bluuebunny/crossref_metadata_2025 huggingface dataset:
Sensitivity schemes for dynamic glucose‐enhanced magnetic resonance imaging to detect glucose uptake and clearance in mouse brain at 3 T
Authors: Huang Jianpan , Lai Joseph H. C. , Han Xiongqi , Chen Zilin , Xiao Peng , Liu Yang , Chen Lin , Xu Jiadi , Chan Kannie W. Y.
Published: November 2021

We investigated three dynamic glucose‐enhanced (DGE) MRI methods for sensitively monitoring glucose uptake and clearance in both brain parenchyma and cerebrospinal fluid (CSF) at clinical field strength (3 T). By comparing three sequences, namely, Carr–Purcell–Meiboom–Gill (CPMG), on‐resonance variable delay multipulse (onVDMP), and on‐resonance spin‐lock (onSL), a high‐sensitivity DGE MRI scheme with truncated multilinear singular value decomposition (MLSVD) denoising was proposed. The CPMG method showed the highest sensitivity in detecting the parenchymal DGE signal among the three methods, while both onVDMP and onSL were more robust for CSF DGE imaging. Here, onVDMP was applied for CSF imaging, as it displayed the best stability of the DGE results in this study. The truncated MLSVD denoising method was incorporated to further improve the sensitivity. The proposed DGE MRI scheme was examined in mouse brain with 50%/25%/12.5% w/w D‐glucose injections. The results showed that this combination could detect DGE signal changes from the brain parenchyma and CSF with as low as a 12.5% w/w D‐glucose injection. The proposed DGE MRI schemes could sensitively detect the glucose signal change from brain parenchyma and CSF after D‐glucose injection at a clinically relevant concentration, demonstrating high potential for clinical translation.
Altering sorption and diffusion coefficients of gases in 6FDA‐based membrane via addition of functionalized Ti‐based fillers
Authors: Suhaimi Nadia Hartini , Yeong Yin Fong , Jusoh Norwahyu , Chew Thiam Leng , Bustam Mohamad Azmi , Mubashir Muhammad
Published: November 2021

In this work, we systematically investigate and analyze the transport properties including carbon dioxide and methane gases, as well as carbon dioxide induced‐plasticization behavior over 6FDA‐based mixed matrix filled with nonfunctionalized and amine‐functionalized MIL‐125 (Ti) particles. First, the sorption behavior and permeability of CO2 and CH4 gases across the membranes were evaluated experimentally. Then, the dual‐mode sorption model was used to determine the gas solubility coefficients of gases, whereas the partial immobilization model was used to quantify the diffusivity coefficients of gases. From the results obtained, the permeability of CO2 and the ideal selectivity of CO2/CH4 increased 86%–118% upon the addition of nonfunctionalized and amine‐functionalized MIL‐125 (Ti) fillers into 6FDA/durene polymer. Such increment was mainly attributed to the altered sorption and diffusion properties of the membrane after incorporating the fillers that promoted the transport of CO2 through the membrane. The coefficients of Langmuir sorption capacity (C′H), Henry's law (KD), and affinity constant (b) obtained for NH2‐MIL‐125 (Ti)/6FDA‐durene increased 35.5%, 179.8%, and 104.4%, respectively, compared to pure 6FDA‐durene membrane. Besides, NH2‐MIL‐125 (Ti)/6FDA‐durene mixed matrix membrane showed the highest diffusivity coefficient of 35.1 × 10−8 cm2/s, resulting in higher CO2/CH4 selectivity of 37.1. In addition, the CO2 plasticization resistance obtained for nonfunctionalized and amine‐functionalized mixed matrix membrane was also improved about 150%–200% compared to pure 6FDA‐durene membrane. Overall, this study revealed that the inclusion of fillers into the polymer matrix has resulted in higher membrane performance than the neat membrane, which associated with the increased of both diffusivity and solubility of CO2. Thus, the incorporation of fillers into polymer matrix has altered the gas transport behavior, and this study could provide basic information on gas transport properties in analyzing the gas separation performance of 6FDA‐based mixed matrix membranes.
Bayesian inference for modified Weibull distribution under simple step‐stress model based on type‐I censoring
Authors: Ramzan Qasim , Amin Muhammad , Faisal Muhammad
Published: November 2021

In this paper, we consider a simple step‐stress accelerated life test (SSALT) model under the tampered random variable (TRV) model for the modified Weibull distribution (MWD) with type‐I censoring. We consider the classical and Bayesian estimation methods for the estimation of unknown parameters of the MWD model. In the classical scenario, we derive the maximum likelihood estimates (MLEs) and approximate confidence intervals (ACIs) for model parameters. Also, a parametric bootstrap resampling technique is used to derive the bootstrap confidence intervals. Under the Bayesian paradigm, the point estimates of the unknown parameters for different symmetric, asymmetric, and balanced loss functions and highest posterior density (HPD) credible intervals (CIs) are derived via Gibbs within metropolis‐hasting sampling procedure. A simulation study is conducted to compare the performance of Bayesian estimates with MLEs. Moreover, we also compare the precision of considered CIs. Finally, a real application is considered for illustration purpose.
Convalescent plasma therapy in an immunocompromised patient with multiple COVID‐19 flares: a case report
Authors: Karaolidou Frini , Loutsidi Natasa‐Eleni , Mellios Zois , Jahaj Edison , Eleftheriou Konstantinos , Pagoni Maria , Mpaltadakis Ioannis , Dimopoulos Athanasios‐Meletios , Kalomenidis Ioannis , Pappas Apostolos G.
Published: November 2021

