bluuebunny/crossref_metadata_2025 huggingface dataset:
Metallicity-dependent wind parameter predictions for OB stars
Authors: Vink Jorick S , Sander Andreas A C
Published: March 2021

Mass-loss rates and terminal wind velocities are key parameters that determine the kinetic wind energy and momenta of massive stars. Furthermore, accurate mass-loss rates determine the mass and rotational velocity evolution of mass stars, and their fates as neutron stars and black holes in function of metallicity (Z). Here, we update our Monte Carlo mass-loss Recipe with new dynamically consistent computations of the terminal wind velocity – as a function of Z. These predictions are particularly timely as the Hubble Space Telescope Ultraviolet Legacy Library of Young Stars as Essential Standards (ULLYSES) project will observe ultraviolet spectra with blue-shifted P Cygni lines of hundreds of massive stars in the low-Z Large and Small Magellanic Clouds (SMC), as well as sub-SMC metallicity hosts. Around 35 000 K, we uncover a weak-wind ‘dip’ and we present diagnostics to investigate its physics with ULLYSES and X-Shooter data. We discuss how the dip may provide important information on wind-driving physics, and how this is of key relevance towards finding a new gold-standard for OB star mass-loss rates. For B supergiants below the Fe iv to iii bi-stability jump, the terminal velocity is found to be independent of Z and M, while the mass-loss rate still varies as $\dot{M} \propto Z^{0.85}$. For O-type stars above the bi-stability jump we, find a terminal-velocity dependence of $\mbox{$v _{\infty }$}\propto Z^{0.19}$ and the Z-dependence of the mass-loss rate is found to be as shallow as $\dot{M} \propto Z^{0.42}$, implying that to reproduce the ‘heavy’ black holes from LIGO/Virgo, the ‘low Z’ requirement becomes even more stringent than was previously anticipated.
A unicorn in monoceros: the 3 M⊙ dark companion to the bright, nearby red giant V723 Mon is a non-interacting, mass-gap black hole candidate
Authors: Jayasinghe T , Stanek K Z , Thompson Todd A , Kochanek C S , Rowan D M , Vallely P J , Strassmeier K G , Weber M , Hinkle J T , Hambsch F-J , Martin D V , Prieto J L , Pessi T , Huber D , Auchettl K , Lopez L A , Ilyin I , Badenes C , Howard A W , Isaacson H , Murphy S J
Published: March 2021

We report the discovery of the closest known black hole candidate as a binary companion to V723 Mon. V723 Mon is a nearby ($d\sim 460\, \rm pc$), bright (V ≃ 8.3 mag), evolved (Teff, giant ≃ 4440 K, and Lgiant ≃ 173 L⊙) red giant in a high mass function, f(M) = 1.72 ± 0.01 M⊙, nearly circular binary (P = 59.9 d, e ≃ 0). V723 Mon is a known variable star, previously classified as an eclipsing binary, but its All-Sky Automated Survey, Kilodegree Extremely Little Telescope, and Transiting Exoplanet Survey Satellite light curves are those of a nearly edge-on ellipsoidal variable. Detailed models of the light curves constrained by the period, radial velocities, and stellar temperature give an inclination of $87.0^{\circ ^{+1.7^\circ }}_{-1.4^\circ }$, a mass ratio of q ≃ 0.33 ± 0.02, a companion mass of Mcomp = 3.04 ± 0.06 M⊙, a stellar radius of Rgiant = 24.9 ± 0.7 R⊙, and a giant mass of Mgiant = 1.00 ± 0.07 M⊙. We identify a likely non-stellar, diffuse veiling component with contributions in the B and V band of ${\sim }63{{\ \rm per\ cent}}$ and ${\sim }24{{\ \rm per\ cent}}$, respectively. The SED and the absence of continuum eclipses imply that the companion mass must be dominated by a compact object. We do observe eclipses of the Balmer lines when the dark companion passes behind the giant, but their velocity spreads are low compared to observed accretion discs. The X-ray luminosity of the system is $L_{\rm X}\simeq 7.6\times 10^{29}~\rm ergs~s^{-1}$, corresponding to L/Ledd ∼ 10−9. The simplest explanation for the massive companion is a single compact object, most likely a black hole in the ‘mass gap’.
Crystal structures of influenza nucleoprotein complexed with nucleic acid provide insights into the mechanism of RNA interaction
Authors: Tang Yun-Sang , Xu Shutong , Chen Yu-Wai , Wang Jia-Huai , Shaw Pang-Chui
Published: March 2021

The nucleoprotein (NP) of influenza virus is the core component of the ribonucleoprotein (RNP) and performs multiple structural and functional roles. Structures of the influenza A, B and D NP molecules have been solved previously, but structural information on how NP interacts with RNA remains elusive. Here we present the crystal structure of an obligate monomer of H5N1 NP in complex with RNA nucleotides to 2.3 Å, and a C-terminal truncation of this mutant, also in complex with RNA nucleotides, to 3 Å. In both structures, three nucleotides were identified near two positive grooves of NP suggested to be important for RNA binding. Structural evidence supports that conformational changes of flexible loops and the C-terminal tail both play important roles in the binding of RNA. Based on the structure, we propose a mechanism by which NP captures RNA by flexible loops and transfers it onto the positive binding grooves. Binding of RNA by NP is a crucial step for template re-encapsidation during transcription and replication and cRNP formation. Our structures thus provide insights into the molecular virology of the influenza virus.
Potential interactions between uraemic toxins and drugs: an application in kidney transplant recipients treated with calcineurin inhibitors
Authors: André Camille , Choukroun Gabriel , Bennis Youssef , Kamel Said , Lemaire-Hurtel Anne Sophie , Masmoudi Kamel , Bodeau Sandra , Liabeuf Sophie
Published: March 2021

Background

The uraemic toxins that accumulate as renal function deteriorates can potentially affect drug pharmacokinetics. This study’s objective was to determine whether plasma concentrations of certain uraemic toxins are correlated with blood concentrations of two immunosuppressants.

