bluuebunny/crossref_metadata_2025 huggingface dataset:
Lacosamide Pharmacokinetics in a Critically Ill Patient Receiving Continuous Venovenous Hemofiltration
Authors: Franquiz Miguel J. , Kalaria Shamir N. , Armahizer Michael J. , Gopalakrishnan Mathangi , McCarthy Paul J. , Badjatia Neeraj
Published: November 2017

Lacosamide is a new‐generation antiepileptic drug (AED) that is eliminated by both hepatic and renal mechanisms. Lacosamide elimination by continuous renal replacement therapy (CRRT) has never been studied. The objective of this case report was to describe lacosamide pharmacokinetics in the setting of CRRT. We describe a single patient admitted to the study center with status epilepticus and multiorgan failure. The patient required both continuous venovenous hemofiltration (CVVH) and several AEDs. He was receiving intravenous lacosamide 200 mg twice/day at steady state prior to sampling. Plasma lacosamide concentrations were derived using a validated high‐performance liquid chromatography method. Parameters were calculated using Phoenix WinNonlin 7.1 software. The peak concentration at steady state was 7.7 mg/L, the trough concentration was 5.9 mg/L (goal 5–12 mg/L). The volume of distribution was 0.7 L/kg, the elimination half‐life was 21 hours, and the sieving coefficient was 0.8 (± 0.06). Lacosamide was cleared by CVVH as demonstrated by the sieving coefficient, but plasma concentrations remained within goal range throughout the dosing interval. These results may suggest that lacosamide 200 mg twice/day is a useful dosing strategy for critically ill patients who require CVVH.
Evaluation of the template‐based modeling in CASP12
Authors: Kryshtafovych Andriy , Monastyrskyy Bohdan , Fidelis Krzysztof , Moult John , Schwede Torsten , Tramontano Anna
Published: November 2017

The article describes results of numerical evaluation of CASP12 models submitted on targets for which structural templates could be identified and for which servers produced models of relatively high accuracy. The emphasis is on analysis of details of models, and how well the models compete with experimental structures. Performance of contributing research groups is measured in terms of backbone accuracy, all‐atom local geometry, and the ability to estimate local errors in models. Separate analyses for all participating groups and automatic servers were carried out. Compared with the last CASP, two years ago, there have been significant improvements in a number of areas, particularly the accuracy of protein backbone atoms, accuracy of sequence alignment between models and available structures, increased accuracy over that which can be obtained from simple copying of a closest template, and accuracy of modeling of sub‐structures not present in the closest template. These advancements are likely associated with more effective strategies to build non‐template regions of the targets ab initio, better algorithms to combine information from multiple templates, enhanced refinement methods, and better methods for estimating model accuracy.
Horizontal transmission of Metarhizium anisopliae (Hypocreales: Clavicipitacea) and the effects of infection on oviposition rate in laboratory populations of Musca domestica (Diptera: Muscidae)
Authors: Baker Dalton K , Rice Steven J , Leemon Diana M , James Peter J
Published: November 2017

BACKGROUND

Effective control of house fly, Musca domestica (L.), populations currently relies on the use of chemical insecticides in most situations. Entomopathogenic fungi such as Metarhizium anisopliae (Metschn.) Sorokin may provide an alternative to chemicals and their efficacy may be enhanced by autodissemination amongst flies. This study assessed the capacity of M. anisopliae for transmission between adult M. domestica flies and the effects of infection on the fecundity of females.

RESULTS

Metarhizium anisopliae was transmitted between adult M. domestica with 91.67–100% mortality resulting across the three ratios of infected: non‐infected flies tested (1:2, 1:5 and 1:10). The mean lethal time (LT50) for female recipients mixed with infected male donor flies at the three ratios was 3.95, 4.79 and 5.65 days, respectively, whereas for male recipients mixed with infected female donors at the same ratios the LT50 was 4.98, 5.98 and 7.44 days, respectively. Infection with M. anisopliae significantly reduced the reproductive capacity of female flies during the first 4 days of infection, with 25% fewer eggs oviposited by infected flies than by those that were uninfected.

CONCLUSION

Autodissemination among house flies and reduction in oviposition in the early stages of infection could contribute significantly to the effectiveness of M. anisopliae used in biocontrol programmes. © 2017 Society of Chemical Industry
Comparing ECMWF high‐resolution analyses with lidar temperature measurements in the middle atmosphere
Authors: Ehard Benedikt , Malardel Sylvie , Dörnbrack Andreas , Kaifler Bernd , Kaifler Natalie , Wedi Nils
Published: November 2017

Middle atmospheric lidar temperature observations conducted above Sodankylä, Finland (67.4°N, 26.6°E), during December 2015 are compared with two estimates of the atmospheric state computed by the integrated forecast system (IFS) of the European Centre for Medium‐Range Weather Forecasts (ECMWF). The first set corresponds to an hourly sampling of the middle atmosphere by high‐resolution analyses and very short‐range forecasts produced by the operational IFS cycle 41r1 at a horizontal resolution of 16 km. The second set is retrieved from the upgraded IFS cycle 41r2 (horizontal resolution 9 km), which was running in parallel with cycle 41r1 during the validation before it became operational. A remarkable agreement between both IFS datasets and the lidar temperature observations above Sodankylä is found below 45 km altitude. Above 45 km altitude, within the sponge layer of the IFS, both IFS datasets depict lower temperatures than the observations, with the 9 km runs showing the coldest temperatures. Various sensitivity experiments conducted with the IFS are analyzed and compared with the lidar observations to investigate the impact of the different changes implemented in IFS cycle 41r2. It is found that both the scientific changes and the horizontal resolution upgrade contribute to the colder mesosphere above Sodankylä. The data assimilation seems to amplify this effect even further.
Neoteric Synthesis and Biological Activities of Chromenopyrazolones, Tosylchromenopyrazolones, Benzoylcoumarins
Authors: Hariprasad Kurma Siva , Anand Ajay , Rathod Balaji Baburao , Zehra Amtul , Tiwari Ashok Kumar , Prakasham Reddy Shetty , Raju Bhimapaka China
Published: November 2017

