bluuebunny/crossref_metadata_2025 huggingface dataset:
An antisense RNA capable of modulating the expression of the tumor suppressor microRNA-34a
Authors: Serviss Jason T. , Richter Felix Clemens , Van den Eynden Jimmy , Andrews Nathanael , Houtman Miranda , Vesterlund Mattias , Schwarzmueller Laura , Johnsson Per , Larsson Erik , Grandér Dan , Pokrovskaja Tamm Katja
Published: December 2017

The microRNA-34a is a well-studied tumor suppressor microRNA (miRNA) and a direct downstream target of TP53 with roles in several pathways associated with oncogenesis, such as proliferation, cellular growth, and differentiation. Due to its broad tumor suppressive activity, it is not surprising that miR34a expression is altered in a wide variety of solid tumors and hematological malignancies. However, the mechanisms by which miR34a is regulated in these cancers is largely unknown. In this study, we find that a long non-coding RNA transcribed antisense to the miR34a host gene, is critical for miR34a expression and mediation of its cellular functions in multiple types of human cancer. We name this long non-coding RNA lncTAM34a, and characterize its ability to facilitate miR34a expression under different types of cellular stress in both TP53 deficient and wild type settings.
Brain and psychological determinants of placebo pill response in chronic pain patients
Authors: Vachon-Presseau Etienne , Berger Sara E. , Abdullah Taha B. , Huang Lejian , Cecchi Guillermo , Griffith James W. , Schnitzer Thomas J. , Apkarian A. Vania
Published: December 2017

Placebo response is universally observed in randomized controlled trials (RCTs), yet these effects are commonly dismissed as consequences of uncontrollable confounds. In this prospective neuroimaging-based RCT performed in chronic back pain patients, we demonstrate that the intensity, but not quality, of pain is diminished with placebo pill ingestion. The response to placebo pills depended on brain: subcortical limbic volume asymmetry, sensorimotor cortical thickness, and functional coupling of the dorsolateral prefrontal cortex (DLPFC) with the periaqueductal grey (PAG), the rostral anterior cingulate cortex (rACC), and the precentral gyrus (PreCG); and psychological factors. All features were present before exposure to the pill; most remained stable across treatment and washout periods, although specific functional coupling between DLPFC and PAG dissipated with repeated exposure. These brain properties and specific psychological factors, such as interoceptive awareness and openness, were also predictive of the magnitude of response (continuous variable). We used machine learning in a fully cross-validated procedure and demonstrated that psychological factors were sufficient for classifying and predicting response magnitude; and response magnitude could also be predicted from a functional network (nodes mainly located in the limbic community, the DLPFC, the orbitofrontal cortex, and the temporo-parietal junction); the combined model explained 36% of the variance. Together, our results demonstrate that placebo pill analgesia observed in clinical trials depends on a combination of brain properties and specific psychological factors.
Central Role of Cognitive Control Networks in Weight Loss During Voluntary Calorie Restriction
Authors: Neseliler Selin , Hu Wen , Larcher Kevin , Zacchia Maria , Dadar Mahsa , Scala Stephanie G. , Lamarche Marie , Zeighami Yashar , Stotland Stephen C. , Larocque Maurice , Marliss Errol B. , Dagher Alain
Published: December 2017

Insufficient responses to hypocaloric diets have been attributed to hormonal adaptations that override self-control of food intake. We tested this hypothesis by measuring brain fMRI reactivity to food cues and circulating energy-balance hormones in 24 overweight/obese participants before, and 1 and 3 months after starting a calorie restriction diet. Increased activity in prefrontal regions at month 1 correlated with weight loss at months 1 and 3. Weight loss was also correlated with increased plasma ghrelin and decreased leptin at month 1, and these changes were associated with greater food cue reactivity in reward-related brain regions. However, the reduction in leptin did not counteract weight loss; indeed, it was correlated with further weight loss at month 3. Activation in a network of prefrontal regions associated with self-control could contribute to individual differences in weight loss and maintenance, whereas we failed to find that the hormonal adaptations play a major role.
Multi-attribute Decision-making is Best Characterized by an Attribute-Wise Reinforcement Learning Model
Authors: Wang Shaoming , Rehder Bob
Published: December 2017

Choice alternatives often consist of multiple attributes that vary in how successfully they predict reward. Some standard theoretical models assert that decision makers evaluate choices either by weighting those attribute optimally in light of previous experience (so-called rational models), or adopting heuristics that use attributes suboptimally but in a manner that yields reasonable performance at minimal cost (e.g., the take-the-best heuristic). However, these models ignore both the possibility that decision makers might learn to associate reward with whole stimuli (a particular combination of attributes) rather than individual attributes and the common finding that decisions can be overly influenced by recent experiences and exhibit cue competition effects. Participants completed a two-alternative choice task where each stimulus consisted of three binary attributes that were predictive of reward, albeit with different degrees of reliability. Their choices revealed that, rather than using only the “best” attribute, they made use of all attributes but in manner that reflected the classic cue competition effect known as overshadowing. The time needed to make decisions increased as the number of relevant attributes increased, suggesting that reward was associated with attributes rather than whole stimuli. Fitting a family of computational models formed by crossing attribute use (optimal vs. only the best), representation (attribute vs. whole stimuli), and recency (biased or not), revealed that models that performed better when they made use of all information, represented attributes, and incorporated recency effects and cue competition. We also discuss the need to incorporate selective attention and hypothesis-testing like processes to account for results with multiple-attribute stimuli.
High accuracy measurements of nanometer-scale distances between fluorophores at the single-molecule level
Authors: Niekamp Stefan , Sung Jongmin , Huynh Walter , Bhabha Gira , Vale Ronald D. , Stuurman Nico
Published: December 2017

