bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the Performance of the De Novo Postoperative Stress Urinary Incontinence Calculator
Authors: Ross James H. , Carter-Brooks Charelle M. , Ruppert Kristine M. , Giugale Lauren E. , Shepherd Jonathan P. , Zyczynski Halina M.
Published: March 2019

Objective

The aim of the study was to determine the performance of a previously published stress urinary incontinence (SUI) risk calculator in women undergoing minimally invasive or transvaginal apical suspensions.

Methods

Using a database of stress-continent women who underwent minimally invasive or transvaginal apical suspensions, we calculated 2 prediction risks for development of SUI within 12 months based on inclusion of a “prophylactic” midurethral sling at the time of prolapse surgery. Observed subjective and objective continence status was abstracted from medical records. Regression models were created for the outcome of de novo SUI to generate receiver operating curves. Concordance (c) indices were estimated for the overall and procedure subgroups to determine the calculator’s ability to discriminate between SUI outcomes.

Results

Analyses included 502 women. De novo SUI was observed in 23.5% of women. The mean ± SD calculated risk of de novo SUI if a sling was performed was 18.9% ± 13.9 at 12 months compared with 36.4% ± 8.3 without sling. The calculator’s discriminative ability for those with a planned sling was moderate (c-index = 0.55, P = 0.037). The calculator failed to discriminate continence outcomes when a sling was not planned in the overall group (c-index = 0.50, P = 0.799) and individual apical procedures.

Conclusions

The SUI risk calculator is significantly limited in its ability to predict de novo SUI in our population of women planning minimally invasive apical suspensions. Refinements to the calculator model are needed to improve its utility in clinical practice.
WACS: Improving ChIP-seq Peak Calling by Optimally Weighting Controls
Authors: Awdeh Aseel , Turcotte Marcel , Perkins Theodore J.
Published: March 2019

Motivation

Chromatin immunoprecipitation followed by high throughput sequencing (ChIP-seq), initially introduced more than a decade ago, is widely used by the scientific community to detect protein/DNA binding and histone modifications across the genome. Every experiment is prone to noise and bias, and ChIP-seq experiments are no exception. To alleviate bias, the incorporation of control datasets in ChIP-seq analysis is an essential step. The controls are used to account for the background signal, while the remainder of the ChIP-seq signal captures true binding or histone modification. However, a recurrent issue is different types of bias in different ChIP-seq experiments. Depending on which controls are used, different aspects of ChIP-seq bias are better or worse accounted for, and peak calling can produce different results for the same ChIP-seq experiment. Consequently, generating “smart” controls, which model the non-signal effect for a specific ChIP-seq experiment, could enhance contrast and increase the reliability and reproducibility of the results.

Results

We propose a peak calling algorithm, Weighted Analysis of ChIP-seq (WACS), which is an extension of the well-known peak caller MACS2. There are two main steps in WACS: First, weights are estimated for each control using non-negative least squares regression. The goal is to customize controls to model the noise distribution for each ChIP-seq experiment. This is then followed by peak calling. We demonstrate that WACS significantly outperforms MACS2 and AIControl, another recent algorithm for generating smart controls, in the detection of enriched regions along the genome, in terms of motif enrichment and reproducibility analyses.

Conclusion

This ultimately improves our understanding of ChIP-seq controls and their biases, and shows that WACS results in a better approximation of the noise distribution in controls.
Unifying Gene Duplication, Loss, and Coalescence on Phylogenetic Networks
Authors: Du Peng , Ogilvie Huw A. , Nakhleh Luay
Published: March 2019

Statistical methods were recently introduced for inferring phylogenetic networks under the multispecies network coalescent, thus accounting for both reticulation and incomplete lineage sorting. Two evolutionary processes that are ubiquitous across all three domains of life, but are not accounted for by those methods, are gene duplication and loss (GDL).

In this work, we devise a three-piece model—phylogenetic network, locus network, and gene tree—that unifies all the aforementioned processes into a single model of how genes evolve in the presence of ILS, GDL, and introgression within the branches of a phylogenetic network. To illustrate the power of this model, we develop an algorithm for estimating the parameters of a phylogenetic network topology under this unified model. The algorithm consists of a set of moves that allow for stochastic search through the parameter space. The challenges with developing such moves stem from the intricate dependencies among the three pieces of the model. We demonstrate the application of the model and the accuracy of the algorithm on simulated as well as biological data.

