bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic rates of Neomysis americana (Smith, 1873) (Mysida: Mysidae) from a temperate estuary vary in response to summer temperature and salinity conditions
Authors: Chapina Rosaura J , Rowe Christopher L , Woodland Ryan J
Published: May 2020

The mysid Neomysis americana (Smith, 1873) is native to shallow shelf waters and estuaries of the western Atlantic coast of North America. Despite the important role mysids such as N. americana play in estuarine ecosystems as both consumers and as prey for higher trophic levels, there is limited information on how metabolism influences their spatial ecology and habitat requirements. In tributaries of Chesapeake Bay, MD, USA, previous research has shown that summer water temperatures can approach the lethal upper tolerance limit for N. americana. We measured the per capita metabolic rate (µgO2 min–1) of N. americana from the upper Patuxent River near Benedict, MD, a tributary of Chesapeake Bay in the laboratory to evaluate the metabolic response to salinity and temperature conditions that mysids experience in natural habitats. Sex-specific and diel patterns in metabolic rate were quantified. Metabolic rates did not differ between night and day and there was no significant difference in metabolic rate between males and females, exclusive of gravid females. Metabolic rates were lowest in salinity treatments of 2 and 8 at 29 °C, and highest in the salinity 2 treatment at 22 °C. Only temperature had a statistically significant, albeit unexpected, effect. This study shows that the metabolic response of N. americana to temperature and salinity conditions is complex and plastic, and that metabolic rates can vary 3–4 fold within realistic summer temperature and salinity conditions. As environmental conditions continue to change, understanding metabolic response of mysids to realistic salinity and temperature conditions is necessary for understanding their distributions in temperate estuaries.
Habitat associations and distributions of two endemic crayfishes, Cambarus (Erebicambarus) maculatus Hobbs & Pflieger, 1988 and Faxonius (Billecambarus) harrisonii (Faxon, 1884) (Decapoda: Astacoidea: Cambaridae), in the Meramec River drainage, Missouri, USA
Authors: Chilton Joe , Rosenberger Amanda E , DiStefano Robert J
Published: May 2020

Understanding the habitat associations and distributions of rare species is important to inform management and policy decisions. Cambarus (Erebicambarus) maculatus  Hobbs & Pflieger, 1988, the freckled crayfish, and Faxonius (Billecambarus) harrisonii (Faxon, 1884), the belted crayfish, are two of Missouri’s endemic crayfish species. Both species are listed as Vulnerable (S3) on Missouri’s Species and Communities of Conservation Concern Checklist due to their limited range within the Meramec River drainage (MRD) and the impact of anthropogenic activities therein. Their distributional overlap offers an opportunity for multi-species research to address gaps in information required for conservation. We sampled 140 sites throughout the MRD during the summers of 2017 and 2018 for crayfishes and associated habitat variables, which we related to crayfish presence in an occupancy modeling framework. We found that C. maculatus occupancy was associated with larger stream size, boulder substrate, dolomite lithology, aquatic vegetation beds, dissolved oxygen, and pool mesohabitat. Faxonius harrisonii occupancy increased with boulder substrate, aquatic vegetation beds, the presence of C. maculatus, and decreased in third-order streams. We also expanded the known range for both species within the MRD. Range estimates (watershed area) for C. maculatus and F. harrisonii were 4,347 km2 and 3,690 km2, respectively. This study demonstrates the importance of targeted rather than opportunistic sampling for species distribution.
Side Effects of Organic Products on Telenomus podisi (Hymenoptera: Platygastridae)
Authors: Battisti Lucas , Warmling Jheniffer V , Vieira Claudinei F , Oliveira Darlin H R , Lima Yuri R A , Potrich Michele , Bueno Adeney F , Lozano Everton R
Published: May 2020

Telenomus podisi Ashmead, 1893 is an important biocontrol agent, both in conventional and organic production systems. It can be used in association with other control strategies, such as natural botanical products and biological insecticides. Studies of selectivity and side effects are fundamental for proper management of insect control strategies because the interaction between different control strategies may negatively affect T. podisi. In this context, the present study evaluated the side effects of commercial natural products on T. podisi under laboratory conditions. Five natural products (insecticide, fungicide, and leaf fertilizer) allowed in organic farming were evaluated at concentrations recommended by the manufacturer in three bioassays. First bioassay (free-choice test), the preference of T. podisi parasitism between treated and non-treated E. heros eggs was assessed. In the second and third bioassay (no-choice tests) the treatments were applied to E. heros eggs, repectively before and after T. podisi parasitism (pre- and post-parasitism) and parasitism, emergence, offspring sex ratio, developmental time, and adult longevity were assessed. The products formulated with Metarhizium anisopliae (Metsch.) Sorok. (Hypocreales), Beauveria bassiana (Bals.) Vuill. (Hypocreales), orange oil fertilizer, and the fungicide copper oxychloride did not have side effects on T. podisi because they did not affect most of the evaluated characteristics. In contrast, azadirachtin A/B had a sublethal effect due to the reduced parasitism in all tests performed and, although it did not affect other aspects, this could compromise the performance of the parasitoid.
Tableaux for essence and contingency
Authors: Venturi Giorgio , Teixeira Yago Pedro
Published: May 2020