To uncover the mechanisms of molecular machines it is useful to probe their structural conformations. Single-molecule Förster resonance energy transfer (smFRET) is a powerful tool for measuring intra-molecular shape changes of single-molecules, but is confined to distances of 2-8 nm. Current super-resolution measurements are error prone at <25 nm. Thus, reliable high-throughput distance information between 8-25 nm is currently difficult to achieve. Here, we describe methods that utilize information about localization and imaging errors to measure distances between two different color fluorophores with ∼1 nm accuracy at any distance >2 nm, using a standard TIRF microscope and open-source software. We applied our two-color localization method to uncover a ∼4 nm conformational change in the “stalk” of the motor protein dynein, revealing unexpected flexibility in this antiparallel coiled-coil domain. These new methods enable high-accuracy distance measurements of single-molecules that can be used over a wide range of length scales.
The accuracy of LD Score regression as an estimator of confounding and genetic correlations in genome-wide association studies
Authors: Lee James J. , McGue Matt , Iacono William G. , Chow Carson C.
Published: December 2017

In order to infer that a single-nucleotide polymorphism (SNP) either affects a phenotype or is linkage disequilibrium with a causal site, we must have some assurance that any SNP-phenotype correlation is not the result of confounding with environmental variables that also affect the trait. In this work we study the properties of LD Score regression, a recently developed method for using summary statistics from genome-wide association studies (GWAS) to ensure that confounding does not inflate the number of false positives. We do not treat the effects of genetic variation as a random variable and thus are able to obtain results about the unbiasedness of this method. We demonstrate that LD Score regression can produce estimates of confounding at null SNPs that are unbiased or conservative under fairly general conditions. This robustness holds in the case of the parent genotype affecting the offspring phenotype through some environmental mechanism, despite the resulting correlation over SNPs between LD Scores and the degree of confounding. Additionally, we demonstrate that LD Score regression can produce reasonably robust estimates of the genetic correlation, even when its estimates of the genetic covariance and the two univariate heritabilities are substantially biased.
Real-time search of all bacterial and viral genomic data
Authors: Bradley Phelim , Den Bakker Henk C , Rocha Eduardo P. C. , McVean Gil , Iqbal Zamin
Published: December 2017

Genome sequencing of pathogens is now ubiquitous in microbiology, and the sequence archives are effectively no longer searchable for arbitrary sequences. Furthermore, the exponential increase of these archives is likely to be further spurred by automated diagnostics. To unlock their use for scientific research and real-time surveillance we have combined knowledge about bacterial genetic variation with ideas used in web-search, to build a DNA search engine for microbial data that can grow incrementally. We indexed the complete global corpus of bacterial and viral whole genome sequence data (447,833 genomes), using four orders of magnitude less storage than previous methods. The method allows future scaling to millions of genomes. This renders the global archive accessible to sequence search, which we demonstrate with three applications: ultra-fast search for resistance genes MCR1-3, analysis of host-range for 2827 plasmids, and quantification of the rise of antibiotic resistance prevalence in the sequence archives.
The Variability Puzzle in Human Memory
Authors: Kahana M.J. , Aggarwal E.V. , Phan T.D.
Published: December 2017

Memory performance exhibits a high level of variability from moment to moment. Much of this variability may reflect inadequately controlled experimental variables, such as word memorability, past practice and subject fatigue. Alternatively, stochastic variability in performance may largely reflect the efficiency of endogenous neural processes that govern memory function. To help adjudicate between these competing views, we conducted a multisession study in which subjects completed 552 trials of a delayed free-recall task. Applying a statistical model to predict variability in each subject’s recall performance uncovered modest effects of word memorability, proactive interference, and other variables. In contrast to the limited explanatory power of these experimental variables, performance on the prior list strongly predicted current list recall. These findings suggest that endogenous factors underlying successful encoding and retrieval drive variability in performance.
Annotated methodological review of Lean Six Sigma
Authors: Muraliraj J. , Zailani Suhaiza , Kuppusamy S. , Santha C.
Published: December 2017

Purpose

Literature reviews are a pervasive aspect in research. An ever mounting field such as Lean Six Sigma requires a perpetual touch on the subject to accentuate insights that can be researched about. The purpose of this paper is to address the published literatures in the field of Lean Six Sigma through multiple criterion for an enhanced understanding of the subject matter through summarizing its current trends, uncovering existing literature gaps and revealing opportunities for future research in the field.

