bluuebunny/crossref_metadata_2025 huggingface dataset:
Jean-Philippe Toussaint
Authors: Brodahl Greta
Published: September 2019

The purpose of this article is to study the intertextual play in four novels grouped under the label « MARIE
MADELEINE MARGUERITE DE MONTALTE » by the Belgian author Jean-Philippe Toussaint. The theoretical tool to study this phenomenon is
the theory of intertextuality and the intertextual typology in particular, extracted from Gérard Genette’s
Palimpsestes: la littérature au second degré (1982) and Tiphaine Samoyault’s Intertexte,
Mémoire de la littérature (2001). The main question the study raises is
what function the intertexts occupy in the tetralogy. The article distinguishes between a diegetic and a metaliterary function.
The study shows that the intertexts, mostly allusions, only play a minor role in the diegesis. However, several allusions occupy a
metaliterary function. Through these, the author debates literary questions. The author’s attitude is playful: He gently
mocks the authors behind the intertexts and enters into a dialogue with them at the same time.
Kindlin-3 stokes the life span of podosomes
Authors: Zhang Hongquan
Published: September 2019

Macrophages and other cell types can form podosomes, highly dynamic adhesive structures that mediate the interaction of these cells with the surrounding matrix. In this issue, Klapproth et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201903109) find that kindlin-3 regulates podosome stability by recruiting leupaxin, with concomitant effects on PTP-PEST phosphatase activity and paxillin phosphorylation.
Gamma-Ray Polarimetry: A New Window for the Nonthermal Universe
Authors: Ilie Cosmin
Published: September 2019

Over the past few decades, impressive progress has been made in the field of photon polarimetry, especially in the hard X-ray and soft gamma-ray energy regime. Measurements of the linear degree of polarization for some of the most energetic astrophysical sources, such as gamma-ray bursts (GRBs) or blazars, are now possible, at energies below the pair creation threshold. As such, a new window has been opened for understanding the exact nature of the nonthermal emission mechanisms responsible for some of the most energetic phenomena in the universe. There are still many open questions and active debates, such as the discrimination between leptonic versus hadronic models of emission for Blazars or ordered versus random field models for GRBs. Because the competing models predict different levels of linear photon polarization at energies above ∼1 MeV, gamma-ray polarimetry in that energy band could provide additional crucial insights. However, no polarimeter for gamma rays with energies above ∼1 MeV has been flown into space, as the sensitivity is severely limited by a quick degradation of the angular resolution and by multiple Coulomb scatterings in the detector. Over the past few years, a series of proposals and demonstrator instruments that aim to overcome those inherent difficulties have been put forth, and the prospects look promising. The paper is organized as follows: Section 1, briefly reviews the history and principles of gamma-ray polarimetry, emphasizing its challenges and successes; Section 2 is dedicated the discussion of gamma-ray polarization and polarimetry, and Section 3 discusses the past and current instruments with which measurements of linear polarization for hard X-rays and soft gamma rays were successfully obtained for astrophysical sources; Section 4 outlines the scientific questions that could be solved by using gamma-ray polarimetry measurements. A summary and outlook are provided in Section 5.
Developmental constraints and resource environment shape early emergence and investment in spines in saplings
Authors: Armani Mohammed , Charles-Dominique Tristan , Barton Kasey E , Tomlinson Kyle W
Published: September 2019

Background and Aims

Herbivory by large mammals imposes a critical recruitment bottleneck on plants in many systems. Spines defend plants against large herbivores, and how early they emerge in saplings may be one of the strongest predictors of sapling survival in herbivore-rich environments. Yet little effort has been directed at understanding the variability in spine emergence across saplings.

Methods

We present a multispecies study examining whether and how sapling size, spine type and species' environmental niche (light and precipitation environment) influence early emergence and biomass investment in spines. A phylogenetically diverse pool of 45 species possessing different spine types (spines, prickles and thorns; that are derived from distinct plant organs: leaf, epidermis or cortex, and branch, respectively), were grown under common-garden conditions, and patterns of spine emergence and biomass allocation to spines at 5 and 15 weeks after transplanting were characterized.

Key Results

Spine type and species' resource niche were the main factors driving early emergence and investment patterns. Spines emerged earliest in leaf spine-bearing species, and latest in thorn-bearing species. The probability of early spine emergence increased with decreasing precipitation, and was greater in species from open than from closed habitats. Sapling investment in spines changed with plant mass but was contingent on spine type and habitat type.