Our work adds to the biologist’s toolbox of methods for phylogenomic inference by accounting for more complex evolutionary processes.
Impact of in vivo protein folding probability on local fitness landscapes
Authors: Faber Matthew S. , Wrenbeck Emily E. , Azouz Laura R. , Steiner Paul J. , Whitehead Timothy A.
Published: March 2019

It is incompletely understood how biophysical properties like protein stability impact molecular evolution and epistasis. Epistasis is defined as specific when a mutation exclusively influences the phenotypic effect of another mutation, often at physically interacting residues. By contrast, nonspecific epistasis results when a mutation is influenced by a large number of non-local mutations. As most mutations are pleiotropic, the in vivo folding probability – governed by basal protein stability – is thought to determine activity-enhancing mutational tolerance, which implies that nonspecific epistasis is dominant. However, evidence exists for both specific and nonspecific epistasis as the prevalent factor, with limited comprehensive datasets to validate either claim. Using deep mutational scanning we probe how in vivo enzyme folding probability impacts local fitness landscapes. We computationally designed two different variants of the amidase AmiE in which catalytic efficiencies are statistically indistinguishable but the enzyme variants have lower probabilities of folding in vivo. Local fitness landscapes show only slight alterations among variants, with essentially the same global distribution of fitness effects. However, specific epistasis was predominant for the subset of mutations exhibiting positive sign epistasis. These mutations mapped to spatially distinct locations on AmiE near the initial mutation or proximal to the active site. Intriguingly, the majority of specific epistatic mutations were codon-dependent, with different synonymous codons resulting in fitness sign reversals. Together, these results offer a nuanced view of how protein folding probability impacts local fitness landscapes, and suggest that transcriptional-translational effects are an equally important determinant as stability in determining evolutionary outcomes.
Cell signalling stabilizes morphogenesis against noise
Authors: Hagolani Pascal , Zimm Roland , Marin-Riera Miquel , Salazar-Ciudad Isaac
Published: March 2019

Embryonic development involves gene networks, extracellular signaling, cell behaviors (cell division, apoptosis, adhesion, etc.) and mechanical interactions. How should gene networks, extracellular signaling and cell behaviors be coordinated to lead to complex and robust morphologies?

To explore this question, we randomly wired genes and cell behaviors into a huge number of networks in EmbryoMaker. EmbryoMaker is a general mathematical model of animal development that simulates how embryos change,i.e.how the 3D spatial position of cells change, over time due such networks. Real gene networks are not random. Random networks, however, allow an unbiased view on the requirements for complex and robust development.

We found that the mere autonomous activation of cell behaviors, especially cell division and contraction, was able to lead to the development of complex morphologies. We also found that complex morphologies tend to be less robust to noise than simple morphologies. However, we found that morphologies that developed through extracellular signaling and complex gene networks were, on average, more robust to noise. This stabilization occurs when gene networks and extracellular signaling partition the embryo into different regions where cell behaviors are regulated in slightly different ways. Our results are consistent with theories proposing that morphological complexity arose in early metazoan evolution as a consequence of the cell bio-mechanics already present in protozoa and that robustness evolved by the co-option of gene networks and extracellular cell signaling.
Distance Measures for Tumor Evolutionary Trees
Authors: DiNardo Zach , Tomlinson Kiran , Ritz Anna , Oesper Layla
Published: March 2019

In recent years, there has been increased interest in studying cancer by using algorithmic methods to infer the evolutionary tree underlying a tumor’s developmental history. Quantitative measures that compare such trees are then vital to benchmarking these algorithmic tree inference methods, understanding the structure of the space of possible trees for a given dataset, and clustering together similar trees in order to evaluate inheritance patterns. However, few appropriate distance measures exist, and those that do exist have low resolution for differentiating trees or do not fully account for the complex relationship between tree topology and how the mutations that label that topology are inherited. Here we present two novel distance measures,CommonAncestorSetdistance (CASet) andDistinctlyInheritedSetComparison distance (DISC), that are specifically designed to account for the subclonal mutation inheritance patterns characteristic of tumor evolutionary trees. We apply CASet and DISC to two simulated and two breast cancer datasets and show that our distance measures allow for more nuanced and accurate delineation between tumor evolutionary trees than existing distance measures. Implementations of CASet and DISC are available at:https://bitbucket.org/oesperlab/stereodist.
Validation and characterization of a DNA methylation alcohol biomarker across the life course
Authors: Yousefi Paul Darius , Richmond Rebecca , Langdon Ryan , Ness Andrew , Liu Chunyu , Levy Daniel , Relton Caroline , Suderman Matthew , Zuccolo Luisa
Published: March 2019