Chromenopyrazolones, tosylchromenopyrazolones and benzoylcoumarins were prepared by the reaction of salicylaldehyde tosylhydrazones with 3‐oxobutanoates. The title compounds were screened for their in vitro anti‐microbial, DPPH, ABTS.+ free radical scavenging, α‐glucosidase inhibitory and anti‐inflammatory activities. The bioactivity profile studies revealed that the trifluoromethyl chromenopyrazolones were effective for anti‐microbial activity. Trifluoromethyl chromenopyrazolones 5 h, 5 j, 5 l, tosyl chromenopyrazolones 5 m‐q and benzoylcoumarin 6 g are the promising α‐glucosidase inhibitors. The methyl chromenopyrazolones 5 b‐d, trifluoromethyl chromenopyrazolones 5 h‐l, tosylchromenopyrazolone 5 m and methoxy benzoylcoumarin 6 h denoted promising anti‐inflammatory activity.
Breaking free from vascular confinement: status and prospects for submicron ultrasound contrast agents
Authors: Pellow Carly , Goertz David E. , Zheng Gang
Published: November 2017

The development of encapsulated microbubbles (~1–6 μm) has expanded the utility of ultrasound from soft tissue anatomical imaging to not only functional intravascular imaging, but therapeutic interventions, with compelling studies of elicited biological effects. The large diameter of these bubbles has confined their utility to the vasculature, but converging interdisciplinary research pathways are giving rise to new submicron ultrasound contrast agents capable of extending their effects beyond the vascular compartment. This article reviews the status and prospects of exogenous agents including nanobubbles, echogenic liposomes, gas vesicles, cavitation seeds, and nanodroplets, and assesses outstanding criticisms preventing their advance.

This article is categorized under:

Diagnostic Tools > In Vivo Nanodiagnostics and Imaging

Therapeutic Approaches and Drug Discovery > Emerging Technologies
Liouville action as path-integral complexity: from continuous tensor networks to AdS/CFT
Authors: Caputa Pawel , Kundu Nilay , Miyaji Masamichi , Takayanagi Tadashi , Watanabe Kento
Published: November 2017

Abstract

We propose an optimization procedure for Euclidean path-integrals that evaluate CFT wave functionals in arbitrary dimensions. The optimization is performed by minimizing certain functional, which can be interpreted as a measure of computational complexity, with respect to background metrics for the path-integrals. In two dimensional CFTs, this functional is given by the Liouville action. We also formulate the optimization for higher dimensional CFTs and, in various examples, find that the optimized hyperbolic metrics coincide with the time slices of expected gravity duals. Moreover, if we optimize a reduced density matrix, the geometry becomes two copies of the entanglement wedge and reproduces the holographic entanglement entropy. Our approach resembles a continuous tensor network renormalization and provides a concrete realization of the proposed interpretation of AdS/CFT as tensor networks. The present paper is an extended version of our earlier report arXiv:1703.00456 and includes many new results such as evaluations of complexity functionals, energy stress tensor, higher dimensional extensions and time evolutions of thermofield double states.
Non-perturbative reheating and Nnaturalness
Authors: Hardy Edward
Published: November 2017

Abstract

We study models in which reheating happens only through non-perturbative processes. The energy transferred can be exponentially suppressed unless the inflaton is coupled to a particle with a parametrically small mass. Additionally, in some models a light scalar with a negative mass squared parameter leads to much more efficient reheating than one with a positive mass squared of the same magnitude. If a theory contains many sectors similar to the Standard Model coupled to the inflaton via their Higgses, such dynamics can realise the Nnaturalness solution to the hierarchy problem. A sector containing a light Higgs with a non-zero vacuum expectation value is dominantly reheated and there is little energy transferred to the other sectors, consistent with cosmological constraints. The inflaton must decouple from other particles and have a flat potential at large field values, in which case the visible sector UV cutoff can be raised to 10 TeV in a simple model.
The Economic and Social Burden of Traumatic Injuries: Evidence from a Trauma Hospital in Port‐au‐Prince, Haiti
Authors: Zuraik Christopher , Sampalis John , Brierre Alexa
Published: November 2017

Introduction

The cost of traumatic injury is unknown in Haiti. This study aims to examine the burden of traumatic injury of patients treated and evaluated at a trauma hospital in the capital city of Port‐au‐Prince.

Methods

A retrospective cross‐sectional chart review study was conducted at the Hospital Bernard Mevs Project Medishare for all patients evaluated for traumatic injury from December 2015 to January 2016, as described elsewhere (Zuraik and Sampalis in World J Surg, https://doi.org/10.1007/s00268‐017‐4088‐2, 2017). Direct medical costs were obtained from patient hospital bills. Indirect and intangible costs were calculated using the human capital approach.

Results

A total of 410 patients were evaluated for traumatic injury during the study period. Total costs for all patients were $501,706 with a mean cost of $1224. Indirect costs represented 63% of all costs, direct medical costs 19%, and intangible costs 18%. Surgical costs accounted for the majority of direct medical costs (29%). Patients involved in road traffic accidents accounted for the largest number of injuries (41%) and the largest percentage of total costs (51%). Patients with gunshot wounds had the highest total mean costs ($1566). Mean costs by injury severity ranged from $62 for minor injuries, $1269 for serious injuries, to $13,675 for critical injuries.

