bluuebunny/crossref_metadata_2025 huggingface dataset:
Hearing the Petition and Making the Order
Authors: French Derek
Published: October 2021

The chapter observes the hearing of winding-up petitions and making orders. Winding up by the court involves a determination of a civil right within the meaning of the European Convention on Human Rights, art 6(1) (right to a fair trial). A winding-up petition is normally heard by an Insolvency and Companies Court (ICC) judge or a district judge. The court hearing a petition for the compulsory winding up of a company has a discretion to hear anyone who can assist the court, as advocate to the court. A foreign creditor has the same rights regarding participation in proceedings as creditors in Great Britain. On hearing a winding-up petition the court may, at its discretion, dismiss it, or adjourn the hearing conditionally or unconditionally, or make an interim order, or any other order that it thinks fit. The court may order the winding up of a company on application made by petition under IA 1986, s 124.
Other Petitioners
Authors: French Derek
Published: October 2021

A company may petition for itself to be wound up by the court. The same applies to a building society, an incorporated friendly society, a limited liability partnership (LLP), and any other entity that may be wound up as a registered company. A company’s power to petition for its own winding up may be exercised by its directors, at least if the company has passed a special resolution that the company be wound up by the court, that being a circumstance in which the court may make a winding-up order. A petition by a company for its own compulsory winding up will usually rely on the circumstance that a special resolution has been adopted that the company be wound up by the court. When a resolution for compulsory winding up has been adopted, the court retains a discretion whether or not to make a winding-up order.
Astrosat: forecasting satellite transits for optical astronomical observations
Authors: Osborn James , Blacketer Laurence , Townson Matthew J , Farley Ollie J D
Published: October 2021

The impact of large-scale constellations of satellites, is a concern for ground-based astronomers. In recent years there has been a significant increase in the number of satellites in low-Earth orbit and this trend is set to continue. The large number of satellites increases the probability that one will enter the field of view of a ground-based telescope at the right solar angle to appear bright enough that it can corrupt delicate measurements. We present a new tool ‘Astrosat’ that will project satellite orbits onto the RA/Dec. coordinate system for a given observer location and time and field of view. This enables observers to mitigate the effects of satellite trails through their images by either avoiding the intersection, post-processing using the information as a prior or shuttering the observation for the duration of the transit. We also provide some analysis on the apparent brightness of the largest of the constellations, Starlink, as seen by a typical observatory and as seen with the naked eye. We show that a naked eye observer can typically expect to see a maximum of 5 Starlink satellites at astronomical twilight, when the sky is dark. With the intended 40 000 satellites in the constellation that number would increase to 30.
Stability of an ionization front in Bondi accretion
Authors: Keto Eric , Kuiper Rolf
Published: October 2021

Spherical Bondi accretion is used in astrophysics as an approximation to investigate many types of accretion processes. Two-phase accretion flows that transition from neutral to ionized have observational support in high-mass star formation, and have application to accretion flows around any ionizing source, but the hydrodynamic stability of two-phase Bondi accretion is not understood. With both semi-analytic and fully numerical methods, we find that these flows may be stable, conditionally stable, or unstable depending on the initial conditions. The transition from an R-type to a D-type ionization front plays a key role in conditionally stable and unstable flows.
Unstable modes of hypermassive compact stars driven by viscosity and gravitational radiation
Authors: Rau Peter B , Sedrakian Armen
Published: October 2021

We study the oscillation modes of differential rotating remnants of binary neutron star inspirals by modelling them as incompressible Riemann ellipsoids parametrized by the ratio f of their internal circulation to the rotation frequency. The effects of viscosity and gravitational radiation on the modes are studied, and it is shown that these bodies exhibit generic instability towards gravitational radiation akin to the Chandrasekhar–Friedman–Schutz instability for uniformly rotating stars. The odd-parity modes are unstable for all values of f (except for the spherical model) and deformations, whereas the even parity unstable modes appear only in highly eccentric ellipsoids. We quantify the modification of the modes with the varying mass of the model and the magnitude of the viscosity. The modes are weakly dependent on the range of the masses relevant to binary neutron star mergers. Large turbulent viscosity can lead to a suppression of the gravitational-radiation instability, whereas kinematical viscosity has a negligible influence on the modes and their damping time-scales.
AlphaFold Protein Structure Database: massively expanding the structural coverage of protein-sequence space with high-accuracy models
Authors: Varadi Mihaly , Anyango Stephen , Deshpande Mandar , Nair Sreenath , Natassia Cindy , Yordanova Galabina , Yuan David , Stroe Oana , Wood Gemma , Laydon Agata , Žídek Augustin , Green Tim , Tunyasuvunakool Kathryn , Petersen Stig , Jumper John , Clancy Ellen , Green Richard , Vora Ankur , Lutfi Mira , Figurnov Michael , Cowie Andrew , Hobbs Nicole , Kohli Pushmeet , Kleywegt Gerard , Birney Ewan , Hassabis Demis , Velankar Sameer
Published: October 2021

