bluuebunny/crossref_metadata_2025 huggingface dataset:
Environmental cystine drives glutamine anaplerosis and sensitizes cells to glutaminase inhibition
Authors: Muir Alexander , Danai Laura V. , Gui Dan Y. , Waingarten Chiara Y. , Heiden Matthew G. Vander
Published: April 2017

Many cancer cell lines depend on extracellular glutamine as a major tri-carboxylic acid (TCA) cycle anaplerotic substrate to support proliferationin vitro. However, recent studies have suggested that some cells that depend on glutamine anaplerosis in culture rely much less on glutamine catabolism to proliferatein vivo, with environmental differences between tumors and cell culture influencing the extent of glutamine catabolism. Here we sought to better understand the environmental differences that cause differential dependence on glutamine for TCA cycle anaplerosis. We find that cells cultured in adult bovine serum, a condition that more closely reflects the nutrients available to cellsin vivo, leads to decreased glutamine catabolism and reliance on glutamine anaplerosis compared to standard tissue culture conditions. By analyzing the nutrient differences between bovine serum and media, we find that levels of a single nutrient, cystine, can account for the differential dependence on glutamine in these different environmental contexts. Further, we show that cystine levels dictate glutamine dependence via the cystine/glutamate antiporter xCT/SLC7A11, and that environmental cystine levels in conjunction withxCT/SLC7A11expression is necessary and sufficient to drive increased glutamine anaplerosis, defining important determinants of glutamine anaplerosis and glutaminase dependence in cancer cells.
Akt regulation of glycolysis mediates bioenergetic stability in epithelial cells
Authors: Hung Yin P. , Teragawa Carolyn , Gilles Taryn , Pargett Michael , Minguet Marta , Distor Kevin , Rocha-Gregg Briana , Kosaisawe Nont , Yellen Gary , Brugge Joan S. , Albeck John G.
Published: April 2017

Cells use multiple feedback controls to regulate metabolism in response to nutrient and signaling inputs. However, feedback creates the potential for unstable network responses. We examined how concentrations of key metabolites and signaling pathways interact to maintain homeostasis in proliferating human cells, using fluorescent reporters for AMPK activity, Akt activity, and cytosolic NADH/NAD+redox. Across various conditions including metabolic (glycolytic or mitochondrial) inhibition or cell proliferation, we observed distinct patterns of AMPK activity, including stable adaptation and highly dynamic behaviors such as periodic oscillations and irregular fluctuations, indicating a failure to reach a steady state. Fluctuations in AMPK activity, Akt activity, and cytosolic NADH/NAD+redox state were temporally linked in individual cells adapting to metabolic perturbations. By monitoring single-cell dynamics in each of these contexts, we identified PI3K/Akt regulation of glycolysis as a multifaceted modulator of single-cell metabolic dynamics that is required to maintain metabolic stability in proliferating cells.
White matter alterations at pubertal onset
Authors: Genc Sila , Seal Marc L , Dhollander Thijs , Malpas Charles B , Hazell Philip , Silk Tim
Published: April 2017

Recent neurodevelopmental research supports the contribution of pubertal stage to local and global grey and white matter remodelling. Little is known, however, about white matter microstructural alterations at pubertal onset. This study investigated differences in white matter properties between pre-pubertal and pubertal children using whole brain fixel-based analysis (FBA) of the microscopic density and macroscopic cross-section of fibre bundles. Diffusion-weighted imaging data were acquired for 74 typically developing children (M=10.4, SD=0.43 years, 31 female) at 3.0T (60 diffusion gradient directions, b-value=2800 s/mm
2
). Group comparisons of fibre density (FD) and fibre cross-section (FC) were made between age-matched pre-pubertal and pubertal groups, and post-hoc analyses were performed on regions of interest (ROIs) defined in the splenium, body and genu of the corpus callosum. Significant fixel-wise differences in FD were observed between the pubertal groups, where the pubertal group had significantly higher FD compared with age-matched pre-pubertal children, localised to the posterior corpus callosum. Post-hoc analyses on mean FD in the corpus callosum ROIs revealed group differences between the pubertal groups in the splenium, but not body or genu. The observed higher apparent fibre density in the splenium suggests that pubertal onset coincides with white matter differences explained by increasing axon diameter. This may be an important effect to account for over pubertal development, particularly for group studies where age-matched clinical and typical populations may be at various stages of puberty.
Efficient and accurate causal inference with hidden con-founders from genome-transcriptome variation data
Authors: Wang Lingfei , Michoel Tom
Published: April 2017

Mapping gene expression as a quantitative trait using whole genome-sequencing and transcriptome analysis allows to discover the functional consequences of genetic variation. We developed a novel method and ultra-fast software Findr for higly accurate causal inference between gene expression traits using cis-regulatory DNA variations as causal anchors, which improves current methods by taking into account hidden confounders and weak regulations. Findr outperformed existing methods on the DREAM5 Systems Genetics challenge and on the prediction of microRNA and transcription factor targets in human lymphoblastoid cells, while being nearly a million times faster. Findr is publicly available athttps://github.com/lingfeiwang/findr.

