bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-HLA Genetic Factors and Their Influence on Heart Transplant Outcomes: A Systematic Review
Authors: van Setten Jessica , Warmerdam Evangeline G. , Groot Olivier Q. , de Jonge Nicolaas , Keating Brendan , Asselbergs Folkert W.
Published: January 2019

Background

Improvement of immunosuppressive therapies and surgical techniques has increased the survival rate after heart transplantation. Nevertheless, a large number of patients still experience complications, such as allograft rejection, vasculopathy, kidney dysfunction, and diabetes in response to immunosuppressive therapy. Variants in HLA genes have been extensively studied for their role in clinical outcomes after transplantation, whereas the knowledge about non-HLA genetic variants in this setting is still limited. Non-HLA polymorphisms are involved in the metabolism of major immunosuppressive therapeutics and may play a role in clinical outcomes after cardiac transplantation. This systematic review summarizes the existing knowledge of associations between non-HLA genetic variation and heart transplant outcomes.

Methods

The current evidence available on genetic polymorphisms associated with outcomes after heart transplantation was identified by a systematic search in PubMed and Embase. Studies reporting on polymorphisms significantly associated with clinical outcomes after cardiac transplantation were included.

Results

A total of 56 studies were included, all were candidate gene studies. These studies identified 58 polymorphisms in 36 genes that were associated with outcomes after cardiac transplantation. Variants in TGFB1, CYP3A5, and ABCB1 are consistently replicated across multiple studies for various transplant outcomes.

Conclusions

The research currently available supports the hypothesis that non-HLA polymorphisms are associated with clinical outcomes after heart transplantation. However, many genetic variants were only identified in a single study, questioning their true effect on the clinical outcomes tested. Further research in larger cohorts with well-defined phenotypes is warranted.
Large-scale gene analysis of rabbit atherosclerosis to discover new biomarkers for coronary artery disease
Authors: Yu Xiaolan , Guan Wen , Zhang Yang , Deng Qing , Li Jingjing , Ye Hao , Deng Shaorong , Han Wei , Yu Yan
Published: January 2019

Atherosclerosis is the pathological basis of coronary artery disease (CAD) and causes high mortality. Thus, early detection is thought to be crucial in reducing the risk of CAD. Uncovering the mechanisms of the progression and regression of atherosclerosis will provide insights into discovering novel biomarkers to identify subjects at risk for CAD and improve prevention. We established atherosclerosis progression and regression in a rabbit model. Then, we extracted mRNA of the abdominal aorta from control, model and recovery groups to perform gene chip analysis. Candidate biomarkers were screened by large-scale gene analysis and validated in patients with CAD or with CAD recovery by ELISA. The differentially expressed genes in the progression and regression of atherosclerosis were mainly enriched in four clusters. Genes associated with inflammation and extracellular matrix were returned to normal or close-to-normal levels much earlier than genes associated with metabolism and sarcoplasmic proliferation, and they were maintained downregulated or upregulated after feeding a normal diet. We then selected four candidate biomarkers and found that lipoprotein lipase (LPL), bone morphogenetic protein 7 and somatostatin concentrations could indicate CAD diagnosis. In addition, LPL and macrophage cationic peptide 2 can be indicators of the prognosis of CAD. Molecular changes during the progression and regression of atherosclerosis in rabbits were revealed, and candidate regulators were identified. The identified factors could be used as novel biomarkers and targets for improving the diagnosis and prognosis of human CAD in the future.
Algebraic structures and stochastic differential equations driven by Lévy processes
Authors: Curry Charles , Ebrahimi–Fard Kurusch , Malham Simon J. A. , Wiese Anke
Published: January 2019

We construct an efficient integrator for stochastic differential systems driven by Lévy processes. An efficient integrator is a strong approximation that is more accurate than the corresponding stochastic Taylor approximation, to all orders and independent of the governing vector fields. This holds provided the driving processes possess moments of all orders and the vector fields are sufficiently smooth. Moreover, the efficient integrator in question is optimal within a broad class of perturbations for half-integer global root mean-square orders of convergence. We obtain these results using the quasi-shuffle algebra of multiple iterated integrals of independent Lévy processes.
The cellular localization of avian influenza virus PB1-F2 protein alters the magnitude of IFN2 promoter and NFκB-dependent promoter antagonism in chicken cells
Authors: James Joe , Smith Nikki , Ross Craig , Iqbal Munir , Goodbourn Steve , Digard Paul , Barclay Wendy S. , Shelton Holly
Published: January 2019

