bluuebunny/crossref_metadata_2025 huggingface dataset:
Modelling glioblastoma tumour-host cell interactions using adult brain organotypic slice co-culture
Authors: Marques-Torrejon Maria Angeles , Gangoso Ester , Pollard Steven M.
Published: July 2017

Glioblastoma (GBM) is an aggressive incurable brain cancer. The cells that fuel the growth of tumours resemble neural stem cells found in the developing and adult mammalian forebrain. These are referred to as GBM stem cells (GSCs). Similar to neural stem cells, GSCs exhibit a variety of phenotypic states: dormant, quiescent, proliferative and differentiating. How environmental cues within the brain influence these distinct states is not well understood. Laboratory models of GBM tumours can be generated using either genetically engineered mouse models, or via intracranial transplantation of cultured tumour initiating cells (mouse or human). Unfortunately, these approaches are expensive, time-consuming, low-throughput and ill-suited for monitoring of live cell behaviours. Here we explored whole adult brain coronal organotypic slices as a complementary strategy to remove the experimental bottleneck. Mouse adult brain slices remain viable in a neural stem cell serum-free basal media for several weeks. GSCs can therefore be easily microinjected into specific anatomical sitesex vivo. We demonstrated distinct responses of engrafted GSCs to different microenvironments in the brain. Within the subependymal zone – one of the adult neural stem cell niches – a subset of injected tumour cells could effectively engraft and respond to endothelial niche signals. GSCs transplanted slices were treated with the anti-mitotic drug temozolomide as proof-of-principle of the utility in modelling responses to existing treatments. Thus, engraftment of mouse or human GSCs onto whole brain coronal organotypic brain slices provides a convenient experimental model for studies of GSC-host interactions and preclinical testing of candidate therapeutic agents.
EndophyteChaetomium globosumD38 and its elicitors promote tanshinones accumulation ofSalvia miltiorrhiza
Authors: Zhai Xin , Luo Dong , Li Xiuqing , Han Ting , Kong Zhouyang , Ji Jiachen , Qin Luping , Zheng Chengjian
Published: July 2017

Due to the low yield of tanshinones and their analogues inSalvia miltiorrhiza, there are all kinds of stimulation strategies having been applied to improve tanshinones output in plant tissue cultures. Endophytic fungi have formed various different relationships with their host plants withstanding host and environmental factors, including symbiotic, mutualistic, commensalistic, and parasitic. Thus we take the assumption that endophytic fungi may be an emerging microbial tool used to promote secondary metabolism, which will promote the production of active compounds through endophyte-based biology method. Our study therefore aimed to examine the effects of live endophytic fungusChaetomium globosumD38 and its elicitors on the accumulation of tanshinones in hairy root cultures ofSalvia miltiorrhiza. C. globosumD38 mainly colonized in the intercellular gap of xylem parenchyma cells ofS. miltiorrhizahairy root, during long term co-existence without any toxicity againstS. miltiorrhizahairy root. Moreover, both of the live fungus and its mycelia extracts could induce the production of tanshinones, in special dihydrotanshinone I and cryptotanshinone. The effects of mycelia extracts were much stronger than that of the live fungus on tanshinones synthesis, which increased the transcriptional activity of genes with repect to tanshinone biosynthetic pathway obviously. Our results indicated that both of the liveC. globosumD38 and its mycelia extracts could be utilized for tanshinones accumulation inS. miltiorrhizahairy root. What’s more, D38 also could be made into biotic fertilizer applying intoS.miltiorrhizaseddlings, which not only promoted host growth but the tanshinones and phenylpropionic acid accumulation. In the soil environment, D38 had formed bitrophic and mutual beneficial relationship with the host and enhanced the primary metabolism on the whole so as to have facilitative effects on phenylpropionic acid accumulation. To sum up,Chaetomium globosumD38 was a highly effective endophytic fungus forS. miltiorrhiza.
Effective normalization for copy number variation in Hi-C data
Authors: Servant N. , Varoquaux N. , Heard E. , Vert JP. , Barillot E.
Published: July 2017

Normalization is essential to ensure accurate analysis and proper interpretation of sequencing data. Chromosome conformation data, such as Hi-C, is not different. The most widely used type of normalization of Hi-C data casts estimations of unwanted effects as a matrix balancing problem, relying on the assumption that all genomic regions interact as much as any other. Here, we show that these approaches, while very effective on fully haploid or diploid genome, fail to correct for unwanted effects in the presence of copy number variations. We propose a simple extension to matrix balancing methods that properly models the copy-number variation effects. Our approach can either retain the copy-number variation effects or remove it. We show that this leads to better downstream analysis of the three-dimensional organization of rearranged genome.
Regulating the UAS/GAL4 system in adultDrosophilawith Tet-off GAL80 transgenes
Authors: Barwell Taylor , DeVeale Brian , Poirier Luc , Zheng Jie , Seroude Frederique , Seroude Laurent
Published: July 2017

