bluuebunny/crossref_metadata_2025 huggingface dataset:
Adhesive contact of the Weierstrass profile
Authors: Afferrante L. , Ciavarella M. , Demelio G.
Published: September 2015

The Weierstrass series was considered in Ciavarellaet al.(Ciavarellaet al.2000Proc. R. Soc. Lond. A456, 387–405. (doi:10.1098/rspa.2000.0522)) to describe a linear contact problem between a rigid fractally rough surface and an elastic half-plane. In such cases, no applied mean pressure is sufficiently large to ensure full contact, and specifically there are not even any contact areas of finite dimension. Later, Gao & Bower (Gao & Bower 2006Proc. R. Soc. A462, 319–348. (doi:10.1098/rspa.2005.1563)) introduced plasticity in the Weierstrass model, but concluded that the fractal limit continued to lead to what they considered unphysical predictions of the true contact size and number of contact spots, similar to the elastic case. In this paper, we deal with the contact problem between rough surfaces in the presence of adhesion with the assumption of a Johnson, Kendall and Roberts (JKR) regime. We find that, for fractal dimensionD>1.5, the presence of adhesion does not qualitatively modify the contact behaviour. However, for fractal dimensionD<1.5, a regularization of the contact area can be observed at a large magnification where the contact area consists of segments of finite size. Moreover, full contact can occur at all scales forD<1.5 provided the mean contact pressure is larger than a certain value. We discuss, however, the implication of our assumption of a JKR regime.
Understanding how porosity gradients can make a better filter using homogenization theory
Authors: Dalwadi M. P. , Griffiths I. M. , Bruna M.
Published: September 2015

Filters whose porosity decreases with depth are often more efficient at removing solute from a fluid than filters with a uniform porosity. We investigate this phenomenon via an extension of homogenization theory that accounts for a macroscale variation in microstructure. In the first stage of the paper, we homogenize the problems of flow through a filter with a near-periodic microstructure and of solute transport owing to advection, diffusion and filter adsorption. In the second stage, we use the computationally efficient homogenized equations to investigate and quantify why porosity gradients can improve filter efficiency. We find that a porosity gradient has a much larger effect on the uniformity of adsorption than it does on the total adsorption. This allows us to understand how a decreasing porosity can lead to a greater filter efficiency, by lowering the risk of localized blocking while maintaining the rate of total contaminant removal.
Prenatal testosterone exposure is related to sexually dimorphic facial morphology in adulthood
Authors: Whitehouse Andrew J. O. , Gilani Syed Zulqarnain , Shafait Faisal , Mian Ajmal , Tan Diana Weiting , Maybery Murray T. , Keelan Jeffrey A. , Hart Roger , Handelsman David J. , Goonawardene Mithran , Eastwood Peter
Published: September 2015

Prenatal testosterone may have a powerful masculinizing effect on postnatal physical characteristics. However, no study has directly tested this hypothesis. Here, we report a 20-year follow-up study that measured testosterone concentrations from the umbilical cord blood of 97 male and 86 female newborns, and procured three-dimensional facial images on these participants in adulthood (range: 21–24 years). Twenty-three Euclidean and geodesic distances were measured from the facial images and an algorithm identified a set of six distances that most effectively distinguished adult males from females. From these distances, a ‘gender score’ was calculated for each face, indicating the degree of masculinity or femininity. Higher cord testosterone levels were associated with masculinized facial features when males and females were analysed together (
n
= 183;
r
= −0.59), as well as when males (
n
= 86;
r
= −0.55) and females (
n
= 97;
r
= −0.48) were examined separately (
p
-values < 0.001). The relationships remained significant and substantial after adjusting for potentially confounding variables. Adult circulating testosterone concentrations were available for males but showed no statistically significant relationship with gendered facial morphology (
n
= 85,
r
= 0.01,
p
= 0.93). This study provides the first direct evidence of a link between prenatal testosterone exposure and human facial structure.
‘Selfish herds’ of guppies follow complex movement rules, but not when information is limited
Authors: Kimbell Helen S. , Morrell Lesley J.
Published: September 2015

Under the threat of predation, animals can decrease their level of risk by moving towards other individuals to form compact groups. A significant body of theoretical work has proposed multiple movement rules, varying in complexity, which might underlie this process of aggregation. However, if and how animals use these rules to form compact groups is still not well understood, and how environmental factors affect the use of these rules even less so. Here, we evaluate the success of different movement rules, by comparing their predictions with the movement seen when shoals of guppies (Poecilia reticulata) form under the threat of predation. We repeated the experiment in a turbid environment to assess how the use of the movement rules changed when visual information is reduced. During a simulated predator attack, guppies in clear water used complex rules that took multiple neighbours into account, forming compact groups. In turbid water, the difference between all rule predictions and fish movement paths increased, particularly for complex rules, and the resulting shoals were more fragmented than in clear water. We conclude that guppies are able to use complex rules to form dense aggregations, but that environmental factors can limit their ability to do so.
Antisocial pool rewarding does not deter public cooperation
Authors: Szolnoki Attila , Perc Matjaž
Published: September 2015

