bluuebunny/crossref_metadata_2025 huggingface dataset:
Bias in two-sample Mendelian randomization when using heritable covariable-adjusted summary associations
Authors: Hartwig Fernando Pires , Tilling Kate , Smith George Davey , Lawlor Deborah A , Borges Maria Carolina
Published: October 2019

Background

Two-sample Mendelian randomization (MR) allows the use of freely accessible summary association results from genome-wide association studies (GWAS) to estimate causal effects of modifiable exposures on outcomes. Some GWAS adjust for heritable covariables in an attempt to estimate direct effects of genetic variants on the trait of interest. One, both or neither of the exposure GWAS and outcome GWAS may have been adjusted for covariables.

Methods

We performed a simulation study comprising different scenarios that could motivate covariable adjustment in a GWAS and analysed real data to assess the influence of using covariable-adjusted summary association results in two-sample MR.

Results

In the absence of residual confounding between exposure and covariable, between exposure and outcome, and between covariable and outcome, using covariable-adjusted summary associations for two-sample MR eliminated bias due to horizontal pleiotropy. However, covariable adjustment led to bias in the presence of residual confounding (especially between the covariable and the outcome), even in the absence of horizontal pleiotropy (when the genetic variants would be valid instruments without covariable adjustment). In an analysis using real data from the Genetic Investigation of ANthropometric Traits (GIANT) consortium and UK Biobank, the causal effect estimate of waist circumference on blood pressure changed direction upon adjustment of waist circumference for body mass index.

Conclusions

Our findings indicate that using covariable-adjusted summary associations in MR should generally be avoided. When that is not possible, careful consideration of the causal relationships underlying the data (including potentially unmeasured confounders) is required to direct sensitivity analyses and interpret results with appropriate caution.

Key messages

Summary genetic associations from large genome-wide associations studies (GWAS) have been increasingly used in two-sample Mendelian randomization (MR) analyses.

Many GWAS adjust for heritable covariates in an attempt to estimate direct genetic effects on the trait of interest.

In an extensive simulation study, we demonstrate that using covariable-adjusted summary associations may bias MR analyses.

The bias largely depends on the underlying causal structure, specially the presence of unmeasured common causes between the covariable and the outcome.

Our findings indicate that using covariable-adjusted summary associations in MR should generally be avoided.
Hypoxia-mediated regulation of mitochondrial transcription factors: Implications for hypertensive renal physiology
Authors: Natarajan Bhargavi , Arige Vikas , Khan Abrar A. , Reddy S. Santosh , Santhoshkumar Rashmi , Sagar B. K. Chandrasekhar , Barthwal Manoj K. , Mahapatra Nitish R.
Published: October 2019

Kidneys have a high resting metabolic rate and low tissue partial pressure of oxygen due to enhanced mitochondrial oxygen consumption and ATP production for active solute transport. Enhanced mitochondrial activity leads to progressive hypoxia from the renal cortex to renal medulla. Renal tubulointerstitial hypoxia (TiH) is severe in hypertensive rats due to increased sodium reabsorption within their nephrons. Additionally, these rats display increased energy demand and therefore, require healthy mitochondria for adequate salt reabsorption. Hence, we sought to study the regulation of mitochondrial biogenesis and expression of mitochondrial transcription factors (mtTFs, viz. Tfam, Tfb1m and Tfb2m) during hypoxic conditions and in rodent models of genetic hypertension. We report that the expressions of HIF-1α (hypoxia inducible factor-1α), PGC-1α (peroxisome proliferator activated receptor-γ co-activator-1α), mtTFs and OXPHOS proteins are elevated in hypertensive rats as compared to their normotensive counterparts. Additionally, studies in cultured kidney cells show that acute hypoxia augments the expression of these genes. We also observe a positive correlation between HIF-1α and mtTFs transcripts in human tissues. Furthermore, we report for the first time to our knowledge, that HIF-1α binds to promoters of Tfam, Tfb1m and Tfb2m genes and augments their promoter activities in NRK52e cells subjected to acute hypoxia. Taken together, this study suggests that acute hypoxia may enhance mitochondrial function to meet the energy demand in renal tubular epithelial cells and in young/pre-hypertensive SHR kidneys.

Translational Statement

Our results suggest that tubulointerstitial hypoxia (TiH) prevailing in prehypertensive rats augments the expression of mitochondrial transcription factors and proteins of electron transport chain. Moreover, previous reports indicate that ATP synthesis in these rats are elevated. Thus, our study provides insights into the molecular mechanism of such enhanced mitochondrial function. We propose that during early stages of kidney diseases (marked by mild TiH) an enhancement of mitochondrial function via stimulation of HIF-1α/PGC-1α production may delay renal tubular damage.
FFPEcap-seq: a method for sequencing capped RNAs in formalin-fixed paraffin-embedded samples
Authors: Vahrenkamp Jeffery M. , Szczotka Kathryn , Dodson Mark K. , Jarboe Elke A. , Soisson Andrew P. , Gertz Jason
Published: October 2019