The UAS/GAL4 system is the most used method InDrosophila melanogasterfor directing the expression of a gene of interest to a specific tissue. However, the ability to control the temporal activity of GAL4 with this system is very limited. This study constructed and characterized Tet-off GAL80 transgenes designed to allow temporal control of GAL4 activity in aging adults. By placing GAL80 under the control of a Tet-off promoter, GAL4 activity is regulated by the presence or absence of tetracycline in the diet. Almost complete inhibition of the expression of UAS transgenes during the pre-adult stages of the life cycle is obtained by using four copies and two types of Tet-off GAL80 transgenes. Upon treatment of newly emerged adults with tetracycline, induction of GAL4 activity is observed but the level of induction is influenced by the concentration of the inducer, the age, the sex and the anatomical location of the expression. The inhibition of GAL4 activity and the maintenance of induced expression is altered in old animals. This study reveals that the repressive ability of GAL80 is affected by the age and sex of the animal which is a major limitation to regulate gene expression with GAL80 in agedDrosophila.
Age-related changes in the neural networks supporting semantic cognition: A meta-analysis of 47 functional neuroimaging studies
Authors: Hoffman Paul , Morcom Alexa M.
Published: July 2017

Semantic cognition is central to understanding of language and the world and, unlike many cognitive domains, is thought to show little age-related decline. We investigated age-related differences in the neural basis of this critical cognitive domain by performing an activation likelihood estimation (ALE) meta-analysis of functional neuroimaging studies comparing young and older people. On average, young people outperformed their older counterparts during semantic tasks. Overall, both age groups activated similar left-lateralised regions. However, older adults displayed less activation than young people in some elements of the typical left-hemisphere semantic network, including inferior prefrontal, posterior temporal and inferior parietal cortex. They also showed greater activation in right frontal and parietal regions, particularly those held to be involved in domain-general controlled processing, and principally when they performed more poorly than the young. Thus, semantic processing in later life is associated with a shift from semantic-specific to domain-general neural resources, consistent with the theory of neural dedifferentiation, and a performance-related reduction in prefrontal lateralisation, which may reflect a response to increased task demands.
Inter-subject phase synchronization and the dynamics of human cognition
Authors: Bolt Taylor , Nomi Jason S. , Vij Shruti G. , Chang Catie , Uddin Lucina Q.
Published: July 2017

Massive whole-brain blood-oxygen-level dependent (BOLD) signal modulation (up to 95% of brain voxels) in response to task stimuli has recently been reported in functional MRI investigations. These findings have two implications. First, they highlight inability of a conventional ‘top-down’ general linear model approach to capture all forms of task-driven brain activity. Second, as opposed to a static ‘active’ or ‘non-active’ localization theory of the neural implementation of cognitive processes, functional neuroimaging should develop and pursuedynamicaltheories of cognition involving the dynamic interactions ofallbrain networks, in line with psychological constructionist theories of cognition. In this study, we describe a novel exploratory, bottom-up approach that directly estimates task-driven brain activity regardless of whether it follows ana priorireference function. Leveraging the property that task-driven brain activity is associated with reductions in BOLD signal variability, we combine the tools of instantaneous phase synchronization and independent component analysis to characterizewhole-braintask-driven activity in terms of group-wise similarity in temporal signal dynamics of brain networks. We applied this novel framework to task fMRI data from a motor, theory of mind and working memory task provided through the Human Connectome Project. We discovered a large number of brain networks that dynamically synchronized to various features of the task scan, some overlapping with areas identified as ‘active’ in the top-down GLM approach. Using the results provided through this novel approach, we provide a more comprehensive description of cognitive processes whereby task-related brain activity is not restricted to dichotomous ‘active’ or ‘non-active’ inferences, but is characterized by the temporal dynamics of brain networks across time.

Significance Statement

This study describes the results of a novel exploratory methodological approach that allows for direct estimation of task-driven brain activity in terms of group-wise similarity in temporal signal dynamics, as opposed to the conventional approach of identifying task-driven brain activity with a hypothesized temporal pattern. This approach applied to three different task paradigms yielded novel insights into the brain activity associated with these tasks in terms of time-varying, low-frequency dynamics of replicable synchronization networks. We suggest that this exploratory methodological approach provides a framework in which the complexity and dynamics of the neural mechanisms underlying cognitive processes can be captured more comprehensively.
Conformational Dynamics and Energy Landscapes of Ligand Binding in RyR1
Authors: Dashti A. , Hail D. Ben , Mashayekhi G. , Schwander P. , des Georges A. , Frank J. , Ourmazd A.
Published: July 2017

Using experimental single-particle cryo-EM snapshots of ryanodine receptor (RyR1), a Ca2+-channel involved in skeletal muscle excitation/contraction coupling, we present quantitative free-energy landscapes, reaction coordinates, and three-dimensional movies of the continuous conformational changes associated with the binding of activating ligands. Our results show multiple routes to ligand binding with comparable branching ratios. All high-probability routes involve significant conformational changes before and after the binding of ligands. We also present new insights into the local structural changes along the ligand-binding route, including accommodations at the calcium, ATP, and caffeine binding sites. These observations shed new light on the mechanisms and conformational routes to ligand binding.
Switchable amplification of fluoresence from a photosynthetic microbe
Authors: Bose Anirban , Raja Sufi O , Chowdhury Rajdeep , Nandi Somen , Ray Sanhita , Bhattacharyya Kankan , Dasgupta Anjan Kr
Published: July 2017