Rewarding cooperation is in many ways expected behaviour from social players. However, strategies that promote antisocial behaviour are also surprisingly common, not just in human societies, but also among eusocial insects and bacteria. Examples include sanctioning of individuals who behave prosocially, or rewarding of free-riders who do not contribute to collective enterprises. We therefore study the public goods game with antisocial and prosocial pool rewarding in order to determine the potential negative consequences on the effectiveness of positive incentives to promote cooperation. Contrary to a naive expectation, we show that the ability of defectors to distribute rewards to their like does not deter public cooperation as long as cooperators are able to do the same. Even in the presence of antisocial rewarding, the spatial selection for cooperation in evolutionary social dilemmas is enhanced. Since the administration of rewards to either strategy requires a considerable degree of aggregation, cooperators can enjoy the benefits of their prosocial contributions as well as the corresponding rewards. Defectors when aggregated, on the other hand, can enjoy antisocial rewards, but due to their lack of contributions to the public good they ultimately succumb to their inherent inability to secure a sustainable future. Strategies that facilitate the aggregation of akin players, even if they seek to promote antisocial behaviour, thus always enhance the long-term benefits of cooperation.
Thalassotalea marina sp. nov., isolated from a marine recirculating aquaculture system, reclassification of Thalassomonas eurytherma as Thalassotalea eurytherma comb. nov. and emended description of the genus Thalassotalea
Authors: Hou Ting-Ting , Liu Ying , Zhong Zhi-Ping , Liu Hong-Can , Liu Zhi-Pei
Published: September 2015

A Gram-stain-negative, facultatively anaerobic bacterium, strain QBLM2T, was isolated from rearing water of a marine recirculating aquaculture system in Tianjin, China. Its taxonomic position was investigated through a polyphasic approach. Cells of strain QBLM2T were non-spore-forming rods, motile by means of a single polar flagellum. Positive for oxidase and catalase. Growth occurred at 15–40 °C (optimum 30 °C), at pH 6.5–10.5 (optimum pH 7.5–8.5) and in the presence of 0–5.0 % (w/v) NaCl (optimum 3 %). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain QBLM2T formed a distinct lineage within the genus Thalassotalea and exhibited sequence similarities of 94.5–96.3 % to members of the genus Thalassotalea. The predominant fatty acids (>10 %) were C17 : 1ω8c and summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c). The major polar lipids were phosphatidylglycerol and phosphatidylethanolamine. Ubiquinone 8 (Q-8) was the major ubiquinone. The DNA G+C content was 37.1 mol%. Based on the data above, strain QBLM2T is considered to represent a novel species of the genus Thalassotalea, for which the name Thalassotalea marina sp. nov. is proposed. The type strain is QBLM2T ( = CGMCC 1.12814T = KCTC 42731T). Phylogenetic analyses indicated that Thalassomonas eurytherma Za6a-12T fell within the genus Thalassotalea, so it is reclassified as Thalassotalea eurytherma comb. nov. and the description of the genus Thalassotalea is emended.
Tracking vaginal, anal and oral infection in a mouse papillomavirus infection model
Authors: Hu Jiafen , Budgeon Lynn R. , Cladel Nancy M. , Balogh Karla , Myers Roland , Cooper Timothy K. , Christensen Neil D.
Published: September 2015

Noninvasive and practical techniques to longitudinally track viral infection are sought after in clinical practice. We report a proof-of-principle study to monitor the viral DNA copy number using a newly established mouse papillomavirus (MmuPV1) mucosal infection model. We hypothesized that viral presence could be identified and quantified by collecting lavage samples from cervicovaginal, anal and oral sites. Nude mice infected at these sites with infectious MmuPV1 were tracked for up to 23 weeks starting at 6 weeks post-infection. Viral DNA copy number was determined by SYBR Green Q-PCR analysis. In addition, we tracked viral DNA load through three complete oestrous cycles to pinpoint whether there was a correlation between the DNA load and the four stages of the oestrous cycle. Our results showed that high viral DNA copy number was reproducibly detected from both anal and cervicovaginal lavage samples. The infection and disease progression were further confirmed by histology, cytology, in situ hybridization, immunohistochemistry and transmission electron microscopy. Interestingly, the viral copy number fluctuated over the oestrous cycle, with the highest level at the oestrus stage, implying that multiple sampling might be necessary to provide a reliable diagnosis. Virus DNA was detected in oral lavage samples at a later time after infection. Lower viral DNA load was found in oral samples when compared with those in anal and vaginal tracts. To our knowledge, our study is the first in vivo study to sequentially monitor papillomavirus infection from mucosal anal, oral and vaginal tracts in a preclinical model.
Suboptimal larval habitats modulate oviposition of the malaria vector mosquitoAnopheles gambiae
Authors: Suh Eunho , Choe Dong-Hwan , Saveer Ahmed M , Zwiebel Laurence J
Published: September 2015