The majority of clinical cancer specimens are preserved as formalin-fixed paraffin-embedded (FFPE) samples. For clinical molecular tests to have wide-reaching impact, they must be applicable to FFPE material. Accurate quantitative measurements of RNA derived from FFPE specimens is challenging because of low yields and high amounts of degradation. Here, we present FFPEcap-seq, a method specifically designed for sequencing capped 5′ ends of RNA derived from FFPE samples. FFPEcap-seq combines enzymatic enrichment of 5′ capped RNAs with template switching to create sequencing libraries. We find that FFPEcap-seq can faithfully capture mRNA expression levels in FFPE specimens while also detecting enhancer RNAs that arise from distal regulatory regions. FFPEcap-seq is a fast and straightforward method for making high-quality 5′ end RNA-seq libraries from FFPE-derived RNA.
Confined-walking mode for an elliptical polarized undulator and its application
Authors: Zou Ying , Zhang Qinglei , Zhang Jidong , Zhuo Jingwei , Jiang Geyang , Liu Ping , Jiang Bocheng , Zheng Lifang , Zhou Qiaogen , Yin Lixin , Wang Yong , Tai Renzhong
Published: October 2019

Elliptical polarized undulators (EPUs) are broadly used in the soft X-ray energy range. They have the advantage of providing photons with both varied energy and polarization through adjustments to the value of the gap and/or shift magnet arrays in an undulator. Yet these adjustments may create a disturbance on the stability of the electron beam in a storage ring. To correct such a disturbance, it is necessary to establish a feed-forward table of key nodes in the gap-shift-defined two-dimensional parameter space. Such a table can only be scanned during machine-study time. For a free-walking mode, whereby an undulator is allowed to manoeuvre in the whole gap-shift space, all the key nodes need to be scanned at the expense of a large amount of machine-study time. This will greatly delay the employment of a full-polarization capable undulator (especially circularly polarized). By analyzing data-collecting patterns of user experiments, this paper defines a reduced set of key nodes in gap-shift parameter space, with the number of key nodes to be scanned for feed-forwarding scaled down to one-third of the original; and introduces a new walking mode for EPUs: confined-walking mode, whereby the undulator is manoeuvred only within the reduced set of key nodes. Such a mode is firstly realized on the EPUs at the DREAMLINE beamline at Shanghai Synchrotron Radiation Facility (SSRF). Under confined-walking mode, the undulator movements are stable and there is no obvious disturbance to the electron beam with the feed-forward system in operation. Successful experiments have been carried out using the circularly polarized light obtained via the new walking mode. This mode is expected to be applied to future EPUs at SSRF with the increasing requirements for various polarization modes.
Regional difference analyzing and prediction model building for Chinese wine consumers’ sensory preference
Authors: Chu Xiaoquan , Li Yue , Xie Yimeng , Tian Dong , Mu Weisong
Published: October 2019

Purpose

The purpose of this paper is to provide further insight into Chinese wine consumers’ preference, grasp the regional sensory preference differences of China and build up a predictive model for wine consumers’ sensory preferences.

Design/methodology/approach

The study involved 3,421 Chinese wine consumers in the survey. Classified statistics were conducted to excavate regional differences of wine consumers’ sensory preferences. By analyzing influencing factors, prediction models for consumers’ sensory attribute preferences were constructed on the basis of multivariate disorder logistic regression method.

Findings

Empirical research showed that the wine with the following sensory attributes was the most preferred by Chinese consumers: dry red, refreshing and soft taste, still type, moderate aroma degree and mellow aroma, and sweet wine was also popular. Consumers’ preference varied from region to region. The proposed predicting method of the study realized more than 70 percent accuracy when conducting prediction for color, sweetness, aroma type and flavor preferences.

Social implications

By shedding light on the latest sensory attribute preferences of Chinese wine consumers, this study will help wine industry participants conduct market segmentation based on the diversification of consumers’ preferences. The wine enterprises can gain guidance from the results to conduct market positioning, adjust strategies and provide specific production for target wine consumers.

Originality/value

Based on the actual situation of Chinese wine market, this study defines sensory attribute indexes of wine from the perspective of wine consumers and presents the most recent comprehensive research on the sensory preferences of Chinese wine consumers through a nationwide survey.
Coexistence of continuity and change in institutional work
Authors: Topal Cagri
Published: October 2019

Purpose

The purpose of this paper is to answer the question of how continuity and change coexist in the work of institutional actors who can combine maintenance, disruption and/or creation. Past studies mention this coexistence without an explanation.

Design/methodology/approach

The paper develops a perspective through literature review.

Findings

Institutional actors are both socialized into the norm-oriented space of continuity and maintenance through their reciprocal relations and associated social knowledge and roles and disciplined into the goal-oriented space of change and disruption/creation through their power relations and associated expert discourse and subject positions. Their institutional existence indicates a particular combination of reciprocity and power and thus their work includes changing degrees of maintenance, disruption and creation, depending on the nature of this combination.

Research limitations/implications

The paper points out research directions on the relational conditions of the actors, which facilitate or constrain their work toward institutional continuity or change.

Practical implications

Organizations whose concern is to continue the existing practices in a stable environment should emphasize reciprocal relations whereas organizations whose concern is to change those practices for more effectiveness in a dynamic environment should emphasize power relations. Also, too much emphasis on either relations leads to inflexibility or instability.