Recently, an alcohol predictor was developed using DNA methylation at 144 CpG sites (DNAm-Alc) as a biomarker for improved clinical or epidemiologic assessment of alcohol-related ill health. We validate the performance and characterize the drivers of this DNAm-Alc for the first time in independent populations. In N=1,049 parents from the Avon Longitudinal Study of Parents and Children (ALSPAC) Accessible Resource for Integrated Epigenomic Studies (ARIES) at midlife, we found DNAm-Alc explained 7.6% of the variation in alcohol intake, roughly half of what had been reported previously, and interestingly explained a larger 9.8% of AUDIT score, a scale of alcohol use disorder. Explanatory capacity in participants from the offspring generation of ARIES measured during adolescence was much lower. However, DNAm-Alc explained 14.3% of the variation in replication using the Head and Neck 5000 (HN5000) clinical cohort that had higher average alcohol consumption. To investigate whether this relationship was being driven by genetic and/or earlier environment confounding we examined how earlier vs. concurrent DNAm-Alc measures predicted AUDIT scores. In both ARIES parental and offspring generations, we observed associations between AUDIT and concurrent, but not earlier DNAm-Alc, suggesting independence from genetic and stable environmental contributions. The stronger relationship between DNAm-Alcs and AUDIT in parents at midlife compared to adolescents despite similar levels of consumption suggests that DNAm-Alc likely reflects long-term patterns of alcohol abuse. Such biomarkers may have potential applications for biomonitoring and risk prediction, especially in cases where reporting bias is a concern.
MicroRNA levels in bone and blood change during bisphosphonate and teriparatide therapy in an animal model of postmenopausal osteoporosis
Authors: Kocijan Roland , Weigl Moritz , Skalicky Susanna , Geiger Elisabeth , Ferguson James , Leinfellner Gabriele , Heimel Patrick , Pietschmann Peter , Grillari Johannes , Redl Heinz , Hackl Matthias
Published: March 2019

MicroRNAs control the activity of a variety of genes that are pivotal to bone metabolism. Therefore, the clinical utility of miRNAs as biomarkers and drug targets for bone diseases certainly merits further investigation. This study describes the use of an animal model of postmenopausal osteoporosis to generate a comprehensive dataset on miRNA regulation in bone tissue and peripheral blood during bone loss and specifically anti-resorptive and osteo-anabolic treatment.

Forty-two Sprague-Dawley rats were randomized to SHAM surgery (n=10) or ovariectomy (OVX, n=32). Eight weeks after surgery, OVX animals were further randomized to anti-resorptive treatment with zoledronate (n=11), osteo-anabolic treatment with teriparatide (n=11), or vehicle treatment (n=10). After 12 weeks of treatment, bone and serum samples were used for microRNA analysis using next-generation sequencing (NGS), mRNA levels using RT-qPCR, and bone microarchitecture analysis using nanoCT.

Ovariectomy resulted in loss of trabecular bone, which was fully rescued using osteo-anabolic treatment, and partially rescued using anti-resorptive treatment. NGS revealed that both, anti-resorptive and anabolic treatment had a significant impact on miRNA levels in bone tissue and serum: out of 426 detected miRNAs, 46 miRNAs were regulated by teriparatide treatment an d 10 by zoledronate treatment (p-adj. < 0.1). Interestingly, teriparatide and zoledronate treatment were able to revert miRNA changes in tissue and serum of untreated OVX animals, such as the up-regulation of miR-203a-3p, a known osteo-inhibitory miRNA. We confirmed previously established mechanisms of miR-203a by analyzing its direct target Dlx5 in femoral head.

Our data reveal a significant effect of ovariectomy-induced bone loss, as well as the two major types of anti-osteoporotic treatment on miRNA transcription in femoral head tissue. These changes are associated with altered activity of target genes relevant to bone formation, such as Dlx5. The observed effects of bone loss and treatment response on miRNA levels in bone are also reflected in the peripheral blood, suggesting the possibility of minimally-invasive monitoring of bone-derived miRNAs using liquid biopsies.

Highlights

microRNA expression in bone tissue is altered by osteo-anabolic and anti-resorptive therapy in OVX rats.

microRNA changes in untreated OVX rats are reverted by anti-osteoporotic therapy.

miR-203a is up-regulated during bone loss and down-regulated following therapy.

Bone tissue and serum levels of miR-203a are highly correlated.
A segregating human allele ofSPO11modeled in mice disrupts timing and amounts of meiotic recombination, causing oligospermia and a decreased ovarian reserve
Authors: Tran Tina N. , Schimenti John C.
Published: March 2019

A major challenge in medical genetics is to characterize variants of unknown significance (VUS), so as to better understand underlying causes of disease and design customized treatments. Infertility has presented an especially difficult challenge with respect to not only determining if a given patient has a genetic basis, but also to identify the causative genetic factor(s). Though genome sequencing can identify candidate variants, in silico predictions of causation are not always sufficiently reliable so as to be actionable. Thus, experimental validation is crucial. Here, we describe the phenotype of mice containing a nonsynonymous (proline-to-threonine at position 306) change inSpo11, corresponding to human SNP rs185545661. SPO11 is a topoisomerase-like protein that is essential for meiosis because it induces DNA double stranded breaks (DSBs) that stimulate pairing and recombination of homologous chromosomes.