Selection of oviposition sites by gravid females is a critical behavioural preference in the reproductive cycle ofAnopheles gambiae, the principal Afrotropical malaria vector mosquito. Several studies suggest this decision is mediated by semiochemicals associated with potential oviposition sites. To better understand the chemosensory basis of this behaviour and identify compounds that can modulate oviposition, we examined the generally held hypothesis that suboptimal larval habitats give rise to semiochemicals that negatively influence the oviposition preference of gravid females. Dual-choice bioassays indicated that oviposition sites conditioned in this manner do indeed foster significant and concentration dependent aversive effects on the oviposition site selection of gravid females. Headspace analyses derived from aversive habitats consistently noted the presence of dimethyl disulphide (DMDS), dimethyl trisulphide (DMTS) and 6-methyl-5-hepten-2-one (sulcatone) each of which unitarily affectedAn. gambiaeoviposition preference. Electrophysiological assays across the antennae, maxillary palp, and labellum of gravidAn. gambiaerevealed differential responses to these semiochemicals. Taken together, these findings validate the hypothesis in question and suggest that suboptimal environments forAn. gambiaelarval development results in the release of DMDS, DMTS and sulcatone that impact the response valence of gravid females to directly modulate the chemical ecology of oviposition site selection.
Speciation driven by hybridization and chromosomal plasticity in a wild yeast
Authors: Leducq Jean-Baptiste , Nielly-Thibault Lou , Charron Guillaume , Eberlein Chris , Verta Jukka-Pekka , Samani Pedram , Sylvester Kayla , Hittinger Chris Todd , Bell Graham , Landry Christian R
Published: September 2015

Hybridization is recognized as a powerful mechanism of speciation and a driving force in generating biodiversity. However, only few multicellular species, limited to a handful of plants and animals, have been shown to fulfill all the criteria of homoploid hybrid speciation. This lack of evidence could lead to the misconception that speciation by hybridization has a limited role in eukaryotes, particularly in single-celled organisms. Laboratory experiments have revealed that fungi such as budding yeasts can rapidly develop reproductive isolation and novel phenotypes through hybridization, showing that in principle homoploid speciation could occur in nature. Here we report a case of homoploid hybrid speciation in natural populations of the budding yeastSaccharomyces paradoxusinhabiting the North American forests. We show that the rapid evolution of chromosome architecture and an ecological context that led to secondary contact between nascent species drove the formation of an incipient hybrid species with a potentially unique ecological niche.

One Sentence Summary

Chromosomal rearrangements and hybridization between two yeast lineages drive hybrid speciation after secondary contact.
Formulation screening by differential scanning fluorimetry: how often does it work?
Authors: Ristic Marko , Rosa Nicholas , Seabrook Shane A. , Newman Janet
Published: September 2015

There is strong evidence to suggest that a protein sample needs to be well folded and uniform in order to form protein crystals, and it is accepted knowledge that the formulation can have profound effects on the behaviour of the protein sample. The technique of differential scanning fluorimetry (DSF) is a very accessible method to determine protein stability as a function of the formulation chemistry and the temperature. A diverse set of 252 soluble protein samples was subjected to a standard formulation-screening protocol using DSF. Automated analysis of the DSF results suggest that in over 35% of cases buffer screening significantly increases the stability of the protein sample. Of the 28 standard formulations tested, three stood out as being statistically better than the others: these included a formulation containing the buffer citrate, long known to be `protein friendly'; bis-tris and ADA were also identified as being very useful buffers in protein formulations.
Structure of the HECT domain of human WWP2
Authors: Gong Wei , Zhang Xiaodan , Zhang Wen , Li Jie , Li Ze
Published: September 2015

WWP2 is a HECT-domain ubiquitin ligase of the Nedd4 family, which is involved in various important biological processes, such as protein degradation, membrane-protein sorting and transportation, the immune response, pluripotency of embryonic stem cells, tumourigenesis and metastasis. The HECT domain provides the intrinsic ubiquitin ligase activity of WWP2. Here, the expression, purification, crystallization and crystallographic analysis of the HECT domain of human WWP2 (HECTWWP2) are reported. HECTWWP2 has been crystallized and the crystals diffracted to 2.50 Å resolution. They belonged to space group P41212 and the structure has been solved via molecular replacement. The overall structure of HECTWWP2 has an inverted T-shape. This structure displays a high degree of conservation with previously published structures of Nedd4 subfamily members.
High-resolution structures ofLactobacillus salivariustransketolase in the presence and absence of thiamine pyrophosphate
Authors: Lukacik Petra , Lobley Carina M. C. , Bumann Mario , Arena de Souza Victoria , Owens Raymond J. , O'Toole Paul W. , Walsh Martin A.
Published: September 2015

Probiotic bacterial strains have been shown to enhance the health of the host through a range of mechanisms including colonization, resistance against pathogens, secretion of antimicrobial compounds and modulation of the activity of the innate immune system.Lactobacillus salivariusUCC118 is a well characterized probiotic strain which survives intestinal transit and has many desirable host-interaction properties. Probiotic bacteria display a wide range of catabolic activities, which determine their competitivenessin vivo. Some lactobacilli are heterofermentative and can metabolize pentoses, using a pathway in which transketolase and transaldolase are key enzymes.L. salivariusUCC118 is capable of pentose utilization because it encodes the key enzymes on a megaplasmid. The crystal structures of the megaplasmid-encoded transketolase with and without the enzyme cofactor thiamine pyrophosphate have been determined. Comparisons with other known transketolase structures reveal a high degree of structural conservation in both the catalytic site and the overall conformation. This work extends structural knowledge of the transketolases to the industrially and commercially importantLactobacillusgenus.
Structure of the dual-function fructose-1,6/sedoheptulose-1,7-bisphosphatase from Thermosynechococcus elongatus bound with sedoheptulose-7-phosphate
Authors: Cotton Charles A. R. , Kabasakal Burak V. , Miah Nishat A. , Murray James W.
Published: September 2015