Conclusion

Injuries lead to a significant economic burden for individuals treated at a semi‐private trauma hospital in the capital city of Port‐au‐Prince, Haiti. Programs aimed at reducing injuries, particularly road traffic accidents, would likely reduce the economic burden to the nation.
Polygene Varianten und Epigenetik bei Adipositas
Authors: Giuranna Johanna , Diebels Inga , Hinney Anke
Published: November 2017

Hintergrund

Durch molekulargenetische Analysen wurde eine kleine Anzahl von Hauptgenen identifiziert, die Übergewicht (Body Mass Index, BMI ≥ 25 kg/m2) und Adipositas (BMI ≥ 30 kg/m2) bei Menschen mit bedingen können. Die zugrunde liegenden Mutationen sind selten. Die genetische Prädisposition zur Entwicklung einer Adipositas ist meist polygener Natur.

Ziel der Arbeit

Darstellung der polygenen Formen der Adipositas und epigenetischer Befunde.

Material und Methoden

Literaturübersicht.

Ergebnisse und Diskussion

Metaanalysen genomweiter Assoziationsstudien (GWAMA) haben bisher mehr als 100 Polygene oder polygene Loci identifiziert, die genomweit mit dem BMI assoziiert sind. Jedes einzelne Polygen leistet nur einen kleinen Beitrag zur Entwicklung einer Adipositas. Effektstärken liegen im Bereich von ca. 100 g bis 1,5 kg. Eine Reihe solcher prädisponierenden Genvarianten (Allele) findet sich bei adipösen Probanden. Allerdings tragen auch normalgewichtige und schlanke Individuen diese Allele, wenn auch in geringerer Frequenz. Diese Allele können durch statistische Analysen als Adipositas-Risikoallele identifiziert und validiert werden. Vor Kurzem haben sogenannte Cross-Disorder- und Cross-Phänotyp-Analysen zur Identifizierung von Genen geführt, die nicht allein durch Analysen der einzelnen Erkrankungen/Phänotypen nachgewiesen werden konnten. Funktionelle in-vitro- und in-vivo-Studien der GWAS-abgeleiteten Polygene könnten zu einem besseren Verständnis der molekulargenetischen Mechanismen der Körpergewichtsregulation führen. Erste genomweite Methylierungsmusteranalysen und Studien zu metastabilen Epiallelen tragen zudem zu einem besseren Verständnis der Pathomechanismen der Adipositas bei.
How discrimination and perspective‐taking influence adolescents' attitudes about justice
Authors: Rasmussen Hannah F. , Ramos Michelle C. , Han Sohyun C. , Pettit Corey , Margolin Gayla
Published: November 2017

Little is known about factors influencing adolescents' justice attitudes. This online study investigates perspective‐taking and experiences with discrimination for their associations with adolescents' beliefs about how justice is best served. Participants included 179 ethnically/racially diverse high school students (Mage = 16.67 years; SD = 1.02). Higher perspective‐taking was associated with less punitive and more restorative attitudes. Youth reporting more personal and ethnic/racial discrimination experiences endorsed more restorative justice attitudes. Perspective‐taking also moderated the associations between reports of family, personal, and religious discrimination and punitive justice attitudes: adolescents reporting higher discrimination showed a stronger inverse relationship between perspective‐taking and punitive attitudes. Findings have implications for school and community programs aiming to implement restorative policies, and for adolescents' civic participation.
Conjugate duality in stochastic controls with delay
Authors: Wang Zimeng , Hodge David J. , Le Huiling
Published: November 2017

In this paper we use the method of conjugate duality to investigate a class of stochastic optimal control problems where state systems are described by stochastic differential equations with delay. For this, we first analyse a stochastic convex problem with delay and derive the expression for the corresponding dual problem. This enables us to obtain the relationship between the optimalities for the two problems. Then, by linking stochastic optimal control problems with delay with a particular type of stochastic convex problem, the result for the latter leads to sufficient maximum principles for the former.
On the Ornstein–Zernike equation for stationary cluster processes and the random connection model
Authors: Last Günter , Ziesche Sebastian
Published: November 2017

In the first part of this paper we consider a general stationary subcritical cluster model in ℝd. The associated pair-connectedness function can be defined in terms of two-point Palm probabilities of the underlying point process. Using Palm calculus and Fourier theory we solve the Ornstein–Zernike equation (OZE) under quite general distributional assumptions. In the second part of the paper we discuss the analytic and combinatorial properties of the OZE solution in the special case of a Poisson-driven random connection model.
A non-local random walk on the hypercube
Authors: Nestoridi Evita
Published: November 2017

In this paper we study the random walk on the hypercube (ℤ / 2ℤ)nwhich at each step flipskrandomly chosen coordinates. We prove that the mixing time for this walk is of the order (n/k)logn. We also prove that ifk=o(n) then the walk exhibits cutoff at (n/ 2k)lognwith windown/ 2k.
The odd couple: analyzing United Kingdom Independence Party (UKIP) and Italian Five Stars Movement’s (FSM’s) European Union (EU)-opposition in the European Parliament (EP)
Authors: Carlotti Benedetta
Published: November 2017