The accessory protein, PB1-F2, of influenza A virus (IAV) functions in a chicken host to prolong infectious virus shedding and thus the transmission window. Here we show that this delay in virus clearance by PB1-F2 in chickens is accompanied by reduced transcript levels of type 1 interferon (IFN)-induced genes and NFκB-activated pro-inflammation cytokines. In vitro, two avian influenza isolate-derived PB1-F2 proteins, H9N2 UDL01 and H5N1 5092, exhibited the same antagonism of the IFN and pro-inflammation induction pathways seen in vivo, but to different extents. The two PB1-F2 proteins had different cellular localization in chicken cells, with H5N1 5092 being predominantly mitochondrial-associated and H9N2 UDL being cytoplasmic but not mitochondrial-localized. We hypothesized that PB1-F2 localization might influence the functionality of the protein during infection and that the protein sequence could alter cellular localization. We demonstrated that the sequence of the C-terminus of PB1-F2 determined cytoplasmic localization in chicken cells and this was linked with protein instability. Mitochondrial localization of PB1-F2 resulted in reduced antagonism of an NFκB-dependent promoter. In parallel, mitochondrial localization of PB1-F2 increased the potency of chicken IFN 2 induction antagonism. We suggest that mitochondrial localization of PB1-F2 restricts interaction with cytoplasmic-located IKKβ, reducing NFκB-responsive promoter antagonism, but enhances antagonism of the IFN2 promoter through interaction with the mitochondrial adaptor MAVS. Our study highlights the differential mechanisms by which IAV PB1-F2 protein can dampen the avian host innate signalling response.
Phase separation provides a mechanism to reduce noise in cells
Authors: Oltsch Florian , Klosin Adam , Julicher Frank , Hyman Anthony A. , Zechner Christoph
Published: January 2019

A central problem in cellular control is how cells cope with the inherent noise in gene expression. Although transcriptional and posttranscriptional feedback mechanisms can suppress noise, they are often slow, and cannot explain how cells buffer acute fluctuations. Here, by using a physical model that links fluctuations in protein concentration to the theory of phase separation, we show that liquid droplets can act as fast and effective buffers for gene expression noise. We confirm our theory experimentally using an engineered phase separating protein that forms liquid-like compartments in mammalian cells. These data suggest a novel role of phase separation in biological information processing.
Aberrant Clonal Hematopoiesis Following Lentiviral Transduction of HSPC in a Rhesus Macaque
Authors: Espinoza Diego Alexander , Fan Xing , Yang Di , Cordes Stefan F , Truitt Lauren L , Calvo Katherine R , Yabe Idalia M , Demirci Selami , Hope Kristin J , Hong So Gun , Krouse Allen , Metzger Mark , Bonifacino Aylin , Lu Rong , Uchida Naoya , Tisdale John F , Wu Xiaolin , DeRavin Suk See , Malech Harry L , Donahue Robert E , Wu Chuanfeng , Dunbar Cynthia E
Published: January 2019

Lentiviral vectors (LV) have been used for the delivery of genes into hematopoietic stem and progenitor cells (HSPC) in clinical trials worldwide. LV, in contrast to retroviral vectors, have not been associated with insertion site-associated malignant clonal expansions, and thus have been considered safer. Here, however, we present a case of markedly abnormal dysplastic clonal hematopoiesis impacting the erythroid, myeloid and megakaryocytic lineages in a rhesus macaque transplanted with HSPCs that were transduced with a LV containing a strong retroviral murine stem cell virus (MSCV) constitutive promoter-enhancer in the LTR. 9 insertions were mapped in the abnormal clone, resulting in overexpression and aberrant splicing of several genes of interest, including the cytokine stem cell factor and the transcription factor PLAG1. This case represents the first clear link between a lentiviral insertion-induced clonal expansion and a clinically abnormal transformed phenotype following transduction of normal primate or human HSPC, and are thus concerning, and suggest that strong constitutive promoters should not be included within LV vectors.
Constrained actin dynamics emerges from variable compositions of actin regulatory protein complexes
Authors: Dobramysl Ulrich , Jarsch Iris K , Shimo Hanae , Inoue Yoshiko , Richier Benjamin , Gadsby Jonathan R , Mason Julia , Walrant Astrid , Butler Richard , Hannezo Edouard , Simons Benjamin D , Gallop Jennifer L
Published: January 2019

Assemblies of actin and its regulators underlie the dynamic morphology of all eukaryotic cells. To begin to understand how diverse regulatory proteins work together to generate actin-rich structures we tracked the assembly of actin regulators and their relative proportions in a cell-free system that generates filopodia-like structures (FLS). We found that heterogeneous mixtures of regulators could give rise to morphologically similar structures and that the FLS actin bundles exhibited simple dynamic behaviour of growth and shrinkage. To explain these observations, we combined experiment with theory, and found that stochastic fluctuations between redundant actin regulatory subcomplexes can account for the actin dynamics. Comparing the localizations of a variety of endogenous actin regulators in Drosophila embryos and distributions of filopodia lengths yielded similar conclusions of heterogenous actin regulatory complexes and filopodia lengths governed by a stochastic growth process. Our results explain how weakly-associating assemblies of regulatory proteins can produce robust functional outcomes.
Tankyrase inhibition sensitizes melanoma to PD-1 immune checkpoint blockade in syngeneic mouse models
Authors: Waaler Jo , Mygland Line , Tveita Anders , Strand Martin Frank , Solberg Nina Therese , Angell Olsen Petter , Lund Kaja , Alam Brinch Shoshy , Lycke Max , Dybing Elisabeth , Nygaard Vegard , Boe Sigurd Laeines , Heintz Karen-Marie , Hovig Eivind , Hammarstrom Clara , Corthay Alexandre , Krauss Stefan
Published: January 2019