The dual-function fructose-1,6/sedoheptulose-1,7-bisphosphatase (FBP/SBPase) in cyanobacteria carries out two activities in the Calvin cycle. Structures of this enzyme from the cyanobacterium Synechocystis sp. PCC 6803 exist, but only with adenosine monophosphate (AMP) or fructose-1,6-bisphosphate and AMP bound. The mechanisms which control both selectivity between the two sugars and the structural mechanisms for redox control are still unresolved. Here, the structure of the dual-function FBP/SBPase from the thermophilic cyanobacterium Thermosynechococcus elongatus is presented with sedoheptulose-7-phosphate bound and in the absence of AMP. The structure is globally very similar to the Synechocystis sp. PCC 6803 enzyme, but highlights features of selectivity at the active site and loop ordering at the AMP-binding site. Understanding the selectivity and control of this enzyme is critical for understanding the Calvin cycle in cyanobacteria and for possible biotechnological application in plants.
Stabilization of porcine pancreatic elastase crystals by glutaraldehyde cross-linking
Authors: Hofbauer Stefan , Brito José A. , Mulchande Jalmira , Nogly Przemyslaw , Pessanha Miguel , Moreira Rui , Archer Margarida
Published: September 2015

Elastase is a serine protease from the chymotrypsin family of enzymes with the ability to degrade elastin, an important component of connective tissues. Excessive elastin proteolysis leads to a number of pathological diseases. Porcine pancreatic elastase (PPE) is often used for drug development as a model for human leukocyte elastase (HLE), with which it shares high sequence identity. Crystals of PPE were grown overnight using sodium sulfate and sodium acetate at acidic pH. Cross-linking the crystals with glutaraldehyde was needed to resist the soaking procedure with a diethyl N-(methyl)pyridinyl-substituted oxo-β-lactam inhibitor. Crystals of PPE bound to the inhibitor belonged to the orthorhombic space group P212121, with unit-cell parameters a = 51.0, b = 58.3, c = 74.9 Å, and diffracted to 1.8 Å resolution using an in-house X-ray source.
Dynamic modeling of sustainable operation in green manufacturing environment
Authors: Orji Ifeyinwa Juliet , Wei Sun
Published: September 2015

Purpose

– Globally, supply chains compete in a complex and rapidly changing environment. Hence, sustainable supplier selection has become a decisive variable in the firm’s financial success. This requires reliable tools and techniques to enhance understanding on how supplier behavior evolves with time and to select the best sustainable supplier. System dynamics (SD) is an approach to investigate the dynamic behavior in which the system alterations correspond to the system variable changes. Fuzzy logic usually solves the challenges of imprecise data and ambiguous human judgment. The paper aims to discuss these issues.

Design/methodology/approach

– This work presents a novel modeling approach for integrating information on supplier behavior in fuzzy environment with SD simulation modeling technique. This results in a more reliable and responsible decision-support system. Supplier behavior with respect to relevant sustainability criteria were sourced through expert interviews and simulated in Vensim to select the best possible sustainable supplier. The simulation runs were carried out in four scenarios, namely, past, current, future and average time horizon for four different suppliers. A multi-criteria decision-making model was presented to compare results from the systems dynamics model.

Findings

– An increase in the rate of investment in sustainability by the different suppliers causes an exponential increase in total sustainability performance of the suppliers. The growth rate of the total performance of suppliers outruns their rate of investment in sustainability after about 12 months.

Originality/value

– While a significant work exists regarding supplier selection, little work has been found that investigates how to insure sustainable suppliers maintain their status for a long period of time.
Spatial overlap in a solitary carnivore: support for the land tenure, kinship or resource dispersion hypotheses?
Authors: Elbroch L. Mark , Lendrum Patrick E. , Quigley Howard , Caragiulo Anthony
Published: September 2015

There are several alternative hypotheses about the effects of territoriality, kinship and prey availability on individual carnivore distributions within populations. The first is the land‐tenure hypothesis, which predicts that carnivores regulate their density through territoriality and temporal avoidance. The second is the kinship hypothesis, which predicts related individuals will be clumped within populations, and the third is the resource dispersion hypothesis, which suggests that resource richness may explain variable sociality, spatial overlap or temporary aggregations of conspecifics.

Research on the socio‐spatial organization of animals is essential in understanding territoriality, intra‐ and interspecific competition, and contact rates that influence diverse ecology, including disease transmission between conspecifics and courtship behaviours.

We explored these hypotheses with data collected on a solitary carnivore, the cougar (Puma concolor), from 2005 to 2012 in the Southern Yellowstone Ecosystem, Wyoming, USA. We employed 27 annual home ranges for 13 cougars to test whether home range overlap was better explained by land tenure, kinship, resource dispersion or some combination of the three.

We found support for both the land tenure and resource dispersion hypotheses, but not for kinship. Cougar sex was the primary driver explaining variation in home range overlap. Males overlapped significantly with females, whereas the remaining dyads (F–F, M–M) overlapped significantly less. In support for the resource dispersion hypothesis, hunting opportunity (the probability of a cougar killing prey in a given location) was often higher in overlapping than in non‐overlapping portions of cougar home ranges. In particular, winter hunt opportunity rather than summer hunt opportunity was higher in overlapping portions of female–female and male–female home ranges.