Conclusions

Different spine types have strikingly different timing of expression, suggesting that developmental origins of spines play a critical role in sapling defences. Furthermore, species from different precipitation and light environments (open vs. closed habitats) showed contrasting patterns of early spine expression, suggesting that resource limitation in their native range may have driven divergent evolution of early defence expression.
New Horizons, new worlds, new names
Authors: Kissick Lucy
Published: September 2019

Lucy Kissick examines the origins and significance of the names approved for Pluto's surprisingly varied surface.
Equality, diversity and inclusion perspectives
Authors: Maguire-Rajpaul Vinesh , Jermak Helen , Kanani Sheila , van Loon Jacco Th. , Habergham-Mawson Stacey
Published: September 2019

An overview of the developments arising from equality, diversity and inclusion events at this year's National Astronomy Meeting, by Vinesh Maguire-Rajpaul on behalf of the organizers.
Q&A Philip Diamond
Authors: Johnson Paul
Published: September 2019

Following the inauguration of the Square Kilometre Array's HQ at Jodrell Bank in July, the director-general of the SKA Organisation opens up about his past, present and future. Interview by Paul Johnson.
Health system resilience in the face of crisis: analysing the challenges, strategies and capacities for UNRWA in Syria
Authors: Jamal Zeina , Alameddine Mohamad , Diaconu Karin , Lough Graham , Witter Sophie , Ager Alastair , Fouad Fouad M
Published: September 2019

Health system resilience reflects the ability to continue service delivery in the face of extraordinary shocks. We examined the case of the United Nations Relief and Works Agency (UNRWA) and its delivery of services to Palestine refugees in Syria during the ongoing crisis to identify factors enabling system resilience. The study is a retrospective qualitative case study utilizing diverse methods. We conducted 35 semi-structured interviews with UNRWA clinical and administrative professionals engaged in health service delivery over the period of the Syria conflict. Through a group model building session with a sub-group of eight of these participants, we then elicited a causal loop diagram of health system functioning over the course of the war, identifying pathways of threat and mitigating resilience strategies. We triangulated analysis with data from UNRWA annual reports and routine health management information. The UNRWA health system generally sustained service provision despite individual, community and system challenges that arose during the conflict. We distinguish absorptive, adaptive and transformative capacities of the system facilitating this resilience. Absorptive capacities enabled immediate crisis response, drawing on available human and organizational resources. Adaptive capacities sustained service delivery through revised logistical arrangements, enhanced collaborative mechanisms and organizational flexibility. Transformative capacity was evidenced by the creation of new services in response to changing community needs. Analysis suggests factors such as staff commitment, organizational flexibility and availability of collaboration mechanisms were important assets in maintaining service continuity and quality. This evidence regarding alternative strategies adopted to sustain service delivery in Syria is of clear relevance to other actors seeking organizational resilience in crisis contexts.
Transitional Justice in Tunisia: When Religion Meets State
Authors: Kazemi Elham
Published: September 2019

ABSTRACT∞

In response to criticisms pointed toward the liberal framework of transitional justice (TJ) and its detachment from local communities and norms, there has been a move toward ‘localism’ in the literature and practice of TJ. Recently, a call was made to incorporate Islamic principles and mechanisms into postconflict and post-transition efforts as a measure to increase the local legitimacy and ownership of TJ as well as its acceptance by the local population. Yet, even here, challenges and obstacles remain. Using Tunisia as an illustrative case study, this article argues that local TJ is not immune to power struggles. More specifically, in countries with a legacy of state-sponsored assertive secularism, religion is more likely to play a role as a marker of political and collective identity leading to polarization in the transition process.
Neoliberalism as Religion: Sacralization of the Market and Post-truth Politics
Authors: Mavelli Luca
Published: September 2019

Since the 2008 financial crisis, depictions of neoliberalism as a religion, system of belief, and “kind of faith” have multiplied in an attempt to explain neoliberalism's remarkable power and resilience. These accounts, however, have remained largely impressionistic. In this article, I interrogate the meanings, implications, and value of conceptualizing neoliberalism as religion and advance two main claims. First, the power of neoliberalism stems from being a rationality of government that continuously evokes religious meanings and significations. Neoliberalism displaces and redraws the boundary between secular and religious and appropriates an aura of sacredness while concealing itself behind an authoritative secular rational façade. Second, one of the outcomes of the neoliberal “sacralization” of the market has been the emergence of so-called “post-truth politics.” The latter, I contend, can be conceptualized as a neoliberal “truth market” of news production, circulation, and consumption that is governed simultaneously by logics of commodification and belief. This analysis aims to contribute to existing debates on secularization, on neoliberalism's resilience, and on post-truth politics. It shows their interconnectedness through a critical approach that focuses on the disarticulation, rearticulation, and deployment of the categories of the secular/profane and religious/sacred in neoliberal regimes of power and knowledge.
Borders, Detention, and the Disruptive Power of the Noisy-Subject
Authors: Ozguc Umut
Published: September 2019

Violent borders are one of the most pressing ethical and political questions of our time. This article seeks to challenge the violent construction of borders through the concept of noise. Drawing on Michel Serres's philosophy of noise and Marie Thompson's emphasis on its affectiveness, the article shows the generative, disruptive, and affective power of noise at the border. I argue that noise creates a disruption in the system and, in doing so, calls for new encounters and relations that operate within and beyond existing power relations. I suggest that the figure of the noisy-subject creates, interrupts, and disturbs the border. The noisy-subject simultaneously prompts disorder and order on the border and transforms it into a third space that is neither simply captured by the sovereign nor fully emancipated from its power. The border as a third space constantly moves with the affective force of its noisy-subjects.
Unusual olfactory perception during radiation sessions for primary brain tumors: a retrospective study
Authors: Obinata Mika , Yamada Kana , Sasai Keisuke
Published: September 2019

