bluuebunny/crossref_metadata_2025 huggingface dataset:
Open Design 3D-Printable Adjustable Micropipette that meets ISO Standard for Accuracy
Authors: Brennan Martin D. , Bokhari Fahad F. , Eddington David T.
Published: February 2017

Scientific communities are drawn to the open source model as an increasingly utilitarian method to produce and share work. Initially used as a means to develop freely available software, open source projects have been applied to hardware including scientific tools. Increasing convenience of 3D printing has fueled the proliferation of open labware projects aiming to develop and share designs for scientific tools that can be produced in-house as cheap alternatives to commercial products. We present our design of a micropipette that is assembled from 3D-printable parts and some hardware that works by actuating a disposable syringe to a user adjustable limit. Graduations on the syringe are used to accurately adjust the set point to the desired volume. Our open design printed micropipette is assessed in comparison to a commercial pipette and meets ISO 8655 standards.
Stroke-associated pattern of gene expression previously identified by machine-learning is diagnostically robust in an independent patient population
Authors: O’Connell Grant C. , Chantler Paul D. , Barr Taura L.
Published: February 2017

Purpose

Our group recently identified a ten gene pattern of differential expression in peripheral blood which may have utility for detection of stroke. The objective of this study was to assess the diagnostic capacity and temporal stability of this stroke-associated transcriptional signature in an independent patient population.

Methods

Publically available whole blood microarray data generated from 23 ischemic stroke patients at 3, 5, and 24 hours post-symptom onset, along with 23 cardiovascular disease controls were obtained via the National Center for Biotechnology Information Gene Expression Omnibus. Expression levels of the ten candidate genes were extracted, compared between groups, and evaluated for their discriminatory ability at each time point.

Results

We observed a largely identical pattern of differential expression between stroke patients and controls across the ten candidate genes as reported in our prior work. Furthermore, the coordinate expression levels of the ten candidate genes were able to discriminate between stroke patients and controls with levels of sensitivity and specificity upwards of 90% across all three time points.

Conclusions

These findings confirm the diagnostic robustness of the previously identified pattern of differential expression in independent patient population, and further suggest that it is temporally stable over the first 24 hours of stroke pathology.
Niche construction in evolutionary theory: the construction of an academic niche?
Authors: Gupta Manan , Prasad N. G. , Dey Sutirth , Joshi Amitabh , Vidya T. N. C.
Published: February 2017

In recent years, fairly far-reaching claims have been repeatedly made about how niche construction, the modification by organisms of their environment, and that of other organisms, represents a vastly neglected phenomenon in ecological and evolutionary thought. The proponents of this view claim that the niche construction perspective greatly expands the scope of standard evolutionary theory and that niche construction deserves to be treated as a significant evolutionary process in its own right, almost at par with natural selection. Claims have also been advanced about how niche construction theory represents a substantial extension to, and re-orientation of, standard evolutionary theory, which is criticized as being narrowly gene-centric and ignoring the rich complexity and reciprocity of organism-environment interactions. We examine these claims in some detail and show that they do not stand up to scrutiny. We suggest that the manner in which niche construction theory is sought to be pushed in the literature is better viewed as an exercise in academic niche construction whereby, through incessant repetition of largely untenable claims, and the deployment of rhetorically appealing but logically dubious analogies, a receptive climate for a certain sub-discipline is sought to be manufactured within the scientific community. We see this as an unfortunate, but perhaps inevitable, nascent post-truth tendency within science.
NIMA-related kinase 1 (NEK1) regulates the localization and phosphorylation of α-Adducin (ADD1) and Myosin X (MYO10) during meiosis
Authors: Brieño-Enríquez Miguel A. , Moak Stefannie L. , Holloway J. Kim , Cohen Paula E.
Published: February 2017

Summary statement:

NEK1 kinase regulates the assembly and function of the meiosis I spindle by phosphorylating α-adducin (ADD1) and thereby facilitating its interaction with Myosin X (MYO10)

NIMA-related kinase 1 (NEK1) is a serine/threonine and tyrosine kinase that is highly expressed in mammalian germ cells. Mutations inNek1induce anemia, polycystic kidney and infertility. In this study we evaluated the role of NEK1 in meiotic spindle formation in both male and female gametes. Our results show that the lack of NEK1 provokes an abnormal organization of the meiosis I spindle characterized by elongated and/or multipolar spindles, and abnormal chromosome congression. The aberrant spindle structure is concomitant with the disruption in localization and protein levels of myosin X (MYO10) and α-adducin (ADD1), both of which are implicated in the regulation of spindle formation during mitosis. Interaction of ADD1 with MYO10 is dependent on phosphorylation, whereby phosphorylation of ADD1 enables its binding to MYO10 on mitotic spindles. Reduction in ADD1 protein in NEK1 mutant mice is associated with hyperphosphorylation of ADD1, thereby preventing the interaction with MYO10 during meiotic spindle formation. Our results reveal a novel regulatory role for NEK1 in the regulation of spindle architecture and function during meiosis.
Cas9-Assisted Targeting of CHromosome segments (CATCH) for targeted nanopore sequencing and optical genome mapping
Authors: Gabrieli Tslil , Sharim Hila , Michaeli Yael , Ebenstein Yuval
Published: February 2017