We offer tableaux systems for logics of essence and accident and logics of non-contingency, showing their soundness and completeness for Kripke semantics. We also show an interesting parallel between these logics based on the semantic insensitivity of the two non-normal operators by which these logics are expressed.
Scaling Up the Surveillance of Childhood Cancer: A Global Roadmap
Authors: Piñeros Marion , Mery Les , Soerjomataram Isabelle , Bray Freddie , Steliarova-Foucher Eva
Published: May 2020

The World Health Organization recently launched the Global Initiative for Childhood Cancer aiming to substantially increase survival among children with cancer by 2030. The ultimate goal concerns particularly less developed countries where survival estimates are considerably lower than in high-income countries where children with cancer attain approximately 80% survival. Given the vast gap in high-quality data availability between more and less developed countries, measuring the success of the Global Initiative for Childhood Cancer will also require substantial support to childhood cancer registries to enable them to provide survival data at the population level. Based on our experience acquired at the International Agency for Research on Cancer in global cancer surveillance, we hereby review crucial aspects to consider in the development of childhood cancer registration and present our vision on how the Global Initiative for Cancer Registry Development can accelerate the measurement of the outcome of children with cancer.
Epigenome-Wide Association Study Using Prediagnostic Bloods Identifies New Genomic Regions Associated With Pancreatic Cancer Risk
Authors: Michaud Dominique S , Ruan Mengyuan , Koestler Devin C , Pei Dong , Marsit Carmen J , De Vivo Immaculata , Kelsey Karl T
Published: May 2020

Background

Epigenome-wide association studies using peripheral blood have identified specific sites of DNA methylation associated with risk of various cancers and may hold promise to identify novel biomarkers of risk; however, few studies have been performed for pancreatic cancer and none using a prospective study design.

Methods

Using a nested case-control study design, incident pancreatic cancer cases and matched controls were identified from participants who provided blood at baseline in 3 prospective cohort studies. DNA methylation levels were measured in DNA extracted from leukocytes using the Illumina MethylationEPIC array. Average follow-up period for this analysis was 13 years.

Results

Several new genomic regions were identified as being differentially methylated in cases and controls; the 5 strongest associations were observed for CpGs located in genes TMEM204/IFT140, MFSD6L, FAM134B/RETREG1, KCNQ1D, and C6orf227. For some CpGs located in chromosome 16p13.3 (near genes TMEM204 and IFT140), associations were stronger with shorter time to diagnosis (eg, odds ratio [OR] = 5.95, 95% confidence interval [CI] = 1.52 to 23.12, for top vs bottom quartile, for <5 years between blood draw and cancer diagnosis), but associations remained statistically significantly higher even when cases were diagnosed over 10 years after blood collection. Statistically significant differences in DNA methylation levels were also observed in the gastric secretion pathway using Gene Set Enrichment Analysis (GSEA) analysis.

Conclusions

Changes in DNA methylation in peripheral blood may mark alterations in metabolic or immune pathways that play a role in pancreatic cancer. Identifying new biological pathways in carcinogenesis of pancreatic cancer using epigenome-wide association studies approach could provide new opportunities for improving treatment and prevention.
Assessing Response Quality by Using Multivariate Control Charts for Numerical and Categorical Response Quality Indicators
Authors: Jin Jiayun , Loosveldt Geert
Published: May 2020

When assessing interview response quality to identify potentially low-quality interviews, both numerical and categorical response quality indicators (mixed indicators) are usually available. However, research on how to use them simultaneously is very rare. In the current article, we extend the application of conventional multivariate control charts to include response quality indicators that are of a mixed type. We analyze data from the eighth round of the European Social Survey in Belgium, characterized by six numerical and two categorical response quality indicators. First, we employ a principal component analysis mix procedure (PCA Mix) to transform the mixed quality indicators into principal components. The principal component scores are subsequently used to construct a Hotelling T2 statistic. To deal with the non-multivariate normal nature of the principal component scores obtained from the PCA Mix, a nonparametric bootstrap method is then applied to calculate the control limit for the T2 statistic. Second, we suggest tools to interpret an identified outlier in terms of finding the responsible original indicator(s). Third, we present a cyclic procedure for determining the “in-control” data, by iteratively removing the outliers until the process is considered as being in control. Lastly, we identify the most important indicators that discriminate the outliers from the in-control data. Our results imply that multivariate control charts based on relevant projection tools such as PCA Mix in combination with the bootstrap technique have great potential for use in evaluating interview response quality and identifying outliers.
Quantifying plant hydraulic function becomes a tall order
Authors: Skelton Robert P
Published: May 2020

This article comments on:

Soriano D, Echeverría A, Anfodillo T, Rosell JA, Olson ME. 2020. Hydraulic traits vary following tip-to-base conduit widening in vascular plants. Journal of Experimental Botany 71, 4232–4242.
Adjunctive sertraline for asymptomatic cryptococcal antigenemia: A randomized clinical trial
Authors: Boulware David R , Nalintya Elizabeth , Rajasingham Radha , Kirumira Paul , Naluyima Rose , Turya Fred , Namanda Sylvia , Rutakingirwa Morris K , Skipper Caleb P , Nikweri Yofesi , Hullsiek Kathy Huppler , Bangdiwala Ananta S , Meya David B
Published: May 2020

