bluuebunny/crossref_metadata_2025 huggingface dataset:
Systematic evaluation and validation of reference and library selection methods for deconvolution of cord blood DNA methylation data
Authors: Gervin Kristina , Salas Lucas A. , Bakulski Kelly M. , van Zelm Menno C. , Koestler Devin C. , Wiencke John K. , Duijts Liesbeth , Moll Henriëtte A. , Kelsey Karl T. , Kobor Michael S. , Lyle Robert , Christensen Brock C. , Felix Janine , Jones Meaghan J.
Published: March 2019

Background

Umbilical cord blood (UCB) is commonly used in epigenome-wide association studies of prenatal exposures. Accounting for cell type composition is critical in such studies as it reduces confounding due to the cell specificity of DNA methylation (DNAm). In the absence of cell sorting information, statistical methods can be applied to deconvolve heterogeneous cell mixtures. Among these methods, reference-based approaches leverage age appropriate cell-specific DNA-methylation profiles to estimate cellular composition. In UCB, four reference datasets comprising DNAm signatures profiled in purified cell populations have been published using the Illumina 450K and 850K EPIC arrays. These datasets are biologically and technically different, and currently there is no consensus on how to best apply them. Here, we systematically evaluate and compare these datasets and provide recommendations for reference-based UCB deconvolution.

Results

We first evaluated the four reference datasets to ascertain both the purity of the samples and the potential cell cross-contamination. We filtered samples and combined datasets to obtain a joint UCB reference. We selected deconvolution libraries using two different approaches: automatic selection using the top differentially methylated probes from the functionpickCompProbesin minfi and a standardized library selected using the IDOL (Identifying Optimal Libraries) iterative algorithm. We compared the performance of each reference separately and in combination, using the two approaches for reference library selection, and validated the results in an independent cohort (Generation R Study, n=191) with matched FACS measured cell counts. Strict filtering and combination of the references significantly improved the accuracy and efficiency of cell type estimates. Ultimately, the IDOL library outperformed the library from the automatic selection method implemented inpickCompProbes.

Conclusion

These results have important implications for epigenetic studies in UCB as implementing this method will optimally reduce confounding due to cellular heterogeneity. This work provides guidelines for future reference-based UCB deconvolution and establishes a framework for combining reference datasets in other tissues.
A high-throughput delayed fluorescence method reveals underlying differences in the control of circadian rhythms inTriticum aestivumandBrassica napus
Authors: Rees Hannah , Duncan Susan , Gould Peter , Wells Rachel , Greenwood Mark , Brabbs Thomas , Hall Anthony
Published: March 2019

Background

A robust circadian clock has been implicated in plant resilience, resource-use efficiency, competitive growth and yield. A huge number of physiological processes are under circadian control in plants including: responses to biotic and abiotic stresses; flowering time; plant metabolism; and mineral uptake. Understanding how the clock functions in crops such asTriticum aestivum(bread wheat) andBrassica napus(oilseed rape) therefore has great agricultural potential. Delayed fluorescence (DF) imaging has been shown to be applicable to a wide range of plant species and requires no genetic transformation. Although DF has been used to measure period length of both mutants and wild ecotypes ofArabidopsis, this assay has never been systematically optimised for crop plants. The physical size of bothB. napusandT. aestivumled us to develop a representative sampling strategy which enables high-throughput imaging of these crops.

Results

In this study, we describe the plant-specific optimisation of DF imaging to obtain reliable circadian phenotypes with the robustness and reproducibility to detect diverging periods between cultivars of the same species. We find that the age of plant material, light regime and temperature conditions all significantly effect DF rhythms and describe the optimal conditions for measuring robust rhythms in each species. We also show that sections of leaf can be used to obtain period estimates with improved throughput for larger sample size experiments.

Conclusions

We present an optimized protocol for high-throughput phenotyping of circadian period specific to two economically valuable crop plants. Application of this method revealed significant differences between the periods of several widely grown elite cultivars. This method also identified intriguing differential responses of circadian rhythms inT. aestivumcompared toB. napus; specifically the dramatic change to rhythm robustness when plants were imaged under constant light versus constant darkness. This points towards diverging networks underling circadian control in these two species.
Genotype-free demultiplexing of pooled single-cell RNA-seq
Authors: Xu Jun , Falconer Caitlin , Nguyen Quan , Crawford Joanna , McKinnon Brett D. , Mortlock Sally , Pébay Alice , Hewitt Alex W. , Senabouth Anne , Andersen Stacey , Palpant Nathan , Chiu Han Sheng , Montgomery Grant W. , Powell Joseph , Coin Lachlan
Published: March 2019