Design/methodology/approach

The literature review on Lean Six Sigma field spans around 17 years that includes peer-reviewed journals from management, business, engineering, healthcare, manufacturing, military among the many disciplines. The study uses a content analysis approach in which several dimensions of the literature were analysed: purpose or focus of study, years of publication, journal name or publications, methodologies, theories used, country of study, industry sub-sectors, active authors in the field, critical success factors, barriers and challenges and the most contribution of Lean Six Sigma papers by universities.

Findings

Eleven important findings from the analysis were summarized among them; the field of Lean Six Sigma had begun to grow significantly since the new millennium particularly after the 2004-2007 or 2008 period; standalone concepts of Lean and Six Sigma are highly researched compared to the integrated concepts; large proportion of perspective, conceptual and descriptive based studies; lack of empirical validity on the fusion between Lean and Six Sigma; lack of theoretical based studies, etc.

Research limitations/implications

The study is limited to 102 journals in commonly searched databases in the subject matter which produced 261 journal papers. This study seeks to broaden the summary of studies done under the keyword “Lean Six Sigma”.

Originality/value

The review analysis uses a content analysis approach in search of valuable gaps in existing research. The study found 261 papers from 102 journals that were published over the past seventeen years (2000-2016). This paper provides scholars, practitioners and managers with insights on the present trends and focus of Lean Six Sigma in addition to what else are lacking in the subject matter, which could pave the way for future research and practical endeavours.
The European rating fund
Authors: Fischer Dirk-Hinnerk
Published: December 2017

Purpose

The complexity of the financial markets and their controlling entities make structural reforms highly problematic and controversial. This paper aims to address the deficiencies of the credit rating agency (CRA) market. The contribution of this paper to this long and ongoing discussion is a reform concept that is based on the introduction of a new public entity.

Design/methodology/approach

The design is based on the market deficiencies and structural issues defined by numerous other researchers.

Findings

The proposed market reform is based on the introduction of an entity that mainly acts as a communication layer which takes over the contract distribution and payment organization between the issuers and the agencies. The distribution of products for ratings gets anonymized and randomized, which eliminates most conflicts of interest that prevent the market players from performing as they should. This process changes the market fundamentally, but it does not impact either side’s capacity to make profit.

Research limitations/implications

The concept can hence solve most issues of the market, but not all.

Practical implications

The concept is a first step toward necessary reform, and this paper fuels a new discussion about a valid CRA market reform. The reform proposal mentioned in this paper focuses on the European Union, but the structure is easily adaptable to other markets.

Originality/value

The structure introduced in this paper is a new concept that has not been proposed before.
Corporate branding and rebranding: an institutional logics perspective
Authors: Stuart Helen
Published: December 2017

Purpose

The purpose of this paper is to demonstrate how the institutional logics framework adds a fresh perspective on corporate branding, particularly in times of organisational change and subsequent corporate rebranding.

Design/methodology/approach

The paper examines previous comprehensive approaches to corporate branding in the face of organisational transformation, applying institutional theory which adds to intelligence already developed regarding corporate branding and rebranding in this situation.

Findings

An understanding of the institutional logics framework provides insights into how corporate branding and rebranding in organisations is affected in an environment where the organisation simultaneously holds values and beliefs inherent to two or more competing institutional forms (Townley, 2002).

Research limitations/implications

Further research is required to develop a model which integrates institutional logics into previous approaches to corporate rebranding.

Practical implications

Consideration of the underlying institutional logics of an organisation and how organisational transformation results in competing institutional logics and institutional pluralism leads to profound thinking about branding and rebranding an organisation.

Originality/value

Although there are a number of studies which look at how to evolve the corporate brand in times of organisational transformation, the institutional logics approach has not yet been applied to this issue, except by the author.
Maternal oxidative stress and reproduction: Testing the constraint, cost and shielding hypotheses in a wild mammal
Authors: Viblanc Vincent A. , Schull Quentin , Roth Jeffrey D. , Rabdeau Juliette , Saraux Claire , Uhlrich Pierre , Criscuolo François , Dobson F. Stephen
Published: December 2017

Oxidative stress has been proposed as a central causal mechanism underlying the life‐history trade‐off between current and future reproduction and survival in wild animals.

While mixed evidence suggests that maternal oxidative stress may act both as a constraint and a cost to reproduction, some studies have reported a lack of association between reproduction and maternal oxidative stress.

The oxidative shielding hypothesis offers an alternative explanation, suggesting that mothers may pre‐emptively mitigate the oxidative costs of reproduction by increasing antioxidant defences prior to reproduction.

We tested the oxidative constraint, cost and shielding hypotheses using a longitudinal field study of oxidative stress levels in a species that breeds using daily energy income, the Columbian ground squirrel (Urocitellus columbianus).