During irradiation sessions for brain tumors or head and neck cancers, some patients experience abnormal olfactory sensations. To date, the frequency of such sensations during these treatment sessions has not been investigated. We analyzed abnormal olfactory sensations in patients who underwent radiation therapy at our institution for primary brain tumors, excluding malignant lymphoma, between January 2009 and January 2018. A total of 191 patients who were awake during radiation treatment and capable of communicating were analyzed in this retrospective medical study. Of these patients, 7 were aware of olfactory sensations during irradiation. The median age of these 7 patients was 13 (range 8–47) years, Six were <20 years of age, accounting for 10% of the total population of similar age (n = 60). However, only 1 of 131 patients aged ≥20 years complained of strange olfactory sensations. Four of seven patients had germ cell tumors, but none had a medulloblastoma. We investigated patients who experienced light sensation, as an internal standard to ascertain the accuracy of this study. Only 10 patients experienced light sensation during their irradiation sessions. This suggests that the frequency of these sensations was possibly underestimated in our study. In conclusion, a considerable number of patients experienced unusual olfactory sensations during radiation treatment. Further prospective studies on abnormal olfactory sensations during irradiation are needed to clarify the underlying mechanism of this sensation.
Paediatric acute lymphadenitis: Emergency department management and clinical course
Authors: Long Michelle , Reddy Deepti N , Akiki Salwa , Barrowman Nicholas J , Zemek Roger
Published: September 2019

Objectives

To describe clinical characteristics and management of acute lymphadenitis and to identify risk factors for complications.

Methods

Health record review of children ≤17 years with acute lymphadenitis (≤2 weeks) in a tertiary paediatric emergency department (2009–2014); 10% of charts were reviewed by a blinded second reviewer. Multivariate logistic regression identified factors associated with intravenous antibiotic treatment, unplanned return visits warranting intervention, and surgical drainage.

Results

Of 1,023 health records, 567 participants with acute lymphadenitis were analyzed. The median age = 4 years (interquartile range [IQR]: 2 to 8 years), and median duration of symptoms = 1.0 day (IQR: 0.5 to 3.0 days). Cervical lymphadenitis was most common. Antibiotics were prescribed in 73.5% of initial visits; 86.9% of participants were discharged home. 29.0% received intravenous antibiotics, 19.3% had unplanned emergency department return visits, and 7.4% underwent surgical drainage. On multivariate analysis, factors associated with intravenous antibiotic use included history of fever (odds ratio [OR]=2.07, 95% confidence interval [CI]: 1.11 to 3.92), size (OR=1.74 per cm, 95% CI: 1.44 to 2.14), age (OR=0.84 per year, 95% CI: 0.76 to 0.92), and prior antibiotic use (OR=4.45, 95% CI: 2.03 to 9.88). The factors associated with unplanned return visit warranting intervention was size (OR=1.30 per cm, 95% CI: 1.06 to 1.59) and age (OR=0.89, 95% CI: 0.80 to 0.97). Factors associated with surgical drainage were age (OR=0.68 per year, 95% CI: 0.53 to 0.83) and size (OR=1.80 per cm, 95% CI: 1.41 to 2.36).

Conclusions

The vast majority of children with acute lymphadenitis were managed with outpatient oral antibiotics and did not require return emergency department visits or surgical drainage. Larger lymph node size and younger age were associated with increased intravenous antibiotic initiation, unplanned return visits warranting intervention and surgical drainage.
Core and ‘Crust’: Consumer Prices and the Term Structure of Interest Rates
Authors: Ajello Andrea , Benzoni Luca , Chyruk Olena
Published: September 2019

We propose a no-arbitrage model of the nominal and real term structures that accommodates the different persistence and volatility of distinct inflation components. Core, food, and energy inflation combine into a single total inflation measure that ties nominal and real risk-free bond prices together. The model successfully extracts market participants’ expectations of future inflation from nominal yields and inflation data. Estimation uncovers a factor structure common to core inflation and interest rates and downplays the pass-through effect of short-lived food and energy shocks on inflation and interest rates. Model forecasts systematically outperform survey forecasts and other benchmarks.

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
From the Political to the Personal: Work and Class in 1970s British Feminist Art
Authors: McLellan Josie
Published: September 2019

How did British feminist art of the 1970s represent work and class, and what light does this shed on the women’s movement more generally? This article discusses the work of artists, including Bobby Baker, the Feministo and Fenix collectives, the Hackney Flashers, and Mary Kelly. These artists were eager to connect feminist activism to other struggles on the Left and were thus initially drawn to document working-class women’s paid work. Their political commitment to represent ‘ordinary’ working lives often led to lengthy periods of research, as well as attempts to make both the creative process and the finished product accessible to new participants and audiences. However, across this period, two changes took place. First, artists began to focus on women’s unpaid work, drawing attention to the tension between domestic work and paid employment, and the lack of easy solutions to this problem. Secondly, most lost faith in art’s power to represent the experience of work beyond the individual and the personal. Early political idealism gave way to sustained soul-searching about the intellectual, moral, and aesthetic difficulties of representing the experience of others, particularly those of a different class background. This article, then, shows that the early British women’s movement was keen to engage with working-class experience and that it did so in a way that was self-reflective. In the end, it was this self-reflection, and the questions that it generated about the morality, politics, and aesthetics of representing others, that led to the personal and psychological turn of the later 1970s.
Evolution of mechanisms and behaviour important for pain
Authors: Walters Edgar T. , Williams Amanda C. de C.
Published: September 2019