Convalescent plasma (CP) transfusion has been utilized as a salvage therapy in immunocompromised patients with severe COVID‐19 pneumonia. We describe the case of a 45‐year‐old immunocompromised patient, who received CP, in order to control multiple COVID‐19 flares and prolonged SARS‐CoV‐2 viraemia lasting for 2 months after the initial diagnosis.
Lectotypification of Uraria prunellifolia and U. paniculata (Leguminosae): Names associated with medicinally important rare plants
Authors: Gogoi Jahnabi , Rana Tikam Singh
Published: November 2021

Uraria prunellifolia and U. paniculata are medicinally important, and rare in occurrence. The former is believed to be extinct in some parts of India, and the latter was recently rediscovered. The nomenclatural history of U. prunellifolia and U. paniculata is discussed here, and both the names are typified.
The biomechanistic aspects of renal cortical injury induced by diesel exhaust particles in rats and the renoprotective contribution of quercetin pretreatment: Histological and biochemical study
Authors: Morsi Ahmed A. , Fouad Hanan , Alasmari Wardah Abdullah , Faruk Eman Mohamed
Published: November 2021

Although several studies have reported a toxic effect of diesel exhaust particles (DEP) exposure on the kidney tissues, the involvement of autophagy/NF‐kB signaling as encountered mechanisms and the protective effects of a natural flavonoid, quercetin on DEP remains unclear. Thirty‐two albino rats were divided as control, quercetin‐treated (60 mg/kg, oral), DEP‐exposed (0.5 mg/kg, intra‐tracheal), and quercetin/DEP‐exposed groups. Specimens of the renal cortex were subjected to histo‐biochemical study and immunohistochemical analysis using anti‐NF‐kB, and anti‐LC3β antibodies followed by morphometric and statistical analyses. The expression level of autophagy genes was quantitatively evaluated using RT‐PCR, as well. The DEP‐exposed rats showed an elevation in the renal tissue levels of MDA and a decrease in the catalase and superoxide dismutase (p < .05). Histologically, there were cytoplasmic vacuolar changes in the lining cells of the renal tubules, glomerular atrophy, and vascular congestion. In addition, renal inflammation was evident as confirmed by the increased NF‐kB immunoexpression. Moreover, the gene expression of Becn1, ATG5, and LC3β increased (p <. 0) due to DEP exposure. Conversely, quercetin pretreatment improved these renal histo‐biochemical alterations (p < .05) and regulated autophagy/NF‐kB pathways. Overall, the study proved the renal toxicity mediated by DEP exposure via precipitating renal inflammation, autophagy activation, and oxidative stress. Quercetin pretreatment could antagonize such machinery to protect the kidney against DEP.
Survey investigating the reasons why UK‐based gundogs ceased working between 2010 and 2019
Authors: Houlton John Edwin Freeman
Published: November 2021

Background

To determine the longevity of the working life of gundogs in the UK, whether owners’ considered retirement was premature and to identify risk factors associated with such work.

Methods

A web‐based survey seeking owner information as to the longevity of their dogs’ working life and why they were retired, euthanised or died. The sample population is six hundred sixty‐five dogs.

Results

The median age at which Springer spaniels stopped work was 11 years and for Cocker spaniels, it was 9 years. The median age for Labrador retrievers was 10 years; for Golden retrievers, 11 years and Flat‐coated retrievers, 9.5 years. Cocker spaniels stopped work at a significantly younger age than Springer spaniels (p = 0.0003) or Labrador retrievers (p = 0.0407). There was no significant difference between the other major breeds. The majority of owners (54.3%) were satisfied with the working lifespan of their dog.

Seventy per cent of dogs were retired, the three most prevalent reasons being lameness (25.2%), old age (23.7%) and deafness (7.8%). Forty‐four dogs died (6.6%) and 158 (24%) were euthanised, with cancer (58%) being the most common reason.

Conclusions

No work‐related issues were identified and gundogs appear to have similar causes of mortality to the general canine population.
Prediction of record values by using quantile regression curves and distortion functions
Authors: Navarro Jorge
Published: November 2021

The purpose of the paper is to provide a general method based on conditional quantile curves to predict record values from preceding records. The predictions are based on conditional median (or median regression) curves. Moreover, conditional quantiles curves are used to provide confidence bands for these predictions. The method is based on the recently introduced concept of multivariate distorted distributions that are used instead of copulas to represent the dependence structure. This concept allows us to compute the conditional quantile curves in a simple way. The theoretical findings are illustrated with a non-parametric model (standard uniform), two parametric models (exponential and Pareto), and a non-parametric procedure for the general case. A real data set and a simulated case study in reliability are analysed.
Challenging problems of quality assurance and quality control (QA/QC) of meteorological time series data
Authors: Faybishenko B. , Versteeg R. , Pastorello G. , Dwivedi D. , Varadharajan C. , Agarwal D.
Published: November 2021