The AlphaFold Protein Structure Database (AlphaFold DB, https://alphafold.ebi.ac.uk) is an openly accessible, extensive database of high-accuracy protein-structure predictions. Powered by AlphaFold v2.0 of DeepMind, it has enabled an unprecedented expansion of the structural coverage of the known protein-sequence space. AlphaFold DB provides programmatic access to and interactive visualization of predicted atomic coordinates, per-residue and pairwise model-confidence estimates and predicted aligned errors. The initial release of AlphaFold DB contains over 360,000 predicted structures across 21 model-organism proteomes, which will soon be expanded to cover most of the (over 100 million) representative sequences from the UniRef90 data set.
The Human Disease Ontology 2022 update
Authors: Schriml Lynn M , Munro James B , Schor Mike , Olley Dustin , McCracken Carrie , Felix Victor , Baron J Allen , Jackson Rebecca , Bello Susan M , Bearer Cynthia , Lichenstein Richard , Bisordi Katharine , Dialo Nicole Campion , Giglio Michelle , Greene Carol
Published: October 2021

The Human Disease Ontology (DO) (www.disease-ontology.org) database, has significantly expanded the disease content and enhanced our userbase and website since the DO’s 2018 Nucleic Acids Research DATABASE issue paper. Conservatively, based on available resource statistics, terms from the DO have been annotated to over 1.5 million biomedical data elements and citations, a 10× increase in the past 5 years. The DO, funded as a NHGRI Genomic Resource, plays a key role in disease knowledge organization, representation, and standardization, serving as a reference framework for multiscale biomedical data integration and analysis across thousands of clinical, biomedical and computational research projects and genomic resources around the world. This update reports on the addition of 1,793 new disease terms, a 14% increase of textual definitions and the integration of 22 137 new SubClassOf axioms defining disease to disease connections representing the DO’s complex disease classification. The DO’s updated website provides multifaceted etiology searching, enhanced documentation and educational resources.
Comparing stimulus-evoked and spontaneous response of the face-selective multi-units in the human posterior fusiform gyrus
Authors: Schwartz Rina , Rozier Camille , Seidel Malkinson Tal , Lehongre Katia , Adam Claude , Lambrecq Virginie , Navarro Vincent , Naccache Lionel , Axelrod Vadim
Published: October 2021

The stimulus-evoked neural response is a widely explored phenomenon. Conscious awareness is associated in many cases with the corresponding selective stimulus-evoked response. For example, conscious awareness of a face stimulus is associated with or accompanied by stimulus-evoked activity in the fusiform face area (FFA). In addition to the stimulus-evoked response, spontaneous (i.e. task-unrelated) activity in the brain is also abundant. Notably, spontaneous activity is considered unconscious. For example, spontaneous activity in the FFA is not associated with conscious awareness of a face. The question is: what is the difference at the neural level between stimulus-evoked activity in a case that this activity is associated with conscious awareness of some content (e.g. activity in the FFA in response to fully visible face stimuli) and spontaneous activity in that same region of the brain? To answer this question, in the present study, we had a rare opportunity to record two face-selective multi-units in the vicinity of the FFA in a human patient. We compared multi-unit face-selective task-evoked activity with spontaneous prestimulus and a resting-state activity. We found that when activity was examined over relatively long temporal windows (e.g. 100–200 ms), face-selective stimulus-evoked firing in the recorded multi-units was much higher than the spontaneous activity. In contrast, when activity was examined over relatively short windows, we found many cases of high firing rates within the spontaneous activity that were comparable to stimulus-evoked activity. Our results thus indicate that the sustained activity is what might differentiate between stimulus-evoked activity that is associated with conscious awareness and spontaneous activity.
Activation of MAPK/ERK signalling in Merlin-null Schwann cells leads to increased and sustained immune cell infiltration in the peripheral nervous system
Authors: Woodhouse Evyn , Laraba Liyam , Lespade Charlotte , Srotyr Marie , Lloyd Alison C , Parkinson David B
Published: October 2021

Aims

Previous work has shown that increased numbers of macrophages are associated with more rapid schwannoma tumour growth and we are interested in signals that control entry of macrophages and other immune cells into these tumours. Activation of the Raf-kinase domain and the Raf/MEK/ERK pathway within Schwann cells has been observed to induce an inflammatory response in peripheral nerves in the absence of injury. Activation of an inducible Raf-kinase transgene in Schwann cells allows modelling of acute demyelination of peripheral nerves without nerve injury. This Raf-oestrogen receptor fusion protein (Raf-TR) is activated by the oestrogen analogue Tamoxifen and so allows targeted, controlled activation of the Raf/MEK/ERK pathway within the Schwann cells.

Here, in order to understand drivers of tumour formation, we assess the effect of MAPK activation in Merlin-null Schwann cells upon immune cell infiltration within the PNS.

Method

RafTR-P0CRE-NF2fl/fl mice of 4-6 weeks age were injected daily (IP) with 2mg of 4-hydroxy-tamoxifen or vehicle (corn oil) control for 5 consecutive days. RafTR was activated on either a Merlin (NF2) wild-type (NF2 fl/fl, P0-CRE-) or NF2 null (NF2 fl/fl, P0-CRE+) background and effects on immune cell infiltration studied in each condition.

Immunofluorescence was performed in the dorsal root ganglia (DRGs) and sciatic nerves of mice to identify various immune cell infiltrates at various timepoints. These will include neutrophils, mast cells, T-Cells and macrophages using the cell markers Csf3r, C-kit, CD3 and IBA1 respectively.

Results

At 21 days post treatment, a significantly increased infiltration of macrophages within the sciatic nerve and dorsal root ganglia was observed in mice treated with Tamoxifen when compared to vehicle controls. Loss of NF2 led to a massive increase in the number of macrophages recruited to peripheral nerves in tamoxifen-treated mice compared to Cre- mice and Cre+ treated with vehicle alone. Further assessment of other immune cell infiltration including neutrophils, mast cells and T cells are ongoing.