A variety of experimental and computational methods have been developed to demultiplex samples from pooled individuals in a single-cell RNA sequencing (scRNA-Seq) experiment which either require adding information (such as hashtag barcodes) or measuring information (such as genotypes) prior to pooling. We introduce scSplit which utilises genetic differences inferred from scRNA-Seq data alone to demultiplex pooled samples. scSplit also extracts a minimal set of high confidence presence/absence genotypes in each cluster which can be used to map clusters to original samples. Using a range of simulated, merged individual-sample as well as pooled multi-individual scRNA-Seq datasets, we show that scSplit is highly accurate and concordant with demuxlet predictions. Furthermore, scSplit predictions are highly consistent with the known truth in cell-hashing dataset. We also show that multiplexed-scRNA-Seq can be used to reduce batch effects caused by technical biases. scSplit is ideally suited to samples for which external genome-wide genotype data cannot be obtained (for example non-model organisms), or for which it is impossible to obtain unmixed samples directly, such as mixtures of genetically distinct tumour cells, or mixed infections. scSplit is available at: https://github.com/jon-xu/scSplit
Identification and characterization of putativeAeromonasspp. T3SS effectors
Authors: Rangel Luiz Thiberio , Marden Jeremiah , Colston Sophie , Setubal João Carlos , Graf Joerg , Gogarten J. Peter
Published: March 2019

The genetic determinants of bacterial pathogenicity are highly variable between species and strains. However, a factor that is commonly associated with virulent Gram-negative bacteria, including manyAeromonasspp., is the type 3 secretion system (T3SS), which is used to inject effector proteins into target eukaryotic cells. In this study, we developed a bioinformatics pipeline to identify T3SS effector proteins, applied this approach to the genomes of 105Aeromonasstrains isolated from environmental, mutualistic, or pathogenic contexts and evaluated the cytotoxicity of the identified effectors through their heterologous expression in yeast. The developed pipeline uses a two-step approach, where candidate families are initially selected using HMM profiles with minimal similarity scores against the Virulence Factors DataBase (VFDB), followed by strict comparisons against positive and negative control datasets, greatly reducing the number of false positives. Using our approach, we identified 21AeromonasT3SS likely effector groups, of which 8 represented known or characterized effectors, while the remaining 13 had not previously been described inAeromonas. We experimentally validated ourin silicofindings by assessing the cytotoxicity of representative effectors inSaccharomyces cerevisiaeBY4741, with 15 out of 21 assayed proteins eliciting a cytotoxic effect in yeast. The results of this study demonstrate the utility of our approach, combining a novelin silicosearch method within vivoexperimental validation, and will be useful in future research aimed at identifying and authenticating bacterial effector proteins from other genera.
Changes in the Physicochemical Properties and Microbial Communities of Rhizospheric Soil after Cassava/Peanut Intercropping
Authors: Tang Xiumei , Luo Saiyun , Huang Zhipeng , Wu Haining , Wang Jin , Shi Guoying , He Liangqiong , Xiong Faqian , Jiang Jing , Liu Jing , Liao Guojian , Tang Ronghua , He Longfei
Published: March 2019

Cassava/peanut intercropping is a popular cultivation method in southern China and has the advantages of apparently increased yield and economic efficiency compared with monoculture, however, the ecological benefits of this method are poorly understood. This study aimed to investigate the effects of intercropping on the physicochemical properties and microbial community structures of soil. Field trials were performed to determine the effects of cassava/peanut intercropping on rhizospheric soil nutrient content, enzyme activities, microbial quantity and microbial community structure. The microbial community was characterized by 16S rRNA tag-based high-throughput sequencing on the Illumina MiSeq platform. Results showed that cassava/peanut intercropping could improve the physicochemical properties of rhizospheric soil by increasing the available nutrient content, pH, bacterial quantity, and some enzyme activities and by altering the microbial community structure. 16S rRNA gene sequencing demonstrated that the microbial community structure varied between the intercropping and monoculture systems. Nitrospirae, Verrucomicrobia and Gemmatimonadetes were more abundant in the intercropping system than in the monocultures. Redundancy analysis (RDA) revealed that the abundances ofDA101,PilimeliaandRamlibacterwere positively correlated with environmental parameters such as available nitrogen and pH, and these were dominant genera in the rhizospheric soil of the intercropped peanut plants.
Mortality among adults living with HIV treated for tuberculosis based on positive, negative, or no bacteriologic test results for tuberculosis: the IeDEA consortium
Authors: Humphrey John M , Mpofu Philani , Pettit April C. , Musick Beverly , Carter E. Jane , Messou Eugene , Marcy Olivier , Crabtree-Ramirez Brenda , Yotebieng Marcel , Anastos Kathryn , Sterling Timothy R. , Yiannoutsos Constantin , Diero Lameck , Wools-Kaloustian Kara ,   International Epidemiology Databases to Evaluate AIDS (IeDEA) Consortium
Published: March 2019

Background

In resource-constrained settings, people living with HIV (PLWH) treated for tuberculosis (TB) despite negative bacteriologic tests have a higher mortality than those treated with positive tests. Many PLWH are treated without bacteriologic testing; their mortality compared to those with bacteriologic testing is uncertain.

Methods

We conducted an observational cohort study among PLWH ≥ 15 years of age who initiated TB treatment at clinical sites affiliated with four regions of the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium from 2012-2014: Caribbean, Central and South America, and Central, East, and West Africa. The primary exposure of interest was the TB bacteriologic test status at TB treatment initiation: positive, negative, or no test result. The hazard for death in the 12 months following TB treatment initiation was estimated using the Cox proportional hazard model, adjusted for patient- and site-level factors. Missing covariates were multiply imputed.