Elevated maternal oxidative damage prior to reproduction was associated with higher maternal investment in litter mass at birth, but not at weaning.

Breeding females increased their antioxidant capacity and decreased their oxidative damage from birth to lactation, compared to non‐breeding females measured at the same time periods. However, lower maternal oxidative stress during lactation was not associated with higher offspring survival or mass growth over this period.

Our results provide little evidence for maternal oxidative stress acting as a constraint on, or cost to, reproduction in Columbian ground squirrels, but partially support the idea that oxidative shielding occurred to buffer potential oxidative costs of reproduction.

A plain language summary is available for this article.
Beyond the everyday: sustaining kinship in western Kenya
Authors: Cooper Elizabeth
Published: December 2017

This article considers the efforts people in western Kenya have been making to uphold an ideology and practice of the natal home and kin group as morally authoritative, in a context where the very survival of many homes and families has been compromised by the devastating effects of AIDS‐related deaths and impoverishment. It traces how orphaned adults, who have little experience or memory of living among natal kin at natal homes, make concerted efforts to reconnect – often in necessarily improvised ways – with what survives of their natal kin and home. For women, in particular, such efforts seem less motivated by immediate material interests and more focused on demonstrating lineal solidarity as a means to affirming their moral personhood and value. The analysis addresses how people lacking shared everyday experiences of kinship and homes sustain the possibility of their kinship futures through a combination of imagination and ideological commitment.
Neurological, nutritional and alcohol consumption factors underlie cognitive and motor deficits in chronic alcoholism
Authors: Fama Rosemary , Le Berre Anne‐Pascale , Hardcastle Cheshire , Sassoon Stephanie A. , Pfefferbaum Adolf , Sullivan Edith V. , Zahr Natalie M.
Published: December 2017

Variations in pattern and extent of cognitive and motor impairment occur in alcoholism (ALC). Causes of such heterogeneity are elusive and inconsistently accounted for by demographic or alcohol consumption differences. We examined neurological and nutritional factors as possible contributors to heterogeneity in impairment. Participants with ALC (n = 96) and a normal comparison group (n = 41) were examined on six cognitive and motor domains. Signs of historically determined subclinical Wernicke's encephalopathy were detected using the Caine et al. criteria, which were based on postmortem examination and chart review of antemortem data of alcoholic cases with postmortem evidence for Wernicke's encephalopathy. Herein, four Caine criteria provided quantification of dietary deficiency, cerebellar dysfunction, low general cognitive functioning and oculomotor abnormalities in 86 of the 96 ALC participants. Subgroups based on Caine criteria yielded a graded effect, where those meeting more criteria exhibited greater impairment than those meeting no to fewer criteria. These results could not be accounted for by history of drug dependence. Multiple regression indicated that compromised performance on ataxia, indicative of cerebellar dysfunction, predicted non‐mnemonic and upper motor deficits, whereas low whole blood thiamine level, consistent with limbic circuit dysfunction, predicted mnemonic deficits. This double dissociation indicates biological markers that contribute to heterogeneity in expression of functional impairment in ALC. That non‐mnemonic and mnemonic deficits are subserved by the dissociable neural systems of frontocerebellar and limbic circuitry, both commonly disrupted in ALC, suggests neural mechanisms that can differentially affect selective functions, thereby contributing to heterogeneity in pattern and extent of dysfunction in ALC.
Symbionts mediate oviposition behaviour in invasive and native woodwasps
Authors: Hajek Ann E. , Tobin Patrick C. , Kroll Stefanie A. , Long Stefan J.
Published: December 2017

Globalization leads to the introduction of invasive species that are often accompanied by associated microorganisms, and this can lead to homogenization of both introduced hosts and microbes with the native biota. One such example is the invasive Eurasian woodwasp Sirex noctilio, which inoculates pines with an obligate nutritional mutualist, the white rot fungus Amylostereum areolatum.

Although S. noctilio has been previously introduced outside of its native range, its arrival in North America was the first time that it was introduced to communities hosting native Sirex species and Amylostereum strains.

We conducted experiments aiming to investigate acceptance versus avoidance of native and non‐native Amylostereum strains and species during ovipositor drilling by females of S. noctilio and a native congener, Sirex nigricornis.

Sirex noctilio preferred wood without prior fungal emplacement, whereas S. nigricornis preferred wood inoculated with one of the strains of Amylostereum that putatively invaded with S. noctilio.

Drilling and presumed oviposition by both woodwasp species were highly aggregated.