Although both male and femaleSpo11P306T/P306Tmice were fertile, they had reduced sperm and oocytes, respectively. Spermatocyte chromosomes exhibited synapsis defects (especially between the X and Y chromosomes), elevated apoptotic cells, persistent markers of DSBs, and most importantly, fewer Type 1 crossovers that causes some chromosomes to have none.Spo11P306T/−mice were sterile and made fewer meiotic DSBs thanSpo11+/−animals, suggesting that theSpo11P306Tallele is a hypomorph and likely is delayed in making sufficient DSBs in a timely fashion. If the consequences are recapitulated in humans, it would predict phenotypes of premature ovarian failure, reduced sperm counts, and possible increased number of aneuploid gametes. These results emphasize the importance of deep phenotyping in order to accurately assess the impact of VUSs in reproduction genes.
An approximate full-likelihood method for inferring selection and allele frequency trajectories from DNA sequence data
Authors: Stern Aaron J. , Wilton Peter R. , Nielsen Rasmus
Published: March 2019

Most current methods for detecting natural selection from DNA sequence data are limited in that they are either based on summary statistics or a composite likelihood, and as a consequence, do not make full use of the information available in DNA sequence data. We here present a new importance sampling approach for approximating the full likelihood function for the selection coefficient. The method treats the ancestral recombination graph (ARG) as a latent variable that is integrated out using previously published Markov Chain Monte Carlo (MCMC) methods. The method can be used for detecting selection, estimating selection coefficients, testing models of changes in the strength of selection, estimating the time of the start of a selective sweep, and for inferring the allele frequency trajectory of a selected or neutral allele. We perform extensive simulations to evaluate the method and show that it uniformly improves power to detect selection compared to current popular methods such as nSL and SDS, under various demographic models and can provide reliable inferences of allele frequency trajectories under many conditions. We also explore the potential of our method to detect extremely recent changes in the strength of selection. We use the method to infer the past allele frequency trajectory for a lactase persistence SNP (MCM6) in Europeans. We also study a set of 11 pigmentation-associated variants. Several genes show evidence of strong selection particularly within the last 5,000 years, includingASIP,KITLG, andTYR. However, selection onOCA2/HERC2seems to be much older and, in contrast to previous claims, we find no evidence of selection onTYRP1.

Author summary

Current methods to study natural selection using modern population genomic data are limited in their power and flexibility. Here, we present a new method to infer natural selection that builds on recent methodological advances in estimating genome-wide genealogies. By using importance sampling we are able to efficiently estimate the likelihood function of the selection coefficient. We show our method improves power to test for selection over competing methods across a diverse range of scenarios, and also accurately infers the selection coefficient. We also demonstrate a novel capability of our model, using it to infer the allele’s frequency over time. We validate these results with a study of a lactase persistence SNP in Europeans, and also study a set of 11 pigmentation-associated variants.
Altered hypothalamic microstructure in human obesity
Authors: Thomas K. , Beyer F. , Lewe G. , Zhang R. , Schindler S. , Schönknecht P. , Stumvoll M. , Villringer A. , Witte A.V.
Published: March 2019

Obesity is a multifactorial disorder driven by sustained energy imbalance. The hypothalamus is an important regulator of energy homeostasis and therefore likely involved in obesity pathophysiology. Animal studies suggest that obesity-related diets induce structural changes in the hypothalamus through inflammation-like processes. Whether this translates to humans is however largely unknown. Therefore, we aimed to assess obesity-related differences in hypothalamic macro- and microstructure based on a multimodal approach using T1-weighted and diffusion-weighted magnetic resonance imaging (MRI) acquired at 3 Tesla in a large well-characterized sample of the Leipzig Research Center for Civilization Diseases (LIFE) cohort (n1 = 338, 48% females, age 21-78 years, BMI 18-43 kg/m2). We found that higher body mass index (BMI) selectively predicted higher mean proton diffusivity (MD) within the hypothalamus, indicative of compromised microstructure in the underlying tissue. Results were independent from confounders and confirmed in another independent sample (n2 = 236). In addition, while hypothalamic volume was not associated with obesity, we identified a sexual dimorphism and larger hypothalamic volumes in the left compared to the right hemisphere. Using two large samples of the general population, we showed that a higher BMI specifically relates to altered microstructure in the hypothalamus, independent from confounders such as age, sex and obesity-associated co-morbidities. This points to persisting microstructural changes in a key regulatory area of energy homeostasis occurring with excessive weight. These findings may help to better understand the pathomechanisms of obesity and other eating-related disorders.
Feeding behavior of Aedes (Aedimorphus) vexans arabiensis, a Rift valley fever virus vector in the Ferlo pastoral ecosystem of Senegal
Authors: Biteye Biram , Fall Assane Gueye , Seck Momar Talla , Ciss Mamadou , Diop Mariame , Gimonneau Geoffrey
Published: March 2019