Our results may indicate that solitary carnivores are more tolerant of sharing key resources with unrelated conspecifics than previously believed, or at least during periods of high resource availability. Further, our results suggest that the resource dispersion hypothesis, which is typically applied to social species, is applicable in describing the spatial organization of solitary carnivores.
Nonparametric Bayes Modeling for Case Control Studies with Many Predictors
Authors: Zhou Jing , Herring Amy H. , Bhattacharya Anirban , Olshan Andrew F. , Dunson David B. ,   The National Birth Defects Prevention Study
Published: September 2015

It is common in biomedical research to run case-control studies involving high-dimensional predictors, with the main goal being detection of the sparse subset of predictors having a significant association with disease. Usual analyses rely on independent screening, considering each predictor one at a time, or in some cases on logistic regression assuming no interactions. We propose a fundamentally different approach based on a nonparametric Bayesian low rank tensor factorization model for the retrospective likelihood. Our model allows a very flexible structure in characterizing the distribution of multivariate variables as unknown and without any linear assumptions as in logistic regression. Predictors are excluded only if they have no impact on disease risk, either directly or through interactions with other predictors. Hence, we obtain an omnibus approach for screening for important predictors. Computation relies on an efficient Gibbs sampler. The methods are shown to have high power and low false discovery rates in simulation studies, and we consider an application to an epidemiology study of birth defects.
A Two-Step Semiparametric Method to Accommodate Sampling Weights in Multiple Imputation
Authors: Zhou Hanzhi , Elliott Michael R. , Raghunathan Trviellore E.
Published: September 2015

Multiple imputation (MI) is a well-established method to handle item-nonresponse in sample surveys. Survey data obtained from complex sampling designs often involve features that include unequal probability of selection. MI requires imputation to be congenial, that is, for the imputations to come from a Bayesian predictive distribution and for the observed and complete data estimator to equal the posterior mean given the observed or complete data, and similarly for the observed and complete variance estimator to equal the posterior variance given the observed or complete data; more colloquially, the analyst and imputer make similar modeling assumptions. Yet multiply imputed data sets from complex sample designs with unequal sampling weights are typically imputed under simple random sampling assumptions and then analyzed using methods that account for the sampling weights. This is a setting in which the analyst assumes more than the imputer, which can led to biased estimates and anti-conservative inference. Less commonly used alternatives such as including case weights as predictors in the imputation model typically require interaction terms for more complex estimators such as regression coefficients, and can be vulnerable to model misspecification and difficult to implement. We develop a simple two-step MI framework that accounts for sampling weights using a weighted finite population Bayesian bootstrap method to validly impute the whole population (including item nonresponse) from the observed data. In the second step, having generated posterior predictive distributions of the entire population, we use standard IID imputation to handle the item nonresponse. Simulation results show that the proposed method has good frequentist properties and is robust to model misspecification compared to alternative approaches. We apply the proposed method to accommodate missing data in the Behavioral Risk Factor Surveillance System when estimating means and parameters of regression models.
Actions of the dual FAAH/MAGL inhibitor JZL195 in a murine neuropathic pain model
Authors: Adamson Barnes Nicholas S. , Mitchell Vanessa A. , Kazantzis Nicholas P. , Vaughan Christopher W.
Published: September 2015

Background and Purpose

While cannabinoids have been proposed as a potential treatment for neuropathic pain, they have limitations. Cannabinoid receptor agonists have good efficacy in animal models of neuropathic pain; they have a poor therapeutic window. Conversely, selective fatty acid amide hydrolase (FAAH) inhibitors that enhance the endocannabinoid system have a better therapeutic window, but lesser efficacy. We examined whether JZL195, a dual inhibitor of FAAH and monacylglycerol lipase (MAGL), could overcome these limitations.

Experimental Approach

C57BL/6 mice underwent the chronic constriction injury (CCI) model of neuropathic pain. Mechanical and cold allodynia, plus cannabinoid side effects, were assessed in response to systemic drug application.

Key Results

JZL195 and the cannabinoid receptor agonist WIN55212 produced dose‐dependent reductions in CCI‐induced mechanical and cold allodynia, plus side effects including motor incoordination, catalepsy and sedation. JZL195 reduced allodynia with an ED50 at least four times less than that at which it produced side effects. By contrast, WIN55212 reduced allodynia and produce side effects with similar ED50s. The maximal anti‐allodynic effect of JZL195 was greater than that produced by selective FAAH, or MAGL inhibitors. The JZL195‐induced anti‐allodynia was maintained during repeated treatment.

Conclusions and Implications

These findings suggest that JZL195 has greater anti‐allodynic efficacy than selective FAAH, or MAGL inhibitors, plus a greater therapeutic window than a cannabinoid receptor agonist. Thus, dual FAAH/MAGL inhibition may have greater potential in alleviating neuropathic pain, compared with selective FAAH and MAGL inhibitors, or cannabinoid receptor agonists.
Effects of cost metric on cost‐effectiveness of protected‐area network design in urban landscapes
Authors: Burkhalter J.C. , Lockwood J.L. , Maslo B. , Fenn K.H. , Leu K.
Published: September 2015