Representativeness and quality of collected meteorological data impact accuracy and precision of climate, hydrological, and biogeochemical analyses and predictions. We developed a comprehensive Quality Assurance (QA) and Quality Control (QC) statistical framework, consisting of three major phases: Phase I—Preliminary data exploration, i.e., processing of raw datasets, with the challenging problems of time formatting and combining datasets of different lengths and different time intervals; Phase II—QA of the datasets, including detecting and flagging of duplicates, outliers, and extreme data; and Phase III—the development of time series of a desired frequency, imputation of missing values, visualization and a final statistical summary. The paper includes two use cases based on the time series data collected at the Billy Barr meteorological station (East River Watershed, Colorado), and the Barro Colorado Island (BCI, Panama) meteorological station. The developed statistical framework is suitable for both real-time and post-data-collection QA/QC analysis of meteorological datasets.
The relationship between the laboratory diagnosis of Lyme neuroborreliosis and climate factors in Kalmar County Sweden — an overview between 2008 and 2019
Authors: Keith Kimberly , Årestedt Kristofer , Tjernberg Ivar
Published: November 2021

The purpose of this study was to describe the epidemiology of Lyme neuroborreliosis (LNB) in Kalmar County, in southern Sweden, between 2008 and 2019, and to analyse the relationship between the LNB incidence and climate factors. Data containing cerebrospinal fluid (CSF) cell counts and borrelia CSF/serum antibody index results was received from the departments of clinical chemistry and microbiology at Kalmar County hospital. For this study, we defined LNB as a case with a positive borrelia antibody CSF/serum index and CSF leukocytes > 5 × 106/L. Climate data including mean temperature, humidity and precipitation covering Kalmar County was collected from the Swedish Meteorological and Hydrological Institute. A total of 5051 paired serum-CSF samples from 4835 patients were investigated of which 251 laboratory LNB cases were found. The average annual LNB incidence in Kalmar County 2008–2019 was 8.8 cases per 100,000 inhabitants. Positive relationships were observed between mean temperature and LNB incidence (p < 0.001) as well as precipitation and LNB incidence (p = 0.003), both with a one calendar month delay. The results suggest an association between climate factors such as mean temperature and precipitation and LNB incidence, presumably through increased/decreased human-tick interactions. This calls for increased awareness of LNB in both the short perspective after periods of warmth and heavy precipitation as well as in a longer perspective in relation to possible climate change. Further studies with larger study groups, covering other geographical areas and over longer periods of time are needed to confirm these findings.
When color coding backfires: A guidance reversal effect when learning with realistic visualizations
Authors: Skulmowski Alexander
Published: November 2021

Digital learning increasingly makes use of realistic visualizations, although realism can be demanding for learners. Color coding is a popular way of helping learners understand visualizations and has been found to aid in learning with detailed visualizations. However, previous research has shown that color coding must not always be an effective aid, and that it even may reduce retention when used with simple visualizations. This study assessed whether the presence of color coding in learning tests has an effect after having learned using a detailed visualization that either featured color cues or one that did not. The results indicate that color coding helps learners the most if the learning tests also feature color coding. Importantly, learning with color-coded visualizations and being tested without color cues leads to the worst results in retention and transfer tests. Regarding transfer, color coding in the testing visualization boosts performance regardless of the presence of color cues in the learning phase. The results of this study challenge popular perspectives aiming at optimizing learning by removing potential sources of difficulty. Depending on the learning test, it may be more effective to keep a certain level of difficulty in the learning task when learning with digital media.
Norms2: Norms About Norms
Authors: Lisciandra Chiara
Published: November 2021

In this paper, I outline and defend the view that variations in compliance levels with one and the same norm represent differentnorms about following norms. In support of this claim, I first argue that classic game-theoretic accounts, which define norms as Nash equilibria of noncooperative games, typically consider variations in compliance levels as separate norms. After that, I suggest a more fine-grained, game-theoretic distinction that accounts for degrees of compliance with the same norm and I show how to incorporate such an account into a psychological framework. Finally, the paper examines what given degrees of compliance can reveal about the dynamics underlying the process of norm change. I will argue that they are indicators of different reactions to the introduction of new norms.
The THESEUS space mission: science goals, requirements and mission concept
Authors: Amati L. , O’Brien P.T. , Götz D. , Bozzo E. , Santangelo A. , Tanvir N. , Frontera F. , Mereghetti S. , Osborne J. P. , Blain A. , Basa S. , Branchesi M. , Burderi L. , Caballero-García M. , Castro-Tirado A. J. , Christensen L. , Ciolfi R. , De Rosa A. , Doroshenko V. , Ferrara A. , Ghirlanda G. , Hanlon L. , Heddermann P. , Hutchinson I. , Labanti C. , Le Floch E. , Lerman H. , Paltani S. , Reglero V. , Rezzolla L. , Rosati P. , Salvaterra R. , Stratta G. , Tenzer C. ,   on behalf of THESEUS Consortium
Published: November 2021