Methods

DRUGTOX was a cross-sectional study of 403 adult patients followed up after kidney transplantation and who had undergone therapeutic drug monitoring (TDM) of calcineurin inhibitors (tacrolimus or cyclosporin) between August 2019 and March 2020. For each patient, immunosuppressant trough concentrations (C0) were measured in whole blood samples and then normalized against the total daily dose (C0:D ratio). The sample was assayed for five uraemic toxins [urea, trimethylamine N-oxide (TMAO), indole acetic acid (IAA), p-cresylsulphate (PCS) and indoxylsulphate (IxS)] using liquid chromatography–tandem mass spectrometry.

Results

The median age was 56 years [interquartile range (IQR) 48–66] and the median estimated glomerular filtration rate was 41 mL/min/1.73 m2 (IQR 30–57). Age, sex, body mass index (BMI), urea, IxS and PCS were significantly associated with an increment in the tacrolimus C0:D ratio. A multivariate analysis revealed an independent association with IxS [odds ratio 1.36 (95% confidence interval 1.00–1.85)] after adjustment for sex, age and BMI, whereas adjustment for age weakened the association for PCS and urea. In a univariate logistic analysis, age, sex, BMI and the TMAO level (but not PCS, IxS, IAA or urea) were significantly associated with an increment in the cyclosporine C0:D ratio.

Conclusions

Even though TDM and dose adaptation of immunosuppressants keep levels within the therapeutic window, increased exposure to tacrolimus (but not cyclosporine) is associated with an accumulation of PCS, IxS and urea.
Genetic data disagree with described subspecies ranges for Seaside Sparrows on the Atlantic coast
Authors: Roeder Mackenzie R , Hill Christopher E , Elphick Chris S , Conway Meaghan , Kocek Alison R , Tegeler Amy , Woltmann Stefan
Published: March 2021

Seaside Sparrows (Ammospiza maritima) are tidal salt marsh endemic passerines found along the Atlantic and Gulf coasts of North America. Currently, there are 7 described subspecies, and “MacGillivray’s” Seaside Sparrow (A. m. macgillivraii) is the name given to the Atlantic coast subspecies breeding from North Carolina to northern Florida. In 2019 the US Fish and Wildlife Service received a petition to list this subspecies under the Endangered Species Act due to shrinking populations and loss of marsh habitat, which necessitated a Species Status Assessment. As part of the Species Status Assessment, we analyzed genetic (microsatellite and mitochondria) data from 464 Seaside Sparrows from Connecticut to Florida, USA, to infer population connectivity (gene flow) among Atlantic coast populations, and to assess the concordance of population genetic data with the putative ranges of the subspecies. Bayesian cluster analysis (program Structure) indicates three genetically distinct population segments: (1) Florida + Georgia, (2) Charleston, South Carolina, and (3) North Carolina to Connecticut. The population in Charleston, South Carolina was the most strongly differentiated based on microsatellite data, and harbored a unique mitochondrial haplotype not shared by other sampling locations, possibly reflecting long-standing isolation. Our results indicate population genetic discordance with currently described ranges of the subspecies of Seaside Sparrow and provide grounds for the consideration of separate management plans for the three populations.
Weak evidence of carry-over effects of overwinter climate and habitat productivity on spring passage of migratory songbirds at a northern stopover site in Ontario
Authors: Horn Lisa C , Remmel Tarmo K , Stutchbury Bridget J M
Published: March 2021

Reduced rainfall in tropical regions decreases the availability of food resources for overwintering songbirds, with negative impacts on their body condition. Increasingly dry conditions at tropical wintering sites as a result of climate change may impact the ability of temperate-breeding songbirds to prepare for and execute their spring migration. We studied the carry-over effects of natural climatic fluctuations created by the El Niño–Southern Oscillation (ENSO) in tropical overwintering areas on 7 long-distance migratory songbirds at a Canadian stopover site. We used the Normalized Difference Vegetation Index as a proxy for tropical habitat productivity and resource availability and a 34-year bird banding dataset from Long Point, Ontario, Canada to assess migration timing and stopover body condition. To increase our ability to detect potential carry-over effects, we employed a novel approach of using recent migratory connectivity studies to restrict the wintering ranges to areas most likely used by individuals passing through southern Ontario. Using linear models, we found that overwinter habitat productivity was significantly negatively influenced by dry ENSO events in the overwintering ranges in 3 of 7 species, with a fourth near-significant. Subregional differences in the effect of ENSO on precipitation patterns may explain why we did not detect a consistent effect of ENSO on overwinter habitat productivity for all species. Despite restricting the wintering range and using a robust dataset for species with diverse life histories, we detected only weak and often conflicting evidence of population-level carry-over effects from dry ENSO events and overwinter habitat productivity. Negative carry-over effects may be strongest and most evident during the earlier stages of migration because birds may be able to compensate to some extent for poor departure condition and late departure while en route.
Taxon-specific phytoplankton growth, nutrient utilization and light limitation in the oligotrophic Gulf of Mexico
Authors: Yingling Natalia , Kelly Thomas B , Shropshire Taylor A , Landry Michael R , Selph Karen E , Knapp Angela N , Kranz Sven A , Stukel Michael R
Published: March 2021