Our understanding of the biology of pain is limited by our ignorance about its evolution. We know little about how states in other species showing various degrees of apparent similarity to human pain states are related to human pain, or how the mechanisms essential for pain-related states evolved. Nevertheless, insights into the evolution of mechanisms and behaviour important for pain are beginning to emerge from wide-ranging investigations of cellular mechanisms and behavioural responses linked to nociceptor activation, tissue injury, inflammation and the environmental context of these responses in diverse species. In February 2019, an unprecedented meeting on the evolution of pain hosted by the Royal Society brought together scientists from disparate fields who investigate nociception and pain-related behaviour in crustaceans, insects, leeches, gastropod and cephalopod molluscs, fish and mammals (primarily rodents and humans). Here, we identify evolutionary themes that connect these research efforts, including adaptive and maladaptive features of pain-related behavioural and neuronal alterations—some of which are quite general, and some that may apply primarily to humans. We also highlight major questions, including how pain should be defined, that need to be answered as we seek to understand the evolution of pain.

This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.
Does epigenetic ‘memory’ of early-life stress predispose to chronic pain in later life? A potential role for the stress regulator
FKBP5
Authors: Géranton S. M.
Published: September 2019

Animal behaviours are affected not only by inherited genes but also by environmental experiences. For example, in both rats and humans, stressful early-life events such as being reared by an inattentive mother can leave a lasting trace and affect later stress response in adult life. This is owing to a chemical trace left on the chromatin attributed to so-called epigenetic mechanisms. Such an epigenetic trace often has consequences, sometimes long-lasting, on the functioning of our genes, thereby allowing individuals to rapidly adapt to a new environment. One gene under such epigenetic control is
FKBP5
, the gene that encodes the protein FKPB51, a crucial regulator of the stress axis and a significant driver of chronic pain states. In this article, we will discuss the possibility that exposure to stress could drive the susceptibly to chronic pain
via
epigenetic modifications of genes within the stress axis such as
FKBP5
. The possibility that such modifications, and therefore, the susceptibility to chronic pain, could be transmitted across generations in mammals and whether such mechanisms may be evolutionarily conserved across phyla will also be debated.

This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.
MNK-eIF4E signalling is a highly conserved mechanism for sensory neuron axonal plasticity: evidence from
Aplysia californica
Authors: Mihail Sandra M. , Wangzhou Andi , Kunjilwar Kumud K. , Moy Jamie K. , Dussor Gregory , Walters Edgar T. , Price Theodore J.
Published: September 2019

Injury to sensory neurons causes an increase in the excitability of these cells leading to enhanced action potential generation and a lowering of spike threshold. This type of sensory neuron plasticity occurs across vertebrate and invertebrate species and has been linked to the development of both acute and persistent pain. Injury-induced plasticity in sensory neurons relies on localized changes in gene expression that occur at the level of mRNA translation. Many different translation regulation signalling events have been defined and these signalling events are thought to selectively target subsets of mRNAs. Recent evidence from mice suggests that the key signalling event for nociceptor plasticity is mitogen-activated protein kinase-interacting kinase (MNK) -mediated phosphorylation of eukaryotic translation initiation factor (eIF) 4E. To test the degree to which this is conserved in other species, we used a previously described sensory neuron plasticity model in
Aplysia californica
. We find, using a variety of pharmacological tools, that MNK signalling is crucial for axonal hyperexcitability in sensory neurons from
Aplysia
. We propose that MNK-eIF4E signalling is a core, evolutionarily conserved, signalling module that controls nociceptor plasticity. This finding has important implications for the therapeutic potential of this target, and it provides interesting clues about the evolutionary origins of mechanisms important for pain-related plasticity.

This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.
Generating Evidence for Chronic Obstructive Pulmonary Disease (COPD) Clinical Guidelines Using EHR Data
Authors: Johnson Amber M. , Bikak Marvi , Griffin Paul M. , Adibuzzaman Mohammad
Published: September 2019

Objectives

The aim of this research was to develop data-driven models using electronic health records (EHRs) to conduct clinical studies for predicting clinical outcomes through probabilistic analysis that considers temporal aspects of clinical data. We assess the efficacy of antibiotics treatment and the optimal time of initiation for in-hospitalized diagnosed with acute exacerbation of COPD (AECOPD) as an application to probabilistic modeling.

Materials and Methods

We developed a semi-automatic Markov Chain Monte Carlo (MCMC) modeling and simulation approach that encodes clinical conditions as computable definitions of health states and exact time duration as input for parameter estimations using raw EHR data. We applied the MCMC approach to the MIMIC-III clinical database, where ICD-9 diagnosis codes (491.21, 491.22, and 494.1) were used to identify data for 697 AECOPD patients of which 25.9% were administered antibiotics.