Cryptococcal antigen (CrAg) screening in HIV-infected persons with CD4 < 100 cells/µl can reduce meningitis and death, yet preemptive fluconazole therapy fails in ∼25%. Sertraline has in vitro and in vivo activity against Cryptococcus and is synergistic with fluconazole in mice. We evaluated the efficacy and safety of sertraline in asymptomatic cryptococcal antigenemia. We conducted a randomized trial of asymptomatic CrAg-positive Ugandans from November 2017 to February 2018. All subjects received WHO standard therapy of fluconazole 800 mg for 2 weeks, then 400 mg for 10 weeks, then 200 mg through 24 weeks. Participants were randomized to receive adjunctive sertraline or placebo, given in once-weekly escalating 100 mg/day doses up to 400 mg/day, which was then given for 8 weeks, then tapered. The primary endpoint was meningitis-free 6-month survival. The data and safety monitoring board halted the trial after 21 subjects were enrolled due to safety concerns. Meningitis-free 6-month survival occurred in 9 of 11 of placebo participants and 10 of 10 of sertraline participants. However, seven serious adverse events (SAEs) occurred (n = 4 sertraline group; n = 3 placebo group). Three SAEs in the sertraline group presented with psychosis and aggressive behavioral changes with one meeting Hunter's criteria for serotonin syndrome while receiving 200 mg/day sertraline. Two transient psychoses were associated with antecedent fluconazole and sertraline interruption. The serotonin syndrome resolved within 1 day, but psychosis persisted for 4 months after sertraline discontinuation. Sertraline was associated with excess SAEs of psychosis. Due to early stopping, we were unable to determine any efficacy for cryptococcal antigenemia.
Unlocking Galactic Wolf–Rayet stars with Gaia DR2 – II. Cluster and association membership
Authors: Rate Gemma , Crowther Paul A , Parker Richard J
Published: May 2020

Galactic Wolf–Rayet (WR) star membership of star-forming regions can be used to constrain the formation environments of massive stars. Here, we utilize Gaia DR2 parallaxes and proper motions to reconsider WR star membership of clusters and associations in the Galactic disc, supplemented by recent near-infrared studies of young massive clusters. We find that only 18–36 per cent of 553 WR stars external to the Galactic Centre region are located in clusters, OB associations or obscured star-forming regions, such that at least 64 per cent of the known disc WR population are isolated, in contrast with only 13 per cent of O stars from the Galactic O star Catalogue. The fraction located in clusters, OB associations or star-forming regions rises to 25–41 per cent from a global census of 663 WR stars including the Galactic Centre region. We use simulations to explore the formation processes of isolated WR stars. Neither runaways, nor low-mass clusters, are numerous enough to account for the low cluster membership fraction. Rapid cluster dissolution is excluded as mass segregation ensures WR stars remain in dense, well-populated environments. Only low-density environments consistently produce WR stars that appeared to be isolated during the WR phase. We therefore conclude that a significant fraction of WR progenitors originate in low-density association-like surroundings which expand over time. We provide distance estimates to clusters and associations host to WR stars, and estimate cluster ages from isochrone fitting.
Recipes for bolometric corrections and Gaia luminosities of B-type stars: application to an asteroseismic sample
Authors: Pedersen May G , Escorza Ana , Pápics Péter I , Aerts Conny
Published: May 2020

We provide three statistical model prescriptions for the bolometric corrections appropriate for B-type stars as a function of (i) Teff, (ii) Teff and log g, and (iii)Teff, log g and [M/H]. These statistical models have been calculated for 27 different filters, including those of the Gaia space mission, and were derived based on two different grids of bolometric corrections assuming LTE and LTE+NLTE, respectively. Previous such work has mainly been limited to a single photometric passband without taking into account non-local thermodynamic equilibrium (NLTE) effects on the bolometric corrections. Using these statistical models, we calculate the luminosities of 34 slowly pulsating B-type (SPB) stars with available spectroscopic parameters, to place them in the Hertzsprung–Russell diagram and to compare their position to the theoretical SPB instability strip. We find that excluding NLTE effects has no significant effect on the derived luminosities for the temperature range 11 500–21 000 K. We conclude that spectroscopic parameters are needed in order to achieve meaningful luminosities of B-type stars. The three prescriptions for the bolometric corrections are valid for any galactic B-type star with effective temperatures and surface gravities in the ranges 10 000–30 000 K and 2.5–4.5 dex, respectively, covering regimes below the Eddington limit.
The impact of light polarization effects on weak lensing systematics
Authors: Lin Chien-Hao , Tan Brent , Mandelbaum Rachel , Hirata Christopher M
Published: May 2020

A fraction of the light observed from edge-on disc galaxies is polarized due to two physical effects: selective extinction by dust grains aligned with the magnetic field and scattering of the anisotropic starlight field. Since the reflection and transmission coefficients of the reflecting and refracting surfaces in an optical system depend on the polarization of incoming rays, this optical polarization produces both (a) a selection bias in favour of galaxies with specific orientations and (b) a polarization-dependent point spread function (PSF). In this work, we build toy models to obtain for the first time an estimate for the impact of polarization on PSF shapes and the impact of the selection bias due to the polarization effect on the measurement of the ellipticity used in shear measurements. In particular, we are interested in determining if this effect will be significant for Wide-Field Infrared Survey Telescope (WFIRST). We show that the systematic uncertainties in the ellipticity components are 8 × 10−5 and 1.1 × 10−4 due to the selection bias and PSF errors respectively. Compared to the overall requirements on knowledge of the WFIRST PSF ellipticity (4.7 × 10−4 per component), both of these systematic uncertainties are sufficiently close to the WFIRST tolerance level that more detailed studies of the polarization effects or more stringent requirements on polarization-sensitive instrumentation for WFIRST are required.
Characterizing EoR foregrounds: a study of the Lockman Hole region at 325 MHz
Authors: Mazumder Aishrila , Chakraborty Arnab , Datta Abhirup , Choudhuri Samir , Roy Nirupam , Wadadekar Yogesh , Ishwara-Chandra C H
Published: May 2020