Results

Among 2,091 PLWH included, the median age at TB treatment initiation was 36 years, 44% were female, 53% had CD4 counts ≤ 200 cells/mm3, and 52% were on antiretroviral treatment (ART). Compared to patients with positive bacteriologic tests, the adjusted hazard for death was higher among patients with no test results (HR 1.56, 95% CI 1.08-2.26) but not different than those with negative tests (HR 1.28, 95% CI 0.91-1.81). Older age was also associated with a higher hazard for death, while being on ART, having a higher CD4 count, West Africa region, and tertiary facility level were associated with lower hazards for death.

Conclusion

PLWH treated for TB with no bacteriologic test results were more likely to die than those treated with positive tests, underscoring the importance of TB bacteriologic diagnosis in resource-constrained settings. Research is needed to understand the causes of death among PLWH treated for TB in the absence of positive bacteriologic tests.
Direct inference of the distribution of fitness effects of spontaneous mutations inChlamydomonas reinhardtii
Authors: Böndel Katharina B. , Kraemer Susanne A. , Samuels Tobias S. , McClean Deirdre , Lachapelle Josianne , Ness Rob W. , Colegrave Nick , Keightley Peter D.
Published: March 2019

Spontaneous mutations are the source of new genetic variation and are thus central to the evolutionary process. In molecular evolution and quantitative genetics, the nature of genetic variation depends critically on the distribution of fitness effects (DFE) of mutations. Spontaneous mutation accumulation (MA) experiments have been the principal approach for investigating the overall rate of occurrence and cumulative effect of mutations, but have not allowed the effects of individual mutations to be studied directly. Here, we crossed MA lines of the green algaChlamydomonas reinhardtiiwith its unmutated ancestral strain to create haploid recombinant lines, each carrying an average of 50% of the accumulated mutations in a variety of combinations. With the aid of the genome sequences of the MA lines, we inferred the genotypes of the mutations, assayed their growth rate as a measure of fitness, and inferred the DFE using a novel Bayesian mixture model that allows the effects of individual mutations to be estimated. We infer that the DFE is highly leptokurtic (L-shaped), and that a high proportion of mutations increase fitness in the laboratory environment. The inferred distribution of effects for deleterious mutations is consistent with a strong role for nearly neutral evolution. Specifically, such a distribution predicts that nucleotide variation and genetic variation for quantitative traits will be insensitive to change in the effective population size.
Mutations inpmrBconfer cross-resistance to the LptD inhibitor POL7080 and colistin inPseudomonas aeruginosa
Authors: Romano Keith P , Warrier Thulasi , Poulsen Bradley E , Nguyen Phuong H , Loftis Alexander R , Saebi Azin , Pentelute Bradley L , Hung Deborah T
Published: March 2019

Pseudomonas aeruginosais a major bacterial pathogen for which there is rising antibiotic resistance. We evaluated the resistance mechanisms ofP. aeruginosaagainst POL7080, a species-specific, first-in-class antibiotic in phase 3 clinical trials targeting the lipopolysaccharide transport protein LptD. We found resistance mutations in the two-component regulatorpmrB. Genome-wide transcriptomics and confocal microscopy studies together suggest that POL7080 is vulnerable to the same resistance mechanisms described previously for polymyxins, including colistin, that involve lipid A modifications to mitigate antibiotic cell surface binding.
Double UP: efficient in utero electroporation via internal controls
Authors: Taylor Russell J. , Carrington Justin , Taylor Kendra L. , Richters Karl E. , Gerlach Leah R. , Dent Erik W.
Published: March 2019

In Utero Electroporation is a powerful tool for testing the role of genes in neuronal migration, but this technique suffers from high degrees of variability due to multiple factors. Therefore, we developed Double UP, a novel approach that combines LoxP-flanked reporters and limiting Cre dosages to generate internal controls. This technique allows for more rigorous quantification of migration, while decreasing the number of animals, reagents and time to complete experiments.
Chromosomal barcoding of E. coli populations reveals lineage diversity dynamics at high resolution
Authors: Lerner Jesse , Manhart Michael , Jasinska Weronika , Gauthier Louis , Serohijos Adrian W.R. , Bershtein Shimon
Published: March 2019

Evolutionary dynamics in large asexual populations is strongly influenced by multiple competing beneficial lineages, most of which segregate at very low frequencies. However, technical barriers to tracking a large number of these rare lineages have so far prevented a detailed elucidation of evolutionary dynamics in large bacterial populations. Here, we overcome this hurdle by developing a chromosomal barcoding technique that allows simultaneous tracking of ∼450,000 distinct lineages in E. coli. We used this technique to gather insights into the evolutionary dynamics of large (>107 cells) E. coli populations propagated for ∼420 generations in the presence of sub-inhibitory concentrations of common antibiotics. By deep sequencing the barcodes, we reconstructed trajectories of individual lineages at high frequency resolution (< 10−5). Using quantitative tools from ecology, we found that populations lost lineage diversity at distinct rates corresponding to their antibiotic regimen. Additionally, by quantifying the reproducibility of these dynamics across replicate populations, we found that some lineages had similar fates over independent experiments. Combined with an analysis of individual lineage trajectories, these results suggest how standing genetic variation and new mutations may contribute to adaptation to sub-inhibitory antibiotic levels. Altogether, our results demonstrate the power of high-resolution barcoding in studying the dynamics of bacterial evolution.
Long-read single-molecule maps of the functional methylome
Authors: Sharim Hila , Grunwald Assaf , Gabrieli Tslil , Michaeli Yael , Margalit Sapir , Torchinsky Dmitry , Arielly Rani , Nifker Gil , Juhasz Matyas , Gularek Felix , Almalvez Miguel , Dufault Brandon , Chandra Sreetama Sen , Liu Alexander , Bhattacharya Surajit , Chen Yi-Wen , Vilain Eric , Wagner Kathryn R. , Pevsner Jonathan , Reifenberger Jeff , Lam Ernest T. , Hastie Alex R. , Cao Han , Barseghyan Hayk , Weinhold Elmar , Ebenstein Yuval
Published: March 2019