Based on the responses of these two Sirex species to the fungal strains and species included in the present study, the invasive S. noctilio would continue its present symbiont associations, whereas the native S. nigricornis would partly use the strain of fungal symbiont putatively introduced with S. noctilio.
Mirabegron: potential off target effects and uses beyond the bladder
Authors: Dehvari Nodi , da Silva Junior Edilson Dantas , Bengtsson Tore , Hutchinson Dana Sabine
Published: December 2017

The β3‐adrenoceptor was initially an attractive target for several pharmaceutical companies due to its high expression in rodent adipose tissue, where its activation resulted in decreased adiposity and improved metabolic outputs (such as glucose handling) in animal models of obesity and Type 2 diabetes. However, several drugs acting at the β3‐adrenoceptor failed in clinical trials. This was thought to be due to their lack of efficacy at the human receptor. Recently, mirabegron, a β3‐adrenoceptor agonist with human efficacy, was approved in North America, Europe, Japan and Australia for the treatment of overactive bladder syndrome. There are indications that mirabegron may act at other receptors/targets, but whether they have any clinical relevance is relatively unknown. Besides overactive bladder syndrome, mirabegron may have other uses such as in the treatment of heart failure or metabolic disease. This review gives an overview of the off‐target effects of mirabegron and its potential use in the treatment of other diseases.

Linked Articles

This article is part of a themed section on Molecular Pharmacology of GPCRs. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.21/issuetoc
Thrombopoietin receptor agonists in patients with persistent or chronic immune thrombocytopenia
Authors: Agnelli Giacchello Jacopo , Valeri Federica , Boccadoro Mario , Borchiellini Alessandra
Published: December 2017

Objectives

To assess long‐term treatment patterns and outcomes in patients with persistent or chronic immune thrombocytopenia (ITP), also considering the impact of the treatment with thrombopoietin receptor agonists (TPO‐RAs) prior to splenectomy.

Methods

Medical records of all patients with persistent or chronic ITP seen at our institution between January 1985 and December 2016 were reviewed. Data on demographic and clinical characteristics were analyzed using descriptive statistics. Wilcoxon rank‐sum test was used to compare medians between groups of patients.

Results

Among 80 patients with persistent or chronic ITP, 34 underwent splenectomy and 59 were treated with TPO‐RAs. Twenty patients were both splenectomized and treated with TPO‐RAs; among them, 9 received TPO‐RAs before splenectomy. Median time to splenectomy from diagnosis of ITP was 25 months in the group of patients pretreated with TPO‐RAs vs 14.5 months in the group of splenectomized patients. These differences were not statistically significant.

Conclusions

Our study provides some initial data on the potential benefits of the treatment with TPO‐RAs that may allow splenectomy to be safely deferred for prolonged periods. More research is needed to evaluate the impact of the treatment with TPO‐RAs prior to splenectomy.
Catch rate and at‐vessel mortality of circle hooks versus J‐hooks in pelagic longline fisheries: A global meta‐analysis
Authors: Reinhardt James F. , Weaver Jennifer , Latham Pamela J. , Dell'Apa Andrea , Serafy Joseph E. , Browder Joan A. , Christman Mary , Foster Daniel G. , Blankinship David R.
Published: December 2017

We conducted a meta‐analysis of literature reporting on the use of circle hooks and J‐hooks in pelagic longline fisheries. Our study included more data than previous meta‐analyses of the effects of hook type, due to both a larger number of relevant studies available in recent years and a more general modelling approach. Data from 42 empirical studies were analysed using a random effects model to compare the effects of circle hooks and J‐hooks on catch rate (43 species) and at‐vessel mortality (31 species) of target and bycatch species. Catch rates with circle hooks were greater for 11 species, including four tuna species, six shark species and one Istiophorid billfish. Catch rates on circle hooks were lower for seven species, including two Istiophorid billfishes and two species of sea turtle. At‐vessel mortality was significantly lower with circle hooks in 12 species, including three tuna species, three Istiophorid billfishes, swordfish (Xiphias gladius) and three shark species. No species had significantly greater at‐vessel mortality when captured with a circle hook rather than a J‐hook. While our general approach increased model variability compared to more detailed studies, results were consistent with trends identified in previous studies that compared the catch rates and at‐vessel mortality (between hook types) for a number of species. Our results suggest that circle hooks can be a promising tool to reduce mortality of some bycatch species in pelagic longline fisheries, although the effects depend on the species and the metric (catch rate or at‐vessel mortality), emphasizing the need for fishery‐specific data in conservation and management decisions.
Reconstructing governability: How fisheries are made governable
Authors: Song Andrew M , Johnsen Jahn P , Morrison Tiffany H
Published: December 2017

Governability is an important concept in the political and environmental social sciences with increasing application to socio‐ecological systems such as fisheries. Indeed, governability analyses of fisheries and related systems such as marine‐protected areas have generated innovative ways to implement sustainability ideals. Yet, despite progress made, we argue that there remain limitations in current conceptions of governability that hinder further analytical development and use. By drawing on general systems theory—specifically cybernetics, control and feedback—we interrogate the conceptual foundations that underpin two key limitations: the need to incorporate the numerous variables that comprise a complex, holistic system into a singular assessment of governability, and the a priori separation of the governor and the governed that precludes analysis of a self‐governing situation. We argue that by highlighting the reciprocal nature of a governor–governed relationship and the co‐produced understanding of governing capacity and objects, a relational approach to governability is possible. This offers a clearer and more pragmatic understanding of how governors and fishers can make fisheries governable.
From Education to Advocacy and Activism: Alternative Approaches for Translating Family Science to Policy
Authors: Letiecq Bethany L. , Anderson Elaine A.
Published: December 2017

