bluuebunny/crossref_metadata_2025 huggingface dataset:
First assessment of the potential introduction by hunters of eastern cottontail rabbits (Sylvilagus floridanus) in Spain
Authors: Delibes-Mateos M. , Castro F. , Piorno V. , Ramírez E. , Blanco-Aguiar J. A. , Aparicio F. , Mínguez L. E. , Ferreira C. C. , Rouco C. , Ríos-Saldaña C. A. , Recuerda P. , Villafuerte R.
Published: October 2018

Context
Humans have introduced lagomorph species in areas outside their native ranges for their meat, fur or value as game species. Assessing the rate of success of lagomorph introductions is vital to address the ecological damage they may cause. Cases of failed lagomorph introductions in apparently suitable areas may also shed light on mechanisms that may deter invasion, which are useful in developing strategies for population control. In Spain, it has been suggested that hunters introduced the non-native eastern cottontail (Sylvilagus floridanus) to compensate for the recent drastic declines of the native European rabbit (Oryctolagus cuniculus).

Aims
Our main goals were to investigate (1) whether Sylvilagus rabbits have indeed been introduced by hunters across Spain, and (2) whether the species has become established in Spanish ecosystems.

Methods
We interviewed 311 hunters or naturalists across Spain. The questionnaires inquired about the characteristics of game management in each locality, including the frequency of rabbit restocking, and particularly whether Sylvilagus rabbits had been released in the surveyed localities. In addition, we sampled 192 rabbit populations (n=3974 individuals) across Spain by using molecular analysis to determine whether Sylvilagus rabbits were present in these areas.

Key results
Our interview results suggest that Sylvilagus rabbits may have been released in 6% of the 311 localities surveyed. However, molecular analyses failed to confirm their persistence, because all samples belonged to O. cuniculus.

Conclusions
We infer that Sylvilagus rabbits failed to establish themselves in Spain, although interviewees reported their introduction. Several reasons may explain the unsuccessful establishment of this species, such as a low propagule pressure, competition with native species, predation, inability to cope with local pathogens and unsuitable climatic conditions.

Implications
The risk of future introductions of non-native game species can be reduced through the implementation of stricter regulations of animal releases into the wild. Long-term monitoring networks should be developed to help identify non-native game species before they become established and spread to neighbouring areas, thereby preventing any ecological or economic impacts these species may cause.
Metaanalysis of the relationship between violent video game play and physical aggression over time
Authors: Prescott Anna T. , Sargent James D. , Hull Jay G.
Published: October 2018

To clarify and quantify the influence of video game violence (VGV) on aggressive behavior, we conducted a metaanalysis of all prospective studies to date that assessed the relation between exposure to VGV and subsequent overt physical aggression. The search strategy identified 24 studies with over 17,000 participants and time lags ranging from 3 months to 4 years. The samples comprised various nationalities and ethnicities with mean ages from 9 to 19 years. For each study we obtained the standardized regression coefficient for the prospective effect of VGV on subsequent aggression, controlling for baseline aggression. VGV was related to aggression using both fixed [β = 0.113, 95% CI = (0.098, 0.128)] and random effects models [β = 0.106 (0.078, 0.134)]. When all available covariates were included, the size of the effect remained significant for both models [β = 0.080 (0.065, 0.094) and β = 0.078 (0.053, 0.102), respectively]. No evidence of publication bias was found. Ethnicity was a statistically significant moderator for the fixed-effects models (
P
≤ 0.011) but not for the random-effects models. Stratified analyses indicated the effect was largest among Whites, intermediate among Asians, and nonsignificant among Hispanics. Discussion focuses on the implications of such findings for current debates regarding the effects of violent video games on physical aggression.
How to play 20 questions with nature and lose: Reflections on 100 years of brain-training research
Authors: Katz Benjamin , Shah Priti , Meyer David E.
Published: October 2018

Despite dozens of empirical studies and a growing body of meta-analytic work, there is little consensus regarding the efficacy of cognitive training. In this review, we examine why this substantial corpus has failed to answer the often-asked question, “Does cognitive training work?” We first define cognitive training and discuss the general principles underlying training interventions. Next, we review historical interventions and discuss how findings from this early work remain highly relevant for current cognitive-training research. We highlight a variety of issues preventing real progress in understanding the underlying mechanisms of training, including the lack of a coherent theoretical framework to guide training research and methodological issues across studies and meta-analyses. Finally, suggestions for correcting these issues are offered in the hope that we might make greater progress in the next 100 y of cognitive-training research.
CXCR6
+
ST2
+
memory T helper 2 cells induced the expression of major basic protein in eosinophils to reduce the fecundity of helminth
Authors: Obata-Ninomiya Kazushige , Ishiwata Kenji , Nakano Hisanobu , Endo Yusuke , Ichikawa Tomomi , Onodera Atsushi , Hirahara Kiyoshi , Okamoto Yoshitaka , Kanuka Hirotaka , Nakayama Toshinori
Published: October 2018