We report on the development of a methylation analysis workflow for optical detection of fluorescent methylation profiles along chromosomal DNA molecules. In combination with Bionano Genomics genome mapping technology, these profiles provide a hybrid genetic/epigenetic genome-wide map composed of DNA molecules spanning hundreds of kilobase pairs. The method provides kilobase pair–scale genomic methylation patterns comparable to whole-genome bisulfite sequencing (WGBS) along genes and regulatory elements. These long single-molecule reads allow for methylation variation calling and analysis of large structural aberrations such as pathogenic macrosatellite arrays not accessible to single-cell second-generation sequencing. The method is applied here to study facioscapulohumeral muscular dystrophy (FSHD), simultaneously recording the haplotype, copy number, and methylation status of the disease-associated, highly repetitive locus on Chromosome 4q.
Capturing digital (in)equity in teaching and learning: a sociocritical approach
Authors: Collin Simon , Brotcorne Périne
Published: March 2019

Purpose

The purpose of this paper is to present a sociocritical approach and describe how it is relevant to the study of digital equity in education.

Design/methodology/approach

The method is based on a synthesis of the literature regarding critical approaches to digital technology in education.

Findings

A sociocritical approach is an attempt to formulate a sociological perspective combined with a critical dimension. It provides a relevant theoretical basis for addressing digital (in)equity issues.

Originality/value

Little use has been made of critical theories in the study of digital technology in education. That may seem surprising insofar as the study of digital technology in education is related to other fields having a well-established critical tradition. The authors build on their work and tailor it to the case of digital technology in education.
The SNARE protein FolVam7 mediates intracellular trafficking to regulate conidiogenesis and pathogenicity in Fusarium oxysporum f. sp. lycopersici
Authors: Li Bing , Gao Ying , Mao Hui‐Ying , Borkovich Katherine A. , Ouyang Shou‐Qiang
Published: March 2019

Soluble N‐ethylmaleimide‐sensitive factor attachment protein receptors (SNAREs) are conserved in fungi, plants and animals. The Vam7 gene encodes a v‐SNARE protein that involved in vesicle trafficking in fungi. Here, we identified and characterized the function of FolVam7, a homologue of the yeast SNARE protein Vam7p in Fusarium oxysporum f. sp. lycopersici (Fol), a fungal pathogen of tomato. FolVam7 contains SNARE and PX (Phox homology) domains that are indispensable for normal localization and function of FolVam7. Targeted gene deletion showed that FolVam7‐mediated vesicle trafficking is important for vegetative growth, asexual development, conidial morphology and plant infection. Further cytological examinations revealed that FolVam7 is localized to vesicles and vacuole membranes in the hyphae stage. Moreover, the ΔFolvam7 mutant is insensitive to salt and osmotic stresses and hypersensitive to cell wall stressors. Taken together, our results suggested that FolVam7‐mediated vesicle trafficking promotes vegetative growth, conidiogenesis and pathogenicity of Fol.
The mediating effect of trust on the relationship between high‐performance work systems and employee outcomes among Chinese indigenous firms
Authors: Min Min , Zhu Ying , Bambacas Mary
Published: March 2019

In this article, we explore the mediating effect of trust on the relationship between high‐performance work systems (HPWS) and employee outcomes. Using a mixed method design, we first conducted focus groups and interviews to gain an understanding of the HPWS in Chinese indigenous firms. Extracting data from the interviews, we then developed a survey which tested our hypotheses. As predicted, data from 907 questionnaires illustrated that employees’ perceptions of the impact of enacted HPWS on building the trust relationship between manager/supervisor and employee in Chinese indigenous firms have a positive effect on employee job satisfaction and intention to stay. The results suggest that organisations may influence how employees perceive manager trustworthiness. It is likely that organisations can design systems that address employee needs, build trust, enhance employee satisfaction and deter them from leaving.
The p53/miRNAs/Ccna2 pathway serves as a novel regulator of cellular senescence: Complement of the canonical p53/p21 pathway
Authors: Xu Shun , Wu Weijia , Huang Haijiao , Huang Ruxiao , Xie Luoyijun , Su Ailing , Liu Shuang , Zheng Ruinian , Yuan Yuan , Zheng Hui‐ling , Sun Xuerong , Xiong Xing‐dong , Liu Xinguang
Published: March 2019