Conclusion

Raf/MEK/ERK signalling, in the absence of tumour suppressor Merlin, significantly increases the infiltration of inflammatory cells such as macrophages into peripheral nerves even in the absence of injury. As this effect is enhanced in NF2 null mice, this suggests that Merlin plays an important role in inhibiting the inflammatory response in peripheral nerves. It also suggests that Merlin could be involved in maintaining the blood nerve barrier (BNB), as in its absence the greater influx of immune cells into the nerves and DRGs suggests a more complete loss of BNB function than just activation of the Raf/MEK/ERK cascade alone.
Clinical Features at Presentation for Glioblastoma Patients Impact Survival Predictions in a Machine Learning Model
Authors: Lawrence Alistair , Sinha Rohit , Mitrasinovic Stefan , Price Stephen
Published: October 2021

Aims

To generate an accurate prediction model for greater than median survival using Random Forest machine learning analysis and to compare the model to a traditional logistic regression analysis model on the same Glioblastoma Dataset.

Method

In this single centre retrospective cohort study, all patients with histologically diagnosed primary GB from October 2014 to April 2019 were included (n=466). Machine learning algorithms encompassing multiple logistic regression and a Random Forest, Gini index-based decision tree model with 100,000 trees were used. 17 clinical, molecular and treatment specific binarily categorised variables were used. The dataset was split 70:30 into training and validating sets.

Results

The dataset contained 466 patients. 326 patients made up the training set and 140 the validation set. The Random Forest model’s accuracy for predicting 18-month survival was 86.4% compared to the Logistic Regression model’s accuracy of 85.7%. The top 5 factors that the Random Forest model used to predict survival over 18 months were; mean MGMT status >10%, if the patient underwent gross total resection, whether the patient had adjuvant temozolomide, whether the patient had a neurological deficit on presentation, and the sex of the patient.

Conclusion

Machine learning can be applied in the context of GB prognostic modelling. The models show that as well as the known factors that affect GB survival, the presenting symptom may also have an impact on prognostication.
Fatal Love
Authors: Devji Faisal
Published: October 2021

̧Interest is commonly seen as the fundamental unit of liberal politics—though in a narrowly economic sense it also forms the basis of a leftist vision of history. But while there has been no dearth of interest-based action as much as analysis in modern Indian politics, its “excessive” character, whether sacrificial, idealistic, or cruel, has permitted the category itself to be questioned, especially where religious relations are concerned. This chapter looks at how Ambedkar, Gandhi, Iqbal, Savarkar, and Jinnah were part of a conversation on the apparent “lack” or limitation of interest in Indian politics. For these men it was the absence of interest as a foundational category in Indian society, attributed to the fact that property did not define social relations there, that made for its violence as much as its spiritualism. Their problem was either to create interests where they didn’t exist, or to dispense with them altogether.
Development of Quality of Life Assessment Questionnaire Associated with Osmophobia in People with Migraine
Authors: Tanik Nermin , Bektas Murat
Published: October 2021

Background

It is important to implement disease-specific precautions to develop quality of life in migraine. The effect of osmophobia, which is one of the specific symptoms of migraine that might help to differentiate migraine from other headache disorders, on quality of life is unknown. The aim of the present study was to develop a practicable and reliable scale that assesses the effect of osmophobia on quality of life in migraine.

Methods

This cross-sectional study was carried out with 163 patients with migraine and 110 healthy individuals for control group. The scale items were constructed based on after literature review, expert opinions, and preliminary trial stage. A semi-structured interview was conducted with the patients by the Neurologist to evaluate the presence of osmophobia retrospectively. Migraine osmophobia-related quality of life assessment (MORA) consisted of 6 items including personal care, eating or cooking, house cleaning, close relationship, social life and traveling.

Results

The Cronbach's α coefficient was 0.86; and the Guttman split-half coefficient was 0.83. Receiver operating characteristic analysis showed an area under the curve of 0.943 (95%) confidence interval [CI] = 0.902–0.984), a cutoff score of >9.5, a sensitivity of 91.6%, a specificity of 85.7%. Mean scores of the MORA differed between people with migraine (with and without osmophobia) and healthy controls (<0.001).

Conclusion

MORA is a valid and reliable self-report questionnaire that assesses the effect of osmophobia on quality of life in migraine. This questionnaire appears to be a practicable diagnostic instrument in clinical practice and research.
Ruminal in situ degradability of forage components and in vitro organic matter digestibility of warm-season grasses treated with calcium oxide
Authors: Ciriaco Francine M , Henry Darren D , Beierbach Romina , Schulmeister Tessa M , Ruiz-Moreno Martin , Garcia-Ascolani Mariana E , Podversich Federico , Dubeux Jose C B , DiLorenzo Nicolas
Published: October 2021