Since the late 2000s economic and immigration crises are testing the European Union (EU). Such challenges have opened up a period of radical change for the EU, among them, the Brexit referendum that will radically change EU’s geography. This turmoil is mirrored by the last European Parliament (EP) election results; extreme right- and left-wing parties succeeded in the electoral competition at the expense of their mainstream counterpart. These forces are generally labelled as ‘Eurosceptic’, even though the literature still lacks a clear-cut definition of Euroscepticism. Starting from this observation, this paper reviews the conceptual evolution of Euroscepticism, stressing its pros and cons and proposes a reconceptualization of it in terms of EU-opposition such that the objects of criticism are clearly identified as the EU-policies, the EU-elite, the EU-regime, and the EU-community. The paper applies ‘EU-opposition’ to examine empirically the activity of two ‘Eurosceptic’ parties in the EP: the Italian Five Stars Movement (FSM) and the British United Kingdom Independence Party (UKIP), using the speeches they deliver in the arena of the EP as the main source of data. From the analysis, it can be seen that UKIP and FSM are an odd couple working in the same party group in the EP, and the concept of EU-opposition is able to better disentangle UKIP and FSM’s criticism of the EU.
Regional, migrant and global affinities to place in 'Seeds: A Permaculture Travel Memoir'
Authors: Gartrell Nina
Published: November 2017

This article explores the traces of an author’s regional identity in a transnational travel memoir in which affinities to place are portrayed as pluralistic and fluid. It does so in order to explore the tenuous balance between ecocentric understanding of self within a community of ‘earth others’ on the one hand and fidelity to a regionally precise ‘home’ on the other. This constitutes an open-endedencounter with regionalism and ‘site-fidelity’ to destabilise the local/global binary. New understandings of foreign landscapes, places and cultures can be brokered upon a dialogue between those newly encountered landscape places, and the more intimately known regions from an individual’s past.
Picking up the pieces
Authors: Buckridge Patrick
Published: November 2017

Given that the Sunshine Coast and its hinterland have been, at least for a time, the haunt of several of several eminent Australian writers — the Palmers, Dark, Herbert, Astley, Wright, Cato, Williamson and Carey, to name a few — it seemed worth asking whether the principal, and for most of the twentieth century the only, newspaper servicing the region since 1903 — the Nambour Chronicle and the North Coast Advertiser — was part of a literary culture to which these writers felt they belonged and were contributing in the first half of the century. If not, why not? And if so, what kinds of contributions did it make to that culture? The tentative finding is that while the Chronicle did not make the kinds of direct, ‘homegrown’ contributions that some other metropolitan and provincial newspapers did, it maintained a literary presence and function by means of a regular diet of imported features, and by its particularly close and consistent relationship with the Nambour Town Library (and also, less consistently, with various School of Arts libraries in the district). The continuing connection between these two Nambour institutions — the Chronicle and the library — was personal and familial as well as civic in nature, and clearly suited the literary demands and expectations of a highly dispersed community that found its unity and identity by other means.
Nathanael O’Reilly, ed., 'New and Selected Poems of Anna Wickham', Perth: UWA Publishing, 2017, 350 pp., ISBN 9 7817 4258 9206, A$29.99
Authors: Cooper Melinda J.
Published: November 2017

Nathanael O’Reilly, ed., New and Selected Poems of Anna Wickham, Perth: UWA Publishing, 2017, 350 pp., ISBN 9 7817 4258 9206, A$29.99
Cuts and the cutting edge: British science funding and the making of animal biotechnology in 1980s Edinburgh
Authors: MYELNIKOV DMITRIY
Published: November 2017

The Animal Breeding Research Organisation in Edinburgh (ABRO, founded in 1945) was a direct ancestor of the Roslin Institute, celebrated for the cloning of Dolly the sheep. After a period of sustained growth as an institute of the Agricultural Research Council (ARC), ABRO was to lose most of its funding in 1981. This decision has been absorbed into the narrative of the Thatcherite attack on science, but in this article I show that the choice to restructure ABRO pre-dated major government cuts to agricultural research, and stemmed from the ARC's wish to prioritize biotechnology in its portfolio. ABRO's management embraced this wish and campaigned against the cuts based on a promise of biotechnological innovation, shifting its focus from farm animal genetics to the production of recombinant pharmaceuticals in sheep milk. By tracing interaction between government policies, research council agendas and local strategies, I show how novel research programmes such as genetic modification could act as a lifeline for struggling institutions.
Equilibrium 𝛽-limits in classical stellarators
Authors: Loizu J. , Hudson S. R. , Nührenberg C. , Geiger J. , Helander P.
Published: November 2017

A numerical investigation is carried out to understand the equilibrium $\unicode[STIX]{x1D6FD}$-limit in a classical stellarator. The stepped-pressure equilibrium code (Hudson et al., Phys. Plasmas, vol. 19 (11), 2012) is used in order to assess whether or not magnetic islands and stochastic field-lines can emerge at high $\unicode[STIX]{x1D6FD}$. Two modes of operation are considered: a zero-net-current stellarator and a fixed-iota stellarator. Despite the fact that relaxation is allowed (Taylor, Rev. Mod. Phys., vol. 58 (3), 1986, pp. 741–763), the former is shown to maintain good flux surfaces up to the equilibrium $\unicode[STIX]{x1D6FD}$-limit predicted by ideal-magnetohydrodynamics (MHD), above which a separatrix forms. The latter, which has no ideal equilibrium $\unicode[STIX]{x1D6FD}$-limit, is shown to develop regions of magnetic islands and chaos at sufficiently high $\unicode[STIX]{x1D6FD}$, thereby providing a ‘non-ideal $\unicode[STIX]{x1D6FD}$-limit’. Perhaps surprisingly, however, the value of $\unicode[STIX]{x1D6FD}$ at which the Shafranov shift of the axis reaches a fraction of the minor radius follows in all cases the scaling laws predicted by ideal-MHD. We compare our results to the High-Beta-Stellarator theory of Freidberg (Ideal MHD, 2014, Cambridge University Press) and derive a new prediction for the non-ideal equilibrium $\unicode[STIX]{x1D6FD}$-limit above which chaos emerges.
Individual differences in anxiety trajectories from Grades 2 to 8: Impact of the middle school transition
Authors: Nelemans Stefanie A. , Hale William W. , Branje Susan J. T. , Meeus Wim H. J. , Rudolph Karen D.
Published: November 2017

