bluuebunny/crossref_metadata_2025 huggingface dataset:
EvoMining reveals the origin and fate of natural product biosynthetic enzymes
Authors: Sélem-Mojica Nelly , Aguilar César , Gutiérrez-García Karina , Martínez-Guerrero Christian E. , Barona-Gómez Fancisco
Published: April 2019

Natural products (NPs), or specialized metabolites, are important for medicine and agriculture alike, and for the fitness of the organisms that produce them. NP genome-mining aims at extracting biosynthetic information from the genomes of microbes presumed to produce these compounds. Typically, canonical enzyme sequences from known biosynthetic systems are identified after sequence similarity searches. Despite this being an efficient process, the likelihood of identifying truly novel systems by this approach is low. To overcome this limitation, we previously introduced EvoMining, a genome-mining approach that incorporates evolutionary principles. Here, we release and use our latest EvoMining version, which includes novel visualization features and customizable databases, to analyse 42 central metabolic enzyme families (EFs) conserved throughout
Actinobacteria
,
Cyanobacteria
,

Pseudomonas

and Archaea. We found that expansion-and-recruitment profiles of these 42 families are lineage specific, opening the metabolic space related to ‘shell’ enzymes. These enzymes, which have been overlooked, are EFs with orthologues present in most of the genomes of a taxonomic group, but not in all. As a case study of canonical shell enzymes, we characterized the expansion and recruitment of glutamate dehydrogenase and acetolactate synthase into scytonemin biosynthesis, and into other central metabolic pathways driving Archaea and Bacteria adaptive evolution. By defining the origin and fate of enzymes, EvoMining complements traditional genome-mining approaches as an unbiased strategy and opens the door to gaining insights into the evolution of NP biosynthesis. We anticipate that EvoMining will be broadly used for evolutionary studies, and for generating predictions of unprecedented chemical scaffolds and new antibiotics. This article contains data hosted by Microreact.
Large-scale death of retinal astrocytes during normal development mediated by microglia
Authors: Puñal Vanessa M. , Paisley Caitlin E. , Brecha Federica S. , Lee Monica A. , Perelli Robin M. , O’Koren Emily G. , Ackley Caroline R. , Saban Daniel R. , Reese Benjamin E. , Kay Jeremy N.
Published: April 2019

Naturally-occurring cell death is a fundamental developmental mechanism for regulating cell numbers and sculpting developing organs. This is particularly true in the central nervous system, where large numbers of neurons and oligodendrocytes are eliminated via apoptosis during normal development. Given the profound impact of death upon these two major cell populations, it is surprising that developmental death of another major cell type – the astrocyte – has rarely been studied. It is presently unclear whether astrocytes are subject to significant amounts of developmental death, or how it occurs. Here we address these questions using mouse retinal astrocytes as our model system. We show that the total number of retinal astrocytes declines by over 3-fold during a death period spanning postnatal days 5-14. Surprisingly, these astrocytes do not die by apoptosis, the canonical mechanism underlying the vast majority of developmental cell death. Instead, we find that microglia kill and engulf astrocytes to mediate their developmental removal. Genetic ablation of microglia inhibits astrocyte death, leading to a larger astrocyte population size at the end of the death period. However, astrocyte death is not completely blocked in the absence of microglia, apparently due to the ability of astrocytes to engulf each other. Nevertheless, mice lacking microglia showed significant anatomical changes to the retinal astrocyte network, with functional consequences for the astrocyte-associated vasculature leading to retinal hemorrhage. These results establish a novel modality for naturally-occurring cell death, and demonstrate its importance for formation and integrity of the retinal gliovascular network.
Deep learning based brain age prediction uncovers associated sequence variants
Authors: Jonsson B.A. , Bjornsdottir G. , Thorgeirsson T.E. , Ellingsen L.M. , Bragi Walters G. , Gudbjartsson D.F. , Stefansson H. , Stefansson K. , Ulfarsson M.O.
Published: April 2019

Machine learning algorithms trained to recognize age-related structural changes in magnetic resonance images (MRIs) of healthy individuals can be used to predict biological brain age in independent samples. The difference between predicted and chronological age, predicted age difference (PAD), is a phenotype holding promise for the study of normal brain ageing and brain diseases, and genetic discoveryviagenome-wide association studies (GWASs). Here, we present a new deep learning approach to predict brain age from a T1-weighted MRI. The method was trained on a dataset of healthy Icelanders (N= 1264) and tested on two datasets, the IXI (N= 544) and UK Biobank (N= 12395) datasets, utilizing transfer learning to improve accuracy on new sites. A GWAS of PAD in the UK Biobank data (discovery set: N=12395, replication set: N=4453) yielded two sequence variants, rs1452628-T (β=-0.08,P= 1.15 · 10−9) and rs2435204-G (β=0.102,P= 9.73 · 10−12). The former is nearKCNK2and correlates with reduced sulcal width, whereas the latter correlates with reduced white matter surface area and tags a well-known inversion at 17q21.31 (H2). The genetic association analysis was also confined to variants known to associate with brain structure, yielding three additional sequence variants associating with PAD.
AVibrio choleraeBolA-like protein is required for proper cell shape and cell envelope integrity
Authors: Fleurie Aurore , Zoued Abdelrahim , Alvarez Laura , Hines Kelly M. , Cava Felipe , Xu Libin , Davis Brigid M. , Waldor Matthew K.
Published: April 2019