One known attribute of the photosynthetic apparatus is photon capture and generation of metabolic energy. The thermodynamic implications of fluorescence, invariably associated with the photosynthetic components is however poorly understood. In this paper we report a density dependent amplification of such fluorescence which can be interpreted as a thermodynamic strategy of controlled energy release by the cell. We show in support of this hypothesis that prolonged photo-exitation of cell free extract ofRhodobacter capsulatusSB1003 at 395 nm, induces fluorescence emission amplifying with time as long as the fluorophore density is above a critical level. The fact that the amplification disappears at low temperature and at dilute condition, is in accordance with the thermodynamic interpretation that energy is released as per requirement. Live cell imaging is also validation of the phenomenon even at the cellular level. Single cells ofRhodobacter capsulatusSB1003 shows time dependent loss of fluorescence, the process being reversed for cellular clusters. To explain the mechanism of this bistable fluorescence (F) amplification, variation of the scale free kinetic constant k=1/F (dF/dt) is studied at varying temperatures in presence and absence of static magnetic field. The sign of k shifts from positive to negative if T is lowered or if the system is diluted. But at low T, k again switches from negative to positive value, if static magnetic field is applied. The chain of events can be explained by a simple model assuming excretion of a porphyrin by the microbe and possible photon dependent aggregation behavior of such porphyrin complex, differential temperature and magnetic field sensitivity of the monomeric or aggregated forms of porphyrin being reported earlier.
Probing tissue-scale deformation byin vivoforce application reveals a fast tissue softening during early embryogenesis
Authors: D’Angelo Arturo , Dierkes Kai , Carolis Carlo , Salbreux Guillaume , Solon Jérôme
Published: July 2017

During development, cell-generated forces induce tissue-scale deformations to shape the organism. Here, we present a method that allows to quantitatively relate such tissue-scale deformations to spatially localized forces and measure mechanical properties of epitheliain vivo. Our approach is based on the application of controlled forces on microparticles embedded in individual cells of an embryo. Combining measurements of the bead displacement with the analysis of induced deformation fields in a continuum mechanics framework, we can quantify tissue material properties and follow their change over time. In particular, we uncover a rapid change in tissue response occurring duringDrosophilacellularization, resulting from a softening of the blastoderm and an increase of external friction. Pharmacological treatments reveal that in addition to actomyosin, the microtubule cytoskeleton is a major contributor to epithelial mechanics at that stage. Overall, our method allows for measuring essential mechanical parameters governing tissue-scale deformations and flows occurring during morphogenesis.
Printed Droplet Microfluidics for on demand dispensing of picoliter droplets and cells
Authors: Cole Russell H. , Tang Shi-yang , Siltanen Christian A. , Shahi Payam , Zhang Jesse Q. , Poust Sean , Gartner Zev J. , Abate Adam R.
Published: July 2017

Although the elementary unit of biology is the cell, high throughput methods for the microscale manipulation of cells and reagents are limited. The existing options are either slow, lack single cell specificity, or utilize fluid volumes out of scale with those of cells. Here, we present Printed Droplet Microfluidics, a technology to dispense picoliter droplets and cells with deterministic control. The core technology is a fluorescence-activated droplet sorter coupled to a specialized substrate that together act as a picoliter droplet and single cell printer, enabling high throughput generation of intricate arrays of droplets, cells, and microparticles. Printed Droplet Microfluidics provides a programmable and robust technology to construct arrays of defined cell and reagent combinations and to integrate multiple measurement modalities together in a single assay.
Systems-level identification of transcription factors critical for mouse embryonic development
Authors: Zhang Kai , Wang Mengchi , Zhao Ying , Wang Wei
Published: July 2017

Dynamic changes in the transcriptional regulatory circuit can influence the specification of distinct cell types. Numerous transcription factors (TFs) have been shown to function through dynamic rewiring during embryonic development but a comprehensive survey on the global regulatory network is still lacking. Here, we performed an integrated analysis of epigenomic and transcriptomic data to reveal key regulators from 2 cells to postnatal day 0 in mouse embryogenesis. We predicted 3D chromatin interactions including enhancer-promoter interactions in 12 tissues across 8 developmental stages, which facilitates linking TFs to their target genes for constructing genetic networks. To identify driver TFs particularly those not necessarily differentially expressed ones, we developed a new algorithm, dubbed as Taiji, to assess the global importance of TFs in development. Through comparative analysis across tissues and developmental stages, we systematically uncovered TFs that are critical for lineage-specific and stage-dependent tissue specification. Most interestingly, we have identified TF combinations that function in spatiotemporal order to form transcriptional waves regulating developmental progress and differentiation. Not only does our analysis provide the first comprehensive map of transcriptional regulatory circuits during mouse embryonic development, the identified novel regulators and the predicted 3D chromatin interactions also provide a valuable resource to guide further mechanistic studies.
TruePaiR: Software for the Accurate Identification of Complementary piRNA Read Pairs in High-Throughput Sequencing Data
Authors: Schreiner Patrick , Atkinson Peter W.
Published: July 2017

piRNAs and their biogenesis pathways are well-conserved in Metazoans (Grimson et al. 2008). piRNAs have been implicated in transcriptional, post-transcriptional, and translational regulation (Grivna et al. 2006; Lin & Yin 2008; Brennecke et al. 2008; Brennecke et al. 2007; Aravin et al. 2007). We analyze the signatures of a critical process in the primary and secondary mechanism of piRNA biogenesis, referred to as the amplification loop.