Variations in the genetic code, from single point mutations to large structural or copy number alterations, influence susceptibility, onset, and progression of genetic diseases and tumor transformation. Next-generation sequencing analysis is unable to reliably capture aberrations larger than the typical sequencing read length of several hundred bases. Long-read, single-molecule sequencing methods such as SMRT and nanopore sequencing can address larger variations, but require costly whole genome analysis. Here we describe a method for isolation and enrichment of a large genomic region of interest for targeted analysis based on Cas9 excision of two sites flanking the target region and isolation of the excised DNA segment by pulsed field gel electrophoresis. The isolated target remains intact and is ideally suited for optical genome mapping and long-read sequencing at high coverage. In addition, analysis is performed directly on native genomic DNA that retains genetic and epigenetic composition without amplification bias. This method enables detection of mutations and structural variants as well as detailed analysis by generation of hybrid scaffolds composed of optical maps and sequencing data at a fraction of the cost of whole genome sequencing.
Genome-wide regulatory model from MPRA data predicts functional regions, eQTLs, and GWAS hits
Authors: Li Yue , Shi Alvin Houze , Tewhey Ryan , Sabeti Pardis C. , Ernst Jason , Kellis Manolis
Published: February 2017

Massively-parallel reporter assays (MPRA) enable unprecedented opportunities to test for regulatory activity of thousands of regulatory sequences. However, MPRA only assay a subset of the genome thus limiting their applicability for genome-wide functional annotations. To overcome this limitation, we have used existing MPRA datasets to train a machine learning model that uses DNA sequence information, regulatory motif annotations, evolutionary conservation, and epigenomic information to predict genomic regions that show enhancer activity when tested in MPRA assays. We used the resulting model to generate global predictions of regulatory activity at single-nucleotide resolution across 14 million common variants. We find that genetic variants with stronger predicted regulatory activity show significantly lower minor allele frequency, indicative of evolutionary selection within the human population. They also show higher over-lap with eQTL annotations across multiple tissues relative to the background SNPs, indicating that their perturbations in vivo more frequently result in changes in gene expression. In addition, they are more frequently associated with trait-associated SNPs from genome-wide association studies (GWAS), enabling us to prioritize genetic variants that are more likely to be causal based on their predicted regulatory activity. Lastly, we use our model to compare MPRA inferences across cell types and platforms and to prioritize the assays most predictive of MPRA assay results, including cell-dependent DNase hypersensitivity sites and transcription factors known to be active in the tested cell types. Our results indicate that high-throughput testing of thousands of putative regions, coupled with regulatory predictions across millions of sites, presents a powerful strategy for systematic annotation of genomic regions and genetic variants.
Uranium XAFS analysis of kidney from rats exposed to uranium
Authors: Kitahara Keisuke , Numako Chiya , Terada Yasuko , Nitta Kiyohumi , Shimada Yoshiya , Homma-Takeda Shino
Published: February 2017

The kidney is the critical target of uranium exposure because uranium accumulates in the proximal tubules and causes tubular damage, but the chemical nature of uranium in kidney, such as its chemical status in the toxic target site, is poorly understood. Micro-X-ray absorption fine-structure (µXAFS) analysis was used to examine renal thin sections of rats exposed to uranyl acetate. The ULIII-edge X-ray absorption near-edge structure spectra of bulk renal specimens obtained at various toxicological phases were similar to that of uranyl acetate: their edge position did not shift compared with that of uranyl acetate (17.175 keV) although the peak widths for some kidney specimens were slightly narrowed. µXAFS measurements of spots of concentrated uranium in the micro-regions of the proximal tubules showed that the edge jump slightly shifted to lower energy. The results suggest that most uranium accumulated in kidney was uranium (VI) but a portion might have been biotransformed in rats exposed to uranyl acetate.
Family business and value-added distribution: a socioemotional wealth approach
Authors: Gallizo Jose Luis , Mar-Molinero Cecilio , Moreno Jordi , Salvador Manuel
Published: February 2017

Purpose

Research has demonstrated that family businesses limit the goal of maximizing profits in exchange for maintaining control of the company and passing control to future generations. However, these decisions are not always shared by the stakeholders who are outside the family context, making tensions arise within the company that may affect profitability and the share prices of the family business. The purpose of this paper is to analyse the internal tensions in family businesses in the value-added (VA) distribution, and whether these tensions harm their performance as a result of the restrictions under which these companies operate.

Design/methodology/approach

A factor analysis has been used to measure the tension that results from VA distribution of a sample of 105 Spanish listed firms for the 2005-2012 period. A regression analysis has been used to study the impact of this tension on their share prices.

Findings

Results show that being a family business has a positive effect on the business tension factor and that returns and share prices are inversely related to tension factors. Thus, the authors conclude that the decision to maintain control over the family business threatens profitability and share prices.

Social implications

An analysis of distribution of VA in family businesses sheds light on whether or not the management in its decisions preserves its socioemotional wealth (SEW) generating tensions among its economic agents, affecting its profitability and continuity. This knowledge is important for company stakeholders and future investors.