Originality/value

The paper provides an explanation on the sources of coexistence of continuity and change in institutional work. It also contributes to the discussions on contingency of institutions, resistance productive of institutional change, reflexivity of institutional actors and intersubjective construction of institutional work.
Data schemas for multiple hazards, exposure and vulnerability
Authors: Murnane Richard J. , Allegri Giovanni , Bushi Alphonce , Dabbeek Jamal , de Moel Hans , Duncan Melanie , Fraser Stuart , Galasso Carmine , Giovando Cristiano , Henshaw Paul , Horsburgh Kevin , Huyck Charles , Jenkins Susanna , Johnson Cassidy , Kamihanda Godson , Kijazi Justice , Kikwasi Wilberforce , Kombe Wilbard , Loughlin Susan , Løvholt Finn , Masanja Alex , Mbongoni Gabriel , Minas Stelios , Msabi Michael , Msechu Maruvuko , Mtongori Habiba , Nadim Farrokh , O’Hara Mhairi , Pagani Marco , Phillips Emma , Rossetto Tiziana , Rudari Roberto , Sangana Peter , Silva Vitor , Twigg John , Uhinga Guido , Verrucci Enrica
Published: October 2019

Purpose

Using risk-related data often require a significant amount of upfront work to collect, extract and transform data. In addition, the lack of a consistent data structure hinders the development of tools that can be used with more than one set of data. The purpose of this paper is to report on an effort to solve these problems through the development of extensible, internally consistent schemas for risk-related data.

Design/methodology/approach

The consortia coordinated their efforts so the hazard, exposure and vulnerability schemas are compatible. Hazard data can be provided as either event footprints or stochastic catalogs. Exposure classes include buildings, infrastructure, agriculture, livestock, forestry and socio-economic data. The vulnerability component includes fragility and vulnerability functions and indicators for physical and social vulnerability. The schemas also provide the ability to define uncertainties and allow the scoring of vulnerability data for relevance and quality.

Findings

As a proof of concept, the schemas were populated with data for Tanzania and with exposure data for several other countries.

Research limitations/implications

The data schema and data exploration tool are open source and, if widely accepted, could become widely used by practitioners.

Practical implications

A single set of hazard, exposure and vulnerability schemas will not fit all purposes. Tools will be needed to transform the data into other formats.

Originality/value

This paper describes extensible, internally consistent, multi-hazard, exposure and vulnerability schemas that can be used to store disaster risk-related data and a data exploration tool that promotes data discovery and use.
The relationship between TQM and SMEs’ performance
Authors: Hilman Haim , Ali Gamal Abdualmajed , Gorondutse Abdullahi Hassan
Published: October 2019

Purpose

The purpose of this paper is to empirically test the association between total quality management (TQM) and small and medium enterprises’ (SMEs) performance. In particular, it examines whether organizational culture (OC) has a mediating effect on the TQM–SME performance relationship.

Design/methodology/approach

The conceptual model for this study was developed based on the literature review of TQM, OC and SME performance. As the research framework, a self-administered questionnaire was used to collect data from managers/owners of SMEs in the Riyadh, Mecca and Eastern regions of the Kingdom of Saudi Arabia. The instrument was evaluated for its validity and reliability. A structural equation model was designed to examine the relationships, using PLS 3.0.

Findings

Statistical outcomes add to the literature through displaying a positive direct effect of TQM and OC on SMEs’ performance, and a significant and positive indirect effect of TQM on SMEs’ performance through OC.

Research limitations/implications

The quantitative cross-sectional research design investigated a sample of manufacturing SMEs. Future research could use qualitative techniques or a case study approach for further information analysis.

Practical implications

The findings of this research provide insights into SMEs’ owners/managers in today’s dynamic manufacturing environment, focussing on TQM as a mechanism for improving their performance. The results can help SMEs by providing guidance on OC, because of its effect on the successful implementation of TQM, therefore improving the level of performance.

Originality/value

The research extends the literature of TQM with a comprehensive understanding of TQM from the perspective of SMEs in Saudi Arabia. It fills the gap in empirical studies that investigate the joint effect of TQM and OC on SMEs’ performance. This paper highlights the theoretical contribution and managerial implications as well as making recommendations for future research.
Integrating performance measurement, system dynamics, and problem-solving methods
Authors: Irfani Dian Prama , Wibisono Dermawan , Basri Mursyid Hasan
Published: October 2019

Purpose

Transport logistics systems in companies with additional public service roles are complex and could benefit from new approaches to performance management. Existing approaches tend to be fragmented; thus, the purpose of this paper is to integrate balanced performance measures, a dynamics model, and the problem-solving method into a new model.

Design/methodology/approach

An integrated framework is developed by reviewing literature and synthesising attributes of performance measurement systems, system dynamics and problem-solving methods. The framework is then applied to a multiple-role company’s sea transportation system. The study uses statistical methods to identify performance indicators, management interviews with document study to develop a dynamics model, and simulation methods to formulate an improvement plan.

Findings

The performance measurement design stage allowed for the identification of balanced, aligned performance indicators, while the system dynamics model illuminated the impact of the system components’ interrelationships on performance output. The problem-solving method allowed for analysis of system performance, identification of constraints and formulation of a performance improvement plan.

Practical implications

This framework can help transport logistics system stakeholders in multiple-role companies avoid silo thinking, misaligned performance objectives, local optima and short-term solutions.

