bluuebunny/crossref_metadata_2025 huggingface dataset:
Hierarchical fragmentation in high redshift galaxies revealed by hydrodynamical simulations
Authors: Faure Baptiste , Bournaud Frédéric , Fensch Jérémy , Daddi Emanuele , Behrendt Manuel , Burkert Andreas , Richard Johan
Published: February 2021

High-redshift star-forming galaxies have very different morphologies compared to nearby ones. Indeed, they are often dominated by bright star-forming structures of masses up to 108–9 M⊙ dubbed ‘giant clumps’. However, recent observations questioned this result by showing only low-mass structures or no structure at all. We use Adaptative Mesh Refinement hydrodynamical simulations of galaxies with parsec-scale resolution to study the formation of structures inside clumpy high-redshift galaxies. We show that in very gas-rich galaxies star formation occurs in small gas clusters with masses below 107–8 M⊙ that are themselves located inside giant complexes with masses up to 108 and sometimes 109 M⊙. Those massive structures are similar in mass and size to the giant clumps observed in imaging surveys, in particular with the Hubble Space Telescope. Using mock observations of simulated galaxies, we show that at very high resolution with instruments like the Atacama Large Millimeter Array or through gravitational lensing, only low-mass structures are likely to be detected, and their gathering into giant complexes might be missed. This leads to the non-detection of the giant clumps and therefore introduces a bias in the detection of these structures. We show that the simulated giant clumps can be gravitationally bound even when undetected in mocks representative for ALMA observations and HST observations of lensed galaxies. We then compare the top-down fragmentation of an initially warm disc and the bottom-up fragmentation of an initially cold disc to show that the process of formation of the clumps does not impact their physical properties.
The cosmic merger rate density of compact objects: impact of star formation, metallicity, initial mass function, and binary evolution
Authors: Santoliquido Filippo , Mapelli Michela , Giacobbo Nicola , Bouffanais Yann , Artale M Celeste
Published: February 2021

We evaluate the redshift distribution of binary black hole (BBH), black hole–neutron star binary (BHNS), and binary neutron star (BNS) mergers, exploring the main sources of uncertainty: star formation rate (SFR) density, metallicity evolution, common envelope, mass transfer via Roche lobe overflow, natal kicks, core-collapse supernova model, and initial mass function. Among binary evolution processes, uncertainties on common envelope ejection have a major impact: the local merger rate density of BNSs varies from ∼103 to ∼20 Gpc−3 yr−1 if we change the common envelope efficiency parameter from αCE = 7 to 0.5, while the local merger rates of BBHs and BHNSs vary by a factor of ∼2–3. The BBH merger rate changes by one order of magnitude, when 1σ uncertainties on metallicity evolution are taken into account. In contrast, the BNS merger rate is almost insensitive to metallicity. Hence, BNSs are the ideal test bed to put constraints on uncertain binary evolution processes, such as common envelope and natal kicks. Only models assuming values of αCE ≳ 2 and moderately low natal kicks (depending on the ejected mass and the supernovae mechanism), result in a local BNS merger rate density within the 90 per cent credible interval inferred from the second gravitational-wave transient catalogue.
Neutron stars mergers in a stochastic chemical evolution model: impact of time delay distributions
Authors: Cavallo L , Cescutti G , Matteucci F
Published: February 2021

We study the evolution of the [Eu/Fe] ratio in the Galactic halo by means of a stochastic chemical evolution model considering merging neutron stars as polluters of europium. We improved our previous stochastic chemical evolution model by adding a time delay distribution for the coalescence of the neutron stars, instead of constant delays. The stochastic chemical evolution model can reproduce the trend and the observed spread in the [Eu/Fe] data with neutron star mergers as unique producers if we assume: (i) a delay time distribution ∝t−1.5, (ii) an $M_{\boldsymbol{ Eu}}= 3 \times 10^{-6} \, \boldsymbol{M}_{\odot }$ per event, (iii) progenitors of neutron stars in the range $9\!-\!50\, \boldsymbol{M}_{\odot}$, and (iv) a constant fraction of massive stars in the initial mass function (0.02) that produce neutron star mergers. Our best model is obtained by relaxing point (iv) and assuming a fraction that varies with metallicity. We confirm that the mixed scenario with both merging neutron stars and supernovae as europium producers can provide a good agreement with the data relaxing the constraints on the distribution time delays for the coalescence of neutron stars. Adopting our best model, we also reproduce the dispersion of [Eu/Fe] at a given metallicity, which depends on the fraction of massive stars that produce neutron star mergers. Future high-resolution spectroscopic surveys, such as 4MOST and WEAVE, will produce the necessary statistics to constrain at best this parameter.
A statistical analysis of the nulling pulsar population
Authors: Sheikh Sofia Z , MacDonald Mariah G
Published: February 2021