Author summary

Understanding how genetic variation between individuals determines variation in observable traits or disease risk is one of the core aims of genetics. It is known that genetic variation often affects gene regulatory DNA elements and directly causes variation in expression of nearby genes. This effect in turn cascades down to other genes via the complex pathways and gene interaction networks that ultimately govern how cells operate in an ever changing environment. In theory, when genetic variation and gene expression levels are measured simultaneously in a large number of individuals, the causal effects of genes on each other can be inferred using statistical models similar to those used in randomized controlled trials. We developed a novel method and ultra-fast software Findr which, unlike existing methods, takes into account the complex but unknown network context when predicting causality between specific gene pairs. Findr’s predictions have a significantly higher overlap with known gene networks compared to existing methods, using both simulated and real data. Findr is also nearly a million times faster, and hence the only software in its class that can handle modern datasets where the expression levels of ten-thousands of genes are simultaneously measured in hundreds to thousands of individuals.
Regulatory functions and chromatin loading dynamics of linker histone H1 during endoreplication in Drosophila
Authors: Andreyeva Evgeniya N. , Bernardo Travis J. , Kolesnikova Tatyana D. , Lu Xingwu , Yarinich Lyubov A. , Bartholdy Boris A. , Guo Xiaohan , Posukh Olga V. , Healton Sean , Willcockson Michael A. , Pindyurin Alexey V. , Zhimulev Igor F. , Skoultchi Arthur I. , Fyodorov Dmitry V.
Published: April 2017

Eukaryotic DNA replicates asynchronously, with discrete genomic loci replicating during different stages of S phase. Drosophila larval tissues undergo endoreplication without cell division, and the latest replicating regions occasionally fail to complete endoreplication, resulting in underreplicated domains of polytene chromosomes. Here we show that linker histone H1 is required for the underreplication (UR) phenomenon in Drosophila salivary glands. H1 directly interacts with the Suppressor of UR (SUUR) protein and is required for SUUR binding to chromatin in vivo. These observations implicate H1 as a critical factor in the formation of underreplicated regions and an upstream effector of SUUR. We also demonstrate that the localization of H1 in chromatin changes profoundly during the endocycle. At the onset of endocycle S (endo-S) phase, H1 is heavily and specifically loaded into late replicating genomic regions and is then redistributed during the course of endoreplication. Our data suggest that cell cycle-dependent chromosome occupancy of H1 is governed by several independent processes. In addition to the ubiquitous replication-related disassembly and reassembly of chromatin, H1 is deposited into chromatin through a novel pathway that is replication-independent, rapid, and locus-specific. This cell cycle-directed dynamic localization of H1 in chromatin may play an important role in the regulation of DNA replication timing.
Time-resolved XAFS measurement using quick-scanning techniques at BSRF
Authors: Chu Shengqi , Zheng Lirong , An Pengfei , Gong Hui , Hu Tiandou , Xie Yaning , Zhang Jing
Published: April 2017

A new quick-scanning X-ray absorption fine-structure (QXAFS) system has been established on beamline 1W1B at the Beijing Synchrotron Radiation Facility. As an independent device, the QXAFS system can be employed by other beamlines equipped with a double-crystal monochromator to carry out quick energy scans and data acquisition. Both continuous-scan and trapezoidal-scan modes are available in this system to satisfy the time scale from subsecond (in the X-ray absorption near-edge structure region) to 1 min. Here, the trapezoidal-scan method is presented as being complementary to the continuous-scan method, in order to maintain high energy resolution and good signal-to-noise ratio. The system is demonstrated to be very reliable and has been combined with in situ cells to carry out time-resolved XAFS studies.
Innovation and ICT use by firms and households in the EU
Authors: Billon Margarita , Marco Rocío , Lera-Lopez Fernando
Published: April 2017

Purpose

The purpose of this paper is to investigate the existence of patterns that combine innovation and information and communication technologies (ICT) use, and the factors explaining them in the European Union.

Design/methodology/approach

The authors use data for firms and households at the regional level in the EU-27. Factorial and cluster analyses are used to the determine combined patterns for both dimensions and to elaborate a taxonomy of the European regions, respectively. Finally, the multiple discriminant analysis serves to identify the factors that characterize the patterns detected.

Findings

The results show the existence of three regional clusters that capture different combinations of patenting and ICT use. Research and development (R&D) expenditure in the business sector, government quality, gross domestic product per capita, the number of researchers, and employment by the highest level of education attained are the key variables explaining the disparities in innovation and ICT use in the European regions.

Research limitations/implications

The conclusions point to the key role played by business R&D and knowledge resources within an institutional framework that facilitates actions oriented to benefiting regions through both knowledge creation and knowledge diffusion derived from the combined activities of innovation and ICT use.