The development of immune checkpoint inhibitors represents a major breakthrough in cancer therapy. Nevertheless, a substantial number of patients fail to respond to checkpoint pathway blockade. β-catenin is the key transcriptional regulator of WNT/β-catenin signaling. Evidence for β-catenin-mediated immune evasion is found in 13% of all cancers, 42% of primary cutaneous melanoma and a mouse melanoma model. Currently, there are no therapeutic strategies available for targeting WNT/β-catenin signaling to counteract checkpoint inhibitor resistance in melanoma. Here we report that a specific small-molecule tankyrase inhibitor, G007-LK, attenuates WNT/β-catenin and YAP signaling pathways in the syngeneic murine B16-F10 melanoma model enabling sensitivity to anti-PD-1 immune checkpoint therapy. RNA sequencing of 18 tankyrase inhibitor-treated human melanoma cell lines and B16-F10 cells revealed a transcriptional response profile for a subpopulation. This cell line sub-group displayed elevated baseline YAP signaling activity and was susceptible to reduce melanocyte inducing transcription factor (MITF) expression upon tankyrase inhibition.
A potential role for the gut microbiota in the specialisation of Drosophila sechellia to its toxic host noni (Morinda citrifolia)
Authors: Heys Chloe , Fisher Adam M , Dewhurst Andrea D , Lewis Zenobia , Lize Anne
Published: January 2019

Adaptation to a novel food source can have significant evolutionary advantages. The fruit fly, Drosophila sechellia, is a specialist of the toxic plant noni (Morinda citrifolia). Little is known as to how D. sechellia has become resistant to the toxins in the fruit - comprised predominantly of octanoic acid - but to date, the behavioural preferences for the fruit and genetic architecture underlying them, have been well studied. Here, we examine whether the gut microbiota could have played a role in adaptation to the fruit. In the first series of experiments, we examine the gut microbiota of wild-type, laboratory reared flies and characterise the gut microbiota when reared on the natural host plant, versus a standard Drosophila diet. We show a rapid transition in the core bacterial diversity and abundance within this species and discover sole precedence of Lactobacillus plantarum when reared on M. citrifolia. We also discover that flies reared on a laboratory diet are more likely to carry bacterial pathogens such as Bacillus cereus, although their function in Drosophila is unknown. Flies reared on a laboratory diet have a significantly reduced weight but with no impact on the risk of death before adulthood, when compared to the wild noni diet. In the second series of experiments, we examine the potential role of the gut microbiota in adaptation to octanoic acid resistance in this species and its sister species, Drosophila melanogaster, to which the fruit is usually fatal. We use a combination of methods to analyse resistance to octanoic acid by conducting life history analysis, behavioural assays and bacterial analysis in both D. sechellia and D. melanogaster. We find that by creating experimental evolution lines of D. melanogaster supplemented with gut microbiota from D. sechellia, we can decrease D. melanogaster aversion to octanoic acid, with the flies even preferring to feed on food supplemented with the acid. We suggest this represents the first step in the evolutionary and ecological specialisation of D. sechellia to its toxic host plant, and that the gut microbiota, Lactobacillus plantarum in particular, may have played a key role in host specialisation.
Social tolerance in Octopus laqueus - a maximal entropy model
Authors: Edsinger Eric , Pnini Reuven , Ono Natsumi , Yanagisawa Ryoko , Dever Kathryn , Miller Jonathan
Published: January 2019

Octopus laqueus is a small tropical octopus found in Okinawa, Japan and the greater Indo-Pacific. Octopus are often viewed as solitary animals but O. laqueus live in close proximity in the wild, and will potentially encounter one another on a regular basis, raising the possibility of sociality in the species. To test for social tolerance and social repulsion in O. laqueus, animals were kept in communal tanks, and the number of dens and sex composition was varied per tank, with a set mixture of sizes and with den occupancy tracked per individual. We found that O. laqueus will socially tolerate other individuals by sharing tanks and dens, including several animals in contact and sharing a den under den-limited conditions, and with typically no loss to cannibalism or escape. However, animals also exhibit significant levels of social repulsion, and individuals often chose a solitary den when given the option. The patterns of den occupancy are observed to be consistent with a maximum entropy model. Overall, the preference to have a den is stronger than the preference to be solitary in O. laqueus, and the animals are socially tolerant of others in the tank and in a den or shelter, a first for octopuses outside mating. The relaxed disposition and social tolerance of O. laqueus make it a promising species to work with in lab, and for development into a genetic model for social behavior in octopuses.
Centromere deletion in Cryptococcus deuterogattii leads to neocentromere formation and chromosome fusions
Authors: Schotanus Klaas , Heitman Joseph
Published: January 2019