The highly stratified, oligotrophic regions of the oceans are predominantly nitrogen limited in the surface ocean and light limited at the deep chlorophyll maximum (DCM). Hence, determining light and nitrogen co-limitation patterns for diverse phytoplankton taxa is crucial to understanding marine primary production throughout the euphotic zone. During two cruises in the deep-water Gulf of Mexico, we measured primary productivity (H13CO3−), nitrate uptake (15NO3−) and ammonium uptake (15NH4+) throughout the water column. Primary productivity declined with depth from the mixed layer to the DCM, averaging 27.1 mmol C m−2 d−1. The fraction of growth supported by NO3− was consistently low, with upper euphotic zone values ranging from 0.01 to 0.14 and lower euphotic zone values ranging from 0.03 to 0.44. Nitrate uptake showed strong diel patterns (maximum during the day), whereas ammonium uptake exhibited no diel variability. To parameterize taxon-specific phytoplankton nutrient and light utilization, we used a data assimilation approach (Bayesian Markov Chain Monte Carlo) including primary productivity, nutrient uptake and taxon-specific growth rate measurements. Parameters derived from this analysis define distinct niches for five phytoplankton taxa (Prochlorococcus, Synechococcus, diatoms, dinoflagellates and prymnesiophytes) and may be useful for constraining biogeochemical models of oligotrophic open-ocean systems.
Law Enforcement and Individuals with Disabilities: Steps towards Service Improvement
Authors: Bezyak Jill L , Clemens Elysia , Lucas Sarah
Published: March 2021

People with disabilities are more likely to interact with law enforcement personnel than the general population. Despite the increased likelihood of interactions, most jurisdictions lack protocols and report barriers to effective interaction and communication with individuals with disabilities. The Community Readiness Model (CRM) is a useful tool for guiding research and training in this area. The purposes of this study were to gain insight into the community of law enforcement personnel’s readiness to accommodate individuals with disabilities and uncover barriers to effectively serving individuals with disabilities. Using the CRM to develop the web-based survey, researchers collected data from 267 law enforcement personnel. Results provide information on the implementation of disability-related trainings, effectiveness when serving individuals with disabilities, and specific strengths and barriers that impact service to individuals with disabilities. Specific implications for law enforcement professionals include the development of trainings and technical assistance addressing specific disabilities and related accommodations.
Circulating plasma microRNAs in systemic sclerosis-associated pulmonary arterial hypertension
Authors: Wuttge Dirk M , Carlsen Anting L , Teku Gabriel , Wildt Marie , Rådegran Göran , Vihinen Mauno , Heegaard Niels H H , Hesselstrand Roger
Published: March 2021

Objectives

SSc-associated pulmonary arterial hypertension (SSc-APAH) is a late but devastating complication of SSc. Early identification of SSc-APAH may improve survival. We examined the role of circulating miRNAs in SSc-APAH.

Methods

Using quantitative RT-PCR the abundance of mature miRNAs in plasma was determined in 85 female patients with ACA-positive lcSSc. Twenty-two of the patients had SSc-APAH. Sixty-three SSc controls without PAH were matched for disease duration. Forty-six selected miRNA plasma levels were correlated with clinical data. Longitudinal samples were analysed from 14 SSc-APAH and 27 SSc patients.

Results

The disease duration was 12 years for the SSc-APAH patients and 12.7 years for the SSc controls. Plasma expression levels of 11 miRNAs were lower in patients with SSc-APAH. Four miRNAs displayed higher plasma levels in SSc-APAH patients compared with SSc controls. There was significant difference between groups for miR-20a-5p and miR-203a-3p when correcting for multiple comparisons (P = 0.002 for both). Receiver operating characteristics curve showed AUC = 0.69–0.83 for miR-21-5p and miR-20a-5p or their combination. miR-20a-5p and miR-203a-3p correlated inversely with NT-pro-Brain Natriuretic Protein levels (r = −0.42 and −0.47). Mixed effect model analysis could not identify any miRNAs as predictor of PAH development. However, miR-20a-5p plasma levels were lower in the longitudinal samples of SSc-APAH patients than in the SSc controls.