Originality/value

The paper provides for the first time a characterization of the European regions that jointly considers innovation and ICT use. It also contributes to the literature by exploring differences in ICT use by households and firms, and the factors explaining them. The study can provide new insights into the design of public policies that may consider the common factors that explain combinations of innovation and technology use.
Constructing and enacting normality online across generations
Authors: Panteli Niki , Marder Ben
Published: April 2017

Purpose

The purpose of this paper is to examine how different age groups construct and enact normality within social networking sites (SNS) and consequently extend theory in the area of online interactions.

Design/methodology/approach

The chosen research site was Facebook and research design involved focus groups across three different age groups: teenagers, young adults and the middle-aged. In total, there were 78 participants. The focus groups explored the metaphoric images of Facebook interactions. In doing so, participants were asked to draw a picture to represent their metaphor and following this, to position themselves and other characters within the picture. The drawings as well as the facilitators’ records provided the main data set for the study.

Findings

Connective and protective encounters were found to be used by different age groups when constructing and enacting normality on SNS. Further, it emerged that the interpretation and enactment of normality across the different age groups significantly varied. The metaphorical images have transpired as being a resourceful way of unpacking these differences.

Research limitations/implications

The study relied on focus groups in order to capture metaphorical images across generations. It did not include interviews with individual participants to elicit the extent to which they agreed with the group metaphor or whether there was anything else they might have presented in the drawings. This could be on the agenda for future research.

Practical implications

The findings of the study suggest that SNS managers and designers should sympathise with the view that users of different ages engage in different ways with SNS and as a result, user interfaces should be customised according to the age of the user.

Social implications

The study has implications for those interested in cross- and inter-generational research.

Originality/value

This is the first study in which the concept of normality has been adopted as a theoretical lens for understanding the interactions on SNS. Further, this work adds to the limited body of research on SNS use across different generations whilst it expands on the range of methodologies used within the information systems field.
Academic publishing in the information age – an editor’s observations
Authors: Rogerson Simon
Published: April 2017

Purpose

This paper aims to explore the evolution of academic publishing from the traditional roots to today’s online publishing cycle which embraces many of the elements of virtual space.

Design/methodology/approach

A case study approach is adopted using the Journal of Information, Communication and Ethics in Society to explore the revolutionary journey.

Findings

The value of using a range of virtual space facilities in tandem is assessed.

Originality/value

The paper can be used as a guide for academic editors and publishers in reaching out to the next generations of the academic population.
How do investors view information disclosure quality rating?
Authors: Tan Youchao , Liu Yuyu
Published: April 2017

Purpose

Following Cheng et al. (2012) and Tan et al. (2015), this paper aims to investigate how does the forward-looking information disclosure quality affect the investors’ decisions and then the investment efficiency.

Design/methodology/approach

The authors obtain the information disclosure quality rating data from the official website of the Shenzhen Stock Exchange (SZSE), and firm financial information is mainly from the China Center for Economic Research (CCER) and China Stock Market and Accounting Research Database (CSMAR). The authors choose firms that publicly traded on the SZSE during the period from 2004 to 2010, and the final sample consists of 2,415 firm-year observations for 345 unique firms.

Findings

The authors find that a firm with a high information disclosure quality rating is trusted by investors more. Forward-looking non-financial information (FNFI) disclosure alleviates financial constraints and improves investment efficiency, including alleviating underinvestment and preventing overinvestment to a larger extent for firms with high information disclosure quality rating, especially for the firms rated A (excellent) or B (good) every year since 2001, when the rating began. Moreover, this study proves that investors trust the firms rated high more but do not guard against the firms rated low enough.

Research limitations/implications

The authors only considered the quantity of FNFI disclosed by firms and ignored other characteristics of FNFI. Limited by the data of information disclosure quality rating, the research sample is just from the SZSE.

Originality/value

This paper extends the research of Cheng et al. (2012) and Tan et al. (2015) to show that one of the reasons behind the extant mix results of the relationship between FNF disclosure and investment efficiency is different information disclosure quality. High-quality FNFI disclosure can alleviate underinvestment and prevent overinvestment at same time.
From analytics to action: how Shell digitized recruitment
Authors: Lam Sue , Hawkes Ben
Published: April 2017

Purpose

The purpose of this paper is to share how Shell HR enabled technological change in their graduate hiring assessments.

Design/methodology/approach

Shell receives over 100,000 applications for their global graduate program each year for fewer than 1,000 technical and commercial positions. The foundation of the recruitment process is the assessments, providing data and insight on which to make selection decisions. The effectiveness of the assessments, along with attracting the best candidates, determines the quality of hire and long-term value to Shell. To stay competitive in the market with job seekers, Shell recruitment wanted to create a streamlined assessment approach that could be delivered through available technology. HR analytics and assessment specialists collaborated to review the current graduate assessments to enhance candidate assessment data, boost candidate experience, leverage technology and make structural changes that improve cost effectiveness, scalability and efficiency for variable hire demand levels. Focus groups, interviews, candidate experience surveys and assessment center data were examined.

Findings

The findings indicate that the assessment process was robust but could be streamlined, particularly by digitizing the process. For example, pre-recorded video interviewing could be utilized early in the assessment process.