Memory T helper (mTh) cells play important roles in the reinfection of pathogens and drive the pathogenesis of diseases. While recent studies have characterized the pathogenic mTh2 cell subpopulations driving allergic inflammation, those that induce immune responses against helminth infection remain unknown. We found that IL-5–producing CXCR6
+
ST2
+
CD44
+
mTh2 cells play a crucial role in the IL-33–dependent inhibition of the fecundity of helminth, whereas other ST2
−
mTh2 cells do not. Although both cell types induced the infiltration of granulocytes, especially eosinophils, into the lungs in response to helminth infection, the ST2
+
mTh2 cell-induced eosinophils expressed higher levels of major basic protein (MBP), which is important for reducing the fecundity of
Nippostrongylus brasiliensis
(Nb), than ST2
−
mTh2 cell-induced ones. Notably, we also found that ST2
+
Treg cells but not ST2
−
Treg cells suppressed CXCR6
+
ST2
+
mTh2 cell-mediated immune responses. Taken together, these findings show that we identified a mechanism against helminth elicited by a subpopulation of IL-5–producing mTh2 cells through the accumulation of eosinophils strongly expressing MBP in the lungs.
HSP90 is a chaperone for DLK and is required for axon injury signaling
Authors: Karney-Grobe Scott , Russo Alexandra , Frey Erin , Milbrandt Jeffrey , DiAntonio Aaron
Published: October 2018

Significance

Defining mechanisms of axon injury signaling is critical to understand axon regeneration. This knowledge can be used to develop strategies of axonal repair. Identification of such injury signals has been limited by traditional in vivo assays of proregenerative injury signaling. Here, we describe an in vitro screening platform that specifically identifies proregenerative axon injury signals in mouse neurons. We show that HSP90 is required for injury signaling and detail a mechanism by which HSP90 chaperones the essential proregenerative kinase, dual leucine zipper kinase (DLK). Thus, this work also describes HSP90 as a previously unidentified regulator of DLK, a critical neuronal stress sensor that drives axon regeneration, degeneration, and neurological disease.
Role of PDGF receptor-α during human cytomegalovirus entry into fibroblasts
Authors: Wu Kai , Oberstein Adam , Wang Wei , Shenk Thomas
Published: October 2018

Significance

Human CMV (HCMV) is a major cause of birth defects, an opportunistic infection in untreated HIV/AIDS, and a life-threatening complication in immunosuppressed transplant patients. HCMV infects multiple different cell types, so understanding mechanisms supporting the entry of the virus into different cells is crucial to deciphering its pathogenesis. Two viral glycoprotein complexes (trimeric and pentameric complexes) are known to control HCMV tropism in different cell types. Here we have refined our understanding of the mechanism by which the cell-surface receptor tyrosine kinase, PDGF receptor-α, supports the entry of HCMV into fibroblasts.
Bayesian approach to SETI
Authors: Grimaldi Claudio , Marcy Geoffrey W.
Published: October 2018

Significance

Ongoing and future initiatives in the search for extraterrestrial intelligence (SETI) will explore the Galaxy on an unprecedented scale to find evidence of communicating civilizations beyond Earth. Here, we construct a Bayesian formulation of SETI to infer the posterior probability of the mean number of radio signals crossing Earth, given a positive or a null outcome of all-sky searches for nonnatural radio emissions. We show that not detecting signals within∼40kly from Earth is compatible with the absence in the entire Galaxy of detectable emitters of a wide range of radiated power. The discovery of even a single emission within∼1kly implies instead that over 100 signals typically cross our planet from the Milky Way.
Cytoprotective metal-organic frameworks for anaerobic bacteria
Authors: Ji Zhe , Zhang Hao , Liu Hao , Yaghi Omar M. , Yang Peidong
Published: October 2018

We report a strategy to uniformly wrap
Morella thermoacetica
bacteria with a metal-organic framework (MOF) monolayer of nanometer thickness for cytoprotection in artificial photosynthesis. The catalytic activity of the MOF enclosure toward decomposition of reactive oxygen species (ROS) reduces the death of strictly anaerobic bacteria by fivefold in the presence of 21% O
2
, and enables the cytoprotected bacteria to continuously produce acetate from CO
2
fixation under oxidative stress. The high definition of the MOF–bacteria interface involving direct bonding between phosphate units on the cell surface and zirconium clusters on MOF monolayer, provides for enhancement of life throughout reproduction. The dynamic nature of the MOF wrapping allows for cell elongation and separation, including spontaneous covering of the newly grown cell surface. The open-metal sites on the zirconium clusters lead to 600 times more efficient ROS decomposition compared with zirconia nanoparticles.
Allosteric potentiation of a ligand-gated ion channel is mediated by access to a deep membrane-facing cavity
Authors: Heusser Stephanie A. , Lycksell Marie , Wang Xueqing , McComas Sarah E. , Howard Rebecca J. , Lindahl Erik
Published: October 2018

Significance

Molecular mechanisms of general anesthetic modulation in pentameric ligand-gated ion channels remain controversial. Here we present molecular simulations and functional data that reveal correlations between dynamic differences in a membrane-accessible cavity and dramatic anesthetic effects, separate inhibitory and potentiating effects within the same electrophysiology recordings, and support a model for communication between the lipid bilayer and ion channel pore. In particular, enhanced electrostatic interactions in the membrane-accessible site were associated with a unique mode of anesthetic potentiation, persisting tens of minutes after washout. These results offer a bridge between lipid- and receptor-based theories of anesthesia, with the potential to inform both mechanistic understanding and drug development.
Active apolar doping determines routes to colloidal clusters and gels
Authors: Massana-Cid Helena , Codina Joan , Pagonabarraga Ignacio , Tierno Pietro
Published: October 2018