Conclusions

Our study links expression levels of the circulating plasma miRNAs, especially miR-20a-5p and miR-203a-3p, to the occurrence of SSc-APAH in female patients with ACA-positive lcSSc.
Predicting Long-Term Outcomes in First-Admission Psychosis: Does the Hierarchical Taxonomy of Psychopathology Aid DSM in Prognostication?
Authors: Martin Elizabeth A , Jonas Katherine G , Lian Wenxuan , Foti Dan , Donaldson Kayla R , Bromet Evelyn J , Kotov Roman
Published: March 2021

The Hierarchical Taxonomy of Psychopathology (HiTOP) is an empirical, dimensional model of psychological symptoms and functioning. Its goals are to augment the use and address the limitations of traditional diagnoses, such as arbitrary thresholds of severity, within-disorder heterogeneity, and low reliability. HiTOP has made inroads to addressing these problems, but its prognostic validity is uncertain. The present study sought to test the prediction of long-term outcomes in psychotic disorders was improved when the HiTOP dimensional approach was considered along with traditional (ie, DSM) diagnoses. We analyzed data from the Suffolk County Mental Health Project (N = 316), an epidemiologic study of a first-admission psychosis cohort followed for 20 years. We compared 5 diagnostic groups (schizophrenia/schizoaffective, bipolar disorder with psychosis, major depressive disorder with psychosis, substance-induced psychosis, and other psychoses) and 5 dimensions derived from the HiTOP thought disorder spectrum (reality distortion, disorganization, inexpressivity, avolition, and functional impairment). Both nosologies predicted a significant amount of variance in most outcomes. However, except for cognitive functioning, HiTOP showed consistently greater predictive power across outcomes—it explained 1.7-fold more variance than diagnoses in psychiatric and physical health outcomes, 2.1-fold more variance in community functioning, and 3.4-fold more variance in neural responses. Even when controlling for diagnosis, HiTOP dimensions incrementally predicted almost all outcomes. These findings support a shift away from the exclusive use of categorical diagnoses and toward the incorporation of HiTOP dimensions for better prognostication and linkage with neurobiology.
Nematode Genome Announcement: Draft Genome of Meloidogyne chitwoodi, an Economically Important Pest of Potato in the Pacific Northwest
Authors: Bali Sapinder , Hu Shengwei , Vining Kelly , Brown Chuck , Mojtahedi Hassan , Zhang Lei , Gleason Cynthia , Sathuvalli Vidyasagar
Published: March 2021

Meloidogyne chitwoodi is one of the most devastating pests of potato in the U.S. Pacific Northwest (PNW). Nematode-infected tubers develop external as well as internal defects, making the potato tubers unmarketable, and resulting in economic losses. Draft genome assemblies of three M. chitwoodi genotypes—race 1, race 2 and race 1 pathotype Roza—were generated using Illumina and PacBio Sequel RS II sequencing. The final assemblies consist of 30, 39, and 38 polished contigs for race 1, race 2 and race 1 pathotype Roza, respectively, with average N50 of 2.37 Mb and average assembled genome size of approximately 47.41 Mb. On average, 10,508 genes were annotated for each genome. Benchmarking universal single-copy ortholog (BUSCO) analysis indicated that 69.80% of the BUSCOs were complete whereas 68.80, 0.93, and 12.67% were single copy, duplicated, and fragmented, respectively. These highly contiguous genomes will enrich resources to study potato–nematode interactions and enhance breeding efforts to develop nematode-resistant potato varieties for the PNW.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Genetic Diversity of Xylella fastidiosa in Mexican Vineyards
Authors: Aguilar-Granados Andrés , Hernández-Macías Bárbara , Santiago-Martínez Guillermo , Ruiz-Medrano Roberto , Kameyama-Kawabe Luis , Hinojosa-Moya Jesús , del Carmen Montes-Horcasitas María , Xoconostle-Cázares Beatriz
Published: March 2021

Xylella fastidiosa is a xylem-inhabiting phytopathogenic bacterium that affects diverse agriculturally relevant crops. In Mexico, X. fastidiosa has been reported in the states of Baja California, Coahuila, and Querétaro. In order to determine the genetic diversity of this bacterium in Mexico, 408 grapevine samples were collected from the main producing states in México. For X. fastidiosa identification, real-time PCR and three-loci end-point PCR were employed. The genotyping of the subspecies was carried out using multilocus sequence typing and analysis, based on seven housekeeping genes: leuA, petC, malF, cysG, holC, nuoL, and gltT. The resulting sequences were compared with those present in extant databases. The presence of X. fastidiosa subsp. fastidiosa in the states of Baja California (sequence type 1), Coahuila (sequence type 1), and Querétaro was confirmed. The isolates from northern Mexico bear high similarity to grapevine isolates from the United States. However, the isolates from Querétaro showed significant differences with currently known sequences, showing that there is genetic variability among the X. fastidiosa subsp. fastidiosa populations from grapevines in northern and central Mexico.
Identification of Two New Loci for Adult Plant Resistance to Leaf Rust and Stripe Rust in the Chinese Wheat Variety ‘Neimai 836’
Authors: Zhou Jingwei , Singh Ravi P. , Ren Yong , Bai Bin , Li Zhikang , Yuan Chan , Li Shunda , Huerta-Espino Julio , Liu Demei , Lan Caixia
Published: March 2021