Originality/value

This is the first study in which the value-added statement is used to analyse how the management style of firms, and especially family businesses, are seeking to preserve their SEW and internal tensions generated by them.
Internal marketing and customer-contact employees’ attitudinal outcomes
Authors: Hernández-Díaz Arleen , Calderon-Abreu Theany , Amador-Dumois Maria , Córdova-Claudio Mario
Published: February 2017

Purpose

Higher education institutions, particularly in the case of public universities, face the challenge of creating more value in an environment of increasing requirements and limitations. The purpose of this paper is to explore the relation of internal marketing (IM) with employees’ attitudinal outcomes, which aim to stimulate and retain motivated and customer-conscious contact employees.

Design/methodology/approach

Survey data of 94 customer-contact employees in a public higher education institution were analysed using partial least squares path modelling to explore and predict key target constructs.

Findings

The results demonstrate the relationship between customer-contact employees’ service empathy (SE), institutional IM initiatives and employees’ attitudinal outcomes in the public sector, specifically higher education institutions.

Research limitations/implications

The current study relies on self-reported data and a small sample of customer-contact employees working only on enrolment-related areas. Further studies should be designed for theory confirmation and generalizability of the results.

Practical implications

Top managers in public higher education institutions must encourage organizational identification through IM initiatives, such as well-established internal communication procedures. Academic management should continuously train and retain customer-contact employees that have developed SE and a sense of belonging to the organization. SE must be incorporated in the job descriptions and training of customer-contact employees.

Originality/value

The study contributes to the limited literature on the use of IM and SE in the public sector, specifically higher education institutions.
The mediating role of supply chain collaboration on the relationship between technology, trust and operational performance
Authors: Salam Mohammad Asif
Published: February 2017

Purpose

The purpose of this paper is to understand the link between trust, technology and supply chain collaboration and their impact on firms’ operational performances.

Design/methodology/approach

Based on extant literature, a hypothesized model was developed and tested using structural equation modelling (i.e. AMOS). A survey was conducted to collect data from the supply chain managers of fast-moving consumer goods (FMCG) companies (more precisely in the food and beverage sector) in Thailand.

Findings

The study findings suggest that through an ongoing relationship, trust evolves and is shaped over time and can form a competitive capability that may not be easy for competitors to replicate. Both trust and technology are found to have significant impact on supply chain collaboration and on firms’ operational performances.

Research limitations/implications

One of the major limitations of the study is that the data were obtained from one single economy, which restricts its generalizability across other economies. The study was a cross-sectional and descriptive sample of the FMCG industry at a given point in time. A more stringent test of the relationships between trust, technology, supply chain collaboration and operational performance requires an in-depth case study or longitudinal study.

Practical implications

The findings will enable supply chain managers in the FMCG industry to understand the strategic role of trust and technology in building supply chain collaboration that leads to superior operational performance.

Originality/value

The paper clearly confirms that trust and technological capabilities are significantly associated with supply chain collaboration and operational performance. Most of the earlier supply chain collaboration research streams are based on developed economies where supply chain collaboration challenges are predictable, while the current study conducted is based on a developing economy setting. This study facilitates the author’s understanding of the challenges in managing supply chain collaboration within a developing economy.
Modeling the enablers of green supply chain management
Authors: Malviya Rakesh Kumar , Kant Ravi
Published: February 2017

Purpose

The purpose of this paper is to identify and develop the relationships among the green supply chain management enablers (GSCMEs), to understand mutual influences of these GSCMEs on green supply chain management (GSCM) implementation, and to find out the driving and the dependence power of GSCMEs.

Design/methodology/approach

This paper has identified 35 GSCMEs on the basis of literature review and the opinions of experts from academia and industry. A nationwide questionnaire-based survey has been conducted to rank these identified GSCMEs. The outcomes of the survey and interpretive structural modeling (ISM) methodology have been applied to evolve mutual relationships among GSCMEs, which helps to reveal the direct and indirect effects of each GSCMEs. The results of the ISM are used as an input to the fuzzy Matriced’ Impacts Croisés Multiplication Appliquéeá un Classement (MICMAC) analysis, to identify the driving and the dependence power of GSCMEs.

Findings

Out of 35 GSCMEs 29 GSCMEs (mean⩾3.00) have been considered for analysis through a nationwide questionnaire-based survey on Indian automobile organizations. The integrated approach is developed, since the ISM model provides only binary relationship among GSCMEs, while fuzzy MICMAC analysis provides precise analysis related to driving and the dependence power of GSCMEs.

Research limitations/implications

The weightage for ISM model development and fuzzy MICMAC are obtained through the judgment of few industry experts. It is the only subjective judgment and any biasing by the person who is judging might influence the final result.

Practical implications

The study provides important guidelines for both practitioners, as well as the academicians. The practitioners need to focus on these GSCMEs more carefully during GSCM implementation. GSCM managers may strategically plan its long-term growth to meet GSCM action plan. While the academicians may be encouraged to categorize different issues, which are significant in addressing these GSCMEs.