Originality/value

This study contributes to the existing body of research by introducing a novel framework integrating performance measurement, system dynamics and the problem-solving method. It also addresses a theoretical gap by showing how interconnecting components of sea transportation systems affect transport logistics performance.
Development of a risk disclosure index and its application in an Indian context
Authors: Shivaani MV , Jain P.K. , Yadav Surendra S.
Published: October 2019

Purpose

This paper aims to gauge the quality of risk disclosure in 3,872 annual reports of Indian corporates, using a risk disclosure index (RDI) developed to capture both quality and quantity of risk disclosures.

Design/methodology/approach

Focussing on 69 risk items, the paper uses manual textual analysis and scores risk items using an ordinal scale, as opposed to the general practice of using a dichotomous scale.

Findings

The average risk index is low, but greater in the post-recession period than in the pre-recession period. Most disclosures are qualitative, both backward and forward-looking, and exhibit a negative tone. In addition, company age and industry sector have a significant impact on disclosure levels.

Research limitations/implications

The choice and weighting of semantic qualities used to construct RDIs used in disclosure studies are inherently subjective. This exploratory study uses univariate analysis and does not explore the reasons for poor disclosure.

Practical implications

In addition to its usefulness for investors and companies’ management, the findings of non-compliance with certain mandatory provisions and a low average RDI is particularly relevant for policymakers and regulatory bodies.

Originality/value

Development of a summary measure/RDI that is novel in its differential weighting of the semantic qualities pertaining to quantification, time-orientation and tone. Further, it serves as an exploratory study about risk disclosure practices in the Indian context that reveals notable differences from findings of previous risk disclosure research. Moreover, the study examines the relationship between firms’ age and risk disclosure levels, a largely ignored aspect in disclosure research.
Building capacity in indigenous governance: Comparing the Australian and American experiences
Authors: Hendrix Burke A. , Delaney Danielle , Witmer Richard C. , Moran Mark , Sanders Will , Ganter Elizabeth
Published: October 2019

This paper compares key aspects of governance structures for Indigenous populations in the United States and Australia. The paper focuses on policy coordination and administration, in particular the nodes of decision‐making in the two countries in relation to government contracting and accountability. The U.S. approach to funding Indigenous organizations stems from the 1975 Indian Self‐Determination and Education Act and its subsequent expansions. Through the development of contracting into permanent compacting via block grants, this approach builds established nodes of Indigenous government and facilitates whole‐of‐government coherence at the level of the American Indian tribe. The U.S. approach seems correlated with better performance and may lighten bureaucratic loads over the long term. The Australian model, on the other hand, seeks to create whole‐of‐government coherence through top‐down financial accountability in a way that hampers the development of Indigenous political capacity. The paper traces the development of these practices through time and illustrates how they contribute to the fragmentation rather than growth of Indigenous political capacities. It suggests ways the Australian model could be improved even in the absence of fundamental reform by drawing on the contracting‐to‐compacting framework of longstanding U.S. practices.
Clinical effectiveness and safety of additional administration of tacrolimus in rheumatoid arthritis patients with an inadequate response to abatacept: A retrospective cohort study
Authors: Suzuki Mochihito , Takahashi Nobunori , Kida Daihei , Hirano Yuji , Kato Takefumi , Yabe Yuichiro , Oguchi Takeshi , Fujibayashi Takayoshi , Hayashi Masatoshi , Asai Shuji , Ishiguro Naoki , Kojima Toshihisa
Published: October 2019

Objective

Abatacept (ABT) demonstrates good clinical efficacy and retention in rheumatoid arthritis (RA) patients. However, no rescue treatment option against inadequate response to ABT exists. Since tacrolimus (TAC) and ABT suppress T lymphocytes via different mechanisms and a combination of these agents could potentially be effective, this study aimed to examine the efficacy and safety of add‐on TAC therapy in RA patients with inadequate response to ABT.

Methods

Of 550 patients treated with ABT and registered in a Japanese multicenter registry, 25 consecutive patients who underwent add‐on TAC therapy and were followed for longer than 24 weeks were included in this study.

Results

Mean patient age was 67.0 years, disease duration was 16.2 years, and duration of ABT treatment was 1.2 years at the initiation of add‐on TAC therapy. Mean TAC dose was 1.2 mg/d at baseline and 1.6 mg/d at week 24. Mean Disease Activity Score of 28 joints – erythrocyte sedimentation rate was significantly improved at week 24 (3.35) relative to baseline (4.97). The proportion of patients who achieved low disease activity or remission was 40.0%, and the European League Against Rheumatism moderate or good response was 72.0%. ABT retention rate was 92.0% at week 24, as calculated by Kaplan‐Meier analysis. Only one patient discontinued add‐on TAC therapy due to an adverse event (itching sensation).

Conclusion

This is the first report describing the efficacy and safety profile of add‐on TAC therapy with a focus on RA patients with inadequate response to ABT. Our findings suggest that add‐on TAC therapy is a worthwhile complementary treatment option in daily clinical practice.
In utero exposure to antidepressant medication and neonatal and child outcomes: a systematic review
Authors: Fitton C. A. , Steiner M. F. C. , Aucott L. , Pell J. P. , Mackay D. F. , Fleming M. , McLay J. S.
Published: October 2019

Objective

The aim of this study is to systematically review published studies, reporting outcomes to offspring following in utero exposure to antidepressant medications, which used an untreated depressed comparison group.