BolA family proteins are conserved in gram-negative bacteria and many eukaryotes. While diverse cellular phenotypes have been linked to this protein family, the molecular pathways through which these proteins mediate their effects are not well-described. Here, we investigated the role of BolA family proteins inVibrio cholerae, the cholera pathogen. LikeEscherichia coli,V. choleraeencodes two BolA proteins, BolA and IbaG. However, in marked contrast toE. coli, wherebolAis linked to cell shape andibaGis not, inV. cholerae, bolAmutants lack morphological defects, whereasibaGproved critical for the generation and/or maintenance of the pathogen’s morphology. Notably, the bizarre-shaped, multi-polar, elongated and wide cells that predominated in exponential phase ΔibaG V. choleraecultures were not observed in stationary phase cultures. TheV. choleraeΔibaGmutant exhibited increased sensitivity to cell envelope stressors, including cell wall acting antibiotics and bile, and was defective in intestinal colonization. ΔibaG V. choleraehad reduced peptidoglycan and lipid II and altered outer membrane lipids, likely contributing to the mutant’s morphological defects and sensitivity to envelope stressors. Transposon-insertion sequencing analysis ofibaG’s genetic interactions suggested thatibaGis involved in several processes involved in the generation and homeostasis of the cell envelope. Furthermore, co-purification studies revealed that IbaG interacts with proteins containing iron-sulfur clusters or involved in their assembly. Collectively, our findings suggest thatV. choleraeIbaG controls cell morphology and cell envelope integrity through its role in biogenesis or trafficking of iron-sulfur cluster proteins.

Importance

BolA-like proteins are conserved across prokaryotes and eukaryotes. These proteins have been linked to a variety of phenotypes, but the pathways and mechanisms through which they act have not been extensively characterized. Here, we unraveled the role of the BolA-like protein IbaG in the cholera pathogenVibrio cholerae. The absence of IbaG was associated with dramatic changes in cell morphology, sensitivity to envelope stressors, and intestinal colonization defects. IbaG was found to be required for biogenesis of several components of theV. choleraecell envelope and to interact with numerous iron-sulfur cluster containing proteins and factors involved in their assembly. Thus, our findings suggest that IbaG governsV. choleraecell shape and cell envelope homeostasis through its effects on iron-sulfur proteins and associated pathways. The diversity of processes involving iron-sulfur containing proteins is likely a factor underlying the range of phenotypes associated with BolA family proteins.
Disease-associated mutations hyperactivate KIF1A motility and anterograde axonal transport of synaptic vesicle precursors
Authors: Chiba Kyoko , Min Chen , Arai Shogo , Hashimoto Koichi , McKenney Richard J. , Niwa Shinsuke
Published: April 2019

KIF1A is a kinesin-family motor involved in the axonal transport of synaptic vesicle precursors (SVPs) along microtubules. In humans, more than ten point mutations inKIF1Aare associated with the motor neuron disease, hereditary spastic paraplegia (SPG). However, not all of these mutations appear to inhibit the motility of the KIF1A motor, and thus, a clear molecular explanation for howKIF1Amutations lead to neuropathy is not available. In this study, we establishedin vitromotility assays with purified full-length human KIF1A and found thatKIF1Amutations associated with the pure form of spastic paraplegia hyperactivate motility of the KIF1A motor. Introduction of the corresponding mutations intoCaenorhabditis elegans KIF1Ahomologueunc-104revealed abnormal accumulation of SVPs at the tips of axons and increased anterograde axonal transport of SVPs. Our data reveal that hyper-activation of kinesin motor activity, rather than its loss-of-function, is a novel cause of motor neuron disease in humans.

Significance Statement

Anterograde axonal transport supplies organelles and protein complexes throughout axonal processes to support neuronal morphology and function. It has been observed that reduced anterograde axonal transport is associated with neuronal diseases. In contrast, here we show that particular disease-associated mutations in KIF1A, an anterograde axonal motor for synaptic vesicle precursors, induce hyperactivation of KIF1A motor activity and increased axonal transport of synaptic vesicle precursors. Our results advance the knowledge of the regulation of motor proteins and axonal transport and cell biology of motor neuron diseases.
Pregnancy-associated plasma protein-aa supports hair cell survival by regulating mitochondrial function
Authors: Alassaf Mroj , Daykin Emily , Mathiaparanam Jaffna , Wolman Marc
Published: April 2019