Historically, translational family science frameworks focused on policy have delimited the roles family scientists can play and the approaches they can implement within the scientific realm. In this article, we call for an expanded translational research‐to‐policy framework that is inclusive of such roles as policy educator, scholar‐advocate, and scholar‐activist. We argue that, depending on the policy topic or context of one's research, different approaches and roles are needed to move family research to policy, especially when working with marginalized and disenfranchised families. We then present 3 approaches to family policy engagement, particularly at the local and state levels: family impact seminars, deliberative policy processes, and community‐based participatory research. Each approach positions the family scientist to perform different roles—from policy educator to scholar‐advocate to scholar‐activist—in their translational work. We offer our reflections across roles and approaches and provide recommendations for future translational family science in the policy arena.
Multiple sulfur isotope constraints on microbial sulfate reduction below an Archean seafloor hydrothermal system
Authors: Aoyama Shinnosuke , Ueno Yuichiro
Published: December 2017

Microbial sulfate reduction is among the most ubiquitous metabolic processes on earth. The oldest evidence of microbial sulfate reduction appears in the ca. 3.5 Ga Dresser Formation in the North Pole area of Pilbara Craton in Western Australia. That evidence was found through analysis of quadruple sulfur isotopes of sulfate and sulfide minerals deposited on the seafloor. However, the activity of microbial sulfate reduction below the Archean seafloor remains poorly understood. Here, we report the quadruple sulfur isotopic compositions of sulfide minerals within hydrothermally altered seafloor basalt and less altered basaltic komatiite collected from the North Pole Dome area. The Δ33S values of the sulfide minerals were nonzero negative, suggesting that sulfate reduction occurred below the Archean seafloor. To constrain the substrate sulfate sources and sulfate reduction processes, we constructed a numerical model. Comparing the modeled and observed sulfur isotopes, we show that the substrate sulfate comprises seawater sulfate with a negative Δ33S anomaly and 34S‐enriched sulfate with no anomalous Δ33S. The latter component probably represents sulfate produced by local hydrothermal processes. The maximum sulfur isotopic fractionation between the putative substrate sulfate and the observed sulfide minerals within the altered basalt and basaltic komatiite is 35‰, which is consistent with a microbial origin. Alternatively, thermochemical sulfate reduction may also produce sulfide. However, considering the hydrothermal temperature inferred from the metamorphic grade of the altered basalt, the sulfur isotopic fractionation produced by inorganic sulfate reduction is probably below 20‰. Collectively, larger fractionations imply the involvement of biological sulfate reduction processes, both in the hydrothermal system below the seafloor and in less altered subsurface settings.
Contribution of crop model structure, parameters and climate projections to uncertainty in climate change impact assessments
Authors: Tao Fulu , Rötter Reimund P. , Palosuo Taru , Gregorio Hernández Díaz‐Ambrona Carlos , Mínguez M. Inés , Semenov Mikhail A. , Kersebaum Kurt Christian , Nendel Claas , Specka Xenia , Hoffmann Holger , Ewert Frank , Dambreville Anaelle , Martre Pierre , Rodríguez Lucía , Ruiz‐Ramos Margarita , Gaiser Thomas , Höhn Jukka G. , Salo Tapio , Ferrise Roberto , Bindi Marco , Cammarano Davide , Schulman Alan H.
Published: December 2017

Climate change impact assessments are plagued with uncertainties from many sources, such as climate projections or the inadequacies in structure and parameters of the impact model. Previous studies tried to account for the uncertainty from one or two of these. Here, we developed a triple‐ensemble probabilistic assessment using seven crop models, multiple sets of model parameters and eight contrasting climate projections together to comprehensively account for uncertainties from these three important sources. We demonstrated the approach in assessing climate change impact on barley growth and yield at Jokioinen, Finland in the Boreal climatic zone and Lleida, Spain in the Mediterranean climatic zone, for the 2050s. We further quantified and compared the contribution of crop model structure, crop model parameters and climate projections to the total variance of ensemble output using Analysis of Variance (ANOVA). Based on the triple‐ensemble probabilistic assessment, the median of simulated yield change was −4% and +16%, and the probability of decreasing yield was 63% and 31% in the 2050s, at Jokioinen and Lleida, respectively, relative to 1981–2010. The contribution of crop model structure to the total variance of ensemble output was larger than that from downscaled climate projections and model parameters. The relative contribution of crop model parameters and downscaled climate projections to the total variance of ensemble output varied greatly among the seven crop models and between the two sites. The contribution of downscaled climate projections was on average larger than that of crop model parameters. This information on the uncertainty from different sources can be quite useful for model users to decide where to put the most effort when preparing or choosing models or parameters for impact analyses. We concluded that the triple‐ensemble probabilistic approach that accounts for the uncertainties from multiple important sources provide more comprehensive information for quantifying uncertainties in climate change impact assessments as compared to the conventional approaches that are deterministic or only account for the uncertainties from one or two of the uncertainty sources.
Pricing, environmental governance efficiency, and channel coordination in a socially responsible tourism supply chain
Authors: Liu Yunzhi , Xiao Tiaojun , Fan Zhi‐Ping , Zhao Xuan
Published: December 2017