Methods

OVID, Scopus, EBSCO Collections, the Cochrane Library and Web of Science databases were searched for relevant publications published between January 1950 and May 2018 and a total of 188 potentially eligible studies were identified.

Results

Following review, 16 primary studies were eligible for inclusion. Antidepressant exposure was associated with an increased risk of lower gestational age, preterm birth, but not low birthweight or being small for gestational age compared to untreated depression. There is some evidence that congenital defects are associated with antidepressant use, particularly between cardiac defects and paroxetine use. There is conflicting evidence regarding neurodevelopment in offspring, with some reports of increased incidence of autistic spectrum disorders and depression, but also reports of no problems when measuring emotional symptoms, peer problems, conduct problems and hyperactivity‐inattention scores.

Conclusion

When compared with an untreated depressed group, antidepressant exposure was associated with adverse outcomes at birth, while there is insufficient data to determine whether the association between antidepressants and congenital defects or developmental disorders is a true association. However, although we compared treated vs. untreated depression there still may be residual confounding as an untreated depressed group is likely to have less severe depression.
Propranolol is a mechanism‐based inhibitor of CYP2D and CYP2D6 in humanized CYP2D6‐transgenic mice: Effects on activity and drug responses
Authors: Tolledo Edgor Cole , Miksys Sharon , Gonzalez Frank J. , Tyndale Rachel F.
Published: October 2019

Background and Purpose

Genetics and drug interactions contribute to large interindividual variation in human CYP2D6 activity. Here, we have characterized propranolol inhibition of human and mouse CYP2D using transgenic (TG) mice, which express both mouse CYP2D and human CYP2D6, and wild‐type (WT) mice. Our purpose was to develop a method for in vivo manipulation of CYP2D6 enzyme activity which could be used to investigate the role of CYP2D6 in drug‐induced behaviours.

Experimental Approach

Dextromethorphan metabolism to dextrorphan was used to measure CYP2D activity and to characterize propranolol inhibition in vitro and in vivo. Effects of propranolol pretreatment (24 hr) on serum levels of the CYP2D6 substrate haloperidol and haloperidol‐induced catalepsy were also studied.

Key Results

Dextrorphan formation velocity in vitro was threefold higher in liver microsomes of TG compared to WT mice. Propranolol acted as a mechanism‐based inhibitor (MBI), inactivating CYP2D in liver microsomes from TG and WT mice, and humans. Pretreatment (24 hr) of TG and WT mice with 20 mg·kg−1 intraperitoneal propranolol reduced dextrorphan formation in vivo and by liver microsomes in vitro. Serum haloperidol levels and catalepsy were increased.

Conclusions and Implications

Propranolol was a potent MBI of dextrorphan formation in liver microsomes from TG and WT mice, and humans. The inhibition parameters in TG overlapped with those in WT mice and in humans. Inhibition of CYP2D with propranolol in vivo in TG and WT mice altered drug responses, allowing further investigation of variations in CYP2D6 on drug interactions and drug responses.
Establishment and characterization of a novel neuroendocrine carcinoma cell line derived from a human ascending colon tumor
Authors: Shinji Seiichi , Sasaki Norihiko , Yamada Takeshi , Koizumi Michihiro , Ohta Ryo , Matsuda Akihisa , Yokoyama Yasuyuki , Takahashi Goro , Hotta Masahiro , Hara Keisuke , Takeda Kohki , Ueda Koji , Kuriyama Sho , Ishiwata Toshiyuki , Ueda Yoshibumi , Murakami Takashi , Kanazawa Yoshikazu , Yoshida Hiroshi
Published: October 2019

The incidence of rare neuroendocrine tumors (NET) is rapidly increasing. Neuroendocrine carcinoma (NEC) is a NET with poorly differentiated histological features, high proliferative properties and associated poor prognoses. As these carcinomas are so rare and, thus, affect only a small number of patients allowing for few cell lines to be derived from patient biopsies, the histological, immunohistochemical, and clinical characteristics associated with colorectal NEC and NEC in other organs have yet to be clearly defined. Herein, we describe the establishment of a novel NEC cell line (SS‐2) derived from a tumor resection of the ascending colon from a 59‐year‐old Japanese woman. The histological, electron microscopic and immunohistochemical features of chromogranin A (CgA) as well as confirmation of synaptophysin positivity in this tumor were typical of those commonly observed in surgically resected colorectal NEC. Further, the Ki‐67 labeling index of the resected tumor was >20% and, thus, the tumor was diagnosed as an NEC of the ascending colon. The SS‐2 cell line maintained characteristic features to those of the resected tumor, which were further retained following implantation into subcutaneous tissues of nude mice. Additionally, when SS‐2 cells were seeded into ultra‐low attachment plates, they formed spheres that expressed higher levels of the cancer stem cell (CSC) marker CD133 compared to SS‐2 cells cultured under adherent conditions. SS‐2 cells may, therefore, contribute to the current knowledge on midgut NEC biological function while providing a novel platform for examining the effects of colorectal NEC drugs, including CSC.
New Zealand adult ocular trauma study: A 10‐year national review of 332 418 cases of ocular injury in adults aged 18 to 99 years
Authors: Wallace Henry B. , Ferguson Reid A. , Sung Justin , McKelvie James
Published: October 2019

Importance

Ocular injury is a common, preventable cause of temporary and permanent disability.