One of the key science goals for the most sensitive telescopes, both current and upcoming, is the detection of the redshifted 21-cm signal from the Cosmic Dawn and Epoch of Reionization. The success of detection relies on accurate foreground modelling for their removal from data sets. This paper presents the characterization of astrophysical sources in the Lockman Hole region. Using 325-MHz data obtained from the Giant Metrewave Radio Telescope, a 6° × 6° mosaiced map is produced with an rms reaching 50 μJy per beam. A source catalogue containing 6186 sources is created, and the Euclidean normalized differential source counts have been derived from it, consistent with previous observations as well as simulations. A detailed comparison of the source catalogue is also made with previous findings – at both lower and higher frequencies. The angular power spectrum (APS) of the diffuse Galactic synchrotron emission is determined for three different Galactic latitudes using the tapered gridded estimator. The values of the APS lie between ∼1 and ∼100 mK2. Fitting a power law of the form Aℓ−β gives values of A and β varying across the latitudes considered. This paper demonstrates, for the first time, the variation of the power-law index for diffuse emission at very high Galactic locations. It follows the same trend that is seen at locations near the Galactic plane, thus emphasizing the need for low-frequency observations for developing better models of the diffuse emission.
A comment on ‘Lense–Thirring frame dragging induced by a fast-rotating white dwarf in a binary pulsar system’ by V. Venkatraman Krishnan et al.
Authors: Iorio Lorenzo
Published: May 2020

We comment on a recent study reporting evidence for the general relativistic Lense–Thirring secular precession of the inclination I of the orbital plane to the plane of the sky of the tight binary system PSR J1141-6545 made of a white dwarf and an emitting radiopulsar of comparable masses. The quadrupole mass moment $Q_2^\mathrm{c}$ and the angular momentum ${\boldsymbol{S}}^\mathrm{c}$ of the white dwarf cause the detectable effects on I with respect to the present-day accuracy in the pulsar’s timing. The history-dependent and model-dependent assumptions to be made on $Q_2^\mathrm{c}$ and ${\boldsymbol{S}}^\mathrm{c}$, required even just to calculate the analytical expressions for the resulting post-Keplerian precessions, may be deemed as too wide in order to claim a successful test of the Einsteinian gravitomagnetic effect. Moreover, depending on how $Q_2^\mathrm{c}$ is calculated, the competing quadrupole-induced rate of change, which is a major source of systematic uncertainty, may be up to ${\lesssim}30{-}50{{\ \rm per\ cent}}$ of the Lense–Thirring effect for most of the allowed values in the 3D parameter space spanned by the white dwarf’s spin period Ps, and the polar angles $i_\mathrm{c},\, \zeta _\mathrm{c}$ of its spin axis. The possible use of the longitude of periastron ϖ is investigated as well. It turns out that a measurement of its secular precession, caused, among other things, also by $Q_2^\mathrm{c},\, {\boldsymbol{S}}^\mathrm{c}$, could help in further restricting the permitted regions in the white dwarf’s parameter space.
Three mechanisms for bar thickening
Authors: Sellwood J A , Gerhard Ortwin
Published: May 2020

We present simulations of bar-unstable stellar discs in which the bars thicken into box/peanut shapes. Detailed analysis of the evolution of each model revealed three different mechanisms for thickening the bars. The first mechanism is the well-known buckling instability, the second is the vertical excitation of bar orbits by passage through the 2:1 vertical resonance, and the third is a gradually increasing fraction of bar orbits trapped into this resonance. Since bars in many galaxies may have formed and thickened long ago, we have examined the models for fossil evidence in the velocity distribution of stars in the bar, finding a diagnostic to discriminate between a bar that had buckled from the other two mechanisms.
The structure of nearly isothermal, adiabatic shock waves
Authors: Coughlin Eric R
Published: May 2020

An explosively generated shock wave with time-dependent radius R(t) is characterized by a phase in which the shocked gas becomes radiative with an effective adiabatic index γ ≃ 1. Using the result that the post-shock gas is compressed into a shell of width ΔR/R ≃ δ, where δ = γ − 1, we show that a choice of self-similar variable that exploits this compressive behaviour in the limit that γ → 1 naturally leads to a series expansion of the post-shock fluid density, pressure, and velocity in the small quantity δ. We demonstrate that the leading-order (in δ) solutions, which are increasingly accurate as γ → 1, can be written in simple, closed forms when the fluid is still approximated to be in the energy-conserving regime (i.e. the Sedov–Taylor limit), and that the density declines exponentially rapidly with distance behind the shock. We also analyse the solutions for the bubble surrounding a stellar or galactic wind that interacts with its surroundings, and derive expressions for the location of the contact discontinuity that separates the shocked ambient gas from the shocked wind. We discuss the implications of our findings in the context of the dynamical stability of nearly isothermal shocks.
Ancient Genomic Regulatory Blocks Are a Source for Regulatory Gene Deserts in Vertebrates after Whole-Genome Duplications
Authors: Touceda-Suárez María , Kita Elizabeth M , Acemel Rafael D , Firbas Panos N , Magri Marta S , Naranjo Silvia , Tena Juan J , Gómez-Skarmeta Jose Luis , Maeso Ignacio , Irimia Manuel
Published: May 2020