The presence of U-1 and A-10 bias within piRNA populations is an indicator, but not an absolute measure of piRNA amplification. By further considering imperfect and perfect sequence complementarity within the first ten base pairs of piRNAs, the active site promoting secondary piRNA biogenesis, we developed practical and statistically powerful metrics to observe relative piRNA amplification. TruePaiR is a fast and effective general software tool to assess the relative utilization of piRNA amplification in high throughput sRNA sequencing data.

The results of TruePaiR runs in seven species and five tissues serve as a benchmark for meaningful context of piRNA amplification. The TruePaiR metrics provide foundational data regarding the in terms of species specificity, tissue specificity, as well as the relative participation based upon origin-based piRNA subsets regarding piRNA amplification. The low degree of variability of same sample TruePaiR runs allows for metric reliability, reproducibility, as well as the ability to detect subtle differences in piRNA amplification within and between species and tissues. Given that TruePaiR serves as an effective and consistent metric of piRNA amplification across species, it can represent a new, meaningful standard in the degree of piRNA amplification in a specific organism and tissue that is or is not expected to undergo piRNA amplification.
TripAdvisor and reputation: a case study of the hotel industry in Cyprus
Authors: Nicoli Nicholas , Papadopoulou Evgenia
Published: July 2017

Purpose

The purpose of this paper is to examine the significance of TripAdvisor on reputation within the hotel industry. TripAdvisor encapsulates key themes in establishing an online reputation strategy in an evolving digital landscape.

Design/methodology/approach

Through the use of an exploratory case study, data were gathered primarily by means of a series of expert interviews within the hotel industry in Cyprus, today a mature holiday destination in Europe. Further data collection included a document search of presentations, annual reports, past surveys and sales and marketing literature from the examined industry.

Findings

Hotel communication practitioners are fully aware of the impact of social media in managing reputation. Constant monitoring, prompt responses, training and transparency were identified as key factors. Online reputation management needs to be taken into consideration when designing a comprehensive integrated communication strategy.

Research limitations/implications

Congruence amongst interviewees in certain areas could be on account of the homogeneity of practitioners, of their background and training and of similar organisational cultures across the locale of study. This leads to limits in the generalisations from this study’s findings.

Practical implications

Encouragement and training of employees were amongst the primary suggestions that emerged. An internal and external environmental scan, recognising possible strengths, weaknesses, opportunities and threats, which could assist in the effective engagement and monitoring of the organisation’s online presence, were also suggested.

Originality/value

The uniqueness of the study lies in its exploration of reputation management of a well-known traveller’s platform by addressing social media content in both a proactive and reactive manner.
Sukuk and conventional bonds: shareholder wealth perspective
Authors: Sherif Mohamed , Erkol Cennet Tuba
Published: July 2017

Purpose

This study aims to comprehensively examine the stock market effects of announcements by firms to issue conventional bonds versus Sukuk. In addition, the authors investigate whether the choice of instrument depends on the tax status and government backing of the issuing firm. They split the sample into whole (2000-2015), pre-crisis (2000-2007) and post-crisis (2010-2015) subsamples.

Design/methodology/approach

The authors use event study methodology, market model and FTSE Bursa Malaysia EMAS index on 14 different event windows of which five are symmetric and nine are asymmetric. Further, parametric and distribution-free tests are used to investigate the difference of cumulative abnormal returns when using the two instruments (Sukuk and conventional bonds). For the choice of issuing conventional bonds or Sukuk, Heckman procedure is employed to control for the self-selection of the announcement effects.

Findings

The analysis indicates only insignificant difference in reaction to Sukuk and conventional bond issuances for the overall period and pre-crisis period. However, and importantly, they find strong evidence supporting the Malaysian stock abnormal return reaction to Sukuk compared to conventional bond issuances after the global financial crisis. Interestingly, they find that tax incentives and government backing are significant determinants in issuing Sukuk over conventional bonds. Such evidence is confirmed when using a wide range of robustness checks including four different market indices and both parametric and non-parametric tests.

Research limitations/implications

The empirical analysis is subject to limitations. First, the sample is limited to Sukuk issues domiciled in Malaysia. Second, given that Sukuk are collateralized whereas conventional bonds are not, it would only seem logical for the former to be issued by riskier firms whereas the latter would be issued by stronger firms with stable cash flows. The future research can explore this issue some more. Finally, comparing Sukuk with other similar ethical sources of traded capital may provide insights into the globalization of such economic, trade and financial reforms in and outside Malaysia.