Approximately 8 per cent of the ∼2800 known pulsars exhibit ‘nulling,’ a temporary broad-band cessation of normal pulsar emission. Nulling behaviour can be coarsely quantified by the nulling fraction, which describes the percentage of time a given pulsar will be found in a null state. In this paper, we perform the most thorough statistical analysis thus far of the properties of 141 known nulling pulsars. We find weak, non-linear correlations between nulling fraction and pulse width, as well as nulling fraction and spin period which could be attributed to selection effects. We also further investigate a recently hypothesized gap at 40 per cent nulling fraction. While a local minimum does exist in the distribution, we cannot confirm a consistent and unique break in the distribution when we investigate with univariate and multivariate clustering methods, nor can we prove the existence of two statistically distinct populations about this minimum. Using the same methods, we find that nulling pulsars are a statistically different population from normal, radio, non-nulling pulsars, which has never been quantitatively verified. In addition, we summarize the findings of the prior nulling pulsar statistics literature, which are notoriously contradictory. This study, in context, furthers the idea that nulling fraction alone does not contain enough information to describe the behaviour of a nulling pulsar and that other parameters such as null lengths and null randomness, in addition to a better understanding of selection effects, are required to fully understand this phenomenon.
Magnetic white dwarfs in post-common-envelope binaries
Authors: Parsons S G , Gänsicke B T , Schreiber M R , Marsh T R , Ashley R P , Breedt E , Littlefair S P , Meusinger H
Published: February 2021

Magnitude-limited samples have shown that 20–25 per cent of cataclysmic variables contain white dwarfs with magnetic fields of Mega Gauss strength, in stark contrast to the approximately 5 per cent of single white dwarfs with similar magnetic field strengths. Moreover, the lack of identifiable progenitor systems for magnetic cataclysmic variables leads to considerable challenges when trying to understand how these systems form and evolve. Here, we present a sample of six magnetic white dwarfs in detached binaries with low-mass stellar companions where we have constrained the stellar and binary parameters including, for the first time, reliable mass estimates for these magnetic white dwarfs. We find that they are systematically more massive than non-magnetic white dwarfs in detached binaries. These magnetic white dwarfs generally have cooling ages of more than 1 Gyr and reside in systems that are very close to Roche lobe filling. Our findings are more consistent with these systems being temporarily detached cataclysmic variables, rather than pre-cataclysmic binaries, but we cannot rule out the latter possibility. We find that these systems can display unusual asymmetric light curves that may offer a way to identify them in larger numbers in future. Seven new candidate magnetic white dwarf systems are also presented, three of which have asymmetric light curves. Finally, we note that several newly identified magnetic systems have archival spectra where there is no clear evidence of magnetism, meaning that these binaries have been previously missed. Nevertheless, there remains a clear lack of younger detached magnetic white dwarf systems.
The antesonic condition for the explosion of core-collapse supernovae – II. Rotation and turbulence
Authors: Raives Matthias J , Thompson Todd A , Couch Sean M
Published: February 2021

In the problem of steady free fall on to a standing shockwave around a central mass, the ‘antesonic’ condition limits the regime of stable accretion to $c_T^2/v_\mathrm{esc}^2\le 3/16$, where cT is the isothermal sound speed in the subsonic post-shock flow, and vesc is the escape velocity at the shock radius. Above this limit, it is impossible to satisfy both the Euler equation and the shock jump conditions, and the system transitions to a wind. This physics explains the existence of a critical neutrino luminosity in steady-state models of accretion in the context of core-collapse supernovae. Here, we extend the antesonic condition to flows with rotation and turbulence using a simple one-dimensional formalism. Both effects decrease the critical post-shock sound speed required for explosion. While quite rapid rotation is required for a significant change to the critical condition, we show that the level of turbulence typically achieved in supernova simulations can greatly impact the critical value of $c_T^2/v_\mathrm{esc}^2$. A core angular velocity corresponding to a millisecond rotation period after contraction of the proto-neutron star results in only a ∼5 per cent reduction of the critical curve. In contrast, near-sonic turbulence with specific turbulent kinetic energy $K/c_T^2=0.5-1$, leads to a decrease in the critical value of $c_T^2/v_{\rm esc}^2$ by ∼20 to 40 per cent. This analysis provides a framework for understanding the role of post-shock turbulence in instigating explosions in models that would otherwise fail and helps explain why multidimensional simulations explode more easily than their one-dimensional counterparts.
Inside out and upside-down: The roles of gas cooling and dynamical heating in shaping the stellar age–velocity relation
Authors: Bird Jonathan C , Loebman Sarah R , Weinberg David H , Brooks Alyson M , Quinn Thomas R , Christensen Charlotte R
Published: February 2021

Kinematic studies of disc galaxies, using individual stars in the Milky Way or statistical studies of global disc kinematics over time, provide insight into how discs form and evolve. We use a high-resolution, cosmological zoom-simulation of a Milky Way-mass disc galaxy (h277) to tie together local disc kinematics and the evolution of the disc over time. The present-day stellar age–velocity relationship (AVR) of h277 is nearly identical to that of the analogous solar-neighbourhood measurement in the Milky Way. A crucial element of this success is the simulation’s dynamically cold multiphase ISM, which allows young stars to form with a low velocity dispersion (σbirth$\sim \!6 - 8 \ \mathrm{km\, s}^{-1}$) at late times. Older stars are born kinematically hotter (i.e. the disc settles over time in an ‘upside-down’ formation scenario), and are subsequently heated after birth. The disc also grows ‘inside-out’, and many of the older stars in the present-day solar neighbourhood are present because of radial mixing. We demonstrate that the evolution of σbirth in h277 can be explained by the same model used to describe the general decrease in velocity dispersion observed in disc galaxies from z ∼ 2–3 to the present-day, in which the disc evolves in quasi-stable equilibrium and the ISM velocity dispersion decreases over time due to a decreasing gas fraction. Thus, our results tie together local observations of the Milky Way’s AVR with observed kinematics of high z disc galaxies.
Galactic potential constraints from clustering in action space of combined stellar stream data
Authors: Reino Stella , Rossi Elena M , Sanderson Robyn E , Sellentin Elena , Helmi Amina , Koppelman Helmer H , Sharma Sanjib
Published: February 2021