Originality/value

Arrangement of GSCMEs in a hierarchy, the categorization into the driver and dependent categories, and fuzzy MICMAC are an exclusive effort in the area of GSCM implementation.
Artful interventions for workplace bullying: exploring forum theatre
Authors: Edwards Margot , Blackwood Kate Marie
Published: February 2017

Purpose

This paper aims to explore the phenomenon of workplace bullying in response to recent calls for the development of different approaches and provide an exploration of artful approaches to intervention.

Design/methodology/approach

The paper offers a unique conceptualisation of workplace bullying and applies a phenomenological lens to the issue. A review of literature explores the potential value of artful interventions, and drawing on authors’ knowledge and experience with the targets of bullying, they design a forum theatre intervention for use in practice.

Findings

This paper argues that phenomenology offers a unique and valuable approach to understanding workplace bullying and its management. In turn, the authors propose that artful ways of engaging with workplace bullying could be an effective way of empowering workers in a “moment” of workplace bullying, and present a forum theatre workshop specifically designed for application in workplace contexts where bullying is prevalent. The three-phase workshop aims to help employees critically reflect on their current work practices and is intended for use in small group teaching.

Research limitations/implications

The long-term impact of this intervention has not been evaluated against more traditional methods of addressing this problem. Future research should evaluate the efficacy of this, and other art-based interventions, in workplace settings.

Originality/value

Workplace bullying research is predominantly conducted from a functionalist perspective, and other methods of inquiry, such as phenomenology, are rarely considered. This paper argues for artful interventions and provides an original, tailored workshop designed to empower employees to recognise and respond to bullying in the workplace.
Predictors of social entrepreneurial intention: an empirical study
Authors: Tiwari Preeti , Bhat Anil K. , Tikoria Jyoti
Published: February 2017

Purpose

The purpose of this paper is to identify the role of cognitive styles (CgStys) and self-efficacy (SEff) in the formation of social entrepreneurial intentions (SEIs) among the students of a premier multi-campus technical university in India using the theory of planned behaviour as the research framework.

Design/methodology/approach

A 54-item questionnaire was responded by 550 students. The data were collected by employing a systematic random sampling method. In the total sample of the respondents, 67 per cent (n=368) were male and 33 per cent (n=182) were female and the average age of the respondents was 20 years. Structural equation modelling has been used for data analysis.

Findings

The results of the study support that the relationship between antecedents (CgStys and SEff) and SEIs was mediated by the attitude towards becoming a social entrepreneur, subjective norms and perceived behavioural control. Findings of this research study also suggest that students with high level of SEff are more inclined towards social entrepreneurial activities.

Research limitations/implications

The study was confined to the students from a technical university, and it may not give the generalized findings for students from the non-technical stream.

Practical implications

The finding of this research study will facilitate policy makers and educators for promoting social entrepreneurial activities at the university level. Based on the results and findings of the study, the educators may improve upon the support system to help and motivate students to opt social entrepreneurship as their career choice.

Originality/value

This is one of its kinds of research conducted in the Indian context. Findings of this research will be helpful in predicting how the intention process of Indian students is affected by their CgStys and SEff.
Measuring the people fleet: general analysis, interventions and needs
Authors: Hesketh Ian , Cooper Cary
Published: February 2017

Purpose

The purpose of this paper is to deepen conceptual understanding of how employee wellbeing is identified and categorised in the workplace, and how management information is used to target workplace interventions.

Design/methodology/approach

This is a conceptual paper reviewing and discussing contemporary literature and practice, with a focus on themes congruent with employee needs and organisational intervention options in relation to wellbeing. This paper considers wellbeing in the context of police work in the UK, and how a framework can help those charged with leading to understand and act in the interest of both the employee and the organisation.

Findings

This paper suggests that the use of an appropriate strategic HR model, such as the General Analysis, Interventions and Needs (GAIN) pyramid (Hesketh and Rhodes, 2015), can assist organisations to develop practical categories and metrics to illustrate employee status in relation to wellbeing.

Practical implications

The arguments posed provide opportunities for practitioners to use workforce-modelling tools that assist in identifying, categorising and targeting wellbeing interventions in the workplace.

Originality/value

This paper highlights that identifying, categorising and prioritising wellbeing interventions in the workplace has hitherto received little academic attention. This paper contributes by providing a greater practical insight into what may work, which is important for leaders in all organisations, particularly those trying to maintain operational performance whilst undergoing programmes of change.
Sex difference and Allee effects shape the dynamics of sex‐structured invasions
Authors: Shaw Allison K. , Kokko Hanna , Neubert Michael G.
Published: February 2017

The rate at which a population grows and spreads can depend on individual behaviour and interactions with others. In many species with two sexes, males and females differ in key life‐history traits (e.g. growth, survival and dispersal), which can scale up to affect population rates of growth and spread. In sexually reproducing species, the mechanics of locating mates and reproducing successfully introduce further complications for predicting the invasion speed (spread rate), as both can change nonlinearly with density.

Most models of population spread are based on one sex, or include limited aspects of sex differences. Here we ask whether and how the dynamics of finding mates interact with sex‐specific life‐history traits to influence the rate of population spread.