Originality/value

This paper sheds light on the success factors of digitizing the recruitment assessment process. Information on bringing data analysis to recommendations and implementation is shared.
HR’s new role: rethinking and enabling digital engagement
Authors: Jesuthasan Ravin
Published: April 2017

Purpose

This paper aims to explore how a new industrial revolution with digital technology at its core is disrupting the workplace. It shares how HR has an opportunity to use data and digital technologies to reinvent how organizations engage with their workforce. It answers the question of how HR pivots from its legacy focus on compliance and being a steward of employment to the work and helping the organization strengthen its connection with its workers through improved digital engagement.

Design/methodology/approach

The paper is based on Willis Towers Watson thought leadership and references recent findings from their research.

Findings

The paper explores how digital technologies have changed how workers connect with their co-workers and the organization. In addition, it examines how digital technologies are changing how work gets done.

Research limitations/implications

The paper is not exclusively based on research.

Practical implications

The paper explores how digital technologies drive engagement, HR’s role as steward of the work and enabler of digital engagement and best practices for enabling digital engagement in the modern workplace.

Originality/value

This paper fulfills a need to assist HR leaders in thinking through the implications of the future of work and how digital technologies will shape that future.
Climate and competition effects on tree growth in Rocky Mountain forests
Authors: Buechling Arne , Martin Patrick H. , Canham Charles D.
Published: April 2017

Climate is widely assumed to influence physiological and demographic processes in trees, and hence forest composition, biomass and range limits. Growth in trees is an important barometer of climate change impacts on forests as growth is highly correlated with other demographic processes including tree mortality and fecundity.

We investigated the main drivers of diameter growth for five common tree species occurring in the Rocky Mountains of the western United States using nonlinear regression methods. We quantified growth at the individual tree level from tree core samples collected across broad environmental gradients. We estimated the effects of both climate variation and biotic interactions on growth processes and tested for evidence that disjunct populations of a species respond differentially to climate.

Relationships between tree growth and climate varied by species and location. Growth in all species responded positively to increases in annual moisture up to a threshold level. Modest linear responses to temperature, both positive and negative, were observed at many sites. However, model results also revealed evidence for differentiated responses to local site conditions in all species. In severe environments in particular, growth responses varied nonlinearly with temperature. For example, in northerly cold locations pronounced positive growth responses to increasing temperatures were observed. In warmer southerly climates, growth responses were unimodal, declining markedly above a threshold temperature level.

Net effects from biotic interactions on diameter growth were negative for all study species. Evidence for facilitative effects was not detected. For some species, competitive effects more strongly influenced growth performance than climate. Competitive interactions also modified growth responses to climate to some degree.

Synthesis. These analyses suggest that climate change will have complex, species‐specific effects on tree growth in the Rocky Mountains due to nonlinear responses to climate, differentiated growth processes that vary by location and complex species interactions that impact growth and potentially modify responses to climate. Thus, robust model simulations of future growth responses to climate trends may need to integrate realistic scenarios of neighbourhood effects as well as variability in tree performance attributed to differentiated populations.
A global survey of bacterial type III secretion systems and their effectors
Authors: Hu Yueming , Huang He , Cheng Xi , Shu Xingsheng , White Aaron P. , Stavrinides John , Köster Wolfgang , Zhu Guoqiang , Zhao Zhendong , Wang Yejun
Published: April 2017

The type III secretion system (T3SS) is an important genetic determinant that mediates interactions between Gram‐negative bacteria and their eukaryotic hosts. Our understanding of the T3SS continues to expand, yet the availability of new bacterial genomes prompts questions about its diversity, distribution and evolution. Through a comprehensive survey of ∼20 000 bacterial genomes, we identified 174 non‐redundant T3SSs from 109 genera and 5 phyla. Many of the bacteria are environmental strains that have not been reported to interact with eukaryotic hosts, while several species groups carry multiple T3SSs. Four ultra‐conserved Microsynteny Blocks (MSBs) were defined within the T3SSs, facilitating comprehensive clustering of the T3SSs into 13 major categories, and establishing the largest diversity of T3SSs to date. We subsequently extended our search to identify type III effectors, resulting in 8740 candidate effectors. Lastly, an analysis of the key transcriptional regulators and circuits for the T3SS families revealed that low‐level T3SS regulators were more conserved than higher‐level regulators. This comprehensive analysis of the T3SSs and their protein effectors provides new insight into the diversity of systems used to facilitate host‐bacterial interactions.
‘It seems like you're going around in circles’: recurrent biographical disruption constructed through the past, present and anticipated future in the narratives of young adults with inflammatory bowel disease
Authors: Saunders Benjamin
Published: April 2017