THESEUS, one of the two space mission concepts being studied by ESA as candidates for next M5 mission within its Comsic Vision programme, aims at fully exploiting Gamma-Ray Bursts (GRB) to solve key questions about the early Universe, as well as becoming a cornerstone of multi-messenger and time-domain astrophysics. By investigating the first billion years of the Universe through high-redshift GRBs, THESEUS will shed light on the main open issues in modern cosmology, such as the population of primordial low mass and luminosity galaxies, sources and evolution of cosmic re-ionization, SFR and metallicity evolution up to the “cosmic dawn” and across Pop-III stars. At the same time, the mission will provide a substantial advancement of multi-messenger and time-domain astrophysics by enabling the identification, accurate localisation and study of electromagnetic counterparts to sources of gravitational waves and neutrinos, which will be routinely detected in the late ‘20s and early ‘30s by the second and third generation Gravitational Wave (GW) interferometers and future neutrino detectors, as well as of all kinds of GRBs and most classes of other X/gamma-ray transient sources. Under all these respects, THESEUS will provide great synergies with future large observing facilities in the multi-messenger domain. A Guest Observer programme, comprising Target of Opportunity (ToO) observations, will expand the science return of the mission, to include, e.g., solar system minor bodies, exoplanets, and AGN.
Trust and The Acquisition and Use of Public Health Information
Authors: Holland Stephen , Cawthra Jamie , Schloemer Tamara , Schröder-Bäck Peter
Published: November 2021

Information is clearly vital to public health, but the acquisition and use of public health data elicit serious privacy concerns. One strategy for navigating this dilemma is to build 'trust' in institutions responsible for health information, thereby reducing privacy concerns and increasing willingness to contribute personal data. This strategy, as currently presented in public health literature, has serious shortcomings. But it can be augmented by appealing to the philosophical analysis of the concept of trust. Philosophers distinguish trust and trustworthiness from cognate attitudes, such as confident reliance. Central to this is value congruence: trust is grounded in the perception of shared values. So, the way to build trust in institutions responsible for health data is for those institutions to develop and display values shared by the public. We defend this approach from objections, such as that trust is an interpersonal attitude inappropriate to the way people relate to organisations. The paper then moves on to the practical application of our strategy. Trust and trustworthiness can reduce privacy concerns and increase willingness to share health data, notably, in the context of internal and external threats to data privacy. We end by appealing for the sort of empirical work our proposal requires.
Distal Humeral Morphology Indicates Locomotory Divergence in Extinct Giant Kangaroos
Authors: Jones Billie , Martín-Serra Alberto , Rayfield Emily J. , Janis Christine M.
Published: November 2021

Previous studies of the morphology of the humerus in kangaroos showed that the shape of the proximal humerus could distinguish between arboreal and terrestrial taxa among living mammals, and that the extinct “giant” kangaroos (members of the extinct subfamily Sthenurinae and the extinct macropodine genus Protemnodon) had divergent humeral anatomies from extant kangaroos. Here, we use 2D geometric morphometrics to capture the shape of the distal humerus in a range of extant and extinct marsupials and obtain similar results: sthenurines have humeral morphologies more similar to arboreal mammals, while large Protemnodon species (P. brehus and P. anak) have humeral morphologies more similar to terrestrial quadrupedal mammals. Our results provide further evidence for prior hypotheses: that sthenurines did not employ a locomotor mode that involved loading the forelimbs (likely employing bipedal striding as an alternative to quadrupedal or pentapedal locomotion at slow gaits), and that large Protemnodon species were more reliant on quadrupedal locomotion than their extant relatives. This greater diversity of locomotor modes among large Pleistocene kangaroos echoes studies that show a greater diversity in other aspects of ecology, such as diet and habitat occupancy.
Advances in nonparametric item response theory for scale construction in quality-of-life research
Authors: Sijtsma Klaas , van der Ark L. Andries
Published: November 2021

We introduce the special section on nonparametric item response theory (IRT) in Quality of Life Research. Starting from the well-known Rasch model, we provide a brief overview of nonparametric IRT models and discuss the assumptions, the properties, and the investigation of goodness of fit. We provide references to more detailed texts to help readers getting acquainted with nonparametric IRT models. In addition, we show how the rather diverse papers in the special section fit into the nonparametric IRT framework. Finally, we illustrate the application of nonparametric IRT models using data from a questionnaire measuring activity limitations in walking. The real-data example shows the quality of the scale and its constituent items with respect to dimensionality, local independence, monotonicity, and invariant item ordering.
Upscaling Mixing-Controlled Reactions in Unsaturated Porous Media
Authors: Perez Lazaro J. , Puyguiraud Alexandre , Hidalgo Juan J. , Jiménez-Martínez Joaquín , Parashar Rishi , Dentz Marco
Published: November 2021