Results

The average time to antibiotic administration was 27 hours, and 32% of patients were administered vancomycin as the initial antibiotic. The model simulations showed a 50% decrease in mortality rate as the number of patients administered antibiotics increased. There was an estimated 5.5% mortality rate when antibiotics were initially administrated after 48 hours vs 1.8% when antibiotics were initially administrated between 24 and 48 hours.

Discussion

Our findings suggest that there may be a mortality benefit in initiation of antibiotics early in patient with severe respiratory failure in settings of COPD exacerbations warranting an ICU admission.

Conclusion

Probabilistic modeling and simulation methods that considers temporal aspects of raw clinical patient data can be used to adequately generate evidence for clinical guidelines.
Efficacy and safety of erythropoietin for traumatic brain injury: a meta-analysis of randomized controlled trials
Authors: Liu Motao , Wang Amy J. , Zhao Gexin , He Hua , Williams Ziv M. , Hu Kejia
Published: September 2019

Objective

Recent studies regarding the effects of erythropoietin (EPO) for treating traumatic brain injury (TBI) have been inconsistent. This study conducts a meta-analysis of randomized controlled trials (RCTs) to assess the safety and efficacy of EPO for TBI patients at various follow-up time points.

Methods

A literature search was performed using PubMed, Web of Science, MEDLINE, Embase, Google Scholar and the Cochrane Library for RCTs studying EPO in TBI patients published through March 2019. Non-English manuscripts and non-human studies were excluded. The assessed outcomes include mortality, neurological recovery and associated adverse effects. Dichotomous variables are presented as risk ratios (RR) with a 95% confidence interval (CI).

Results

A total of seven RCTs involving 1197 TBI patients were included in this study. Compared to the placebo arm, treatment with EPO did not improve acute hospital mortality or short-term mortality. However, there was a significant improvement in mid-term (6 months) follow-up survival rates. EPO administration was not associated with neurological function improvement. Regarding adverse effects, EPO treatment did not increase the incidence of thromboembolic events or other associated adverse events.

Conclusions

This meta-analysis indicates a slight mortality benefit for TBI patients treated with EPO at mid-term follow-up. EPO does not improve in-hospital mortality, nor does it increase adverse events including thrombotic, cardiovascular and other associated complications. Our analysis did not demonstrate a significant beneficial effect of EPO intervention on the recovery of neurological function. Future RCTs are required to further characterize the use of EPO in TBI.
Neuropsychological stratification of Chronic Obstructive Pulmonary Disease: building affect into clinically relevant neuro-biomarkers of breathlessness
Authors: Finnegan Sarah L. , Faull Olivia K. , Harmer Catherine J. , Herigstad Mari , Rahman Najib M. , Reinecke Andrea , Pattinson Kyle T.S.
Published: September 2019

Background

Chronic breathlessness profoundly affects quality of life for its sufferers. Often, reported breathlessness is inconsistent with airway pathophysiology and objective disease markers. While a mechanistic understanding of this discordance has thus far remained elusive, factors such as mood, attention and expectation have all been implicated as important perceptual modulators. Therefore, here we have developed a model capable of exploring these relationships aiding patient stratification and revealing clinically-relevant neuro-biomarkers.

Methods

A cohort of 100 participants with mild-to-moderate chronic obstructive pulmonary disease (COPD) underwent a comprehensive assessment that included functional brain imaging while viewing and rating breathlessness-related word cues, self-report questionnaires and clinical measures.

Results

Using an exploratory factor analysis across psychological and physiological measures, we identified two distinctive neuropsychological behavioural profiles that differed across four key factors corresponding to mood, symptom burden, and two capability measures. These profiles stratified participants into high and low symptom groups, which did not differ in spirometry values. The low symptom load group demonstrated greater FMRI activity to breathlessness-related word cues in the anterior insula.

Conclusions

Our findings reveal two clear groups of individuals within our COPD cohort, divided by behavioural rather than clinical factors. Furthermore, indices of depression, anxiety, vigilance and perceived capability were linked to differences in brain activity within key regions thought to be involved in monitoring bodily sensations (interoception). These findings demonstrate the complex relationship between affect and interoceptive processing, providing the foundations for the development of targeted treatment programmes that harness clinical and symptom-relevant biomarkers.
Use of consensus term and definition for delayed cerebral ischaemia after aneurysmal subarachnoid haemorrhage
Authors: Rowland Matthew J , Pattinson Kyle T.S. , Vergouwen Mervyn D.I. , Watkinson Peter J
Published: September 2019

Background and purpose

In 2010, a multidisciplinary research group proposed a consensus term and definition for the complication of delayed cerebral ischaemia (DCI) following aneurysmal subarachnoid haemorrhage (SAH). We assessed the use of this term and its definition as an endpoint in observational studies and clinical trials.

Methods

Firstly, we performed a MEDLINE abstract search from Jan 2008 to Dec 2017 for observational cohort studies and clinical trials to investigate the used terminology over the years. Next, we studied trends in citations of the original paper citing the consensus definitions since publication in 2010.