Significance

Collections of polar active particles have been unable to form stable and long-living structures due to the presence of self-propulsion. We solve this timely issue by introducing the concept of “active doping” and show that a few light-activated apolar, i.e., non–self-propelling, units can be used to rapidly trigger the formation of solid clusters and gels composed of passive colloidal particles. Our active doping can be used to assemble disparate microscopic objects, including synthetic or biological ones, paving the way toward the extension of fundamental concepts of gel and glass formation to active out-of-equilibrium systems.
Beyond Verismo: Massenet's La Navarraise and ‘Realism’ in Fin-de-siècle Paris
Authors: Bentley Charlotte
Published: October 2018

The ‘réalisme’ of Massenet's La Navarraise divided critics at its belated Parisian première on 3 October 1895. While the opera has typically been read as a straightforward attempt at French verismo, this article suggests a more complex set of ways in which modernity and the modern world shaped critical perceptions of and responses to realism. Placing La Navarraise within its wider cultural and technological contexts, I argue that the critics’ ambivalence to its realism provides insight into the changing and contested nature of critical perception and subjectivity in Paris in the final years of the nineteenth century.
Single-nucleotide variants in human RNA: RNA editing and beyond
Authors: Guo Yan , Yu Hui , Samuels David C , Yue Wei , Ness Scott , Zhao Ying-yong
Published: October 2018

Through analysis of paired high-throughput DNA-Seq and RNA-Seq data, researchers quickly recognized that RNA-Seq can be used for more than just gene expression quantification. The alternative applications of RNA-Seq data are abundant, and we are particularly interested in its usefulness for detecting single-nucleotide variants, which arise from RNA editing, genomic variants and other RNA modifications. A stunning discovery made from RNA-Seq analyses is the unexpectedly high prevalence of RNA-editing events, many of which cannot be explained by known RNA-editing mechanisms. Over the past 6–7 years, substantial efforts have been made to maximize the potential of RNA-Seq data. In this review we describe the controversial history of mining RNA-editing events from RNA-Seq data and the corresponding development of methodologies to identify, predict, assess the quality of and catalog RNA-editing events as well as genomic variants.
Opening the Black Box of Citations: A Qualitative Analysis on the Basis of the Taxonomy of Erikson and Erlandson
Authors: Marí-Sáez Víctor-M , Ceballos-Castro Gonzalo
Published: October 2018

Over recent years, citation practice has become progressively more pertinent to academic production, a relevance that poses the challenge of addressing this object of study not only from a quantitative perspective, but also using qualitative approaches. On the basis of these premises, the aim of this article is to analyze, from a qualitative perspective, the literature on communication for development and social change (CDSC) published in the top 10 communication journals in Spain. To this end, a qualitative analysis of the most frequently cited papers on this topic was performed on the basis of the citation categories suggested by M. G. Erikson and P. A. Erlandson (2014), as well as the implications and consequences of their widespread use. The conclusions of this article point to the predominance of citations that, in many cases, reveal a disturbing disregard for the cited works and a general lack of scholarly debate between authors and conflicting paradigms.
Explaining farm structural change in the European agriculture: a novel analytical framework
Authors: Neuenfeldt Sebastian , Gocht Alexander , Heckelei Thomas , Ciaian Pavel
Published: October 2018

In this paper, we analyse the drivers of farm structural change in the EU-27, applying a novel analytical framework in the field of agricultural economics known as the multiplicative competitive interaction (MCI) model. MCI offers a more parsimonious specification for estimating models of regional farm group shares compared to the often-applied Markov approach. The MCI framework enables farm group-specific equations, which are used to account for drivers specific to certain farm groups. The MCI framework explains farm group shares at the regional level taken from the Farm Structure Survey (FSS) using socio-economic variables from the Farm Accountancy Data Network (FADN) and other databases for the period 1989–2013. We consider eight production specialisations and two size classes at the NUTS 2 regional level. The results indicate that the past farm structure explains approximately 36 per cent of the EU farm structure variation across regions and time, followed by natural conditions (16 per cent), agricultural prices (14 per cent), macroeconomic variables (9 per cent), subsidies (7 per cent), population (6 per cent) and agricultural income (6 per cent). Further, we have run a simulation experiment where we derived elasticities of structural change with respect to time-varying variables. The structural change appears to be the most elastic with respect to income and macroeconomic variables.
Structured illumination approaches for super-resolution in plant cells
Authors: Shaw Sidney L , Thoms David , Powers James
Published: October 2018