Biographical disruption and related concepts continue to be widely drawn upon in explaining how individuals experience chronic illness. Through in‐depth examination of the narrative experiences of two young adults with inflammatory bowel disease (IBD), this article aims to contribute to the continuing theoretical elaboration of biographical disruption, and in turn offer new insights into how young adults experience this condition. The cases are analysed from an interaction‐based, constructionist perspective, through which it is argued that the relapse‐remission nature of IBD can give rise to a particular form of recurrent biographical disruption, constructed in narrative through a complex configuration of past, present and anticipated future experiences. The two young adults are found to give different meaning to this recurrent disruption in terms of its significance and consequences – whilst Samuel represents an ongoing cycle of profound disruption and biographical reinstatement, Edith normalises the cycle of disruption and its role in her ongoing biography. Therefore, moving beyond the notion of ‘normal illness’ observed in previous research literature, the concept of ‘normal recurrent disruption’ is proposed. Finally, it is argued that this recurrent biographical disruption may be experienced particularly severely in young adulthood owing to the unique pressures and expectations of this lifestage.
Who Receives Medicaid in Old Age? Rules and Reality
Authors: Borella Margherita , De Nardi Mariacristina , French Eric
Published: April 2017

Medicaid is a government programme that also provides health insurance to the elderly who have few assets and either low income or catastrophic health care expenses. We ask how the Medicaid rules map into the reality of Medicaid recipiency, and we ask what other observable characteristics are important to determine who ends up on Medicaid. The data show that both singles and couples with high retirement income can end up on Medicaid at very advanced ages. We find that, conditioning on a large number of observable characteristics, including those that directly relate to Medicaid eligibility criteria, single women are more likely to end up on Medicaid – so are non‐white people, but, surprisingly, their higher recipiency is concentrated in the higher income percentiles. We also find that people with low incomes who have a high‐school diploma or higher degree are much less likely to end up receiving Medicaid than their less‐educated counterparts. All of these effects are large and depend on retirement income in a very non‐linear way.
Dynamics of mono‐ and dual‐species biofilm formation and interactions between Staphylococcus aureus and Gram‐negative bacteria
Authors: Makovcova Jitka , Babak Vladimir , Kulich Pavel , Masek Josef , Slany Michal , Cincarova Lenka
Published: April 2017

Microorganisms are not commonly found in the planktonic state but predominantly form dual‐ and multispecies biofilms in almost all natural environments. Bacteria in multispecies biofilms cooperate, compete or have neutral interactions according to the involved species. Here, the development of mono‐ and dual‐species biofilms formed by Staphylococcus aureus and other foodborne pathogens such as Salmonella enterica subsp. enterica serovar Enteritidis, potentially pathogenic Raoultella planticola and non‐pathogenic Escherichia coli over the course of 24, 48 and 72 h was studied. Biofilm formation was evaluated by the crystal violet assay (CV), enumeration of colony‐forming units (CFU cm−2) and visualization using confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). In general, Gram‐negative bacterial species and S. aureus interacted in a competitive manner. The tested Gram‐negative bacteria grew better in mixed dual‐species biofilms than in their mono‐species biofilms as determined using the CV assay, CFU ml−2 enumeration, and CLSM and SEM visualization. In contrast, the growth of S. aureus biofilms was reduced when cultured in dual‐species biofilms. CLSM images revealed grape‐like clusters of S. aureus and monolayers of Gram‐negative bacteria in both mono‐ and dual‐species biofilms. S. aureus clusters in dual‐species biofilms were significantly smaller than clusters in S. aureus mono‐species biofilms.
Convergence, Divergence and Hybridity: A Regulatory Governance Perspective on Health Technology Assessment in England and Germany
Authors: Wright John S. F. , Barron Anthony J. G. , Shah Sara M. B. , Klingler Corinna
Published: April 2017

Countries adopt different methods and processes to evaluate the benefits and costs of health technologies. It is important to identify and analyse the factors that influence the uptake and use of these methods and processes across countries. In this article, we introduce a regulatory governance approach to the analysis of convergence, divergence and hybridity in Health Technology Assessment (HTA) methods, discussing and critically analysing national processes for HTA in two major EU member states: England and Germany. We argue that any reasonably sophisticated account of national approaches to HTA must recognise that globalisation and the emergence of advanced industrial society involves the potential for widely varying processes, methods and evidential requirements. We suggest that this potential also confronts health policy analysts with the challenge of constructing analytical frameworks capable of identifying the diverse institutional, domestic and other factors that shape national approaches to HTA.
Health Care Organization and Delivery in Argentina: A Case of Fragmentation, Inefficiency and Inequality
Authors: Novick Gabriel E.
Published: April 2017

Fragmentation is a common trait of most Latin‐American systems. In Argentina the lack of integration among sub systems has a deep impact on health care access and financial sustainability, leading to exclusion, inefficiency, inequality, lack of transparency in administration and one of the highest burdens of household catastrophic out‐of‐pocket spending in Latin America. The national budget, although within the average of the region, is insufficient to cover the health care needs of the uninsured and to fully address the imbalances in social determinants of health. In this article, we first present the organizational and financial structure of the health care system. We then analyse the system dynamics and local health care history, and we explore a few possible lines of action and reforms for the next decade. This analysis may provide lessons for other countries in the region with analogous contexts and facing similar challenges.
Impact of early personal‐history characteristics on the Pace of Aging: implications for clinical trials of therapies to slow aging and extend healthspan
Authors: Belsky Daniel W. , Caspi Avshalom , Cohen Harvey J. , Kraus William E. , Ramrakha Sandhya , Poulton Richie , Moffitt Terrie E.
Published: April 2017