Stream stars removed by tides from their progenitor satellite galaxy or globular cluster act as a group of test particles on neighbouring orbits, probing the gravitational field of the Milky Way. While constraints from individual streams have been shown to be susceptible to biases, combining several streams from orbits with various distances reduces these biases. We fit a common gravitational potential to multiple stellar streams simultaneously by maximizing the clustering of the stream stars in action space. We apply this technique to members of the GD-1, Palomar 5 (Pal 5), Orphan, and Helmi streams, exploiting both the individual and combined data sets. We describe the Galactic potential with a Stäckel model, and vary up to five parameters simultaneously. We find that we can only constrain the enclosed mass, and that the strongest constraints come from the GD-1, Pal 5, and Orphan streams whose combined data set yields $M(\lt 20\, \mathrm{kpc}) = 2.96^{+0.25}_{-0.26} \times 10^{11} \, \mathrm{ M}_{\odot}$. When including the Helmi stream in the data set, the mass uncertainty increases to $M(\lt 20\, \mathrm{kpc}) = 3.12^{+3.21}_{-0.46} \times 10^{11} \, \mathrm{M}_{\odot}$.
The dynamics of the globular cluster NGC 3201 out to the Jacobi radius
Authors: Wan Zhen , Oliver William H , Baumgardt Holger , Lewis Geraint F , Gieles Mark , Hénault-Brunet Vincent , de Boer Thomas , Balbinot Eduardo , Da Costa Gary , Mackey Dougal
Published: February 2021

As part of a chemodynamical survey of five nearby globular clusters with 2dF/AAOmega on the Anglo-Australian Telescope (AAT), we have obtained kinematic information for the globular cluster NGC 3201. Our new observations confirm the presence of a significant velocity gradient across the cluster which can almost entirely be explained by the high proper motion of the cluster (${\sim}9\, \mathrm{mas\, yr^{-1}}$). After subtracting the contribution of this perspective rotation, we found a remaining rotation signal with an amplitude of ${\sim}1\, \mathrm{km\, s^{-1}}$ around a different axis to what we expect from the tidal tails and the potential escapers, suggesting that this rotation is internal and can be a remnant of its formation process. At the outer part, we found a rotational signal that is likely a result from potential escapers. The proper motion dispersion at large radii reported by Bianchini et al. ($3.5\pm 0.9\, \mathrm{km\, s^{-1}}$) has previously been attributed to dark matter. Here, we show that the LOS dispersion between 0.5 and 1 Jacobi radius is lower ($2.01\pm 0.18\, \mathrm{km\, s^{-1}}$), yet above the predictions from an N-body model of NGC 3201 that we ran for this study ($1.48\pm 0.14\, \mathrm{km\, s^{-1}}$). Based on the simulation, we find that potential escapers cannot fully explain the observed velocity dispersion. We also estimate the effect on the velocity dispersion of different amounts of stellar-mass black holes and unbound stars from the tidal tails with varying escape rates and find that these effects cannot explain the difference between the LOS dispersion and the N-body model. Given the recent discovery of tidal tail stars at large distances from the cluster, a dark matter halo is an unlikely explanation. We show that the effect of binary stars, which is not included in the N-body model, is important and can explain part of the difference in dispersion. We speculate that the remaining difference must be the result of effects not included in the N-body model, such as initial cluster rotation, velocity anisotropy, and Galactic substructure.
The AGN–galaxy–halo connection: the distribution of AGN host halo masses to z = 2.5
Authors: Aird James , Coil Alison L
Published: February 2021

It is widely reported, based on clustering measurements of observed active galactic nucleus (AGN) samples, that AGNs reside in similar mass host dark matter haloes across the bulk of cosmic time, with log $\mathcal {M}/\mathcal {M}_{\odot }\sim 12.5\!-\!13.0$ to z ∼ 2.5. We show that this is due in part to the AGN fraction in galaxies rising with increasing stellar mass, combined with AGN observational selection effects that exacerbate this trend. Here, we use AGN specific accretion rate distribution functions determined as a function of stellar mass and redshift for star-forming and quiescent galaxies separately, combined with the latest galaxy–halo connection models, to determine the parent and subhalo mass distribution function of AGNs to various observational limits. We find that while the median (sub)halo mass of AGNs, $\approx 10^{12}\mathcal {M}_{\odot }$, is fairly constant with luminosity, specific accretion rate, and redshift, the full halo mass distribution function is broad, spanning several orders of magnitude. We show that widely used methods to infer a typical dark matter halo mass based on an observed AGN clustering amplitude can result in biased, systematically high host halo masses. While the AGN satellite fraction rises with increasing parent halo mass, we find that the central galaxy is often not an AGN. Our results elucidate the physical causes for the apparent uniformity of AGN host haloes across cosmic time and underscore the importance of accounting for AGN selection biases when interpreting observational AGN clustering results. We further show that AGN clustering is most easily interpreted in terms of the relative bias to galaxy samples, not from absolute bias measurements alone.
Human METTL18 is a histidine-specific methyltransferase that targets RPL3 and affects ribosome biogenesis and function
Authors: Małecki Jędrzej M , Odonohue Marie-Francoise , Kim Yeji , Jakobsson Magnus E , Gessa Luca , Pinto Rita , Wu Jie , Davydova Erna , Moen Anders , Olsen Jesper V , Thiede Bernd , Gleizes Pierre-Emmanuel , Leidel Sebastian A , Falnes Pål Ø
Published: February 2021