The advent of super-resolution techniques in biological microscopy has opened new frontiers for exploring the molecular distribution of proteins and small molecules in cells. Improvements in optical design and innovations in the approaches for the collection of fluorescence emission have produced substantial gains in signal from chemical labels and fluorescent proteins. Structuring the illumination to elicit fluorescence from specific or even random patterns allows the extraction of higher order spatial frequencies from specimens labeled with conventional probes. Application of this approach to plant systems for super-resolution imaging has been relatively slow owing in large part to aberrations incurred when imaging through the plant cell wall. In this brief review, we address the use of two prominent methods for generating super-resolution images in living plant specimens and discuss future directions for gaining better access to these techniques.
Environmental Surveillance Reveals Complex Enterovirus Circulation Patterns in Human Populations
Authors: Majumdar Manasi , Sharif Salmaan , Klapsa Dimitra , Wilton Thomas , Alam Muhammad Masroor , Fernandez-Garcia Maria Dolores , Rehman Lubna , Mujtaba Ghulam , McAllister Gina , Harvala Heli , Templeton Kate , Mee Edward T , Asghar Humayun , Ndiaye Kader , Minor Philip D , Martin Javier
Published: October 2018

Background

Enteroviruses are common human pathogens occasionally associated with severe disease, notoriously paralytic poliomyelitis caused by poliovirus. Other enterovirus serotypes such as enterovirus A71 and D68 have been linked to severe neurological syndromes. New enterovirus serotypes continue to emerge, some believed to be derived from nonhuman primates. However, little is known about the circulation patterns of many enterovirus serotypes and, in particular, the detailed enterovirus composition of sewage samples.

Methods

We used a next-generation sequencing approach analyzing reverse transcriptase polymerase chain reaction products synthesized directly from sewage concentrates.

Results

We determined whole-capsid genome sequences of multiple enterovirus strains from all 4 A to D species present in environmental samples from the United Kingdom, Senegal, and Pakistan.

Conclusions

Our results indicate complex enterovirus circulation patterns in human populations with differences in serotype composition between samples and evidence of sustained and widespread circulation of many enterovirus serotypes. Our analyses revealed known and divergent enterovirus strains, some of public health relevance and genetically linked to clinical isolates. Enteroviruses identified in sewage included vaccine-derived poliovirus and enterovirus D-68 stains, new enterovirus A71 and coxsackievirus A16 genogroups indigenous to Pakistan, and many strains from rarely reported serotypes. We show how this approach can be used for the early detection of emerging pathogens and to improve our understanding of enterovirus circulation in humans.
Fragile legitimacy: the rise and crisis of the EU’s ‘sustainable biofuels’ policy
Authors: Kupzok Nils
Published: October 2018

The EU’s biofuels policy has made a full normative turn: introduced to advance sustainable development, it was curtailed as a threat to the global environment. Central to the crisis of legitimation was a contested scientific idea, emissions from indirect land-use changes. This article takes up the large impact of this small idea to discuss a central question of contemporary institutionalist and constructivist scholarship: Why and under what conditions can ideas and events become catalysts for change? Tracing the rise and crisis of the EU’s biofuels policy, my central theoretical intervention is to conceptualize the fragile legitimacy of policies and institutions. In addition, I specify the scope condition that heighten or reduce a policy’s fragility, arguing that it depends on: (a) a tight/loose coupling of legitimacy to underlying authoritative discourses, (b) the volatility of these sources of authority and (c) the agenda-setting power of groups opposing the status quo.
Tomato Seeds Preferably Transmit Plant Beneficial Endophytes
Authors: Bergna Alessandro , Cernava Tomislav , Rändler Manuela , Grosch Rita , Zachow Christin , Berg Gabriele
Published: October 2018

Endophytes with plant growth-promoting activity can improve the health and development of plants during all life stages. However, less is known about their stability and transmission across plant genotypes, habitats, and generations. By combining community and isolate analyses, we found that each plant habitat and genotype harbored distinct bacterial communities and plant growth-promoting bacteria (PGPB). Soil, root endosphere, and rhizosphere were the habitats with the highest bacterial diversity, while seeds hosted more selective communities. Seeds generated under field conditions showed traces of a bacterial community composition connected to the suppression of plant pathogens. In contrast, seeds of the successive generation grown in a pathogen-free and low-nutrient environment showed a predominance of bacteria that facilitate the uptake of nutrients. These modifications of the microbiome can be explained by an adaptation to prevalent environmental conditions. Cultivation approaches revealed microhabitat-specific PGPB that were assigned to various species of Bacillus, Stenotrophomonas, and Ralstonia. Tracking down these bacteria among the whole tomato plant allowed us to identify the seed as a primary vehicle of PGPB transmission. This previously undescribed vertical transmission of PGPB represents a strategy to maintain plant beneficial bacteria over generations and has an impact for the design of seed treatments.
Role of Fresh Dead Wood in the Epidemiology and the Biological Control of the Chestnut Blight Fungus
Authors: Meyer Joana Beatrice , Chalmandrier Loïc , Fässler Fabio , Schefer Christopher , Rigling Daniel , Prospero Simone
Published: October 2018

