bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of domain growth on spatial correlations
Authors: Ross Robert J. H. , Yates C. A. , Baker R. E.
Published: February 2016

Mathematical models describing cell movement and proliferation are important research tools for the understanding of many biological processes. In this work we present methods to include the effects of domain growth on the evolution of spatial correlations between agent locations in a continuum approximation of a one-dimensional lattice-based model of cell motility and proliferation. This is important as the inclusion of spatial correlations in continuum models of cell motility and proliferation without domain growth has previously been shown to be essential for their accuracy in certain scenarios. We include the effect of spatial correlations by deriving a system of ordinary differential equations that describe the expected evolution of individual and pair density functions for agents on a growing domain. We then demonstrate how to simplify this system of ordinary differential equations by using an appropriate approximation. This simplification allows domain growth to be included in models describing the evolution of spatial correlations between agents in a tractable manner.
How domain growth is implemented determines the long term behaviour of a cell population through its effect on spatial correlations
Authors: Ross Robert J. H. , Baker R. E. , Yates C. A.
Published: February 2016

Domain growth plays an important role in many biological systems, and so the inclusion of domain growth in models of these biological systems is important to understanding how these biological systems function. In this work we present methods to include the effects of domain growth on the evolution of spatial correlations in a continuum approximation of a lattice-based model of cell motility and proliferation. We show that, depending on the way in which domain growth is implemented, different steady-state densities are predicted for an agent population. Furthermore, we demonstrate that the way in which domain growth is implemented can result in the evolution of the agent density depending on the size of the domain. Continuum approximations that ignore spatial correlations cannot capture these behaviours, while those that account for spatial correlations do. These results will be of interest to researchers in developmental biology, as they suggest that the nature of domain growth can determine the characteristics of cell populations.
Generation of mutation hotspots in ageing bacterial colonies
Authors: Sekowska Agnieszka , Wendel Sofie , Nørholm Morten H. H. , Danchin Antoine
Published: February 2016

How do ageing bacterial colonies generate adaptive mutants? Over a period of two months, we isolated on ageing colonies outgrowing mutants able to use a new carbon source, and sequenced their genomes. This allowed us to uncover exquisite details on the molecular mechanism behind their adaptation: most mutations were located in just a few hotspots in the genome and over time, mutations increasingly originated from 8-oxo-guanosine, formed exclusively on the transcribed strand.
Productive infection of field strains of avian coronavirus infectious bronchitis virus in chicken peripheral blood-derived monocytes
Authors: Zhang Yueting , Whittaker Gary R.
Published: February 2016

The avian coronavirus infectious bronchitis virus (IBV) typically infects the respiratory tract of chickens, but can also spread to other organs. However, the mechanisms of virus dissemination are presently unclear. We show that peripheral blood-derived monocytes/macrophages from chickens (chPBMC) are productively infected by clinical strains of IBV, accompanied by induction of apoptosis. Our data suggest that chPBMCs play a role in the dissemination of IBV, and may be important for viral pathogenesis.
Does the choice of nucleotide substitution models matter topologically?
Authors: Hoff Michael , Orf Stefan , Riehm Benedikt , Darriba Diego , Stamatakis Alexandros
Published: February 2016

Background

In the context of a master level programming practical at the computer science department of the Karlsruhe Institute of Technology, we developed and make available an open-source code for testing all 203 possible nucleotide substitution models in the Maximum Likelihood (ML) setting under the common Akaike, corrected Akaike, and Bayesian information criteria. We address the question if model selection matters topologically, that is, if conducting ML inferences under the optimal, instead of a standard General Time Reversible model, yields different tree topologies. We also assess, to which degree models selected and trees inferred under the three standard criteria (AIC, AICc, BIC) differ. Finally, we assess if the definition of the sample size (#sites versus #sites × #taxa) yields different models and, as a consequence, different tree topologies.

Results

We find that, all three factors (by order of impact: nucleotide model selection, information criterion used, sample size definition) can yield topologically substantially different final tree topologies (topological difference exceeding 10%) for approximately 5% of the tree inferences conducted on the 39 empirical datasets used in our study.

Conclusions

We find that, using the best-fit nucleotide substitution model may change the final ML tree topology compared to an inference under a default GTR model. The effect is less pronounced when comparing distinct information criteria. Nonetheless, in some cases we did obtain substantial topological differences.
A Concise Genealogy and Anatomy of Habitus
Authors: Wacquant Loïc
Published: February 2016

Retracing the philosophical origins and initial usage of habitus by Bourdieu to account for the historical disjuncture wrought by the Algerian war of national liberation and the postwar modernization of the French countryside allows us to clear up four recurrent misunderstandings about the concept: (1) habitus is never the replica of a single social structure but a dynamic, multiscalar, and multilayered set of schemata subject to ‘permanent revision’ in practice; (2) habitus is not necessarily coherent and unified but displays varying degrees of integration and tension; (3) because it is not always congruent with the cosmos in which it evolves, habitus is suited to analysing crisis and change no less than cohesion and perpetuation; but (4) it is not a self-sufficient mechanism for the generation of action: the dissection of dispositions must always proceed in close connection with the mapping of the system of positions that alternately excite, suppress, or redirect the socially constituted capacities and inclinations of the agent. Crucially, in Bourdieu's hands, habitus is not an abstract concept issued from and aimed at theoretical disquisition, but a stenographic manner of designating a research posture that puts the genetic mode of thinking at the heart of social analysis.
Border Effect Between Hong Kong and Mainland China
Authors: Fan Simon C. , Wei Xiangdong , Wu Jia
Published: February 2016