To support cell survival, mitochondria must balance energy production with oxidative stress. Inner ear hair cells are particularly vulnerable to oxidative stress; thus require tight mitochondrial regulation. We identified a novel molecular regulator of the hair cells’ mitochondria and survival: Pregnancy-associated plasma protein-aa (Pappaa). Hair cells in zebrafish pappaa mutants exhibit mitochondrial defects, including elevated mitochondrial calcium, transmembrane potential, and reactive oxygen species (ROS) production and reduced antioxidant expression. In pappaa mutants, hair cell death is enhanced by stimulation of mitochondrial calcium or ROS production and suppressed by a mitochondrial ROS scavenger. As a secreted metalloprotease, Pappaa stimulates extracellular insulin-like growth factor 1 (IGF1) bioavailability. We found that the pappaa mutants’ enhanced hair cell loss can be suppressed by stimulation of IGF1 availability and that Pappaa-IGF1 signaling acts post-developmentally to support hair cell survival. These results reveal Pappaa as an extracellular regulator of hair cell survival and essential mitochondrial function.
Vireo: Bayesian demultiplexing of pooled single-cell RNA-seq data without genotype reference
Authors: Huang Yuanhua , McCarthy Davis J , Stegle Oliver
Published: April 2019

The joint analysis of multiple samples using single-cell RNA-seq is a promising experimental design, offering both increased throughput while allowing to account for batch variation. To achieve multi-sample designs, genetic variants that segregate between the samples in the pool have been proposed as natural barcodes for cell demultiplexing. Existing demultiplexing strategies rely on access to complete genotype data from the pooled samples, which greatly limits the applicability of such methods, in particular when genetic variation is not the primary object of study. To address this, we here present Vireo, a computationally efficient Bayesian model to demultiplex single-cell data from pooled experimental designs. Uniquely, our model can be applied in settings when only partial or no genotype information is available. Using simulations based on synthetic mixtures and results on real data, we demonstrate the robustness of our model and illustrate the utility of multi-sample experimental designs for common expression analyses.
Discriminating tactile speed in absence of raised texture elements: Role of deformation and vibratory cues
Authors: Moscatelli Alessandro , Ryan Colleen P. , Ciotti Simone , Cosentino Lucia , Ernst Marc O. , Lacquaniti Francesco
Published: April 2019

Motion encoding in touch relies on multiple cues, such as displacements of traceable texture elements, friction-induced vibrations, and gross fingertip deformations by shear force. We evaluated the role of deformation and vibration cues in tactile speed discrimination. To this end, we tested the discrimination of speed of a moving smooth glass plate, and compared the precision of the responses when the same task was performed with a plate having a fine texture. Participants performed the task with and without masking vibrations. Speed discrimination was nearly as precise among the two surface types, as assessed by the steep slope of the psychometric function. Consistent with our previous work, high-frequency vibrations impaired the ability of the participants in discriminating surface speed. Results of the current study showed that it is possible to discriminate motion speed even in absence of a raised texture.

Highlights

On a smooth surface, humans are able to discriminate the speed of a moving surface by frictional motion cues

The precision of speed discrimination is nearly the same with smooth and fine-textured surface types

High frequency vibrations impair the ability to discriminate speed of moving surfaces
Determination of the molecular basis for coprogen import by Gram-negative bacteria
Authors: Grinter Rhys , Lithgow Trevor
Published: April 2019

In order to survive in mixed microbial communities, some species of fungi secrete coprogens, siderophores that facilitate capture of the scarce nutrient iron. The TonB-dependent transporter FhuE is integrated in the outer membrane of Gram-negative bacteria and has been reported to scavenge these fungally produced coprogens. In this work, anEscherichia colistrain was engineered that is dependent solely on FhuE for its access to siderophore-sequestered iron. Using this tool, it is shown that while FhuE is highly active in the import of coprogens, it has some level of promiscuity, acting as a low-affinity transporter for related siderophores. The crystal structure of FhuE in complex with coprogen was determined, providing a structural basis to explain this selective promiscuity. The structural data, in combination with functional analysis, presented in this work show that FhuE has evolved to specifically engage with planar siderophores. A potential evolutionary driver, and a critical consequence of this selectivity, is that it allows FhuE to exclude antibiotics that mimic nonplanar hydroxamate siderophores: these toxic molecules could otherwise cross the outer membrane barrier through a Trojan horse mechanism.
The consequences of the heritage experience in brand museums on the consumer–brand relationship
Authors: Pulh Mathilde , Mencarelli Rémi , Chaney Damien
Published: April 2019

Purpose

This paper aims to investigate the consequences of the heritage experience in brand museums on the consumer–brand relationship. By highlighting its heritage within a museum, the brand proposes a specific experience that deserves attention because it is based on memory and communal identity, thus creating or strengthening a relationship with consumers.

Design/methodology/approach

Ethnographic case studies were conducted through direct observation and extensive interviews with 72 visitors at two brand museums, the Fallot Mustard Mill and the House of the Laughing Cow.

Findings

The results highlight the emergence/strengthening of the relationship between consumers and the brand through the development of intimacy with the brand and the emergence of supportive behaviors toward the brand in the form of commercial support, ambassadorship and volunteering.

Research limitations/implications

By characterizing and articulating the different relational consequences of visiting a brand museum, this research contributes to the literature dedicated to heritage experiences in consumption contexts and to the literature dedicated to consumer–brand relationships in servicescapes.

Practical implications

The study shows the necessity of grounding “heritage” in the physical setting of the brand museum to create a meaningful experience for visitors and, in turn, a deep relationship. Managers should treat brand museums as a relational tool in the marketing strategy of the brand and approach them from the perspective of long-term profitability.