We present a hybrid approach for modelling invasions of populations with two sexes that links individual‐level mating behaviour (in an individual‐based model) to population‐level dynamics (in an integrodifference equation model).

We find that limiting the amount of time during which individuals can search for mates causes a demographic Allee effect which can slow, delay, or even prevent an invasion. Furthermore, any sex‐based asymmetries in life history or behaviour (skewed sex ratio, sex‐biased dispersal, and sex‐specific mating behaviours) amplify these effects. In contrast, allowing individuals to mate more than once ameliorates these effects, enabling polygynandrous populations to invade under conditions where monogamously mating populations would fail to establish.

We show that details of individuals’ mating behaviour can impact the rate of population spread. Based on our results, we propose a stricter definition of a mate‐finding Allee effect, which is not met by the commonly used minimum mating function. Our modelling approach, which links individual‐ and population‐level dynamics in a single model, may be useful for exploring other aspects of individual behaviour that are thought to impact the rate of population spread.
Molecular characterization of a new gene cluster for steroid degradation in Mycobacterium smegmatis
Authors: Fernández‐Cabezón Lorena , García‐Fernández Esther , Galán Beatriz , García José L.
Published: February 2017

The C‐19 steroids 4‐androstene‐3,17‐dione (AD), 1,4‐androstadiene‐3,17‐dione (ADD) or 9α‐hydroxy‐4‐androstene‐3,17‐dione (9OH‐AD), which have been postulated as intermediates of the cholesterol catabolic pathway in Mycobacterium smegmatis, cannot be used as sole carbon and energy sources by this bacterium. Only the ΔkstR mutant which constitutively expresses the genes repressed by the KstR regulator can metabolize AD and ADD with severe difficulties but still cannot metabolize 9OH‐AD, suggesting that these compounds are not true intermediates but side products of the cholesterol pathway. However, we have found that some M. smegmatis spontaneous mutants mapped in the PadR‐like regulator (MSMEG_2868) can efficiently metabolize all C‐19 steroids. We have demonstrated that the PadR mutants allow the expression of a gene cluster named C‐19+ (MSMEG_2851 to MSMEG_2901) encoding steroid degrading enzymes, that are not expressed under standard culture conditions. The C‐19+ cluster has apparently evolved independently from the upper cholesterol kstR‐regulon, but both clusters converge on the lower cholesterol kstR2‐regulon responsible for the metabolism of C and D steroid rings. Homologous C‐19+ clusters have been found only in other actinobacteria that metabolize steroids, but remarkably it is absent in Mycobacterium tuberculosis.
Debating Food Security Policy in Two Different Ideational Settings: A Comparison of Australia and Norway
Authors: Farsund Arild Aurvåg , Daugbjerg Carsten
Published: February 2017

Food security has emerged as a relatively new policy issue in agricultural policy making in developed countries. This policy problem is addressed within an institutional landscape in which agricultural ideas and institutions are well‐established. In this article, food security policy making in Australia and Norway is compared. In Australia, agricultural normalism (agricultural markets and production are considered to be similar to those of other economic sectors) has been dominant since the mid‐1980s, while Norwegian agricultural policy making has been dominated by agricultural exceptionalism (agriculture is considered a unique economic sector with special market and production conditions). It is demonstrated in the article how these two opposing institutionalised ideational foundations have influenced the nature of the food security debate in the two countries. In Australia, the debate emphasises the positive role of the market and trade in providing global food security. In Norway, the debate highlights the need to regulate market forces and restrict trade in order to allow countries to develop their own agricultural sectors.
HOW AND WHY DOES WORK MATTER? EMPLOYMENT CONDITIONS, ROUTINE ACTIVITIES, AND CRIME AMONG ADULT MALE OFFENDERS*
Authors: APEL ROBERT , HORNEY JULIE
Published: February 2017

An inverse relationship between employment and crime is well established, although the mechanisms that account for the correlation remain poorly understood. In the current study, we investigate the role of work quality, measured objectively (hours, income) as well as subjectively (commitment). A routine activities perspective is proposed for the work–crime relationship, and it inspires hypotheses about the way that work reduces crime indirectly, in part, through unstructured leisure and substance‐using behaviors that tend to carry situational inducements to offend. The results derive from within‐person analyses of monthly data provided by adult male offenders recently admitted to state prison in the Second Nebraska Inmate Study (N = 717; NT = 21,965). The findings indicate that employment significantly reduces self‐report crime but only when employed men report strong commitment to their jobs, whereas other work characteristics are unrelated to crime. This indicates that, among serious criminally involved men, the subjective experience of work takes priority over its objective characteristics. The results also indicate that routine activities only partly mediate the relationship among work, job commitment, and crime, whereas the majority of the work–crime relationship remains unmediated.
Low prevalence of non‐alcoholic fatty liver disease in patients with type 1 diabetes is associated with decreased subclinical cardiovascular disease
Authors: Serra‐Planas Enric , Aguilera Eva , Castro Laura , Rodríguez Raúl , Salinas Isabel , Lucas Anna , Joaquín Clara , Puig Rocio , Mauricio Dídac , Puig‐Domingo Manel
Published: February 2017

Background

Non‐alcoholic fatty liver disease (NAFLD) has been proposed as an independent cardiovascular risk factor. The present study evaluated the prevalence of NAFLD in a cohort of type 1 diabetic (T1D) patients and its potential relationship with subclinical cardiovascular disease (CVD).