Protein methylation occurs primarily on lysine and arginine, but also on some other residues, such as histidine. METTL18 is the last uncharacterized member of a group of human methyltransferases (MTases) that mainly exert lysine methylation, and here we set out to elucidate its function. We found METTL18 to be a nuclear protein that contains a functional nuclear localization signal and accumulates in nucleoli. Recombinant METTL18 methylated a single protein in nuclear extracts and in isolated ribosomes from METTL18 knockout (KO) cells, identified as 60S ribosomal protein L3 (RPL3). We also performed an RPL3 interactomics screen and identified METTL18 as the most significantly enriched MTase. We found that His-245 in RPL3 carries a 3-methylhistidine (3MH; τ-methylhistidine) modification, which was absent in METTL18 KO cells. In addition, both recombinant and endogenous METTL18 were found to be automethylated at His-154, thus further corroborating METTL18 as a histidine-specific MTase. Finally, METTL18 KO cells displayed altered pre-rRNA processing, decreased polysome formation and codon-specific changes in mRNA translation, indicating that METTL18-mediated methylation of RPL3 is important for optimal ribosome biogenesis and function. In conclusion, we have here established METTL18 as the second human histidine-specific protein MTase, and demonstrated its functional relevance.
Roles for hENT1 and dCK in gemcitabine sensitivity and malignancy of meningioma
Authors: Yamamoto Masahiro , Sanomachi Tomomi , Suzuki Shuhei , Uchida Hiroyuki , Yonezawa Hajime , Higa Nayuta , Takajo Tomoko , Yamada Yuki , Sugai Asuka , Togashi Keita , Seino Shizuka , Okada Masashi , Sonoda Yukihiko , Hirano Hirofumi , Yoshimoto Koji , Kitanaka Chifumi
Published: February 2021

Background

High-grade meningiomas are aggressive tumors with high morbidity and mortality rates that frequently recur even after surgery and adjuvant radiotherapy. However, limited information is currently available on the biology of these tumors, and no alternative adjuvant treatment options exist. Although we previously demonstrated that high-grade meningioma cells were highly sensitive to gemcitabine in vitro and in vivo, the underlying molecular mechanisms remain unknown.

Methods

We examined the roles of hENT1 (human equilibrative nucleoside transporter 1) and dCK (deoxycytidine kinase) in the gemcitabine sensitivity and growth of meningioma cells in vitro. Tissue samples from meningiomas (26 WHO grade I and 21 WHO grade II/III meningiomas) were immunohistochemically analyzed for hENT1 and dCK as well as for Ki-67 as a marker of proliferative activity.

Results

hENT1 and dCK, which play critical roles in the intracellular transport and activation of gemcitabine, respectively, were responsible for the high gemcitabine sensitivity of high-grade meningioma cells and were strongly expressed in high-grade meningiomas. hENT1 expression was required for the proliferation and survival of high-grade meningioma cells and dCK expression. Furthermore, high hENT1 and dCK expression levels correlated with stronger tumor cell proliferative activity and shorter survival in meningioma patients.

Conclusions

The present results suggest that hENT1 is a key molecular factor influencing the growth capacity and gemcitabine sensitivity of meningioma cells and also that hENT1, together with dCK, may be a viable prognostic marker for meningioma patients as well as a predictive marker of their responses to gemcitabine.
A serum-based DNA methylation assay provides accurate detection of glioma
Authors: Sabedot Thais S , Malta Tathiane M , Snyder James , Nelson Kevin , Wells Michael , deCarvalho Ana C , Mukherjee Abir , Chitale Dhananjay A , Mosella Maritza S , Sokolov Artem , Asmaro Karam P , Robin Adam , Rosenblum Mark L , Mikkelsen Tom , Rock Jack , Poisson Laila M , Lee Ian , Walbert Tobias , Kalkanis Steven , Iavarone Antonio , Castro Ana Valeria , Noushmehr Houtan
Published: February 2021

Background

The detection of somatic mutations in cell-free DNA (cfDNA) from liquid biopsy has emerged as a noninvasive tool to monitor the follow-up of cancer patients. However, the significance of cfDNA clinical utility remains uncertain in patients with brain tumors, primarily because of the limited sensitivity cfDNA has to detect real tumor-specific somatic mutations. This unresolved challenge has prevented accurate follow-up of glioma patients with noninvasive approaches.

Methods

Genome-wide DNA methylation profiling of tumor tissue and serum cfDNA of glioma patients.

Results

Here, we developed a noninvasive approach to profile the DNA methylation status in the serum of patients with gliomas and identified a cfDNA-derived methylation signature that is associated with the presence of gliomas and related immune features. By testing the signature in an independent discovery and validation cohorts, we developed and verified a score metric (the “glioma-epigenetic liquid biopsy score” or GeLB) that optimally distinguished patients with or without glioma (sensitivity: 100%, specificity: 97.78%). Furthermore, we found that changes in GeLB score reflected clinicopathological changes during surveillance (eg, progression, pseudoprogression, and response to standard or experimental treatment).