We study mixing-controlled chemical reactions in unsaturated porous media from a pore-scale perspective. The spatial heterogeneity induced by the presence of two immiscible phases, here water and air, in the pore space generates complex flow patterns that dominate reactive mixing across scales. To assess the impact of different macroscopic saturation states (the fraction of pore volume occupied by water) on mixing-controlled chemical reactions, we consider a fast irreversible reaction between two initially segregated dissolved species that mix as one solution displaces the other in the heterogeneous flow field of the water phase. We use the pore-scale geometry and water distributions from the laboratory experiments reported by Jiménez-Martínez et al. (Geophys. Res. Lett. 42: 5316–5324, 2015). We analyze reactive mixing in three complementary ways. Firstly, we post-process experimentally observed spatially distributed concentration data; secondly, we perform numerical simulations of flow and reactive transport in the heterogeneous water phase, and thirdly, we use an upscaled mixing model. The first approach relies on an exact algebraic map between conservative and reactive species for an instantaneous irreversible bimolecular reaction that allows to estimate reactive mixing based on experimental conservative transport data. The second approach is based on reactive random walk particle tracking simulations in the numerically determined flow field in the water phase. The third approach uses a dispersive lamella approach that accounts for the impact of flow heterogeneity on mixing in terms of effective dispersion coefficients, which are estimated from both experimental data and numerical random walk particle tracking simulations. We observe a significant increase in reactive mixing for decreasing saturation, which is caused by the stronger heterogeneity of the water phase and thus of the flow field. This is consistently observed in the experimental data and the direct numerical simulations. The dispersive lamella model, parameterized by the effective interface width, provides robust estimates of the evolution of the product mass obtained from the experimental and numerical data.
Voxel-Based Analysis of the Relation of 3′-Deoxy-3′-[18F]fluorothymidine ([18F]FLT) PET and Diffusion-Weighted (DW) MR Signals in Subcutaneous Tumor Xenografts Does Not Reveal a Direct Spatial Relation of These Two Parameters
Authors: Schelhaas Sonja , Frohwein Lynn Johann , Wachsmuth Lydia , Hermann Sven , Faber Cornelius , Schäfers Klaus P. , Jacobs Andreas H.
Published: November 2021

Purpose

Multimodal molecular imaging allows a direct coregistration of different images, facilitating analysis of the spatial relation of various imaging parameters. Here, we further explored the relation of proliferation, as measured by [18F]FLT PET, and water diffusion, as an indicator of cellular density and cell death, as measured by diffusion-weighted (DW) MRI, in preclinical tumor models. We expected these parameters to be negatively related, as highly proliferative tissue should have a higher density of cells, hampering free water diffusion.

Procedures

Nude mice subcutaneously inoculated with either lung cancer cells (n = 11 A549 tumors, n = 20 H1975 tumors) or colorectal cancer cells (n = 13 Colo205 tumors) were imaged with [18F]FLT PET and DW-MRI using a multimodal bed, which was transferred from one instrument to the other within the same imaging session. Fiducial markers allowed coregistration of the images. An automatic post-processing was developed in MATLAB handling the spatial registration of DW-MRI (measured as apparent diffusion coefficient, ADC) and [18F]FLT image data and subsequent voxel-wise analysis of regions of interest (ROIs) in the tumor.

Results

Analyses were conducted on a total of 76 datasets, comprising a median of 2890 data points (ranging from 81 to 13,597). Scatterplots showing [18F]FLT vs. ADC values displayed various grades of relations (Pearson correlation coefficient (PCC) varied from − 0.58 to 0.49, median: -0.07). When relating PCC to tumor volume (median: 46 mm3, range: 3 mm3 to 584 mm3), lung tumors tended to have a more pronounced negative spatial relation of [18F]FLT and ADC with increasing tumor size. However, due to the low number of large tumors (> ~ 200 mm3), this conclusion has to be treated with caution.

Conclusions

A spatial relation of water diffusion, as measured by DW-MRI, and cellular proliferation, as measured by [18F]FLT PET, cannot be detected in the experimental datasets investigated in this study.
Colchicine Is Safe Though Ineffective in the Treatment of Severe COVID-19: a Randomized Clinical Trial (COLCHIVID)
Authors: Absalón-Aguilar Abdiel , Rull-Gabayet Marina , Pérez-Fragoso Alfredo , Mejía-Domínguez Nancy R. , Núñez-Álvarez Carlos , Kershenobich-Stalnikowitz David , Sifuentes-Osornio José , Ponce-de-León Alfredo , González-Lara Fernanda , Martín-Nares Eduardo , Montesinos-Ramírez Sharon , Ramírez-Alemón Martha , Ramírez-Rangel Pamela , Márquez Manlio F. , Plata-Corona Juan Carlos , Juárez-Vega Guillermo , Gómez-Martín Diana , Torres-Ruiz Jiram
Published: November 2021

Background

Colchicine is an available, safe, and effective anti-inflammatory drug and has been suggested as a COVID-19 treatment, but its usefulness in hospitalized severe COVID-19 patients has not been thoroughly demonstrated.

Objective

To address the safety and efficacy of colchicine in hospitalized patients with severe COVID-19.

Design

We conducted a triple-blind parallel non-stratified placebo-controlled clinical trial.

Participants

We recruited 116 hospitalized patients with severe COVID-19 in Mexico.

Interventions

Patients were randomized to receive 1.5 mg of colchicine or placebo at the time of the recruitment in the study (baseline) and 0.5 mg BID PO to complete 10 days of treatment.

Main Measures

The primary composite outcome was the progression to critical disease or death. Besides, we evaluated immunological features at baseline and after recovery or disease progression in 20 patients.

Key Results

Fifty-six patients were allocated to colchicine and 60 patients received placebo. The study was suspended after the second interim analysis demonstrated colchicine had no effect on the primary outcome (OR 0.83, 95%CI 0.35–1.93, P = 0.67), nor in the days of ICU and hospital stays. Adverse events were similar between groups (OR 1.63, 95% CI 0.66–3.88, P = 0.37). After colchicine treatment, patients had higher BUN and lower serum levels of IL-8, IL-12p70, and IL-17A.

Conclusions

Colchicine is safe but not effective in the treatment of severe COVID-19.