This study examined the impact of the middle school transition on general anxiety trajectories from middle childhood to middle adolescence, as well as how youths’ individual vulnerability and exposure to contextual stressors were associated with anxiety trajectories. Participants were 631 youth (47% boys,Mage = 7.96 years at Time 1), followed for 7 successive years from second to eighth grade. Teachers reported on youths’ individual vulnerability to anxiety (anxious solitude) in second grade; youth reported on their anxiety in second to eighth grade and aspects of their social contexts particularly relevant to the school transition (school hassles, peer victimization, parent–child relationship quality, and friendship quality) in sixth to eighth grade. The results revealed two subgroups that showed either strongly increasing (5%) or decreasing (14%) levels of anxiety across the transition and two subgroups with fairly stable levels of either high (11%) or low (70%) anxiety over time. Youth in the latter two subgroups could be distinguished based on their individual vulnerability to anxiety, whereas youth with increasing anxiety reported more contextual stressors and less contextual support than youth with decreasing anxiety. In sum, findings suggest that the middle school transition has the potential to alter developmental trajectories of anxiety for some youth, for better or for worse.
Childhood attachment and behavioral inhibition: Predicting intolerance of uncertainty in adulthood
Authors: Zdebik Magdalena A. , Moss Ellen , Bureau Jean-François
Published: November 2017

Intolerance of uncertainty (IU), the tendency to react negatively to uncertain situations, has been identified as an important cognitive component of anxiety disorders, yet little is known about its etiology. Links to temperament, particularly behavioral inhibition (BI), and insecure attachment have been proposed in the development of IU, but no prospective empirical investigation has been performed thus far. In the current study, attachment to caregiver and BI of 60 children were assessed at age 6, using observational measures. Mother's anxiety symptoms were assessed when participants were 14 years old. IU was reported by participants when they were 21 years old, as was neuroticism. Two types of insecure attachment (ambivalent and disorganized–controlling) and BI were positively related to IU over a 15-year span, even after controlling for participants’ neuroticism and maternal anxiety. Attachment and BI had no significant interacting effect on the development of IU. Maternal anxiety was positively related to child BI and insecure attachment, but not IU. This study is the first to provide empirical support for a link between ambivalent and disorganized–controlling attachment and BI in preschool children to the development of IU in adulthood. Results have etiological and preventative implications not only for anxiety disorders but also for all disorders related to IU.
Comparison of high and low trans-fatty acid consumers: analyses of UK National Diet and Nutrition Surveys before and after product reformulation
Authors: Hutchinson Jayne , Rippin Holly L , Jewell Jo , Breda Joao J , Cade Janet E
Published: November 2017

Objective

The WHO encourages the virtual elimination of artificial trans-fatty acids (TFA), which increase CHD risk. Our UK analysis explores whether voluntary reformulation results in differential TFA intakes among socio-economic groups by determining characteristics of high TFA consumers before and after product reformulation.

Design

Food intake was collected by 7d weighed records pre-reformulation and 4d diaries post-reformulation. Sociodemographic characteristics of TFA consumers above the WHO limit, and of the top 10 % of TFA consumers as a percentage food energy, were compared with those of lower TFA consumers. Multivariate logistic regression determined independent socio-economic predictors of being a top 10 % consumer.

Subjects

UK National Diet and Nutrition Surveys (NDNS) for adults aged 19–64 years pre-reformulation (2000/01; N 1724) and post-reformulation (2010/11–2011/12; N 848).

Results

Post-reformulation 2·5 % of adults exceeded the WHO limit, v. 57 % pre-reformulation. In unadjusted analyses, high TFA consumption was associated with lower income, lower education and long-term illness/disability pre- but not post-reformulation. In adjusted pre-reformulation analyses, degree holders were half as likely as those without qualifications to be top 10 % consumers (OR=0·51; 95 % CI 0·28, 0·92). In adjusted post-reformulation analyses, those with higher income were 2·5–3·3 times more likely to be top 10 % consumers than lowest income households. Pre-reformulation, high consumers consumed more foods containing artificial TFA, whereas ruminant TFA were more prominent post-reformulation.

Conclusions

High TFA consumption was associated with socio-economic disadvantage pre-reformulation, but evidence of this is less clear post-reformulation. Voluntary reformulation appeared effective in reducing TFA content in many UK products with mixed effects on dietary inequalities relating to income and education.
HISTORY COMES TO LIFE
Authors: COWLES HENRY M.
Published: November 2017