Conclusions

Our results suggest that the GeLB score can be used as a complementary approach to diagnose and follow up patients with glioma.
Diagnostic Pathology of Tumors of Peripheral Nerve
Authors: Belakhoua Sarra M , Rodriguez Fausto J
Published: February 2021

Neoplasms of the peripheral nervous system represent a heterogenous group with a wide spectrum of morphological features and biological potential. They range from benign and curable by complete excision (schwannoma and soft tissue perineurioma) to benign but potentially aggressive at the local level (plexiform neurofibroma) to the highly malignant (malignant peripheral nerve sheath tumors [MPNST]). In this review, we discuss the diagnostic and pathologic features of common peripheral nerve sheath tumors, particularly those that may be encountered in the intracranial compartment or in the spine and paraspinal region. The discussion will cover schwannoma, neurofibroma, atypical neurofibromatous neoplasms of uncertain biological potential, intraneural and soft tissue perineurioma, hybrid nerve sheath tumors, MPNST, and the recently renamed enigmatic tumor, malignant melanotic nerve sheath tumor, formerly referred to as melanotic schwannoma. We also discuss the diagnostic relevance of these neoplasms to specific genetic and familial syndromes of nerve, including neurofibromatosis 1, neurofibromatosis 2, and schwannomatosis. In addition, we discuss updates in our understanding of the molecular alterations that represent key drivers of these neoplasms, including neurofibromatosis type 1 and type 2,SMARCB1, LZTR1, andPRKAR1Aloss, as well as the acquisition ofCDKN2A/Bmutations and alterations in the polycomb repressor complex members (SUZ12andEED) in the malignant progression to MPNST. In summary, this review covers practical aspects of pathologic diagnosis with updates relevant to neurosurgical practice.
The Role of Surgery in IDH-Wild-Type Lower-Grade Gliomas: Threshold at a High Extent of Resection Should be Pursued
Authors: Wang Peng , Luo Chen , Hong Peng-jie , Rui Wen-ting , Wu Shuai
Published: February 2021

BACKGROUND

While maximizing extent of resection (EOR) is associated with longer survival in lower-grade glioma (LGG) patients, the number of cases remains insufficient in determining a EOR threshold to elucidate the clinical benefits, especially in IDH-wild-type LGG patients.

OBJECTIVE

To identify the effects of EOR on the survival outcomes of IDH-wild-type LGG patients.

METHODS

IDH-wild-type LGG patients were retrospectively reviewed. The effect of EOR and other predictor variables on overall survival (OS) and progression-free survival (PFS) was analyzed using Cox regression models and the Kaplan-Meier method.

RESULTS

A total of 94 patients (median OS: 48.9 mo; median follow-up: 30.6 mo) were included in this study. In the multivariable Cox regression analysis, postoperative residual volume was associated with prolonged OS (HR = 2.238; 95% confidence interval [CI], 1.130-4.435; P = .021) and PFS (HR = 2.075; 95% CI, 1.113-3.869; P = .022). Thresholds at a minimum EOR of 97.0% or a maximum residue of 3.0 cm3 were necessary to impact OS positively. For the telomerase reverse transcriptase (TERT)p-wild-type group, such an association was absent. Significant differences in survival existed between the TERTp-wild-type and mutant patients who underwent relatively incomplete resections (residual ≥2.0 cm3 + TERTp wild type: median OS of 62.6 mo [95% CI: 39.7-85.5 mo]; residual ≥2.0 cm3 + TERTp mutant: median OS of 20.0 mo [95% CI:14.6-25.4 mo]).

CONCLUSION

Our results support the core role of maximal safe resection in the treatment of IDH-wild-type LGGs, especially for IDH-wild-type + TERTp-mutant LGGs. Importantly, the survival benefits of surgery could only be elucidated at a high EOR cut-off point.
Privity: Rights, Standing, and the Road Not Taken
Authors: Liau Timothy
Published: February 2021

Privity is generally understood as a rule comprising a burdens limb and a more controversial benefits or ‘rights’ limb. This rendition of privity is too simplistic. Privity has multiple aspects, but its underlying complexity has been obscured by an overwhelming focus on ‘rights’, explaining in part the persistent unclarity plaguing the area. In this article, I argue that an elision of concepts has hampered our understanding of privity and its reform. The literature on contractual rights to performance and secondary rights to damages for their breach is legion. By contrast, standing, as a separate and distinct concept, has been overlooked. These are concepts that need to be more clearly differentiated. While not a panacea to resolve all issues, it is a necessary step to a firmer handle over the distinct issues at stake, and to opening up a novel angle to privity reform—third-party standing—the road not taken.
A two-centre survey of caregiver perspectives on opioid use for children’s acute pain management
Authors: Jun Esther , Ali Samina , Yaskina Maryna , Dong Kathryn , Rajagopal Manasi , Drendel Amy L , Fowler Megan , Poonai Naveen
Published: February 2021

Background

Given the current opioid crisis, caregivers have mounting fears regarding the use of opioid medication in their children. We aimed to determine caregivers’ a) willingness to accept, b) reasons for refusing, and c) past experiences with opioids.