Originality/value

While the literature has examined the spectacular and esthetic experiences brand museums offer, this study is the first to characterize the heritage experience and to document its consequences in terms of the consumer–brand relationship.
A cultural analysis of the secondary housing tourism in Vilcabamba, Ecuador
Authors: Martín Juan Carlos , Bustamante-Sánchez Natalia Soledad
Published: April 2019

Purpose

This study aims to determine the level of satisfaction of secondary housing tourists in Vilcabamba.

Design/methodology/approach

The analysis of satisfaction of this tourism segment in a destination is essential for the different economic agents when evaluating various policies. The analysis is based on the answers provided to 16 items in a questionnaire administered to a representative sample (281 respondents). The authors have used the fuzzy logic to reduce ambiguity in the answers associated to subjective views of human beings who express themselves linguistically. A method based on the degree of similarity to ideal solutions has been used to obtain a classification of relevant satisfaction items.

Findings

The results indicate that the ideal solutions segments are represented by multicultural characteristics of second home tourists and the number of years they have been visiting Vilcabamba. The authors find that foreign tourists are more satisfied than Ecuadorians. Analyzing the most critical factors, it is seen that accessibility to the destination, socio-cultural environment and quality of water achieve a high priority.

Research limitations/implications

Second home tourists’ satisfaction has been studied with a limited set of 16 attributes, and some attributes also have a multidimensional nature, so a further study analyzing the scale will be needed in the future.

Originality/value

The present study fills an existing gap in the literature of secondary housing tourism where the existing previous research has been mainly focused on retirees’ secondary housing tourism. The study provides interesting insights into local and national authorities, as well as other economic agents, to designing strategies and planning processes of the destinations for secondary housing tourists.
Indicators of candidates for gentrification: a spatial framework
Authors: Bengtsson Ingemar , Kopsch Fredrik
Published: April 2019

Purpose

The purpose of this paper is to establish measurable factors that can be used as early indicators of which neighborhoods are most likely to undergo a process of gentrification in a reasonably near future.

Design/methodology/approach

Using 1990 data on key demographic variables for 128 neighborhoods in Stockholm, Sweden a model that allows both for testing of spatial clustering and for spatial spillovers between neighborhoods is estimated. It is hypothesized not only that gentrification depends on inter-neighborhood characteristics but also that gentrified neighborhoods will cluster and preferably be located in proximity to existing high income neighborhoods.

Findings

The findings confirm the stated hypotheses. Among the results, it is shown that neighborhoods that gentrified between 1990 and 2012 were more likely to have been poor in 1990 and located closer to the CBD, they were also more likely to be close to neighborhoods with lower proportions of low income residents. It is also found that gentrified neighborhoods tend to cluster over space.

Originality/value

Much of the previous literature on gentrification has concerned the actual driving forces behind gentrifying neighborhoods. This paper is more concerned with indicators that can be used to spot neighborhoods that are likely to undergo a gentrification process in the future. Such information can be valuable for real estate developers in the private sector, as it may lead to more successful investments. It may also be useful for city developers at the municipal organization.
A new model for Islamic cooperative mortgage of housing finance
Authors: Nasir Aslina , Abdullah Lazim
Published: April 2019

Purpose

This study aims to propose a new model of Islamic cooperative mortgage of housing finance (ICOM) to provide a lower monthly initial amount with a longer tenure for the low- and middle-income members. This model is developed to ease the burden on borrowers concerning the high initial down payment (ID).

Design/methodology/approach

The ICOM model is a no-interest mortgage and is developed based on the cooperative home mortgage model by Ebrahim (2009). The model is verified using numerical examples to ensure its feasibility to produce lower monthly initial amounts and compared to the cooperative home mortgage.

Findings

From the numerical example, the ICOM model shows a lower monthly initial amount with a longer tenure compared to the cooperative home mortgage. The monthly payment is also lower than the cooperative home mortgage.

Research limitations/implications

The authors compare their model with Ebrahim’s (2009) cooperative home mortgage because of a constraint of limited previous studies on housing finance. Therefore, this model is developed by considering the unaffordability of the initial down payment among low-income borrowers. As this model introduces a lower monthly initial amount, the authors expect it can reduce the unaffordability problem of high initial down payment.

Practical implications

The authors also expect that a lower monthly initial amount with a longer tenure can ease the burden among the low-income borrowers by reducing their consumption on housing.

Originality/value

This paper provides a non-interest Islamic cooperative mortgage and lower monthly initial amount with a longer tenure for the low- and middle-income borrowers.
Going the distance: a lesson study on deriving the distance formula
Authors: Chua Von Christopher Gulpric
Published: April 2019

Purpose

The purpose of this paper is to determine the challenges that Filipino Mathematics teachers face while developing students’ ability to derive the distance formula; allow teachers to collaboratively formulate a lesson designed to address the challenges they have identified from their own practice; and determine how successful the lesson was and how it can be improved so that other teachers dealing with similar difficulties may be able to implement it. The teacher-participants employed Lesson Study (LS) as an approach to improving pedagogical practice. Data were based on the pre- and post-lesson discussions and individual reflection papers of the teacher participants.