Trial Registration

ClinicalTrials.gov Identifier: NCT04367168.
Basal stress controls ice-flow variability during a surge cycle of Hagen Bræ, Greenland
Authors: Winton Øyvind A. , Simonsen Sebastian B. , Solgaard Anne M. , McNabb Robert , Karlsson Nanna B.
Published: November 2021

Basal conditions play an essential role in the dynamics of outlet glaciers, but direct observations at the bed of glaciers are challenging to obtain. Instead, inverse methods can be used to infer basal parameters from surface observations. Here, we use a simple ice-flow model as a forward model in an inversion scheme to retrieve the spatio-temporally variable basal stress parameter for Hagen Bræ, North Greenland, from 1990 to 2020. Hagen Bræ is a surge-type glacier with up to an order of magnitude variability of winter velocities near the grounding line. We find that downstream changes in the basal stress parameter can explain most of the variation of flow velocity, and we further identify a region of high resistance ~20–40 km from the grounding line. We hypothesise that this region of high resistance plays an important role in controlling glacier discharge.
A “Sideways” Supply Response in California Winegrapes
Authors: Consoli Sarah , Fraysse Elizabeth A. , Slipchenko Natalya , Wang Yi , Amirebrahimi Jahon , Qin Zhiran , Yazma Neil , Lybbert Travis J.
Published: November 2021

This paper explores growers’ supply response to the 2005 “Sideways effect” demand shock (Cuellar, Karnowsky, and Acosta, 2009) triggered by the 2004 release of the movie Sideways. We use a modified difference-in-difference approach to evaluate the supply response in California and regional supply response differences within California. We use U.S. Department of Agriculture data for the period 1999–2012 and find evidence of a supply response in the post-release period that is consistent with the “Sideways effect” on wine demand. The positive supply response for Pinot Noir is stronger than the negative response for Merlot and concentrated in lower value Central Valley vineyards. (JEL Classifications: D25, Q12)
Shell shape, morphometrics and relative growth of four sympatric limpet species from the Algarve coast (southern Portugal)
Authors: Vasconcelos Paulo , Janeiro Flávio , Pereira Fábio , Moura Paula , Carvalho André N. , Gaspar Miguel B.
Published: November 2021

This study analysed and compared the shell shape, morphometrics and relative growth of four sympatric limpet species (Patella depressa,Patella ulyssiponensis,Patella vulgataandSiphonaria pectinata) collected at Praia da Luz in Lagos (Algarve coast – southern Portugal). Morphometric relationships were established through regression analysis between linear (shell length, width and height), ponderal (total weight), area (shell base and surface areas) and volume variables (shell internal and total volumes). Relative growth (isometryvsallometry) was analysed to assess variation in the growth rate of morphometric variables throughout the species ontogeny. In addition, morphometric indices (ellipticity, conicity, density, surface area and volumetry) were calculated to further characterize shell shape. Overall, 1482 individuals with broad size and weight ranges were analysed (P. depressa= 354;P. ulyssiponensis= 306;P. vulgata= 408;S. pectinata= 414). All regressions were highly significant (P< 0.001) and the morphometric variables were strongly correlated (r= 0.761 to 0.994). Among 28 morphometric relationships, there were 14 isometries, 13 positive allometries and only one negative allometry. The morphometric indices revealed clear morphological differences between species and were mostly size-dependent, reflecting gradual changes in shell shape during growth. The main results are compared with a compilation of analogous data reported for these limpet species throughout their distributional range. Overall, the general trends in relative growth are discussed in terms of the species life habits, main traits and functional morphology.
Protecting an icon: Javan rhinoceros frontline management and conservation
Authors: Wilson Steven Graham , Biggs Duan , Kark Salit
Published: November 2021

Managers of threatened species in remote protected areas play a pivotal role in shaping the outcomes of management and conservation programmes. The island of Java supports the last remaining population of the Javan rhinoceros Rhinoceros sondaicus, a Critically Endangered megaherbivore with only 72 individuals persisting in the wild, in Ujung Kulon National Park. Substantial resources are being invested to manage the Javan rhinoceros and it is difficult to monitor it in the rainforest to assess whether management actions have been successful. Insights from frontline staff into the outcomes of past conservation actions and the future actions required may be key to enhancing the outcomes of conservation actions for threatened species. To study the perceptions of frontline staff towards the conservation of the Javan rhinoceros, management actions and their outcomes, we surveyed all 36-frontline staff in Ujung Kulon National Park. Although staff perceptions of conservation outcomes were generally positive, they noted key anthropogenic threats and challenges to rhinoceros protection inherent to the survival of the last Javan rhinoceros population. Staff identified increased threat of disease transfer from domestic stock to the rhinoceros, in spite of protective fencing, and the combined effects of illegal firewood collection and agricultural encroachment on rhinoceros habitat. Systematically recording and incorporating the perceptions of frontline staff in remote and often inaccessible protected areas can help identify important areas for future conservation and threat mitigation that can facilitate better protection for the Javan rhinoceros and other iconic species.
Narratives Behind Livestock Methane Mitigation Studies Matter
Authors: Rigolot Cyrille
Published: November 2021