Background

The current study evaluates the nationwide incidence, demographics and visual outcomes of adults with ocular injury in New Zealand.

Design

Nationwide retrospective review.

Participants

New Zealanders aged 18‐99 years from 2007 to 2016 with ocular injury requiring assessment by a registered medical practitioner.

Methods

New Zealand national and regional datasets were used to evaluate population‐level statistics over a 10‐year period. Visual and clinical outcome data were assessed using a random sample of 150 patients from a tertiary hospital.

Main Outcome Measures

Annual incidence, aetiology, demographics, injury location, visual outcomes, protective eyewear use, surgical intervention and follow‐up.

Results

A total of 332 418 adult eye injuries were recorded nationally. The annual incidence of eye injury was 1007/100 000 population/year. Patients were predominantly male (76.1%), of New Zealand‐European ethnicity (74.6%) and aged between 20 and 29 years (21.1%). The most common mechanism of injury was “struck by object” (55.4%). Injuries occurred most commonly at home (48.4%), followed by commercial (15%) and industrial locations (13.8%). Injuries were more common in rural regions (P < .001). Protective eyewear use was reported in 6% of cases (n = 9, 95% confidence interval = 3.2‐11.0). Most ocular injuries were managed exclusively in primary care (70.5%).

Conclusions and Relevance

Adults with the highest risk of ocular injury are rural males aged 20 to 29 years. Protective eyewear use is uncommon in adults presenting with ocular injury and the majority of injuries are managed in primary care. Promotion of appropriate injury prevention strategies is an important public health message.
New insights into the rational use of HCV+ organs worldwide
Authors: Morales Jose M. , Sawinski Deirdre
Published: October 2019

Hepatitis C (HCV) is a worldwide health problem. Effective therapies for HCV infection, coupled with an increase in deceased donors due to the opioid epidemic, have led to the broader availability and the use of HCV‐infected donor organs, including HCV nucleic acid test‐positive (NAT+) donors in HCV‐negative recipients. In this review, we discuss the prevalence of HCV infection, trends in the use of HCV‐infected donors, and outcomes for those who receive HCV‐seropositive or HCV NAT+ donor organs. We discuss management considerations such as hepatitis B reactivation, selection of the optimal direct‐acting antiviral regimen, and potential complications. We also present a framework for the rational use of HCV‐infected donor organs in the future.
Moving from Evidence‐Light to Evidence‐Based Practice: Randomized Control Trials in Family Law
Authors: Danser Renee , Faith‐Slaker April
Published: October 2019

In a resource‐constrained environment, such as the access to justice field, it is critical to develop better knowledge about effective and efficient service delivery. This article discusses the need for more rigorous evaluation and research in the field, both in order to better reach individuals with legal needs and to maximize court resources. Various evaluation methodologies will be explained, along with examples of current randomized control trial studies being conducted at the Harvard Access to Justice Lab.
Effect of walking on depression prevalence for diabetes using information communication technology: Prospective study
Authors: Yamashita Tomoko , Yamashita Kazuhiko , Sato Mitsuru , Takase Yoshimasa
Published: October 2019

Aim

This study aimed to evaluate the prevention of diabetic depression and its impact on medical costs through the implementation of a step count monitoring system using information and communication technology.

Methods

This study carried out a longitudinal analysis of a prospective cohort. A total of 296 participants were enrolled in the intervention group and 882 participants in the control group. The participants in the intervention group were provided with pedometers, which each participant was asked to scan using devices stationed throughout the city. Activity data were stored in real time by a cloud system. The experiment lasted 30 months.

Results

None of the diabetes patients in the intervention group was diagnosed with depression during the study period, compared with 4.09% in the control group. Thus, the intervention suppressed the increase in medical costs for the people who did not develop depression in the diabetic group.

Conclusions

The prevalence rate of depression among the participants with diabetes was lowered significantly. The medical costs of the participants who did not have diabetes were also reduced by implementing the step count monitoring system with information and communication technology. This shows that the use of an information and communication technology pedometer system can have favorable effects in terms of preventing depression in diabetes patients and further benefits for non‐diabetic people. Geriatr Gerontol Int 2019; 19: 1147–1152.
A retrospective review of cutaneous lymphoma in Botswana
Authors: Rodriguez Olaf , Sowash Madeleine , Mosojane Karen I. , Ralefala Tlotlo , Grover Surbhi , Haun Paul , Kovarik Carrie , Williams Victoria L.
Published: October 2019

Background

Primary cutaneous lymphoma (PCL) represents a heterogeneous collection of non‐Hodgkin lymphomas originating in the skin. Our study describes the clinical and histological findings of cutaneous lymphoma within Botswana to expand the paucity of data on this rare disease in sub‐Saharan Africa.

Methods

We conducted a retrospective review from the dermatology clinic at Princess Marina Hospital (Gaborone, Botswana) of patients evaluated by skin biopsy for cutaneous lymphoma between 2008 and 2017. Patients with initial diagnostic suspicion for cutaneous lymphoma had biopsies re‐reviewed by experienced dermatopathologists and were given a final diagnosis of either (i) cutaneous lymphoma, (ii) atypical lymphocytic infiltrate (ALI), or (iii) a reactive cutaneous process.