Design/methodology/approach

An action research methodology through LS approach was employed by the teacher participants. Data were based on the pre- and post-lesson discussions and individual reflection papers of the teacher participants.

Findings

Based on the post-lesson discussion, the teachers agreed that the process of creating a lesson that seeks to develop the students’ ability to derive formulas are crucial to building understanding of the underlying mathematical concept. Also, teachers’ participation in LS was found to have been insightful as it developed in them a greater appreciation towards establishing a professional learning community that is directed towards examining problems that concerns majority of the teachers involved.

Originality/value

Research in Philippine education has recently seen the increasing interest in LS as a potent pedagogical practice. Nonetheless, papers that report on LS practice in the local context remains to be lacking. This study contributes to the development of this research area and raises the need for Filipino Mathematics teachers to engage in both LS and action research to generate knowledge from their experiences.
SEC charges “ICO Superstore” as unregistered broker-dealer
Authors: Sikora Jr. John J. , Wink Stephen P. , Yatter Douglas K. , Culhaci Naim
Published: April 2019

Purpose

To analyze the settled order of the US Securities and Exchange Commission (SEC) against TokenLot LLC (TokenLot), which was the SEC’s first action charging a seller of digital tokens as an unregistered broker-dealer.

Design/methodology/approach

Analyzes the SEC’s order within the context of other recent actions by the SEC on cryptocurrencies and digital tokens and discusses future implications of the order in this area.

Findings

The SEC’s order against TokenLot as an unregistered broker-dealer was a logical next step in its enforcement activity in the cryptocurrency and digital token space.The order demonstrates that the SEC expects firms in the cryptocurrency space to use the well-established constructs of federal securities laws to evaluate their business activities to ensure those activities are legally compliant.

Originality/value

Practical guidance from experienced securities and financial services lawyers analyzing recent developments in a nascent area of SEC enforcement.
Successful work cultures: recommendations for leaders in healthcare
Authors: Vazquez Christian E.
Published: April 2019

Purpose

The purpose of this study is to gather information about work culture characteristics from four successful pediatric heart programs to better understand how they continue to maintain high standards of quality and safety.

Design/methodology/approach

For this qualitative study, data were collected through semi-structured in-depth individual interviews with four physician leaders. Those interviews were transcribed and coded for themes, first individually and then across all four.

Findings

Three themes emerged from the analysis. According to the experts, the three most salient elements for sustaining a successful work culture that is conducive to maintaining high standards of care are: the ‘right’ people, an effective leadership team and efficient systems.

Research limitations/implications

This was a small homogenous sample, which is a limitation of the study. All of the programs were from non-profit teaching hospitals in urban areas. This study has important research implications, as it offers descriptive information useful for guiding a future explanatory study.

Practical implications

Recommendations have been made for leaders in healthcare settings to benchmark against the work being done at these programs that maintain high standards of quality and safety.

Social implications

This information has important social and practical implications as healthcare leaders continue to work on improving quality and safety that affects patients across the country.

Originality/value

This study contributes to the literature by offering perspectives on successful work cultures from a diverse compilation of physician leaders and medical institutions across the USA.
Family involvement, corporate governance and dividends in Turkey
Authors: Sener Pinar , Akben Selcuk Elif
Published: April 2019

Purpose

The purpose of this paper is to investigate the relationship between dividends and family involvement as well as corporate governance characteristics among Turkish public firms.

Design/methodology/approach

Using panel data on Turkish firms listed on the Borsa Istanbul 100 index for 2006–2014, three models are estimated. For the first two models, where the dependent variables are the dividend payout ratio and dividend yield, respectively, tobit regressions are run. The last model, which employs a dividend dummy as the dependent variable, is estimated with logistic regression.

Findings

There is a positive and concave relationship between family ownership and dividends. The existence of a family chairman reduces dividends. There is a positive association between board size and dividends and this relationship is weaker for firms with higher levels of family ownership. Finally, the ratio of independent directors on the board is negatively associated with dividends.

Practical implications

The findings imply that firms with substantial family ownership and active family participation in management are more likely to send a negative signal to minority shareholders by paying lower dividends. In addition, minority shareholders should pay attention to the board structure of firms in which they invest.

Originality/value

This study is one of the few to analyze the nonlinear relationship between family ownership and dividend payments as well as the role of family management in a developing country. Second, it investigates the role of board characteristics in explaining dividend payment decisions.
The impact of politics and economic policy uncertainty on anomaly-based investment strategies
Authors: Mbanga Cedric , Jones Jeffrey Scott , Hoelscher Seth A.
Published: April 2019

Purpose

The purpose of this paper is to explore the overlooked relationship between politics and the performance of anomaly-based investment strategies.

Design/methodology/approach

Monthly long-short portfolios are formed based on relative mispricing scores according to the Stambaugh et al. (2012, 2015) relative mispricing measure. Portfolio performance is examined throughout various presidential terms. The design also introduces economic policy uncertainty (EPU) as a possible explanatory variable for portfolio performance.

Findings

The analysis reveals that anomaly-based returns are higher under Republican administrations than they are under Democratic administrations. Moreover, the results show that the impact of EPU on the relationship between the political party affiliation of the president and future anomaly-based returns are driven by the election and post-election years.