A common goal in conservation planning is to acquire areas that are critical to realizing biodiversity goals in the most cost‐effective manner. The way monetary acquisition costs are represented in such planning is an understudied but vital component to realizing cost efficiencies. We sought to design a protected‐area network within a forested urban region that would protect 17 birds of conservation concern. We compared the total costs and spatial structure of the optimal protected‐area networks produced using three acquisition‐cost surrogates (area, agricultural land value, and tax‐assessed land value). Using the tax‐assessed land values there was a 73% and 78% cost savings relative to networks derived using area or agricultural land value, respectively. This cost reduction was due to the considerable heterogeneity in acquisition costs revealed in tax‐assessed land values, especially for small land parcels, and the corresponding ability of the optimization algorithm to identify lower‐cost parcels for inclusion that had equal value to our target species. Tax‐assessed land values also reflected the strong spatial differences in acquisition costs (US$0.33/m2–$55/m2) and thus allowed the algorithm to avoid inclusion of high‐cost parcels when possible. Our results add to a nascent but growing literature that suggests conservation planners must consider the cost surrogate they use when designing protected‐area networks. We suggest that choosing cost surrogates that capture spatial‐ and size‐dependent heterogeneity in acquisition costs may be relevant to establishing protected areas in urbanizing ecosystems.
Challenging gender stereotypes: Theory of mind and peer group dynamics
Authors: Mulvey Kelly Lynn , Rizzo Michael T. , Killen Melanie
Published: September 2015

To investigate the social cognitive skills related to challenging gender stereotypes, children (N= 61, 3–6 years) evaluated a peer who challenged gender stereotypic norms held by the peer's group. Participants with false belief theory of mind (FBToM) competence were more likely than participants who did not haveFBToM to expect a peer to challenge the group's stereotypes and propose that the group engage in a non‐stereotypic activity. Further, participants withFBToM rated challenging the peer group more positively. Participants withoutFBToM did not differentiate between their own and the group's evaluation of challenges to the group's stereotypic norms, but those with ToM competence asserted that they would be more supportive of challenging the group norm than would the peer group. Results reveal the importance of social‐cognitive competencies for recognizing the legitimacy of challenging stereotypes, and for understanding one's own and other group perspectives.
Three Decades of Policy Layering and Politically Sustainable Reform in theEuropeanUnion's Agricultural Policy
Authors: Daugbjerg Carsten , Swinbank Alan
Published: September 2015

The study of policy reform has tended to focus on single‐stage reforms taking place over a relatively short period. Recent research has drawn attention to gradual policy changes unfolding over extended periods. One strategy of gradual change is layering, in which new policy dimensions are introduced by adding new policy instruments or by redesigning existing ones to address new concerns. The limited research on single‐stage policy reforms highlights that these may not endure in the postenactment phase when circumstances change. We argue that gradual policy layering may create sustainability dynamics that can result in lasting reform trajectories. TheEuropeanUnion'sCommonAgriculturalPolicy (CAP) has changed substantially over the last three decades in response to emerging policy concerns by adding new layers. This succession of reforms proved durable and resilient to reversal in the lead‐up to the 2013CAPreform when institutional and political circumstances changed.
Reduced risk of Efavirenz Discontinuation in Naïve Patients Starting First‐Line Antiretroviral Therapy with Single Tablet versus dual Tablet Regimen
Authors: Fabbiani M , Zaccarelli M , Latini A , Sterrantino G , D'Ettorre G , Grima P , Mondi A , Rossetti B , Borchi B , Giuliani M , Antinori A , De Luca A , Di Giambenedetto S
Published: September 2015

Objectives

Despite not being approved in Europe as first‐line therapy, the efavirenz (EFV)‐containing single tablet regimen (STR) is frequently used in clinical practice in naïve patients but few data are available on this strategy. In our study, we aimed to assess the risk of EFV discontinuation in patients starting antiretroviral therapy with STR vs. nonSTR.

Methods

This was a multicentre study retrospectively enrolling naïve patients starting EFV+TDF+FTC. Patients were followed from the time of treatment initiation to the discontinuation of the EFV‐containing regimen, comparing STR vs. nonSTR. Two different analyses were performed: (A) nonSTR patients censored at the last observation (switch to STR not considered as the end of observation); (B) nonSTR patients censored at the time of switch to STR.

Results

The study included 235 patients, of whom 74 (31.5%) directly started STR. Among patients starting nonSTR, 108 (67.1%) switched to STR after a median period of 6 months. Forty‐four EFV discontinuations were observed (13 among STR vs. 31 among nonSTR patients). The overall estimated probability of discontinuation was 30% at 5 years, about half (14.8%) of these occurring during the first year. Analysis A did not show significant differences between STR and nonSTR regarding the probability of efavirenz discontinuation (19.9% vs. 24.7% at 5 years, P = 0.630). In contrast, Analysis B showed that the probability of EFV discontinuation was similar (8.3%) between STR and nonSTR patients up to 8 months. Thereafter, a significantly higher rate of discontinuation was observed in nonSTR patients (47.5% vs. 19.9% at 5 years, P = 0.034).

Conclusions

Our data suggest that an early switch to STR during the first months of treatment could reduce the risk of EFV discontinuation.
Pemphigus vulgaris: a clinical study of 44 cases over a 20‐year period
Authors: Svecova Danka
Published: September 2015

Background

Pemphigus vulgaris (PV) is a rare, life‐threatening, autoimmune bullous disease with unpredictable progression and prognosis.