Aging is a multifactorial process characterized by the progressive deterioration of physiological functions. Among the multiple molecular mechanisms, microRNAs (miRNAs) have increasingly been implicated in the regulation of Aging process. However, the contribution of miRNAs to physiological Aging and the underlying mechanisms remain elusive. We herein performed high‐throughput analysis using miRNA and mRNA microarray in the physiological Aging mouse, attempted to deepen into the understanding of the effects of miRNAs on Aging process at the “network” level. The data showed that various p53 responsive miRNAs, including miR‐124, miR‐34a and miR‐29a/b/c, were up‐regulated in Aging mouse compared with that in Young mouse. Further investigation unraveled that similar as miR‐34a and miR‐29, miR‐124 significantly promoted cellular senescence. As expected, mRNA microarray and gene co‐expression network analysis unveiled that the most down‐regulated mRNAs were enriched in the regulatory pathways of cell proliferation. Fascinatingly, among these down‐regulated mRNAs, Ccna2 stood out as a common target of several p53 responsive miRNAs (miR‐124 and miR‐29), which functioned as the antagonist of p21 in cell cycle regulation. Silencing of Ccna2 remarkably triggered the cellular senescence, while Ccna2 overexpression delayed cellular senescence and significantly reversed the senescence‐induction effect of miR‐124 and miR‐29. Moreover, these p53 responsive miRNAs were significantly up‐regulated during the senescence process of p21‐deficient cells; overexpression of p53 responsive miRNAs or knockdown of Ccna2 evidently accelerated the cellular senescence in the absence of p21. Taken together, our data suggested that the p53/miRNAs/Ccna2 pathway might serve as a novel senescence modulator independent of p53/p21 pathway.
Impaired decision making following escalation of cocaine self‐administration predicts vulnerability to relapse in rats
Authors: Cocker Paul John , Rotge Jean‐Yves , Daniel Marie‐Laure , Belin‐Rauscent Aude , Belin David
Published: March 2019

Impairments in cost‐benefit decision making represent a cardinal feature of drug addiction. However, whether these alterations predate drug exposure, thereby contributing to facilitating loss of control over drug intake, or alternatively arise as a result of drug use and subsequently confer vulnerability to relapse has yet to be determined. Male Sprague‐Dawley rats were trained to self‐administer (SA) cocaine during 19 daily long‐access (12‐h) sessions; conditions reliably shown to promote escalation. One week after cocaine SA, rats underwent an extinction/relapse test immediately followed by conditioned stimuli–, stress‐, and drug‐primed reinstatement challenges. The influence of escalated cocaine intake on decision making was measured over time by four test sessions of a rodent analogue of the Iowa Gambling Task (rGT), once prior to cocaine exposure and then 1 day, 1 week, and 1 month after the last SA session. Substantial individual variability was observed in the influence of escalated cocaine SA on decision‐making performance. A subset of rats displayed pronounced deficits, while others showed unaffected or even improved performance on the rat Gambling Task (rGT) 24 hours after the last SA session. When challenged with a relapse test after 1 week of forced abstinence, animals that showed impaired decision making following SA displayed an increased propensity to respond for cocaine under extinction. These data suggest that decision‐making deficits in individuals with drug addiction are not antecedent to—but arise as a consequence of—drug exposure. Moreover, these data indicate that susceptibility to the deleterious effects of drugs on decision making confers vulnerability toward relapse.
Clinical characteristics and outcomes of patients enrolled in clinical trials compared with those of patients outside clinical trials in advanced gastric cancer
Authors: Han Jae Joon , Kim Jin Won , Suh Koung Jin , Kim Ji‐won , Kim Se Hyun , Kim Yu Jung , Kim Jee Hyun , Lee Jong Seok , Lee Keun‐Wook
Published: March 2019

Aims

Participating in clinical trials could give cancer patients potential benefits such as experimental treatment, meticulous follow‐up, and management of toxicities. We hypothesized that patients participating in clinical trials would achieve better survival outcomes than those not enrolled in trials. We assessed whether the trial effect can improve survival for patients with advanced gastric cancer.

Methods

We retrospectively enrolled metastatic or recurrent gastric cancer patients who received palliative chemotherapy from January 2010 to December 2012. All patients in this study received fluoropyrimidine and platinum as the first‐line palliative chemotherapy. Patients participating in clinical trials were matched 1:1 with patients not enrolled in trial based on propensity‐score.

Results

A total of 229 patients were identified, 83 (36.2%) among them participated in 14 clinical trials for advanced gastric cancer. The number of patients enrolled in phase I, II and III trials were 10, 54 and 19, respectively. The median overall survival of the total study patients was 13.0 months (95% confidence interval, 10.7–15.3 months). In the propensity‐score matched population, a total of 78 matched pairs of patients were generated. The median overall survival of the 78 patients who participated in the clinical trials was 6 months longer than that of patients not enrolled in trials, although this benefit was marginally significant (15 months vs 9 months, hazard ratio, 0.709; p = 0.068). Participation in clinical trials was a significant factor to predict better overall survival in multivariate analysis (hazard ratio, 0.533, p = 0.001).