Practical implications

The examination of returns on a long-short portfolio may be of particular value to investment companies, such as hedge funds, who regularly employ this type of strategy.

Originality/value

While the impact of presidential terms on raw equity returns has been well examined, the paper is the first to examine the impact of presidential terms on the return of an anomaly-based investment strategy. EPU is also introduced as an important contributing factor.
Investigation of clinical factors associated with longer overall survival in advanced melanoma patients treated with sequential ipilimumab
Authors: Muto Yusuke , Kitano Shigehisa , Tsutsumida Arata , Namikawa Kenjiro , Takahashi Akira , Nakamura Yoshio , Yamanaka Takeharu , Yamamoto Noboru , Yamazaki Naoya
Published: April 2019

Melanoma is one of the most serious form of skin cancer. Nowadays, ipilimumab is used for advanced melanoma refractory to first‐line anti‐programmed death 1 (PD‐1) antibodies. Thirty patients (male : female ratio, 18:12; median age, 60.5 years) sequentially treated with ipilimumab after anti‐PD‐1 antibody (nivolumab or pembrolizumab), while 58 (male : female ratio, 27:31; median age, 66.5 years) with anti‐PD‐1 antibody only. The kind of therapy and schedules were as follows: nivolumab, 2 mg/kg at 3‐week intervals or at 3 mg/kg every 2 week; pembrolizumab, 2 mg/kg every 3 weeks; ipilimumab, 3 mg/kg at 3‐week intervals for four doses. The sequential therapy was selected for the patients with disease progression and/or recovered from severe (immune‐related [ir]) adverse events (AE) after PD‐1 blockade monotherapy. We evaluated multiple parameters and analyzed their relevance to overall survival (OS). The best objective response rate was 6.7% in sequential ipilimumab treatment. Median OS was 163 days (range, 16–489). Baseline absolute lymphocyte count (ALC) and performance status (PS) before sequential ipilimumab were associated with OS in univariate analyses. Baseline PS and irAE within 6 weeks after ipilimumab administration showed significant differences on multivariate analysis. Prior to first‐line PD‐1 blockade, these parameters were not associated with OS. The other factors (i.e. age, sex, number of doses, absolute neutrophil counts, neutrophil : lymphocyte ratio, lactate dehydrogenase and C‐reactive protein) were not associated with OS. [Correction added on 17 April 2019, after first online publication: ‘not related to OS' has been amended to ‘not associated with OS’.] Ipilimumab as sequential therapy did not appear to improve OS and was associated with more severe irAE than PD‐1 blockade monotherapy. We need to carefully consider treating patients with poor PS and low ALC.
What kind of ‘a girls’ thing’? Frictions and continuities in the framing and taming of the HPV vaccine in Finland
Authors: Virtanen Mikko J.
Published: April 2019

This article focuses on two different ways of framing and taming the uncertainties of the human papillomavirus (HPV) vaccine in the context of the Finnish welfare state: the bio‐medical rationale of population‐level cancer reduction based on epidemiological assessments, and the meaning formation of Finnish vaccination‐aged girls. Epidemiologists run analyses estimating the cost‐effectiveness and public health benefit of vaccinations, while the adolescent girls face the burdensome choice of whether to undergo vaccination. The processes of framing the complexities and actively taming them are analysed utilising a cultural‐sociological framework. Firstly, the taming work of the epidemiologists is examined by focusing on the creation of the vaccination campaign. The aetiological complexities between some HPV types and cervical cancer are tamed into a clear campaign message of vaccination as a scientifically proven protection against deadly cancer. Secondly, the girls’ own ways of framing the complexities of the HPV vaccine and taming the decision whether to undergo vaccination or not are analysed based on their comments in an Internet discussion forum. Finally, the framings and tamings of both sites are discussed together, and some interesting continuities and disjunctions between the two are revealed.
Greening the poor: the trap of moralization
Authors: Malier Hadrien
Published: April 2019

This article uses ethnographic data to engage a critical reflection on the tension between individual responsibility for the environment and inequality. While research has shown that the majority of sustainable consumers are middle and upper class, educated and white individuals, the study explores how the ethical injunction to ecological sustainability is being introduced to lower‐income neighbourhoods in France. It draws on the observation of a national programme which aims at supporting inhabitants of public housing estates in the process of greening their lifestyle in order to fight climate change and fuel poverty. The paper analyses how environmental responsibilization is specific in that it calls upon a responsibility towards others, towards the common good. Using the Foucauldian concept of ‘subjectivation’, it describes and analyses the moral work implied by such behaviour change programmes. It demonstrates that a negative representation of poor households and a moral framing of the responsibility for the environment lead to a moralization of their lifestyle under the heading of ‘eco‐friendly behaviours’. A paradoxical result of such endeavours is that the social group with the least impactful lifestyle on the environment is the one which is moralized in the most intrusive and resolute manner. The article shows, however, that the tenants manage to resist the normalizing discourse on sustainable living, for reasons which are not anti‐environmentalist. This piece thus provides interesting results for sustainability studies as well as for the sociology of the regulation of underprivileged neighbourhoods.
The risk of intrapartum/neonatal mortality and morbidity following birth at 37 weeks of gestation: a nationwide cohort study
Authors: Eskes M , Ensing S , Groenendaal F , Abu‐Hanna A , Ravelli ACJ
Published: April 2019

Objective

To assess intrapartum/neonatal mortality and morbidity risk in infants born at 37 weeks of gestation compared with infants born at 39–41 weeks of gestation.