Host-vector contact is a key factor in vectorial capacity assessment and thus the transmission of mosquito-borne viruses such as Rift Valley Fever (RVF), an emerging zoonotic disease of interest in West Africa. The knowledge of the host-feeding patterns of vector species constitutes a key element in the assessment of their epidemiological importance in a given environment. The aim of this work was to identify the blood meal origins of Aedes vexans arabiensis Patton (Diptera: Culicidae), the main vector of RVF virus in the Ferlo pastoral ecosystem of Senegal. Engorged female mosquitoes were collected in Younouféré in the pastoral ecosystem in the Ferlo region during the 2014 rainy season. CDC light CO2-baited traps were set at six sites for two consecutive nights every month from July to November. Domestic animals present around traps were identified and counted for each trapping session. Blood meal sources of engorged mosquitoes were identified using a vertebrate-specific multiplexed primer set based on cytochrome b. Blood meal sources were successfully identified for 319 out of 416 blood-fed females (76.68%), of which 163 (51.1%) were single meals, 146 (45.77%) mixed meals from two different hosts and 10 (3.13%) mixed meals from three different hosts. Aedes vexans arabiensis fed preferentially on mammals especially on horse compared to other hosts (P < 0.001). Proportions of single and mixed meals showed significant temporal (P < 0.001) and spatial variations (P < 0.001) according to hosts availability. Aedes vexans arabiensis shows an opportunistic feeding behavior depending on the host availability. Results were discussed in relation with the Rift valley fever virus transmission and vector involvement as well as its primary hosts.
Health service utilisation lags behind maternal diseases or illnesses during pregnancy in rural south Ethiopia: A prospective cohort study
Authors: Tadesse Moges , Loha Eskindir , Johansson Kjell Arne , Lindtjørn Bernt
Published: March 2019

Maternal survival has improved substantially in the last decades, but evidence on maternal morbidity and health service utilisation for various maternal diseases are scarce in low resource settings. We aimed to measure health service utilisation for maternal illnesses during pregnancy. A cohort study of 794 pregnant women in rural southern Ethiopia was carried-out from May 2017 to July 2018. Disease or illness identification criteria were: symptoms, signs, physical examination, and screening of anaemia. Follow-up was done every two weeks. Data on health service utilisation was obtained from women and confirmed by visiting the health facility. Multilevel, multiple responses, repeated measures, and generalized linear mixed model analysis were used. The cumulative incidence of women experiencing illness episodes was 91%, and there were 1.7 episodes of diseases or illnesses per woman. About 22% of pregnant women were anaemic and 8% hypertensive. Fourteen pregnant women experienced abortions, 6 had vaginal bleeding, 48% pain in the pelvic area, 4% oedema, and 72% tiredness. However, health service utilisation was only 7%. About 94% of anaemic women did not get iron-folic-acid tablet supplementation. Only two mothers with blurred vision and severe headache were referred for further treatment. The main reasons for not using the health services were: the perception that symptoms would heal by themselves (47%), illness to be minor (42%), financial constraints (10%), and lack of trust in health institutions (1%). Risk factors were being older women, poor, having a history of abortion, living far away from the health institution, travelled longer time to reach a health institution, and monthly household expenditure >=30 USD. In Conclusion, there was a high incidence of diseases or illnesses; however health service utilisation was low. Poor understanding of severe and non-severe symptoms was an important reason for low health service utilisation. Therefore, community-based maternal diseases or illness survey could help for early detection. Ministry of Health should promote health education that encourages women to seek appropriate and timely care.
Multi-omics co-localization with genome-wide association studies reveals a context-specific genetic mechanism at a childhood onset asthma risk locus
Authors: Soliai Marcus M. , Kato Atsushi , Stanhope Catherine T. , Norton James E. , Naughton Katherine A. , Klinger Aiko I. , Kern Robert C. , Tan Bruce K. , Schleimer Robert P. , Nicolae Dan L. , Pinto Jayant M. , Ober Carole
Published: March 2019

Background

Genome-wide association studies (GWASs) have identified thousands of variants associated with asthma and other complex diseases. However, the functional effects of most of these variants are unknown. Moreover, GWASs do not provide context-specific information on cell types or environmental factors that affect specific disease risks and outcomes. To address these limitations, we used an upper airway (sinonasal) epithelial cell culture model to assess transcriptional and epigenetic responses to an asthma-promoting pathogen, rhinovirus (RV), and provide context-specific functional annotations to variants discovered in GWASs of asthma.

Methods

Using genome-wide genetic, gene expression and DNA methylation data in vehicle- and RV-treated airway epithelial cells (AECs) from 104 individuals, we mapped cis expression and methylation quantitative trait loci (cis-eQTLs and cis-meQTLs, respectively) in each condition. A Bayesian test for co-localization between AEC molecular QTLs and adult onset and childhood onset GWAS variants was used to assign function to variants associated with asthma. Mendelian randomization was applied to demonstrate DNA methylation effects on gene expression at asthma colocalized loci.

Results

Co-localization analyses of airway epithelial cell molecular QTLs with asthma GWAS variants revealed potential molecular disease mechanisms of asthma, including QTLs at the TSLP locus that were common to both exposure conditions and to both childhood and adult onset asthma, as well as QTLs at the 17q12-21 asthma locus that were specific to RV exposure and childhood onset asthma, consistent with clinical and epidemiological studies of these loci.