This study applies newly developed methodologies to investigate the border effect between Hong Kong and mainland China. It makes three contributions to a better understanding of the border effect puzzle. First, the special relationship between mainland China and Hong Kong provides us with a unique opportunity to disentangle the factors underlying the observed border effect. Second, in addition to estimating the border effect between mainland China and Hong Kong, we also estimate that between the mainland provinces of Guangdong and Shanghai. This comparison between two types of border effects facilitates a better understanding of the extent of domestic market integration in China. Third, owing to the nature of our data and the new estimation approach we adopt, our estimated border effects are less subject to the measurement error‐related and estimation‐related biases commonly seen in previous studies. We find the estimated border effect between Hong Kong and mainland China to be approximately 266 km, which is substantially larger than that between Guangdong and Shanghai (1.3 km). Both are substantially smaller than the estimated border effects found in many previous studies.
State Capitalism: A New Perspective on Land Sale in China
Authors: Tian Wei , Sheng Liugang , Zhao Hongyan
Published: February 2016

This paper presents a new perspective for understanding the land sale behaviour of local governments in China, focusing on the ‘institutional trinity’ of the land market; namely, state ownership, economic performance‐based political promotion and the unbalanced fiscal structure. The paper argues that the main motivations of local government to sell land are to promote industrial growth and to enhance government fiscal capacity. These two hypotheses are tested using prefecture‐level data covering approximately 330 municipalities during the period of 1999–2007. The paper finds that industrial output and fiscal expenditure increase by approximately 1.8% and 1.0%, respectively, if the area of land sale doubles. Evidence also shows that land sale promotes industrial growth by boosting fixed asset investment and foreign direct investment. Interestingly, the paper also finds that the land‐sale strategy of local governments is more effective in the eastern provinces than in other regions.
New Structural Economics and Resource Financed Infrastructure
Authors: Lin Justin Yifu , Wang Yan
Published: February 2016

The world economy needs a growth‐lifting strategy, and infrastructure financing appears to hold the key. Two new development banks have been established: the New Development Bank and the Asian Infrastructural Investment Bank (AIIB). However, what conceptual framework will they formulate? This paper addresses infrastructural financing issues from the angle of structural transformation as a strategy for global development. Based on the new structural economics (Lin, , ) we stress the ‘real’ side of transforming natural resources to productive assets using the resource financed infrastructure. As one of the innovative instruments, this approach could, first, combine two otherwise isolated supply chains, resource extraction and infrastructure building, and, thereby, bring developmental results many years ahead of what other conventional approaches could. Second, this could serve as one of the ‘least‐cost’ options for developing countries, and benefit borrowers disproportionately due to its feature of ‘non‐recourse’ loans. Finally, in a low‐yield environment, the rate of return from investing in bottleneck‐releasing infrastructure could be attractive to many investors. Future prospects of development financing, including the ‘one belt one road’ initiative are discussed.
Microbial Safety of Wood in Contact with Food: A Review
Authors: Aviat Florence , Gerhards Christian , Rodriguez‐Jerez José‐juan , Michel Valérie , Bayon Isabelle Le , Ismail Rached , Federighi Michel
Published: February 2016

Food packaging is multifunctional: it protects from harvest to table. Four main groups of materials for direct food contact are mentioned in the literature: wood, glass, plastic, and metal. In this review, the focus is on wooden packaging for direct contact with food. In Europe, wood as a food contact material is subject to European Regulation (EC) No 1935/2004 states that materials must not transfer their constituents to food. Today, wooden packaging, like other packaging materials, does not have a Europe‐wide harmonized specific regulation, so member countries legislate at different levels. Wood has been safely used for centuries in contact with food but is usually questioned because of its microbiological behavior compared with smooth surfaces. Based on a review of published conclusions from scientific studies over the last 20 y and after a description of the general properties of wooden packaging, we focus on the microbiological status of natural wood. Then, we discuss the parameters influencing the survival of microorganisms on wood. Finally, we report on the transfer of microorganisms from wood to food and the factors influencing this phenomenon. This review demonstrates that the porous nature of wood, especially when compared with smooth surfaces, is not responsible for the limited hygiene of the material used in the food industry and that it may even be an advantage for its microbiological status. In fact, its rough or porous surface often generates unfavorable conditions for microorganisms. In addition, wood has the particular characteristic of producing antimicrobial components able to inhibit or limit the growth of pathogenic microorganisms.
Salt Reduction in a Model High‐Salt Akawi Cheese: Effects on Bacterial Activity, pH, Moisture, Potential Bioactive Peptides, Amino Acids, and Growth of Human Colon Cells
Authors: Gandhi Akanksha , Shah Nagendra P.
Published: February 2016