Methods

One hundred T1D patients (mean [±SD] age 39.4 ± 7.8 years, disease duration 21.7 ± 8.6 years) were included in the present cross‐sectional study. All subjects underwent abdominal ultrasonography for detection of NAFLD, carotid ultrasonography to measure the carotid intima–media thickness (CIMT) and atheroma plaques, and cardiac tomography for evaluation of the coronary artery calcium score (CACS).

Results

Of the study cohort, 12% had NAFLD and 23% had a CACS >0. The T1D subjects with NAFLD had a greater CIMT than those without NAFLD (0.65 ± 0.17 vs 0.55 ± 0.14 mm; P = 0.029), but there were no significant differences between the two groups with regard to CACS, glycemic control, or the presence of carotid plaques. Patients with high liver enzyme concentrations (>20 U/L) had a higher CIMT (0.60 ± 0.16 vs 0.54 ± 0.13; P = 0.04) and there was a higher proportion of altered CACS (17 [73.9%] vs 6 [26.1%]; P = 0.001) and detection of carotid plaques (10 [76.9%] vs 3 [23.1%]; P = 0.014) in this group.

Conclusions

A low prevalence of NAFLD was found in the T1D cohort that was associated globally with a low proportion of abnormal CVD imaging markers, although these imaging parameters were worse in subjects in whom NAFLD was detected.
Gastric antral vascular ectasia in systemic sclerosis: Where do we stand?
Authors: El‐Gendy Hala , Shohdy Kyrillus S. , Maghraby Gehad G. , Abadeer Kerolos , Mahmoud Moustafa
Published: February 2017

Gastric antral vascular ectasia (GAVE) continues to be a challenge in both diagnosis and treatment. GAVE has a diverse group of associations and presumed causes, including cirrhosis, chronic renal failure and autoimmune connective tissue diseases. However, in most occasions, the management plan of GAVE itself is the same whatever the underlying disease by using Argon plasma coagulation (APC). Herein, we will discuss three cases of systemic sclerosis‐associated GAVE presenting with either acute or chronic gastrointestinal bleeding showing variable responses to APC. Anemia and telangiectasia may be the first striking presentation of systemic sclerosis (SSc). Renal artery stenosis, aortic stenosis, widespread cutaneous and mucosal telangiectasia and hypertension seem to be associated with poor prognosis and should prompt rapid intervention and careful follow‐up. Moreover, the hunt for molecular underpinnings of the broad array of vascular lesions in SSc has to include von Willebrand factor and endoglin. Eventually, we will review the recent alternatives that can be effective in SSc‐GAVE, such as band ligation, hematopoietic stem cells transplantation and immunotherapy.
Effects of 25‐hydroxyvitamin D and vitamin D‐binding protein on bone mineral density and disease activity in Malaysian patients with rheumatoid arthritis
Authors: Wong Tze Hao , Gupta Esha Das , Radhakrishnan Ammu K. , Gun Suk Chyn , Chembalingam Gandhi , Yeap Swan Sim
Published: February 2017

Aim

Vitamin D3 [25(OH)D] has been shown to be important in bone health and can influence rheumatoid arthritis (RA) disease activity. Vitamin D‐binding protein (VDBP) levels vary with race and may modulate ‘bioavailable’ levels of 25(OH)D. The aim of this study was to explore the relationships between 25(OH)D, VDBP and clinical factors on bone mineral density (BMD) in a group of multi‐ethnic Malaysian RA patients and healthy controls.

Methods

A cross‐sectional study of 77 female RA patients and 29 controls was performed. Serum 25(OH)D was measured using the Elecsys® Vitamin D total assay. Serum VDBP was measured using a Quantikine® enzyme‐linked immunosorbent assay kit. BMD was assessed using dual‐energy X‐ray absorptiometry (DXA).

Results

Overall, mean 25(OH)D levels were 42.66 ± 21.75 nmol/L with no significant difference between RA patients and controls. 25(OH)D levels were significantly higher in Chinese, compared to Malay/Indian subjects. In RA patients, menopausal status and body mass index (BMI) were significantly associated with BMD but not 25(OH)D or RA Disease Activity Score of 28 joints (DAS28). There was no significant correlation between 25(OH)D and DAS28, even after correction for menopausal status and BMI. VDBP levels were not significantly different between the races and did not significantly correlate with BMD, 25(OH)D overall, or DAS28 in RA patients.