Originality/value

To the author’s knowledge, no research has been conducted studying the differential and conflicting results to announcement of Sukuk issuance in the literature, nor the stock market effects of announcements to issue Sukuk over the pre-crisis (2000-2007) and post-crisis (2010-2015) periods. Thus, the study attempts to assess previous findings and contribute additional evidence that investigates the issue in rich setting.
Asparagus racemosus
Authors: Noor Sabahu , Bhat Z.F. , Kumar Sunil , Kousar Insha
Published: July 2017

Purpose

This paper aims to explore the possibility of utilization of Asparagus racemosus as a novel natural preservative in meat products.

Design/methodology/approach

Chevon sausages were used as a study model and prepared by incorporating different levels of A. racemosus, namely, T1 (0.25 per cent), T2 (0.50 per cent) and T3 (0.75 per cent) and were vacuum packaged and assessed for various lipid oxidative stability and storage quality parameters under refrigerated (4  ±  1°C) conditions.

Findings

Significantly (p < 0.05) lower thiobarbituric acid reacting substances (mg malonaldehyde/kg) values were observed for the products containing A. racemosus in comparison to control indicating a significant effect on the lipid oxidative stability. The products containing A. racemosus also showed significantly (p < 0.05) lower values for various microbiological characteristics like total plate count (log cfu/g), psychrophilic count (log cfu/g), yeast and mould count (log cfu/g), anaerobic count (log cfu/g) and free fatty acid (% oleic acid) values indicating the antimicrobial and antifungal properties of A. racemosus. No significant (p > 0.05) effect was observed on the cooking yield and moisture content of the products. Significantly (p < 0.05) higher scores were observed for various sensory parameters of the products containing A. racemosus during the entire period of storage.

Originality/value

A. racemosus successfully improved the lipid oxidative stability and storage quality of the model meat product without compromising the sensorial characteristics and has a great potential as a novel natural preservative in muscle foods.
Beyond unsustainable leadership: critical social theory for sustainable leadership
Authors: Bendell Jem , Sutherland Neil , Little Richard
Published: July 2017

Purpose

The purpose of this paper is to prepare the conceptual groundwork for the future study of leadership for sustainable development. The paper demonstrates the relevance of Critical Leadership Studies to future research on sustainable development policies and practices. A critical approach is also applied to concepts of sustainable development, with three paradigms of thought described.

Design/methodology/approach

The approach taken is an extensive literature review in fields of leadership and sustainable development, with a focus on some of the broad assumptions and assertions in those literatures.

Findings

A key finding is that leadership studies drawing from critical social theory can provide important insights into future research and education on leadership for sustainability. This literature shows that some assumptions about leadership may hinder opportunities for social or organisational change by reducing the analysis of factors in change or reducing the agency of those not deemed to be leading. These limitations are summarised as “seven unsustainabilities” of mainstream leadership research.

Research limitations/implications

The paper calls for the emerging field of sustainable leadership to develop an understanding of significant individual action that includes collective, emergent and episodic dimensions. The paper then summarises key aspects of the papers in this special issue on leadership for sustainability.

Practical implications

The implications for practice are that efforts to promote organisational contributions to sustainable development should not uncritically draw upon mainstream approaches to leadership or the training of leaders.

Originality/value

The authors consider this the first paper to provide a synthesis of insights from Critical Leadership Studies for research in sustainability.
Falling into a routine: from habits to situated practices
Authors: Cohn Simon , Lynch Rebecca
Published: July 2017

In line with the concept of ‘nudging’ people to change their behaviour, there has been increased attention on habit as a focus for psychologically‐based health interventions. It is hoped that behaviours initiated by interventions not only become so regular that they are normalised into people's everyday lives, but that through repetition they may eventually become fixed and habitual. In this paper we draw on people's accounts of participating in a trial designed to encourage greater physical activity, and attend to the ways they describe their engagement with interventions within wider narratives of their everyday lives. In contrast to the idea that habit refers to automatic behaviour cued by external stimuli and governed by unconscious cognitive processes, our study describes how people identify many diverse elements that are felt to have equal significance in achieving a routine. Paradoxically, the sense of stability derives not from exact repetition, but from the ability for an assemblage of elements to be configured slightly differently each time. We consequently argue that attending to the diverse range of contextual elements bracketed off from interventions designed to be tested in trials, and the idea that continuity might emerge from variation, demands a reconceptualisation of the concept of habit adopted within many areas of current health psychology.
Human resource management policy choices, management practices and health workforce sustainability: remote Australian perspectives
Authors: Onnis Leigh‐ann
Published: July 2017