This study evaluated the effects of sodium chloride reduction and its substitution with potassium chloride on Akawi cheese during storage for 30 d at 4 °C. Survival of probiotic bacteria (Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium longum) and starter bacteria (Streptococcus thermophilus and Lactobacillus delbrueckii ssp. bulgaricus), angiotensin‐converting enzyme‐inhibitory and antioxidant activities, and concentrations of standard amino acids as affected by storage in different brine solutions (10% NaCl, 7.5% NaCl, 7.5% NaCl+KCl [1:1], 5% NaCl, and 5% NaCl+KCl [1:1]) were investigated. Furthermore, viability of human colon cells and human colon cancer cells as affected by the extract showing improved peptide profiles, highest release of amino acids and antioxidant activity (that is, from cheese brined in 7.5% NaCl+KCl) was evaluated. Significant increase was observed in survival of probiotic bacteria in cheeses with low salt after 30 d. Calcium content decreased slightly during storage in all cheeses brined in various solutions. Further, no significant changes were observed in ACE‐inhibitory activity and antioxidant activity of cheeses during storage. Interestingly, concentrations of 4 essential amino acids (phenylalanine, tryptophan, valine, and leucine) increased significantly during storage in brine solutions containing 7.5% total salt. Low concentration of cheese extract (100 μg/mL) significantly improved the growth of normal human colon cells, and reduced the growth of human colon cancer cells. Overall, the study revealed that cheese extracts from reduced‐NaCl brine improved the growth of human colon cells, and the release of essential amino acids, but did not affect the activities of potential bioactive peptides.
What matters is more than just the choice of pharmaceutical agent
Authors: Kidd Brian , Day Ed , Strang John
Published: February 2016

Commentary to: Which medications are suitable for agonist drug maintenance?
Posttranscriptional regulation ofFOXOexpression: microRNAs and beyond
Authors: Urbánek P , Klotz L‐O
Published: February 2016

Forkhead box, class O (FOXO) transcription factors are major regulators of diverse cellular processes, including fuel metabolism, oxidative stress response and redox signalling, cell cycle progression and apoptosis. Their activities are controlled by multiple posttranslational modifications and nuclear‐cytoplasmic shuttling. Recently, post‐transcriptional regulation of FOXO synthesis has emerged as a new regulatory level of their functions. Accumulating evidence suggests that this post‐transcriptional mode of regulation of FOXO activity operates in response to stressful stimuli, including oxidative stress. Here, we give a brief overview on post‐transcriptional regulation of FOXO synthesis by microRNAs (miRNAs) and by RNA‐binding regulatory proteins, human antigen R (HuR) and quaking (QKI). Aberrant post‐transcriptional regulation of FOXOs is frequently connected with various disease states. We therefore discuss characteristic examples ofFOXOregulation at the post‐transcriptional level under various physiological and pathophysiological conditions, including oxidative stress and cancer. The picture emerging from this summary points to a diversity of interactions between miRNAs/miRNA‐induced silencing complexes and RNA‐binding regulatory proteins. Better insight into these complexities of post‐transcriptional regulatory interactions will add to our understanding of the mechanisms of pathological processes and the role of FOXO proteins.

Linked Articles

This article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visithttp://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc
Translational mixed‐effects PKPD modelling of recombinant human growth hormone – from hypophysectomized rat to patients
Authors: Thorsted A , Thygesen P , Agersø H , Laursen T , Kreilgaard M
Published: February 2016

Background and Purpose

We aimed to develop a mechanistic mixed‐effects pharmacokinetic (PK)–pharmacodynamic (PD) (PKPD) model for recombinant human growth hormone (rhGH) in hypophysectomized rats and to predict the human PKPD relationship.

Experimental Approach

A non‐linear mixed‐effects model was developed from experimental PKPD studies of rhGH and effects of long‐term treatment as measured by insulin‐like growth factor 1 (IGF‐1) and bodyweight gain in rats. Modelled parameter values were scaled to human values using the allometric approach with fixed exponents for PKs and unscaled for PDs and validated through simulations relative to patient data.

Key Results

The final model described rhGH PK as a two compartmental model with parallel linear and non‐linear elimination terms, parallel first‐order absorption with a total s.c. bioavailability of 87% in rats. Induction of IGF‐1 was described by an indirect response model with stimulation of kin and related to rhGH exposure through an Emax relationship. Increase in bodyweight was directly linked to individual concentrations of IGF‐1 by a linear relation. The scaled model provided robust predictions of human systemic PK of rhGH, but exposure following s.c. administration was over predicted. After correction of the human s.c. absorption model, the induction model for IGF‐1 well described the human PKPD data.

Conclusions

A translational mechanistic PKPD model for rhGH was successfully developed from experimental rat data. The model links a clinically relevant biomarker, IGF‐1, to a primary clinical end‐point, growth/bodyweight gain. Scaling of the model parameters provided robust predictions of the human PKPD in growth hormone‐deficient patients including variability.
Report on the use of non‐clinical studies in the regulatory evaluation of oncology drugs
Authors: Hayakawa Yoshihiro , Kawada Manabu , Nishikawa Hiroyoshi , Ochiya Takahiro , Saya Hideyuki , Seimiya Hiroyuki , Yao Ryoji , Hayashi Masahiro , Kai Chieko , Matsuda Akira , Naoe Tomoki , Ohtsu Atsushi , Okazaki Taku , Saji Hideo , Sata Masataka , Sugimura Haruhiko , Sugiyama Yuichi , Toi Masakazu , Irimura Tatsuro
Published: February 2016