Results

Thirty‐eight cases were identified with a mean age of 50.0 years and a male:female (M:F) ratio of 13:6. Final diagnoses included: 27 cases of cutaneous lymphoma, eight cases of ALI, and three cases of reactive cutaneous processes. Subtypes of cutaneous lymphoma diagnosed included: mycosis fungoides (MF) (81.5%), plasmablastic lymphoma (7.4%), Epstein‐Barr virus‐positive T‐cell lymphoma (3.7%), subcutaneous panniculitis‐like T‐cell lymphoma (3.7%), and peripheral T‐cell lymphoma, not otherwise specified (3.7%). The most common immunohistochemical staining profile in MF cases was CD8 predominance over CD4.

Conclusions

Primary cutaneous lymphoma causes significant morbidity and mortality globally. Given the limited resources in sub‐Saharan Africa, it is essential to educate providers on the manifestations and histology of PCL. This study is an important step towards understanding the demographics, clinical presentation, histologic features, and mortality of patients diagnosed with PCL in Botswana and similar low‐resource settings.
Quo Vadis? A study of the state and development of coaching in Portugal
Authors: Fontes Andrea , Dello Russo Silvia
Published: October 2019

Although coaching programs are becoming increasingly widespread across the world, in some countries this practice has only been introduced in recent years. To better understand the coaching context in one such country, Portugal, and to identify future trends and directions, a survey was carried out among 255 coaches via social media, using the snowball approach. We aimed to uncover the predominant background of coaches and whether this is associated with features of their practice, most notably their theoretical positions and the use of any tools or instruments. We also explored aspects related to the coachees’ most recurrent needs for coaching, and the positive and negative effects that coaches observe more frequently. The results of this descriptive study reveal, among other things, that there is room for more theory‐driven methodologies that can be replicated and standardized and, therefore, ultimately contribute to coaching professionalization.
Dual‐purpose Guzerá cattle exhibit high dairy performance under heat stress
Authors: Santana Mário L. , Pereira Rodrigo J. , Bignardi Annaiza B. , El Faro Lenira , Pires Maria F. Á. , Andrade Ricardo G. , Perez Bruno C. , Bruneli Frank A. T. , Peixoto Maria G. C. D.
Published: October 2019

The present study evaluated the heat stress response pattern of dual‐purpose Guzerá cattle for test‐day (TD) milk yield records of first lactation and estimated genetic parameters and trends related to heat stress. A total of 31,435 TD records from 4,486 first lactations of Guzerá cows, collected between 1986 and 2012, were analysed. Two random regression models considered days in milk (DIM) and/or temperature × humidity‐dependent (THI) covariate. Impacts of −0.037, −0.019 and −0.006 kg/day/THI for initial and intermediate stages of lactation were observed when considering the mean maximum daily temperature and humidity to calculate THI. Heritability estimates ranged from 0.16 to 0.35 throughout lactation and THI values, suggesting the possibility to expect gains from selection for such trait. The variable trajectory of breeding values for dual‐purpose Guzerá sires in response to changes in THI values confirms that the genotype × environment interaction due to heat stress can have some effect on TD milk yield. Despite the high dairy performance of Guzerá cattle under heat stress, estimated genetic trends showed a progressive reduction in heat tolerance. Therefore, new strategies should be adopted to prevent negative impacts of heat stress over milk production in Guzerá animals in future.
The desire for physiological pacing: Are we there yet?
Authors: Kaye Gerry
Published: October 2019

Pacing is a well established therapy for bradycardia support and certain types of heart failure. Despite technological advances the optimal pacing lead position remains controversial. Right ventricular pacing, particularly apical has been the site of choice but the induction of abnormal cardiac depolarization and the recognition of an increased risk of impairment of left ventricular systolic function, heart failure and mortality has driven a desire for a true physiological pacing system. A number of different lead positions have been determined and of these His bundle pacing appears to most closely mimic normal ventricular conduction. This article reviews the background to the development of physiological pacing, evaluates historical data for right ventricular pacing and the basis for change and new lead positions.
Contrasting feeding and agonistic behaviour of two blenny species on a small and remote island in the equatorial Atlantic Ocean
Authors: Quimbayo Juan P. , Giglio Vinicius J. , Ferreira Carlos E. L. , Fraga Alana , Nunes José A. C. C. , Mendes Thiago C.
Published: October 2019

We investigated the feeding rates, agonistic behaviour and diet of two blenny species,Entomacrodus vomerinusandOphioblennius trinitatis, by direct observation and gut content analysis. Both species coexist in small and shallow tide pools in the St Peter and St Paul's Archipelago, equatorial North Atlantic Ocean. The feeding rate ofO. trinitatiswasc. 55%higher thanE. vomerinus. On the other hand, agonistic rate ofO. trinitatiswas negatively related to body size, whereas inE. vomerinuswas positively related. Both species showed a high diet overlap, in which detritus was the most important food item (86% inO. trinitatisand 80% inE. vomerinus). Feeding activity was more intense during the morning forO. trinitatisbut afternoon forE. vomerinus. These behavioural observations support the importance of temporal feeding partitioning as the main strategy allowing species co‐existence in tide pools.
Commercial fisheries in a mega unregulated floodplain river: Assessment of the most favourable hydrological conditions for its preservation
Authors: Rabuffetti Ana Pia , Espínola Luis A. , Abrial Elie , Amsler Mario L. , Blettler Martin C. M. , Eurich Maria F. , Eberle Eliana G.
Published: October 2019