Conclusion

Trial effect may contribute to prolongation of overall survival in patients who participate in clinical trials for advanced gastric cancer. Physicians may discuss trial effect to encourage participation in clinical trials.
Performing Healing: Repetition, Frequency, and Meaning Response in a Chol Maya Ritual
Authors: Rodríguez Lydia , López Sergio D.
Published: March 2019

This article explores the role that repetition plays in symbolic healing through a close examination of the speech patterns and actions performed by a healer in a Chol Maya ritual aimed at curing a woman of kisiñ—the “embarrassment‐sickness.” The authors examine the repetition of speech patterns in the healing chant and the frequency with which other paralinguistic elements, such as taps, co‐occur with the chant verses. The sound patterns generated during the ritual, specifically those created by the rhythmic tapping of the patient's body with a bough bouquet, are yet another form of repetition often overlooked in analyses of healing rituals, which have concentrated on other symbolic elements used by healers. It is argued that the repetition of phrases in parallel verses serves as metapragmatic commentary on the healing process as a restructuring of the patient's body, which has been unstructured by the disease.
“Hay que agacharse”: The Embodiment of Culture in the Participant Observer Experience and the Return tothe West
Authors: Müller‐Schwarze Nina
Published: March 2019

Dichotomous categories, such asthe Westandthe rest,primitiveandmodern, are discussed within a phenomenological theory that suggests humans create structures through which we perceive objects. The perception ofcultureas an object and its construction through the epistemological practices of fieldwork and interpretation within the metaphor ofWestandnon‐Westernreveals the structure of sociocultural anthropological inquiry and expresses embodiment of the cosmology of nations. Experiences of, and shared understandings regarding, the body, soul, knowledge, thoughts, emotions, memories, spirits, voice, and speech are compared from descriptions, participant observation, and embodiment as a multi‐site ethnographic performance artist expressing new genres of ethnography.Harmonyis defined as social location.
Making Sense of Near‐Death Experience Research: Circumstance Specific Alterations of Consciousness
Authors: Craffert Pieter F.
Published: March 2019

The growing body of research on near‐death experiences (NDEs) is an indication of the large number of people claiming such experiences. A surprising feature of the research is that conceptually there is no agreement on what anNDEis and consequently a large number of definitions characterize this field of research. In order to address the definitional quagmire, a first step consists of making sense ofNDEdefinitions. An analysis of existing definitions shows that the term is currently used for at least three distinct phenomena: a cluster of experiences encountered in the process of dying, for that cluster of experiences in circumstances of fear‐death and danger, and for that cluster of experiences independently from any life‐threatening circumstances. Secondly, the nested assumptions that characterize identified patterns inNDEresearch are identified. It is shown that pro‐survivalists seeNDEs as a unitary entity with a single explanation, while others restrict the study ofNDEs to life‐threatening circumstances and see them as a cluster of composite experiences. Based on this analysis it is argued that the pattern of experiences labeledNDEs can be modified tocircumstance specific alterations of consciousness.
Paediatric haematohidrosis: an overview of a rare but clinically distinct condition
Authors: Hansson Karl , Johansson Emma K. , Albåge Margareta , Ballardini Natalia
Published: March 2019

Haematohidrosis is a rare and dramatic condition in which bleeding occurs spontaneously from intact skin. We report the case of a nine‐year‐old boy with a typical clinical presentation. The case highlights how challenging it can be for medical professionals to recognise and evaluate rare conditions. A review of the literature was performed, showing that haematohidrosis is mainly a paediatric condition. Our case together with findings from the review indicates that treatment with Beta blockers may be effective for treatment of haematohidrosis in children.

Conclusion: Paediatric haematohidrosis is a rare, but clinically distinct condition. Treatment with Beta blockers may be tested.
Availability and readability of patient education materials for deprescribing: An environmental scan
Authors: Fajardo Michael Anthony , Weir Kristie Rebecca , Bonner Carissa , Gnjidic Danijela , Jansen Jesse
Published: March 2019

Aims

To identify and evaluate content and readability of freely available online deprescribing patient education materials (PEMs).

Methods

Systematic review of PEMs using MEDLINE, Embase, CINAHL, PsycINFO and The Cochrane Library of Systematic Reviews from inception to 25 September 2017 to identify PEMs. Additionally, deprescribing researchers and health professionals were surveyed to identify additional materials. Known repositories of materials were searched followed by a systematic Google search (22–28 January 2018). Materials were evaluated using an approach informed by the Patient Education Material Assessment Tool and the International Patient Decision Aids Standards Inventory. Readability of text‐based materials was assessed using the US‐based Gunning–Fog Index and Flesch–Kincaid Grade level.

Results

Forty‐eight PEMs were identified. PEMs addressing deprescribing of medications for symptom control (81%) were most common. Preventative medications were rarely addressed and material (39%) focused on older people. Only 37% of PEMs provided information about both potential benefits (e.g. reducing risk of side effects) and harms (e.g. withdrawal symptoms, increased risk of disease) of deprescribing, while 40% focussed on benefits only. Readability indices indicated an average minimum reading level of Grade 12. Option Grids and Decision Aids (mean reading level below Grade 10) were most suitable for people with average literacy levels.