A recent study in AGU Advances highlights the key role of production efficiency changes in livestock methane emission mitigation, which outperforms demand‐side efforts (Chang et al., 2021, https://doi.org/10.1029/2021AV000391). While acknowledging the high value of Chang et al.’s analysis, this commentary argues that the way its results are emphasized and discussed matters. As it is, the proposed narrative might even inadvertently (not intentionally) contribute to a “climate delay discourse,” that is, a discourse that fully accepts climate change but justifies inadequate efforts. From a climate emergency perspective, one important result of the study is that total emissions have increased substantially in the last two decades, at odds with climate change mitigation targets. A more transformative narrative would highlight the need to cultivate synergies between production and more ambitious demand‐side efforts, rather than the differences between their respective mitigation potentials.
Multi‐Century Changes in the Ocean Carbon Cycle Controlled by the Tropical Oceans and the Southern Ocean
Authors: Chikamoto Megumi O. , DiNezio Pedro
Published: November 2021

The oceanic absorption of anthropogenic carbon dioxide (CO2) is expected to continue in the following centuries, but the processes driving these changes remain uncertain. We studied these processes in a simulation of future changes in global climate and the carbon cycle following the RCP8.5 high emission scenario. The simulation shows increasing oceanic uptake of anthropogenic CO2 peaking towards the year 2080 and then slowing down but remaining significant in the period up to the year 2300. These multi‐century changes in uptake are dominated by changes in sea‐air CO2 fluxes in the tropical and southern oceans. In the tropics, reductions in upwelling and vertical gradients of dissolved carbon will reduce the vertical advection of carbon‐rich thermocline waters, suppressing natural outgassing of CO2. In the Southern Ocean, the upwelling of waters with relatively low dissolved carbon keeps the surface carbon relatively low, enhancing the uptake of CO2 in the next centuries. The slowdown in CO2 uptake in the subsequent centuries is caused by the decrease in CO2 solubility and storage capacity in the ocean due to ocean warming and changes in carbon chemistry. A collapse of the Atlantic Meridional Overturning Circulation (AMOC) predicted for the next century causes a substantial reduction in the uptake of anthropogenic CO2. In sum, predicting multi‐century changes in the global carbon cycle depends on future changes in carbon chemistry along with changes in oceanic and atmospheric circulations in the Southern and tropical oceans, together with a potential collapse of the AMOC.
Using Traffic Density and Foliar Chemistry Variables to Understand Interactions Between Air Pollution and Household Income
Authors: Cobley L. A. E. , Pataki D. E. , Adler F. R. , Hinners S. J.
Published: November 2021

We utilize traffic density and Convolvulus arvensis leaf chemistry to understand spatial patterns linking atmospheric pollution and household income in the Salt Lake City metropolitan area, USA. We hypothesize that traffic density will explain variation in atmospheric NOx and O3 concentrations. In addition, we expect foliar %N and nitrogen isotope ratios (δ15N) to be elevated and carbon isotope ratios (δ13C) to be depleted on high traffic density roads. These hypotheses were supported: we found the highest NOx and lowest O3 concentrations on high‐traffic density roads. Also, NOx concentrations were higher in low‐income neighborhoods. Low‐income neighborhoods contained a greater density of high‐traffic roads than high‐income neighborhoods. Foliar %N was highest in low‐income neighborhoods and was correlated with NOx and O3, while δ15N was more depleted with increasing O3. These findings indicate that the distribution of high‐traffic density roads plays a significant role in inequities in pollution exposure between high‐ and low‐income neighborhoods, which is reflected in leaf chemistry.
The Influence of Sediment Transport on Stationary and Mobile Knickpoints in River Profiles
Authors: Hergarten Stefan
Published: November 2021

The analysis of stationary and mobile knickpoints has been one of the most powerful concepts in tectonic geomorphology for decades. While several models combining bedrock incision and sediment transport are available, the existing theory of knickpoints focuses on detachment‐limited erosion without consideration of sediment transport. On the other hand, fully transport‐limited systems do not maintain distinct knickpoints. This study addresses the existence and the properties of slope‐break knickpoints in fluvial systems between the two extremes with the help of the shared stream‐power model, which allows for a continuous shift between detachment‐limited and transport‐limited erosion. The most important result is that both stationary and mobile knickpoints remain sharp and are not smeared by sediment transport. The system responds to tectonic signals in two phases where the first phase is similar to the detachment‐limited model. Comparing rivers with the same equilibrium profile at a given uplift rate, the velocity of knickpoint migration increases toward transport‐limited conditions. The second phase of the response is dominated by changes in sediment flux and affects the entire river segment downstream of the mobile knickpoint including the fault where the tectonic signal was initiated. During this phase, the mobile knickpoint is flattened in the sense that the difference in steepness index across a slope‐break knickpoint decreases through time. It is also shown that large parts of the theory for the nonlinear model, in particular knickpoint sharpening and stretching, remain valid, but the effect of nonlinearity decreases with increasing contribution of sediment transport.
Low‐Rate Faulting on the Margin of the Colorado Plateau and Rio Grande Rift in North‐Central New Mexico
Authors: Thompson Jobe Jessica A. , Chupik Colin
Published: November 2021