Results

The number of publications citing the 2010 consensus definitions has steadily increased from 18 in 2011 to 54 in 2017. Between 2010 and 2017, 527 papers were published with delayed cerebral ischemia, or another term to describe the same complication, as an endpoint. However, the term delayed cerebral ischemia was used only in 131/527 (25%) of papers and only 14/81 (17%) of clinical trials/cohort studies published in 2017 cited the consensus definitions when outlining study endpoints.

Conclusions

Despite publication of consensus terminology and definitions for DCI in 2010, the majority of cohort studies and clinical trials in patients with SAH are not using these. Researchers and editors should be reminded of the importance of using these consensus terminology and definitions in future studies, which will promote the comparability of results between studies, understand the true impact of an intervention, aggregate results in meta-analyses, and construct guidelines with a high level of evidence.
Not all seabird species can overcome marine threats when predator removal at their colonies is prioritised
Authors: Borrelle Stephanie B. , Jones Holly P. , Richard Yvan , Salguero-Gómez Roberto
Published: September 2019

Seabirds are globally threatened. In the face of multiple threats, it is critical to understand how conservation strategies that mitigate one threat intersect with others to impact population viability. Marine threats, including pollution, climate change, and fisheries could derail gains to seabird populations resulting from arduous predator eradication efforts. However, this potentially negative effect is yet to be evaluated. We test whether mortality from marine threats can subvert the on-going recovery of 17 seabird species from 37 colonies on islands worldwide where predators were removed. We use demographic modelling to estimate potential adult mortality from fisheries, plastic ingestion, and climate change. For 82% of the species we examine, marine threats do not impede recovery following predator eradication. However, for six colonies of three species, Calonectris diomedea, C. borealis, and Ardenna carneipes, mortality from multiple marine threats may interrupt their recovery. Combining our demographic approach with comparative phylogenetic methods, we explore whether foraging niche, range, and morphometric traits inform the vulnerability to marine threats using an expanded dataset of 81 seabird species. Our analyses reveal surface filtering and pursuit diving species, and species with smaller at-sea distributions to be most vulnerable to declines due to multiple threats. However, these traits do not necessarily predict species’ vulnerability to marine threats in the absence of predators at nesting colonies, suggesting that shared traits may not be useful to infer vulnerability to multiple marine threats. Post-eradication monitoring to determine whether species require additional conservation management following predator eradication are essential in the face of intensifying pressures in the marine environment.
Predictability of the antigenic evolution of human influenza A H3 viruses
Authors: Aguas R. , Ferguson N.M.
Published: September 2019

The current influenza A antigenic evolution paradigm suggesting that antigenic evolution is highly constrained, with successful new viruses being near optimal at maximizing their antigenic distance from past strains. This begs the question of whether influenza’s antigenic evolution is fundamentally predictable, or if it takes place on a much higher dimensional antigenic space with multiple possible trajectories. We tackle this issue by building a genotype to phenotype map validated on historical hemagglutination inhibition assay data by using machine learning methods. This map uses amino acid physiochemical properties for inference, learning the expected antigenic distance given the differences in polarity and hydrophobicity observed across any two viral sequences, and is thus applicable to newly sampled viruses with previously unseen amino acids. This allows us to accurately blindly predict the antigenic relevance of soon to be vaccine viral strains. We couple the genotype to phenotype map with a molecular evolutionary simulation algorithm to explore the limits of influenza’s antigenic evolution and infer to what extent it is in fact predictable. Although we do uncover some canalization of antigenic trajectories, we find that multiple antigenic lineages are equally viable at any one point in time even though typically only one of those trajectories is actually realized.
Towards Intelligent Intra-cortical BMI (i2BMI): Low-power Neuromorphic Decoders that outperform Kalman Filters
Authors: Shaikh Shoeb , So Rosa , Sibindi Tafadzwa , Libedinsky Camilo , Basu Arindam
Published: September 2019

Fully implantable wireless intra-cortical Brain Machine Interfaces (iBMI) is one of the most promising next frontiers in the nascent field of neurotechnology. However, scaling the number of channels in such systems by another 10X is difficult due to power and bandwidth requirements of the wireless transmitter. One promising solution for that is to include more processing, up to the decoder, in the implant so that transmission data rate is reduced drastically. Earlier work on neuromorphic decoders only showed classification of discrete states. We present results for continuous state decoding using a low power neuromorphic decoder chip termed Spike-input Extreme Learning Machine (SELMA). We compared SELMA against state of the art Steady State Kalman Filter (SSKF) across two different datasets involving a total of 4 non-human primates (NHPs). Results show at least a 10% or more increase in the fraction of variance accounted for by SELMA over SSKF across the datasets. Furthermore, estimated energy consumption comparison shows SELMA consuming ≈ 9 nJ/update against SSKF’s ≈ 7.4 nJ/update for an iBMI with a 10 degree of freedom control. Thus, SELMA yields better performance against SSKF with a marginal increase in energy consumption paving the way for reducing transmission data rates in future scaled BMI systems.
Sub-Optimal Learning of Tactile-Spatial Predictions in Patients with Complex Regional Pain Syndrome
Authors: Brown Christopher A. , Scholtes Ingrid , Shenker Nicholas , Lee Michael C.
Published: September 2019

