mutations thus identified have not been reported. In OCUM‐8 cells, a novel CD44‐IGF1R fusion gene is discovered, the protein product of which ligates the amino‐terminus of CD44 to the transmembrane and tyrosine‐kinase domains of IGF1R. Furthermore, both CD44 and IGF1R are markedly amplified in the OCUM‐8 genome and abundantly expressed. CD44‐IGF1R has a transforming ability, and the suppression of its kinase activity leads to rapid cell death of OCUM‐8. To the best of our knowledge, this is the first report describing the transforming activity of IGF1R fusion genes. However, OCUM‐9 seems to possess multiple oncogenic events in its genome. In particular, a novel BORCS5‐ETV6 fusion gene is identified in the OCUM‐9 genome. BORCS5‐ETV6 possesses oncogenic activity, and suppression of its message partially inhibits cell growth. Prevalence of these novel fusion genes among SGC awaits further investigation, but we validate the significance of cell lines as appropriate reagents for detailed genomic analyses of SGC.
Small lung tumor biopsy samples are feasible for high quality targeted next generation sequencing
Authors: Kage Hidenori , Kohsaka Shinji , Shinozaki‐Ushiku Aya , Hiraishi Yoshihisa , Sato Jiro , Nagayama Kazuhiro , Ushiku Tetsuo , Takai Daiya , Nakajima Jun , Miyagawa Kiyoshi , Aburatani Hiroyuki , Mano Hiroyuki , Nagase Takahide
Published: June 2019

Next‐generation sequencing (NGS) has been implemented in clinical oncology to analyze multiple genes and to guide therapy. In patients with advanced lung cancer, small biopsies such as computed tomography‐guided needle biopsy (CTNB), endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) and transbronchial biopsy (TBB) are less invasive and are preferable to resection to make a pathological diagnosis. However, the quality of DNA/RNA and NGS from small lung tumor biopsy samples is unknown. Between April 2017 and March 2018, 107 consecutive samples were obtained from thoracic tumors or metastatic sites for targeted NGS analysis. Fifteen samples were obtained through CTNB, 11 through EBUS‐TBNA, 11 through TBB and 70 through surgical resection. All samples were formalin‐fixed and paraffin‐embedded. DNA and RNA quality was measured using the ddCq method and the percentage of RNA fragments above 200 nucleotides (DV200), respectively. Our custommade probes were designed to capture exon sequences of 464 cancer‐related genes and transcripts of 463 genes. DNA and RNA yield from the 3 biopsy methods were similar, and less than the yield obtained from resected samples. The quality of DNA and RNA was similar across all methods. Overall, 12 of 15 CTNB samples (80%), all 11 EBUS‐TBNA samples, and 9 of 11 TBB samples (82%) underwent successful NGS assays from DNA. NGS analysis from RNA was successful in all 12 CTNB samples, 9 of 11 EBUS‐TBNA samples (82%), and 8 of 11 TBB samples (73%). CTNB, EBUS‐TBNA and TBB mostly resulted in adequate DNA and RNA quality and enabled high‐quality targeted NGS analysis.
Aspirin inhibits inflammation and scar formation in the injury tendon healing through regulating JNK/STAT‐3 signalling pathway
Authors: Wang Yunjiao , He Gang , Tang Hong , Shi Youxing , Kang Xia , Lyu Jingtong , Zhu Min , Zhou Mei , Yang Mingyu , Mu Miduo , Chen Wan , Zhou Binghua , Zhang Jiqiang , Tang Kanglai
Published: June 2019

Objectively

Tendinopathy is a common problem in sports medicine which can lead to severe morbidity. Aspirin, as the classical representative of non‐steroidal anti‐inflammatory drugs (NSAIDs) for its anti‐inflammatory and analgesic actions, has been commonly used in treating tendinopathy. While its treatment effects on injury tendon healing are lacking, illuminating the underlying mechanism may provide scientific basis for clinical treatment.

Materials and methods

Firstly, we used immunohistochemistry and qRT‐PCR to detect changes in CD14, CD206, iNOS, IL‐6, IL‐10, MMP‐3, TIMP‐3, Col‐1a1, biglycan, Comp, Fibronectin, TGF‐β1，ACAN，EGR‐1 and FMOD. Next, Western blot was used to measure the protein levels (IL‐6, IL‐10, TGF‐β1, COMP, TIMP‐3, STAT‐3/P‐STAT‐3 and JNK/P‐JNK) in TSCs. Then, migration and proliferation of TSCs were measured through wound healing test and BrdU staining. Finally, the mechanical properties of injury tendon were detected.

Results

After aspirin treatment, the inflammation and scar formation in injury tendon were significantly inhibited by aspirin. Still, tendon's ECM was positively balanced. Increasing migration and proliferation ability of TSCs induced by IL‐1β were significantly reversed. JNK/STAT‐3 signalling pathway participated in the process above. In addition, biomechanical properties of injury tendon were significantly improved.

Conclusions

Taken together, the findings suggested that aspirin inhibited inflammation and scar formation via regulation of JNK/STAT‐3 signalling and decreased rerupture risk of injury tendon. Aspirin could be an ideal therapeutic strategy in tendon injury healing.