An experiment was designed to evaluate the effects of CaO on ruminal in situ degradability (RISD) of forage components and in vitro organic matter digestibility (IVOMD) of warm-season forages. Bahiagrass (Paspalum notatum; BH) or Tifton 85 bermudagrass (Cynodon spp.; BM) hay were stored in 20-L buckets in two consecutive years (n = 4/treatment) as follows: 1) untreated dry BH or BM (DH); 2) hydrated BH or BM stored for 7 d (W7); 3) hydrated BH or BM stored for 14 d (W14); 4) hydrated BH or BM + 5% [dry matter (DM) basis] CaO stored for 7 d (CO5-7); 5) hydrated BH or BM + 5% (DM basis) CaO stored for 14 d (CO5-14); and 6) hydrated BH or BM + 10% (DM basis) CaO stored for 14 d (CO10). With exception of the dry treatment (DH), tap water was added to forages under the remaining treatments to reach a DM concentration of 50%. Ruminal in situ degradability of DM, organic matter (OM), crude protein (CP), neutral detergent fiber (NDF), and acid detergent fiber (ADF) of BH and BM was determined for 24, 48, and 72 h in two ruminally cannulated steers consuming BH. Data were analyzed as a randomized block design using bucket as the experimental unit. The model included the fixed effect of treatment and the random effect of year. Concentration of NDF was reduced (P < 0.001) when BH and BM were treated with 10% and 5% CaO and compared with DH. However, only CO10 promoted a reduction (P = 0.007) in ADF concentration of BH, whereas CO10 and CO5, regardless of storage length, reduced (P ≤ 0.006) ADF concentration of BM, when compared with DH. At all ruminal incubation time points, a treatment effect (P < 0.001) was observed on RISD of DM, OM, CP, NDF, and ADF of BH and BM, where all treatments containing CaO promoted greater degradability when compared with DH, W7, and W14, which did not differ (P > 0.05). Ruminal degradability of forage components was greatest (P < 0.05) for CO10, followed by CO5-7 and CO5-14, which did not differ (P > 0.05). In vitro organic matter digestibility was increased (P < 0.001) in both BH and BM when CaO was applied and compared to DH. Treatment of BH and BM with CaO seems to be an effective method of promoting increased digestibility of forage components, including fiber fractions, when applied at 5% of the forage DM with potential additional benefits to BH when applied at 10%.
Characterization and Pathogenicity of Diplodia, Lasiodiplodia, and Neofusicoccum Species Causing Botryosphaeria Canker and Dieback of Apple Trees in Central Chile
Authors: Díaz Gonzalo A. , Valdez Adrían , Halleen Francois , Ferrada Enrique , Lolas Mauricio , Latorre Bernardo A.
Published: October 2021

In recent years, the number of apple trees affected by Botryosphaeria cankers and dieback has considerably increased in central Chile. This study aimed to identify the species of Botryosphaeriaceae associated with canker and dieback symptoms, estimate disease incidence and distributions, and study their pathogenicity and virulence on apple and other fruit crops. A field survey of 34 commercial orchards of apple (7 to 30 years old) was conducted in 16 localities, obtaining 270 symptomatic branch and trunk samples in 2017 and 2018 growing seasons. The incidence of Botryosphaeria canker and dieback ranged between 5 and 40%, and a total of 255 isolates of Botryosphaeriaceae spp. were obtained from 238 cankers. Morphological identification along with phylogenetic studies of the internal transcribed spacer (ITS) region (ITS1-5.8S-ITS2) of the rDNA, part of the translation elongation factor 1-α (tef1-α), and part of the β-tubulin (tub2) genes allowed us to identify Diplodia mutila (n = 49 isolates), D. seriata (n = 136 isolates), Lasiodiplodia theobromae (n = 16 isolates), and Neofusicoccum arbuti (n = 54 isolates). L. theobromae was isolated mainly from apple dieback from northern localities. All pathogens tested were pathogenic, causing canker and dieback symptoms on lignified twigs of apple, pear, walnut, and green grapevine shoots in the field. Isolates of N. arbuti were the most virulent, reproducing more severe cankers on the lignified tissues inoculated. This study reports, for the first time, D. mutila and L. theobromae associated with Botryosphaeria canker and dieback in Chile, and it is the first description of N. arbuti causing apple dieback worldwide.
NEW METHOD FOR REDUCING ARTIFACTUAL FLOW DEFICITS CAUSED BY COMPENSATION TECHNIQUES IN THE CHORIOCAPILLARIS WITH OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY
Authors: Nesper Peter L. , Fawzi Amani A.
Published: October 2021

Purpose:

To mitigate artifactual choriocapillaris flow deficits in optical coherence tomography angiography, which are a side effect of inverse structural optical coherence tomography compensation.

Methods:

In a modified algorithm, we set pixels in the original structural optical coherence tomography that were greater than one SD above the mean intensity (hyperreflective regions) to the mean pixel intensity of the image to remove hyporeflective regions in the inverse slab. We compared this algorithm to the original using flow deficit density and multiscale structural similarity index obtained from three distinct thresholding methods (local Phansalkar, global MinError (I), and global Li).

Results:

We included 16 eyes of 16 healthy subjects (31.1 ± 6.9 years, 10 females). Using the modified optical coherence tomography correction, flow deficit density was lower compared with the original algorithm using Phansalkar (P < 0.001) but higher using Li thresholding (P = 0.049). Multiscale structural similarity index was increased after applying the modified algorithm with all three thresholding methods (P < 0.001), indicating a closer relationship to the original optical coherence tomography angiography scan.