In Complex Regional Pain Syndrome (CRPS), tactile sensory deficits have motivated the therapeutic use of sensory discrimination training. However, the hierarchical organisation of the brain is such that low-level sensory processing can be dynamically influenced by higher-level knowledge, e.g. knowledge learnt from statistical regularities in the environment. It is unknown whether the learning of such statistical regularities is impaired in CRPS. Here, we employed a hierarchical Bayesian model of predictive coding to investigate statistical learning of tactile-spatial predictions in CRPS. Using a sensory change-detection task, we manipulated bottom-up (spatial displacement of a tactile stimulus) and top-down (probabilistic structure of occurrence) factors to estimate hierarchies of prediction and prediction error signals, as well as their respective precisions or reliability. Behavioural responses to spatial changes were influenced by both the magnitude of spatial displacement (bottom-up) and learnt probabilities of change (top-down). The Bayesian model revealed that patients’ predictions (of spatial displacements) were found to be less precise, deviating further from the ideal (statistical optimality) compared to healthy controls. This imprecision was less context-dependent, i.e. more enduring across changes in probabilistic context and less finely-tuned to statistics of the environment. This caused greater precision on prediction errors, resulting in predictions that were driven more by momentary spatial changes and less by the history of spatial changes. These results suggest inefficiencies in higher-order statistical learning in CRPS. This may have implications for therapies based on sensory re-training whose effects may be more short-lived if success depends on higher-order learning.
Maternally-transferred thyroid hormones and life-history variation in birds
Authors: Hsu Bin-Yan , Pakanen Veli-Matti , Boner Winnie , Eeva Tapio , Doligez Blandine , Groothuis Ton G.G. , Korpimäki Erkki , Laaksonen Toni , Lelono Asmoro , Monaghan Pat , Sarraude Tom , Tschirren Barbara , Thomson Robert L. , Tolvanen Jere , Vásquez Rodrigo A. , Ruuskanen Suvi
Published: September 2019

Life-history traits vary largely across species and several physiological parameters have been proposed to be associated with life-history variation, such as metabolic rates, glucocorticoids, and oxidative stress. Interestingly, the association between thyroid hormones (THs) and life history variation has never been considered, despite a close interaction between THs and these physiological traits. Because of the crucial effects on embryonic development, THs can also induce transgenerational plasticity when transferred to developing offspring, for instance, via egg yolks in birds. In this study, we compiled a unique data set of maternal yolk THs in 34 bird species across 17 families and 6 orders, and tested for associations with various life-history traits. Our phylogenetic mixed models indicated that both concentrations and total amounts of the two most important forms of THs (T3 and T4) were higher in the eggs of migratory species than in those of resident species, and that there were higher total amounts of T3 in the eggs of precocial species than in those of altricial species. However, maternal THs did not show clear associations with any traits of the pace-of-life syndrome, such as developmental duration, growth rate, or lifespan. When taking environmental factors into account, we found that captive species deposited higher TH concentrations and larger amounts in the egg yolks than wild species. These findings suggest that maternal THs are likely involved in the evolution of life-history variation, or vice versa.
Antibody against envelope protein from human endogenous retrovirus activates neutrophils in systemic lupus erythematosus
Authors: Tokuyama Maria , Gunn Bronwyn M. , Venkataraman Arvind , Kong Yong , Kang Insoo , Townsend Michael J. , Costenbader Karen H. , Alter Galit , Iwasaki Akiko
Published: September 2019

Neutrophil activation and the formation of neutrophil extracellular trap (NET) are hallmarks of innate immune activation in systemic lupus erythematosus (SLE) and contribute to the systemic interferon signature. Here we report that the expression of an endogenous retrovirus (ERV) locus ERV-K102, encoding an envelope protein, was significantly elevated in SLE patient blood and was correlated with higher interferon status. Induction of ERV-K102 expression most strongly correlated with reduced transcript levels of epigenetic silencing factors. SLE IgG promoted phagocytosis of ERV-K102 envelope protein by neutrophils through immune complex formation. ERV immune complex phagocytosis resulted in subsequent NET formation consisting of DNA, neutrophil elastase, and citrullinated histone H3. Finally, analysis of anti-ERV-K102 IgG in SLE patients showed that IgG2 likely mediates this effect. Together, we identified an immunostimulatory ERV-K envelope protein elevated in SLE that may be a target of SLE IgG and able to promote neutrophil activation.

eTOC summary

Using ERVmap, the authors determined that the expression of ERV-K102 locus was elevated in SLE patient blood and correlated with the interferon signature. The envelope protein encoded by this locus activates human neutrophils through immune complex formation with SLE IgG.
Carbon Assimilation Strategies in Ultrabasic Groundwater: Clues from the Integrated Study of a Serpentinization-Influenced Aquifer
Authors: Seyler L.M. , Brazelton W.J. , McLean C. , Putman L.I. , Hyer A. , Kubo M.D.Y. , Hoehler T. , Cardace D. , Schrenk M.O.
Published: September 2019