The human fungal pathogen Cryptococcus deuterogattii is RNAi-deficient and lacks active transposons in its genome. C. deuterogattii has regional centromeres that contain only transposon relics. To investigate impact of centromere loss on the C. deuterogattii genome, either centromere 9 or 10 was deleted. Deletion of either centromere resulted in neocentromere formation and interestingly, the genes covered by these neocentromeres maintained wild-type expression levels. In contrast to cen9Δ mutants, cen10Δ mutant strains exhibited growth defects and were aneuploid for chromosome 10. At an elevated growth temperature (37°C), the cen10Δ chromosome was found to have undergone fusion with another native chromosome in some isolates and this fusion restored wild-type growth. Following chromosomal fusion, the neocentromere was inactivated, and the native centromere of the fused chromosome served as the active centromere. The neocentromere formation and chromosomal fusion events observed in this study in C. deuterogattii may be similar to events that triggered genomic changes within the Cryptococcus/Kwoniella species complex and may contribute to speciation throughout the eukaryotic domain.
The Malaria Cell Atlas: a comprehensive reference of single parasite transcriptomes across the complete Plasmodium life cycle
Authors: Howick Virginia M. , Russell Andrew , Andrews Tallulah , Heaton Haynes , Reid Adam J. , Natarajan Kedar Nath , Butungi Hellen , Metcalf Tom , Verzier Lisa H. , Rayner Julian , Berriman Matthew , Herren Jeremy , Billker Oliver , Hemberg Martin , Talman Arthur , Lawniczak Mara
Published: January 2019

Malaria parasites adopt a remarkable variety of morphological life stages as they transition through multiple mammalian host and mosquito vector environments. Here we profile the single-cell transcriptomes of thousands of individual parasites, deriving the first high-resolution transcriptional atlas of the entire Plasmodium berghei life cycle. We then use our atlas to precisely define developmental stages of single cells from three different human malaria parasite species, including parasites isolated directly from infected individuals. The Malaria Cell Atlas provides both a comprehensive view of gene usage in a complex eukaryotic parasite and an open access reference data set for the study of malaria parasites.
Alpha Neurofeedback Training with a portable Low-Priced and Commercially Available EEG Device Leads to Faster Alpha Enhancement
Authors: Naas Adrian , Rodrigues João , Knirsch Jan-Philipp , Sonderegger Andreas
Published: January 2019

Introduction

Findings of recent studies have proposed that it is possible to enhance cognitive capacities of healthy individuals by means of individual upper alpha (around 10 to 13.5 Hz) neurofeedback training. Although these results are promising, most of this research was conducted based on high-priced EEG systems developed for clinical and research purposes only. This study addresses the question whether such effects can also be shown with an easy to use and comparably low priced Emotiv Epoc EEG headset available for the average consumer. In addition, critical voices were raised regarding the control group designs of studies addressing the link between neurofeedback training and cognitive performance. Based on an extensive literature review revealing considerable methodological issues in an important part of the existing research, the present study addressed the question whether individual upper alpha neurofeedback has a positive effect on alpha amplitudes (i.e. increases alpha amplitudes) and short-term memory performance focussing on a methodologically sound, single-blinded, sham controlled design.

Method

Participants (N = 33) took part in four test sessions over four consecutive days of either neurofeedback training or sham feedback (control group). In the experimental group, five three-minute periods of visual neurofeedback training were administered each day whereas in the control group, the same amount of sham feedback was presented. Performance on eight digit-span tests as well as participants’ affective states were assessed before and after each of the daily training sessions.

Results

Participants in the neurofeedback training (NFT) group showed faster and greater alpha enhancement compared to the control group. Contrary to the authors’ expectations, alpha enhancement was also observed in the control group. Surprisingly, exploratory analyses showed a significant correlation between the initial alpha level and the alpha improvement during the course of the study. This finding suggests that participants with high initial alpha levels profit more from alpha NFT interventions. digit-span performance increased in both groups over the course of time. However, the increase in individual upper relative alpha did not explain significant variance of digit-span improvement. In the discussion, the authors explore the appearance of the alpha enhancement in the control group and possible reasons for the absence of a connection between NFT and short-term memory.
Phosphorylation-dependent routing of RLP44 towards brassinosteroid or phytosulfokine signalling
Authors: Gómez Borja Garnelo , Holzwart Eleonore , Kolbeck Andreas , Shi Chaonan , Lozano-Durán Rosa , Wolf Sebastian
Published: January 2019