Non‐clinical studies are necessary at each stage of the development of oncology drugs. Many experimental cancer models have been developed to investigate carcinogenesis, cancer progression, metastasis, and other aspects in cancer biology and these models turned out to be useful in the efficacy evaluation and the safety prediction of oncology drugs. While the diversity and the degree of engagement in genetic changes in the initiation of cancer cell growth and progression are widely accepted, it has become increasingly clear that the roles of host cells, tissue microenvironment, and the immune system also play important roles in cancer. Therefore, the methods used to develop oncology drugs should continuously be revised based on the advances in our understanding of cancer. In this review, we extensively summarize the effective use of those models, their advantages and disadvantages, ranges to be evaluated and limitations of the models currently used for the development and for the evaluation of oncology drugs.
The Privileged Status of Category Representations in Early Development
Authors: Cimpian Andrei
Published: February 2016

The ability to carve the world into broad categories (e.g., DOG) made up of distinct individuals (e.g., Lassie and Toto) is essential for adaptive behavior and has been the focus of extensive research in cognitive and developmental psychology. Classic work on the development of category representations has revealed that they emerge early: Even infants can conceive of distinct objects as equivalent members of the same category. However, more recently, research on conceptual development has begun to suggest a stronger conclusion, namely that mental representations of categories are privileged by our cognitive systems relative to representations of similar, but noncategorical, entities. According to this research, which I review in this article, our minds may be structured to facilitate the acquisition, retention, and manipulation of category‐level information. This conclusion goes beyond current theories of conceptual development.
Weight gain in Turner Syndrome: association to puberty induction? – longitudinal analysis of KIGS data
Authors: Reinehr Thomas , Lindberg Anders , Toschke Christina , Cara Jose , Chrysis Dionisis , Camacho‐Hübner Cecilia
Published: February 2016

Context

Girls with Turner Syndrome (TS) treated or not treated with growth hormone (GH) are prone to overweight. Therefore, we hypothesize that puberty induction inTSis associated with weight gain.

Methods

We analyzed weight changes (BMI‐SDS) between onset ofGHtreatment and near adult height (NAH) in 887 girls withTSenrolled inKIGS(Pfizer International Growth Database). Puberty was induced with estrogens in 646 (72·8%) girls withTS.

Results

Weight status did not change significantly betweenGHtreatment start and 1 year later (mean difference −0·02BMI‐SDS), but increased significantly (P< 0·001) untilNAH(+0·40BMI‐SDS). TheBMI‐SDSincreased +0·21 until start of puberty (P< 0·001). Girls with spontaneous and induced puberty showed similarBMI‐SDSchanges. Puberty induction at ≥12 years was associated with a significant (P< 0·001) less increase ofBMI‐SDS(+0·7BMI‐SDS) between baseline andNAHcompared to puberty induction at <12 year (+1·0BMI‐SDS). In multiple linear regression analyses changes ofBMI‐SDSbetween baseline andNAHwere negatively associated with baselineBMI‐SDS(P< 0·001),GHdoses (P= 0·015), and age at puberty induction (P< 0·001), positively with years onGHtreatment (P= 0·004), while duration and dose of estrogens, its route of administration (transdermal/oral), changes of height‐SDS, thyroxin and oxandrolone treatment, and karyotype did not correlate significantly to changes ofBMI‐SDSin this time period.

Conclusions

Puberty does not seem to play a major role in weight gain in girls withTSsince the majority of the increases inBMI‐SDSoccurred before puberty. However, late puberty induction seems to decrease the risk of weight gain.
Prevalence and correlates of vitamin D deficiency in adults after traumatic brain injury
Authors: Jamall Omer A. , Feeney Claire , Zaw‐Linn Joanna , Malik Aysha , Niemi Mari E.K. , Tenorio‐Jimenez Carmen , Ham Timothy E. , Jilka Sagar R. , Jenkins Peter O. , Scott Gregory , Li Lucia M. , Gorgoraptis Nikolaos , Baxter David , Sharp David J. , Goldstone Anthony P.
Published: February 2016

Objectives

Traumatic brain injury (TBI) is a major cause of long‐term disability with variable recovery. Preclinical studies suggest that vitamin D status influences the recovery after TBI. However, there is no published clinical data on links between vitamin D status and TBI outcomes. The aim was to determine the (i) prevalence of vitamin D deficiency/insufficiency, and associations of vitamin D status with (ii) demographic factors and TBI severity, and with (iii) cognitive function, symptoms and quality of life, in adults after TBI.

Design

Retrospective audit of patients seen between July 2009 and March 2015. Serum vitamin D (25‐hydroxy‐cholecalciferol) was categorized as deficient (<40 nmol/l), insufficient (40–70 nmol/l) or replete (>70 nmol/l).

Patients

A total of 353 adults seen in tertiary hospital clinic (75·4% lighter skinned, 74·8% male, age median 35·1 year, range 26·6–48·3 year), 0·3–56·5 months after TBI (74·5% moderate–severe).

Measurements

Serum vitamin D concentrations; Addenbrooke's Cognitive Examination (ACE‐R), Beck Depression Inventory‐II (BDI‐II), SF‐36 Quality of Life, Pittsburgh Sleep Quality Index.