The invasive fungus Cryphonectria parasitica, the causal agent of chestnut blight, is able to survive and sporulate on the bark of fresh dead Castanea sativa wood for at least 2 years. Here, we experimentally investigated the role of fresh dead wood in the epidemiology of chestnut blight, specifically in the spread of the hyperparasitic virus Cryphonectria hypovirus 1, which acts as biocontrol agent of C. parasitica. A total of 152 artificially initiated, virulent bark cankers in four chestnut stands were treated with virus-infected asexual spores originating either from sporulating dead wood or from a spore suspension. Molecular markers for both the virus and the fungal carrier were used to examine the spread of the applied biocontrol virus. Fourteen months after treatment, 42 to 76% of the conidial spray-treated cankers and 50 to 60% of the cankers exposed to a sporulating dead stem had been virus infected by the applied hypovirulent conidia in all four study sites. Virus infection reduced canker expansion and promoted canker healing (callusing). Thus, fresh chestnut dead wood may play an important role in supporting the successful spread of natural hypovirulence in chestnut forests. Further, combined with the application of virus-infected conidial suspensions, it may help promote the establishment of artificially released hypoviruses in chestnut stands to control chestnut blight.
Timing of Perennial Canker Development in Apple Trees Caused by Neofabraea perennans and Neofabraea kienholzii
Authors: Aguilar Christian G. , Mazzola Mark , Xiao Chang-Lin
Published: October 2018

Members of the genera Neofabraea and Phlyctema have been reported to incite canker diseases of apple trees and a postharvest decay of apple fruit referred to as “bull’s-eye rot.” Neofabraea kienholzii was recently identified as participating in the bull’s-eye rot disease complex of apple and other pome fruit. In this study, apple twigs inoculated with N. kienholzii were shown to develop symptoms of a canker disease closely resembling perennial canker of pome fruit trees caused by N. perennans. Cankers resulting from infection by either Neofabraea spp. were more likely to be induced when twig inoculations occurred in October, and to a lesser degree in April, compared with all other inoculation dates evaluated in this study. Although N. kienholzii tended to induce cankers that were smaller in size compared with N. perennans, both pathogens shared similar seasonal trends in the initiation and expansion of tree cankers. N. perennans and N. kienholzii were recovered from inoculated twigs 6 months postinoculation regardless of when inoculations were conducted, indicating that both pathogens can survive on diseased twigs year-round. In addition, acervuli were observed more often on twigs inoculated in September and April compared with those inoculated in other months. Data from this work should help further our understanding of the epidemiology of N. kienholzii. This information also highlights the importance of proper branch pruning, canker removal, and aphid control. Such management activities should be conducted in a manner that helps minimize further spread of the pathogen.
Hormetic Effects of Mixtures of Dimethachlone and Prochloraz on Sclerotinia sclerotiorum
Authors: Zhang Ran , Zhang Yuchao , Xu Qianru , Li Jianhong , Zhu Fuxing
Published: October 2018

Previous studies showed that dimethachlone has significant hormetic effects on phytopathogenic fungus Sclerotinia sclerotiorum. The present study investigated hormetic effects of mixtures of dimethachlone and prochloraz on mycelial growth and virulence of two dimethachlone-resistant isolates of S. sclerotiorum. The stimulatory dimethachlone dosage range was around 1 to 100 μg/ml in potato dextrose agar (PDA) medium for mycelial growth of the two isolates, and dimethachlone at 10 and 50 μg/ml had the maximum percent stimulations of 80.6 and 19.3% for isolates JMS14 and HLJ4, respectively. Prochloraz at 0.0003 and 0.002 μg/ml had the maximum percent stimulations of 9.3 and 11.1% for isolates JMS14 and HLJ4, respectively. However, dimethachlone and prochloraz mixed at their respective stimulatory concentrations had the maximum percent stimulations of 48.1 and 9.3% for isolates JMS14 and HLJ4, respectively. After the mycelia with increased and inhibited growth on fungicide-amended PDA were subcultured on PDA without fungicide, mycelial growth for the second generation increased compared with the nontreated control. After the mycelia grown on fungicide-amended PDA were inoculated on rapeseed leaves, the amplitude of virulence stimulation was much greater than that of mycelial growth on PDA amended with fungicide, and the inhibited mycelia also showed substantially increased virulence on leaves. The mixture of dimethachlone at 100 μg/ml and prochloraz at 0.03 μg/ml in PDA inhibited mycelial growth of isolate JMS14 by 59.4%; however, after the inhibited mycelia were inoculated on rapeseed leaves, virulence was stimulated by 69.0%. Spraying sublethal doses of dimethachlone and prochloraz on rapeseed leaves also exhibited significant stimulatory effects on virulence. For isolate JMS14, the stimulatory concentration ranges for dimethachlone and prochloraz were around 1 to 600 μg/ml and 0.0003 to 0.18 μg/ml, respectively. The fitted curve of virulence stimulation for the mixture of dimethachlone and prochloraz shifted to the left on the x axis, denoting dose-additive interactions between the two fungicides with regard to virulence stimulation. Spraying dimethachlone alone at 10 to 50 μg/ml had significant stimulations on virulence, whereas prochloraz alone at 10 to 50 μg/ml had significant inhibitory effects on virulence, and the mixture of dimethachlone and prochloraz at the concentration ratio of 1:1 had greater inhibitory effects than prochloraz alone, indicating dose-additive interactions for the inhibitory effects. Dimethachlone and prochloraz and their mixtures increased tolerance of mycelia to hydrogen peroxide. Dimethachlone significantly increased, whereas prochloraz reduced mycelial cell membrane permeability, and the mixture of the two fungicides had effect-additive interactions with respect to effects on cell membrane permeability. These studies will advance our understanding of hormesis of fungicide mixtures.
A practical approach to predict expansion of evidence networks: a case study in treatment-naive advanced melanoma
Authors: Halfpenny Nicholas J.A. , Scott David A. , Thompson Juliette C. , Gurung Binu , Quigley Joan M.
Published: October 2018