Plants rely on a complex network of cell surface receptors to integrate developmental and environmental cues into behaviour adapted to the conditions. The largest group of these receptors, leucine-rich repeat receptor-like kinases, form a complex interaction network that is modulated and extended by receptor-like proteins. This raises the question of how specific outputs can be generated when receptor proteins are engaged in a plethora of promiscuous interactions. RECEPTOR-LIKE PROTEIN 44 (RLP44) acts to promote both brassinosteroid and phytosulfokine signalling, which orchestrate a wide variety of cellular responses. However, it is unclear how these activities are coordinated. Here, we show that RLP44 is phosphorylated in its highly conserved C-terminal cytosolic tail and that this post-translational modification governs its subcellular localization. RLP44 variants in which phosphorylation is blocked enter endocytosis prematurely, leading to an almost entirely intracellular localization, whereas phospho-mimicking or ectopic phosphorylation results in preferential RLP44 localization at the plasma membrane. Phosphorylation of the C-terminus is essential for brassinosteroid-associated functions of RLP44. In contrast, RLP44’s role in phytosulfokine signalling is not affected by its phospho-status. Detailed mutational analysis suggests that phospho-charge, rather than modification of individual amino acids determines routing of RLP44 to its target receptor complexes, providing a framework to understand how a common component of different receptor complexes can get specifically engaged in a particular signalling pathway.
Identification of erythroid cell positive blood transcriptome phenotypes associated with severe respiratory syncytial virus infection
Authors: Rinchai Darawan , Altman Matthew B , Konza Oceane , Hässler Signe , Martina Federica , Toufiq Mohammed , Garand Mathieu , Kabeer Basirudeen , Palucka Karolina , Mejias Asuncion , Ramilo Octavio , Bedognetti Davide , Mariotti-Ferrandiz Encarnita , Klatzmann David , Chaussabel Damien
Published: January 2019

Biomarkers to assess the severity of acute respiratory syncytial virus (RSV) infection are needed. We conducted a meta-analysis of 490 unique profiles from six public RSV blood transcriptome datasets. A repertoire of 382 well-characterized transcriptional modules was used to define dominant host responses to RSV infection. The consolidated RSV cohort was stratified according to four traits: “interferon response” (IFN), “neutrophil-driven inflammation” (Infl), “cell cycle” (CC), and “erythrocytes” (Ery). Eight prevalent blood transcriptome phenotypes were thus identified. Among those three Ery+ phenotypes comprised higher proportions of patients requiring intensive care. We posit that the erythrocyte module is linked to an overabundance of immunosuppressive erythroid cells that might underlie progression to severe RSV infection. These findings outline potential priority areas for biomarker development and investigations into the immune biology of RSV infection. The approach that was employed here will also permit to delineate prevalent blood transcriptome phenotypes in other settings.
Chromatin conformation remains stable upon extensive transcriptional changes driven by heat shock
Authors: Ray Judhajeet , Munn Paul R. , Vihervaara Anniina , Ozer Abdullah , Danko Charles G. , Lis John T.
Published: January 2019

Heat shock (HS) initiates rapid, extensive, and evolutionarily conserved changes in transcription that are accompanied by chromatin decondensation and nucleosome loss at heat shock loci. Here we have employed in situ Hi-C to determine how heat stress affects long-range chromatin conformation in human and Drosophila cells. We found that compartments, topologically-associated domains (TADs), and looping interactions all remain unchanged by an acute HS. Knockdown of Heat Shock Factor 1 (HSF1), the master transcriptional regulator of the HS response, identified HSF1-dependent genes and revealed that up-regulation is often mediated by distal HSF1 bound enhancers. HSF1-dependent genes were usually found in the same TAD as the nearest HSF1 binding site. However, the HSF1 binding sites and the target promoters did not exhibit a focal increase in contact frequencies compared with surrounding regions, nor did we find evidence of increased contact frequency following HS. Integrating information about HSF1 binding strength, RNA polymerase abundance at the enhancer, and contact frequency with a target promoter in the non-heat shock (NHS) condition accurately predicted which up-regulated genes were direct targets of HSF1 during HS. Our results suggest that the chromatin conformation necessary for a robust HS response is pre-established in normal (uninduced) cells of diverse metazoan species.
DNA aptamers for the recognition of HMGB1 from Plasmodium falciparum
Authors: Joseph Diego F. , Nakamoto Jose A. , Ruiz Oscar Andree Garcia , Peñaranda Katherin , Sanchez-Castro Ana Elena , Castillo Pablo Soriano , Milón Pohl
Published: January 2019

Rapid Diagnostic Tests (RDTs) for malaria are restricted to a few biomarkers and antibody-mediated detection. However, the expression of commonly used biomarkers varies geographically and the sensibility of immunodetection can be affected by batch-to-batch differences or limited thermal stability. In this study we aimed to overcome these limitations by identifying a potential biomarker and by developing molecular sensors based on aptamer technology. Using gene expression databases, ribosome profiling analysis, and structural modeling, we find that the High Mobility Group Box 1 protein (HMGB1) of Plasmodium falciparum is highly expressed, structurally stable and steadily present along all blood-stages of P. falciparum infection. To develop biosensors, we used in vitro evolution techniques to produce DNA aptamers for the recombinantly expressed HMG-box, the conserved domain of HMGB1. An evolutionary approach for evaluating the dynamics of aptamer populations suggested three predominant aptamer motifs. Representatives of the aptamer families were tested for binding parameters to the HMG-box domain using microscale thermophoresis and rapid kinetics. Dissociation constants of the aptamers varied over two orders of magnitude between nano- and micromolar ranges while the aptamer-HMG-box interaction occurred in less than 30 seconds. The specificity of aptamer binding to the HMG-box of P. falciparum compared to its human homolog depended on pH conditions. Altogether, our study proposes HMGB1 as a potential biomarker and a set of sensing aptamers that can be further developed into rapid diagnostic tests for P. falciparum detection.
The phase transitions of 4-aminopyridine-based indolocarbazoles: twinning, local- and pseudo-symmetry
Authors: Kader Thomas , Stöger Berthold , Fröhlich Johannes , Kautny Paul
Published: January 2019