We investigated how the two rounds of whole-genome duplication that occurred at the base of the vertebrate lineage have impacted ancient microsyntenic associations involving developmental regulators (known as genomic regulatory blocks, GRBs). We showed that the majority of GRBs identified in the last common ancestor of chordates have been maintained as a single copy in humans. We found evidence that dismantling of the duplicated GRB copies occurred early in vertebrate evolution often through the differential retention of the regulatory gene but loss of the bystander gene’s exonic sequences. Despite the large evolutionary scale, the presence of duplicated highly conserved noncoding regions provided unambiguous proof for this scenario for multiple ancient GRBs. Remarkably, the dismantling of ancient GRB duplicates has contributed to the creation of large gene deserts associated with regulatory genes in vertebrates, providing a potentially widespread mechanism for the origin of these enigmatic genomic traits.
MISCAST: MIssense variant to protein StruCture Analysis web SuiTe
Authors: Iqbal Sumaiya , Hoksza David , Pérez-Palma Eduardo , May Patrick , Jespersen Jakob B , Ahmed Shehab S , Rifat Zaara T , Heyne Henrike O , Rahman M Sohel , Cottrell Jeffrey R , Wagner Florence F , Daly Mark J , Campbell Arthur J , Lal Dennis
Published: May 2020

Human genome sequencing efforts have greatly expanded, and a plethora of missense variants identified both in patients and in the general population is now publicly accessible. Interpretation of the molecular-level effect of missense variants, however, remains challenging and requires a particular investigation of amino acid substitutions in the context of protein structure and function. Answers to questions like ‘Is a variant perturbing a site involved in key macromolecular interactions and/or cellular signaling?’, or ‘Is a variant changing an amino acid located at the protein core or part of a cluster of known pathogenic mutations in 3D?’ are crucial. Motivated by these needs, we developed MISCAST (missense variant to protein structure analysis web suite; http://miscast.broadinstitute.org/). MISCAST is an interactive and user-friendly web server to visualize and analyze missense variants in protein sequence and structure space. Additionally, a comprehensive set of protein structural and functional features have been aggregated in MISCAST from multiple databases, and displayed on structures alongside the variants to provide users with the biological context of the variant location in an integrated platform. We further made the annotated data and protein structures readily downloadable from MISCAST to foster advanced offline analysis of missense variants by a wide biological community.
NanoSPC: a scalable, portable, cloud compatible viral nanopore metagenomic data processing pipeline
Authors: Xu Yifei , Yang-Turner Fan , Volk Denis , Crook Derrick
Published: May 2020

Metagenomic sequencing combined with Oxford Nanopore Technology has the potential to become a point-of-care test for infectious disease in public health and clinical settings, providing rapid diagnosis of infection, guiding individual patient management and treatment strategies, and informing infection prevention and control practices. However, publicly available, streamlined, and reproducible pipelines for analyzing Nanopore metagenomic sequencing data are still lacking. Here we introduce NanoSPC, a scalable, portable and cloud compatible pipeline for analyzing Nanopore sequencing data. NanoSPC can identify potentially pathogenic viruses and bacteria simultaneously to provide comprehensive characterization of individual samples. The pipeline can also detect single nucleotide variants and assemble high quality complete consensus genome sequences, permitting high-resolution inference of transmission. We implement NanoSPC using Nextflow manager within Docker images to allow reproducibility and portability of the analysis. Moreover, we deploy NanoSPC to our scalable pathogen pipeline platform, enabling elastic computing for high throughput Nanopore data on HPC cluster as well as multiple cloud platforms, such as Google Cloud, Amazon Elastic Computing Cloud, Microsoft Azure and OpenStack. Users could either access our web interface (https://nanospc.mmmoxford.uk) to run cloud-based analysis, monitor process, and visualize results, as well as download Docker images and run command line to analyse data locally.
Macrophage development and activation involve coordinated intron retention in key inflammatory regulators
Authors: Green Immanuel D , Pinello Natalia , Song Renhua , Lee Quintin , Halstead James M , Kwok Chau-To , Wong Alex C H , Nair Shalima S , Clark Susan J , Roediger Ben , Schmitz Ulf , Larance Mark , Hayashi Rippei , Rasko John E J , Wong Justin J-L
Published: May 2020

Monocytes and macrophages are essential components of the innate immune system. Herein, we report that intron retention (IR) plays an important role in the development and function of these cells. Using Illumina mRNA sequencing, Nanopore direct cDNA sequencing and proteomics analysis, we identify IR events that affect the expression of key genes/proteins involved in macrophage development and function. We demonstrate that decreased IR in nuclear-detained mRNA is coupled with increased expression of genes encoding regulators of macrophage transcription, phagocytosis and inflammatory signalling, including ID2, IRF7, ENG and LAT. We further show that this dynamic IR program persists during the polarisation of resting macrophages into activated macrophages. In the presence of proinflammatory stimuli, intron-retaining CXCL2 and NFKBIZ transcripts are rapidly spliced, enabling timely expression of these key inflammatory regulators by macrophages. Our study provides novel insights into the molecular factors controlling vital regulators of the innate immune response.
Large shift of the Pacific Walker Circulation across the Cenozoic
Authors: Yan Qing , Korty Robert , Zhang Zhongshi , Brierley Chris , Li Xiangyu , Wang Huijun
Published: May 2020