Results

In total, 46·5% of patients after TBI had vitamin D deficiency and 80·2% insufficiency/deficiency. Patients with vitamin D deficiency had lower ACE‐R scores than those of vitamin D replete (mean effect size ± SEM 4·5 ± 2·1, P = 0·034), and higher BDI‐II scores than those of vitamin D insufficient (4·5 ± 1·6, P = 0·003), correcting for age, gender, time since TBI and TBI severity. There was no association between vitamin D status and markers of TBI severity, sleep or quality of life.

Conclusion

Vitamin D deficiency is common in patients after TBI and associated with impaired cognitive function and more severe depressive symptoms.
The influence of thiazide intake on calcium and parathyroid hormone levels in patients with primary hyperparathyroidism
Authors: Riss Philipp , Kammer Michael , Selberherr Andreas , Bichler Christoph , Kaderli Reto , Scheuba Christian , Niederle Bruno
Published: February 2016

Objective

The effects of thiazide medication in patients with primary hyperparathyroidism (PHPT) have so far not been elucidated. The aim of this study was to analyse the extent to which the administration of thiazides may influence biochemical parameters and therefore the diagnosis of PHPT in a large cohort of patients.

Design and patients

The biochemical parameters of 1066 patients with PHPT were analysed, and drug history was documented. Calcium (Ca)/creatinine clearance ratio (CCCR) was calculated. The results of patients given thiazides (n = 170) and those not given thiazides (n = 896) were analysed and compared.

Measurements

Twenty‐four‐hour urinary calcium excretion (24hU), albumin‐corrected serum calcium, PTH, creatinine, 1,25OH‐ and 25OH‐vitamin D were measured, and CCCR was calculated.

Results

24hUCa and CCCR were significantly lower in patients on thiazides (P = 0·02 and P = 0·0068, resp.), and serum creatinine was significantly higher in those subjects (P < 0·0001). Serum Ca levels only proved different in an analysis of covariance among patients younger than 60 years (P = 0·003). Nevertheless, PTH was not different in both groups (P = 0·917).

Conclusions

According to recently published guidelines, 24hUCa measurement is necessary to give indication for surgery in asymptomatic patients and to distinguish between PHPT and familial hypocalciuric hypercalcaemia [FHH]. Thiazides significantly decrease 24hUCa, yet neither increase serum Ca nor influence PTH levels in patients with PHPT. However, discontinuing thiazides is crucial for a correct CCCR calculation to pre‐operatively rule out FHH. As a consequence, the withdrawal of thiazide medication must be recommended for the diagnosis of PHPT prior to surgery.
α‐ketoglutarate is associated with delayed wound healing in diabetes
Authors: Tan Qin , Wang Wei , Yang Chuan , Zhang Jinglu , Sun Kan , Luo Heng cong , Mai Li fang , Lao Yu , Yan Li , Ren Meng
Published: February 2016

Aim

A high level of matrix metalloproteinase 9 (MMP‐9) is a predictor of poor wound healing in diabetic foot ulcers. In skin keratinocytes, site‐specific DNA demethylation plays an important role in MMP‐9 expression. Ten‐eleven translocation enzyme 2 (TET2) protein, one member of TET family, could rely on α‐ketoglutarate (α‐KG) as cosubstrate to exhibit catalytic activity of DNA demethylation. Here, we aimed to explore the changes of α‐KG and its relationship with MMP‐9 and TET2 during diabetic wound healing.

Methods

Seventy‐one cases of patients with diabetic foot ulcers and 53 cases of nondiabetic ulcers were enrolled. Serum, urine and wound fluids were collected for measurement of α‐KG levels and MMP‐9 expression. Skin tissues were collected for the measurement of TET2 and MMP‐9 expression. Clinical parameters were collected, and transcutaneous oxygen pressure (TcPO2) levels of feet were detected.

Results

The levels of α‐KG, TET2 and MMP‐9 were significantly increased in diabetic wound compared with nondiabetic wound (P = 0·010, 0·016 and 0·025). There was a significant correlation between a low TcPO2 and a high α‐KG level of wound fluids (r = −0·395, P = 0·002). Further analysis showed that α‐KG concentration had a positive correlation with both haemoglobin A1c (HbA1C) and 2 h postprandial blood glucose (PBG) (r = 0·393, P = 0·005; r = 0·320, P = 0·025, respectively).

Conclusions

The levels of α‐KG, TET2 and MMP‐9 were significantly increased in diabetic wound compared with nondiabetic wound. Elevated α‐KG was related to local hypoxia ischaemia status and systematic poor glycaemic control.
Ribonucleic acid sequencing data mining: A new tool for understanding neuroimmunological conditions
Authors: Sato Wakiro , Yamamura Takashi
Published: February 2016

RNA sequencing is a next‐generation sequencing‐based approach for comprehensive gene expression analysis. The “big data’’ of RNA sequencing have been deposited in public databases. Two recent studies attempted to use such data to answer clinically relevant questions pertaining to neuroimmunology.
Astrocyte‐intrinsic regulation of central nervous system inflammation and neurodegeneration
Authors: Rothhammer Veit , Quintana Francisco J.
Published: February 2016