The phase transitions and polymorphism of three 4-aminopyridine-based indolocarbazole analogues are analyzed with respect to symmetry relationships and twinning. Seven polymorphs were structurally characterized using single-crystal diffraction. 5NICz (the indolo[3,2,1-jk]carbazole derivative with the C atom in the 5-position replaced by N) crystallizes as a P21/a high-temperature (270 K) polymorph and as a Pca21 low-temperature (150 K) polymorph. Even though their space-group symmetry is not related by a group–subgroup relationship, the local symmetries of both belong to the same order–disorder (OD) groupoid family. Both are polytypes of a maximum degree of order and are twinned by point operations of the other polytype. 2NICz (C atom in the 2-position replaced by N) likewise crystallizes in a high-temperature (Pcca, 280 K) polymorph and a low-temperature (P21/c, 150 K) polymorph. Here, the space-group symmetries are related by a group–subgroup relationship. The low-temperature phase is twinned by the point operations lost on cooling. The crystal structure of bulk 2,5NICz (N-substitution at the 2- and 5-positions) was unrelated to 2NICz and 5NICz and no phase transition was observed. Isolated single crystals of a different polymorph of 2,5NICz, isotypic with 2NICz, were isolated. However, the analogous phase transition in this case takes place at distinctly higher temperatures (> 300 K).
Modeling the factors affecting the quality of life in diabetic patients in India using total interpretive structural modeling
Authors: Ajmera Puneeta , Jain Vineet
Published: January 2019

Purpose

Diabetes mellitus has become a major world health problem that has unenviable impacts on health of the people including quality of life (QOL) also and in which person’s physical and psychological state, social commitments and relationships and his interaction with the environment is affected. This shows that there is an urgent need for behavior change and considerable educational strategies for proper management and rehabilitation (Reddy, 2000). This research has identified and ranked the significant factors which affect the QOL in diabetic patients in India. The paper aims to discuss these issues.

Design/methodology/approach

In this paper, nine factors which affect the QOL in diabetic patients in India have been identified through review of the literature and evaluated by total interpretive structural modeling (TISM) approach, i.e. an extended version of ISM. In this approach, interpretations of the interrelationship among factors have been discussed. Therefore, TISM approach has been used to develop the model and the mutual interactions among these factors.

Findings

The results of the model and MICMAC analysis indicate that diet restriction, body pain and satisfaction with treatment are the top-level factors.

Practical implications

Identification of the factors that have a remarkable effect on the QOL in diabetic patients is very important so that the doctors and other healthcare professionals may handle these factors efficiently and proper rehabilitation can be provided to such patients.

Originality/value

This paper has used an application of the TISM approach to interpret the mutual relationship by using the tool of interpretive matrix and has developed a framework to calculate the drive and the dependence power of factors using MICMAC analysis. The issues related to QOL are extremely important, as they can strongly anticipate a person’s capability to govern his lifestyle with disease like diabetes mellitus and maintain good health in the long run. This shows the urgent requirement of an optimized model which can predict and interpret the relationships among these factors. In this research, the interrelationships among these factors have been developed and interpretations of these interactions have been given to develop a comprehensive model so that QOL of diabetic patients may be improved.
M-PACT+: supporting families affected by parental substance misuse
Authors: Laing Karen , McWhirter Jennifer , Templeton Lorna , Hannah-Russell Claire
Published: January 2019

Purpose

The purpose of this paper is to present the findings from an evaluation of an intervention (Moving Parents and Children Together (M-PACT+)) aiming to address the effects of parental substance misuse (PSM) in school settings. The paper considers the evidence of effectiveness, and goes on to explore how schools were involved with the intervention.

Design/methodology/approach

A theory of change was developed for the intervention, which identified key steps of change that were expected for the beneficiaries (family members and children). Mixed methods were then used to form a portfolio of data to support or refute the theory. The data included quantitative validated scale data and questionnaires at various points in time with staff, and participants (including children), and qualitative data obtained from school staff, intervention staff, families and children.

Findings

This paper concludes that the evidence supports the theory that providing M-PACT+ in school settings can begin to address the effects of PSM for the families that engage with it. Further, the paper shows that the ethos of the schools involved influences how families are identified and referred, and that interventions of this kind are most likely to succeed where they are integrated into an ethos where there is a shared responsibility for a broad child well-being agenda between schools and other community agencies.