Objectives

This study aimed to analyze long‐term outcomes in patients with PV, focusing on factors that may influence the prognosis of the disease, including the phenotype of PV, age at onset, multiplicity of mucosal involvement, relapse and remission rates, and survival functions.

Methods

A retrospective analysis was conducted in 44 patients who were diagnosed and monitored from 1993 to 2012. Statistical analyses were conducted using the Mann–Whitney test and Kruskal–Wallis test. Survival data were analyzed using Kaplan–Meier and log rank tests. Fisher's exact test was used to assess statistical significance at P < 0.05.

Results

A total of 79.5% of patients were identified as having mucocutaneous PV. The female : male gender ratio was 1.58; in severe PV, this increased to 2.8. The difference between the genders in age at onset was statistically significant (P = 0.05). Furthermore, multiple mucosal involvements in the oral cavity and at other sites were associated with severe mucocutaneous PV. Multiple relapses occurred more frequently in patients with severe PV than in those with mild PV (P = 0.001). The remission survival of females was longer than that of males (P = 0.003).

Conclusions

Poor prognosis factors include the severe mucocutaneous type of PV, especially in female patients, and multiple mucosal involvements in the oral cavity and other mucosal sites. Female patients were younger than male patients and were more often observed to have severe mucocutaneous PV and to have a higher median period of remission survival than male patients.
The EGS Guidelines: a surgical approach to glaucoma
Authors: Hommer A.
Published: September 2015

Also the first step in treating glaucoma is medical therapy in most cases there are patients where lasertrabeculoplasty is the appropriate initial treatment. In addition there are patients, where the target pressure could not be reached and/or the disease is progressing despite maximum medical therapy. In consequence of the risk for the visual function incisional surgery is the next therapeutic step. In the presentation EGS recommendations and flow charts for the different glaucoma surgeries will be presented and discussed.
Fundus autofluorescence imaging in White Dot Syndromes
Authors: De Bats F. , Wolff B. , Mathis T. , Scemama Timsit C. , Cahuzac A. , Uzzan J. , Mauget‐Faÿsse M.
Published: September 2015

The term ‘white dot syndromes’ (WDS) refers to several inflammatory diseases of the retina and choroid caused by immune dysregulation. Retinal and choroidal changes observed with multimodal imaging are transient and may disappear quickly in some cases. Multimodal imaging with color fundus photography, fluorescein, indocyanine green angiographies, spectral Domain Optical Coherence Tomography help in identifying the diagnosis. They also help assess the level of inflammatory activity and detect complications. Fundus autofluorescence (AF) imaging is an in vivo imaging method that allows a metabolic mapping of natural or pathological fundus fluorophores. Blue fundus AF imaging is obtained with a confocal laser scanning ophthalmoscope using an excitation short wavelength (SW) at 488 nanometers. In this work, SW‐AF imaging was obtained using a HRA Heidelberg instrument. SW‐AF imaging is an important, non invasive and complementary technique that helps early diagnosis and follow‐up of WDS. The characteristics of the SW‐AF abnormalities are often pathognomonic of each inflammatory disease. Further prospective studies including more patients will be necessary to confirm these results.
General structure of the retina
Authors: Grzybowski A.
Published: September 2015

The invention of the ophthalmoscope in the 19th century led to the development of ophthalmology as a discipline. The retina is an accessible part of the central nervous system and has consequently been studied extensively. There is now a growing use of OCT to obtain information related to brain neurodegenerative disorders like multiple sclerosis, Alzheimer's and Parkinson diseases as well as migraine.

Two aspects of human retinal structure based on physiology and morphology can be distinguished. They are the various retinal layers that consist of either neuron perikarya or neuronal processes. The other, is the distinction between central (macula, fovea) and periphery parts of the retina. Major cell‐types in the retina are pigment epithelial, photoreceptor, horizontal, bipolar, amacrine, ganglion and glial cells and an understanding of their roles in healthy and unhealthy retina remains a challenge. Ocular photoreception for example, was thought to be mediated exclusively by rods and cones until the beginning of the 21st century and only recently have photosensitive retinal ganglion cells (pRGCs) been discovered. The aim is to discuss certain aspects of retinal structure related to function.
Role of SD‐OCT in the follow‐up of a patient with macular edema associated with mucopoysaccharidosis type II (Hunter syndrome) undergoing idursulfase enzyme replacement therapy
Authors: Sanchez J.I. , Ascaso F.J. , Perez I. , Almenara C. , Esteban O. , Martinez M. , Idoate A. , Torralba M.A.
Published: September 2015

Purpose

Purpose: Mucopolysaccharidosis (MPS) type II (Hunter syndrome) is a variable, progressive, multisystem disorder including severe airway obstruction, cardiomyopathy, skeletal deformities and neurological problems. It is an X‐linked recessive disease caused by deficiency of the lysosomal enzyme iduronate‐2‐sulphatase, leading to accumulation of glycosaminoglycans. Several ophthalmological disorders, including corneal opacities, glaucoma and retinal degeneration, have been previously reported. This is the first case of bilateral macular edema associated with MPS II. The patient underwent idursulfase enzyme replacement therapy with good response. We point out the utility of spectral domain optical coherence tomography (SD‐OCT) in the diagnosis and follow‐up of this condition.

Methods

SD‐OCT, fundus autofluorescence and retinography were used in the diagnosis and follow‐up of the visual disorder.