The characterization of leaf rust (caused by Puccinia triticina) and stripe rust (caused by Puccinia striiformis f. sp. tritici) resistance genes is the basis for breeding resistant wheat varieties and managing epidemics of these diseases in wheat. A cross between the susceptible wheat variety ‘Apav#1’ and resistant variety ‘Neimai 836’ was used to develop a mapping population containing 148 F5 recombinant inbred lines (RILs). Leaf rust phenotyping was done in field trials at Ciudad Obregón, Mexico, in 2017 and 2018, and stripe rust data were generated at Toluca, Mexico, in 2017 and in Mianyang, Ezhou, and Gansu, China, in 2019. Inclusive complete interval mapping (ICIM) was used to create a genetic map and identify significant resistance quantitative trait loci (QTL) with 2,350 polymorphic markers from a 15K wheat single-nucleotide polymorphism (SNP) array and simple-sequence repeats (SSRs). The pleiotropic multipathogen resistance gene Lr46/Yr29 and four QTL were identified, including two new loci, QLr.hzau-3BL and QYr.hzau-5AL, which explained 3 to 16% of the phenotypic variation in resistance to leaf rust and 7 to 14% of that to stripe rust. The flanking SNP markers for the two loci were converted to Kompetitive Allele-Specific PCR (KASP) markers and used to genotype a collection of 153 wheat lines, indicating the Chinese origin of the loci. Our results suggest that Neimai 836, which has been used as a parent for many wheat varieties in China, could be a useful source of high-level resistance to both leaf rust and stripe rust.
Optimizing Inoculum Production Methods for Infesting Soil with Phytophthora Species
Authors: Davis E. Anne , Weiland Jerry E. , Scagel Carolyn F.
Published: March 2021

Inoculum production is an important part of conducting research with soilborne Phytophthora species. One common method is to incubate Phytophthora cultures in nutrient-amended vermiculite. However, inoculum levels often vary among batches of inoculum, even when production methods remain the same, and incubation typically takes ≥6 weeks, increasing risks for delayed experiments if the resulting inoculum level is too low. A more reliable and rapid method is needed for future studies. Experiments were conducted to determine inoculum levels of Phytophthora cinnamomi and Phytophthora plurivora after incubation in V8 juice-amended vermiculite (standard method); evaluate how inoculum viability was affected by air-drying; develop a modified method that takes less time to produce a vermiculite-based inoculum; and evaluate the effect of storage on inoculum viability. Results showed that the standard method produced inoculum levels from 716 to 1,808 colony forming units (CFUs)/g and that drying to <78% moisture content significantly reduced viability. The modified method used 2-week-old Phytophthora cultures to infest vermiculite at 80% moisture content and produced inoculum levels from 214 to 525 CFU/g. Storage for >1 day generally reduced inoculum viability. Although inoculum levels from the modified method were lower than the standard method, inoculum levels for each isolate were more consistent between trials, and the modified method was 6 to 8 weeks faster. Production with the modified method can also be easily scaled up by infesting a greater volume of vermiculite with additional cultures of Phytophthora. These results are important because they help explain variability in soilborne Phytophthora inoculum production and storage and provide a new method for producing inoculum more quickly.
Conditioned pain modulation predicts persistent pain after knee replacement surgery
Authors: Dürsteler Christian , Salazar Yusmely , Rodriguez Uxia , Pelfort Xavier , Verdié Lluís Puig
Published: March 2021

Introduction:

Persistent pain after total knee replacement is an underestimated outcome leading to significant health burden. Sensory testing has been explored to help surgeons in decision making and better patient selection. Patients with different chronic pain syndromes exhibit a poor descending pain inhibition that can be quantified through experimental paradigms (conditioned pain modulation). A poor preoperative descending pain inhibition response predicted persistence of pain after surgery in previous studies.

Methods:

This study investigated the correlation between a preoperative inefficient endogenous analgesia and a bad postoperative pain outcome (painful prosthesis). One hundred forty-six patients were studied preoperatively by quantitative sensory testing. Conditioned pain modulation was calculated as the relative decrease in pain intensity (thermal stimulus) during heterotopic painful stimulation.

Results:

Approximately 21.2% of patients had a bad pain outcome (painful prosthesis), 6 months after surgery. Preoperatively, 47.9% of patients exhibited an insufficient endogenous analgesia. The probability to develop persistent pain after surgery in that group was higher than that in patients with a sufficient endogenous analgesia (31.4% [20.9–43.6, 95% CI] vs 11.8% [5.5–21.3, 95% CI], respectively; P < 0.004). Correlation between conditioned pain modulation values and postoperative intensity of pain was also established. Besides, a preoperative lower quality of life (mental component) predicted a worse pain outcome, too.

Conclusions:

This cohort study shows that preoperative sensory testing predicts a bad pain outcome after total knee replacement. This tool could help clinicians in a better indication of patients with advanced knee osteoarthritis for replacement surgery.

Registration Details:

ClinicalTrials.gov: NCT01811888 (prospective).
Propranolol Therapy in Infantile Hemangioma: It Is Not Just About the Beta
Authors: Lee James C. , Modiri Omeed , England Ryan W. , Shawber Carrie J. , Wu June K.
Published: March 2021

Background:

Propranolol, a nonselective β-adrenergic receptor antagonist, is approved by the U.S. Food and Drug Administration to treat problematic infantile hemangiomas, but a subset of patients experience treatment complications. Parents wary of long-term use and side effects consult plastic surgeons on surgical options or as a second opinion. Understanding the mechanism(s) of action of propranolol will allow plastic surgeons to better inform parents.

Methods:

A systemic literature search was performed to query published translational and basic science studies on propranolol effects on infantile hemangiomas and cells derived from these lesions.