Originality/value

This paper explores the evaluation of a unique family intervention. The findings will be of value to those seeking to implement such interventions in partnership with schools and/or community agencies.
Entrepreneurial change in government-led development: Ethiopian universities
Authors: L.M. Mudde Huub , van Dijk Meine Pieter , Gerba Dugassa Tessema , Chekole Alemfrie Derese
Published: January 2019

Purpose

The purpose of this paper is answer the research question to what extent Ethiopian universities can be considered to be entrepreneurial and explains possible differences among these universities.

Design/methodology/approach

The paper is inspired by a mixed methods study at nine universities in Ethiopia applying the entrepreneurial university framework of the European Commission/OECD: a content analysis of university policy and educational documents, a structured survey with 203 respondents, in particular staff and students, and in-depth interviews and focus group discussions with 223 people comprising university top-management, faculty, students and external stakeholders.

Findings

Findings indicate that entrepreneurial activities in Ethiopian universities are at their infant stage with limited differences among the universities. The universities are operating in a top-down, central governmental-led development that is not enabling entrepreneurial behaviour at the level of the individual institutions. The paper argues that within this context, leadership is the lever for an entrepreneurial turn at the universities.

Social implications

Entrepreneurship development is a priority in many African countries as an instrument for employability of the predominant young populations towards which universities are expected to contribute considerably. The study highlights the tension between a strong say of the government in university operations and creating an autonomous, integrated entrepreneurial culture.

Originality/value

The results of this study have relevance for the higher education community in terms of understanding the complexity of transforming institutions into more entrepreneurial organisations in Africa. To the best of the authors’ knowledge, there is no previous study that examines entrepreneurial characteristics of several universities in Ethiopia.
Understanding self-efficacy and the dynamics of part-time work and career aspiration
Authors: Gbadamosi Gbolahan , Evans Carl , Richardson Mark , Chanthana Yos
Published: January 2019

Purpose

Building on the self-efficacy theory and self-theories, the purpose of this paper is to investigate students working part-time whilst pursuing full-time higher education in Cambodia. It explores individuals’ part-time working activities, career aspirations and self-efficacy.

Design/methodology/approach

Data were collected in a cross-sectional survey of 850 business and social sciences degree students, with 199 (23.4 per cent) usable responses, of which 129 (65.2 per cent of the sample) indicated they currently have a job.

Findings

Multiple regression analysis confirmed part-time work as a significant predictor of self-efficacy. There was a positive recognition of the value of part-time work, particularly in informing career aspirations. Female students were significantly more positive about part-time work, demonstrating significantly higher career aspirations than males. Results also suggest that students recognise the value that work experience hold in identifying future career directions and securing the first graduate position.

Practical implications

There are potential implications for approaches to curriculum design and learning, teaching and assessment for universities. There are also clear opportunities to integrate work-based and work-related learning experience into the curriculum and facilitate greater collaboration between higher education institutions and employers in Cambodia.

Social implications

There are implications for recruitment practices amongst organisations seeking to maximise the benefits derived from an increasingly highly educated workforce, including skills acquisition and development, and self-efficacy.

Originality/value

It investigates the importance of income derived from part-time working to full-time university students in a developing South-East Asian country (Cambodia), where poverty levels and the need to contribute to family income potentially predominate the decision to work while studying.
Evaluating factors affecting patient satisfaction using the Kano model
Authors: Materla Tejaswi , Cudney Elizabeth A. , Hopen Deborah
Published: January 2019

Purpose

Healthcare providers are increasing their focus on patient satisfaction and patient-oriented services as they play a significant role in managing rising costs, elevating service quality and establishing sustainable quality improvement strategies. In recent years, the Kano model has gained popularity in the healthcare industry and has been employed to improve patient satisfaction. The purpose of this paper is to illustrate how the Kano model can be deployed to identify a wide range of complex patient needs and convey its potential usefulness in the continuous improvement of the healthcare sector.

Design/methodology/approach

This paper provides a case study of implementing the Kano model to identify diverse patient needs and aims to eliminate the gaps identified in prior research, which include generically applying the Kano model to all service units of the healthcare system and using a predetermined service quality scale. This study emphasizes the importance of scale development and individual attention to each healthcare service unit in determining intricate patient needs. A cross-sectional study was conducted at the Student Health Services (SHS) of Missouri University of Science and Technology where the data were collected using the Kano survey. The respondents included undergraduate and graduate students that have utilized the healthcare services offered. A total of 138 patients were surveyed using a Kano model-based questionnaire that included demographics and treatment as well as service expectations.

Findings

Of the 21 quality attributes evaluated by the patients, 16 were categorized as one-dimensional, 3 as indifferent, and 2 as attractive attributes using the Kano model. None of the quality attributes showed a dominant must-be feature. The students considered the availability of appropriately qualified medical staff within 10 minutes of the check-in process and provision of after-hours care as attractive attributes that create greater satisfaction.