Design

Nationwide cohort study.

Setting

The Netherlands.

Population

A total of 755 198 women delivering at term of a singleton without congenital malformations during 2010–14.

Methods

We used data from the national perinatal registry (PERINED). Analysis was performed with logistic regression and stratification for the way labour started and type of care.

Main outcome measures

Intrapartum or neonatal mortality up to 28 days and adverse neonatal outcome (neonatal mortality, 5‐minute Apgar <7, and/or neonatal intensive care unit admission).

Results

At 37 weeks of gestation intrapartum/neonatal mortality was 1.10‰ compared with 0.59‰ at 39–41 weeks (P < 0.0001). Adjusted odds ratio (aOR) for 37 weeks compared with 39–41 weeks was 1.84 (95% CI) 1.39–2.44). Adverse neonatal outcome at 37 weeks was 21.4‰ compared with 12.04‰ at 39–41 weeks (P < 0.0001) with an aOR 1.63 (95% CI 1.53–1.74). Spontaneous start of labour at 37 weeks of gestation was significantly associated with increased intrapartum/neonatal mortality with an aOR of 2.20 (95% CI 1.56–3.10), in both primary (midwifery‐led) care and specialist care. Neither induction of labour nor planned caesarean section showed increased intrapartum/neonatal mortality risk.

Conclusions

Birth at 37 weeks of gestation is independently associated with a higher frequency of clinically relevant adverse perinatal outcomes than birth at 39–41 weeks. In particular, spontaneous start of labour at 37 weeks of gestation doubles the risk for intrapartum/neonatal mortality. Extra fetal monitoring is warranted.

Tweetable abstract

Birth at 37 weeks of gestation gives markedly higher intrapartum/neonatal mortality risk than at 39–41 weeks, especially with spontaneous start of labour.
A guide to the application of Hill numbers to DNA‐based diversity analyses
Authors: Alberdi Antton , Gilbert M. Thomas P.
Published: April 2019

With the advent of DNA sequencing‐based techniques, the way we detect and measure biodiversity is undergoing a radical shift. There is also an increasing awareness of the need to employ intuitively meaningful diversity measures based on unified statistical frameworks, so that different results can be easily interpreted and compared. This article aimed to serve as a guide to implementing biodiversity assessment using the general statistical framework developed around Hill numbers into the analysis of systems characterized using DNA sequencing‐based techniques (e.g., diet, microbiomes and ecosystem biodiversity). Specifically, we discuss (a) the DNA‐based approaches for defining the types upon which diversity is measured, (b) how to weight the importance of each type, (c) the differences between abundance‐based versus incidence‐based approaches, (d) the implementation of phylogenetic information into diversity measurement, (e) hierarchical diversity partitioning, (f) dissimilarity and overlap measurement and (g) how to deal with zero‐inflated, insufficient and biased data. All steps are reproduced with real data to also provide step‐by‐step bash and R scripts to enable straightforward implementation of the explained procedures.
KCNQ1OT1 promotes autophagy by regulating miR‐200a/FOXO3/ATG7 pathway in cerebral ischemic stroke
Authors: Yu Shijia , Yu Mingjun , He Xin , Wen Lulu , Bu Zhongqi , Feng Juan
Published: April 2019

Dysregulation of long noncoding RNAs (lncRNAs) is associated with abnormal development and pathophysiology in the brain. Increasing evidence has indicated that ischemic stroke is becoming the most common cerebral disease in aging populations. The treatment of ischemic stroke is challenging, due in part to ischemia and reperfusion (I/R) injury. In this study, we revealed that potassium voltage‐gated channel subfamily Q member 1 opposite strand 1 (KCNQ1OT1) was significantly upregulated in ischemic stroke. Knockdown of KCNQ1OT1 remarkably reduced the infarct volume and neurological impairments in transient middle cerebral artery occlusion (tMCAO) mice. Mechanistically, KCNQ1OT1 acted as a competing endogenous RNA of miR‐200a to regulate downstream forkhead box O3 (FOXO3) expression, which is a transcriptional regulator of ATG7. Knockdown of KCNQ1OT1 might inhibit I/R‐induced autophagy and increase cell viability via the miR‐200a/FOXO3/ATG7 pathway. This finding offers a potential novel strategy for ischemic stroke therapy.
Impaired frontostriatal functional connectivity among chronic opioid using pain patients is associated with dysregulated affect
Authors: McConnell Patrick A. , Garland Eric L. , Zubieta Jon‐Kar , Newman‐Norlund Roger , Powers Shannon , Froeliger Brett
Published: April 2019