Network meta-analysis (NMA) is a statistical method used to produce comparable estimates of efficacy across a range of treatments that may not be compared directly within any single trial. NMA feasibility is determined by the comparability of the data and presence of a connected network. In rapidly evolving treatment landscapes, evidence networks can change substantially in a short period of time. We investigate methods to determine the optimum time to conduct or update a NMA based on anticipated available evidence. We report the results of a systematic review conducted in treatment-naive advanced melanoma and compare networks of evidence available at retrospective, current, and prospective time points. For included publications, we compared the primary completion date of trials from clinical trials registries (CTRs) with the date of their first available publication to provide an estimate of publication lag. Using CTRs we were able to produce anticipated networks for future time points based on projected study completion dates and average publication lags which illustrated expansion and strengthening of the initial network. We found that over a snapshot of periods between 2015 and 2018, evidence networks in melanoma changed substantively, adding new comparators and increasing network connectedness. Searching CTRs for ongoing trials demonstrates it is possible to anticipate future networks at a certain time point. Armed with this information, sensible decisions can be made over when best to conduct or update a NMA. Incorporating new and upcoming interventions in a NMA enables presentation of a complete, up-to-date and evolving picture of the evidence.
Cutaneous adverse events of anti-programmed death 1 antibodies combined with anti-cytotoxic T-lymphocyte-associated protein 4 therapy use in patients with metastatic melanoma
Authors: Hwang Shelley Ji Eun , Park John Jae Won , Wakade Deepal , Chou Shaun , Byth Karen , Fernandez-Penas Pablo
Published: October 2018

To date, cutaneous toxicities of combination therapies of anti-programmed death-1 (anti-PD1) and ipilimumab are poorly described. Understanding cutaneous presentations will aid clinicians with early diagnoses and treatments. We aim to describe and compare the cutaneous toxicities between the combination therapies and anti-PD1 monotherapy. This is a cohort study comparing previously published data on 82 patients with metastatic melanoma on anti-PD1 monotherapy, with a new group of 25 patients with metastatic melanoma receiving combined ipilimumab and pembrolizumab between January 2015 to February 2016. A single institution, internal referrals were received from medical oncology teams from May 2012 to February 2015 for the anti-PD1 monotherapy group and from January 2015 to February 2016 for combination group. All patients who were treated with either anti-PD1 therapy or combination therapies during the timeframe within the institution were included in the study. Kaplan–Meier curves were used to illustrate the time taken to develop cutaneous toxicities in the monotherapy and combination groups. Of the 25 patients, 88% developed new cutaneous lesions since the treatment. Immune-related lesions; lichenoid reaction (64%) and vitiligo (28%) were the most frequent. The incidence of lichenoid reaction increased rapidly in the early phase of treatment. Approximately one-third developed their first lichenoid reaction within 12 days of commencing treatment in combination group compared to 14 months in the anti-PD1 monotherapy. The rate of incidence of vitiligo was comparable in both groups. There was no statistical significance in the development of cutaneous toxicities and the treatment response between the two groups. The time taken to develop immune-related cutaneous toxicities was shorter for those on combination therapy versus anti-PD1 monotherapy.
Short article: Frequency, pathophysiology, and clinical classification of intestinal failure type II and III at a tertiary referral center
Authors: Rosas-Flota Ximena , Castillo-Martínez Lilia , Reyes-Ramírez Ana L. , Osorio-Alamillo Yahiel , Murguía-Vázquez Maria , Serralde-Zúñiga Aurora E.
Published: October 2018

Objective

Intestinal failure (IF) is a complex disease that is gaining significance and attention throughout the world. In Mexico, there are no available data on this condition. The aim of this study was to determine the frequency and characteristics of patients with IF type II and III hospitalized at a tertiary referral center in our country.

Patients and methods

A cross-sectional study was carried out from August 2016 to July 2017. Adult patients hospitalized in noncritical areas with a recent diagnosis of IF type II or III according to the European Society for Clinical Nutrition and Metabolism classification were included. Demographic, anthropometric, nutritional therapy, biochemical, and clinical characteristics were registered. Nutritional risk was determined by the Nutritional Risk Score 2002.

Results

During the study, 4144 patients were admitted to noncritical areas; 21 (5/1000) of these patients were included. The mean age of the patients was 51±18.8 years, and the mean BMI was 17.6±5.5 kg/m2. Fifteen (71.5%) patients were diagnosed with IF type II and six (28.5%) with IF type III. The primary diagnosis was surgical complications in seven (33.3%) of the cases and the principal pathophysiological mechanism was short bowel syndrome in nine (42.8%) patients. The most frequent (37%) clinical classification was D2: more than 20 kcal/kg/day and 1001–2000 ml/day and parenteral nutrition and PN2: 1001–2000 ml/day (52.3%) based on the modified European Society for Clinical Nutrition and Metabolism clinical classification.