We investigate the pricing and environmental governance efficiency decisions and channel coordination of a dyadic tourism supply chain with corporate social responsibility. We consider two cases: only the theme park exhibits (environmental) social responsibility; and both theme park and tour operator exhibit social responsibility. For each case, we design a coordination mechanism. In the first case, we find that (a) if the environmental governance investment is relatively inexpensive, then the retail price, environmental governance efficiency, and sale quantity may simultaneously increase with the theme park's environmental responsibility (extra investment on the treatment of ungoverned environmental damage) under the centralized system; (b) it is more likely to achieve a win‐win outcome if the theme park cares more about the environment when the channel is coordinated; (c) the theme park's environmental responsibility enables itself to gain more coordination benefit when its negotiation power is relatively high. In the second case, we find that (a) the environmental governance efficiency or sale quantity increases with the tour operator's social responsibility; (b) both members’ profits may increase with the tour operator's social responsibility.
Diabetic foot ulcer management in clinical practice in the UK: costs and outcomes
Authors: Guest Julian F , Fuller Graham W , Vowden Peter
Published: December 2017

The aim of this study was to estimate the patterns of care and annual levels of health care resource use attributable to managing diabetic foot ulcers (DFUs) in clinical practice by the UK's National Health Service (NHS), and the associated costs of patient management.

This was a retrospective cohort analysis of the records of 130 patients with a newly diagnosed DFU in The Health Improvement Network (THIN) database. Patients' characteristics, wound‐related health outcomes and health care resource use were quantified, and the total NHS cost of patient management was estimated at 2015–2016 prices.

Patients were predominantly managed in the community by nurses, with minimal clinical involvement of specialist physicians. 5% of patients saw a podiatrist, and 5% received a pressure‐offloading device. Additionally, 17% of patients had at least one amputation within the first 12 months from initial presentation of their DFU. 14% of DFUs were documented as being clinically infected at initial presentation, although an additional 31% of patients were prescribed an antimicrobial dressing at the time of presentation. Of all the DFUs, 35% healed within 12 months, and the mean time to healing was 4·4 months. Over the study period, 48% of all patients received at least one prescription for a compression system, but significantly more patients healed if they never received compression (67% versus 16%; P < 0·001). The mean NHS cost of wound care over 12 months was an estimated £7800 per DFU (of which 13% was attributable to amputations), ranging from £2140 to £8800 per healed and unhealed DFU, respectively, and £16 900 per amputated wound.

Consolidated medical records from a primary care held database provided ‘real‐world evidence’ highlighting the consequences of inefficient and inadequate management of DFUs in clinical practice in the UK. Clinical and economic benefits to both patients and the NHS could accrue from strategies that focus on (i) wound prevention, (ii) improving wound‐healing rates and (iii) reducing infection and amputation rates.
Health‐related quality of life and patient burden in patients with split‐thickness skin graft donor site wounds
Authors: Humrich Marco , Goepel Lisa , Gutknecht Mandy , Lohrberg David , Blessmann Marco , Bruning Guido , Diener Holger , Dissemond Joachim , Hartmann Bernd , Augustin Matthias
Published: December 2017

Split‐thickness skin grafting is a common procedure to treat different kinds of wounds. This systematic, multicentre, observational, cross‐sectional study of adult patients with split‐thickness skin graft (STSG) donor site wounds was conducted to evaluate quality of life (QoL) impairments caused by donor site wounds following split‐thickness skin grafting. Therefore, 112 patients from 12 wound centres in Germany were examined based on patient and physician questionnaires as well as a physical examination of the donor site wound. Most indications for skin grafting were postsurgical treatment (n = 51; 42.5%) and chronic wounds (n = 47; 39.2%). European QoL visual analoque scale (EQ VAS) averaged 64.7 ± 23.3, European QoL 5 dimensions (EQ‐5D) averaged 77.4 ± 30.0.

Wound‐QoL (range: 0‐4) was rated 0.8 ± 0.8 post‐surgery and 0.4 ± 0.6 at the time of survey (on average 21 weeks between the time points). Compared to averaged Wound‐QoL scores of chronic wounds donor site‐related QoL impairments in split‐thickness skin‐graft patients were less pronounced. There were significant differences in patient burden immediately after surgery compared to the time of the survey, with medium effect sizes. This supports the hypothesis that faster healing of the donor site wound leads to more favourable patient‐reported outcomes.
A comprehensive approach to assigning periodontal prognosis
Authors: Martinez‐Canut Pedro , Llobell Arturo
Published: December 2017

Aim

The purpose of this retrospective case series study was to evaluate the usefulness and performance of a comprehensive approach to assigning periodontal prognosis by assessing the risk of tooth loss due to periodontal disease (TLPD) and estimate the survival time (ST) of periodontally compromised teeth (PCT).