Preclinical studies have shown effects of chronic exposure to addictive drugs on glutamatergic‐mediated neuroplasticity in frontostriatal circuitry. These initial findings have been paralleled by human functional magnetic resonance imaging (fMRI) research demonstrating weaker frontostriatal resting‐state functional connectivity (rsFC) among individuals with psychostimulant use disorders. However, there is a dearth of human imaging literature describing associations between long‐term prescription opioid use, frontostriatal rsFC, and brain morphology among chronic pain patients. We hypothesized that prescription opioid users with chronic pain, as compared with healthy control subjects, would evidence weaker frontostriatal rsFC coupled with less frontostriatal gray matter volume (GMV). Further, those opioid use‐related deficits in frontostriatal circuitry would be associated with negative affect and drug misuse. Prescription opioid users with chronic pain (n = 31) and drug‐free healthy controls (n = 30) underwent a high‐resolution anatomical and an eyes‐closed resting‐state functional scan. The opioid group, relative to controls, exhibited weaker frontostriatal rsFC, and less frontostriatal GMV in both L.NAc and L.vmPFC. Frontostriatal rsFC partially mediated group differences in negative affect. Within opioid users, L.NAc GMV predicted opioid misuse severity. The current study revealed that prescription opioid use in the context of chronic pain is associated with functional and structural abnormalities in frontostriatal circuitry. These results suggest that opioid use‐related abnormalities in frontostriatal circuitry may undergird disturbances in affect that may contribute to the ongoing maintenance of opioid use and misuse. These findings warrant further examination of interventions to treat opioid pathophysiology in frontostriatal circuitry over the course of treatment.
Quality of acute stroke care in a regional Victorian hospital, Australia
Authors: Yang Tze Wei Wilson , Islam Md Rafiqul
Published: April 2019

Objective

The quality of acute stroke care in a regional Victorian hospital (study hospital) was assessed by comparing with selected standard indicators of Acute Stroke Clinical Care.

Design

A retrospective review of records of patients with stroke was performed manually and by reviewing electronic database.

Setting

The study was carried out in Goulburn Valley Health, one of the five regional referral and teaching hospitals in Victoria, Australia.

Participants

Patients with stroke who were discharged from the study hospital between October 2015 and March 2016.

Main outcome measures

Timeliness of brain imaging, proportion of patients thrombolysed if arrived within 4.5 hours of stroke and timeliness of thrombolysis.

Results

A total of 66 patients' records was found. Brain imaging was completed for 45%, compared to 25.8% nationally, if arrived to the study hospital within 1 hour of stroke and 100% imaging completed within 24 hours of arrival, compared to 75.6% nationally. When patients arrived to the emergency department within 4.5 hours of stroke, 37.5% (23.6% nationally and 18.6% in similar‐ sized hospitals) of them were thrombolysed, while none was thrombolysed within 60 minutes of arrival. Door‐to‐thrombolysis time was 85 minutes, 7 minutes longer than national standard. Symptoms onset to thrombolysis time was 225 minutes, 55 minutes longer than national standard.

Conclusion

The timeliness of brain imaging and thrombolysis was comparable in the study hospital to that of the national standard, while other stroke management indicators still require improvement. Continuing efforts for improvement and revisiting possible areas of delay are warranted.
Assessing bone transformation in late Miocene and Plio‐Pleistocene deposits of Kenya and South Africa
Authors: Aufort J. , Gommery D. , Gervais C. , Segalen L. , Labourdette N. , Coelho‐Diogo C. , Balan E.
Published: April 2019

Bone reactivity offers a potential way to record local physical–chemical conditions prevailing in fossilization environments and archaeological sites. In the present study, a series of fossil bone samples from the karstic environments of the Bolt's Farm cave system (Cradle of Humankind, South Africa) and from fluvio‐lacustrine environments of the Tugen Hills (Gregory Rift, Kenya) is analysed. The chemical composition and infrared and nuclear magnetic resonance (NMR) spectroscopic properties of fossil samples point to a transformation of the biogenic apatite and formation of secondary apatite. Depending on the sample, the secondary apatite corresponds to a carbonate‐bearing hydroxy‐ or fluor‐apatite. The maximum fraction of secondary apatite is close to 60%, coinciding with previous observations in experimental alteration of bone in aqueous solutions and suggesting that a fraction of pristine biological apatite is likely to be preserved. The present results also suggest that the acetic acid treatment of fossil samples moderately increases their average crystallinity but may dissolve carbonate‐rich domains of secondary apatite.
Comfort with discussions about death, religiosity, and attitudes about end‐of‐life care
Authors: Hong Seokho , Cagle John G.
Published: April 2019

In end‐of‐life (EOL) care research, death anxiety and religiosity are often overlooked. Terror management theory (TMT) may provide a useful conceptual model with which to examine how comfort discussing death and religiosity influence attitudes related to EOL care. A telephone‐based survey was conducted among community‐dwelling adults in the Unites States. Via random sampling, with over‐sampling of Hispanics/African Americans, 123 completed survey interviews (response rate = 46%) were analyzed. Respondents were more likely to have better attitudes toward EOL care if they were older or white, religiously active, and comfortable with the subject of death. Religiosity and comfort discussing death were correlated with each other and remained significant predictors of attitudes about EOL care even without demographic covariates. Findings suggest that promoting an open dialogue about mortality may improve attitudes about EOL care and utilization of palliative care services. The study also provides evidence about the utility and applicability of TMT for EOL care.