Methods

A novel electronic survey of caregivers of children aged 4 to 16 years who had an acute musculoskeletal injury and presented to two Canadian paediatric emergency departments (ED) (March to November 2017). Primary outcome was caregiver willingness to accept opioids for moderate pain for their children.

Results

Five hundred and seventeen caregivers participated; mean age was 40.9 (SD 7.1) years with 70.0% (362/517) mothers. Children included 62.2% (321/516) males with a mean age of 10.0 (SD 3.6) years. 49.6% of caregivers (254/512) reported willingness to accept opioids for ongoing moderate pain in the ED, while 37.1% (190/512) were ‘unsure’; 33.2% (170/512) of caregivers would accept opioids for at-home use, but 45.5% (233/512) were ‘unsure’. Caregivers’ primary concerns were side effects, overdose, addiction, and masking of diagnosis. Caregiver fear of addiction (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.01 to 1.25) and side effects (OR 1.25, 95% CI 1.11 to 1.42) affected willingness to accept opioids in the emergency department; fears of addiction (OR 1.19, 95% CI 1.07 to 1.32), and overdose (OR 1.15, 95% CI 1.04 to 1.27) affected willingness to accept opioids for at-home use.

Conclusions

Only half of the caregivers would accept opioids for moderate pain, despite ongoing pain following nonopioid analgesics. Caregivers’ fears of addiction, side effects, overdose, and masking diagnosis may have influenced their responses. These findings are a first step in understanding caregiver analgesic decision making.
On the relationship between interdisciplinarity and impact: Distinct effects on academic and broader impact
Authors: Zhang Lin , Sun Beibei , Jiang Lidan , Huang Ying
Published: February 2021

Addressing many of the world’s contemporary challenges requires a multifaceted and integrated approach and, in this respect, interdisciplinary research (IDR) is increasingly recognized as central to both academic interests and national science policies. In spite of the growing attention given to IDR, the impact of IDR remains under-investigated. In this study, we analyzed the influence of interdisciplinarity on citation impact (particularly, WoS citation) and broader impact (particularly, PloS usage) at the article level. We measured IDR in terms of three different elements of diversity—variety, balance, and disparity—as well as the integrated diversity overall. The results of negative binomial regression analysis with field fixed effects and robust standard errors show the positive effects of interdisciplinarity on both academic and broader impact. From an analysis of trends over time, the results show that higher interdisciplinary publications tend to attract more citations and have higher PLoS usage. Compared to citations, which need a more extended period to accumulate, the advantage of measuring impact with PLoS usage is its immediacy. Also, there are signs that PLoS usage and citations can mutually reinforce each other.
The role of IL-23 in joint disease
Authors: Schett Georg
Published: February 2021

The myeloid cell-derived cytokine interleukin (IL-23) has been identified as an orchestrator of chronic inflammatory disease. IL-23 is instrumental in the activation of effector T cells and innate lymphoid cells, which in turn allow the mobilization of pro-inflammatory macrophages and neutrophils from the bone marrow and the initiation of inflammation in the joints, the gut and the skin. While the role of IL-23 in mounting chronic skin inflammation in the context of psoriasis is well established, increasing evidence suggests that also colitis and psoriatic arthritis are controlled by IL-23. Psoriasis, Crohn’s disease and psoriatic arthritis share a common genetic link to IL-23 receptor haplotypes and a therapeutic response to neutralization of IL-23. By controlling the expression of downstream effector cytokines IL-17A and TNFa, IL-23 triggers entheseal and synovial inflammation in patients with psoriatic arthritis by activating T cells and permitting the influx of macrophages and neutrophils into entheses and joints. Furthermore, IL-23 also influences structural changes in the joints of patients with psoriatic arthritis by enhancing osteoclast mediated bone resorption leading to bone erosion, as well as by modulating bone-forming osteoblasts resulting in bony spur formation and ankylosis. In summary, IL-23 represents a highly specialized inflammatory mediator, which is involved in the communication of inflammation across organs. IL-23 is positioned at the initiation point of a pro-inflammatory cytokine cascade that precipitates the development of psoriatic arthritis.
A systematic review of studies that used NIRS to measure neural activation during emotion processing in healthy individuals
Authors: Westgarth Matthew M P , Hogan Christy A , Neumann David L , Shum David H K
Published: February 2021

Functional neuroimaging provides an avenue for earlier diagnosis and tailored treatment of psychological disorders characterised by emotional impairment. Near-infrared spectroscopy (NIRS) offers ecological advantages compared to other neuroimaging techniques and suitability of measuring regions involved in emotion functions. A systematic review was conducted to evaluate the capacity of NIRS to detect activation during emotion processing and to provide recommendations for future research. Following a comprehensive literature search, we reviewed 85 journal articles, which compared activation during emotional experience, regulation or perception with either a neutral condition or baseline period among healthy participants. The quantitative synthesis of outcomes was limited to thematical analysis, owing to the lack of standardisation between studies. Although most studies found increased prefrontal activity during emotional experience and regulation, the findings were more inconsistent for emotion perception. Some researchers reported increased activity during the task, some reported decreases, some no significant changes, and some reported mixed findings depending on the valence and region. We propose that variations in the cognitive task and stimuli, recruited sample, and measurement and analysis of data are the primary causes of inconsistency. Recommendations to improve consistency in future research by carefully considering the choice of population, cognitive task and analysis approach are provided.
Schizophrenia and the Environment: Within-Person Analyses May be Required to Yield Evidence of Unconfounded and Causal Association—The Example of Cannabis and Psychosis
Authors: van Os Jim , Pries Lotta-Katrin , ten Have Margreet , de Graaf Ron , van Dorsselaer Saskia , Bak Maarten , Wittchen Hans-Ulrich , Rutten Bart P F , Guloksuz Sinan
Published: February 2021