Conclusion

In this study, a high frequency of IF was found; surgical complications and short bowel syndrome were the main mechanisms involved, and D2 was the most frequent clinical category.
Can epinephrine therapy be detrimental to patients with hypertrophic cardiomyopathy with hypotension or cardiac arrest? A systematic review
Authors: Ilicki Jonathan , Bruchfeld Samuel , Djärv Therese
Published: October 2018

Approximately 10% of sudden cardiac deaths among patients under 35 years of age is owing to hypertrophic cardiomyopathy (HCM)-related cardiac arrest (CA). CA is often associated with pre-arrest or peri-arrest hypotension and is treated by a set of interventions, including the administration of epinephrine. It is debated whether epinephrine increases or decreases survival to discharge following CA. HCM is associated with septal hypertrophy with a dynamic left ventricular outflow tract obstruction and impaired peripheral vasoconstriction in response to α1-adrenergic stimulation, both of which could cause epinephrine to have a different effect than in the general population. This systematic review of the literature aimed to investigate if patients with HCM in CA have a detrimental hemodynamic response to epinephrine. A literature search was performed in October 2016 using Medline (OVID), Embase (Elsevier), and Cochrane Library (Wiley). The initial search generated 2429 articles, of which 22 articles were found to meet inclusion criteria: four physiology studies, 13 case reports of hypotensive HCM patients, and five case reports of HCM patients in CA. The reviewed studies demonstrate that epinephrine effect varies in patients with HCM: in some cases, the expected hypertensive effect was obtained, but in others, a paradoxical hypotensive effect, or no effect, was observed. The probable mechanism of this effect is an increased left ventricular outflow tract obstruction. Other drugs were considered in several of these cases. In summary, the retrieved studies jointly suggest that patients with HCM may respond differently to epinephrine than patients without HCM. The suitability of epinephrine in HCM-associated CA is questionable.
Age and CD20 Expression Are Significant Prognostic Factors in Human Herpes Virus-8-negative Effusion-based Lymphoma
Authors: Kubota Tomomi , Sasaki Yosuke , Shiozawa Eisuke , Takimoto Masafumi , Hishima Tsunekazu , Chong Ja-Mun
Published: October 2018

Human herpes virus-8 (HHV-8)-negative effusion-based lymphoma (HHV-8-negative EBL) can be distinguished from primary effusion lymphoma based on clinical and pathologic findings. Although the morphology between the 2 is similar and they both originate from body cavities with serous effusions and are characterized by lack of tumor masses, HHV-8-negative EBL generally occurs in older patients, and has favorable response to therapy and better prognosis than primary effusion lymphoma. However, no systematic studies have investigated prognostic factors in patients with HHV-8-negative EBL. In this report, clinical and pathologic characteristics of 67 cases of HHV-8-negative EBL, including 2 of our own cases, were analyzed. Univariate analyses revealed older age (70 y and above), Japanese ethnicity, pericardial effusion, CD20 expression, and chemotherapy with rituximab were significantly favorable prognostic factors. Peritoneal effusion was identified as an unfavorable prognostic factor. In the multivariate analysis, age and CD20 expression were independent prognostic factors (P=0.013 and 0.003, respectively). A past history of induced fluid overload, hepatitis C viral infection, and peritoneal effusion were significantly correlated with patients aged below 70 years, while pericardial and pleural effusions were significantly correlated with patients aged 70 years and above. A comparison of cases with and without CD20 expression revealed that Japanese ethnicity and pericardial effusion were significantly correlated with CD20 expression, whereas a past history of induced fluid overload and peritoneal effusion were significantly correlated with the absence of CD20. We concluded that older age and CD20 expression are significant and favorable independent prognostic factors of HHV-8-negative EBL.
Rates of generation and destruction of the continental crust: implications for continental growth
Authors: Dhuime Bruno , Hawkesworth Chris J. , Delavault Hélène , Cawood Peter A.
Published: October 2018

Less than 25% of the volume of the juvenile continental crust preserved today is older than 3 Ga, there are no known rocks older than approximately 4 Ga, and yet a number of recent models of continental growth suggest that at least 60–80% of the present volume of the continental crust had been generated by 3 Ga. Such models require that large volumes of pre-3 Ga crust were destroyed and replaced by younger crust since the late Archaean. To address this issue, we evaluate the influence on the rock record of changing the rates of generation and destruction of the continental crust at different times in Earth's history. We adopted a box model approach in a numerical model constrained by the estimated volumes of continental crust at 3 Ga and the present day, and by the distribution of crust formation ages in the present-day crust. The data generated by the model suggest that new continental crust was generated continuously, but with a marked decrease in the net growth rate at approximately 3 Ga resulting in a temporary reduction in the volume of continental crust at that time. Destruction rates increased dramatically around 3 billion years ago, which may be linked to the widespread development of subduction zones. The volume of continental crust may have exceeded its present value by the mid/late Proterozoic. In this model, about 2.6–2.3 times of the present volume of continental crust has been generated since Earth's formation, and approximately 1.6–1.3 times of this volume has been destroyed and recycled back into the mantle.