In northern New Mexico, seismic hazard outside of the Rio Grande Rift (RGR) is generally considered low due to limited historical seismicity and few mapped Quaternary faults. Although the region has a complex tectonic history, nearly all known faults are considered inactive because of a lack of faulted Quaternary deposits. Analysis of lidar and existing geologic and geomorphic mapping permits identification and characterization of four faults on the Colorado Plateau/RGR margin. The Gallina, Willow Creek, and East and West Brazos Peak faults are normal or dextral‐normal faults that strike NW‐SE with lengths from 15 to 50 km. The Willow Creek fault has scarp heights <0.5–6.4 m on five Quaternary surfaces, with displacement increasing with relative surface age. An ∼5‐m‐high scarp on the ∼250 ka Brazos basalt yields an ∼0.02 mm/yr minimum dip‐slip rate. Oblique slip is recorded by dextral offset (∼40 m) of a middle Quaternary (?) terrace riser, a linear and en‐echelon stepping fault pattern, and a consistent down‐to‐the‐northeast fault expression. The West Brazos Peak fault displaces late Quaternary (?) surfaces by <4 m down‐to‐the‐southwest. We interpret these faults are Laramide‐aged faults reactivated as normal or dextral‐oblique faults in the Quaternary, consistent with regional stress and geodetic data. Although the faults have low slip rates (<0.1 mm/yr), the fault lengths suggest they may rupture in M6‐7 earthquakes and may pose a previously unrecognized seismic hazard to the region. Dextral transtension within the eastern Colorado Plateau is consistent with geodetic strain rates and earthquake focal mechanisms.
Peak ependymal cell stretch overlaps with the onset locations of periventricular white matter lesions
Authors: Visser Valery L. , Rusinek Henry , Weickenmeier Johannes
Published: November 2021

Deep and periventricular white matter hyperintensities (dWMH/pvWMH) are bright appearing white matter tissue lesions in T2-weighted fluid attenuated inversion recovery magnetic resonance images and are frequent observations in the aging human brain. While early stages of these white matter lesions are only weakly associated with cognitive impairment, their progressive growth is a strong indicator for long-term functional decline. DWMHs are typically associated with vascular degeneration in diffuse white matter locations; for pvWMHs, however, no unifying theory exists to explain their consistent onset around the horns of the lateral ventricles. We use patient imaging data to create anatomically accurate finite element models of the lateral ventricles, white and gray matter, and cerebrospinal fluid, as well as to reconstruct their WMH volumes. We simulated the mechanical loading of the ependymal cells forming the primary brain-fluid interface, the ventricular wall, and its surrounding tissues at peak ventricular pressure during the hemodynamic cycle. We observe that both the maximum principal tissue strain and the largest ependymal cell stretch consistently localize in the anterior and posterior horns. Our simulations show that ependymal cells experience a loading state that causes the ventricular wall to be stretched thin. Moreover, we show that maximum wall loading coincides with the pvWMH locations observed in our patient scans. These results warrant further analysis of white matter pathology in the periventricular zone that includes a mechanics-driven deterioration model for the ventricular wall.
An open-source automated PEG precipitation assay to measure the relative solubility of proteins with low material requirement
Authors: Oeller Marc , Sormanni Pietro , Vendruscolo Michele
Published: November 2021

The solubility of proteins correlates with a variety of their properties, including function, production yield, pharmacokinetics, and formulation at high concentrations. High solubility is therefore a key requirement for the development of protein-based reagents for applications in life sciences, biotechnology, diagnostics, and therapeutics. Accurate solubility measurements, however, remain challenging and resource intensive, which limits their throughput and hence their applicability at the early stages of development pipelines, when long-lists of candidates are typically available in minute amounts. Here, we present an automated method based on the titration of a crowding agent (polyethylene glycol, PEG) to quantitatively assess relative solubility of proteins using about 200 µg of purified material. Our results demonstrate that this method is accurate and economical in material requirement and costs of reagents, which makes it suitable for high-throughput screening. This approach is freely-shared and based on a low cost, open-source liquid-handling robot. We anticipate that this method will facilitate the assessment of the developability of proteins and make it substantially more accessible.
Candidate genes of SARS-CoV-2 gender susceptibility
Authors: Russo Cristina , Morello Giovanna , Malaguarnera Roberta , Piro Salvatore , Furno Debora Lo , Malaguarnera Lucia
Published: November 2021

The severe acute respiratory syndrome coronavirus (SARS-CoV-2) initiated a global viral pandemic since late 2019. Understanding that Coronavirus disease (COVID-19) disproportionately affects men than women results in great challenges. Although there is a growing body of published study on this topic, effective explanations underlying these sex differences and their effects on the infection outcome still remain uncertain. We applied a holistic bioinformatics method to investigate molecular variations of known SARS-CoV-2 interacting human proteins mainly expressed in gonadal tissues (testis and ovary), allowing for the identification of potential genetic targets for this infection. Functional enrichment and interaction network analyses were also performed to better investigate the biological differences between testicular and ovarian responses in the SARS-CoV-2 infection, paying particular attention to genes linked to immune-related pathways, reactions of host cells after intracellular infection, steroid hormone biosynthesis, receptor signaling, and the complement cascade, in order to evaluate their potential association with sexual difference in the likelihood of infection and severity of symptoms. The analysis revealed that within the testis network TMPRSS2, ADAM10, SERPING1, and CCR5 were present, while within the ovary network we found BST2, GATA1, ENPEP, TLR4, TLR7, IRF1, and IRF2. Our findings could provide potential targets for forthcoming experimental investigation related to SARS-CoV-2 treatment.