The challenges for health professionals working in remote regions are diverse, particularly where voluntary turnover is high. This study examined the influence of management practices on workforce sustainability in remote regions of northern Australia using human resource management (HRM) policy choices. In this study, 24 semi‐structured interviews withHRmanagers, health professionals and health managers revealed that the impact ofHRMpolicy choices on remote workforce sustainability is significantly influenced by management practices. The emergent themes depict work environments where ineffective management practices for recruitment, remuneration, resourcing and relationships have profound consequences. Despite these contextual challenges, examples emerged where effective management practices created stability and improved retention. Hence, the findings suggest that sustainable remote health workforces are achievable where localised management practices improve equity, where employee–manager relationships are fostered, and where there is equitable access to resources and professional development.
The impact of chronic psychiatric disorders on cognitive decline
Authors: Villeneuve R. , Blanchard C. , Rullier L. , Raoux N. , Bergua V. , Dartigues J.‐F. , Pérès K. , Amieva H.
Published: July 2017

Objectives

Based on seemingly contradictory results in the existing literature, the objective of our study was to investigate whether older individuals suffering from chronic psychiatric disorders show a more rapid decline in cognitive performances than their non‐psychiatric counterparts, or if the pattern of decline through older age is similar in both groups.

Method

A total of 820 older adults were selected from the Ageing Multidisciplinary Investigation (AMI) cohort study, which studies health‐related issues of people over 65 years old living in rural areas. Among them, 30 suffer from chronic psychiatric disorders. Cognition was assessed with four neuropsychological tests: the Mini–Mental State Examination, the Digit Symbol Substitution Test, the Free and Cued Selective Reminding test and the Isaacs Set Test. Linear mixed models were used to compare the evolution of cognitive performances in the two groups between baseline and the four‐year follow‐up.

Results

Despite lower performances at baseline, the pattern of cognitive decline of the psychiatric group is similar to that of the control group.

Conclusion

As suggested by this study conducted in rural communities, community‐dwelling people suffering from chronic psychiatric disorders should not be considered at greater risk of age‐related accelerated cognitive decline than the non‐psychiatric older population.
The experience of initiating injection drug use and its social context: a qualitative systematic review and thematic synthesis
Authors: Guise Andy , Horyniak Danielle , Melo Jason , McNeil Ryan , Werb Dan
Published: July 2017

Background and aim

Understanding the experience of initiating injection drug use and its social contexts is crucial to inform efforts to prevent transitions into this mode of drug consumption and support harm reduction. We reviewed and synthesized existing qualitative scientific literature systematically to identify the socio‐structural contexts for, and experiences of, the initiation of injection drug use.

Methods

We searched six databases (Medline, Embase, PsychINFO, CINAHL, IBSS and SSCI) systematically, along with a manual search, including key journals and subject experts. Peer‐reviewed studies were included if they qualitatively explored experiences of or socio‐structural contexts for injection drug use initiation. A thematic synthesis approach was used to identify descriptive and analytical themes throughout studies.

Results

From 1731 initial results, 41 studies reporting data from 1996 participants were included. We developed eight descriptive themes and two analytical (higher‐order) themes. The first analytical theme focused on injecting initiation resulting from a social process enabled and constrained by socio‐structural factors: social networks and individual interactions, socialization into drug‐using identities and choices enabled and constrained by social context all combine to produce processes of injection initiation. The second analytical theme addressed pathways that explore varying meanings attached to injection initiation and how they link to social context: seeking pleasure, responses to increasing tolerance to drugs, securing belonging and identity and coping with pain and trauma.

Conclusions

Qualitative research shows that injection drug use initiation has varying and distinct meanings for individuals involved and is a dynamic process shaped by social and structural factors. Interventions should therefore respond to the socio‐structural influences on injecting drug use initiation by seeking to modify the contexts for initiation, rather than solely prioritizing the reduction of individual harms through behavior change.
Fine‐scale drivers of beetle diversity are affected by vegetation context and agricultural history
Authors: Ross Catherine E. , Barton Philip S. , McIntyre Sue , Cunningham Saul A. , Manning Adrian D.
Published: July 2017

Environmental gradients have been shown to affect animal diversity, but knowledge of fine‐scale drivers of insect diversity is, in many cases, poorly developed. We investigated the drivers of beetle diversity and composition at different microhabitats, and how this may be mediated by past agricultural activities. The study was undertaken in temperate eucalypt grassy woodland near Canberra, south‐eastern Australia, with a 200‐year history of pastoral land use. We sampled beetles using pitfall traps at three microhabitats (open grassland, logs and under trees). We analysed the effects of soil properties, vegetation structure, and plant composition on beetle composition, and compared beetle responses among the microhabitats. We found that microhabitat was a strong determinant of the way beetle communities responded to their environment. Soil nutrients (C, N and P) were the strongest drivers of beetle species richness, abundance and composition at open and log microhabitat, however vegetation structure (tree basal area) was more important for beetle richness, abundance and biomass under trees. We also found significant differences in beetle composition among distinct ground‐layer plant communities at log and tree microhabitat. We show that prior agricultural land use, particularly fertilization, has altered soil and plant communities, and that these effects continue to flow through the system affecting beetle assemblages. These findings have implications for future management of microhabitat structures in temperate grassy woodlands with a history of agricultural use.
Identification of positive selection signatures in pigs by comparing linkage disequilibrium variances
Authors: Li X. , Yang S. , Dong K. , Tang Z. , Li K. , Fan B. , Wang Z. , Liu B.
Published: July 2017