Conclusion:

We demonstrate a new method that significantly reduced the introduction of artifactual flow deficits in the choriocapillaris during postprocessing. Given the improved multiscale structural similarity index, we believe our algorithm more accurately represents the choriocapillaris.
Mechanically and Physiologically Optimizing Prosthetic Elevated Vacuum Systems in People with Transtibial Amputation: A Pilot Study
Authors: Youngblood Robert T. , Hafner Brian J. , Czerniecki Joseph M. , Larsen Brian G. , Allyn Katheryn J. , Sanders Joan E.
Published: October 2021

Introduction

The most suitable elevated vacuum (EV) pressure may differ for each individual prosthesis user depending on suspension needs, socket fit, prosthetic components, and health. The mechanical and physiological effects of EV were evaluated in an effort to determine the optimal vacuum pressure for three individuals.

Methods

Instrumented EV sockets were created based on the participants’ regular EV sockets. Inductive distance sensors were embedded into the wall of the socket at select locations to measure limb movement relative to the socket. Each participant conducted an activity protocol while limb movement, limb fluid volume, and user-reported comfort were measured at various socket vacuum pressure settings.

Results

Increased socket vacuum pressure resulted in reduced limb-socket displacement for each participant; however, 81% to 93% of limb movement was eliminated by a vacuum pressure setting of 12 (approximately −9 inHg). Relative limb-socket displacement by sensor location varied for each participant, suggesting distinct differences related to socket fit or residual limb tissue content. The rate of limb fluid volume change and the change in socket comfort did not consistently differ with socket vacuum pressure, suggesting a more complex relationship unique to each individual.

Conclusions

Practitioners may use individual responses to optimize socket vacuum pressure settings, balancing the mechanical and physiological effects of EV for improved clinical outcomes.

Clinical Relevance

Understanding the effects of various socket vacuum pressure settings on individuals’ outcomes may improve clinical implementation of EV. In this study, the highest available vacuum setting did not always produce maximum comfort and limb fluid volume benefit, and similar levels of suspension were achieved with lower vacuum settings.
Splice correction therapies for familial hypercholesterolemic patients with low-density lipoprotein receptor mutations
Authors: McIntosh Craig S. , Watts Gerald F. , Wilton Steve D. , Aung-Htut May T.
Published: October 2021

Purpose of review

Antisense oligomers (ASOs) have been available for decades: however, only recently have these molecules been applied clinically. This review aims to discuss the possible development of antisense-mediated splice correction therapies as precision medicines for familial hypercholesterolemic patients carrying mutations that compromise normal splicing of the low-density lipoprotein receptor (LDLR) gene transcript.

Recent findings

Three antisense drugs are currently being assessed in ongoing clinical trials for dyslipidemias, aiming to lower the plasma concentrations of lipoproteins that lead to end-organ damage, principally coronary artery disease. Although a handful of drugs may be applicable to many patients with familial hypercholesterolemia (FH), mutation-specific personalised antisense drugs may be even more effective in selected patients. Currently, there is no therapy that effectively addresses mutations in the LDLR, the major cause of FH. Many mutations in the LDLR that disrupt normal pre-mRNA processing could be applicable to splice correction therapy to restore receptor activity.

Precision medicine could provide long-term economic and social benefits if they can be implemented effectively and sustainably. Many mutations found in the LDLR gene could be amendable to therapeutic splice correction and we should consider developing a therapeutic ASO platform for these mutations.
Worldwide epidemiology of neuro-coronavirus disease in children: lessons for the next pandemic
Authors: Alcamo Alicia M. , McGuire Jennifer L. , Kanthimathinathan Hari Krishnan , Roa Juan David , Fink Ericka L.
Published: October 2021

Purpose of review

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has overwhelmed the global community, negatively impacting patient health and research efforts; associated neurological manifestations are a significant cause of morbidity. This review outlines the worldwide epidemiology of neurologic manifestations of different SARS-CoV-2 clinical pediatric phenotypes, including acute coronavirus disease 2019 (COVID-19), multisystem inflammatory syndrome in children (MIS-C) and postacute sequelae of COVID-19 (PASC). We discuss strategies to develop adaptive global research platforms for future investigation into emerging pediatric neurologic conditions.

Recent findings

Multicenter, multinational studies show that neurological manifestations of acute COVID-19, such as smell/taste disorders, headache, and stroke, are common in hospitalized adults (82%) and children (22%), associated with increased mortality in adults. Neurological manifestations of MIS-C are reported in up to 20% of children, including headache, irritability, and encephalopathy. Data on PASC are emerging and include fatigue, cognitive changes, and headache. Reports of neurological manifestations in each phenotype are limited by lack of pediatric-informed case definitions, common data elements, and resources.

Coordinated, well resourced, multinational investigation into SARS-CoV-2-related neurological manifestations in children is critical to rapid identification of global and region-specific risk factors, and developing treatment and mitigation strategies for the current pandemic and future health neurologic emergencies.
The Effect of Lidocaine Delivered by Jet Injection on First Attempt Venous Access Success Rates in the Pediatric Emergency Department
Authors: Redmond Paul , Blackshear Chad , Davis Justin
Published: October 2021

Background

Jet injection of 1% lidocaine (J-Tip) has been used in the pediatric emergency department (PED) to reduce pain associated with venipuncture, but there are limited data on the effect of J-Tip on first-attempt venous access success rates. We sought to determine if using a J-Tip altered the first-attempt venous access success rate in the PED. Then, we examined the effect of J-Tip use on pain scores and resource utilization during peripheral venous access.