Conclusion

This study provides information on functional effects of asthma risk variants in airway epithelial cells and insight into a disease-relevant viral exposure that modulates genetic effects on transcriptional and epigenetic responses in cells and on risk for asthma in GWASs.
Conformational changes in the third PDZ domain of the neuronal postsynaptic density protein 95
Authors: Camara-Artigas Ana , Murciano-Calles Javier , Martínez Jose C.
Published: March 2019

PDZ domains are protein–protein recognition modules that interact with other proteins through short sequences at the carboxyl terminus. These domains are structurally characterized by a conserved fold composed of six β-strands and two α-helices. The third PDZ domain of the neuronal postsynaptic density protein 95 has an additional α-helix (α3), the role of which is not well known. In previous structures, a succinimide was identified in the β2–β3 loop instead of Asp332. The presence of this modified residue results in conformational changes in α3. In this work, crystallographic structures of the following have been solved: a truncated form of the third PDZ domain of the neuronal postsynaptic density protein 95 from which α3 has been removed, D332P and D332G variants of the protein, and a new crystal form of this domain showing the binding of Asp332 to the carboxylate-binding site of a symmetry-related molecule. Crystals of the wild type and variants were obtained in different space groups, which reflects the conformational plasticity of the domain. Indeed, the overall analysis of these structures suggests that the conformation of the β2–β3 loop is correlated with the fold acquired by α3. The alternate conformation of the β2–β3 loop affects the electrostatics of the carboxylate-binding site and might modulate the binding of different PDZ-binding motifs.
Employers’ ratings of importance of skills and competencies college graduates need to get hired
Authors: Baird Anthony M. , Parayitam Satyanarayana
Published: March 2019

Purpose

Higher education institutions play an important role in the economic growth of any country, through skills and productivity of their graduates. Employers have some expectations about the skills the graduates possess when they graduate out of universities. The purpose of this paper is to examine the skills employers look for in graduates before they hire them.

Design/methodology/approach

Using a structured survey instrument, this paper gathered data from 50 organizations employing over 50 people. The data consisted of 21 skills the employers rate as important. These skills were categorized into four dimensions: analytical skills, career professional and readiness skills, communications skills, and personality, leadership skills and team/group work. After checking the reliability of the scale, χ2 test and rank correlation were used to analyze the importance of these skills.

Findings

The findings from a study of employers in the northeastern part of USA suggest that the top six skills and competencies rated with highest importance by employers were: interpersonal skills/works well with others; critical thinking/problem-solving skills; listening skills; oral/speech communication skills; professionalism; and personal motivation. Of all 21 skills, the highly ranked skills needed were interpersonal skills followed by critical thinking and problem solving and listening.

Research limitations/implications

The present research is based on self-report measures and, hence, the limitations of social desirability bias and common method bias are inherent. However, adequate care is taken to minimize these limitations. The research has implications for the higher educational institutions and researches in the field of education.

Practical implications

In addition to the employers, this study contributes to higher educational institutions. The study suggests that employers look for interpersonal skills and problem-solving skills before making hiring decisions. Educational institutions need to focus on enhancing these skills in classrooms by emphasizing the teamwork. The implications for both academicians and practitioners are discussed in the paper.

Social implications

The findings from the study help in creating a fruitful social environment in organizations.

Originality/value

This study provides new insights about the changing pattern of skills students need to secure before seeking employment.
Grey system analysis in the field of medicine and health
Authors: Lixia Zhang , Hong Tang , Miao He
Published: March 2019

Purpose

The purpose of this paper is to predict hospital respiratory system infection rate by using the gray GM(1,1) model, and to provide theoretical basis for the prospective study on hospital respiratory system infection management.

Design/methodology/approach

The annual respiratory system infection rate of a comprehensive third-class hospital in Yan’an is collected from 2011 to 2017. The GM(1,1) model is used for prediction, and mean absolute percentage error is used to evaluate the prediction accuracy of the model.

Findings

GM(1,1) statistical prediction model is established with good fitting degree and high reliability of extrapolation prediction.

Originality/value

The GM(1,1) model can well predict the respiratory system infection rate of the hospital.
Talking about digital textbooks. The teacher perspective
Authors: Håkansson Lindqvist Marcia
Published: March 2019

Purpose

An increasing amount of students’ and teachers’ work in the classroom involves digital technologies such as tablets and laptop computers. The purpose of this paper is to gain insight into the possibilities and challenges related to teachers’ use of digital textbooks and, through this work, the conditions for technology-enhanced learning (TEL).

Design/methodology/approach

This study was based on interviews with two teachers. In the analysis, The Ecology of Resources Model (Luckin, 2010) was used.

Findings

The findings of this study show that teachers see challenges in finding time to review digital textbooks and support the work with the textbooks in the classroom. However, the teachers in this study prioritize this work, seeing it as providing structure and improved accessibility for students.

Practical implications

The findings of this study point toward the need to support teachers in their work with reviewing and using digital textbooks, as well as other digitalized resources. How schools as organizations can support teachers’ activities, both individually and collaboratively, will be important. If this work is supported it may, in turn, have impact on TEL and promoting students’ use of digital textbooks and improving student outcomes.