Hypotheses about the link between cannabis use and psychosis apply to the within-person level but have been tested mostly at the between-person level. We used a within-person design, in which a person serves as his own control, thus removing the need to consider confounding by any fixed (genetic and nongenetic) characteristic to study the prospective association between cannabis use and the incidence of attenuated psychotic experiences, and vice versa, adjusted for time-varying confounders. We combined 2 general population cohorts (at baseline: Early Developmental Stages of Psychopathology Study, n = 1395; Netherlands Mental Health Survey and Incidence Study-2, n = 6603), which applied a similar methodology to study cannabis use and attenuated psychotic experiences with repeated interviews (T0, T1, T2, and T3) over a period of approximately 10 years. The Hausman test was significant for the adjusted models, indicating the validity of the fixed-effects model. In the adjusted fixed-effects model, prior cannabis use was associated with psychotic experiences (aOR = 7.03, 95% CI: 2.39, 20.69), whereas prior psychotic experiences were not associated with cannabis use (aOR = 0.59, 95% CI: 0.21, 1.71). Longitudinal studies applying random-effects models to study associations between risk factors and mental health outcomes, as well as reverse causality, may not yield precise estimates. Cannabis likely impacts causally on psychosis but not the other way round.
The evolutionary history of ACE2 usage within the coronavirus subgenus Sarbecovirus
Authors: Wells H L , Letko M , Lasso G , Ssebide B , Nziza J , Byarugaba D K , Navarrete-Macias I , Liang E , Cranfield M , Han B A , Tingley M W , Diuk-Wasser M , Goldstein T , Johnson C K , Mazet J A K , Chandran K , Munster V J , Gilardi K , Anthony S J
Published: February 2021

Severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and SARS-CoV-2 are not phylogenetically closely related; however, both use the angiotensin-converting enzyme 2 (ACE2) receptor in humans for cell entry. This is not a universal sarbecovirus trait; for example, many known sarbecoviruses related to SARS-CoV-1 have two deletions in the receptor binding domain of the spike protein that render them incapable of using human ACE2. Here, we report three sequences of a novel sarbecovirus from Rwanda and Uganda that are phylogenetically intermediate to SARS-CoV-1 and SARS-CoV-2 and demonstrate via in vitro studies that they are also unable to utilize human ACE2. Furthermore, we show that the observed pattern of ACE2 usage among sarbecoviruses is best explained by recombination not of SARS-CoV-2, but of SARS-CoV-1 and its relatives. We show that the lineage that includes SARS-CoV-2 is most likely the ancestral ACE2-using lineage, and that recombination with at least one virus from this group conferred ACE2 usage to the lineage including SARS-CoV-1 at some time in the past. We argue that alternative scenarios such as convergent evolution are much less parsimonious; we show that biogeography and patterns of host tropism support the plausibility of a recombination scenario, and we propose a competitive release hypothesis to explain how this recombination event could have occurred and why it is evolutionarily advantageous. The findings provide important insights into the natural history of ACE2 usage for both SARS-CoV-1 and SARS-CoV-2 and a greater understanding of the evolutionary mechanisms that shape zoonotic potential of coronaviruses. This study also underscores the need for increased surveillance for sarbecoviruses in southwestern China, where most ACE2-using viruses have been found to date, as well as other regions such as Africa, where these viruses have only recently been discovered.
Cytochromecoxidase subunit I barcode species delineation methods imply critically underestimated diversity in ‘common’Hermeuptychiabutterflies (Lepidoptera: Nymphalidae: Satyrinae)
Authors: Tan Denise , Parus Anamaria , Dunbar Michelle , Espeland Marianne , Willmott Keith R
Published: February 2021

DNA ‘barcoding’ has contributed greatly to resolving species limits in rapidly diverging tropical insect groups. Here, we explored species diversity in the widespread, cryptic Neotropical butterfly genus Hermeuptychia by generating 601 new sequences of the cytochrome c oxidase I (COI) barcode, tripling available information. Our dataset focused in particular on Ecuador, a biogeographically pivotal country, with additional sequences from Brazil, Costa Rica, French Guiana, Guatemala, Mexico, Panama and Peru. We examined the performance of two phylogeny-based approaches for objectively delineating species, Generalized Mixed Yule Coalescent (GMYC) and Poisson Tree Processes (PTP), as well as a clustering-based approach, Automatic Barcode Gap Discovery (ABGD), on the combined dataset, including our data and 302 published sequences. In general, GMYC and PTP tended to cluster or split likely species as assessed from morphology, depending on model settings, whereas ABGD was less sensitive and produced a more plausible classification. Numerous sequences formed well-supported clades, putative species, that were unrepresented in previously published datasets. The average diversity across all methods was 45 species, in contrast to the 11 species recognized in the current taxonomy. The resulting COI dataset, in combination with ongoing genomic and morphological research, should significantly clarify our understanding of Hermeuptychia species diversity.
Evolutionary novelty in communication between the sexes
Authors: Broder E. Dale , Elias Damian O. , Rodríguez Rafael L. , Rosenthal Gil G. , Seymoure Brett M. , Tinghitella Robin M.
Published: February 2021