Material and Methods

The Long‐Term Outcome (LTO) index was utilized to assess the risk of TLPD, at baseline, in 100 patients following periodontal maintenance for a mean 24.7 year (±2.4). A TLPD prediction model was utilized to assign ST to PCT. The performance of the TLPD prediction based on both parameters was assessed.

Results

The mean TLPD rate increased as the LTO index increased (Kruskal–Wallis p < .001). The percentage of TLPD increased as the ST decreased, with significantly differences between the LTO categories <4 and ≥4 for all ST intervals (Mann–Whitney p < .001 to p .021).

Only 21% of PCT were lost. This percentage was 58% for teeth assigned the shortest ST and increased to 71% and 88% for these teeth in LTO ≥4 patients.

Conclusions

This approach might be useful to predict TLPD in patients with an initial higher risk of TLPD while it was not useful in patients with lower risk of TLPD.
Examining the content and moderators of women's fears for giving birth: A meta‐synthesis
Authors: Sheen Kayleigh , Slade Pauline
Published: December 2017

Aims and objectives

This meta‐synthesis aimed to identify key elements contributing to FOC derived from women's own reports.

Background

Fear of childbirth (FOC) encompasses fear or anxiety about giving birth, which can resemble a phobic response. FOC holds implications for women's antenatal and postnatal well‐being, and decisions made about the birth but a clear definition of the construct does not exist.

Method

A meta‐synthesis was conducted by searching databases (Web of Knowledge, CINAHL, EBSCO, MEDLINE, PsychInfo and PsychArticles) for qualitative studies describing women's perspectives with respect to fear, anxiety, concerns, phobia or stress about birth. A total of 25 papers, reporting findings from 24 studies, fulfilled eligibility criteria and were included in the synthesis.

Results

Six key elements of FOC were identified; fears of the unknown, potential for injury, pain, capacity to give birth, losing control and adequacy of support from care providers. A single overarching theme linking all elements was “the unpredictability of childbirth.” Three moderators of FOC were also identified; awareness of negative birthing experiences, information received about birth and support received from care providers.

Conclusions

Findings highlight the role of uncertainty in the birthing process as an overarching theme underpinning women's fears. Enhancing tolerance of uncertainty may be a way to reduce women's FOC.

Relevance to clinical practice

Identification of the elements and moderators of FOC provide an insight into the potential mechanisms that contribute to women's fears, which can be used to inform methods of identifying women with FOC or a basis upon which to base supportive strategies to reduce women's fears for giving birth.
Institutional and Legal Context in Natural Experiments: The Case of State Antitakeover Laws
Authors: KARPOFF JONATHAN M. , WITTRY MICHAEL D.
Published: December 2017

We argue and demonstrate empirically that a firm's institutional and legal context has first‐order effects in tests that use state antitakeover laws for identification. A priori, the size and direction of a law's effect on a firm's takeover protection depends on (i) other state antitakeover laws, (ii) preexisting firm‐level takeover defenses, and (iii) the legal regime as reflected by important court decisions. In addition, (iv) state antitakeover laws are not exogenous for many easily identifiable firms. We show that the inferences from nine prior studies related to nine different outcome variables change substantially when we include controls for these considerations.
Nocturnal activation of melatonin receptor type 1 signaling modulates diurnal insulin sensitivity via regulation of PI3K activity
Authors: Owino Sharon , Sánchez‐Bretaño Aida , Tchio Cynthia , Cecon Erika , Karamitri Angeliki , Dam Julie , Jockers Ralf , Piccione Giuseppe , Noh Hye Lim , Kim Taekyoon , Kim Jason K. , Baba Kenkichi , Tosini Gianluca
Published: December 2017

Recent genetic studies have highlighted the potential involvement of melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2) in the pathogenesis of type 2 diabetes. Here, we report that mice lacking MT1 (MT1 KO) tend to accumulate more fat mass than WT mice and exhibit marked systemic insulin resistance. Additional experiments revealed that the main insulin signaling pathway affected by the loss of MT1 was the activation of phosphatidylinositol‐3‐kinase (PI3K). Transcripts of both catalytic and regulatory subunits of PI3K were strongly downregulated within MT1 KO mice. Moreover, the suppression of nocturnal melatonin levels within WT mice, by exposing mice to constant light, resulted in impaired PI3K activity and insulin resistance during the day, similar to what was observed in MT1 KO mice. Inversely, administration of melatonin to WT mice exposed to constant light was sufficient and necessary to restore insulin‐mediated PI3K activity and insulin sensitivity. Hence, our data demonstrate that the activation of MT1 signaling at night modulates insulin sensitivity during the day via the regulation of the PI3K transcription and activity. Lastly, we provide evidence that decreased expression of MTNR1A (MT1) in the liver of diabetic individuals is associated with poorly controlled diabetes.