“With an anxiety that almost amounted to agony, I collected the instruments of life around me, that I might infuse a spark of being into the lifeless thing that lay at my feet.” So recalled Victor Frankenstein, reflecting on the creative act. By its end, however,Frankensteinhas less to do with the scientist's creativity and more to do with his monster's. This is why Mary Shelley inverts this Promethean moment in the book's final scene, as the monster stands over the lifeless body of his creator. Frankenstein's last words mark the inversion: his “instruments of life,” he laments, had given rise to “an instrument of mischief,” a creature animated by a desire for human fulfillment. To live may mean behaving instrumentally, but some instruments get the better of you. Frankenstein learns this lesson the hard way; but does his monster? He echoes his creator's words—“Fear not that I shall be the instrument of future mischief”—and promises his own end, when he will “collect my funeral pile and consume to ashes this miserable frame.” One's frame is mere matter, but such an act is proof of the life that animates it. On the cusp of death, then, the monster lives.Frankensteinreminds us that the question “What is life?” can only be answered by experiment, from the medical horrors that gave the monster life to the fatal act with which he plans to abandon it. At life's end, as at its beginning, creator and creation combine; we become our instruments, or they surpass us.
Short-Term Effects of the Empathic Talk: The Role of Perceived Empathy, Interpersonal Dispositions, and Vagal Tone on Experiencing Depth
Authors: Dufey Michele , Wilson Juan Enrique
Published: November 2017

The present study examines the immediate impact of empathic attitudes on the receiver, by comparing an empathic conversation (EC) with a neutral one (NC) on experiencing depth (EXP), perceived empathy and vagal tone. We also evaluate if empathy effects depend on personality dispositions relevant to interpersonal functioning. An experimental, counterbalanced, within-subject design was implemented wherein participants (n = 27, age M = 22.6, SD = 4.0, 52% females) talked about a personal, meaningful topic for 20 minutes under both the EC and NC conditions. At the group level, main results indicated that the EC was more effective than the NC in promoting increases in EXP over time (F(1, 25) = 21.04, p < .001, ηp2 = .457) and perceived empathy in women (F(1, 25) = 9.42, p = .005, ηp2 = .264). At the individual level, the NC particularly precluded EXP gains in people expressing a better interpersonal functioning (βs < –.46, ps < .05 for attachment security and empathy and β = .38, p < .05 for aggression), and who also inhibited their vagal tone throughout this very condition (β = .40, p = .024). We conclude that the empathic context has an immediate positive impact on healthy psychological variables, whereas a more impersonal setting would drive people away from this positive effect. Those results are discussed in the light of the role of interpersonal proximity (being empathic to another’s experience and the lack of this attitude) in psychotherapy and healthy functioning.
Tolerance of Chickpeas to Postemergence Broadleaf Herbicides
Authors: Boydston Rick A. , Nelson Howard , Chaves-Cordoba Bernardo
Published: November 2017

Chickpea producers currently have no POST applied herbicides labeled for broadleaf weed control and rely heavily on PRE herbicides to manage weeds. Severe crop losses from broadleaf weed competition and harvest losses from weeds impeding harvest can occur when PRE herbicides perform poorly. Chickpea tolerance to POST applications of acifluorfen at 0.42 kg ai ha-1 and fomesafen at 0.28 kg ai ha-1 was tested at two sites in 2015. In 2016, both herbicides were tested on chickpeas when applied alone and in combination with pyridate at three sites. Acifluorfen and fomesafen injured chickpeas from 8 to 25% at 1 week after treatment (WAT) and 3 to 8% at 4 WAT in 2015 and from 16 to 40% at 1 WAT and 2 to 36% at 4 WAT in 2016. Pyridate applied POST at 1.00 kg ai ha-1 did not injure chickpeas or reduce yields. When pyridate was tank mixed with either acifluorfen or fomesafen, chickpea injury increased, but chickpeas recovered and yielded similar to nontreated checks or pyridate-treated plots. A low rate of metribuzin at 0.06 kg ai ha-1 tank mixed with pyridate had little impact on chickpea injury or weed control. In 2015, Russian thistle was controlled 100% by acifluorfen and fomesafen at Prosser at 28 DAT and both herbicides controlled the weed only 63% at Wilbur at 25 DAT. In 2016, all herbicide treatments reduced broadleaf weed densities equally ranging from 95 to 100% at Paterson, 50 to 100% at Prosser, and 78 to 98% at Wilbur. Chickpea yield was similar among POST herbicide treatments in all site-years. Acifluorfen, fomesafen, and pyridate have potential to improve control of susceptible broadleaf weeds that escape PRE herbicides chickpea production, but the potential for crop injury with acifluorfen and fomesafen warrant further evaluation.
Antithrombotic treatment in peripheral artery disease
Authors: Olinic Dan-Mircea , Tataru Dan Alexandru , Homorodean Calin , Spinu Mihail , Olinic Maria
Published: November 2017

Abstract. This review treats antithrombotic use for peripheral arterial disease (PAD). In asymptomatic patients, there are no scientific data to support single antiplatelet therapy (SAPT) for primary prophylaxis. In symptomatic PAD, SAPT with aspirin or clopidogrel is indicated. The efficacy of aspirin is controversial. Clopidogrel may be preferred over aspirin. Ticagrelor is not superior to clopidogrel in reducing major adverse cardiovascular events and major adverse limb events, but lowers the risk of ischaemic stroke. In symptomatic PAD, dual antiplatelet therapy (DAPT) with clopidogrel and aspirin does not provide benefit over SAPT with aspirin alone and is associated with increased risk of major bleeding. DAPT with ticagrelor 60 mg b. i. d. and aspirin provides a significant major adverse cardiovascular events reduction in symptomatic PAD patients and may be considered in PAD patients with prior myocardial infarction. The use of a new thrombin receptor antagonist, vorapaxar, on top of SAPT or DAPT with aspirin and/or clopidogrel, reduces the risk of acute limb ischaemia and peripheral artery revascularization in patients with symptomatic PAD, at the cost of an increased risk for bleeding. Rivaroxaban (2.5 mg b. i. d.) plus aspirin (100 mg daily) is the first antithrombotic association that proved significant benefit for PAD patients, in terms of strong endpoints – total mortality and cardiovascular mortality. Therefore, this association shows the strongest evidence for secondary prevention of symptomatic PAD patients. In PAD patients undergoing percutaneous peripheral interventions, at least four weeks of DAPT with aspirin and clopidogrel is recommended after infrainguinal stent implantation. Stenting below-the-knee arteries is often followed by a longer period of DAPT, but no specific evidence is available. Anticoagulation is mandatory to prevent arterial occlusion during radial or brachial invasive procedures. The strategy includes use of unfractioned heparin, bivalirudin or enoxaparin. Vitamin K antagonists may be considered after autologous vein infrainguinal bypass.
Experimentally simulating the dynamics of quantum light and matter at deep-strong coupling
Authors: Langford N. K. , Sagastizabal R. , Kounalakis M. , Dickel C. , Bruno A. , Luthi F. , Thoen D. J. , Endo A. , DiCarlo L.
Published: November 2017