Methods

We prospectively evaluated children over 6 months of age who required peripheral venous access in the PED. The exposure group received 0.25 mL of 1% buffered lidocaine via jet injection 90 seconds before peripheral venous access. The control group received no local anesthesia. Parent and nurse surveys were completed during the visit.

Results

There was no difference in first attempt success rate between the exposure (n = 136) and control (n = 90) groups (87% vs 88%, P = 0.82). J-Tip use was associated with improved pain scores based on child report (median 1 vs 3; P < 0.001), parent report (median 1 vs 3; P < 0.001), and nurse assessment (median 0 vs 3; P < 0.001).

Conclusions

Use of J-Tip in the PED to reduce pain associated with peripheral venous access did not lead to a reduction in first-attempt success rates for peripheral venous access. J-Tip was well received among nurses and parents and was associated with improved pain scores.
Arabidopsis thaliana
endonuclease V is a ribonuclease specific for inosine-containing single-stranded RNA
Authors: Endo Megumi , Kim Jung In , Shioi Narumi Aoki , Iwai Shigenori , Kuraoka Isao
Published: October 2021

Endonuclease V is highly conserved, both structurally and functionally, from bacteria to humans, and it cleaves the deoxyinosine-containing double-stranded DNA in
Escherichia coli
, whereas in
Homo sapiens
it catalyses the inosine-containing single-stranded RNA. Thus, deoxyinosine and inosine are unexpectedly produced by the deamination reactions of adenine in DNA and RNA, respectively. Moreover, adenosine-to-inosine (A-to-I) RNA editing is carried out by adenosine deaminase acting on dsRNA (ADARs). We focused on
Arabidopsis thaliana
endonuclease V (AtEndoV) activity exhibiting variations in DNA or RNA substrate specificities. Since no ADAR was observed for A-to-I editing in
A. thaliana
, the possibility of inosine generation by A-to-I editing can be ruled out. Purified AtEndoV protein cleaved the second and third phosphodiester bonds, 3′ to inosine in single-strand RNA, at a low reaction temperature of 20–25°C, whereas the AtEndoV (Y100A) protein bearing a mutation in substrate recognition sites did not cleave these bonds. Furthermore, AtEndoV, similar to human EndoV, prefers RNA substrates over DNA substrates, and it could not cleave the inosine-containing double-stranded RNA. Thus, we propose the possibility that AtEndoV functions as an RNA substrate containing inosine induced by RNA damage, and not by A-to-I RNA editing
in vivo
.
Direct statistical simulation of low-order dynamosystems
Authors: Li Kuan , Marston J. B. , Tobias Steven M.
Published: October 2021

In this paper, we investigate the effectiveness of direct statistical simulation (DSS) for two low-order models of dynamo action. The first model, which is a simple model of solar and stellar dynamo action, is third order and has cubic nonlinearities while the second has only quadratic nonlinearities and describes the interaction of convection and an aperiodically reversing magnetic field. We show how DSS can be used to solve for the statistics of these systems of equations both in the presence and the absence of stochastic terms, by truncating the cumulant hierarchy at either second or third order. We compare two different techniques for solving for the statistics: timestepping, which is able to locate only stable solutions of the equations for the statistics, and direct detection of the fixed points. We develop a complete methodology and symbolic package in Python for deriving the statistical equations governing the low-order dynamic systems in cumulant expansions. We demonstrate that although direct detection of the fixed points is efficient and accurate for DSS truncated at second order, the addition of higher order terms leads to the inclusion of many unstable fixed points that may be found by direct detection of the fixed point by iterative methods. In those cases, timestepping is a more robust protocol for finding meaningful solutions to DSS.
Time-varying Bose–Einstein condensates
Authors: Van Gorder Robert A.
Published: October 2021

Bose–Einstein condensates (BECs), a state of matter formed when a low-density gas of bosons is cooled to near absolute zero, continue to motivate novel work in theoretical and experimental physics. Although BECs are most commonly studied in stationary ground states, time-varying BECs arise when some aspect of the physics governing the condensate varies as a function of time. We study the evolution of time-varying BECs under non-autonomous Gross–Pitaevskii equations (GPEs) through a mix of theory and numerical experiments. We separately derive a perturbation theory (in the small-parameter limit) and a variational approximation for non-autonomous GPEs on generic bounded space domains. We then explore various routes to obtain time-varying BECs, starting with the more standard techniques of varying the potential, scattering length, or dispersion, and then moving on to more advanced control mechanisms such as moving the external potential well over time to move or even split the BEC cloud. We also describe how to modify a BEC cloud through evolution of the size or curvature of the space domain. Our results highlight a variety of interesting theoretical routes for studying and controlling time-varying BECs, lending a stronger theoretical formulation for existing experiments and suggesting new directions for future investigation.
The Wiener–Hopf technique, its generalizations and applications: constructive and approximate methods
Authors: Kisil Anastasia V. , Abrahams I. David , Mishuris Gennady , Rogosin Sergei V.
Published: October 2021

This paper reviews the modern state of the Wiener–Hopf factorization method and its generalizations. The main constructive results for matrix Wiener–Hopf problems are presented, approximate methods are outlined and the main areas of applications are mentioned. The aim of the paper is to offer an overview of the development of this method, and demonstrate the importance of bringing together pure and applied analysis to effectively employ the Wiener–Hopf technique.
Guiding caregivers through disclosure: a qualitative investigation into caregivers’ responses to a disclosure intervention for HIV-infected children in Soweto, South Africa
Authors: Joyce Celeste , Ramsammy Candice , Galvin Lisa , Leshabane Given , Liberty Afaaf , Otwombe Kennedy , Buckley Janice , Milovanovic Minja , Violari Avy
Published: October 2021