Fluctuations in the Pacific Walker Circulation (PWC), a zonally oriented overturning cell across the tropical Pacific, can cause widespread climatic and biogeochemical perturbations. It remains unknown how the PWC developed during the Cenozoic era, with its substantial changes in greenhouse gases and continental positions. Through a suite of coupled model simulations on tectonic timescales, we demonstrate that the PWC was ∼38° broader and ∼5% more intense during the Early Eocene relative to present. As the climate cooled from the Early Eocene to the Late Miocene, the width of the PWC shrank, accompanied by an increase in intensity that was tied to the enhanced Pacific zonal temperature gradient. However, the locations of the western and eastern branches behave differently from the Early Eocene to the Late Miocene, with the western edge remaining steady with time due to the relatively stable geography of the western tropical Pacific; the eastern edge migrates westward with time as the South American continent moves northwest. A transition occurs in the PWC between the Late Miocene and Late Pliocene, manifested by an eastward shift (both the western and eastern edges migrate eastward by >12°) and weakening (by ∼22%), which we show here is linked with the closure of the tropical seaways. Moreover, our results suggest that rising CO2 favors a weaker PWC under the same land-sea configurations, a robust feature across the large spread of Cenozoic climates considered here, supporting a weakening of the PWC in a warmer future.
Pater Knows Best: Withdrawal of Medical Treatment from Infants in Scotland
Authors: Brown Jonathan , Christie Sarah
Published: May 2020

The cases of Charlie Gard and Alfie Evans placed the withdrawal of treatment from terminally ill infants at the forefront of medical law and ethics. In the medico-legal context, Scottish court procedures materially differ from those in England. This article considers these differences in light of the possibility that a similar case might soon be called before the Scottish courts. The Court of Session would then be required to consider whether to utilise its parens patriae jurisdiction to consent to the withdrawal of treatment as if it were the parent of the infant. The operation of this jurisdiction is such that the outcome of any Scottish case cannot be said to be certain, as the Scottish courts are bound to pay more heed to parental autonomy than their English counterparts do.
Multispecies Diffusion of Yttrium, Rare Earth Elements and Hafnium in Garnet
Authors: Bloch E M , Jollands M C , Devoir A , Bouvier A -S , Ibañez-Mejia M , Baumgartner L P
Published: May 2020

We report experimental data for Y, La, Lu and Hf diffusion in garnet, in which diffusant concentrations and silica activity have been systematically varied. Experiments were conducted at 950 and 1050 °C, at 1 atm pressure and oxygen fugacity corresponding to the quartz–fayalite–magnetite buffer. At Y and REE concentrations below several hundred ppm we observe both slow and fast diffusion mechanisms, which operate simultaneously and correspond to relatively high and low concentrations, respectively. Diffusivity of Y and REE is independent of silica activity over the studied range. General formulae for REE diffusion in garnet, incorporating data from this and previous studies, are  logDREE(f)(m2 s−1)=−10·24(±0·21)−221057(±4284)2·303RT(K) for the ‘fast’ REE diffusion mechanism at 1 atm pressure, and  logDREE(s)(m2 s−1)=−9·28(±0·65)−265200(±38540)+10800(±2600)×P(GPa)2·303RT(K) for the ‘slow’ REE diffusion mechanism. These slow and fast diffusion mechanisms are in agreement with previous, apparently conflicting, datasets for REE diffusion in garnet. Comparison with high-pressure experiments suggests that at high pressures (>∼1 GPa minimum) the fast diffusion mechanism no longer operates to a significant degree. When Y and/or REE surface concentrations are greater than several hundred ppm, complex concentration profiles develop. These profiles are consistent with a multi-site diffusion–reaction model, whereby Y and REE cations diffuse through, and exchange between, different crystallographic sites. Diffusion profiles of Hf do not exhibit any of the complexities observed for Y and REE profiles, and can be modeled using a standard (i.e. single mechanism) solution to the diffusion equation. Hafnium diffusion in garnet shows a negative dependence on silica activity, and is described by  logDHf(m2 s−1)=−8·85(±0·38)−299344(±15136)+12500(±900)×P(GPa)2·303RT(K)−0·52(±0·09)×log⁡10aSiO2. In many natural garnets, diffusion of both Lu and Hf would be sufficiently slow that the Lu–Hf system can be reliably used to date garnet growth. In cases in which significant Lu diffusion does occur, preferential retention of 176Hf/177Hf relative to 176Lu/177Hf will skew isochron relationships such that their apparent ages may not correspond to anything meaningful (e.g. garnet growth, peak temperature or the closure temperature of Lu or Hf). Late-stage reheating events are capable of causing larger degrees of preferential retention of 176Hf/177Hf relative to 176Lu/177Hf and partial to full resetting of the Sm–Nd system within garnet, thus increasing the separation between garnet Lu–Hf and Sm–Nd isochron dates, owing to the fact that these systems are more significantly disturbed through diffusion as more radiogenic 176Hf and 143Nd have accumulated.
A Qualitative Exploratory Study of the Knowledge, Forensic, and Legal Challenges from the Perspective of Police Cybercrime Specialists
Authors: De Paoli Stefano , Johnstone Jason , Coull Natalie , Ferguson Ian , Sinclair Georgina , Tomkins Patrick , Brown Maureen , Martin Rebecca
Published: May 2020