Selection affects the patterns of linkage disequilibrium (LD) around the site of a beneficial allele with an increase in LD among the hitchhiking alleles. Comparing the differences in regional LD between pig populations could help to identify putative genomic regions with potential adaptations for economic traits. In this study, using Illumina Porcine SNP60K BeadChip genotyping data from 207 Chinese indigenous, 117 South American village and 408 Large White pigs, we estimated the variation of genome‐wide LD between populations using the varld program. The top 0.1% standardized VarLD scores were used as a criterion for all comparisons, and compared with LD blocks, a total of four selection signatures on Sus scrofa chromosome (SSC) 7, 9, 13 and 14 were identified in all populations. These signatures overlapped with quantitative trait loci for linoleic acid content, age at puberty, number of muscle fibers per unit area, hip structure and body weight traits in pigs. Among them, one of the signatures (56.5–56.6 Mb on SSC7) in Large White pigs harbored the ADAMTSL3 gene, which is known to affect body length. The findings of this study seem to point toward recent selection in different pig populations. Further investigations are encouraged to confirm the selection signatures detected by varld in the present study.
Evaluation of 2‐benzylidene‐1‐tetralone derivatives as antagonists of A1 and A2A adenosine receptors
Authors: Legoabe Lesetja J. , Van der Walt Mietha M. , Terre'Blanche Gisella
Published: July 2017

Antagonists of the adenosine receptors (A1 and A2A) are thought to be beneficial in neurological disorders, such as Alzheimer's and Parkinson's disease. The aim of this study was to explore 2‐benzylidene‐1‐tetralone derivatives as antagonists of A1 and/or A2A adenosine receptors. In general, the test compounds were found to be selective for the A1 adenosine receptor, with only three test compounds possessing affinity for both the A1 and A2A adenosine receptor. The 2‐benzylidene‐1‐tetralones bearing a hydroxyl substituent at either position C5, C6 or C7 of ring A displayed favourable adenosine A1 receptor binding, while C5 hydroxy substitution led to favourable A2A adenosine receptor affinity. Interestingly, para‐hydroxy substitution on ring B in combination with ring A bearing a hydroxy at position C6 or C7 provided the 2‐benzylidene‐1‐tetralones with both A1 and A2A adenosine receptor affinity. Compounds 4 and 8 displayed the highest A1 and A2A adenosine receptor affinity with values below 7 μm. Both these compounds behaved as A1 adenosine receptor antagonists in the performed GTP shift assays. In conclusion, the 2‐benzylidene‐1‐tetralone derivatives can be considered as lead compounds to design a new class of dual acting adenosine A1/A2A receptor antagonists that may have potential in treating both dementia and locomotor deficits in Parkinson's disease.
Coumarins and adenosine receptors: New perceptions in structure–affinity relationships
Authors: Fonseca André , Matos Maria João , Vilar Santiago , Kachler Sonja , Klotz Karl‐Norbert , Uriarte Eugenio , Borges Fernanda
Published: July 2017

Adenosine receptor (AR) subtypes are involved in several physiological and pharmacological processes. Ligands that are able to selectively modulate one receptor subtype can delay or slow down the progression of diverse diseases. In this context, our research group focused its investigation into the discovery and development of novel, potent and selective AR ligands based on coumarin scaffold. Therefore, a series of 3‐phenylcarboxamidocoumarins were synthesized and their affinity for the human AR subtypes was screened by radioligand binding assays for A1, A2A and A3 receptors and for A2B by adenylyl cyclase assay. Compound 26 was found to be the most remarkable, with a hA1/hA3 and hA2A/hA3 selectivity of 42, for the A3 AR (Ki = 2.4 μm). Receptor‐driven molecular modelling studies have provided valuable information on the binding/selectivity data of compound 26 and for the following optimization process. Moreover, compound 26 presents drug‐like properties according to the general guidelines linked to the concept.
The Stony Brook Temperament Study: Early Antecedents and Pathways to Emotional Disorders
Authors: Klein Daniel N. , Finsaas Megan C.
Published: July 2017

In this article, we summarize findings from the Stony Brook Temperament Study, which seeks to elucidate the early antecedents and pathways to later depressive and anxiety disorders. The study focuses on parents’ internalizing disorders and children's early temperament as distal risk factors that operate, in part, through biobehavioral reward and threat systems. We summarize findings linking parents’ emotional disorders and observations of children's early temperament to subsequent neural measures of children's affective processing. Next, we review findings showing that children's temperament and affective processing predict subsequent depression and anxiety. We also show that many of these associations are moderated by environmental factors, such as parenting and stress. Finally, we relate our findings to literature on the relationships of early temperament and affective processing to anxiety and depression in youth.
The cost of oropharyngeal cancer in England: A retrospective hospital data analysis
Authors: Keeping S.T. , Tempest M.J. , Stephens S.J. , Carroll S.M. , Simcock R. , Jones T.M. , Shaw R.
Published: July 2017

Objectives

To estimate the total costs of treating head and neck cancers, specifically oropharyngeal, laryngeal and oral cavity cancer, in secondary care facilities in England during the period 2006/2007 to 2010/2011.