Results

Macular edema was successfully managed with idursulfase enzyme replacement therapy stabilizing visual loss. Central macular thickness measured by SD‐OCT decreased significantly.

Conclusion

Idursulfase enzyme replacement therapy seems to be a good treatment option for macular edema associated with MPS II. Furthermore, SD‐OCT played a key role in the diagnosis and follow‐up of this condition.
TrkB signaling in Müller glia stimulates neuroprotection after optic nerve injury
Authors: Harada T. , Namekata K. , Guo X. , Kimura A. , Harada C.
Published: September 2015

Purpose

Brain‐derived neurotrophic factor (BDNF) is a neurotrophic factor that regulates neural cell survival mainly by activating TrkB receptors. Several lines of evidence support a key role for BDNF‐TrkB signaling in survival of adult retinal ganglion cells (RGCs) in acute and chronic models of optic nerve damage. On the other hand, glial cells have recently attracted considerable attention as mediators of neural cell survival. To further elucidate the role of glial cells in BDNF‐mediated neuroprotection, we examined the effect of optic nerve injury (ONI) on TrkBGFAP KO mice, in which TrkB is deleted in retinal glial cells.

Methods

We examined the effect of ONI in WT and TrkBGFAP KO mice at day (d) 7 and 14 after ONI by spectral‐domain optical coherence tomography (SD‐OCT), retrograde labeling of RGCs, immunohistochemistry and quantitative real‐time PCR analyses.

Results

ONI‐induced RGC loss and retinal degeneration occurred quickly in TrkBGFAP KO mice at d7 after ONI, but the severity was comparable with WT mice at d14. We next examined the effects of ONI on the production of trophic factors in the retina. ONI markedly increased mRNA expression levels of basic fibroblast growth factor (bFGF) in WT mice at d3, but not in TrkBGFAP KO mice. Immunohistochemical analysis at d7 revealed that ONI induced bFGF upregulation mainly in Müller glia. On the other hand, glial cell line‐derived neurotrophic factor (GDNF) expression level was slightly decreased in TrkBGFAP KO mice compared with WT mice at d3, but not at d10.

Conclusions

These results demonstrate that BDNF signaling in retinal glia plays important roles in the early stage of neural protection after traumatic injury. Additionally, our genetic models provide a system in which glia‐specific gene functions can be examined in central nervous system tissues in vivo.
A novel mutation in CNNM4 (G492C) associated with Jalili Syndrome
Authors: Lopez Torres L.T. , Schorderet D. , Valmaggia C. , Todorova M.
Published: September 2015

Purpose

To describe a new G492C homozygous mutation in a consanguineous family from Saudi Arabia with autosomal recessive cone‐rod dystrophy (arCRD) associated with amelogenesis imperfecta and mental deficiency (Jalili syndrome).

Methods

Both parents and their five children were included in the study. They underwent a complete ophthalmic examination including fundus imaging and optical coherence tomography. Both affected children underwent electrophysiological evaluation including full‐field ERG and EOG (ISCEV standard). Direct Sanger sequencing of all exons and intron‐exon junctions of CNNM4 was conducted.

Results

ArCRD was diagnosed in two children with childhood‐onset visual impairment and nystagmus. Ophthalmoscopy showed macular atrophy with pigment mottling, attenuated retinal vasculatur and optic disc pallor. Electrophysiology revealed non‐recordable scotopic and photopic ERGs, completely attenuated off‐response of the on‐off ERG and reduced Arden‐ratio of the EOG. Both affected children showed mental deficiency and had clinical signs of amelogenesis imperfecta presenting with dysplastic, hypomineralized teeth.Sanger sequencing identified a new c.[1474G>T] mutation in CNNM4, located in exon 2 leading to a substitution of the glycine amino acid to cystein at cDNA position 492. This mutation was homozygous in the two affected children and was heterozygous in the unaffected father, mother and both sisters. One unaffected son was homozygous normal.

Conclusions

Genetic testing enabled to confirm the diagnosis of Jalili syndrome by identifying a yet unreported G492C mutation in CNNM4.
Stability in the storm: Is China the perpetrator of global volatility, or a victim?
Authors: Pettifor Ann
Published: September 2015

As financial markets stagger from announcement to announcement, Ann Pettifor pins the blame for financial chaos not on China's leaders but on a dominant economic model that remains unquestioned in the west.
Whither Labour? Seeking reinvention and a realistic radicalism
Authors: Wright Tony
Published: September 2015

As Jeremy Corbyn takes the reins, Tony Wright calls on Labour to engage in a serious act of self‐investigation and redefinition. Te next general election is not lost already, he says, but much work must be done to win the battle of ideas that comes before it.
No maps, no manuals: Retrieving radical republicanism, restoring popular sovereignty
Authors: Nabulsi Karma
Published: September 2015

Confronting the despair and disenfranchisement at the heart of contemporary democracy, Karma Nabulsi argues for the practical, regenerative power of republicanism, with its focus on active public engagement for the common good.
Containing tensions: Psychoanalysis and modern policymaking
Authors: Cooper Andrew
Published: September 2015

Andrew Cooper outlines a psychoanalytic approach to policymaking, one which ‘insists on the thick textures of social and personal suffering, desire and aspiration as its point of departure for theory and action and speaks to the inherent value of participatory democracy’.