Astrocytes constitute the majority of cells in the mammalian brain, where they carry out fine‐tuned tasks that include, for example, the formation of the blood–brain barrier, the provision of structural support, the regulation of ion homeostasis and neurotransmitter recycling, and the modulation of neuronal function. In the context of autoimmune inflammation in the central nervous system during multiple sclerosis, these and other functions are challenged, while astrocytes modulate the local inflammatory response not only by regulating the blood–brain barrier permeability, but also by controlling the recruitment and activation of inflammatory cells and neurotoxicity. In the present review, we discuss astrocyte‐intrinsic mechanisms that affect multiple sclerosis pathology and might provide potential targets for therapeutic intervention.
Economic Analysis and Species at Risk: Lessons Learned and Future Challenges
Authors: Adamowicz Wiktor L. (Vic)
Published: February 2016

The Canadian Species at Risk Act (SARA) has been in existence for 13 years. It was, and in many ways continues to be, controversial. The U.S. Endangered Species Act (ESA) originated in 1973 and has also been controversial. In the 1990s, concerns were raised by economists in Canada and the United States on the design of endangered species (ES) policy. Their concerns surrounded the reconsideration of the ESA and the establishment of SARA. What have we learned since the implementation of SARA over this time? How has the U.S. experience with the ESA informed SARA and its approach? How has the role of economic analysis in ES policy evolved? What continue to be the challenges and what are the opportunities? This paper reviews the concerns raised in the past, and evaluates the lessons learned regarding economics and ES. The unique aspects of the economic analysis of ES problems relative to other environmental concerns are outlined. The paper concludes with a discussion of ways to lessen the tension in debate about the role of economics in ES policy, and embrace the potential for more effective policy analysis and design through integration of economic analysis into conservation policy.

Au Canada, la Loi sur les espèces en péril (LEP) est entrée en vigueur il y a 13 ans. Elle avait soulevé la controverse et, à certains égards, c'est encore le cas. Aux États‐Unis, l'Endangered Species Act (ESA – loi sur les espèces en voie de disparition) a vu le jour en 1973 et a aussi fait l'objet de controverse. Au cours des années 1990, des économistes canadiens et américains ont exprimé des préoccupations au sujet de la conception des politiques visant à protéger les espèces en voie de disparition. Leurs préoccupations ont mené à un réexamen de l'ESA et à la mise en œuvre de la LEP. Quelles leçons avons‐nous apprises depuis la mise en œuvre de la LEP? De quelle façon l'expérience des États‐Unis avec l'ESA a‐t‐elle influencé l’élaboration de la LEP et sa stratégie? De quelle façon le rôle de l'analyse économique des politiques visant à protéger les espèces en voie de disparition a‐t‐il évolué? Quels sont, encore aujourd'hui, les défis à relever et les occasions à saisir? Le présent article passe en revue les préoccupations passées et examine les leçons apprises concernant l’économie et les espèces en voie de disparition. Il met en lumière les caractéristiques uniques de l'analyse économique des problèmes liés aux espèces en voie de disparition comparativement à d'autres préoccupations environnementales. Il inclut une discussion sur les façons d'atténuer les tensions dans le débat sur le rôle de l’économie dans l’élaboration des politiques visant à protéger les espèces en voie de disparition et accueille la possibilité de procéder à l'analyse et à la conception efficaces de politiques grâce à l'intégration de l'analyse économique dans l’élaboration des politiques de la conservation.—
Competition in Canada's Agricultural Value Chains: The Case of Grain
Authors: Brewin Derek G.
Published: February 2016

To open this address, I would like to advocate for membership in the Canadian Agricultural Economics Society (CAES). The fact that applied economics offers theory and methods that help us address topics as diverse as the Canadian grain value chain and the economics of species at risk speaks well for the future of our discipline. There is a vast array of work for us to do. Membership in the CAES offers an excellent link to the most up‐to‐date research in this area through our journal and conferences. Every society I attend inspires me to examine my own research and look at problems in new ways using new tools I learned from presentations made by the members of CAES. The main message of my address is to promote the application of Game Theory strategies as a way to understand behavior in the grain value chain. These tools are already being applied in areas as different as optimizing tradable systems of environmental goods and assessing competitive behavior in beef packing.

Tout d'abord, je tiens à mentionner que j'appuie l'adhésion à la Société canadienne d'agroéconomie (SCAE). Le fait que l’économie appliquée offre la théorie et les méthodes qui nous aident à examiner des sujets aussi variés que la chaîne de valeur des grains du Canada et l’économie des espèces en péril augure bien pour l'avenir de notre discipline. La diversité du travail à accomplir est immense. Être membre de la SCAE procure un lien privilégié à la recherche de pointe grâce à notre Revue et à nos conférences. Aujourd'hui, mon message vise principalement à promouvoir l'application des stratégies de la théorie des jeux pour comprendre le comportement au sein de la chaîne de valeur des grains. Certains domaines, tels que l'optimisation des systèmes d’échange des biens environnementaux et l’évaluation du comportement concurrentiel dans le secteur du conditionnement du bœuf, utilisent déjà ces outils. La panoplie d'outils à notre disposition est mise en valeur dans notre Revue et lors de nos congrès. Tous les congrès auxquels j'assiste me motivent à examiner ma propre recherche et à analyser les problèmes sous un angle différent grâce aux nouveaux outils mis au point et présentés par les membres de la SCAE.
Treatment of perianal fistula in Crohn's disease: a systematic review and meta‐analysis comparing seton drainage and anti‐tumour necrosis factor treatment
Authors: de Groof E. J. , Sahami S. , Lucas C. , Ponsioen C. Y. , Bemelman W. A. , Buskens C. J.
Published: February 2016

Aim

The introduction of anti‐tumour necrosis factor (anti‐TNF; infliximab and adalimumab) has changed the management of Crohn's perianal fistula from almost exclusively surgical treatment to one with a much larger emphasis on medical therapy. The aim of this systematic review was to provide an overview of the success rates of setons and anti‐TNF for Crohn's perianal fistula.