Therapies to extend healthspan are poised to move from laboratory animal models to human clinical trials. Translation from mouse to human will entail challenges, among them the multifactorial heterogeneity of human aging. To inform clinical trials about this heterogeneity, we report how humans’ pace of biological aging relates to personal‐history characteristics. Because geroprotective therapies must be delivered by midlife to prevent age‐related disease onset, we studied young‐adult members of the Dunedin Study 1972–73 birth cohort (n = 954). Cohort members’ Pace of Aging was measured as coordinated decline in the integrity of multiple organ systems, by quantifying rate of decline across repeated measurements of 18 biomarkers assayed when cohort members were ages 26, 32, and 38 years. The childhood personal‐history characteristics studied were known predictors of age‐related disease and mortality, and were measured prospectively during childhood. Personal‐history characteristics of familial longevity, childhood social class, adverse childhood experiences, and childhood health, intelligence, and self‐control all predicted differences in cohort members’ adulthood Pace of Aging. Accumulation of more personal‐history risks predicted faster Pace of Aging. Because trials of anti‐aging therapies will need to ascertain personal histories retrospectively, we replicated results using cohort members’ retrospective personal‐history reports made in adulthood. Because many trials recruit participants from clinical settings, we replicated results in the cohort subset who had recent health system contact according to electronic medical records. Quick, inexpensive measures of trial participants’ early personal histories can enable clinical trials to study who volunteers for trials, who adheres to treatment, and who responds to anti‐aging therapies.
DNA damage and senescence in osteoprogenitors expressing Osx1 may cause their decrease with age
Authors: Kim Ha‐Neui , Chang Jianhui , Shao Lijian , Han Li , Iyer Srividhya , Manolagas Stavros C. , O'Brien Charles A. , Jilka Robert L. , Zhou Daohong , Almeida Maria
Published: April 2017

Age‐related bone loss in mice results from a decrease in bone formation and an increase in cortical bone resorption. The former is accounted by a decrease in the number of postmitotic osteoblasts which synthesize the bone matrix and is thought to be the consequence of age‐dependent changes in mesenchymal osteoblast progenitors. However, there are no specific markers for these progenitors, and conclusions rely on results from in vitro cultures of mixed cell populations. Moreover, the culprits of such changes remain unknown. Here, we have used Osx1‐Cre;TdRFP mice in which osteoprogenitors express the TdRFP fluorescent protein. We report that the number of TdRFP‐Osx1 cells, freshly isolated from the bone marrow, declines by more than 50% between 6 and 24 months of age in both female and male mice. Moreover, TdRFP‐Osx1 cells from old mice exhibited markers of DNA damage and senescence, such as γH2AX foci, G1 cell cycle arrest, phosphorylation of p53, increased p21CIP1 levels, as well as increased levels of GATA4 and activation of NF‐κB – two major stimulators of the senescence‐associated secretory phenotype (SASP). Bone marrow stromal cells from old mice also exhibited elevated expression of SASP genes, including several pro‐osteoclastogenic cytokines, and increased capacity to support osteoclast formation. These changes were greatly attenuated by the senolytic drug ABT263. Together, these findings suggest that the decline in bone mass with age is the result of intrinsic defects in osteoprogenitor cells, leading to decreased osteoblast numbers and increased support of osteoclast formation.
Women's attitude towards routine human platelet antigen‐screening in pregnancy
Authors: Winkelhorst Dian , Loeff Rosanne M. , van den Akker‐Van Marle M. Elske , de Haas Masja , Oepkes Dick
Published: April 2017

Introduction

Fetal and neonatal alloimmune thrombocytopenia is a potentially life‐threatening disease with excellent preventative treatment available for subsequent pregnancies. To prevent index cases, the effectiveness of a population‐based screening program has been suggested repeatedly. Therefore, we aimed to evaluate women's attitude towards possible future human platelet antigen‐screening in pregnancy.

Material and methods

We performed a cross‐sectional questionnaire study among healthy pregnant women receiving prenatal care in one of seven participating midwifery practices. Attitude was assessed using a questionnaire based on the validated Multidimensional Measurement of Informed Choice model, containing questions assessing knowledge, attitude and intention to participate.

Results

A total of 143 of the 220 women (65%) completed and returned the questionnaire. A positive attitude towards human platelet antigen‐screening was expressed by 91% of participants, of which 94% was based on sufficient knowledge. Attitude was more likely to be negatively influenced by the opinion that screening can be frightening. Informed choices were made in 87% and occurred significantly less in women from non‐European origin, 89% in European women vs. 60% in non‐European women (p = 0.03).