The diversity of signalling traits within and across taxa is vast and striking, prompting us to consider how novelty evolves in the context of animal communication. Sexual selection contributes to diversification, and here we endeavour to understand the initial conditions that facilitate the maintenance or elimination of new sexual signals and receiver features. New sender and receiver variants can occur through mutation, plasticity, hybridization and cultural innovation, and the initial conditions of the sender, the receiver and the environment then dictate whether a novel cue becomes a signal. New features may arise in the sender, the receiver or both simultaneously. We contend that it may be easier than assumed to evolve new sexual signals because sexual signals may be arbitrary, sexual conflict is common and receivers are capable of perceiving much more of the world than just existing sexual signals. Additionally, changes in the signalling environment can approximate both signal and receiver changes through a change in transmission characteristics of a given environment or the use of new environments. The Anthropocene has led to wide-scale disruption of the environment and may thus generate opportunity to directly observe the evolution of new signals to address questions that are beyond the reach of phylogenetic approaches.
Trajectory of individual immunity and vaccination required for SARS-CoV-2 community immunity: a conceptual investigation
Authors: Saad-Roy Chadi M. , Levin Simon A. , Metcalf C. Jessica E. , Grenfell Bryan T.
Published: February 2021

SARS-CoV-2 is an international public health emergency; high transmissibility and morbidity and mortality can result in the virus overwhelming health systems. Combinations of social distancing, and test, trace, and isolate strategies can reduce the number of new infections per infected individual below 1, thus driving declines in case numbers, but may be both challenging and costly. These interventions must also be maintained until development and (now likely) mass deployment of a vaccine (or therapeutics), since otherwise, many susceptible individuals are still at risk of infection. We use a simple analytical model to explore how low levels of infection, combined with vaccination, determine the trajectory to community immunity. Understanding the repercussions of the biological characteristics of the viral life cycle in this scenario is of considerable importance. We provide a simple description of this process by modelling the scenario where the effective reproduction number

R

eff

is maintained at 1. Since the additional complexity imposed by the strength and duration of transmission-blocking immunity is not yet clear, we use our framework to probe the impact of these uncertainties. Through intuitive analytical relations, we explore how the necessary magnitude of vaccination rates and mitigation efforts depends crucially on the durations of natural and vaccinal immunity. We also show that our framework can encompass seasonality or preexisting immunity due to epidemic dynamics prior to strong mitigation measures. Taken together, our simple conceptual model illustrates the importance of individual and vaccinal immunity for community immunity, and that the quantification of individuals immunized against SARS-CoV-2 is paramount.
How spiders hunt heavy prey: the tangle web as a pulley and spider's lifting mechanics observed and quantified in the laboratory
Authors: Greco Gabriele , Pugno Nicola M.
Published: February 2021

The spiders of Theridiidae's family display a peculiar behaviour when they hunt extremely large prey. They lift the quarry, making it unable to escape, by attaching pre-tensioned silk threads to it. In this work, we analysed for the first time in the laboratory the lifting hunting mechanism and, in order to quantify the phenomenon, we applied the lifting mechanics theory. The comparison between the experiments and the theory suggests that, during the process, spiders do not stretch the silk too much by keeping it in the linear elastic regime. We thus report here further evidence for the strong role of silk in spiders' evolution, especially how spiders can stretch and use it as an external tool to overcome their muscles’ limits and capture prey with large mass, e.g. 50 times the spider's mass.
Chiasmata and the kinetochore component Dam1 are crucial for elimination of erroneous chromosome attachments and centromere oscillation at meiosis I
Authors: Wakiya Misuzu , Nishi Eriko , Kawai Shinnosuke , Yamada Kohei , Katsumata Kazuhiro , Hirayasu Ami , Itabashi Yuta , Yamamoto Ayumu
Published: February 2021

Establishment of proper chromosome attachments to the spindle requires elimination of erroneous attachments, but the mechanism of this process is not fully understood. During meiosis I, sister chromatids attach to the same spindle pole (mono-oriented attachment), whereas homologous chromosomes attach to opposite poles (bi-oriented attachment), resulting in homologous chromosome segregation. Here, we show that chiasmata that link homologous chromosomes and kinetochore component Dam1 are crucial for elimination of erroneous attachments and oscillation of centromeres between the spindle poles at meiosis I in fission yeast. In chiasma-forming cells, Mad2 and Aurora B kinase, which provides time for attachment correction and destabilizes erroneous attachments, respectively, caused elimination of bi-oriented attachments of sister chromatids, whereas in chiasma-lacking cells, they caused elimination of mono-oriented attachments. In chiasma-forming cells, in addition, homologous centromere oscillation was coordinated. Furthermore, Dam1 contributed to attachment elimination in both chiasma-forming and chiasma-lacking cells, and drove centromere oscillation. These results demonstrate that chiasmata alter attachment correction patterns by enabling error correction factors to eliminate bi-oriented attachment of sister chromatids, and suggest that Dam1 induces elimination of erroneous attachments. The coincidental contribution of chiasmata and Dam1 to centromere oscillation also suggests a potential link between centromere oscillation and attachment elimination.