Conclusions

Over 1/3 of deprescribing PEMs present potential benefits and harms of deprescribing indicating most of the freely available materials are not balanced. Most PEMs are pitched above average reading levels making them inaccessible for low health literacy populations.
Predicting Web 2.0 use among US teens—Expanding the power of the skill, will and tool model
Authors: Grant David G.
Published: March 2019

There is a need to understand antecedents to US teens’ use of information and communication technology (ICT). Research on the “digital divide” for access to ICT reports conflicting findings based on gender and demographic factors of parent income and education. This study expanded the “tool‐will‐skill” framework to examine how demographic factors, access to ICT tools, teen will factors and social networking skill explain variation in Internet use among US teens. The study analyzed national data from Pew Research Center’s survey of 1,060 US teens. Principal component analysis (PCA) identified six latent variables for teen will. A pre‐diagram depicts a conceptual framework and causal assumption of relationships between demographic factors, tool factors (ie, Internet access, smartphone access and tablet access), will factors (from PCA) and skill factors (Facebook, Instagram, Snapchat and Twitter). Multiple linear path analysis was conducted, and results reported. Recommendations are suggested for instructional practice, educational policy and future research.
Latent class analysis of non‐formal learners’ self‐directed learning patterns in open educational resource repositories
Authors: Kim Dongho , Lee In‐Heok , Park Joo‐Ho
Published: March 2019

Open educational resources (OERs) are increasingly adopted in non‐formal education contexts. However, little research has been conducted to investigate the self‐directed learning patterns of non‐formal learners using OERs. A lack of knowledge about non‐formal learners precludes discussions on how to support their self‐regulated learning in open learning environments. We explored the self‐directed learning patterns of 1892 non‐formal online learners who were using OER repositories. In addition, we examined whether differences existed in future intentions to use OERs between learners with different learning patterns. Four latent classes were identified, and learners’ age was found to affect class membership. We also found that non‐formal learners’ use of self‐directed learning strategies predicted their future intentions to use OERs. This study advanced our understanding of the subpopulations of non‐formal learners using OERs. Future research will benefit from the findings related to designing OER environments that can accommodate diverse self‐directed learners.
Global Poverty and Inequality: Change and Continuity in Late Development
Authors: Sumner Andy
Published: March 2019

This contribution assesses the ‘converging divergence’ thesis that global inequality is falling and national inequality is rising. The article argues that falling global inequality is primarily due to China's development and that national inequality has risen in some developing countries and fallen in others. In light of the dominance of China's development in the global picture, questions arise as to what has changed and what has not changed outside of China. A set of changes and continuities is presented. It is then argued that these changes and continuities provide for the contemporary relevance an older conceptual lens — that of ‘late development’.
Convergence Is Not Equality
Authors: Bangura Yusuf
Published: March 2019

Despite the fall in global income inequality in the last two decades, levels of living among individuals in the world are still very different and are likely to remain so for a very long time. The uneven rate of decline in inequality and growth volatility in commodity‐dependent countries suggest that there is no reason to believe that global inequality will continue to fall until it reaches acceptably low levels. Global disparities in incomes and welfare, especially in social protection, are at the heart of the problem of migration and populism in Western democracies in recent years. They bring out in bold relief the lack of fit between claims of global convergence and people's perceptions on incomes and well‐being between the global North and South. In this regard, it is more realistic to talk about ‘multiple geographies of 21st century development’ than a ‘one world’ or single geography of global development. Issues of power, and the way global and national relationships and rules allocate advantages and disadvantages, or promote convergence and divergence, between and within countries, need to be front and centre in the discussion on global convergence.
From ‘Global’ to ‘Revolutionary’ Development
Authors: Büscher Bram
Published: March 2019

This article argues that Horner and Hulme's call for moving towards ‘global development’ to do justice to changing 21st century development geographies neither contributes to advancing our understanding of contemporary development challenges nor helps articulate realistic responses to tackle them. A key problem is that they try to explain several general trends in the geography of development with reference to mainstream statistics without appropriate critical reflection or adequate theorization. Focusing specifically on the environmental and conservation aspects of development, this article contends that these omissions not only confuse the debate on the current state and geographies of development, they risk something more serious, namely the reinforcement of a generic development narrative which will intensify 21st century development challenges. The article concludes that what we need is not global development but revolutionary development.
Impact of glycaemic control on fracture risk in 5368 people with newly diagnosed Type 1 diabetes: a time‐dependent analysis
Authors: Thayakaran R. , Perrins M. , Gokhale K. M. , Kumaran S. , Narendran P. , Price M. J. , Nirantharakumar K. , Toulis K. A.
Published: March 2019

Aims

To assess whether glycaemic control is associated with a lifelong increased risk of fracture in people with newly diagnosed Type 1 diabetes.

Methods

People with newly diagnosed Type 1 diabetes between 1 January 1995 and 10 May 2016 were identified in The Health Improvement Network database. Longitudinal HbA1c measurements from diagnosis to fracture or study end or loss to follow‐up were collected. A Cox proportional hazards model with HbA1c included as a time‐dependent variable was fitted to these data.

Results

Some 5368 people with newly diagnosed Type 1 diabetes were included. The estimated adjusted hazard ratio (aHR) for HbA1c was statistically significant [aHR 1.007; 95% confidence interval (CI) 1.002–1.011 (mmol/mol) and aHR 1.07; 95% CI 1.03–1.12 (%)]. An incremental higher risk of fracture was observed with increasing levels of HbA1c.