Serpentinization is a low-temperature metamorphic process by which ultramafic rock chemically reacts with water. These reactions provide energy and materials that may be harnessed by chemosynthetic microbial communities at hydrothermal springs and in the subsurface. However, the biogeochemistry of microbial populations that inhabit these environments are understudied and are complicated by overlapping biotic and abiotic processes. We applied metagenomics, metatranscriptomics, and untargeted metabolomics techniques to environmental samples taken from the Coast Range Ophiolite Microbial Observatory (CROMO), a subsurface observatory consisting of twelve wells drilled into the ultramafic and serpentinite mélange of the Coast Range Ophiolite in California. Using a combination of DNA and RNA sequence data and mass spectrometry data, we determined that several carbon assimilation strategies, including the Calvin-Benson-Bassham cycle, the reverse tricarboxylic acid cycle, the reductive acetyl-CoA pathway, and methylotrophy are used by the microbial communities inhabiting the serpentinite-hosted aquifer. Our data also suggests that the microbial inhabitants of CROMO use products of the serpentinization process, including methane and formate, as carbon sources in a hyperalkaline environment where dissolved inorganic carbon is unavailable.

Importance

This study describes the metabolic pathways by which microbial communities in a serpentinite-influenced aquifer may produce biomass from the products of serpentinization. Serpentinization is a widespread geochemical process, taking place over large regions of the seafloor, particularly in slow-spreading mid ocean ridge and subduction zone environments. The serpentinization process is implicated in the origin of life on Earth and as a possible environment for the discovery of life on other worlds in our solar system. Because of the difficulty in delineating abiotic and biotic processes in these environments, major questions remain related to microbial contributions to the carbon cycle and physiological adaptation to serpentinite habitats. This research explores multiple mechanisms of carbon assimilation in serpentinite-hosted microbial communities.
Targeting the methyltransferase SETD8 impairs tumor cell survival and overcomes drug resistance independently of p53 status in multiple myeloma
Authors: Herviou Laurie , Izard Fanny , Karmous-Gadacha Ouissem , Gourzones Claire , Bellanger Celine , Desmedt Eva , Ma Anqi , Vincent Laure , Cartron Guillaume , Vanderkerken Karin , Jin Jian , De Bruyne Elke , Grimaud Charlotte , Julien Eric , Moreaux Jérôme
Published: September 2019

Multiple myeloma (MM) is a malignancy of plasma cells that largely remains incurable. The search for new therapeutic targets is therefore essential. Here we show that a higher expression of the lysine methyltransferase SETD8, which is responsible for histone H4K20 mono-methylation, is an adverse prognosis factor associated with a poor outcome in two cohorts of newly diagnosed patients. Remarkably, primary malignant plasma cells are particularly addicted to SETD8 activity. Indeed, pharmacological inhibition of this enzyme by the chemical compound UNC0379 demonstrated a significantly higher toxicity in MM cells compared to normal cells from the bone marrow microenvironment. Moreover, RNA sequencing and functional studies revealed that SETD8 inhibition induces a mature non-proliferating plasma cell signature and an activation of the p53 canonical pathway, which together leads to an impairment of myeloma cell proliferation and survival. However, UNC0379 treatment triggers a deadly level of replicative stress in p53 deficient MM cells, indicating that the cytotoxicity associated with SETD8 inhibition is independent of the p53 status. Consistent with this, the combination of UNC0379 with the conventional cytotoxic agent melphalan strongly enhances DNA damage and overcomes drug resistance in myeloma cells. Thus, targeting SETD8 could be of therapeutic interest to improve MM treatment in high-risk patients independently of the p53 status.
Novel function of TRIP6, in brain ciliogenesis
Authors: Shukla Shalmali , Urbanek Pavel , Frappart Lucien , Hänold Ronny , Nagel Sigrun , Monajembashi Shamci , Grigaravicius Paulius , Min Woo Kee , Tapias Alicia , Kassel Olivier , Heuer Heike , Wang Zhao-Qi , Ploubidou Aspasia , Herrlich Peter
Published: September 2019

TRIP6, a member of the zyxin-family of LIM domain proteins, is a focal adhesion component. trip6 deletion in the mouse revealed, unexpectedly, in view of its ubiquitous expression, a function in the brain: ependymal and choroid plexus epithelial cells were poorly developed, carrying fewer and shorter cilia, and the mice developed hydrocephalus. TRIP6 disruption, via RNAi or inhibition of its homodimerization, in a choroid plexus epithelial cell line, confirmed its function in ciliogenesis. Zyxin-family members carry numerous protein interaction domains. In common with assembly of other multiprotein complexes, ciliogenesis may be facilitated by molecular assembly factors. Super-resolution microscopy demonstrated TRIP6 localization at the pericentriolar material and along the ciliary axoneme. The requirement for homodimerization which doubles its interaction sites, its punctate localization along the axoneme, and its co-localization with other cilia components suggest a scaffold/co-transporter function for TRIP6 in cilia. This is the first discovery of a protein assembly factor essential for mammalian ciliogenesis.