Research limitations/implications

The research was conducted at a university SHS center. Therefore, respondents in the survey are in a younger age group, which may affect patient expectations. In addition, expectations of an SHS center may be different than expectations of visiting a primary care physician and other healthcare units.

Originality/value

This study contributes to a better understanding of the identification of healthcare needs using the Kano model and advocates focusing on shifts in the categories over time and changes in the demographic environment.
Greek gynecology healthcare professionals towards quality management systems
Authors: Dinas Konstantinos , Vavoulidis Eleftherios , Pratilas Georgios Chrysostomos , Basonidis Alexandros , Liberis Anastasios , Zepiridis Leonidas , Sotiriadis Alexandros , Papaevangeliou Dimitra , Stathopoulou Aliki , Leimoni Eirini , Pantazis Konstantinos , Tziomalos Konstantinos , Aletras Vassilis , Tsiotras George
Published: January 2019

Purpose

Today, quality management systems (QMS) are a promising candidate for the improvement of healthcare services. The purpose of this paper is to investigate the opinions/attitudes of gynecology healthcare professionals toward quality and quality management in healthcare facilities (HFs) in Greece.

Design/methodology/approach

An anonymous self-administered questionnaire was distributed to healthcare professionals, asking for opinions on quality objectives associated with the everyday workflow in HFs (e.g. management of patients, resources, etc.) and on QMS. The study was conducted in Hippokration Hospital of Thessaloniki, including 187 participants. Statistical assessment and analysis of the questionnaires were carried out.

Findings

Although 87.5 percent recognized the importance of potential QMS implementation and accreditation, over 50 percent believed that it would lead rather to increased workload and bureaucracy than to any considerable quality improvement. More than 60 percent were completely unaware of the implementation of quality objectives such as quality handbook, quality policy, audit meetings and accreditation status in their HFs. This unawareness was also reported in terms of patient, data, human and general resources management. Finally, awareness over medical malpractice and positive attitude toward official reporting were detected.

Originality/value

Most respondents acknowledged the significance of quality, QMS implementation and accreditation in Greek hospitals. However, there was a critical gap in knowledge about quality management objectives/processes that could be possibly resolved by expert teams and well-organized educational programs aiming to educate personnel regarding the various quality objectives in Greek HFs.
Understanding and improving the care pathway for children with autism
Authors: Hurt Lisa , Langley Kate , North Kate , Southern Alex , Copeland Lauren , Gillard Jonathan , Williams Sharon
Published: January 2019

Purpose

The purpose of this paper is to describe current care pathways for children with autism including enablers and barriers, as experienced by health professionals, education professionals and families in South Wales, UK.

Design/methodology/approach

This study is based on a mixed-methods approach using focus group discussions, creative writing workshops and visualisation using rich pictures.

Findings

The experiences of the care pathways differed significantly across the three groups. Health professionals described the most rigidly structured pathways, with clear entry points and outcomes. Education professionals and parents described more complex and confusing pathways, with parents assuming the responsibility of coordinating the health and education activity in a bid to link the two independent pathways. All three groups identified enablers, although these differed across the groups. The barriers were more consistent across the groups (e.g. poor communication, missing information, lack of transparency, limited post-diagnosis services and access to services based on diagnosis rather than need).

Practical implications

This research could inform the design of new services which are premised on multi-agency and multi-disciplinary working to ensure children with Autism spectrum disorders (ASD) receive joined up services and support.

Originality/value

Although this study did not represent all professional groups or all experiences of autism, the authors examined three different perspectives of the ASD pathway. In addition, the authors triangulated high-level process maps with rich pictures and creative writing exercises, which allowed the authors to identify specific recommendations to improve integration and reduce duplication and gaps in provision.
Failure demand: a concept evaluation in UK primary care
Authors: Walley Paul , Found Pauline , Williams Sharon
Published: January 2019

Purpose

The purpose of this paper is to assess failure demand as a lean concept that assists in waste analysis during quality improvement activity. The authors assess whether the concept’s limited use is a missed opportunity to help us understand improvement priorities, given that a UK Government requirement for public service managers to report failure demand has been removed.

Design/methodology/approach

The authors look at the literature across the public sector and then apply the failure demand concept to the UK’s primary healthcare system. The UK National Health Service (NHS) demand data are analysed and the impact on patient care is elicited from patient interviews.

Findings

The study highlighted the concept’s value, showing how primary care systems often generate failure demand partly owing to existing demand and capacity management practices. This demand is deflected to other systems, such as the accident and emergency department, with a considerable detrimental impact on patient experience.

Research limitations/implications

More research is needed to fully understand how best to exploit the failure demand concept within wider healthcare as there are many potential barriers to its appropriate and successful application.

Practical implications

The authors highlight three practical barriers to using failure demand: first, demand within the healthcare system is poorly understood; second, systems improvement understanding is limited; and third, need to apply the concept for improvement and not just for reporting purposes.

Originality/value

The authors provide an objective and independent insight into failure demand that has not previously been seen in the academic literature, specifically in relation to primary healthcare.