Conclusions

In Malaysian RA patients, menopausal status and BMI were more important influences on BMD than 25(OH)D or RA disease activity. The utility of measuring VDBP levels in this population remains uncertain.
Can Macroeconomic Variables Explain Managed Fund Returns? The Australian Case
Authors: Wang Luo , Li Bin , Liu Benjamin
Published: February 2017

We investigate the relationship between 24 different categories of Australian managed funds and 13 macroeconomic variables from the third quarter of 1998 to the first quarter of 2013. Using principal component and regression analyses, we find that fund returns can be significantly explained by principal components that reflect both the international and domestic variables, especially at the next two quarters. The relationships between fund returns and macroeconomic variables are predominantly negative. Further, the pooled regression results show that, at a more general level, the explanatory power of macroeconomic variables is relatively weak on fixed interest and on international shares funds, but is strong on multiple assets, property, and Australian shares funds.
Copy number variations in testicular maturation arrest
Authors: Halder A. , Kumar P. , Jain M. , Iyer V. K.
Published: February 2017

Testicular maturation arrest is characterized by interruption of germ cell development and differentiation. Genetic factors play important role in the causation of human disease, including male infertility. The objective was to study copy number variations in testicular maturation arrest using single nucleotide polymorphism (SNP) microarray technique. Conventional cytogenetics, targeted fluorescence in situ hybridization (FISH) and sequence‐tagged site (STS) polymerase chain reaction (PCR) were used to confirm some of the SNP microarray findings. SNP microarray on 68 cases of testicular maturation arrest detected copy number variations (CNVs) mostly on sex chromosomes involving pseudoautosomal regions (PAR) 1, 2 and 3 as well as azoospermic factors (AZFs) besides three cases of chromosomal abnormalities (two Klinefelter syndromes and one case of dicentric Y). The AZF deletion was observed in 14 (20.6%) cases and the AZFc gain was observed in 6 (8.8%) cases. PAR 1 and 2 CNVs was observed in 5 (7.3%) cases. PAR 3 CNVs was detected in 19 cases and 2 controls. The TSPY2 gene gain (within PAR 3 CNVs) was observed in 16 cases and 1 control. CNV containing autosomal genes possibly associated with male infertility in this study was SPATA31A2‐A5 (9p12) in five cases. In this study, SNP microarray identified possible underlying aetiology in 55.9% (38/68) cases besides identifying minimal critical region of AZFc deletion as 0.51 mb (Y:24356128–24873665) involving TTY5, RBMY2FP, RBMY1F, RBMY1J, TTY6 and PRY genes. SNP microarray seems superior, sensitive, specific as well as cost‐effective method and has potential to be the first tier investigations to explore underlying genomic factors of testicular maturation arrest. The present study is an attempt to find out probable genomic factors with idiopathic testicular maturation arrest.
Factors associated with villus atrophy in symptomatic coeliac disease patients on a gluten‐free diet
Authors: Mahadev S. , Murray J. A. , Wu T.‐T. , Chandan V. S. , Torbenson M. S. , Kelly C. P. , Maki M. , Green P. H. R. , Adelman D. , Lebwohl B.
Published: February 2017

Background

Duodenal injury persists in some coeliac disease patients despite gluten‐free diet, and is associated with adverse outcomes.

Aim

To determine the prevalence and clinical risk factors for persistent villus atrophy among symptomatic coeliac disease patients.

Methods

A nested cross‐sectional analysis was performed on coeliac disease patients with self‐reported moderate or severe symptoms while following a gluten‐free diet, who underwent protocol‐mandated duodenal biopsy upon enrolment in the CeliAction clinical trial. Demographic factors, symptom type, medication use, and serology were examined to determine predictors of persistent villus atrophy.

Results

Of 1345 symptomatic patients, 511 (38%, 95% CI, 35–41%) were found to have active coeliac disease with persistent villus atrophy, defined as average villus height to crypt depth ratio ≤2.0. On multivariable analysis, older age (OR, 5.1 for ≥70 vs. 18–29 years, 95% CI, 2.5–10.4) was a risk factor while longer duration on gluten‐free diet was protective (OR, 0.37, 95% CI, 0.24–0.55 for 4–5.9 vs. 1–1.9 years). Villus atrophy was associated with use of proton‐pump inhibitors (PPIs; OR, 1.6, 95% CI, 1.1–2.3), non‐steroidal anti‐inflammatory drugs (NSAIDs; OR, 1.64, 95% CI, 1.2–2.2), and selective serotonin reuptake inhibitors (SSRIs; OR, 1.74, 95% CI, 1.2–2.5). Symptoms were not associated with villus atrophy after adjusting for covariates.

Conclusions

A majority of symptomatic coeliac disease patients did not have active disease on follow‐up histology. Symptoms were poorly predictive of persistent mucosal injury. The impact of NSAIDs, PPIs, and SSRIs on mucosal healing in coeliac disease warrants further study.
A phase 2 study of simtuzumab in patients with primary, post‐polycythaemia vera or post‐essential thrombocythaemia myelofibrosis
Authors: Verstovsek Srdan , Savona Michael R. , Mesa Ruben A. , Dong Hua , Maltzman Julia D. , Sharma Shringi , Silverman Jeffrey , Oh Stephen T. , Gotlib Jason
Published: February 2017