Awareness of Human Immunodeficiency Virus (HIV) status improves health outcomes in HIV infected children, yet disclosure is often delayed by hesitant caregivers. This qualitative investigation explored how 30 caregivers responded to a HIV Disclosure study conducted between 2017 and 2020 at Chris Hani Baragwanath Academic Hospital, Soweto, South Africa. Caregivers were assisted in disclosing to their children, aged 7-13 years; followed by a sub-sample of caregivers interviewed to elaborate on findings.1) Barriers to disclosure included caregivers being ill-equipped, fear of negative consequences and children considered lacking emotional or cognitive readiness. 2) Deflecting diagnosis and the need for medication motivated caregivers to disclosure. 3) Apprehension was evident during disclosure, however, overall disclosure was a positive experience with the support of the healthcare providers. These results highlight the significant role healthcare providers play in supporting caregivers through the disclosure process and how, in turn, this has a positive impact on the community as a whole.
Back to the medical classes-Part I-Strategy for return to the presential practices during COVID-19 pandemics in a Brazilian Medical School
Authors: Nogueira Saad Maria Auxiliadora , Jardim Pereira Vinicius César , Bueno Arnaldo Costa , Vieira Alan Araujo , Pombo March Maria de Fátima , Salgado Quintans Maria Dolores , Mendonça Barcellos Bruno , da Cunha Ferreira Laura , Moura Ronchini Karla Regina Oliveira , Coca Velarde Luis Guillermo , Araújo Cardoso Claudete Aparecida , da Silva André Ricardo Araujo
Published: October 2021

Introduction

In Brazil, practices of medical students have been interrupted due to COVID-19 to meet emergency demands.

Aim

To describe a strategy for a controlled return to the presential practices for medical students.

Methods

We developed a standardized protocol to be applied before and during the return of the practical classes in medical students of Universidade Federal Fluminense, in the follow months after COVID-19 pandemic beginning. The protocol was comprised in three parts: Remote training on COVID-19 prevention; Face-to-face training focused in COVID-19 prevention, handwashing and personal protective equipment use; Investigation of students COVID-19 status before starting practical activities and weekly monitoring for COVID-19 during seven weeks. The training was done by medical teachers in small groups for medical students of the last lective semester.

Results

The classes were interrupted on March 12, 2020 and returned in August 10, 2020. Seventy-one students were trained and followed. The mean age was 26.6 years (26.7 ±0.835) and 54% were female. Forty-nine (69%) students over 71 had a private health insurance, 60 (84.5%) shared a house/apartment with one or more person and 12(16.9%) reported a previous comorbidity. Eighteen (25.4%) over 71 reported previous symptoms of COVID-19, being positive in two students. During the follow-up, fourteen (19.7%) over 71 students were placed in quarantine due to signals/symptoms compatible with COVID-19 or contact with symptomatic case. Only two cases (2.8%) were confirmed and occurred in Brazilian epidemiological week 37.

Conclusion

The protocol was successful in minimizing COVID-19 acquisition during practical classes of medical students.
Investigating the transparency of reporting in two-sample summary data Mendelian randomization studies
Authors: Woolf Benjamin , Cara Nina Di , Moreno-Stokoe Christopher , Skrivankova Veronika , Drax Katie , Higgins Julian P.T. , Hemani Gibran , Munafò Marcus R. , Smith George Davey , Yarmolinsky James , Richmond Rebecca C.
Published: October 2021

Background

Two-sample Mendelian randomization (2SMR) is an increasingly popular epidemiological method that uses genetic variants as instruments for making causal inferences. Clear reporting of methods employed in such studies is important for evaluating their underlying quality. However, the quality of methodological reporting of 2SMR studies is currently unclear.

Objectives

We aimed to assess the reporting quality of studies that used MR-Base, one of the most popular platforms for implementing 2SMR analysis.

Methods

We created a bespoke reporting checklist to evaluate reporting quality of 2SMR studies. We then searched Web of Science Core Collection, PsycInfo, MEDLINE, EMBASE and Google Scholar citations of the MR-Base descriptor paper to identify published MR studies that used MR-Base for any component of the MR analysis. Study screening and data extraction were performed by at least two independent reviewers.

Results

87 studies were included in the primary analysis. Reporting quality was generally poor across studies with a mean of 53% (SD = 14%) of items reported in each study. Many items required for evaluating the validity of key assumptions made in MR were poorly reported: only 44% of studies provided sufficient details for assessing if the genetic variant associates with the exposure (‘relevance’ assumption), 31% for assessing if there are any variant-outcome confounders (‘independence’ assumption), 89% for the assessing if the variant causes the outcome independently of the exposure (‘exclusion restriction’ assumption), and 32% for assumptions of falsification tests. We did not find evidence of a change in reporting quality over time or a difference in reporting quality between studies that used MR-Base and a random sample of MR studies that did not use this platform.

Discussion

The quality of reporting of two-sample Mendelian randomization studies in our sample was generally poor. Journals and researchers should implement the STROBE-MR guidelines to improve reporting quality.