The quantum Rabi model describing the fundamental interaction between light and matter is a cornerstone of quantum physics. It predicts exotic phenomena like quantum phase transitions and ground-state entanglement in ultrastrong and deep-strong coupling regimes, where coupling strengths are comparable to or larger than subsystem energies. Demonstrating dynamics remains an outstanding challenge, the few experiments reaching these regimes being limited to spectroscopy. Here, we employ a circuit quantum electrodynamics chip with moderate coupling between a resonator and transmon qubit to realise accurate digital quantum simulation of deep-strong coupling dynamics. We advance the state of the art in solid-state digital quantum simulation by using up to 90 second-order Trotter steps and probing both subsystems in a combined Hilbert space dimension of ∼80, demonstrating characteristic Schrödinger-cat-like entanglement and large photon build-up. Our approach will enable exploration of extreme coupling regimes and quantum phase transitions, and demonstrates a clear first step towards larger complexities such as in the Dicke model.
Host STING-dependent MDSC mobilization drives extrinsic radiation resistance
Authors: Liang Hua , Deng Liufu , Hou Yuzhu , Meng Xiangjiao , Huang Xiaona , Rao Enyu , Zheng Wenxin , Mauceri Helena , Mack Matthias , Xu Meng , Fu Yang-Xin , Weichselbaum Ralph R.
Published: November 2017

Radiotherapy induces and promotes innate and adaptive immunity in which host STING plays an important role. However, radioresistance in irradiated tumors can also develop, resulting in relapse. Here we report a mechanism by which extrinsic resistance develops after local ablative radiation that relies on the immunosuppressive action of STING. The STING/type I interferon pathway enhances suppressive inflammation in tumors by recruiting myeloid cells in part via the CCR2 pathway. Germ-line knockouts of CCR2 or treatment with an anti-CCR2 antibody results in blockade of radiation-induced MDSC infiltration. Treatment with anti-CCR2 antibody alleviates immunosuppression following activation of the STING pathway, enhancing the anti-tumor effects of STING agonists and radiotherapy. We propose that radiation-induced STING activation is immunosuppressive due to (monocytic) M-MDSC infiltration, which results in tumor radioresistance. Furthermore, the immunosuppressive effects of radiotherapy and STING agonists can be abrogated in humans by a translational strategy involving anti-CCR2 antibody treatment to improve radiotherapy.
The activity of TRAF RING homo- and heterodimers is regulated by zinc finger 1
Authors: Middleton Adam J. , Budhidarmo Rhesa , Das Anubrita , Zhu Jingyi , Foglizzo Martina , Mace Peter D. , Day Catherine L.
Published: November 2017

Ubiquitin chains linked through lysine63 (K63) play a critical role in inflammatory signalling. Following ligand engagement of immune receptors, the RING E3 ligase TRAF6 builds K63-linked chains together with the heterodimeric E2 enzyme Ubc13-Uev1A. Dimerisation of the TRAF6 RING domain is essential for the assembly of K63-linked ubiquitin chains. Here, we show that TRAF6 RING dimers form a catalytic complex where one RING interacts with a Ubc13~Ubiquitin conjugate, while the zinc finger 1 (ZF1) domain and linker-helix of the opposing monomer contact ubiquitin. The RING dimer interface is conserved across TRAFs and we also show that TRAF5–TRAF6 heterodimers form. Importantly, TRAF5 can provide ZF1, enabling ubiquitin transfer from a TRAF6-bound Ubc13 conjugate. Our study explains the dependence of activity on TRAF RING dimers, and suggests that both homo- and heterodimers mediated by TRAF RING domains have the capacity to synthesise ubiquitin chains.
Primer synthesis by a eukaryotic-like archaeal primase is independent of its Fe-S cluster
Authors: Holzer Sandro , Yan Jiangyu , Kilkenny Mairi L. , Bell Stephen D. , Pellegrini Luca
Published: November 2017