Method

Studies evaluating the effect of setons and anti‐TNF on Crohn's perianal fistula were included. Studies assessing perianal fistula in children, rectovaginal and rectourinary fistulae were excluded. The primary end‐point was the fistula closure rate. Partial closure and recurrence rates were secondary end‐points.

Results

Ten studies on seton drainage were included (n = 305). Complete closure varied from 13.6% to 100% and recurrence from 0% to 83.3%. In 34 anti‐TNF studies (n = 1449), complete closure varied from 16.7% and 93% (partial closure 8.0–91.2%) and recurrence from 8.0% to 40.9%. Four randomized controlled trials (n = 1028) comparing anti‐TNF with placebo showed no significant difference in complete or partial closure in meta‐analysis (risk difference 0.12, 95% CI −0.06 to 0.30 and 0.09, 95% CI −0.23 to 0.41, respectively). Subgroup analysis (n = 241) showed a significant advantage for complete fistula closure with anti‐TNF in two trials with follow‐up > 4 weeks (46% vs 13%, P = 0.003 and 30% vs 13%, P = 0.03). Of four included cohort studies, two revealed a significant difference in response in favour of combined treatment (P = 0.001 and P = 0.014).

Conclusion

Closure and recurrence rates after seton drainage as well as anti‐TNF vary widely. Despite a large number of studies, no conclusions can be drawn regarding the preferred strategy. However, combination therapy with (temporary) seton drainage, immunomodulators and anti‐TNF may be beneficial in achieving perianal fistula closure.
Function and clinical implications of short‐chain fatty acids in patients with mixed refractory constipation
Authors: Shi Y. , Chen Q. , Huang Y. , Ni L. , Liu J. , Jiang J. , Li N.
Published: February 2016

Aim

The present study was designed to investigate the function and clinical implications of stool short‐chain fatty acids (SCFAs) in patients with mixed refractory constipation.

Method

Ascending colon specimens obtained from 30 patients with ascending colon cancer were regarded as the control group. Ascending colon specimens obtained from patients with mixed refractory constipation were regarded as the experimental group and were divided into three subgroups, according to Wexner scores [A constipation scoring system to simplify evaluation and management of constipated patients. Dis Colon Rectum 1996; 39: 681–5] of 16–20, 21–25 and 26–30, with 30 patients in each group. The stool SCFAs were extracted and quantitatively analysed using gas chromatography‐mass spectrometry (GC‐MS). The expression of G protein‐coupled receptor 43 (GPR43) and of choline acetyltransferase (ChAT) were detected by immunofluorescence, reverse transcription‐polymerase chain reaction (RT‐PCR) and western blotting of colon samples.

Results

The levels of acetate, propionate and butyrate were significantly lower in the experimental group than in the control group (P < 0.05). Compared with the control group, the densitometric quantification and mean density of GPR43 and ChAT proteins, and expression of GPR43 and CHAT genes, were significantly decreased in the patients with mixed refractory constipation (P < 0.05).

Conclusion

In the patients with mixed refractory constipation, the levels of stool SCFAs, including acetate, propionate and butyrate, as well as the levels of GPR43 and ChAT expressed in the colon, which were all negatively correlated with the Wexner score, were decreased and may be associated with the pathogenesis of mixed refractory constipation.
4D left ventricular resultant wall motion and blood flow assessed by phase‐shift velocity mapping at high‐field 3T MRI
Authors: Samnøy Stig F. , Cuypers Jochem , Greve Gottfried , Larsen Terje H.
Published: February 2016

Background

Contractility and elasticity of the myocardium are important variables for detecting anomalies that may influence pump function. It is important to assess both wall motion and blood flow to detect regional left ventricular (LV) dysfunction and abnormal flow patterns. This study discusses four‐dimensional (4D) phase‐contrast magnetic resonance imaging (MRI) for simultaneous quantification and visualization of LV wall motion and blood flow.

Methods

In thirteen healthy subjects, a three‐directional retrospective cardiac triggered phase‐shift velocity mapping technique was used to acquire velocity data of the LV throughout the cardiac cycle. All short‐axis slices of the LV wall were segmented in six sectors of 60° starting from the anterior hinge point between the right and left ventricles, from base to apex. Velocity data in resultant, radial, circumferential and longitudinal directions were calculated and presented as coloured three‐directional vectors.

Results

Our findings showed a reduction in maximum wall velocities from base to apex, whereas for the radial and circumferential directions no significant differences were noted (13·1 ± 2·7 and 13·0 ± 2·9 cm s−1, respectively. P = 0·9). The longitudinal maximum velocities (21·0 ± 0·6 cm s−1) were significantly higher than the radial and circumferential components (P = 0·002). We found that the inclination angle of the resultant blood flow was changed towards the left ventricular outflow tract during systole.