The extant literature has demonstrated that there is a need for more empirical research on the subject of policing cybercrime. This article makes a contribution and offers a qualitative exploration of the problem of policing cybercrime from an international perspective. It structures the analysis around three main challenges: the knowledge, forensic, and legal challenges. A literature review supports the evidence that these issues are core challenges when policing cybercrime. Through 13 semi-structured interviews with cybercrime specialists from 8 countries, these three challenges are further investigated. A thematic analysis of the interviews, whilst confirming some of the previous literature findings, also outlines novel findings. Interview analysis shows that in some areas little recent progress has been made, in particular the recording of cybercrime. However, in other areas new creative solutions have been implemented, including filling the policing skills gap with civilian specialists. The article concludes by offering recommendations for addressing some of the challenges for policing cybercrime.
Global, regional, and national burden of other musculoskeletal disorders 1990–2017: results from the Global Burden of Disease Study 2017
Authors: Safiri Saeid , Kolahi Ali Asghar , Cross Marita , Carson-Chahhoud Kristin , Almasi-Hashiani Amir , Kaufman Jay , Mansournia Mohammad Ali , Sepidarkish Mahdi , Ashrafi-Asgarabad Ahad , Hoy Damian , Collins Gary , Woolf Anthony D , March Lyn , Smith Emma
Published: May 2020

Objectives

To describe the level and trends of point prevalence, deaths and disability-adjusted life years (DALYs) for other musculoskeletal (MSK) disorders, i.e. those not covered by specific estimates generated for RA, OA, low back pain, neck pain and gout, from 1990 to 2017 by age, sex and sociodemographic index.

Methods

Publicly available modelled estimates from the Global Burden of Disease (GBD) 2017 study were extracted and reported as counts and age-standardized rates per 100 000 population for 195 countries and territories between 1990 and 2017.

Results

Globally, the age-standardized point prevalence estimates and deaths rates of other MSK disorders in 2017 were 4151.1 and 1.0 per 100 000. This was an increase of 3.4% and 7.2%, respectively. The age-standardized DALY rate in 2017 was 380.2, an increase of 3.4%. The point prevalence estimate was higher among females and increased with age. This peaked in the 65–69 year age group for both females and males in 2017, followed by a decreasing trend for both sexes. At the national level, the highest age-standardized point prevalence estimates in 2017 were seen in Bangladesh, India and Nepal. The largest increases in age-standardized point prevalence estimates were observed in Romania, Croatia and Armenia.

Conclusion

The burden of other MSK disorders is proven to be substantial and increasing worldwide, with a notable intercountry variation. Data pertaining to specific diseases within this overarching category are required for future GBD MSK estimates. This would enable policymakers to better allocate resources and provide interventions appropriately.
Acute encephalopathy in children in Muzaffarpur, India: a review of aetiopathogenesis
Authors: Sarkar Abhirup , Datta Debatri , Datta Sudip Kumar , John T Jacob
Published: May 2020

The acute encephalopathy occurring in children in Muzaffarpur, India, also recognised in other litchi-cultivating areas of India, Bangladesh, Vietnam and China, had previously been linked to litchi consumption. Recently, it has been identified as hypoglycaemic encephalopathy of an unusual aetiology with three key factors: undernutrition, prolonged fasting and litchi consumption. A second set of investigators has independently reconfirmed the diagnosis and the three-factor aetiology. Skipping the evening meal with an intake of large amounts of litchi in undernourished children is causative. Early-morning hypoglycaemia with an inadequate glycogen store leads to initiation of gluconeogenesis and fatty acid β-oxidation, but methylene cyclopropyl alanine and glycine present in the litchi aril block the fatty acid β-oxidation cycle. The outcomes are uncorrected hypoglycaemia and encephalopathy due to the entry of metabolic intermediates that cross the blood-brain barrier and affect neuronal function. Suggested measures include early 10% dextrose infusion. Awareness about the disease is of prime importance. The diagnosis and aetiopathogenesis are still under question from a part of the scientific community. This review was undertaken to present a comprehensive view of hypoglycaemic encephalopathy and to remove some of the lingering doubts.
A Furosemide Excretion Stress Test Predicts Mortality in Mice After Sepsis and Outperforms the Furosemide Stress Test During Vasopressin Administration
Authors: Street Jonathan M. , Bellomo Tiffany R. , Koritzinsky Erik H. , Kojima Hiroshi , Yuen Peter S. T. , Star Robert A.
Published: May 2020

Objectives:

The furosemide stress test measures the volume of urine produced after a furosemide challenge. Furosemide stress test has previously demonstrated sensitive and specific prediction of progression to Kidney Disease: Improving Global Outcomes guideline defined acute kidney injury stage III in the ICU. Furosemide is actively excreted into the nephron lumen where it inhibits the sodium-potassium-chloride cotransporter, causing diuresis. We hypothesize that furosemide excretion is a more direct measure of tubule health than diuresis.