This paper deals with the hydrological variability effects on the primary commercial fish species inhabiting the main channel and the floodplain of the large Paraná River in its middle reaches in Argentina. Analysing more than eight decades (1935–2016) of information on the most frequent and abundant commercial species in conjunction with hydrological levels and temperature, our results show that spring–summer floods of a certain magnitude (c. 6 m) and durations (> 80 days) are crucial for sustaining commercial fisheries. Moreover, the frequency of these floods was modulated by the decadal climatic fluctuations that have occurred over the past 100 years in the Paraná Basin. An insight into the probable incidence of some anthropogenic influences is also provided.
Does meal‐time insulin dosing based on fat‐protein counting give positive results in postprandial glycaemic profile after a high protein‐fat meal in adolescents with type 1 diabetes: a randomised controlled trial
Authors: Kaya N. , Kurtoğlu S. , Gökmen Özel H.
Published: October 2019

Background

The present study investigated the effects of fat‐protein (CFP) counting in addition to carbohydrate (CARB) counting for calculating prandial insulin dosage on blood glucose profile in patients with type 1 diabetes (T1D) on basal‐bolus insulin therapy.

Methods

In this single centre, cross‐over, randomised, controlled study, control meal (SM: standard meal using a carbohydrate counting method) and three test meals (HPM: high protein meal using a carbohydrate counting method; HPFM‐a: high protein‐fat meal using a carbohydrate counting method; HPFM‐b: high protein‐fat meal using a carbohydrate and fat‐protein counting method) were compared on postprandial early (0–120 min), late (120–240 min) and total (0–240 min) glucose response in 30 patients with T1D, aged 16–18 years.

Results

The glucose levels of 0–90 min did not change after different meal consumptions (P > 0.05), whereas 120–240 min glucose levels were higher after HPFM‐a consumption compared to HPFM‐b consumption (P < 0.05). There were no significant differences between meals with respect to the early postprandial glucose response (0–120 min) (P = 0.405). In late response (120–240 min), HPFM‐b [area under the curve (AUC) = 20 609 (582) mg dL−1 × dk] was significantly lower than SM [AUC = 24 092 (9015) mg dL−1 × dk], HPM [AUC = 24 072 (5853) mg dL−1 × dk] and HPFM‐a [AUC = 25 986 (6979) mg dL−1 × dk] (P = 0.032).

Conclusions

Meal‐related insulin dosing based on carbohydrate plus fat/protein counting has given positive results in the postprandial glycaemic profile as a result of lower postprandial glycaemic levels compared to conventional carbohydrate counting in patients with T1D after a high protein‐fat meal.
Language and embodiment—Or the cognitive benefits of abstract representations
Authors: Kompa Nikola A.
Published: October 2019

Cognition, it is often heard nowadays, is embodied. My concern is with embodied accounts of language comprehension. First, the basic idea will be outlined and some of the evidence that has been put forward in their favor will be examined. Second, their empiricist heritage and their conception of abstract ideas will be discussed. Third, an objection will be raised according to which embodied accounts underestimate the cognitive functions language fulfills. The remainder of the paper will be devoted to arguing for the cognitive indispensability of non‐embodied, abstract representations by highlighting some of the cognitive benefits they bestow upon us.
Burning mouth syndrome: a review
Authors: Currie C.C. , Jääskeläinen S.K.
Published: October 2019

Burning mouth syndrome (BMS) is characterised by chronic daily intraoral burning or dysaesthetic sensations, often combined with taste alterations and dry mouth, which cannot be explained by any clinically evident oral or systemic pathology. Around 1%–3.7% of the population suffer from the condition, with highest prevalence figures in menopausal and post‐menopausal women up to 12%–18%, and BMS can have a significant impact on quality of life. BMS still seems to be poorly understood in terms of aetiology, although there is growing evidence from multiple lines of research that neuropathic changes at different levels of the neuraxis are critically involved in its pathogenesis. With accurate neurophysiological, psychophysical, neuropathological and neuroimaging methods, clinically homogenous BMS can be subdivided into three major types of neuropathic pain, that may coexist. According to some preliminary evidence, efficacy of different treatments may depend on the neurophysiological subtype of BMS. However, as these subtypes cannot be distinguished with standard clinical examination and detailed diagnostic methods are not routinely applied in the clinic nor in the treatment trials, management of BMS remains challenging, with little high quality evidence available. This review aims to address the current evidence and understanding in relation to aetiology, diagnosis and management of BMS.
The problems of life after death
Authors: Atkinson Thomas Charles
Published: October 2019

In this paper, I state the what I call the “problem of life after death,” survey some responses to it, and highlight a way in which the field might progress. Put simply, the problem of life after death is the problem of reconciling the fact that when we die, we will be totally destroyed with the belief that we will exist again at some time after our deaths. Contemporary solutions to the problem have focussed on the “logical” version of this problem. I highlight that the problem would be better thought of as an evidential problem.