Conclusions

Using this 4D MRI velocity mapping technique, we present an improved method for quantification and visualization of ventricular wall velocities in the radial, circumferential and longitudinal directions, as well as for the intracavity blood flow.
Visualization of Innovation in Global Supply Chain Networks
Authors: Basole Rahul C. , Bellamy Marcus A. , Park Hyunwoo
Published: February 2016

This methodological note identifies and describes a data‐driven visualization approach to study innovations in supply chain networks (ISCN). We demonstrate its value and applicability with illustrative examples to pertinent structure‐related ISCN research questions in the global electronics industry. Our visualization approach can be used to reveal and understand important clusters, patterns, trends, and outliers of ISCN not necessarily identified with traditional methods. The broader aim of this note is to demonstrate the complementary value of emerging visual analytic approaches in managerial decision‐making contexts and describe how actionable insights can be achieved.
Learning the association between a context and a target location in infancy
Authors: Bertels Julie , San Anton Estibaliz , Gebuis Titia , Destrebecqz Arnaud
Published: February 2016

Extracting the statistical regularities present in the environment is a central learning mechanism in infancy. For instance, infants are able to learn the associations between simultaneously or successively presented visual objects (Fiser & Aslin, ; Kirkham, Slemmer & Johnson, ). The present study extends these results by investigating whether infants can learn the association between a target location and the context in which it is presented. With this aim, we used a visual associative learning procedure inspired by the contextual cuing paradigm, with infants from 8 to 12 months of age. In two experiments, in which we varied the complexity of the stimuli, we first habituated infants to several scenes where the location of a target (a cartoon character) was consistently associated with a context, namely a specific configuration of geometrical shapes. Second, we examined whether infants learned the covariation between the target location and the context by measuring looking times at scenes that either respected or violated the association. In both experiments, results showed that infants learned the target–context associations, as they looked longer at the familiar scenes than at the novel ones. In particular, infants selected clusters of co‐occurring contextual shapes and learned the covariation between the target location and this subset. These results support the existence of a powerful and versatile statistical learning mechanism that may influence the orientation of infants’ visual attention toward areas of interest in their environment during early developmental stages. A video abstract of this article can be viewed at: https://www.youtube.com/watch?v=9Hm1unyLBn0
Some Reflections on the Ubiquity of Regulation
Authors: Capie Forrest , Wood Geoffrey
Published: February 2016

The authors argue, using historical examples from finance, the production of wine and music, that competition within the rule of law, without government regulation, produces desirable outcomes.
Energy Policy: The Return of the Regulatory State
Authors: Robinson Colin
Published: February 2016

Energy is regulated by the state in most countries. The United Kingdom had a period, around the turn of the present century, when traditional regulation was reduced and the energy sector was exposed to market forces, but there has since been reversion to the regulatory norm. The recent history of energy policy, especially as it concerns electricity generation, is examined and the stated reasons for having such a policy are discussed: for example, enhancing security of supply, avoiding the effects of fossil fuel price increases and combating future climate change and its effects. These reasons are found to lack substance and a case is made for moving away from centralised action, returning to a much more competitive market with less government intervention.
The Economic Impact and Civic Pride Effects of Sports Teams and Mega‐Events: Do The Public and the Professionals Agree?
Authors: Groothuis Peter A. , Rotthoff Kurt W.
Published: February 2016

Often sports leagues, organising committees, and team owners justify the use of public funds to build sports stadiums by the perceived economic impacts and civic pride generated by the teams or mega‐events. Since the 1980s many economic studies have examined the economic impact and civic pride created by professional sports teams. Most of the economic literature finds sports teams or mega‐events have little or no economic impact, but there are mixed findings on the magnitude of civic pride. Overall, most of the economic literature suggests that the benefits created by sports teams or events do not outweigh the cost of public subsidies provided. We conduct a survey of public opinion on US residents’ perceptions of economic impacts and civic pride benefits from mega‐events such as the Super Bowl and the Winter Olympics. Our study asks the question: Do residents believe that mega‐events and sports teams generate positive economic impacts and civic pride or not? We find that, like economists, the public doubts that public funding of mega‐events is a good idea.
The Thirteenth‐Century Economics of Thomas Aquinas
Authors: Koehler Benedikt
Published: February 2016

In the Middle Ages, discourse on economics, such as it was, proceeded for the most part as an application of theological doctrine. But economic analysis as an independent discipline per se was taking shape in thirteenth‐century scholasticism. This is shown by a review of relevant sections of Thomas Aquinas’ Summa theologiae regarding property rights and the division of labour; wealth and income policies; consumer protection and fair trade; and the distinction between usurious and licit financial returns.
Is The Television Licence fee fit for Purpose in the Digital Era?
Authors: Weeds Helen
Published: February 2016

In the context of the UK's ongoing review of the BBC's Royal Charter, this article discusses the future of the television licence fee. As channels proliferate and new ways of watching television take hold, there is increasing pressure on the TV licence system. Drawing on an analysis of the rationale for public service broadcasting, the article considers whether the licence fee can be adapted to reflect this new world or should be replaced by a different funding model. It concludes that while modernising the TV licence fee to close the ‘iPlayer loophole’ would patch up the current system, it would be preferable to replace the licence fee altogether, perhaps with a household levy. Subscription may be a useful top‐up for non‐essential services where a broad reach is less important. The ban on the carrying of advertising by the BBC should also be reconsidered.