Design:

We developed a furosemide excretion stress test to evaluate this hypothesis in a murine model of septic-acute kidney injury.

Setting:

Basic science laboratory.

Subjects:

Male and female 8-week old CD-1 mice.

Interventions:

Sepsis was induced by cecal ligation and puncture in male and female mice. Furosemide stress test/furosemide excretion stress test started 42 hours post-cecal ligation and puncture with a 1 mg/kg furosemide bolus and urine was collected for 12 hours. The mice were then euthanized or monitored until 7 days post-cecal ligation and puncture. In another cohort, mice were treated with vasopressin, which decreases urine volume. Furosemide concentration was determined by high performance liquid chromatography.

Measurements and Main Results:

Urine production during the 12-hour collection varied from 0.08 to 2.62 mL. Both urine production (furosemide stress test) and furosemide excretion (furosemide excretion stress test) predicted mortality (area under the receiver operating characteristic curve = 0.925 and 0.916) and time of death (R
2 = 0.26 and 0.74). Male and female mice demonstrated consistent results. Following vasopressin treatment, furosemide stress test specificity fell to 33% (p = 0.016) but furosemide excretion stress test specificity was maintained.

Conclusions:

The furosemide stress test and furosemide excretion stress test performed similarly in predicting mortality; however, furosemide excretion stress test was superior in predicting time to death and maintained performance when challenged with vasopressin treatment in a mouse sepsis model.
Extracorporeal Membrane Oxygenation for Poisonings Reported to U.S. Poison Centers from 2000 to 2018: An Analysis of the National Poison Data System*
Authors: Cole Jon B. , Olives Travis D. , Ulici Alexandru , Litell John M. , Bangh Stacey A. , Arens Ann M. , Puskarich Michael A. , Prekker Matthew E.
Published: May 2020

Objectives:

To assess trends in the use of extracorporeal membrane oxygenation for poisoning in the United States.

Design:

Retrospective cohort study.

Setting:

The National Poison Data System, the databased owned and managed by the American Association of Poison Control Centers, the organization that supports and accredits all 55 U.S. Poison Centers, 2000–2018.

Patients:

All patients reported to National Poison Data System treated with extracorporeal membrane oxygenation.

Interventions:

None.

Measurements and Main Results:

In total, 407 patients met final inclusion criteria (332 adults, 75 children). Median age was 27 years (interquartile range, 15–39 yr); 52.5% were male. Median number of ingested substances was three (interquartile range, 2–4); 51.5% were single-substance exposures. Extracorporeal membrane oxygenation use in poisoned patients in the United States has significantly increased over time (z = 3.18; p = 0.001) in both adults (age > 12 yr) and children (age ≤ 12 yr), increasing by 9–100% per year since 2008. Increase in use occurred more commonly in adults. We found substantial geographical variation in extracorporeal membrane oxygenation use by geospatially mapping the ZIP code associated with the initial call, with large, primarily rural areas of the United States reporting no cases. Overall survival was 70% and did not vary significantly over the study period for children or adults. Patients with metabolic and hematologic poisonings were less likely to survive following extracorporeal membrane oxygenation than those with other poisonings (49% vs 72%; p = 0.004).

Conclusions:

The use of extracorporeal membrane oxygenation to support critically ill, poisoned patients in the United States is increasing, driven primarily by increased use in patients greater than 12 years old. We observed no trends in survival over time. Mortality was higher when extracorporeal membrane oxygenation was used for metabolic or hematologic poisonings. Large, predominantly rural regions of the United States reported no cases of extracorporeal membrane oxygenation for poisoning. Further research should focus on refining criteria for the use of extracorporeal membrane oxygenation in poisoning.
Eligibility Criteria and Endpoints in Metastatic Renal Cell Carcinoma Trials
Authors: Wong Sarah E. , Quinn David I. , Bjarnason Georg A. , North Scott A. , Sridhar Srikala S.
Published: May 2020

Objectives:

Treatments for metastatic renal cell carcinoma (mRCC) are often compared across trials, but trial eligibility criteria and endpoints differ. In an effort to better align trials, the Definition for the Assessment of Time to event Endpoints in CANcer trials (DATECAN) project published recommendations in 2015 to be used in mRCC clinical trial design. We analyzed mRCC trial criteria to determine if DATECAN’s recommendations were followed.

Materials and Methods:

We compared eligibility criteria across 29 phase 3 mRCC trials conducted between 2003 and 2019. We then evaluated endpoints used in 10 phase 3 trials activated between 2015 and 2019 to determine their compliance with DATECAN’s recommendations.

Results:

Among the 29 trials, performance status, renal function, and disease characteristics differed in terms of requirements and measures used. In terms of endpoints, the 10 trials did not entirely follow DATECAN’s recommendations. In total, 7/10 trials’ primary endpoint was progression-free survival (PFS) as recommended; 4/9 trials used PFS as an endpoint but did not publish their definition of PFS, and the 5 that did, included “death from any cause” instead of DATECAN’s recommendation of “death from kidney cancer.”

Conclusions:

Key eligibility criteria were somewhat inconsistent across the phase 3 mRCC trials studied. Endpoints in the newer trials did not align with DATECAN’s recommendations. Not only is greater standardization needed to facilitate meta-analyses and cross-trial comparisons, but as evident from lack of adherence to DATECAN’s recommendations, greater promotion and adoption of recommendations are needed to better harmonize trial design.