This article is part of a discussion meeting issue ‘Earth dynamics and the development of plate tectonics'.
Geological archive of the onset of plate tectonics
Authors: Cawood Peter A. , Hawkesworth Chris J. , Pisarevsky Sergei A. , Dhuime Bruno , Capitanio Fabio A. , Nebel Oliver
Published: October 2018

Plate tectonics, involving a globally linked system of lateral motion of rigid surface plates, is a characteristic feature of our planet, but estimates of how long it has been the modus operandi of lithospheric formation and interactions range from the Hadean to the Neoproterozoic. In this paper, we review sedimentary, igneous and metamorphic proxies along with palaeomagnetic data to infer both the development of rigid lithospheric plates and their independent relative motion, and conclude that significant changes in Earth behaviour occurred in the mid- to late Archaean, between 3.2 Ga and 2.5 Ga. These data include: sedimentary rock associations inferred to have accumulated in passive continental margin settings, marking the onset of sea-floor spreading; the oldest foreland basin deposits associated with lithospheric convergence; a change from thin, new continental crust of mafic composition to thicker crust of intermediate composition, increased crustal reworking and the emplacement of potassic and peraluminous granites, indicating stabilization of the lithosphere; replacement of dome and keel structures in granite-greenstone terranes, which relate to vertical tectonics, by linear thrust imbricated belts; the commencement of temporally paired systems of intermediate and high dT/dP gradients, with the former interpreted to represent subduction to collisional settings and the latter representing possible hinterland back-arc settings or ocean plateau environments. Palaeomagnetic data from the Kaapvaal and Pilbara cratons for the interval 2780–2710 Ma and from the Superior, Kaapvaal and Kola-Karelia cratons for 2700–2440 Ma suggest significant relative movements. We consider these changes in the behaviour and character of the lithosphere to be consistent with a gestational transition from a non-plate tectonic mode, arguably with localized subduction, to the onset of sustained plate tectonics.

This article is part of a discussion meeting issue ‘Earth dynamics and the development of plate tectonics'.
Crustal evolution and mantle dynamics through Earth history
Authors: Korenaga Jun
Published: October 2018

Resolving the modes of mantle convection through Earth history, i.e. when plate tectonics started and what kind of mantle dynamics reigned before, is essential to the understanding of the evolution of the whole Earth system, because plate tectonics influences almost all aspects of modern geological processes. This is a challenging problem because plate tectonics continuously rejuvenates Earth's surface on a time scale of about 100 Myr, destroying evidence for its past operation. It thus becomes essential to exploit indirect evidence preserved in the buoyant continental crust, part of which has survived over billions of years. This contribution starts with an in-depth review of existing models for continental growth. Growth models proposed so far can be categorized into three types: crust-based, mantle-based and other less direct inferences, and the first two types are particularly important as their difference reflects the extent of crustal recycling, which can be related to subduction. Then, a theoretical basis for a change in the mode of mantle convection in the Precambrian is reviewed, along with a critical appraisal of some popular notions for early Earth dynamics. By combining available geological and geochemical observations with geodynamical considerations, a tentative hypothesis is presented for the evolution of mantle dynamics and its relation to surface environment; the early onset of plate tectonics and gradual mantle hydration are responsible not only for the formation of continental crust but also for its preservation as well as its emergence above sea level. Our current understanding of various material properties and elementary processes is still too premature to build a testable, quantitative model for this hypothesis, but such modelling efforts could potentially transform the nature of the data-starved early Earth research by quantifying the extent of preservation bias.

This article is part of a discussion meeting issue ‘Earth dynamics and the development of plate tectonics’.
Global tectonic evolution of Venus, from exogenic to endogenic over time, and implications for early Earth processes
Authors: Hansen Vicki L.
Published: October 2018

Venus provides a rich arena in which to stretch one's tectonic imagination with respect to non-plate tectonic processes of heat transfer on an Earth-like planet. Venus is similar to Earth in density, size, inferred composition and heat budget. However, Venus' lack of plate tectonics and terrestrial surficial processes results in the preservation of a unique surface geologic record of non-plate tectonomagmatic processes. In this paper, I explore three global tectonic domains that represent changes in global conditions and tectonic regimes through time, divided respectively into temporal eras. Impactors played a prominent role in the ancient era, characterized by thin global lithosphere. The Artemis superstructure era highlights sublithospheric flow processes related to a uniquely large super plume. The fracture zone complex era, marked by broad zones of tectonomagmatic activity, witnessed coupled spreading and underthrusting, since arrested. These three tectonic regimes provide possible analogue models for terrestrial Archaean craton formation, continent formation without plate tectonics, and mechanisms underlying the emergence of plate tectonics. A bolide impact model for craton formation addresses the apparent paradox of both undepleted mantle and growth of Archaean crust, and recycling of significant Archaean crust to the mantle.

This article is part of a discussion meeting issue ‘Earth dynamics and the development of plate tectonics’.