Results:

In experimental studies, propranolol was antiproliferative and cytotoxic against hemangioma endothelial and stem cells and affected infantile hemangioma perivascular cell contractility. Propranolol inhibited migration, network formation, vascular endothelial growth factor A production, and vascular endothelial growth factor receptor 2 activation and down-regulated PI3K/AKT and mitogen-activated protein kinase signaling in hemangioma endothelial cells, but it increased ERK1/2 activity in hemangioma stem cells. At effective clinical doses, measured propranolol plasma concentration is 100 times higher than necessary for complete β-adrenergic receptor blockade, yet was 10 to 100 times less than required to induce hemangioma stem cell death.

Conclusions:

Propranolol targets multiple cell types in infantile hemangiomas by means of β-adrenergic receptor–dependent and –independent mechanisms. Plasma concentration played a significant role. At clinically relevant doses, incomplete infantile hemangioma suppression may explain the rebound phenomenon and worsening ulceration, and propranolol off target effects may lead to commonly reported adverse effects, such as sleep and gastrointestinal disturbances. Propranolol limitations and complications underscore the importance of surgical treatment options in cases of rebound and severe adverse effects. Surgical intervention remains an important treatment choice when parents are hesitant to use propranolol.
Management of Patients with Textured Surface Breast Implants
Authors: Savetsky Ira L. , Gabriel Allen , Rohrich Rod J. , Avashia Yash J.
Published: March 2021

The purpose of this special topic article is to present an evidence-based approach and provide recommendations for the management of both asymptomatic and symptomatic patients with textured surface breast implants. There are currently no scientific data to support complete removal of a benign capsule. When unnecessary capsulectomies are performed, the patient is at higher risk for developing postoperative complications. Ultimately, the decision to keep, exchange, or remove breast implants is the patient’s decision and the procedure should be performed only by a qualified surgeon.
Vaginal Canal Reconstruction in Penile Inversion Vaginoplasty with Flaps, Peritoneum, or Skin Grafts: Where Is the Evidence?
Authors: Salibian Ara A. , Schechter Loren S. , Kuzon William M. , Bouman Mark-Bram , van der Sluis Wouter B. , Zhao Lee C. , Bluebond-Langner Rachel
Published: March 2021

Background:

To optimize neovaginal dimensions, several modifications of the traditional penile inversion vaginoplasty are described. Options for neovaginal lining include skin grafts, scrotal flaps, urethral flaps, and peritoneum. Implications of these techniques on outcomes remain limited.

Methods:

A systematic review of recent literature was performed to assess evidence on various vaginal lining options as adjunct techniques in penile inversion vaginoplasty. Study characteristics, neovaginal depth, donor-site morbidity, lubrication, and complications were analyzed in conjunction with expert opinion.

Results:

Eight case series and one cohort study representing 1622 patients used additional skin grafts when performing penile inversion vaginoplasty. Neovaginal stenosis ranged from 1.2 to 12 percent, and neovaginal necrosis ranged from 0 to 22.8 percent. Patient satisfaction with lubrication was low in select studies. Three studies used scrotal flaps to line the posterior vaginal canal. Average neovaginal depth was 12 cm in one study, and neovaginal stenosis ranged from 0 to 6.3 percent. In one study of 24 patients, urethral flaps were used to line the neovagina. Neovaginal depth was 11 cm and complication rates were comparable to other series. Two studies used robotically assisted peritoneal flaps with or without skin grafts in 49 patients. Average neovaginal depth was approximately 14 cm, and complication rates were low.

Conclusions:

Skin grafts, scrotal flaps, urethral flaps, and peritoneal flaps may be used to augment neovaginal canal dimensions with minimal donor-site morbidity. Further direct comparative data on complications, neovaginal depth, and lubrication are needed to assess indications in addition to advantages and disadvantages of the various lining options.
Perioperative Transgender Hormone Management: Avoiding Venous Thromboembolism and Other Complications
Authors: Hontscharuk Rayisa , Alba Brandon , Manno Catherine , Pine Elyse , Deutsch Madeline B. , Coon Devin , Schechter Loren
Published: March 2021

This review discusses the current evidence regarding perioperative hormone therapy for transgender individuals, with an emphasis on strategies to reduce the risk of perioperative venous thromboembolism. Historically, surgeons routinely discontinued estrogen therapy in the perioperative period with the goal of reducing the risk of venous thromboembolism. However, abrupt estrogen cessation may also lead to adverse emotional and physiologic effects, including an exacerbation of one’s gender dysphoria. The data on the relationship of feminizing hormones and venous thromboembolism in the perioperative setting are largely based on extrapolation of hormone regimens that are no longer in use and may not accurately reflect the actual risk of venous thromboembolism. Future studies will allow surgeons to engage in evidence-based, patient-centered, informed consent while also minimizing the risk of complications, such as venous thromboembolism.
The efficacy of escitalopram in major depressive disorder: a multicenter randomized, placebo-controlled double-blind study
Authors: Wang Xiaoliang , Fan Yimin , Li Guanjun , Li Huafang
Published: March 2021