Originality/value

This small study provides interesting insights into how teachers prioritize their work with digital textbooks to, despite challenges related to time, individualize and support students’ work with digital textbooks and other digital resources. Research on teachers’ use of digital textbooks in practice is limited.
Research trends in the study of gamification
Authors: Alsawaier Raed S.
Published: March 2019

Purpose

The purpose of this paper is to examine the research design of several publications on the study of gamification and proposes a mixed-method research design for creating a holistic understanding of the gamification phenomenon. It presents an argument in support of combining both qualitative and quantitative data sources through mixed-method design as being equally important in illuminating all aspects of the research problem.

Design/methodology/approach

The paper covers a number of methodological themes relevant to the study of gamification: research design trends in the study of gamification; the importance of mixed-method design in the study of gamification; methodological challenges; conclusion and recommendations.

Findings

Majority of the studies on gamification before 2015 are either quantitative or described as mixed method but overly focused on quantitative data sources. However, there is a tendency between 2015 and 2017 to adopt mixed-method design.

Research limitations/implications

The study does not examine all research done on the topic of gamification but relies on 56 empirical studies reviewed by Hamari, Koivisto, Sarsa (2014) and Seaborn and Fels (2015) between 2009 and 2015.

Originality/value

The author believes it to be one of the few studies of its kind on proposing a methodological design for the study of gamification as a pedagogical tool.
Competency based superior performance and organizational effectiveness
Authors: Shet Sateesh V. , Patil S.V. , Chandawarkar Meena R.
Published: March 2019

Purpose

The purpose of this paper is to explore the relationship between competency-based performance management and organizational effectiveness (OE). It signifies the importance of developing competency-based performance concept in organizations. Since conventional performance management systems (PMSs) are diminishing and as organizations are looking for breakthrough PMSs, this research attempted to fill the gap from stakeholder’s perspective – employee, manager and organization in devising new approach in PMS.

Design/methodology/approach

The research design involved developing scale for “competency-based superior performance” and validating scale for “organizational effectiveness,” The data for this survey are collected from 292 respondents through structured questionnaire. Hypotheses depicting aforementioned relationships were empirically tested in the context of competency-based performance practices in organizations based in India. Structural equation modeling (SEM) technique was used for data analysis.

Findings

The empirical results provide methods to accelerate the performance management initiatives based on a leadership competency model (LCM), which are necessary for building performance culture in the organization. The paper contributes by developing a new scale for measuring competency-based performance practices. The scale for OE is revisited. A positive relationship between competency-based superior performance and OE with productivity, adaptability and flexibility has been empirically confirmed using SEM.

Research limitations/implications

The paper limits the performance measurement concept using leadership competencies.

Practical implications

The developed model will act as a building block for performance measurement in organizations. This paper promotes LCM to be applied in creating a performance-based culture.

Originality/value

This is a unique attempt to test the relationship between competency-based performance management and OE.
Exploring primary care responses to domestic violence and abuse (DVA): operationalisation of a national initiative
Authors: McGarry Julie , Hussain Basharat , Watts Kim
Published: March 2019

Purpose

In the UK, the Identification and Referral to Improve Safety (IRIS) initiative has been developed for use within primary care to support women survivors of domestic violence and abuse (DVA). However, while evaluated nationally, less is known regarding impact of implementation at a local level. The purpose of this paper is to explore the effectiveness of IRIS within one locality in the UK.

Design/methodology/approach

A qualitative study using interviews/focus groups with primary care teams and women who had experienced DVA in one primary care setting in the UK. Interviews with 18 participants from five professional categories including: general practitioners, practice nurses, practice managers, assistant practice managers and practice receptionists. Focus group discussion/interview with seven women who had accessed IRIS. Data were collected between November 2016 and March 2017.

Findings

Five main themes were identified for professionals: Team role approach to training, Professional confidence, Clear pathway for referral and support, Focussed support, Somewhere to meet that is a “safe haven”. For women the following themes were identified: Longevity of DVA; Lifeline; Face to face talking to someone; Support and understood where I was coming from; A place of safety.

Practical implications

IRIS played a significant role in helping primary care professionals to respond effectively. For women IRIS was more proactive and holistic than traditional approaches.

Originality/value

This study was designed to assess the impact that a local level implementation of the national IRIS initiative had on both providers and users of the service simultaneously. The study identifies that a “whole team approach” in the primary care setting is critical to the effectiveness of DVA initiatives.
Long and winding road?
Authors: Csillag Sara , Gyori Zsuzsanna , Svastics Carmen
Published: March 2019

Purpose

The purpose of this paper is to explore and analyse the barriers entrepreneurs with disabilities (EWD) face when establishing their own enterprises, as well as the supporting factors in starting and running a business.

Design/methodology/approach

This is an explorative study. Data were collected using semi-structured interviews with ten Hungarian entrepreneurs with physical disabilities or sight-loss, during the summer of 2018.

Findings

The paper classifies the barriers and supporting factors, as personal, economic and social. Based on the perceptions of the entrepreneurs, personal characteristics, identity and various types of family support play an important role in becoming entrepreneurs, but the entrepreneurial ecosystem generally is not favourable in Hungary, and there are no special support programmes focussing on EWD.