Simtuzumab, a monoclonal antibody inhibitor of extracellular matrix enzyme lysyl oxidase‐like‐2, showed preclinical promise and was well tolerated in clinical studies. A phase 2, open‐label study of simtuzumab was conducted in patients with primary myelofibrosis (MF), post‐polycythaemia vera MF and post‐essential thrombocythaemia MF. Fifty‐four patients were randomized to receive simtuzumab alone (200 or 700 mg [n = 12 each group]) or simtuzumab (200 or 700 mg) with ruxolitinib (n = 15 each group) for 24 weeks. Simtuzumab alone or in combination with ruxolitinib showed no clinical benefit at 24 weeks. The mean serum simtuzumab trough concentrations appeared to increase dose‐proportionally between the 200‐mg and 700‐mg treatment groups. Therapy‐related serious adverse events were pyrexia, pain in extremity (both in 1 patient) and infusion reaction (in another patient). Bone marrow fibrosis (BMF) score was reduced at 24 weeks in 2 patients (16·7%) in the simtuzumab 700‐mg group, 1 (6·7%) in the simtuzumab 200‐mg + ruxolitinib group, and 2 (13·3%) in the simtuzumab 700‐mg + ruxolitinib group; similar numbers of patients had increased BMF. Simtuzumab alone or with ruxolitinib was well tolerated but did not produce clinical benefit nor consistently reduce BMF in patients with MF by 24 weeks.
Advanced stage nodular lymphocyte predominant Hodgkin lymphoma in children and adolescents: clinical characteristics and treatment outcome – a report from the SFCE & CCLG groups
Authors: Shankar Ananth G. , Roques Gaelle , Kirkwood Amy A. , Lambilliotte Anne , Freund Katja , Leblanc Thierry , Hayward Janis , Abbou Samuel , Ramsay Alan D. , Schmitt Claudine , Gorde‐Grosjean Stephanie , Pacquement Hélène , Haouy Stephanie , Boudjemaa Sabah , Aladjidi Nathalie , Hall Georgina W. , Landman‐Parker Judith
Published: February 2017

Advanced stage nodular lymphocyte predominant Hodgkin lymphoma (nLPHL) is extremely rare in children and as a consequence, optimal treatment for this group of patients has not been established. Here we retrospectively evaluated the treatments and treatment outcomes of 41 of our patients from the UK and France with advanced stage nLPHL. Most patients received chemotherapy, some with the addition of the anti CD20 antibody rituximab or radiotherapy. Chemotherapy regimens were diverse and followed either classical Hodgkin lymphoma or B non‐Hodgkin lymphoma protocols. All 41 patients achieved a complete remission with first line treatment and 40 patients are alive and well in remission. Eight patients subsequently relapsed and 1 patient died of secondary cancer (9 progression‐free survival events). The median time to progression for those who progressed was 21 months (5·9–73·8). The median time since last diagnosis is 87·3 months (8·44–179·20). Thirty‐six (90%), 30 (75%) and 27 (68%) patients have been in remission for more than 12, 24 and 36 months, respectively. Overall, the use of rituximab combined with multi‐agent chemotherapy as first line treatment seems to be a reasonable therapeutic option.
Outcome predictors of radical cystectomy in patients with cT4 prostate cancer: a multi‐institutional study of 62 patients
Authors: Spahn Martin , Morlacco Alessandro , Boxler Silvan , Joniau Steven , Briganti Alberto , Montorsi Francesco , Gontero Paolo , Bader Pia , Frohneberg Detlef , van Poppel Hein , Karnes Robert Jeffrey ,   the European Multicenter Prostate Cancer Clinical and Translational Research Group (EMPAcT)
Published: February 2017

Objectives

To identify which patients with macroscopic bladder‐infiltrating T4 prostate cancer (PCa) might have favourable outcomes when treated with radical cystectomy (RC).

Materials and Methods

We evaluated 62 patients with cT4cN0–1 cM0 PCa treated with RC and pelvic lymph node dissection between 1972 and 2011. In addition to descriptive statistics, the Kaplan–Meier method and log‐rank tests were used to depict survival rates. Univariate and multivariate Cox regression analysis tested the association between predictors and progression‐free, PCa‐specific and overall survival.

Results

Of the 62 patients, 19 (30.6%) did not have clinical progression during follow‐up, two (3.2%) had local recurrence, and 32 (51.6%) had haematogenous and nine (14.5%) combined pelvic and distant metastasis. Forty patients (64.5%) died, 34 (54.8%) from PCa and six (9.7%) from other causes. The median (range) survival time of the 19 patients who were metastasis‐free at last follow‐up was 86 (1–314) months, 8/19 patients had a follow‐up of >5 years, and five patients survived metastasis‐free for >15 years. Patients without seminal vesicle invasion (SVI) had the best outcomes, with an estimated 10‐year PCa‐specific survival of 75% compared with 24% for patients with SVI.

Conclusion

For cT4 PCa RC can be an appropriate treatment for local control and part of a multimodality‐treatment approach. Although recurrences are probable, these do not necessarily translate into cancer‐specific death. Men without SVI had a 75% 10‐year PCa‐specific survival. Although outcomes for patients with SVI are not as favourable, there can be good local control; however, these patients are at higher risk of progression and may need more aggressive systemic treatment.