DNA replication depends on primase, the specialised polymerase responsible for synthesis of the RNA primers that are elongated by the replicative DNA polymerases. In eukaryotic and archaeal replication, primase is a heterodimer of two subunits, PriS and PriL. Recently, a third primase subunit named PriX was identified in the archaeon Sulfolobus solfataricus. PriX is essential for primer synthesis and is structurally related to the Fe–S cluster domain of eukaryotic PriL. Here we show that PriX contains a nucleotide-binding site required for primer synthesis, and demonstrate equivalence of nucleotide-binding residues in PriX with eukaryotic PriL residues that are known to be important for primer synthesis. A primase chimera, where PriX is fused to a truncated version of PriL lacking the Fe–S cluster domain retains wild-type levels of primer synthesis. Our evidence shows that PriX has replaced PriL as the subunit that endows primase with the unique ability to initiate nucleic acid synthesis. Importantly, our findings reveal that the Fe–S cluster is not required for primer synthesis.
A structurally distinct TGF-β mimic from an intestinal helminth parasite potently induces regulatory T cells
Authors: Johnston Chris J. C. , Smyth Danielle J. , Kodali Ravindra B. , White Madeleine P. J. , Harcus Yvonne , Filbey Kara J. , Hewitson James P. , Hinck Cynthia S. , Ivens Alasdair , Kemter Andrea M. , Kildemoes Anna O. , Le Bihan Thierry , Soares Dinesh C. , Anderton Stephen M. , Brenn Thomas , Wigmore Stephen J. , Woodcock Hannah V. , Chambers Rachel C. , Hinck Andrew P. , McSorley Henry J. , Maizels Rick M.
Published: November 2017

Helminth parasites defy immune exclusion through sophisticated evasion mechanisms, including activation of host immunosuppressive regulatory T (Treg) cells. The mouse parasiteHeligmosomoides polygyruscan expand the host Treg population by secreting products that activate TGF-β signalling, but the identity of the active molecule is unknown. Here we identify anH. polygyrusTGF-β mimic (Hp-TGM) that replicates the biological and functional properties of TGF-β, including binding to mammalian TGF-β receptors and inducing mouse and human Foxp3+Treg cells.Hp-TGM has no homology with mammalian TGF-β or other members of the TGF-β family, but is a member of the complement control protein superfamily. Thus, our data indicate that through convergent evolution, the parasite has acquired a protein with cytokine-like function that is able to exploit an endogenous pathway of immunoregulation in the host.
Singlet oxygen-mediated selective C–H bond hydroperoxidation of ethereal hydrocarbons
Authors: Sagadevan Arunachalam , Hwang Kuo Chu , Su Ming-Der
Published: November 2017

Singlet O2 is a key reactive oxygen species responsible for photodynamic therapy and is generally recognized to be chemically reactive towards C=C double bonds. Herein, we report the hydroperoxidation/lactonization of α-ethereal C–H bonds by singlet O2 (1Δg) under exceptionally mild conditions, i.e., room temperature and ambient pressure, with modest to high yields (38~90%) and excellent site selectivity. Singlet O2 has been known for > 90 years, but was never reported to be able to react with weakly activated C–H bonds in saturated hydrocarbons. Theoretical calculations indicate that singlet O2 directly inserts into the α-ethereal C–H bond in one step with conservation of steric configuration in products. The current discovery of chemical reaction of singlet oxygen with weakly activated solvent C–H bonds, in addition to physical relaxation pathway, provides an important clue to a 35-year-old unresolved mystery regarding huge variations of solvent dependent lifetime of singlet O2.
Changes in cortical network connectivity with long-term brain-machine interface exposure after chronic amputation
Authors: Balasubramanian Karthikeyan , Vaidya Mukta , Southerland Joshua , Badreldin Islam , Eleryan Ahmed , Takahashi Kazutaka , Qian Kai , Slutzky Marc W. , Fagg Andrew H. , Oweiss Karim , Hatsopoulos Nicholas G.
Published: November 2017

Studies on neural plasticity associated with brain–machine interface (BMI) exposure have primarily documented changes in single neuron activity, and largely in intact subjects. Here, we demonstrate significant changes in ensemble-level functional connectivity among primary motor cortical (MI) neurons of chronically amputated monkeys exposed to control a multiple-degree-of-freedom robot arm. A multi-electrode array was implanted in M1 contralateral or ipsilateral to the amputation in three animals. Two clusters of stably recorded neurons were arbitrarily assigned to control reach and grasp movements, respectively. With exposure, network density increased in a nearly monotonic fashion in the contralateral monkeys, whereas the ipsilateral monkey pruned the existing network before re-forming a denser connectivity. Excitatory connections among neurons within a cluster were denser, whereas inhibitory connections were denser among neurons across the two clusters. These results indicate that cortical network connectivity can be modified with BMI learning, even among neurons that have been chronically de-efferented and de-afferented due to amputation.
Mitochondrial dynamics controls anti-tumour innate immunity by regulating CHIP-IRF1 axis stability
Authors: Gao Zhengjun , Li Yiyuan , Wang Fei , Huang Tao , Fan Keqi , Zhang Yu , Zhong Jiangyan , Cao Qian , Chao Tong , Jia Junling , Yang Shuo , Zhang Long , Xiao Yichuan , Zhou Ji-Yong , Feng Xin-Hua , Jin Jin
Published: November 2017

Macrophages, dendritic cells and other innate immune cells are involved in inflammation and host defense against infection. Metabolic shifts in mitochondrial dynamics may be involved in Toll-like receptor agonist-mediated inflammatory responses and immune cell polarization. However, whether the mitochondrial morphology in myeloid immune cells affects anti-tumor immunity is unclear. Here we show that FAM73b, a mitochondrial outer membrane protein, has a pivotal function in Toll-like receptor-regulated mitochondrial morphology switching from fusion to fission. Switching to mitochondrial fission via ablation ofFam73b(also known asMiga2) promotes IL-12 production. In tumor-associated macrophages, this switch results in T-cell activation and enhances anti-tumor immunity. We also show that the mitochondrial morphology affects Parkin expression and its recruitment to mitochondria. Parkin controls the stability of the downstream CHIP–IRF1 axis through proteolysis. Our findings identify mechanisms associated with mitochondrial dynamics that control anti-tumor immune responses and that are potential targets for cancer immunotherapy.