Conclusions

In people with newly diagnosed Type 1 diabetes, higher HbA1c is associated with an increased risk for fractures.
Gastrin analogue administration adds no significant glycaemic benefit to a glucagon‐like peptide‐1 receptor agonist acutely or after washout of both analogues
Authors: Bokvist Krister , Ding Ying , Landschulz William H. , Sinha Vikram , Pastrak Aleksandra , Belin Ruth M.
Published: March 2019

Aim

To determine if a 4‐week course of 14 mg weekly GLP‐1 agonist LY2428757 combined with 3 mg or 2 mg daily gastrin analogue TT223 (LY+TT223) results in long‐term glycaemic changes.

Materials and methods

Patients with in adequately‐controlled type 2 diabetes mellitus ±metformin (N=151) were randomized to a 4‐week course of LY+TT223 (3 mg), LY+TT223 (2 mg), LY+TT223 placebo (LY‐only) or LY placebo+TT223 placebo (placebo). The primary objective was change in HbA1c from baseline to 5 month safter completion of therapy (i.e. at 6 months) and safety and tolerability with LY+TT223 versus LY‐only.

Results

LY groups showed HbA1c reductions during the active treatment phase. These did not persist during follow‐up phase. Combining TT223 with LY did not result in additional glycaemic effects during treatment or follow‐up. At 6 months, LSM ± SE for change in HbA1c from baseline was: LY+TT223 (3 mg): ‐0.1 ± 0.2%; LY+TT223 (2 mg): 0.1 ± 0.2%; LY‐only: ‐0.2 ± 0.2%; placebo: 0.04 ± 0.2%. Secondary analyses were consistent with primary results. LY+TT223 was not superior to LY for other time points or end points, including insulin secretory response to mixed meal tolerance tests. The most common adverse events (nausea and vomiting) were more frequent with LY+TT223 versus LY‐only. The safety profile was consistent with previous findings.

Conclusion

GLP‐1+gastrin combination therapy did not improve glycaemic control versus GLP‐1 alone.
COMPETITION FOR UNIVERSITY PLACES AND PARENTAL TIME INVESTMENTS: EVIDENCE FROM THE UNITED KINGDOM
Authors: Borra Cristina , Sevilla Almudena
Published: March 2019

Across the industrialized world college‐educated parents invest more time in their children relative to noncollege‐educated parents. Yet, the reason for the education gradient in parental time investments is not well understood. Using 24‐hour diary surveys since the 1970s we document an inverse U‐shape in the education gradient in the United Kingdom. Theories unfolding gradually and monotonically cannot easily explain this pattern. Using an exogenous increase in the number of students going on to university in the 1980s, we show that an alternative explanation based on competition for university places can explain the temporal and spatial variation in the education gradient. (JEL J13, J24)
Plastic eta factor and blunting line for characterization of fracture toughness of dissimilar metal weld
Authors: Kumar Suranjit , Kumar Anshu , Singh Pawan Kumar , Chattopadhyay Jayanta
Published: March 2019

This paper addresses the fracture toughness evaluation procedure of different zones of dissimilar metal weld (DMW). Experiments have been conducted on compact tension specimens from DMW joint having initial notch in centre of weld and fusion boundaries. Plastic eta factors (ηp) and slope of blunting line (bl) for above specimens have been evaluated numerically. Experimental load, load line displacement, and crack growth data along with numerically evaluated ηp and bl have been used for calculation of fracture resistance curve and initiation fracture toughness, and finally, it has been compared with that evaluated as per ASTM E1820 and ESIS standard.
Livestock disturbances in Mediterranean temporary ponds: A mesocosm experiment with sheep manure and simulated trampling
Authors: Van den Broeck Maarten , Rhazi Laila , Waterkeyn Aline , El Madihi Mohammed , Grillas Patrick , Kneitel Jamie M. , Brendonck Luc
Published: March 2019

The number and quality of temporary wetlands are declining worldwide and many of the remaining habitats are used as pastures and drinking sites for livestock. Livestock can impact wetlands through a combination of herbivory (defoliation), trampling (physical disturbance), and defecation (nutrient input), but how these influence community structure is still poorly understood. It is nonetheless generally accepted that wetland management can include some grazing, and that properly managed livestock can play a major role in wetland conservation. In Mediterranean temporary ponds, however, it is suggested that grazing might negatively affect macrophyte biodiversity within the pond basin. The impact of livestock on the characteristic freshwater fauna also remains understudied.

Using an outdoor mesocosm experiment, we focused on two effects of sheep livestock (trampling and defecation) and their combination, on water quality and on faunal and floral communities from Moroccan temporary ponds. Communities from forested and agricultural sites (pond type) were also compared in a factorial design with treatments.

We found that sheep‐simulated trampling and nutrient input decreased hatching invertebrate and plant richness, while lasting effects on water quality and actively colonising communities were limited. Temporary pond communities from forested and agricultural sites differed in species composition and interacted with treatments in their effects on hatching crustaceans and macrophyte species composition. Treatments had a larger effect on the species composition of forest ponds compared to agricultural ponds.

These results highlight the complex effects livestock may have on aquatic communities. Water quality, taxonomic groups, and trophic levels responded negatively to trampling and waste treatments and these responses changed with pond type. With worldwide declines of seasonal wetland habitat, the effects of land use (i.e. livestock grazing) on these ecosystems and their biota are important to consider for integrated and sustainable management.