Other: Funding

ESRC, CRUK, MRC, John Climax Benevolent Fund, University of Bristol, and the Wellcome Trust. Registration: This study pre-registered on the OSF, and the protocol can be found at DOI 10.17605/OSF.IO/NFM27
Efficacy and safety of a third SARS-CoV-2 vaccination in multiple sclerosis vaccine non-responders
Authors: König Marton , Torgauten Hilde Marie , Øverås Mathias Herstad , Chopra Adity , Rudjord Lorentzen Åslaug , Tran The Trung , Mjaaland Siri , Aaberge Ingeborg Sundsvalen , Myhr Kjell-Morten , Wergeland Stig , Berge Tone , Harbo Hanne Flinstad , Fredvik Torkildsen Øivind , Holmøy Trygve , Celius Elisabeth Gulowsen , Munthe Ludvig Andre , Vaage John Torgils , Lund-Johansen Fridtjof , Nygaard Gro Owren
Published: October 2021

Importance

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to protect against coronavirus disease of 2019 (COVID-19) is recommended for patients with multiple sclerosis (pwMS). However, approximately 80% of all pwMS treated with anti-CD20 therapy (rituximab, ocrelizumab) or fingolimod have low or absent humoral immunity after vaccination with two doses of SARS-CoV-2 mRNA vaccines. The efficacy and safety of a third vaccine dose in this group is largely unknown.

Objective

To characterize the humoral immunogenicity and the safety of a third dose of mRNA-COVID-19 vaccine in anti-CD20-or fingolimod-treated pwMS with low or absent humoral immunity (i.e., anti-SARS-CoV-2 IgG <70 arbitrary units (AU) and <5 AU, respectively) after two vaccinations.

Design, setting and participants

130 anti-CD20- or fingolimod-treated pwMS with low or absent humoral immunity despite full vaccination against SARS-CoV-2, received a third dose of SARS-CoV-2 mRNA vaccine. Humoral immunity (i.e., antibody response against SARS-CoV-2) and the frequency and characteristics of side-effects were analyzed in all participants.

Exposures

A third vaccine dose against SARS-CoV-2 with BNT162b2- or mRNA-1273-COVID-19 vaccine.

Main outcomes and measures

Patient- and treatment-specific variables were acquired using a digital questionnaire, the Norwegian Immunization Registry and hospital journals. Humoral immunity was assessed by measuring SARS-CoV-2 SPIKE receptor-binding domain (RBD) IgG response. Low/absent humoral immunity was assumed in cases of AU<70 after anti-SPIKE protein-based serology 3-5 weeks after revaccination.

Results

A third dose of SARS-CoV-2 mRNA vaccine increased anti-SARS-CoV-2 SPIKE RBD IgG levels significantly. The proportion of patients with assumed protective humoral immunity (anti-SARS-CoV-2 SPIKE RBD IgG > 70 AU) were 25% among patients using anti-CD20 therapy and 7% among those treated with fingolimod. No adverse events were registered during the study period.

Conclusion and relevance

A third dose of mRNA-COVID-19 vaccine was associated with significantly increased levels of anti-SARS-CoV-2 SPIKE RBD IgG, – and hence assumed protective humoral immunity - in anti-CD20- or fingolimod-treated pwMS with low or absent humoral immunity despite full vaccination. The effect of a third vaccine dose was limited and more prominent among those treated with anti-CD20 therapy.
VIKING II, a Worldwide Observational Cohort of Volunteers with Northern Isles Ancestry
Authors: Kerr Shona M. , Edwards Rachel , Buchanan David , Dean John , Miedzybrodzka Zosia , Wilson James F.
Published: October 2021

Introduction

The purpose of VIKING II is to create an observational cohort of volunteers with ancestry from the Northern Isles of Scotland, primarily for identifying genetic variants influencing disease. The new online protocol is separate to, but follows on from, earlier genetic epidemiological clinic-based studies in the isolated populations of Orkney and Shetland. These populations are favourable for the study of rarer genetic variants due to genetic drift, the large number of relatives, and availability of pedigree information.

Methods and Analysis

Online methods are being used to recruit ∼4,000 people who have Northern Isles ancestry, living anywhere in the world. The option for participants to have actionable genetic results returned is offered. Broad consent will be taken electronically. Data will be collected at baseline through an online questionnaire and longitudinally through linkage to NHS data in the electronic health record. The questionnaire collects a variety of phenotypes including personal and family health. DNA will be extracted from saliva samples then genome-wide genotyped and exome sequenced. VIKING II aims to capitalise on the special features of the Northern Isles populations to create a research cohort that will facilitate the analysis of genetic variants associated with a broad range of traits and disease endpoints.

Ethics and Dissemination

The South East Scotland Research Ethics Committee gave the study a favourable opinion. VIKING II is sponsored by the University of Edinburgh and NHS Lothian. Summary research findings will be disseminated to participants and funding bodies, presented at conferences and reported in peer-reviewed publications.

Article Summary

Strengths and limitations of this study

Detailed data and biological sample collection of research volunteers with unique ancestry.

Consent for access to routinely collected clinical EHR data and for future re-contact, providing a longitudinal component.

Optional consent for return of actionable genetic results.

4,000 participants is a relatively small number for certain types of genetic analyses, so the cohort is underpowered on its own, in some study designs.

Resources to maintain the cohort, and to store data and DNA samples, are significant, with sustainability dependent on infrastructure support and continued funding.