Research limitations/implications

Sample size is a serious limitation: the ten entrepreneurs do not represent in any sense the entire EWD community in Hungary, so the patterns found cannot be considered a generally valid picture.

Originality/value

The article contributes to the literature on entrepreneurship and disabilities, especially through the systematic review of the possible barriers and supporting factors and to the existing empirical body of knowledge by shedding light on the barriers and supporting factors in a rarely investigated region, in Central Europe: Hungary.
SEC sues asset managers for using untested, error-filled quantitative investment models
Authors: Cohen Wendy E. , Marshall Richard D. , Yacker Allison C. , Zinman Lance A.
Published: March 2019

Purpose

To explain actions the US Securities and Exchange Commission (SEC) brought on August 27, 2018, against a group of affiliated investment advisers and broker-dealers for what the SEC considered misleading and insufficient representations and disclosures, insufficient compliance policies and procedures, and insufficient research and oversight concerning the use of faulty quantitative models to manage certain client accounts.

Design/methodology/approach

Explains the SEC’s findings concerning the advisers’ and broker-dealers’ failure to confirm that certain models worked as intended, to disclose the risks associated with the use of those models, to disclose the role of a research analyst in developing the models, to disclose the use of volatility overlays along with the associated risks, to determine whether a fund’s holdings were sufficient to support a consistent dividend payout without a return of capital, and to take sufficient steps to confirm the advertised performance of another investment manager whose products they were marketing. Provides insight into the SEC’s position and offers key takeaways.

Findings

These cases are significant for advisers who use quantitative models to implement their investment strategies in the management of client accounts and signal the SEC’s continued focus on investment advisers’ compliance with disclosure obligations to discretionary account investors.

Practical implications

Each manager should consider its own facts and circumstances, and should consult with counsel, in assessing how and to what extent to incorporate the SEC’s conclusions in crafting disclosure and other communications with investors on matters such as adequate representations, testing and validation of models, disclosure of errors, and verifying performance claims.

Originality/value

Practical guidance from experienced securities lawyers.
An investigation of the impact of 2017 business rates revaluation on independent high street retailers in the north of England
Authors: Greenhalgh Paul Michael , Johnson Lynn , Huntley Victoria
Published: March 2019

Purpose

Many national retailers have complained about increases in business rates tax bills since the 2017 revaluation. What impact has the 2017 business rates revaluation had on independent high street retailers in market towns in the north of England? The paper aims to discuss these issues.

Design/methodology/approach

The study uses Valuation Office Agency rating list data to determine rateable value and business rates payable for independent high street retailers in eight northern market towns either side of the 2017 rating revaluation. The data were analysed using business rates matrices to reveal the impact of the new rating list on independent retailers in the eight locations.

Findings

Analysis reveals that the majority of independent retailers in the northern market towns sampled have experienced reductions in both the rateable value of their premises and business rates payable. Increase in the rates relief threshold has extended relief to almost half of the independent retailers in the study, most of whom receive 100 per cent relief.

Practical implications

Charity shops receive at least 80 per cent rates relief which means they are able to afford to pay higher rents. This “sets the tone” for landlords setting market rents in that location which are then used as comparable evidence by the VOA when determining rateable values at revaluation further polarising the gap between rate payers and those to are exempt.

Originality/value

Focussing on independent retailers on high streets in markets towns in north of England, this study provides an alternative perspective to the orthodox view of business rates revaluations having a negative impact on retailers.
Property investment: gearing and the equity rate of return
Authors: French Nick
Published: March 2019

Purpose

The purpose of this paper is to comment upon the relatively straightforward but often misunderstood role of gearing (or leverage) on the potential equity return of a property investment.

Design/methodology/approach

This education briefing is an explanation of the upside and downside risk of borrowing (at different levels) to successful investment.

Findings

The use of gearing can greatly enhance equity returns but at an increased risk.

Practical implications

The process of borrowing at a bank rate below the return rate on an investment project can increase the equity return of the project as long as all incomes and discount rate remain at appropriate levels.

Originality/value

This is a review of existing models.
Hospital mergers, acquisitions and regulatory policy implications
Authors: Walia Bhavneet , Boudreaux Christopher John
Published: March 2019

Purpose

The purpose of this paper is to review the literature on hospital mergers and acquisitions (M&As).

Design/methodology/approach

The authors conduct a systematic review of the literature on hospital M&As to summarize their effects upon cost of health care delivery (access), efficiency, market power, cost and price. Implications for health care industry policy are provided.

Findings

A significant majority of results conclude lower costs, increased efficiency, but higher prices (due to a market concentration effect) following hospital merger or acquisition. These results are consistent with industrial organization theory and suggest that regulatory policy (e.g. price cap regulation) will raise allocative efficiency, consumer surplus and overall market surplus within markets for hospital services.

Originality/value

This is the first study to review the price, cost and efficiency effects of M&As with respect to industrial organization theory in the context of hospitals. This study also provides regulatory policy implications.