The aim of the study was to conduct a multicenter randomized double-blinded placebo-controlled clinical study to evaluate the efficacy of a generic form of escitalopram in treating major depressive disorder (MDD). A total of 390 MDD patients admitted to hospitals in six cities in China were randomized to receive the generic version of escitalopram, the proprietary form of escitalopram (Lexapro) or placebo. During the 8-week treatment, the Hamilton rating scale for depression-17 (HAM-D17), Hamilton Anxiety Rating Scale (HAMA), Montgomery-Åsberg Depression Rating Scale (MADRS), Clinical Global Impressions scale (CGI), current visual analogue scale pain levels (VAS-P1) and Sheehan Disability Scale (SDS) assessments were performed at week 0, 1, 2, 4, 6 and 8 to evaluate treatment responses. HAM-D17, MADRS, HAMA and CGI-S levels of patients who received escitalopram or Lexapro decreased steadily during 8 weeks’ treatment, whereas the placebo group showed a relatively smaller reduction of these levels (P < 0.001). SDS and VAS-P1 both decreased after treatment with generic escitalopram or proprietary escitalopram Lexapro. Our results indicated that both the generic escitalopram and proprietary escitalopram Lexapro had potent efficacy in treating MDD.
When we can trust computers (and when we can't)
Authors: Coveney Peter V. , Highfield Roger R.
Published: March 2021

With the relentless rise of computer power, there is a widespread expectation that computers can solve the most pressing problems of science, and even more besides. We explore the limits of computational modelling and conclude that, in the domains of science and engineering which are relatively simple and firmly grounded in theory, these methods are indeed powerful. Even so, the availability of code, data and documentation, along with a range of techniques for validation, verification and uncertainty quantification, are essential for building trust in computer-generated findings. When it comes to complex systems in domains of science that are less firmly grounded in theory, notably biology and medicine, to say nothing of the social sciences and humanities, computers can create the illusion of objectivity, not least because the rise of big data and machine-learning pose new challenges to reproducibility, while lacking true explanatory power. We also discuss important aspects of the natural world which cannot be solved by digital means. In the long term, renewed emphasis on analogue methods will be necessary to temper the excessive faith currently placed in digital computation.

This article is part of the theme issue ‘Reliability and reproducibility in computational science: implementing verification, validation and uncertainty quantificationin silico’.
Reproducible validation and replication studies in nanoscale physics
Authors: Clementi N. C. , Barba L. A.
Published: March 2021

Credibility building activities in computational research include verification and validation, reproducibility and replication, and uncertainty quantification. Though orthogonal to each other, they are related. This paper presents validation and replication studies in electromagnetic excitations on nanoscale structures, where the quantity of interest is the wavelength at which resonance peaks occur. The study uses the open-source software
PyGBe
: a boundary element solver with treecode acceleration and GPU capability. We replicate a result by Rockstuhl
et al.
(2005, doi:10/dsxw9d) with a two-dimensional boundary element method on silicon carbide (SiC) particles, despite differences in our method. The second replication case from Ellis
et al.
(2016, doi:10/f83zcb) looks at aspect ratio effects on high-order modes of localized surface phonon-polariton nanostructures. The results partially replicate: the wavenumber position of some modes match, but for other modes they differ. With virtually no information about the original simulations, explaining the discrepancies is not possible. A comparison with experiments that measured polarized reflectance of SiC nano pillars provides a validation case. The wavenumber of the dominant mode and two more do match, but differences remain in other minor modes. Results in this paper were produced with strict reproducibility practices, and we share reproducibility packages for all, including input files, execution scripts, secondary data, post-processing code and plotting scripts, and the figures (deposited in Zenodo). In view of the many challenges faced, we propose that reproducible practices make replication and validation more feasible.

This article is part of the theme issue ‘Reliability and reproducibility in computational science: implementing verification, validation and uncertainty quantification
in silico
’.
The importance of uncertainty quantification in model reproducibility
Authors: Volodina Victoria , Challenor Peter
Published: March 2021

Many computer models possess high-dimensional input spaces and substantial computational time to produce a single model evaluation. Although such models are often ‘deterministic’, these models suffer from a wide range of uncertainties. We argue that uncertainty quantification is crucial for computer model validation and reproducibility. We present a statistical framework, termed history matching, for performing global parameter search by comparing model output to the observed data. We employ Gaussian process (GP) emulators to produce fast predictions about model behaviour at the arbitrary input parameter settings allowing output uncertainty distributions to be calculated. History matching identifies sets of input parameters that give rise to acceptable matches between observed data and model output given our representation of uncertainties. Modellers could proceed by simulating computer models’ outputs of interest at these identified parameter settings and producing a range of predictions. The variability in model results is crucial for inter-model comparison as well as model development. We illustrate the performance of emulation and history matching on a simple one-dimensional toy model and in application to a climate model.

This article is part of the theme issue ‘Reliability and reproducibility in computational science: implementing verification, validation and uncertainty quantificationin silico’.
Uncertainty quantification patterns for multiscale models
Authors: Ye D. , Veen L. , Nikishova A. , Lakhlili J. , Edeling W. , Luk O. O. , Krzhizhanovskaya V. V. , Hoekstra A. G.
Published: March 2021

Uncertainty quantification (UQ) is a key component when using computational models that involve uncertainties, e.g. in decision-making scenarios. In this work, we present uncertainty quantification patterns (UQPs) that are designed to support the analysis of uncertainty in coupled multi-scale and multi-domain applications. UQPs provide the basic building blocks to create tailored UQ for multiscale models. The UQPs are implemented as generic templates, which can then be customized and aggregated to create a dedicated UQ procedure for multiscale applications. We present the implementation of the UQPs with multiscale coupling toolkit Multiscale Coupling Library and Environment 3. Potential speed-up for UQPs has been derived as well. As a proof of concept, two examples of multiscale applications using UQPs are presented.