Design

Patient records were extracted from an English hospital database to estimate the number of patients treated for oropharyngeal, laryngeal and oral cavity cancer in England. Identified resource use was linked to published United Kingdom cost estimates to quantify the reimbursement of treatment through the Payment by Results system.

Setting

Retrospective hospital data analysis.

Participants

From the hospital data, patient records of patients treated for oropharyngeal, laryngeal and oral cavity cancer were selected.

Main outcome measures

Annual total costs of treatment, stratified by inpatient and outpatient setting and by male and female patients.

Results

From 2006/2007 to 2010/2011, total costs of treatment across the three head and neck cancer sites were estimated to be approximately £309 million, with 90% attributable to inpatient care (bundled costs). Oropharyngeal cancer accounted for 37% of total costs. Costs and patient numbers increased over time, largely due to a rise in oropharyngeal cancer, where total costs increased from £17.21 million to £30.32 million, with over 1400 (52%) more inpatients treated in 2010/11 compared to 2006/07.

Conclusions

In 4 years, the number of patients with oropharyngeal cancer receiving some form of inpatient care increased by more than half, and associated costs increased by three quarters. This reinforces the case for prevention and early detection strategies to help contain this epidemiological and economic burden.
Postoperative complications in individuals aged 70 and over undergoing elective surgery for colorectal cancer
Authors: Fagard K. , Casaer J. , Wolthuis A. , Flamaing J. , Milisen K. , Lobelle J.‐P. , Wildiers H. , Kenis C.
Published: July 2017

Aim

This study aims to describe the nature, incidence, severity and outcomes of in‐hospital postoperative complications (POCs) in older patients undergoing elective surgery for colorectal cancer.

Method

Patients ≥ 70 years old were identified from a prospectively collected database (2009–2015) focusing on the implementation of geriatric screening and assessment in patients with cancer. Medical and surgical POCs were retrieved retrospectively from the medical records, and the severity of the POCs was graded by the Clavien–Dindo (CD) grading system. The following outcomes were analysed comparing patients with and without CD ≥ 2 and CD ≥ 3 POCs: length of stay (LOS), transfer to the intensive care unit, 30‐day readmission rates, 30‐day and 1‐year mortality.

Results

In the 190 patients included, medical POCs (40.5%) were more frequent than surgical POCs (17.9%), and 37.9% experienced CD ≥ 2 POCs. The most common medical POCs were infections (26.8%), transient confusion or altered mental function (12.1%), cardiac arrhythmia (4.7%), and ileus/gastroparesis/prolonged recovery of transit (4.7%). The most common surgical POCs were surgical site infections (12.1%), wound dehiscence/bleeding (4.7%), anastomotic leak (3.7%) and surgical site bleeding (3.7%). The reoperation rate was 7.9%. CD ≥ 2 POCs led to 11 intensive care unit admissions and increased median postoperative LOS by 114% (P < 0.0001 for both), but did not significantly alter 30‐day readmission and 30‐day and 1‐year mortality rates. CD ≥ 3 POCs increased LOS by 162% (P < 0.0001) and showed an increased 1‐year mortality (P = 0.07).

Conclusion

This study shows that in‐hospital medical and surgical complications after surgery for colorectal cancer in patients ≥ 70 years old are frequent and that complications lead to less favourable outcomes.
Reduced risk of emergency admission for colorectal cancer associated with the introduction of bowel cancer screening across England: a retrospective national cohort study
Authors: Geraghty J. , Shawihdi M. , Devonport E. , Sarkar S. , Pearson M. G. , Bodger K.
Published: July 2017

Aim

We wanted to find out if roll‐out of the bowel cancer screening programme (BCSP) across England was associated with a reduced risk of emergency hospital admission for people presenting with colorectal cancer (CRC) during this period.

Method

This is a retrospective cohort study of 27 763 incident cases of CRC over a 1‐year period during the roll‐out of screening across parts of England. The primary outcome was the number of emergency (unplanned) hospital admissions during the diagnostic pathway. The primary exposure was to those living in an area where the BCSP was active at the time of diagnosis. Patients were categorized into three exposure groups: BCSP not active (reference group), BCSP active < 6 months or BCSP active ≥ 6 months.

Results

The risk of emergency admission for CRC in England was associated with increasing age, female gender, comorbidity and social deprivation. After adjusting for these factors in logistic regression, the odds ratio (OR) for emergency admission in patients diagnosed ≥ 6 months after the start‐up of local screening was 0.83 (CI 0.76–0.90). The magnitude of risk reduction was greatest for cases of screening age (OR 0.75; CI 0.63–0.90) but this effect was apparent also for cases outside the 60–69‐year age group (OR 0.85; CI 0.77–0.94). Living in an area with active BCSP conferred no reduction in risk of emergency admission for people diagnosed with oesophagogastric cancer during the same period.

Conclusion

The start‐up of bowel cancer screening in England was associated with a substantial reduction in the risk of emergency admission for CRC in people of all ages. This suggests that the roll‐out of the programme had indirect benefits beyond those related directly to participation in screening.