Conclusions

Pregnant women in the Netherlands expressed a positive attitude towards human platelet antigen‐screening in pregnancy. We therefore expect a high rate of informed uptake when human platelet antigen‐screening is implemented. In future counseling on human platelet antigen‐screening, ethnicity and possible anxiety associated with a screening test need to be specifically addressed.
Studies on supplementary desalted mother liquor on digestibility of nutrients, ruminal fermentation, and energy and nitrogen balance in Thai native cattle
Authors: Sakai Takashi , Angthong Wanna , Takeda Motoharu , Oishi Kazato , Hirooka Hiroyuki , Kumagai Hajime
Published: April 2017

Four Thai native steers were used to determine the adequate levels of supplementary desalted mother liquor (DML) for energy and nitrogen balances and ruminal fermentation. The crude protein and sodium chloride contents of DML were 25.5% and 60.3% on a dry matter (DM) basis, respectively. A 4 × 4 Latin square design experiment was conducted by adding different amounts of DML to three experimental diets (T1: 1.1%, T2: 2.2%, T3: 3.4% sodium chloride concentration with supplementary DML on a DM basis) and comparing their effects with those of a control diet (C) containing 1.0% commercial salt on a DM basis. The animals were given the experimental diets and rice straw daily at 1.2% and 0.8% of body weight, respectively, on a DM basis. No significant differences in the apparent digestibility of nutrients were observed among treatments. T3 achieved the lowest nitrogen retention (P < 0.05), followed by C, T2 and T1. The ratios of energy retention to gross energy were higher in T1 and T3 than T2, and that in C was lowest (P < 0.05). Supplementary NaCl concentration at 1% and 2% can be replaced with DML without an adverse effect on the digestibility of nutrients or on the nitrogen and energy retention.
The effect of authentic m‐learning activities on student engagement and motivation
Authors: Alioon Yasaman , Delialioğlu Ömer
Published: April 2017

Authentic collaborative m‐learning activities were designed, developed and implemented for a computer networking course. The effect of the activities on student engagement and motivation were analyzed using a mixed method research design. Moreover, the effect of the iterative design of the content and instructional process of authentic m‐learning activities on students' engagement and motivation were analyzed in the study. The activities were implemented for two consecutive semesters and were modified based on the findings from the first semester. Student engagement survey and motivation questionnaire were used to collect quantitative data, student interview protocol was used to collect qualitative data for further investigation. The findings from the first semester indicated that the engagement categories “personal development” and “satisfaction from the course” had the highest mean scores. In the second semester, the highest mean score belonged to the “personal development” category, followed by “collaborative learning.” Comparison of the results from two semesters revealed that the improvements in the content of the activities and instructional process increased the “collaboration” among students as well as their “interaction with instructor.” Paired sample t‐tests revealed a difference in indicators of student motivation within groups in both semesters. Analysis of the interview data showed that students perceived the authentic activities as an appropriate tool for enhancement in “communication” and “collaboration” opportunities.
Source organic matter analysis of saltmarsh sediments using SIAR and its application in relative sea‐level studies in regions of C4 plant invasion
Authors: Craven Kieran F. , Edwards Robin J. , Flood Rory P.
Published: April 2017

The introduction of invasive Spartina grasses (C4 plant) into previously C3‐dominated saltmarshes of western Europe complicates the reconstruction of past relative sea‐level (RSL) using sediment geochemistry‐based approaches. We apply a Bayesian mixing model (SIAR – Stable Isotope Analysis in R) to identify organic carbon (Corg) source contributions to saltmarsh sediment and correct δ13C values for the contaminating influence of C4 vegetation. We first assess the performance of SIAR by simulation, producing synthetic saltmarsh sediment samples with variable contributions from three organic matter sources (C3 plants, C4 plants and particulate organic matter (POM)) and then comparing these known contributions to those determined by SIAR. For each source type, SIAR 68% credible intervals include true source contribution in 70% of calculations (n = 60) and all three sources were incorporated within credible intervals for 45% of sediment samples (n = 20). SIAR improves the mean absolute error of source contribution predictions by up to 26% compared to a conventional ternary mixing model approach. We then apply SIAR to real sediment samples recovered along transects spanning the intertidal zones at two contrasting saltmarshes in the inner and outer Shannon estuary, western Ireland. SIAR identified decreasing Corg contributions from POM with increasing elevation in the intertidal zone, reflecting differences in tidal inundation with height. Sediment δ13C values across the intertidal zones varied by 4.4‰ in the inner estuary and 9.4‰ in the outer estuary. Removal of the invasive C4 signatures reduced these differences to 0.5‰ and to 2.4‰ in the inner and outer estuary, respectively, with the larger range due to increased deposition of marine POM. Although subtle, when used in combination with additional proxies, these geochemical gradients can assist in RSL reconstruction. This will be most effective when POM from marine sources is a significant carbon source.
Decision‐making and future planning for children with life‐limiting conditions: a qualitative systematic review and thematic synthesis
Authors: Popejoy E. , Pollock K. , Almack K. , Manning J. C. , Johnston B.
Published: April 2017

Background

In the last decade, the number of children with life‐limiting and life‐threatening conditions in England has almost doubled, and it is estimated that worldwide, there are 1.2 million children with palliative care needs. Families and professionals caring for children with life‐limiting conditions are likely to face a number of difficult treatment decisions and develop plans for future care over the course of the child's life, but little is known about the process by which these decisions and plans are made.