This article is part of the theme issue ‘Reliability and reproducibility in computational science: implementing verification, validation and uncertainty quantificationin silico’.
Assessing uncertainties from physical parameters and modelling choices in an atmospheric large eddy simulation model
Authors: Jansson Fredrik , Edeling Wouter , Attema Jisk , Crommelin Daan
Published: March 2021

In this study, we investigate uncertainties in a large eddy simulation of the atmosphere, employing modern uncertainty quantification methods that have hardly been used yet in this context. When analysing the uncertainty of model results, one can distinguish between uncertainty related to physical parameters whose values are not exactly known, and uncertainty related to modelling choices such as the selection of numerical discretization methods, of the spatial domain size and resolution, and the use of different model formulations. While the former kind is commonly studied e.g. with forward uncertainty propagation, we explore the use of such techniques to also assess the latter kind. From a climate modelling perspective, uncertainties in the convective response and cloud formation are of particular interest, since these affect the cloud-climate feedback, one of the dominant sources of uncertainty in current climate models. Therefore we analyse the DALES model in the RICO case, a well-studied convection benchmark. We use the VECMA toolkit for uncertainty propagation, assessing uncertainties stemming from physical parameters as well as from modelling choices. We find substantial uncertainties due to small random initial state perturbations, and that the choice of advection scheme is the most influential of the modelling choices we assessed.

This article is part of the theme issue ‘Reliability and reproducibility in computational science: implementing verification, validation and uncertainty quantificationin silico’.
Asymptotic solutions of the SIR and SEIR models well above the epidemic threshold
Authors: Kozyreff Gregory
Published: March 2021

A simple and explicit expression of the solution of the SIR epidemiological model of Kermack and McKendrick is constructed in the asymptotic limit of large basic reproduction numbers R0. The proposed formula yields good qualitative agreement already when R0 ⩾ 3 and rapidly becomes quantitatively accurate as larger values of R0 are assumed. The derivation is based on the method of matched asymptotic expansions, which exploits the fact that the exponential growing phase and the eventual recession of the outbreak occur on distinct time scales. From the newly derived solution, an analytical estimate of the time separating the first inflexion point of the epidemic curve from the peak of infections is given. Finally, we use the same method on the SEIR model and find that the inclusion of the “exposed” population can dramatically alter the time scales of the outbreak.
Contemporary syphilis is characterised by rapid global spread of pandemicTreponema pallidumlineages
Authors: Beale Mathew A. , Marks Michael , Cole Michelle J. , Lee Min-Kuang , Pitt Rachel , Ruis Christopher , Balla Eszter , Crucitti Tania , Ewens Michael , Fernández-Naval Candela , Grankvist Anna , Guiver Malcolm , Kenyon Chris R. , Khairulin Rafil , Kularatne Ranmini , Arando Maider , Molini Barbara J. , Obukhov Andrey , Page Emma E. , Petrovay Fruzsina , Rietmeijer Cornelis , Rowley Dominic , Shokoples Sandy , Smit Erasmus , Sweeney Emma L. , Taiaroa George , Vera Jaime H. , Wennerås Christine , Whiley David M. , Williamson Deborah A. , Hughes Gwenda , Naidu Prenilla , Unemo Magnus , Krajden Mel , Lukehart Sheila A. , Morshed Muhammad G. , Fifer Helen , Thomson Nicholas R.
Published: March 2021

Syphilis is an important sexually transmitted infection caused by the bacteriumTreponema pallidumsubspeciespallidum. The last two decades have seen syphilis incidence rise in many high-income countries, yet the evolutionary and epidemiological relationships that underpin this are poorly understood, as is the globalT. pallidumpopulation structure. We assembled a geographically and temporally diverse collection of clinical and laboratory samples comprising 726T. pallidumgenomes. We used detailed phylogenetic analysis and clustering to show that syphilis globally can be described by only two deeply branching lineages, Nichols and SS14. We show that both of these lineages can be found circulating concurrently in 12 of the 23 countries sampled. To provide further phylodynamic resolution we subdividedTreponema pallidumsubspeciespalliduminto 17 distinct sublineages. Importantly, like SS14, we provide evidence that two Nichols sublineages have expanded clonally across 9 countries contemporaneously with SS14. Moreover, pairwise genome analysis showed that recent isolates circulating in 14 different countries were genetically identical in their core genome to those from other countries, suggesting frequent exchange through international transmission pathways. This contrasts with the majority of samples collected prior to 1983, which are phylogenetically distinct from these more recently isolated sublineages. Bayesian temporal analysis provided evidence of a population bottleneck and decline occurring during the late 1990s, followed by a rapid population expansion a decade later. This was driven by the dominantT. pallidumsublineages circulating today, many of which are resistant to macrolides. Combined we show that the population of contemporary syphilis in high-income countries has undergone a recent and rapid global expansion.