Methods

The purpose of this review is to synthesize findings from qualitative research that has investigated decision‐making and future planning for children with life‐limiting conditions. A systematic search of six online databases was conducted and identified 887 papers for review; five papers were selected for inclusion, using predefined criteria. Reference list searching and contacting authors identified a further four papers for inclusion.

Results

Results sections of the papers were coded and synthesized into themes. Nineteen descriptive themes were identified, and these were further synthesized into four analytical themes. Analytical themes were ‘decision factors’, ‘family factors’, ‘relational factors’ and ‘system factors’.

Conclusions

Review findings indicate that decision‐making and future planning is difficult and needs to be individualized for each family. However, deficits in understanding the dynamic, relational and contextual aspects of decision‐making remain and require further research.
Navigating uncharted terrain: Domestic adoptions in Kenya
Authors: Stuckenbruck Denise , Roby Jini L.
Published: April 2017

Over 2 million children are cared for in kinship care in Kenya, and approximately 100,000 are believed to be living in residential care centres. Under leading international policy instruments ratified and domesticated by Kenya, domestic adoption is considered an option to be promoted and regulated in ensuring children's right to family‐based care. In this qualitative study, the authors interviewed 21 participants regarding the cultural and social contexts of domestic adoption in Kenya. Common beliefs and attitudes reflect a misunderstanding of the legal implications of adoption, the centrality of lineage as a vehicle for defining family membership and inheritance, and strong stigma regarding infertility. Main barriers to adoption include fear of exposing infertility, worry about corrupt practices, and reluctance to grant full inheritance rights to a child unrelated by blood. Despite these challenges, some couples are adopting to fulfil their desire for a child, as an expression of charity, and in some cases for practical reasons such as obtaining insurance for a kin child. The authors recommend placing children in adoption only with proper preparation and ethical procedures and suggest long‐term approaches to promoting adoptions that will ensure full rights of family membership for the child.
Reported normal values and weighted means for commonly used echocardiography pulsed Doppler and tissue Doppler measurements
Authors: Dencker Magnus , Stagmo Martin
Published: April 2017

Pulsed Doppler (PW) and tissue Doppler imaging (TDI) measurements are part of every echocardiography examination for evaluation of left ventricular (LV) diastolic function and filling pressure. The purpose of this study was to summarize published data on normal values for PW and TDI measurements. A PubMed search was performed on the 10th of October 2016 to identify relevant articles. Studies were considered relevant if they included more than 200 healthy individuals. A total of 13 studies were identified. Of these, 13 studies with 7777 subjects reported PW measurement over the mitral valve, six studies with 4082 subjects reported PW measurement in the pulmonary vein and 10 studies with 5988 subjects reported TDI. We also report weighted mean values for 14 different variables. As expected, measurements varied with age. There were no major differences between men and women. In contrast, there was a large difference in reported values between studies, in corresponding age groups. This review therefore raises caution about relying on normal values from just one study.
The Mozart study: a relation between dynamic hyperinflation and physical activity in patients with chronic obstructive pulmonary disease?
Authors: van Leuteren R. W. , Dijkhuis S. , de Jongh F. H. C. , van der Valk P. D. L. P. M. , Tabak M. , Brusse‐Keizer M. G. J.
Published: April 2017

Background

Many patients with chronic obstructive pulmonary disease (COPD) experience dyspnoea during exercise, resulting in a reduction of physical activity (PA). Dynamic hyperinflation (DH) is seen as a major cause of dyspnoea in COPD.

Objective

The objective of the current study was to investigate the relationship between DH, in terms of the amount of DH and the development and recovery rate of DH in patients with COPD, and PA.

Methods

Thirty‐five patients with stable COPD were included from an outpatient clinic (14 GOLD II and 21 GOLD III, median age 65). PA was assessed using an accelerometer. Subjects underwent metronome‐paced tachypnoea (MPT) to induce DH. To quantify the amount of DH during MPT, a decrease in inspiratory capacity (IC) or a change in IC as percentage of total lung capacity was used.

Results

No significant correlations were found between the parameters describing DH and PA. Secondary correlation analyses showed a negative correlation between static hyperinflation (SH) and PA (r = −0·39; P = 0·02). The pattern of breathing during MPT and the test itself showed high interpatient variability.

Conclusions

The absence of a significant correlation between DH and PA is contrary to previous studies. SH did show a correlation with PA. The variety in results and the technical difficulties in execution of the measurements ask for a new, more reliable, method to detect DH and investigate its relation with PA in patients with COPD.